SPIRIT 2025 and TIDieR: A Practical Guide to Transparent Nutrition RCT Protocols

Abstract

This article provides researchers and clinical development professionals with a comprehensive guide to applying the updated SPIRIT 2025 and TIDieR guidelines specifically to nutrition and diet-related randomized controlled trials (RCTs). It covers the foundational principles of these reporting standards, offers step-by-step methodological application, addresses common troubleshooting scenarios in complex nutrition interventions, and explores validation strategies to enhance protocol quality and regulatory success. By integrating these frameworks, researchers can improve the transparency, reproducibility, and patient-centeredness of their nutrition trial protocols, ultimately accelerating the development of robust dietary evidence.

Understanding SPIRIT 2025 and TIDieR: The Pillars of Robust Nutrition Research

The Critical Need for Reporting Guidelines in Nutrition Science

The Current Landscape of Reporting Completeness in Nutrition RCTs

Randomized controlled trials (RCTs) represent the gold standard for generating evidence in nutritional science, informing public health policies, clinical practice guidelines, and therapeutic recommendations. The reliability of this evidence base, however, depends fundamentally on the completeness and transparency of trial planning and reporting. Research protocols serve as the foundational documents that specify planned methods and conduct, yet recent evidence reveals significant shortcomings in their reporting quality within the nutrition field.

A comprehensive meta-research study assessing 200 nutrition and diet-related RCT protocols published in 2019 and 2021 found an overall reporting completeness of just 52.0% (SD = 10.8%) when evaluated against the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and TIDieR (Template for Intervention Description and Replication) guidelines [1] [2]. This concerning gap indicates that nearly half of the critical information needed to properly evaluate, replicate, and appraise nutrition trials is missing from their protocols.

The reporting deficiencies were particularly pronounced for specific methodological elements [1] [3]:

• Data collection methods: 0% of protocols fully described these procedures
• Materials used in the intervention: Only 5.5% provided adequate descriptions
• Public access to full protocol documents: Rarely addressed
• Data sharing and statistical code availability: Infrequently mentioned

Table 1: Adherence to SPIRIT and TIDieR Items in Nutrition RCT Protocols

Reporting Item	Adherence Rate	Significance
Eligibility criteria	98.5%	Well-reported
Intervention description	98.5%	Well-reported
Data collection methods	0%	Critically under-reported
Intervention materials	5.5%	Critically under-reported
Data sharing statements	<20%	Substantially under-reported

Several factors were identified as positively associated with improved reporting completeness. Protocols with a higher number of authors demonstrated better reporting (β = 0.53), suggesting the value of collaborative multidisciplinary teams [1]. More recently published protocols (2021 vs. 2019) showed significant improvement (β = 3.19), reflecting a positive temporal trend [1] [3]. Journals that required reporting guidelines during submission (β = 6.50) and author self-declared adherence to SPIRIT (β = 5.15) were also strong predictors of completeness [1].

Updated Reporting Guidelines: SPIRIT 2025 and Its Relevance to Nutrition Research

The recent publication of the SPIRIT 2025 statement represents a significant advancement in protocol reporting standards [4] [5] [6]. This updated guideline reflects methodological developments and incorporates lessons from a decade of implementation since the original 2013 statement. The revision process involved 317 participants in a Delphi survey and 30 international experts in a consensus meeting, ensuring comprehensive stakeholder input [5].

Key updates in SPIRIT 2025 particularly relevant to nutrition science include [4] [6]:

• A new open science section consolidating items on trial registration, protocol sharing, data sharing, and statistical code availability
• Enhanced emphasis on assessment and reporting of harms (integrating CONSORT Harms 2022)
• Improved guidance for description of interventions and comparators (incorporating TIDieR elements)
• A new item on patient and public involvement in trial design, conduct, and reporting

The SPIRIT 2025 statement now consists of a 34-item checklist and a diagram illustrating the schedule of enrollment, interventions, and assessments [4]. For nutrition researchers, these updates address several field-specific challenges, including the complex nature of dietary interventions, difficulties with blinding, and the need for precise documentation of intervention components and delivery.

Table 2: Key SPIRIT 2025 Updates Relevant to Nutrition Science

Update Category	Specific Changes	Relevance to Nutrition Research
Open Science	New section on protocol, data, and code sharing	Addresses reproducibility challenges in nutrition studies
Intervention Description	Enhanced details on materials, procedures	Critical for complex dietary interventions and controls
Harms Assessment	Integrated CONSORT Harms guidance	Improves safety monitoring for nutritional products
Patient Involvement	New item on stakeholder engagement	Enhances relevance of nutrition trials to end-users

Special Considerations for Nutrition Trial Protocols

Nutrition research presents unique methodological challenges that necessitate specialized reporting considerations. Unlike pharmaceutical trials, nutrition interventions often involve complex dietary manipulations, whole foods or food patterns, and behavioral components that are difficult to standardize and document [7] [8]. The regulatory landscape for nutrition research also differs significantly, with ambiguous boundaries between food and drug definitions creating particular challenges for investigators [8].

Documentation requirements for nutrition trials must address several distinctive aspects [8]:

• Source and composition of food stuffs or bioactive ingredients
• Stability and shelf-life of dietary interventions
• Preparation methods and quality control procedures
• Compliance assessment methodologies
• Background diet and potential confounding dietary factors

The FDA regulatory framework requires special attention as investigations assessing the effect of a food, food component, or supplement on the "diagnosis, cure, mitigation, treatment, or prevention of disease" may require an Investigational New Drug (IND) application [8]. While exemptions exist for some types of nutrition research—such as studies supporting health claims or evaluating nutritional structure/function effects—consultation with regulatory experts is often advisable during protocol development.

Controlled-feeding trials present additional documentation challenges, requiring precise specification of [8]:

• Food procurement and storage conditions
• Preparation environment and protocols
• Quality assurance procedures
• Waste tracking methods
• Compliance monitoring systems

Implementation Protocols for Enhancing Nutrition RCT Protocol Quality

Protocol Development Workflow

The following diagram illustrates a systematic workflow for developing comprehensive nutrition RCT protocols that adhere to SPIRIT 2025 guidelines:

Essential Research Reagent Solutions for Nutrition Trials

Table 3: Key Research Reagent Solutions for Nutrition Intervention Studies

Reagent Category	Specific Components	Documentation Requirements
Dietary Interventions	Purified nutrients, Whole foods, Fortified products, Dietary supplements	Certificate of Analysis, Batch/Lot numbers, Purity assays, Stability data, Storage conditions
Control Materials	Placebo products, Control diets, Washout diets	Composition matching, Blindability, Palatability assessment, Contamination controls
Compliance Biomarkers	Biological samples (blood, urine), Dietary biomarkers, Nutritional status indicators	Collection protocols, Storage conditions, Analysis methods, Validation data
Assessment Tools	FFQs, Dietary recalls, Food diaries, Physical activity measures	Validation studies, Administration protocols, Scoring algorithms, Cultural adaptation documentation

Detailed Methodology for Intervention Description

The TIDieR checklist provides a framework for comprehensive intervention description, with particular importance for nutrition studies [1]. Implementation should include:

Materials Documentation Protocol:

• Source Verification: Document suppliers, batch numbers, and certificates of analysis for all intervention components
• Composition Analysis: Specify macronutrient, micronutrient, and bioactive compound composition through laboratory verification where possible
• Stability Monitoring: Establish stability testing protocols and shelf-life determinations for intervention materials
• Storage Conditions: Document storage temperature, humidity, light exposure, and other relevant environmental factors

Intervention Delivery Protocol:

• Preparation Procedures: Standardize preparation methods, including cooking techniques, portioning, and timing
• Quality Control: Implement regular quality checks and sensory evaluation where appropriate
• Delivery Documentation: Record time of delivery, administration method, and supervision
• Adherence Assessment: Employ multiple adherence measures (intake records, biomarkers, returned product counts)

Control Group Protocol:

• Control Matching: Carefully design control interventions to match sensory properties while differing in specific nutrients of interest
• Blinding Procedures: Document blinding methods and assess blinding success where feasible
• Background Diet Control: Specify strategies to account for or control background dietary intake

The Emerging SPIRIT-Nut Extension and Future Directions

Recognizing the unique reporting needs in nutrition research, the SPIRIT-Nut extension is currently under development [9]. This official SPIRIT extension aims to consolidate existing and new guidance specifically for reporting protocols of randomized controlled trials of nutritional interventions. While the SPIRIT 2025 statement provides comprehensive general guidance, the SPIRIT-Nut extension will provide field-specific adaptations and examples relevant to nutrition researchers.

The development of SPIRIT-Nut represents a crucial step toward addressing the documented reporting gaps in nutrition trial protocols, particularly in areas such as:

• Intervention sourcing and composition
• Dietary assessment methodology
• Compliance monitoring techniques
• Background diet characterization
• Nutrient biomarker application

Research indicates that journal endorsement of reporting guidelines significantly improves reporting completeness [1]. Nutrition journals should therefore actively promote and require adherence to SPIRIT 2025 and subsequent specialized extensions like SPIRIT-Nut. Similarly, funding agencies can play a pivotal role by mandating guideline adherence as a condition of grant awards.

The integration of open science practices—including prospective protocol registration, statistical analysis plan publication, and data sharing—represents another critical advancement for nutrition science. These practices enhance transparency, enable meta-research, and ultimately strengthen the evidence base for dietary recommendations and nutrition policy.

The consistently documented incompleteness in nutrition RCT protocol reporting underscores the critical importance of standardized reporting guidelines. The recent publication of SPIRIT 2025 provides an updated framework for addressing these deficiencies, while the ongoing development of SPIRIT-Nut promises field-specific guidance tailored to the unique methodological challenges of nutrition research.

Widespread adoption of these guidelines by researchers, journals, funders, and institutions is essential to enhance the methodological rigor, transparency, and reliability of nutrition science. Through improved protocol reporting, the nutrition research community can strengthen the evidence base needed to inform effective public health policies, clinical guidelines, and individual dietary recommendations that promote optimal health and combat diet-related chronic diseases.

The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement serves as the foundational guideline for designing and reporting randomized trial protocols. First established in 2013, SPIRIT provides an evidence-based checklist to ensure protocol completeness and research transparency, addressing concerns about a "credibility crisis" in scientific research where key methodological elements were frequently omitted from trial protocols [10] [4]. The protocol functions as the central document for trial planning, conduct, reporting, and external review, serving multiple stakeholders including investigators, research ethics committees, funders, journal editors, and patients [4] [11].

After more than a decade of use and significant evolution in trial methodologies, the SPIRIT Executive Group undertook a systematic update to incorporate the latest evidence and emerging perspectives. Developed in parallel with the updated CONSORT 2025 statement to ensure harmonization, SPIRIT 2025 was created through an extensive consensus process involving 317 participants representing statisticians, trial investigators, systematic reviewers, clinicians, journal editors, and patient representatives [4]. This update reflects "the evolving trials environment and methodological advancements," including growing international support for open science practices and greater patient involvement in research [4].

Key Updates in SPIRIT 2025

Structural and Content Changes

The SPIRIT 2025 statement introduces several substantial modifications to the original checklist, based on empirical evidence and expert consensus. The updated guideline comprises a checklist of 34 minimum protocol items, representing significant restructuring from the 2013 version [4] [11]. Notable changes include the addition of two new protocol items, revision of five items, deletion or merger of five items, and integration of key items from other relevant reporting guidelines such as CONSORT Harms 2022, SPIRIT-Outcomes 2022, and TIDieR (Template for Intervention Description and Replication) [4].

A major structural innovation in SPIRIT 2025 is the creation of a dedicated open science section that consolidates items critical to promoting access to information about trial methods and results [4]. This section emphasizes transparency elements including trial registration, sharing of the full protocol and statistical analysis plan, data sharing arrangements, disclosure of funding sources and conflicts of interest, and dissemination policies [11]. The updated guideline also harmonizes wording between SPIRIT and CONSORT checklist items to improve consistency and usability across the trial lifecycle from protocol development to results reporting [4].

Table: Key Structural Changes in SPIRIT 2025

Change Type	Number of Items	Description and Examples
New Items	2	• Patient and public involvement (Item 11)• Open science section consolidating transparency items
Revised Items	5	• Enhanced emphasis on harms assessment• Improved intervention/comparator description• Updated blinding procedures
Deleted/Merged Items	5	Streamlining of redundant or overlapping items
Integrated Guidelines	3	Incorporation of key elements from CONSORT Harms, SPIRIT-Outcomes, and TIDieR

New and Modified Items

One of the most significant additions to SPIRIT 2025 is Item 11, which requires details of, or plans for, patient or public involvement in the design, conduct, and reporting of the trial [4] [11]. This addition formally recognizes the importance of incorporating patient perspectives throughout the research process to ensure trials address meaningful outcomes and are conducted in ways that reflect participant needs and preferences.

The updated guideline also strengthens the description of interventions and comparators (Item 15), requiring "sufficient details to allow replication including how, when, and by whom they will be administered" [11]. This enhancement aligns with TIDieR recommendations, which provide more detailed guidance for describing interventions [12]. The updated item also includes criteria for discontinuing or modifying allocated interventions, strategies to improve adherence, and specifications of permitted or prohibited concomitant care [11].

Another crucial modification appears in Item 17, which places additional emphasis on the assessment of harms, requiring researchers to specify "how harms are defined and will be assessed (e.g., systematically, non-systematically)" [11]. This change integrates recommendations from the CONSORT Harms 2022 extension, ensuring that protocols adequately plan for the systematic identification, monitoring, and reporting of adverse events [4].

The newly organized open science section (Items 4-8) represents a comprehensive approach to research transparency, encompassing trial registration, protocol and statistical analysis plan accessibility, data sharing policies, funding and conflicts of interest disclosure, and dissemination plans [11]. This consolidation reflects the growing recognition that transparency at the protocol stage is essential for reducing selective reporting and facilitating the interpretation of completed trials.

Significance for Nutrition RCT Protocols

Current Landscape of Nutrition Trial Protocols

Recent metaresearch examining nutrition- and diet-related RCT protocols reveals both progress and persistent challenges in protocol reporting. A comprehensive analysis of 1,068 nutrition and diet-related RCT protocols published between 2012 and 2022 demonstrated a promising annual increase in published protocols, with a mean of 103 publications per year, supporting "the raising awareness and the importance of promoting these publications" [10]. The study found that most protocols focused on adults or elderly participants (63.4%), with supplementation (37.9%) and nutrition education/counseling (33.1%) representing the most frequent intervention types [10].

However, the same research revealed significant gaps in the adoption of reporting guidelines. While 75.3% of journals publishing these protocols endorsed CONSORT, only 33.8% endorsed SPIRIT, and a mere 2.7% endorsed TIDieR [10]. Similarly, researcher adherence to these guidelines remained "far from ideal," with only 32.1% of protocols mentioning SPIRIT, 27.8% mentioning CONSORT, and 1.9% mentioning TIDieR [10]. These findings highlight a substantial implementation gap between guideline availability and actual reporting practices in nutrition research.

A separate meta-research study assessing reporting completeness in 200 nutrition and diet-related RCT protocols identified particular deficiencies in data handling, study monitoring, and public access to protocol documents, datasets, and statistical code [2]. The reporting of materials used for interventions was identified as the most incompletely reported TIDieR item, indicating specific challenges in the precise description of nutrition interventions [2]. These reporting gaps "might be an indication that tailored reporting guidance for this area is needed" to improve the transparency and replicability of nutrition research [2].

Table: Reporting Completeness in Nutrition RCT Protocols

Reporting Aspect	Current Status in Nutrition Protocols	SPIRIT 2025 Enhancement
Intervention Description	Materials for intervention most incompletely reported TIDieR item [2]	Enhanced Item 15 with sufficient detail for replication
Data Sharing	Low reporting of public access to datasets and statistical code [2]	New open science section with data sharing requirements (Item 6)
Harms Monitoring	Often inadequately addressed in nutrition trials	Strengthened harms assessment (Item 17)
Patient Involvement	Rarely systematically reported	New patient and public involvement item (Item 11)
Adherence Monitoring	Often limited to subjective measures [13]	Specific strategies for monitoring adherence (Item 15c)

Addressing Nutrition-Specific Methodological Challenges

Nutrition trials present unique methodological challenges that SPIRIT 2025 helps address through its updated items. Complex intervention descriptions required for dietary interventions, behavioral nutrition approaches, and supplement regimens are better accommodated through the enhanced intervention details in Item 15, which aligns with TIDieR recommendations for comprehensive intervention reporting [2] [12]. This is particularly important given findings that nutrition protocols often lack sufficient detail to enable replication of interventions [2].

The strengthened requirements for adherence monitoring (Item 15c) present both challenges and opportunities for nutrition trials. While the updated item references strategies such as "drug tablet return, sessions attended" [11], some experts have expressed concern that this represents a potential weakening from the previous mention of laboratory tests in SPIRIT 2013 [13]. For nutrition research, this highlights the need to develop and implement more robust, objective measures of adherence to dietary interventions, which may include biomarkers, digital monitoring technologies, or validated dietary assessment tools.

The new emphasis on patient and public involvement (Item 11) holds particular significance for nutrition research, where dietary behaviors, food preferences, and cultural considerations substantially influence intervention acceptability and adherence. Involving patients and the public in the design of nutrition trials can help ensure that interventions are practical, acceptable, and meaningful to target populations, potentially enhancing recruitment, retention, and real-world applicability of findings.

Implementation Framework and Experimental Protocols

SPIRIT 2025 Development Methodology

The SPIRIT 2025 update followed a rigorous, evidence-based methodology in accordance with EQUATOR Network guidance for developers of health research guidelines [4]. The process began with a scoping review of literature from 2013 to 2022 identifying published comments suggesting modifications or reflecting on strengths and challenges of SPIRIT 2013 [4]. Researchers also conducted a broader search for empirical and theoretical evidence relevant to SPIRIT and risk of bias in randomized trials, creating the SPIRIT-CONSORT Evidence Bibliographic database to inform the update process [4].

Based on the gathered evidence, a preliminary list of potential additions to the SPIRIT 2013 checklist was created for review in an international, three-round online Delphi survey with 317 participants representing diverse stakeholders including statisticians/methodologists/epidemiologists (n=198), trial investigators (n=73), systematic reviewers/guideline developers (n=73), clinicians (n=58), journal editors (n=47), and patients and members of the public (n=17) [4]. During each survey round, participants rated the importance of modifications on a five-point Likert scale and provided comments or suggestions for additional items.

The Delphi survey results were discussed at a two-day online consensus meeting in March 2023, attended by 30 invited international experts representing various relevant groups [4]. Meeting participants discussed potential new and modified SPIRIT checklist items, with anonymous polling used in cases of ongoing disagreement. The executive group then met in person in April 2023 to develop a draft checklist, which underwent a further round of review by consensus meeting participants before finalization [4].

SPIRIT 2025 Development Methodology

Implementation Protocol for Nutrition RCTs

Implementing SPIRIT 2025 for nutrition and diet-related randomized trials requires a systematic approach to protocol development. The following experimental protocol provides a framework for creating SPIRIT 2025-compliant nutrition trial protocols:

Protocol Title: Development and Validation of SPIRIT 2025-Compliant Nutrition RCT Protocols

Background: Inadequate reporting of trial protocols remains a significant challenge in nutrition research, with recent studies indicating that fewer than two-thirds of SPIRIT items are fully reported in published nutrition protocol manuscripts [2]. Implementing the updated SPIRIT 2025 guideline addresses this gap by providing a structured framework for comprehensive protocol development.

Primary Objective: To develop and validate a methodology for creating SPIRIT 2025-compliant protocols for nutrition and diet-related randomized controlled trials.

Methods - Study Design: This implementation protocol follows a multi-phase development process aligned with SPIRIT 2025 requirements. The study incorporates the participants, interventions, comparators, outcomes, and study designs (PICOS) framework recommended for systematic protocol development [10].

Intervention - SPIRIT 2025 Integration:

• Administrative Information Framework: Implement SPIRIT 2025 Items 1-3 covering title, structured summary, protocol versioning, and roles and responsibilities, with particular attention to nutrition-specific contributor roles including dietitians, nutrition scientists, and behavioral specialists.
• Open Science Integration: Apply the new open science section (Items 4-8) by registering trials in approved registries, creating data sharing plans for nutrition datasets, documenting funding sources, and developing dissemination strategies including plain language summaries for nutrition studies.
• Methodological Enhancements: Incorporate updated items on patient involvement (Item 11), trial design (Item 12), and detailed intervention descriptions (Item 15) using TIDieR elements to comprehensively describe nutrition interventions.
• Outcome and Harms Reporting: Implement strengthened requirements for outcome specification (Item 16) and harms monitoring (Item 17), particularly important for nutrition trials evaluating dietary patterns, supplements, or behavioral interventions.

Outcomes - Primary Implementation Endpoints:

• Completeness of Reporting: Proportion of SPIRIT 2025 items fully addressed in resulting nutrition trial protocols, compared to historical controls using SPIRIT 2013.
• Stakeholder Usability: Protocol developer satisfaction measured using a 5-point Likert scale assessing clarity, comprehensiveness, and applicability to nutrition research.
• Review Efficiency: Time from protocol submission to approval by research ethics committees and journal editors, comparing SPIRIT 2025-compliant protocols with historical controls.

Data Collection and Analysis:

• Baseline Assessment: Extract data from the STAR-NUT project Open Science Framework repository (https://osf.io/b38z9/) to establish historical reporting completeness benchmarks for nutrition protocols [2].
• Implementation Phase: Apply the SPIRIT 2025 framework to a series of nutrition trial protocols across diverse domains (supplementation, dietary patterns, behavioral nutrition).
• Evaluation Phase: Assess reporting completeness using the expanded SPIRIT 2025 checklist, analyze stakeholder feedback, and compare review timelines.

Ethics and Dissemination: The implementation protocol will be submitted for research ethics committee approval where applicable. Results will be disseminated through peer-reviewed publications, conference presentations, and nutrition methodology workshops to support broad adoption of SPIRIT 2025 in nutrition research.

Essential Research Toolkit

Table: Research Reagent Solutions for SPIRIT 2025 Implementation

Tool or Resource	Function in Protocol Development	Access Information
SPIRIT 2025 Checklist	Core guideline with 34 minimum items for trial protocols	Available through consortium website (www.consort-spirit.org) and simultaneous publication in multiple journals [14]
SPIRIT 2025 Explanation & Elaboration	Detailed guidance with examples of good reporting for each checklist item	Published in BMJ with open access [11]
TIDieR (Template for Intervention Description and Replication)	Complementary guideline for comprehensive intervention description, critical for nutrition interventions	Available through EQUATOR Network; checklist in multiple languages [12]
SPIRIT-Outcomes 2022 Extension	Specialized guidance for outcome reporting in trial protocols	Integrated into SPIRIT 2025 but available as standalone resource [14]
CONSORT Harms 2022	Guidance for harms reporting in randomized trials	Incorporated into SPIRIT 2025 Item 17 on harms assessment [4]
STAR-NUT Project Database	Meta-research data on nutrition trial protocol reporting for benchmarking	Openly available at https://osf.io/b38z9/ [2]
Suc-Leu-Tyr-AMC	Suc-Leu-Tyr-AMC, CAS:94367-20-1, MF:C29H33N3O8, MW:551.6 g/mol	Chemical Reagent
Dynorphin A 1-10	Dynorphin A 1-10, CAS:79994-24-4, MF:C57H91N19O12, MW:1234.5 g/mol	Chemical Reagent

SPIRIT 2025 Implementation Resource Integration

The SPIRIT 2025 statement represents a significant advancement in the standard for randomized trial protocols, with particular relevance for nutrition and diet-related research. The updated guideline addresses critical gaps in protocol reporting through its enhanced focus on open science practices, patient involvement, comprehensive intervention description, and systematic harms assessment. For the nutrition research community, which faces unique methodological challenges in describing complex interventions and ensuring adherence, these updates provide a robust framework for improving protocol completeness and research transparency.

Implementation of SPIRIT 2025 across nutrition research requires systematic approach to protocol development, leveraging available resources including the SPIRIT 2025 explanation and elaboration document, complementary TIDieR guidelines for intervention description, and benchmarking data from initiatives like the STAR-NUT project. As noted in recent meta-research, improved adherence to reporting guidelines in nutrition protocols is essential for building "a trustworthy evidence base for public health policies, advances in clinical practice and, ultimately, improvements in patients' lives" [2].

The successful adoption of SPIRIT 2025 will depend on collaborative efforts across multiple stakeholders, including researchers, funders, journal editors, research ethics committees, and patient representatives. By embracing these updated standards, the nutrition research community can enhance the methodological rigor, transparency, and clinical utility of trial evidence, ultimately strengthening the foundation for evidence-based nutrition policy and practice.

Complete and transparent reporting is a cornerstone of scientific reproducibility, particularly in nutrition and diet-related randomized controlled trials (RCTs) where complex interventions pose unique methodological challenges. Research protocols and published papers that lack crucial details make it difficult for other scientists to assess the study's validity, replicate the findings, or build upon the research effectively. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guideline provides a framework for drafting complete clinical trial protocols, while the TIDieR (Template for Intervention Description and Replication) guideline extends item 5 of the CONSORT statement to ensure comprehensive intervention description. These guidelines are especially critical in nutrition science, where intervention details—such as dietary composition, delivery methods, and participant adherence strategies—show tremendous variability and complexity. Without standardized reporting, nutrition research faces a reproducibility crisis that undermines evidence-based clinical and public health decisions [15].

Recent meta-research studies reveal significant reporting deficiencies in the nutrition literature. An assessment of 200 diet- or nutrition-related RCT protocols found an overall reporting completeness of just 52.0% (SD = 10.8%) when evaluated against combined SPIRIT and TIDieR checklists. Adherence to specific TIDieR items was particularly poor, with only 5.5% of protocols adequately describing materials used in the intervention, despite 98.5% naming the intervention itself [1]. Another study examining 100 recently published nutrition-related RCTs found that approximately half lacked data-sharing statements, and 97% did not include analysis code sharing statements [16]. These reporting gaps fundamentally impede the replicability of nutrition science and represent a significant source of research waste.

Quantitative Assessment of Reporting Completeness

Current State of TIDieR Implementation

A meta-research study analyzing 200 randomly sampled nutrition and diet-related RCT protocols published in 2019 and 2021 revealed substantial variability in the reporting completeness of different TIDieR elements. While basic intervention descriptions were present in most protocols, critical details enabling replication were frequently omitted. The findings demonstrate that reporting completeness remains suboptimal across the nutrition research landscape, with specific deficits in intervention documentation that directly impact replicability [1].

Table 1: TIDieR Reporting Completeness in Nutrition RCT Protocols (n=200)

TIDieR Item	Reporting Frequency	Key Deficiencies Identified
Intervention Description	98.5% (n=197)	Basic naming without sufficient operational details
Intervention Materials	5.5% (n=11)	Brand information, quality specifications, and source details omitted
Intervention Modifications	Not Reported	Adaptation during trials rarely documented
Intervention Fidelity	Not Reported	Delivery quality assessment methods typically missing

Factors Influencing Reporting Quality

Multivariable regression analysis of nutrition RCT protocols identified several factors significantly associated with improved reporting completeness. A higher number of authors was positively associated with better reporting (β = 0.53, 95% CI: 0.28-0.78), suggesting collaborative writing contributes to more comprehensive protocols. More recently published protocols showed better adherence to reporting guidelines (β = 3.19, 95% CI: 0.24-6.14), indicating gradual improvement over time. Most importantly, journal policies requiring reporting guidelines during submission were strongly associated with improved completeness (β = 6.50, 95% CI: 2.56-10.43), as was author mention of SPIRIT adherence (β = 5.15, 95% CI: 2.44-7.86) [1]. These findings highlight the critical role of journal policies and author awareness in driving reporting quality improvements.

Application Notes: Implementing TIDieR in Nutrition Research

Protocol Development Workflow

The following diagram illustrates a systematic workflow for developing a nutrition RCT protocol that integrates both SPIRIT and TIDieR guidelines to ensure completeness and replicability:

TIDieR-Specific Implementation Protocol

Comprehensive Nutrition Intervention Description Framework

• WHAT: Intervention Components

  • Provide the specific name of the nutrition intervention and all constituent components
  • Describe physical forms (e.g., capsule, liquid, solid food) and sensory properties (e.g., taste, texture, appearance)
  • Specify brand names, manufacturers, quality control measures, and composition verification methods
  • Document nutrient profiles using standardized databases (e.g., USDA FoodData Central) with version information

• WHO: Delivery and Receipt

  • Outline qualifications and training of intervention administrators
  • Describe participant instructions provided, including timing, frequency, and co-consumption considerations
  • Specify language level and educational materials used for participant communication
  • Document fidelity assessment methods (e.g., direct observation, pill counts, food diaries)

• HOW: Mode and Environment

  • Detail delivery modes (e.g., in-person, remote, self-administered)
  • Describe setting context (e.g., clinical, free-living, controlled feeding environment)
  • Specify supervision level and monitoring intensity throughout intervention period

• WHEN: Timing and Duration

  • Define intervention schedule with precise timing, frequency, and duration
  • Specify relationship to meals, fasting periods, or circadian timing
  • Document seasonal considerations for nutrition interventions

• MODIFICATIONS: Adaptation Protocols

  • Pre-specify allowable adaptations with decision rules and documentation requirements
  • Establish protocols for documenting any deviations from planned intervention
  • Create system for categorizing modifications as planned versus unplanned

This framework directly addresses the most commonly underreported elements in nutrition trials, particularly materials (5.5% reported) and intervention modifications (rarely documented) [1].

Experimental Protocols for Nutrition Intervention Research

Nutrition-Specific RCT Methodology

Robust methodology is essential for generating reproducible evidence in nutrition science. The randomized controlled trial (RCT) design represents the gold standard for establishing cause-and-effect relationships in nutritional interventions [17]. Proper implementation requires attention to several nutrition-specific methodological considerations:

Table 2: Essential Methodology for Nutrition-Related RCTs

Methodological Element	Nutrition-Specific Application	Reporting Guidance
Randomization	Stratified by baseline nutritional status, dietary patterns, or genetic polymorphisms	Report method of sequence generation, implementation mechanism, and who generated assignment
Blinding	Use matched placebos with identical sensory properties; document blinding success assessment	Describe similarity of intervention and control; report blinding index assessment
Control Group	Select appropriate control (placebo, usual care, active comparator, waitlist) with scientific rationale	Justify choice of comparator; detail placebo composition and matching procedures
Adherence Monitoring	Implement multiple methods (biological biomarkers, dietary recalls, returned product weighing)	Specify primary adherence measure and predetermined adherence thresholds
Data Collection	Use validated dietary assessment tools (FFQs, 24-hour recalls, biomarkers) with timing specified	Name specific assessment tools and versions; describe staff training and standardization

Statistical analysis approaches must be pre-specified in statistical analysis plans, which are currently missing in 97% of nutrition RCT publications [16]. Analysis of covariance (ANCOVA) and linear mixed models are preferred over simple change-from-baseline analyses, as they provide greater statistical power and better account for baseline imbalances [18]. Covariate adjustment should include pre-specified potential confounding variables common in nutrition research, such as age, sex, body mass index, physical activity level, and baseline nutritional status [18].

Reproducibility Enhancement Protocol

Transparency and Reproducibility Framework

• STUDY REGISTRATION

  • Register protocol in publicly accessible trial registry before participant enrollment
  • Include all WHO minimum dataset items with nutrition-specific extensions
  • Document any protocol amendments with rationale and dates

• STATISTICAL ANALYSIS PLAN

  • Develop detailed statistical analysis plan before data collection completion
  • Pre-specify primary, secondary, and exploratory outcomes with complete definitions
  • Document handling of missing data, adherence considerations, and sensitivity analyses

• DATA SHARING

  • Create anonymized dataset with comprehensive data dictionary
  • Use standardized formats for nutritional data (e.g., Darwin Core for biodiversity, USDA formats for composition)
  • Provide analysis code in open-source languages (e.g., R, Python) with commented documentation

Currently, only about half of nutrition RCTs include data sharing statements, and only 3% include code sharing statements [16], highlighting a substantial opportunity for improvement in research transparency.

The Researcher's Toolkit for Replicable Nutrition Science

Essential Research Reagent Solutions

Table 3: Research Reagent Solutions for Nutrition Intervention Studies

Reagent Category	Specific Examples	Function in Nutrition Research	Documentation Requirements
Reference Standards	USP standards, NIST SRMs, certified reference materials	Quality control and assay validation; instrument calibration	Source, catalog number, lot number, expiration date, certificate of analysis
Dietary Assessment Tools	USDA Automated Multiple-Pass Method, Food Frequency Questionnaires, diet diaries	Quantify dietary intake and patterns; assess intervention adherence	Validation study references, version information, processing algorithms
Biological Specimen Collection	EDTA tubes, PAXgene RNA tubes, stool collection kits with preservatives	Biomarker analysis; microbiome assessment; metabolomic profiling	Collection conditions, processing protocols, storage temperature and duration
Nutritional Formulations	Certified ingredients, pharmaceutical-grade supplements, food-grade matrices	Intervention delivery; dose-response assessment	Composition verification, contaminant testing, stability data, organoleptic properties
Placebo/Control Materials	Matched sensory qualities, inert fillers, micronutrient-free equivalents	Blinding maintenance; control for non-specific effects	Matching verification method, composition details, similarity testing results
Dermorphin	Dermorphin, CAS:77614-16-5, MF:C40H50N8O10, MW:802.9 g/mol	Chemical Reagent	Bench Chemicals
Natriuretic Peptide, C-Type	Natriuretic Peptide, C-Type, CAS:127869-51-6, MF:C93H157N27O28S3, MW:2197.6 g/mol	Chemical Reagent	Bench Chemicals

Intervention Fidelity Assessment Tools

The following diagram illustrates a comprehensive system for monitoring and evaluating intervention fidelity throughout a nutrition RCT:

The consistent implementation of TIDieR guidelines within nutrition RCT protocols represents a methodological imperative for enhancing the replicability and translational impact of nutrition science. The current evidence indicates significant reporting deficiencies in critical intervention details, with only 5.5% of protocols adequately describing intervention materials and even fewer documenting modifications and fidelity assessment [1]. These deficits directly undermine the reproducibility and utility of nutrition research findings.

Successful implementation requires a multifaceted approach addressing both individual researcher practices and systemic journal policies. The demonstrated association between journal endorsement of reporting guidelines and improved reporting completeness (β = 6.50, 95% CI: 2.56-10.43) [1] highlights the powerful role that editorial policies can play in driving improvement. Similarly, the positive relationship between author awareness of SPIRIT and reporting quality (β = 5.15, 95% CI: 2.44-7.86) [1] underscores the importance of researcher education in reporting standards.

Moving forward, the nutrition research community must prioritize complete intervention documentation through TIDieR implementation, statistical analysis plan development (currently missing in 97% of publications) [16], and data sharing practices (absent in approximately 50% of trials) [16]. By adopting the structured protocols and frameworks outlined in this article, nutrition researchers can significantly enhance the reproducibility, credibility, and clinical relevance of our scientific evidence base, ultimately supporting more effective nutrition policies and practices.

The Synergy Between SPIRIT and TIDieR in a Complete Protocol Framework

The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2025 statement provides an evidence-based checklist of 34 minimum items to address in a trial protocol, serving as the foundational blueprint for trial design, conduct, and reporting [19] [4]. Simultaneously, the TIDieR (Template for Intervention Description and Replication) guideline offers a structured framework for describing interventions in sufficient detail to allow their replication [12]. When integrated systematically, these frameworks create a synergistic relationship that addresses a critical gap in clinical trial methodology: the frequent inadequate description of complex interventions, which remains a substantial barrier to research transparency, reproducibility, and clinical implementation.

The recent SPIRIT 2025 update reflects evolving methodological standards by incorporating a new open science section, emphasizing patient and public involvement, and strengthening requirements for describing interventions and comparators [19] [4] [20]. This enhanced focus on intervention description creates natural alignment points with the TIDieR checklist, particularly for nutrition research where interventions often involve complex, multi-component approaches with inherent implementation challenges. This integration is especially relevant for nutrition RCT protocols, where accurate replication depends on precise documentation of dietary components, delivery methods, adherence monitoring, and contextual factors that may modify intervention effects.

Theoretical Synergy Between SPIRIT and TIDieR

Complementary Roles in Protocol Development

SPIRIT 2025 and TIDieR serve complementary but distinct functions in the clinical trial ecosystem. SPIRIT establishes the comprehensive protocol architecture, while TIDieR provides the granular specificity needed for intervention reproducibility. The theoretical synergy between these frameworks emerges from their shared commitment to research transparency but different scopes of application.

SPIRIT 2025 functions as the structural skeleton of trial protocols, addressing administrative elements, scientific rationale, ethical considerations, statistical methods, and overall trial management [19]. The guideline organizes content into logical sections including administrative information, introduction, methods, and ethical considerations. Within this structure, intervention description represents one critical component among many. TIDieR, in contrast, drills down exclusively on the intervention itself, providing a comprehensive taxonomy for describing what the intervention entails (materials, procedures), who provides it, how it is delivered, where it is implemented, when and how much is administered, and how tailoring, modification, and adherence are addressed [12]. This specialized focus makes TIDieR an indispensable tool for fulfilling SPIRIT's requirements for intervention description.

The integration of these frameworks creates a bidirectional relationship where SPIRIT provides the contextual framework for the intervention within the overall trial design, while TIDieR ensures the intervention itself is described with sufficient richness to enable evaluation, replication, and translation into practice. For nutrition research, this synergy is particularly valuable as dietary interventions often involve complex behavioral components, cultural adaptations, and individual tailoring that challenge standard reporting approaches.

Integration Logic and Workflow

The relationship between SPIRIT and TIDieR in protocol development follows a logical workflow where SPIRIT items identify what information must be included, while TIDieR provides guidance on how to structure the intervention-specific details. This integrated approach creates a comprehensive protocol framework that addresses both macroscopic trial design and microscopic intervention specifics.

Practical Application in Nutrition RCT Protocols

Mapping TIDieR Elements to SPIRIT 2025 Requirements

The practical integration of SPIRIT and TIDieR involves systematically mapping TIDieR's comprehensive intervention description items to specific SPIRIT checklist requirements. This mapping creates a structured approach to intervention reporting that satisfies both guidelines while enhancing protocol completeness. For nutrition RCTs, this integration ensures that complex dietary interventions are described with sufficient detail to enable faithful replication and accurate interpretation of results.

Table 1: Mapping TIDieR Items to SPIRIT 2025 Requirements for Nutrition RCTs

TIDieR Item	Relevant SPIRIT 2025 Section	Integration Strategy for Nutrition RCTs
Why (Rationale)	Introduction: Background and rationale (Item 9a)	Expand scientific justification with nutrition-specific evidence for intervention approach
What (Materials)	Methods: Interventions (Item 16)	Detail specific foods, supplements, dietary patterns with composition data
What (Procedures)	Methods: Interventions (Item 16)	Describe dietary counseling methods, meal preparation, delivery systems
Who (Provider)	Methods: Interventions (Item 16)	Specify qualifications of dietitians, nutritionists, food service staff
How (Delivery mode)	Methods: Interventions (Item 16)	Document individual/group sessions, telehealth, feeding provisions
Where (Location)	Methods: Interventions (Item 16)	Clarify clinical, community, or home-based intervention settings
When/How Much (Dosage)	Methods: Interventions (Item 16)	Define intervention duration, frequency, intensity, follow-up period
Tailoring	Methods: Interventions (Item 16)	Describe personalized nutrition approaches, cultural adaptations
Modifications	Methods: Interventions (Item 16)	Plan for protocol adjustments during trial with documentation process
How Well (Adherence)	Methods: Data collection (Item 25)	Specify dietary assessment methods, compliance monitoring, biomarker verification

This mapping demonstrates how TIDieR items provide the substantive content needed to fully address SPIRIT's requirements for intervention description. The EMBOLDEN trial protocol provides a practical example of this integration, describing a multifaceted intervention incorporating physical activity, healthy eating, and social participation while following SPIRIT guidelines [21]. The protocol details specific nutritional components alongside other intervention elements, demonstrating how complex, multi-domain interventions can be comprehensively documented within the SPIRIT framework.

Methodological Considerations for Nutrition Interventions

Nutrition RCTs present unique methodological challenges that necessitate careful application of the SPIRIT-TIDieR integrated framework. Unlike pharmaceutical interventions with standardized manufacturing and dosing, nutrition interventions involve complex biological matrices, variable composition, and diverse implementation contexts that influence both efficacy and reproducibility.

First, intervention specificity requires precise documentation of nutritional composition that goes beyond generic descriptions. Using TIDieR's "what" (materials) guidance, researchers should specify exact food sources, nutrient profiles, growing conditions, processing methods, preparation techniques, and storage conditions that may modify biological effects. This precision enables accurate interpretation of trial outcomes and facilitates replication across different settings and populations.

Second, control group design demands careful attention to comparator descriptions. The SPIRIT 2025 update specifically emphasizes the explanation for choice of comparator (Item 9b) [19], while TIDieR requires equal detail for both experimental and comparator interventions [12]. For nutrition RCTs, this might involve detailing placebo composition, wait-list control conditions, attention control activities, or minimal intervention comparators with the same rigor applied to the active intervention.

Third, implementation variability necessitates comprehensive documentation of delivery context and quality assurance measures. The integrated framework should describe staff training protocols, standardization procedures, fidelity monitoring, and adaptation processes that maintain intervention integrity across different sites and populations. This is particularly important for multi-center nutrition trials where regional food availability, cultural preferences, and culinary traditions may require planned flexibility within standardized protocols.

Experimental Protocols and Methodologies

Protocol Development Workflow

Developing a nutrition RCT protocol using the integrated SPIRIT-TIDieR framework follows a systematic workflow that ensures both comprehensive protocol structure and granular intervention detail. This methodology transforms protocol development from an unstructured writing process to a systematic documentation exercise that addresses all critical elements of trial design and intervention specification.

The workflow begins with establishing the SPIRIT foundation, including defining the scientific rationale and trial methodology based on SPIRIT's administrative and introduction sections [19]. This foundation establishes the trial's overarching structure, eligibility criteria, outcome measures, and statistical approach. The second phase focuses on intervention specification using TIDieR's comprehensive framework to characterize what the intervention entails, how it will be implemented, and how adherence will be monitored [12]. The final integration phase maps TIDieR elements to corresponding SPIRIT sections, verifies completeness against both checklists, and incorporates external feedback through peer review or stakeholder engagement.

Key Research Reagent Solutions for Nutrition RCTs

Nutrition RCTs require specialized "research reagents" - standardized tools, assessments, and materials that ensure methodological rigor and intervention fidelity. These reagents represent the practical implementation of the SPIRIT-TIDieR integrated framework by providing concrete methods for executing and monitoring the intervention as planned.

Table 2: Essential Research Reagent Solutions for Nutrition RCT Protocols

Reagent Category	Specific Tools/Methods	Function in Nutrition RCT	SPIRIT-TIDieR Alignment
Dietary Assessment	24-hour recalls, Food frequency questionnaires, Food diaries	Quantify dietary intake and compliance	Supports adherence monitoring (TIDieR) and outcome assessment (SPIRIT)
Biomarker Verification	Blood nutrients, Metabolomics, Nutritional biomarkers	Objectively verify intervention compliance and biological effects	Provides objective adherence measures (TIDieR) and secondary outcomes (SPIRIT)
Food Composition Data	USDA SR, Local food databases, Laboratory analysis	Standardize nutrient composition of interventions	Enables precise intervention description (TIDieR) and replication (SPIRIT)
Intervention Fidelity Tools	Session checklists, Provider training manuals, Quality assurance protocols	Maintain intervention standardization across sites	Documents implementation quality (TIDieR) and methods rigor (SPIRIT)
Behavior Change Measures	Theory-based questionnaires, Motivational interviewing fidelity tools	Assess mechanisms of action for behavioral nutrition interventions	Captures intervention processes (TIDieR) and mechanistic outcomes (SPIRIT)

These research reagents operationalize the theoretical principles embodied in both SPIRIT and TIDieR guidelines. For example, dietary assessment tools provide the methodological foundation for evaluating intervention adherence (addressing TIDieR's "how well" item) while simultaneously generating data for outcome assessment (addressing SPIRIT's data collection and management items) [19] [12]. Similarly, standardized training manuals for intervention staff ensure consistent implementation across different providers and settings, fulfilling both TIDieR's requirement for describing "who provided" the intervention and SPIRIT's emphasis on standardized procedures.

Implementation Strategies and Best Practices

Structured Approach to Intervention Description

Implementing the integrated SPIRIT-TIDieR framework requires a structured approach to intervention description that moves beyond general statements to operational specifics. For nutrition RCTs, this involves systematically addressing each TIDieR element within the corresponding SPIRIT protocol section, creating a comprehensive narrative that enables both scientific review and practical replication.

Begin with the rationale and theory (TIDieR "why") in the SPIRIT introduction section (Item 9a), explicitly linking the intervention design to theoretical frameworks and prior evidence. For complex nutrition interventions, this should include the rationale for specific dietary components, their proposed mechanisms of action, and how the intervention addresses identified gaps in current literature. The EMBOLDEN trial protocol exemplifies this approach by providing substantial background on mobility, frailty, and social participation before introducing their multifaceted intervention [21].

Progress to procedural specifics (TIDieR "what," "how," "where") within the SPIRIT interventions section (Item 16), providing sufficient detail to enable implementation by different research teams in varied settings. For nutrition interventions, this includes standardized recipes, meal provision systems, counseling protocols, and educational materials. The level of detail should approach what would be required for a clinical dietitian to replicate the intervention in their practice without additional information.

Conclude with evaluation methods (TIDieR "how well") in SPIRIT data collection and management sections (Items 25-27), specifying how adherence will be measured, monitored, and maintained. For nutrition RCTs, this typically involves multiple complementary methods such as self-reported dietary intake, biomarker verification, attendance records, and interventionist ratings of participant engagement.

Navigating Common Implementation Challenges

Several practical challenges emerge when implementing the integrated SPIRIT-TIDieR framework for nutrition RCTs. Anticipating and addressing these challenges proactively enhances protocol quality and facilitates smoother ethical review and implementation.

First, balancing comprehensiveness with conciseness presents an ongoing tension. SPIRIT and TIDieR collectively identify numerous essential elements that must be documented, potentially creating lengthy, complex protocols. To address this challenge, use structured appendices for detailed intervention manuals, recipe books, counseling scripts, and training protocols that are referenced in the main protocol text. This approach maintains readability while ensuring accessibility of comprehensive implementation details.

Second, accommodating necessary flexibility within standardized protocols requires careful planning. Unlike pharmaceutical interventions with fixed formulations, nutrition interventions often require cultural adaptation, individual tailoring, and seasonal menu variations. Document these planned adaptations explicitly in the protocol, distinguishing between prespecified flexibility and unplanned modifications that would constitute protocol deviations. This distinction maintains intervention integrity while acknowledging real-world implementation realities.

Third, addressing resource implications of comprehensive intervention description necessitates strategic planning. Detailed intervention documentation requires substantial upfront investment in manual development, staff training, and fidelity monitoring. However, this investment yields significant returns through enhanced intervention fidelity, more accurate outcome interpretation, and greater potential for knowledge translation. Frame these activities as essential methodological components rather than optional extras in budget justifications and resource planning.

From Theory to Practice: A Step-by-Step Guide to Implementing SPIRIT and TIDieR

The credibility and utility of clinical research are fundamentally rooted in the transparency and completeness of its planning. For randomized controlled trials (RCTs), the study protocol serves as the foundational blueprint, guiding every aspect of the study from conception through execution and analysis. The SPIRIT 2025 Statement (Standard Protocol Items: Recommendations for Interventional Trials) provides an evidence-based framework to ensure trial protocols address all essential methodological, ethical, and administrative elements [4]. This guidance is particularly crucial for nutritional intervention trials, where intervention complexity, variability in delivery, and unique methodological challenges demand exceptionally clear reporting.

Recent evidence underscores the urgent need for improved reporting in nutrition research. A 2024 meta-research study evaluating 200 nutrition and diet-related RCT protocols revealed a concerning overall reporting completeness of only 52.04% against SPIRIT and TIDieR standards [2] [3]. The most frequently omitted items concerned data handling, study monitoring, and public access to protocol documents and statistical code [2]. Such deficiencies impede critical appraisal, replication, and synthesis of evidence, ultimately weakening the foundation of nutritional science and evidence-based practice.

This application note provides detailed guidance for implementing the SPIRIT 2025 checklist specifically for nutrition trial protocols. It integrates complementary guidance from the TIDieR (Template for Intervention Description and Replication) checklist [12] [22] to address the unique descriptive challenges of nutritional interventions. Furthermore, it references the ongoing development of SPIRIT-Nut, an official extension being developed to provide tailored reporting standards for nutritional trials [9]. By adopting these structured approaches, researchers can enhance the rigor, reproducibility, and translational potential of nutrition science.

Key Updates in SPIRIT 2025: Implications for Nutrition Research

The SPIRIT 2025 statement represents a significant evolution from its 2013 predecessor, reflecting a decade of methodological advancement and growing emphasis on research transparency. Developed through a systematic process involving a scoping review, a Delphi survey with 317 participants, and a consensus meeting with 30 international experts, the updated guideline incorporates the latest evidence and user feedback [4]. For nutrition researchers, several key changes are particularly relevant.

The updated checklist consists of 34 minimum items, representing a refinement through the addition of two new items, revision of five, and deletion/merger of five others from the original 33-item list [4]. A major structural change is the introduction of a dedicated Open Science section, which consolidates items critical to promoting access to information about trial methods and results. This includes explicit requirements for sharing the full protocol, statistical analysis plan, and de-identified participant-level data [4]. Given the historical challenges with data sharing in nutrition science, this emphasis provides an opportunity to enhance field-wide transparency.

Substantively, SPIRIT 2025 places additional emphasis on the assessment of harms (safety monitoring) and provides enhanced guidance on describing interventions and comparators, the latter being enriched by integration of key elements from the TIDieR checklist [4]. A notable addition is a new item addressing how patients and the public will be involved in trial design, conduct, and reporting [4]. This recognizes the critical importance of stakeholder engagement in ensuring that nutrition research addresses questions meaningful to patients and communities. The explanatory document strongly recommends using the official SPIRIT 2025 Explanation and Elaboration document alongside the checklist to fully understand the intent and implementation of each item [4].

Critical SPIRIT 2025 Items for Nutrition Trials and TIDieR Integration

Table 1: Essential SPIRIT 2025 Items with Nutrition-Specific Application Notes

SPIRIT 2025 Item Number & Topic	Essential Requirements	Nutrition-Specific Application Notes	Integrated TIDieR Guidance [12] [22]
6a, 11: Intervention & Comparator Description	Rationale, specific ingredients, dosage, administration procedures.	Detail nutritional composition, source/brand, preparation methods, quality control.	TIDieR Items 1-4, 8: Name, rationale, materials, procedures, timing/dose.
12: Outcome Measures	Clearly defined primary/secondary outcomes, measurement tools, timing.	Specify nutritional status biomarkers, dietary assessment methods, validation.	TIDieR Item 9: Describe any tailoring of the intervention to individuals.
18a, 22: Statistical Methods	Pre-specified analysis plan for primary/secondary outcomes, handling of missing data.	Plan for dietary compliance, intake variability, and covariate adjustment.	TIDieR Item 12: Report actual intervention adherence/fidelity.
26-29: Ethics, Monitoring, & Harms	Ethics approval, DSMB, adverse event collection/reporting.	Document nutrition-specific safety issues (e.g., nutrient toxicity, interactions).	TIDieR Items 11-12: Plan and report on intervention fidelity/adherence.
30-34: Open Science & Dissemination	Protocol/data sharing, registration, funding/conflict disclosure.	Share detailed dietary assessment tools, recipe packages, compliance data.	TIDieR Item 3: Provide access to informational materials used.

For nutrition trials, the description of interventions and comparators (Items 6a and 11) demands exceptional detail. The integration of TIDieR checklist elements is crucial here [4]. Beyond simply naming a diet, researchers must document the specific foods and nutrients involved, preparation methods, and strategies to ensure dietary compliance [23]. For supplement trials, this includes detailing the manufacturer, chemical form, bioavailability, and quality control measures. The rationale for chosen nutritional interventions should be grounded in biological mechanisms or previous evidence, as emphasized by TIDieR's "Why" element [22].

The selection and description of outcome measures (Item 12) require similar precision. Nutrition trials often include biomarkers, dietary intake assessments, and clinical outcomes. The protocol should specify the assay methodologies, laboratory quality control, dietary assessment tools (e.g., 24-hour recalls, food frequency questionnaires), and their validity in the study population. Furthermore, the statistical analysis plan (Items 18a, 22) must pre-specify how dietary non-compliance, intake variability, and relevant covariates will be handled analytically [2].

The new Open Science items (30-34) have profound implications for nutrition research. Publicly sharing the full protocol, as enabled by platforms like the EQUATOR Network, reduces selective reporting and facilitates meta-research [14] [2]. Sharing detailed dietary protocols and assessment tools allows other researchers to replicate and build upon nutritional interventions, accelerating scientific progress. The explicit requirement to declare funding sources and conflicts of interest is vital for maintaining trust, especially in nutrition research where funding sources can influence outcomes and perceptions.

Experimental Protocols for Assessing Reporting Completeness

Meta-research studies that evaluate the quality of trial protocols provide valuable methodologies for understanding current reporting practices. The following protocol, adapted from a 2024 study published in Clinical Nutrition, outlines a robust approach for such assessments, which can also serve as a quality assurance checklist for protocol developers [2].

Protocol for a Meta-Research Study on Reporting Completeness

Objective: To assess the adherence of published nutrition and diet-related RCT protocols to the SPIRIT 2025 and TIDieR reporting guidelines and to explore factors associated with higher reporting completeness.

Search Strategy and Data Sources:

• Perform systematic searches in six major bibliographic databases: PubMed, Embase, CINAHL, Web of Science, PsycINFO, and the Global Health Database [2].
• Use a comprehensive search strategy combining terms for "randomized controlled trial," "protocol," and "nutrition" or "diet."
• Apply no language restrictions, and supplement database searches by scanning reference lists of relevant reviews.

Study Selection:

• Include a random sample of 200 published protocols of nutrition and diet-related RCTs.
• Define eligibility criteria: peer-reviewed, full-text protocols of RCTs where the intervention is primarily nutritional (e.g., foods, diets, supplements) aimed at preventing or treating disease or improving health.
• Exclude protocols for non-randomized studies, those where the nutritional intervention is not the primary focus, or protocols unavailable in full text.

Data Extraction Process:

• Develop a standardized, piloted data extraction form based on the SPIRIT 2025 34-item checklist and the TIDieR 12-item checklist [2] [12].
• Extract additional bibliometric and study characteristics: year of publication, journal type, number of authors, trial registration status, declared funding, and self-reported guideline adherence.
• Perform all extractions in duplicate by independent reviewers, with procedures to resolve disagreements through consensus or third-party adjudication.

Data Analysis:

• Calculate an overall reporting completeness score for each protocol as the proportion of fully reported SPIRIT and TIDieR items.
• Calculate the frequency of adequate reporting for each individual checklist item.
• Use multivariable regression analyses to explore associations between protocol characteristics (e.g., publication year, journal type, registration status) and the overall reporting completeness score.

Table 2: Key Findings from a Recent Application of This Protocol [2] [3]

Characteristic	Result (n=200 protocols)	Association with Reporting Completeness
Overall Reporting Completeness	52.04% (±10.78)	Higher scores were associated with protocols published in 2021 vs. 2019.
Lowest Reported SPIRIT Items	Data management (0%), study monitoring, public access to documents.	Associated with the journal's requirement of a reporting guideline checklist.
Lowest Reported TIDieR Item	Materials used for the intervention (35.5%).	Higher in protocols with trial registration and self-declared SPIRIT adherence.
Type of Nutrition Intervention	Supplementation (48%), Foods, Nutrition Education.	Highest scores for food-based interventions (62.2%); lowest for nutrition education (51.9%).
Trial Registration	Majority were registered.	Registered protocols scored significantly higher (58.1%) than non-registered (49.3%).

Visual Workflow for Protocol Development

The following diagram illustrates the integrated process of developing a nutrition trial protocol using the SPIRIT 2025 and TIDieR frameworks, highlighting critical decision points and feedback loops for ensuring reporting completeness.

The Researcher's Toolkit for Nutrition Trial Protocols

Table 3: Essential Resources for Developing SPIRIT 2025-Compliant Nutrition Protocols

Resource Name	Type	Primary Function	Access URL
SPIRIT 2025 Checklist	Reporting Guideline	Core checklist of 34 essential items for trial protocols.	consort-spirit.org [24]
SPIRIT 2025 E&E Document	Explanatory Guide	Detailed explanation and examples for each SPIRIT item.	Published in BMJ, JAMA, Lancet, Nature Medicine [14] [4]
TIDieR Checklist & Guide	Reporting Guideline	12-item checklist for detailed intervention description.	equator-network.org/tidier [12]
EQUATOR Network	Resource Library	Central repository for all reporting guidelines.	equator-network.org [14]
SPIRIT-Nut (Under Development)	Specialized Extension	Forthcoming SPIRIT extension for nutritional interventions.	OSF Project Page [9]
ClinicalTrials.gov	Registry	Primary platform for trial registration and results.	clinicaltrials.gov
Calcitonin Salmon	Calcitonin Salmon for Research|RUO	Research-grade Calcitonin Salmon for metabolic bone disease studies. This product is For Research Use Only (RUO) and is not intended for personal use.	Bench Chemicals
[Sar9,Met(O2)11]-Substance P	[Sar9,Met(O2)11]-Substance P, CAS:110880-55-2, MF:C64H100N18O15S, MW:1393.7 g/mol	Chemical Reagent	Bench Chemicals

The SPIRIT 2025 statement provides a robust, contemporary framework for elevating the quality and transparency of nutrition trial protocols. When integrated with the TIDieR checklist for intervention description, it directly addresses the critical reporting gaps identified in current nutrition research practice, particularly concerning intervention materials, data management, and open science practices [2] [3]. The ongoing development of the SPIRIT-Nut extension promises to offer even more tailored guidance in the future [9].

Adherence to these guidelines is more than a bureaucratic exercise; it is a fundamental component of methodological rigor. By systematically addressing each item in the SPIRIT 2025 and TIDieR checklists, nutrition researchers can produce protocols that facilitate ethical review, improve trial conduct, enable accurate interpretation of results, and allow for meaningful replication and synthesis. This structured approach is essential for building a more trustworthy, cumulative, and impactful evidence base in nutritional science.

The credibility of nutritional science depends on the precise description of interventions, enabling replication, unbiased interpretation of results, and practical application. The Template for Intervention Description and Replication (TIDieR) was developed to address widespread inadequacies in intervention reporting across health research [12]. This guide provides a detailed framework for applying TIDieR specifically to complex nutrition interventions, ensuring they are described with the rigor required for high-quality randomized controlled trial (RCT) protocols developed within the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) framework [25].

The recent update to SPIRIT in 2025 further emphasizes the importance of comprehensive intervention description, reinforcing the synergistic relationship between SPIRIT, which dictates what should be in a trial protocol, and TIDieR, which provides the granular detail on how to describe the intervention itself [25] [26]. This is particularly crucial in nutrition research, where a recent metaresearch study found that only 1.9% of published nutrition RCT protocols mentioned using the TIDieR guideline, highlighting a significant gap in reporting practices [10].

SPIRIT 2025 and TIDieR: A Synergistic Framework for Nutrition RCT Protocols

The SPIRIT 2025 statement provides an updated, evidence-based checklist of 34 minimum items for trial protocols [25]. Its enhanced focus on open science, patient and public involvement, and detailed description of interventions aligns perfectly with the TIDieR checklist's goals. For nutrition researchers, these guidelines should be used in tandem from the protocol development stage.

• Synergy in Application: The SPIRIT checklist mandates the description of interventions in Item 11, while TIDieR expands this into a comprehensive, 12-point checklist that ensures every facet of a complex nutrition intervention is documented. This includes aspects often overlooked in nutrition research, such as the rationale for the intervention, the materials used, and the procedures for tailoring the intervention to individual participants.
• Addressing a Critical Gap: The under-utilization of TIDieR in nutrition research, as evidenced by the low mention rate in published protocols, poses a threat to the field's cumulative knowledge [10]. Adopting this framework mitigates this risk, ensuring that nutrition interventions—from simple supplements to multi-component behavioral counseling—can be understood, replicated, and translated into practice.

Table: Aligning SPIRIT 2025 and TIDieR for Nutrition RCT Protocols

SPIRIT 2025 Section/Item	Corresponding TIDieR Item	Application to Nutrition Interventions
Item 11: Description of Interventions	TIDieR 1-12 (All items)	The TIDieR checklist provides the detailed content required to fully satisfy SPIRIT's requirement for intervention description.
Item 5: Protocol & SAP Access	TIDieR Guide: Publication	Supports TIDieR's recommendation to provide a detailed manual or other materials for replication.
Item 11: Patient & Public Involvement	TIDieR 8 (Tailoring)	Informs how interventions were modified based on participant feedback or needs.
New Open Science Section	TIDieR 12 (Adherence)	Enhances transparency by mandating access to protocols, data, and analysis plans.

The TIDieR Checklist: A Detailed Guide for Nutrition Interventions

The TIDieR checklist comprises 12 essential items. The following section adapts each item for the specific challenges of describing nutrition interventions, providing examples and protocols.

Brief Name and Why

• Item 1: Brief Name: Provide a specific, not generic, name.
  • Example: "Vitamin D3 and Calcium-Fortified Skim Milk Intervention" instead of "Dairy Supplement."
• Item 2: Why (Rationale): Describe the underlying biological, behavioral, or operational principles.
  • Example: "The rationale for combining dietary counseling with a micronutrient-fortified lipid-based supplement is based on the hypothesis that addressing both behavioral barriers and multiple micronutrient deficiencies will synergistically improve linear growth in stunted children, as per the framework proposed by Golden for moderate undernutrition [27]."

What (Materials and Procedures)

• Item 3: What (Materials): Describe all physical materials provided to participants in detail.
  • Protocol: For supplements, specify the product name, manufacturer, batch number, dosage form, and nutrient composition per unit. For food-based interventions, provide recipes, sourcing information, and nutritional analysis.
• Item 4: What (Procedures): Describe each activity performed by participants or interveners, including the intensity, duration, and frequency.
  • Protocol: For dietary counseling, outline the session structure, key messages, behavior change techniques used (e.g., Motivational Interviewing, goal setting), and any educational materials provided.

Table: Describing "What" for Different Nutrition Interventions

Intervention Type	Materials (TIDieR 3)	Procedures (TIDieR 4)
Oral Nutritional Supplement (ONS)	Product: 'Pediasure', Abbott. Two 237mL bottles daily provide 474 kcal, 20g protein, 28.4g carbohydrate, 22.4g fat, and 100% RDI for vitamins A, D, zinc, and iron.	Participants consume one bottle with breakfast and one with dinner for 120 days. Empty bottles are returned for compliance checks.
Dietary Counseling	USDA MyPlate booklet; 3-day food diary forms; digital kitchen scale (Model: OXO 1130800).	Four weekly, 45-minute, one-on-one sessions with a registered dietitian using Motivational Interviewing to set and review personalized goals for fruit/vegetable intake.
Therapeutic Diet (e.g., Mediterranean)	Weekly food box containing olive oil (500mL), nuts (200g), fresh produce; recipe cards.	Participants follow provided recipes for 2 main meals/day. Adherence is measured via a validated 14-item Mediterranean Diet Adherence Screener (MEDAS).

Who, How, and Where

• Item 5: Who Provided: Detail the expertise and training of the interveners.
  • Protocol: "Dietary counseling was provided by one of three Registered Dietitians, each with >5 years of experience in behavioral weight management. All underwent a 2-day training program on the specific counseling protocol and achieved >90% fidelity in mock sessions."
• Item 6: How: Describe the mode of delivery.
  • Example: "The intervention was delivered via individual, face-to-face sessions," or "Supplements were delivered to participants' homes monthly."
• Item 7: Where: Specify the location.
  • Example: "Counseling sessions were conducted in a private room at the community health clinic. Supplement consumption occurred at participants' homes."

When, How Much, and Tailoring

• Item 8: When and How Much: Detail the duration, dose, and intensity.
  • Protocol: "The intervention lasted 12 weeks. The 'dose' of counseling was four 30-minute sessions (total 120 minutes). The 'dose' of the supplement was two servings per day, as per manufacturer's instructions."
• Item 9: Tailoring: Explain if, how, and why the intervention was tailored.
  • Example: "The dietary counseling goals were tailored based on the participant's baseline 24-hour dietary recall. For example, participants with low fruit intake were initially counseled on increasing fruit consumption, while those with high sugar-sweetened beverage intake focused on beverage substitution."

Modifications, Fidelity, and Access

• Item 10: Modifications: Document any changes during the trial.
  • Protocol: "A log was maintained by the research team to record any deviations from the planned intervention protocol, along with the reason for the change (e.g., supply chain issue necessitating a temporary change in supplement brand)."
• Item 11: How Well (Planned Fidelity): Describe how adherence was assessed and enhanced.
  • Protocol: "Adherence to supplement consumption was measured by counting returned empty bottles and via a self-reported daily diary. Participants were considered adherent if they consumed >80% of provided servings. Adherence to counseling was assessed by audio-recording 10% of sessions and scoring them against a fidelity checklist."
• Item 12: How Well (Actual Fidelity): Report the actual adherence data in the results.
  • This is for the final research report, not the protocol, but the methods for measuring it must be planned in the protocol.

Case Study Application: A Pediatric Undernutrition Trial

The SPROUT trial, which evaluated oral nutritional supplements (ONS) with dietary counseling (DC) in Vietnamese children, serves as an excellent model for TIDieR application [27].

Diagram 1: SPROUT Trial Workflow. This diagram outlines the participant flow and key intervention components of the case study RCT. WAZ: Weight-for-age z-score; ONS: Oral Nutritional Supplement; DC: Dietary Counseling.

TIDieR Analysis of the SPROUT Trial

• Brief Name: "Oral Nutritional Supplement with Dietary Counseling (ONS+DC) for Pediatric Undernutrition."
• Why: The rationale was to test the hypothesis that a multi-nutrient ONS, designed to support catch-up growth with ingredients like arginine, vitamin K2, and casein phosphopeptides, alongside DC, would improve anthropometric and functional outcomes more effectively than DC alone [27].
• What (Materials): The ONS was a polymeric formula providing a complete blend of macronutrients and micronutrients, including specific growth-supporting nutrients. The control was the child's "habitual milk." [27].
• What (Procedures) & How Much: The ONS+DC group received two servings of ONS daily for 120 days. Both groups received DC at baseline, day 30, and day 120 [27].
• Fidelity: While not explicitly detailed in the abstract, a robust trial protocol would have included methods for monitoring returned supplement containers and attendance at counseling sessions to measure adherence.

Experimental Protocols for Key Nutrition Trial Components

Protocol 1: Implementing and Monitoring a Supplement-Based Intervention

This protocol provides a step-by-step guide for a blinded supplement trial.

• Blinding and Packaging: The supplement and matched placebo are manufactured, encapsulated, and packaged to be identical. A third-party (e.g., the pharmacy) holds the randomization code.
• Dispensing and Compliance: Participants receive monthly supplies in blister packs or bottles labeled with a unique ID. A medication event monitoring system (MEMS) cap or a daily diary is used to track intake.
• Biomarker Collection: Collect and bank blood/urine samples at baseline, mid-point, and end-line to objectively measure compliance via biomarkers (e.g., serum 25(OH)D for vitamin D, RBC folate for folic acid).
• Adverse Event Monitoring: Implement a standardized system for participants to report any adverse events, which are then assessed for relatedness to the study product.

Protocol 2: Standardizing and Fidelity-Testing Dietary Counseling

This protocol ensures the behavioral intervention is delivered consistently.

• Counselor Training: Develop a detailed intervention manual. Train all counselors and require them to achieve a minimum fidelity score (e.g., >85%) on role-play assessments before seeing participants.
• Fidelity Monitoring: Audio-record a random 10-20% of all counseling sessions. An independent evaluator scores them using a structured checklist aligned with the manual's key elements.
• Ongoing Supervision: Hold weekly group supervision meetings led by a senior investigator to discuss protocol challenges, maintain motivation, and prevent "counselor drift."

The Scientist's Toolkit: Research Reagent Solutions for Nutrition RCTs

Table: Essential Materials and Tools for Complex Nutrition Interventions

Item/Tool	Function in Nutrition RCTs	Example/Specification
Polymeric ONS	Provides a complete blend of macro- and micronutrients to address multiple deficiencies and support growth/function.	Example: A formula with arginine, vitamin K2 (as MK-7), and casein phosphopeptides for bone and linear growth [27].
Biomarker Assay Kits	To objectively measure nutrient status, compliance, and biochemical efficacy.	Examples: ELISA kits for 25(OH)D, ferritin; LC-MS for specific nutrient metabolites.
Dietary Assessment Software	To quantify dietary intake and adherence to dietary prescriptions at baseline and follow-up.	Examples: NDS-R, ASA24; Software for analyzing data from 24-hour recalls or food frequency questionnaires.
Body Composition Analyzers	To measure changes in lean mass and fat mass, beyond simple anthropometry.	Examples: Bioelectrical Impedance Analysis (BIA) devices, DEXA scanners (gold standard).
Standardized Intervention Manual	To ensure consistency and fidelity in the delivery of behavioral (e.g., counseling) interventions.	Contains: Session-by-session scripts, key messages, handouts, and troubleshooting guides for counselors.
Adherence Measurement Tools	To quantify participant compliance with the intervention protocol.	Examples: MEMS caps for supplements, session attendance logs, self-reported diaries, pill counts.
Cbz-L-Trp-OH	Cbz-L-Trp-OH, CAS:7432-21-5, MF:C19H18N2O4, MW:338.4 g/mol	Chemical Reagent
Spinacine	Spinacine, CAS:59981-63-4, MF:C7H9N3O2, MW:167.17 g/mol	Chemical Reagent

Diagram 2: SPIRIT-TIDieR Synergy. This diagram illustrates the complementary relationship between the SPIRIT 2025 guideline for trial protocols and the TIDieR checklist for intervention description, leading to a comprehensively documented study.

The integrity and applicability of randomized controlled trial (RCT) evidence depend fundamentally on the prospective definition of meaningful outcomes. In nutritional sciences, a historical over-reliance on narrow clinical or biomarker status often fails to capture the full impact of interventions on patients' lived experiences. The updated SPIRIT 2025 statement and TIDieR (Template for Intervention Description and Replication) guidelines provide a critical framework for addressing these limitations by emphasizing patient-centered outcomes and comprehensive harm assessment [4] [6]. This guidance is particularly salient for nutrition research, where a recent meta-research study revealed that only 52.0% of diet or nutrition-related RCT protocols adequately report SPIRIT and TIDieR items, with significant gaps in describing outcomes, harms, and intervention materials [28] [2]. This application note synthesizes contemporary reporting standards with methodological protocols to advance the measurement of what truly matters to patients and populations in nutrition research.

Updated Guidelines: SPIRIT 2025 and TIDieR

Key SPIRIT 2025 Enhancements

The SPIRIT 2025 statement reflects a systematic update incorporating the latest evidence and methodological consensus. Developed through a rigorous process involving 317 participants in a Delphi survey and 30 experts in a consensus meeting, the guideline introduces substantive changes to improve protocol completeness [20] [4]. Notable enhancements relevant to outcome and harm assessment include:

• Integration of key items from SPIRIT-Outcomes 2022 and CONSORT Harms 2022 into the main checklist, providing more specific guidance on defining and analyzing outcomes and adverse events [4] [6].
• A new open science section consolidating items critical to promoting transparency, including trial registration and plans for sharing protocols, data, and analytical code [4].
• Explicit requirement for describing patient and public involvement in trial design, conduct, and reporting, ensuring outcome selection reflects patient priorities [20] [6].
• Restructured checklist with 34 items (after additions, revisions, and mergers) that harmonizes wording with CONSORT 2025 for consistent reporting from protocol to results publication [24].

Table 1: Key SPIRIT 2025 Changes Affecting Outcome and Harm Assessment

Modification Type	Specific Change	Impact on Outcome/Harm Assessment
New Items	Open science section; Patient and public involvement	Enhances transparency and relevance of selected outcomes
Revised Items	Integration of SPIRIT-Outcomes & CONSORT Harms extensions	Standardizes methodology for defining, collecting, and analyzing outcomes and adverse events
Structural Changes	Harmonization with CONSORT 2025	Aligns protocol planning with results reporting for clearer audit trail

TIDieR Framework for Nutrition Interventions

The TIDieR checklist extends SPIRIT and CONSORT by providing 12 items to improve the completeness, replicability, and transparent reporting of interventions [2]. For nutrition research, this is particularly crucial as the "materials" item (only 5.5% adherence in nutrition protocols) is essential for replicating dietary interventions and understanding potential mechanisms affecting outcomes and harms [28]. The combination of SPIRIT 2025 and TIDieR provides comprehensive guidance for protocols that fully describe both the intervention and the outcomes it is designed to affect.

Outcome Measurement Framework

Moving Beyond Clinical Status

Traditional nutrition trials frequently prioritize physiological biomarkers (e.g., cholesterol levels, inflammatory markers) or clinical status endpoints. While valuable, these measures alone may not capture changes that patients perceive as meaningful improvements in their daily functioning, well-being, or quality of life. The updated guidelines encourage a multidimensional outcome framework that integrates biological, functional, and experiential dimensions [4] [6].

Table 2: Outcome Domains for Comprehensive Nutrition Trial Assessment

Domain	Traditional Clinical Status Measures	Patient-Centered Supplementations
Physiological	Biomarkers (e.g., blood glucose, vitamin levels), body composition	Symptoms related to biochemical changes (e.g., fatigue, cognitive fogginess)
Functional	Clinical disease status, morbidity events	Physical functioning, activities of daily living, work productivity
Experiential	—	Health-related quality of life, symptom burden, satisfaction with diet
Behavioral	Dietary adherence (biomarkers)	Dietary adherence (self-efficacy, barriers, acceptability)

Implementing Patient-Centered Outcomes

The SPIRIT 2025 statement explicitly requires describing how patients and the public will be involved in trial design, conduct, and reporting [20] [6]. The following workflow diagram outlines a protocol for integrating patient perspectives in outcome selection:

Figure 1: Protocol for developing patient-centered outcome sets in nutrition trials.

Measurement Selection and Timing

SPIRIT 2025 emphasizes precise specification of outcome measurement methods, timing, and metrics [4]. The explanation and elaboration document provides detailed examples for defining:

• Specific measurement instruments with evidence of validity, reliability, and responsiveness in the target population.
• Accurate timing of assessments aligned with biologically plausible and patient-relevant timeframes for change.
• Clear definition of metrics including scales, units, and methods of aggregation (e.g., change from baseline, absolute values, time-to-event).
• Plans for managing multiple timepoints and addressing missing data.

Comprehensive Harm Assessment Protocol

Beyond Traditional Adverse Event Monitoring

Nutritional interventions are often perceived as low-risk, leading to inadequate harm assessment in trials. However, dietary changes and supplements can produce gastrointestinal symptoms, metabolic shifts, nutrient interactions, and psychological impacts. The integration of CONSORT Harms 2022 recommendations into SPIRIT 2025 strengthens protocols by requiring systematic plans for collecting, analyzing, and reporting harm-related data [4] [6].

Implementing Comprehensive Harm Assessment

The following diagram illustrates a comprehensive methodology for harm assessment in nutrition trials:

Figure 2: Comprehensive harm assessment protocol for nutrition trials.

Nutrition-Specific Harm Considerations

Nutrition trial protocols should explicitly address:

• Novel methods for active harm elicitation tailored to the specific intervention (e.g., gastrointestinal symptoms for fiber interventions, flushing for niacin supplements).
• Standardized causality assessment procedures for determining relatedness to nutritional interventions.
• Plans for collecting patient-reported harms to capture symptomatic experiences that may not be observed by clinicians.
• Specific analytical approaches for harm data, which often differs from efficacy analysis (e.g., using absolute risk differences rather than relative measures).

The Scientist's Toolkit: Research Reagent Solutions

Table 3: Essential Methodological Tools for Outcome and Harm Assessment

Tool Category	Specific Instrument/Technique	Application in Nutrition Trials
Patient-Reported Outcome (PRO) Measures	PROMIS (Patient-Reported Outcomes Measurement Information System)	Measures generic health domains (fatigue, physical function) with high validity
Nutrition-Specific PROs	ORTO-15, Nutrition Impact Symptoms questionnaire	Assesses nutrition-specific concerns like orthorexic behaviors or symptom interference with eating
Harm Elicitation Tools	Systematic adverse event questionnaire, Patient-Reported Harms questionnaire	Actively elicits symptomatic adverse events rather than relying on spontaneous reporting
Dietary Adherence Measures	24-hour dietary recalls, food frequency questionnaires, biomarker validation	Objectively measures intervention adherence, critical for interpreting outcomes
Data Management Platforms	REDCap, OpenClinica	Manages complex outcome and harm data with audit trails and regulatory compliance
L-Alanine-15N	L-Alanine-15N Stable Isotope|Research Compound	L-Alanine-15N is a nitrogen-15 labeled amino acid for protein turnover, metabolic, and enzymatic mechanism studies. For Research Use Only. Not for human use.
Fmoc-Val-OH-15N	Fmoc-Val-OH-15N, CAS:125700-35-8, MF:C20H21NO4, MW:340.4 g/mol	Chemical Reagent

Experimental Protocol: Implementing Guideline Recommendations

Outcome Measurement Methodology

Title: Standard Operating Procedure for Multidimensional Outcome Assessment in Nutrition RCTs

Background: This protocol implements SPIRIT 2025 and TIDieR recommendations for comprehensive outcome assessment in nutrition trials, addressing the low (52.0%) reporting completeness found in recent research [28].

Materials:

• Validated measurement instruments (see Table 3)
• Data collection platform (e.g., REDCap)
• Trained research coordinators
• Statistical analysis plan template

Procedure:

• Outcome Selection Phase (3 months)

  • Conduct systematic review of outcomes in similar nutrition interventions
  • Convene patient advisory panel (3-5 patients with lived experience) to identify priority outcomes
  • Draft comprehensive outcome list including physiological, functional, and experiential domains
  • Finalize core outcome set through stakeholder prioritization exercise

• Measurement Refinement Phase (2 months)

  • Select validated instruments for each outcome with demonstrated responsiveness
  • Define precise timing of assessments aligned with biologically plausible change timelines
  • Develop standardized operating procedures for all measurements
  • Pilot test assessment battery for feasibility and patient burden

• Protocol Documentation Phase (1 month)

  • Document all primary, secondary, and exploratory outcomes per SPIRIT 2025 Item 12
  • Specify measurement instruments, timing, and metrics per SPIRIT 2025 Item 13
  • Describe patient involvement in outcome selection per SPIRIT 2025
  • Upload detailed measurement protocols as supplementary documents

Statistical Considerations:

• Pre-specify analytical approach for each outcome in statistical analysis plan
• Define methods for handling missing outcome data
• Specify adjustment for multiple comparisons if applicable
• Plan sensitivity analyses using different outcome metrics

Harm Assessment Methodology

Title: Comprehensive Harm Monitoring for Nutritional Intervention Trials

Background: This protocol addresses the inadequate harm reporting in nutrition trials by implementing CONSORT Harms 2022 recommendations through SPIRIT 2025.

Materials:

• Structured harm elicitation questionnaires
• Causality assessment form
• Severity grading criteria (e.g., CTCAE or nutrition-adapted version)
• Data safety monitoring board charter

Procedure:

• Harm Identification Protocol

  • Implement multiple complementary methods:
    • Spontaneous reporting: Train staff to document all participant complaints without filtering
    • Active elicitation: Administer structured questionnaire at each visit asking about specific symptoms
    • Systematic assessment: Use patient-reported outcome measures for common symptoms
    • Objective monitoring: Schedule laboratory tests and physical examinations for expected harms

• Harm Documentation and Classification

  • Record all potential harms using standardized case report forms
  • Assess severity using predefined grading system
  • Evaluate relatedness to intervention using predefined algorithm
  • Document expectedness based on existing literature

• Analysis and Reporting Plan

  • Pre-specify analytical approach in statistical analysis plan:
    • Present absolute risks for each intervention group
    • Use appropriate descriptive statistics for harm data
    • Account for recurring events and variable follow-up times
  • Establish data safety monitoring board with predefined stopping guidelines
  • Plan for transparent reporting of all harms regardless of relatedness

Adherence to the updated SPIRIT 2025 and TIDieR guidelines addresses critical deficiencies in nutrition trial protocols, particularly in defining meaningful, patient-centered outcomes and implementing comprehensive harm assessment. The methodologies and protocols presented provide actionable guidance for researchers to enhance the relevance, transparency, and ethical rigor of nutrition intervention studies. By moving beyond narrow clinical status to incorporate the patient experience throughout the outcome assessment process, nutrition science can generate evidence that truly informs clinical practice and public health policy while meeting the highest standards of research integrity.

Incorporating Open Science and Patient Involvement as per SPIRIT 2025

The SPIRIT 2025 statement represents a significant evolution in the standards for clinical trial protocol development, introducing substantial enhancements to promote research transparency and patient-centered design. This update, developed through international consensus incorporating input from methodologies, statisticians, journal editors, and patient contributors, responds to the evolving landscape of randomized controlled trials (RCTs) by strengthening guidance on open science practices and patient involvement [4]. For nutrition researchers, these updated guidelines provide a critical framework for addressing the unique methodological challenges in nutritional interventions, which often involve complex blinding procedures, dietary adherence monitoring, and standardization of interventions across diverse settings.

The impetus for this update stemmed from persistent evidence that trial protocols often lack completeness in reporting key elements, despite the foundational role protocols play in study planning, conduct, and external review [11]. Empirical studies specific to nutrition research have confirmed these reporting gaps, revealing an average reporting completeness of only 52.0% (SD = 10.8%) in nutrition and diet-related RCT protocols published in 2019 and 2021 [1]. The updated SPIRIT 2025 checklist aims to address these deficiencies through structured guidance that promotes methodological rigor while accommodating emerging best practices in trial transparency and stakeholder engagement.

Core Principles and Key Updates in SPIRIT 2025

Structural Revisions and Harmonization

The SPIRIT 2025 statement introduces several foundational changes to the protocol guideline structure, most notably through the creation of a dedicated open science module that consolidates items critical to promoting access to trial information [29] [4]. This restructuring aligns with international movements toward greater research transparency and reproducibility. Additionally, the update involved careful harmonization with the concurrently developed CONSORT 2025 statement to ensure consistent terminology and reporting recommendations across both the protocol and results reporting phases of trials [30] [4]. This coordinated approach reduces confusion for researchers and promotes more seamless translation from planned methods to reported outcomes.

The updated guideline comprises a 34-item checklist (an expansion from the previous version) that includes two entirely new items, substantial revisions to five items, and the deletion or merger of five other items [4] [31]. This refinement process was informed by a comprehensive evidence synthesis, including a scoping review of literature from 2013-2022, analysis of user feedback, and incorporation of recommendations from key SPIRIT and CONSORT extensions covering harms, outcomes, and non-pharmacological treatments [30] [4].

Enhanced Emphasis on Intervention Description

SPIRIT 2025 strengthens requirements for describing interventions and comparators, integrating elements from the TIDieR (Template for Intervention Description and Replication) guideline to ensure comprehensive reporting of intervention details [4]. This enhancement is particularly relevant for nutrition trials, where interventions often involve complex dietary regimens, specialized foods, or behavioral components that require meticulous description to enable replication. The updated guidance specifies that protocols must provide sufficient details to allow replication, including how, when, and by whom interventions will be administered, and should reference where additional materials describing the intervention can be accessed [11].

Table 1: Key Updates in SPIRIT 2025 Relevant to Nutrition RCTs

Update Category	Specific Changes	Relevance to Nutrition Research
New Items	Patient and public involvement; Data sharing	Essential for complex dietary interventions; Enables secondary data analysis of nutrition studies
Revised Items	Intervention description; Harms assessment; Outcomes	Critical for standardized nutrition interventions; Important for documenting nutritional adverse effects
Open Science Section	Trial registration; Protocol access; Data sharing	Promotes transparency in nutrition science; Facilitates meta-research
Restructured Guidance	Harmonization with CONSORT 2025	Ensures consistency from protocol to publication

Practical Application: Implementing the Open Science Module

The newly consolidated open science section in SPIRIT 2025 addresses growing demands for greater research transparency and encompasses several critical elements that nutrition researchers must now explicitly address in their protocols.

Data Sharing Plans

SPIRIT 2025 introduces specific requirements for describing plans to share individual de-identified participant data, statistical code, and other research materials [11] [4]. For nutrition researchers, this represents an opportunity to facilitate secondary analyses exploring diet-disease relationships across diverse populations and settings. A compliant data sharing plan should specify:

• Where de-identified data will be accessible (e.g., repository names)
• How data can be accessed (e.g., through a data request portal)
• What materials will be available (e.g., data dictionaries, statistical code, intervention manuals)
• Any restrictions on data access and the approval process for requests

Nutrition studies often collect sensitive dietary intake data, so protocols should also describe methods for protecting participant confidentiality while enabling appropriate data sharing.

Protocol and Statistical Analysis Plan Accessibility

The updated guideline emphasizes that the full protocol and statistical analysis plan should be accessible, typically through deposition in public repositories or institutional websites [11]. This requirement helps mitigate selective reporting and facilitates methodological review. For nutrition RCTs, which often involve complex randomization schemes and multiple secondary outcomes, making detailed statistical plans publicly accessible enhances credibility and allows peer reviewers to assess the appropriateness of planned analyses before study completion.

Enhanced Registration and Dissemination Policies

SPIRIT 2025 maintains and strengthens requirements for trial registration, specifying that protocols should include the trial registry name, identifying number, and date of registration [11]. Additionally, the updated guideline expands dissemination policies to include plans for communicating results not only to traditional academic audiences but also to trial participants, healthcare professionals, and the public through mechanisms such as plain language summaries [11] [4]. For nutrition research, which often has direct implications for public health guidance, these enhanced dissemination requirements promote broader translation of findings to practice.

Table 2: SPIRIT 2025 Open Science Requirements and Implementation Examples

Requirement	SPIRIT Item	Implementation Examples for Nutrition Researchers
Trial Registration	Item 4: Registry name, number, and date	ClinicalTrials.gov; WHO primary registries; Registration before first participant enrollment
Protocol Access	Item 5: Access to full protocol and statistical analysis plan	Institutional website; Repository (e.g., Open Science Framework); Supplemental materials
Data Sharing	Item 6: Plan for sharing de-identified data	Restricted-access repository; Data use agreements; Anonymization procedures
Dissemination Policy	Item 8: Plans to communicate results to various audiences	Plain language summaries; Participant newsletters; Professional guideline development

Methodological Guidance: Patient and Public Involvement in Nutrition Research

Incorporating Patient Perspectives Throughout the Trial Lifecycle

SPIRIT 2025 introduces a new checklist item (Item 11) specifically addressing patient and public involvement, requiring protocols to detail how patients or public contributors will participate in trial design, conduct, and reporting [4]. This formal recognition of stakeholder engagement represents a significant shift toward more patient-centered research practices. For nutrition studies, which often involve complex dietary changes with substantial participant burden, meaningful patient involvement can improve trial feasibility, relevance, and participant retention.

The explanation and elaboration document for SPIRIT 2025 provides specific guidance on implementing this requirement, suggesting that protocols describe:

• The specific roles patients or public contributors will play in trial activities
• The timing and frequency of their involvement throughout the trial lifecycle
• How their input will be collected, considered, and documented
• Resources and support provided to facilitate their participation [11]

Practical Framework for Nutrition RCTs

The following workflow diagram illustrates a systematic approach to integrating patient and public involvement throughout the nutrition RCT lifecycle, aligning with SPIRIT 2025 requirements.

Diagram 1: Patient Involvement Across RCT Lifecycle

Experimental Protocols for Nutrition Research

Standardized Protocol for Assessing SPIRIT 2025 Adherence

Objective: To systematically evaluate the completeness of reporting in nutrition and diet-related RCT protocols using the updated SPIRIT 2025 checklist.

Methods:

• Data Sources: Identify published nutrition RCT protocols through systematic searches of electronic databases (e.g., PubMed, Cochrane Central Register of Controlled Trials)
• Selection Criteria: Include protocols of randomized trials evaluating nutritional interventions with human participants, with no restrictions on publication language or date
• Data Extraction: Develop a standardized data extraction form based on the 34-item SPIRIT 2025 checklist
• Quality Assessment: Assess each protocol for adherence to SPIRIT items using a predefined scoring system
• Statistical Analysis: Calculate overall and item-specific adherence percentages; use multivariable regression to identify factors associated with higher completeness

This methodology builds upon previous research that found nutrition protocols published in 2019 and 2021 had an overall reporting completeness of 52.0% (SD = 10.8%), with significant variability across SPIRIT items [1].

Implementation Protocol for Patient Involvement in Nutrition RCTs

Objective: To establish and evaluate a structured framework for meaningful patient and public involvement in nutrition RCTs, consistent with SPIRIT 2025 requirements.

Methods:

• Stakeholder Recruitment: Identify and recruit patient partners representing the target population for the nutrition intervention
• Integration Plan: Develop a written terms of reference document specifying roles, responsibilities, and frequency of engagement
• Implementation Activities:
  • Protocol Development: Convene patient advisory group to review and provide feedback on proposed interventions, outcome measures, and participant materials
  • Trial Conduct: Involve patient partners in monitoring recruitment and retention, reviewing adverse event reports, and refining data collection procedures
  • Dissemination: Collaborate with patient partners to interpret findings and develop appropriate dissemination products for diverse audiences
• Evaluation: Document the impact of patient involvement on protocol modifications, participant experiences, and result interpretation

Empirical evidence suggests that protocols mentioning SPIRIT adherence showed significantly higher reporting completeness scores (β = 5.15, 95% CI: 2.44-7.86) [1], indicating the potential value of explicitly documenting stakeholder engagement methods.

Table 3: Research Reagent Solutions for SPIRIT 2025 Implementation

Tool/Resource	Function	Application in Nutrition RCTs
SPIRIT 2025 Checklist	Provides minimum item set for protocol content	Foundation for protocol structure; Ensures comprehensive methodological reporting
SPIRIT 2025 Explanation & Elaboration	Offers contextual guidance and reporting examples	Illustrates application of items to complex nutrition interventions; Provides rationale for requirements
TIDieR Checklist	Guides detailed intervention description	Specifies essential elements for reporting dietary interventions, supplements, and behavioral components
CONSORT-Nut Extension	Adapts reporting standards for nutrition trials	Addresses methodology specific to nutritional interventions (under development) [32]
EQUATOR Network Repository	Central database of reporting guidelines	Identifies additional relevant standards for specific nutrition study designs
Clinical Trial Registries	Platforms for protocol registration and results reporting	Meets SPIRIT requirements for transparency; ClinicalTrials.gov; WHO registries

The SPIRIT 2025 statement represents a substantial advancement in trial protocol standards that directly addresses evolving priorities in clinical research, particularly through its strengthened emphasis on open science practices and patient involvement. For nutrition researchers, these updated guidelines provide a critical opportunity to enhance the methodological rigor, transparency, and relevance of dietary intervention studies. By systematically implementing the new requirements—particularly those related to data sharing, protocol accessibility, and meaningful stakeholder engagement—the nutrition research community can address identified deficiencies in current reporting practices and produce more useful, credible, and implementable evidence to inform dietary guidance and clinical practice.

This guide provides a practical framework for writing robust clinical trial protocols in nutrition research, anchored in the SPIRIT 2025 and TIDieR reporting guidelines. Effective protocol design is critical for scientific rigor, ethical conduct, and reliable translation of research findings into practice.

The Reporting Landscape for Nutrition Trial Protocols

Clinical trial protocols serve as the foundational plan for study execution, ensuring methodological rigor, reproducibility, and ethical oversight. Adherence to standardized reporting guidelines like SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and TIDieR (Template for Intervention Description and Replication) is essential for transparency and completeness [33]. The SPIRIT 2025 statement provides an evidence-based checklist of 34 minimum items to address in a trial protocol [20].

However, recent evidence indicates significant room for improvement in nutrition research. A 2024 meta-research study evaluating 200 diet or nutrition-related RCT protocols found an overall reporting completeness of only 52.0% (SD = 10.8%) [1]. Adherence to specific SPIRIT and TIDieR items varied considerably:

Table: Completeness of Reporting in Nutrition RCT Protocols (n=200)

Reporting Item	Adherence Rate	Guideline
Eligibility criteria	98.5%	SPIRIT
Description of intervention	98.5%	TIDieR
Materials used in intervention	5.5%	TIDieR
Data collection methods	0%	SPIRIT

Several factors were positively associated with better reporting completeness: higher number of authors, more recent publication, journal endorsement of reporting guidelines, and self-reported adherence to SPIRIT [1].

Annotated Protocol Examples for Core Nutrition Study Designs

Example: Enteral Nutrition Delivery Trial

Adapted from the Protein Bolus Nutrition (Pro BoNo) Study [34]

Study Title: Protein delivery in intermittent and continuous enteral nutrition with a protein-rich formula in critically ill patients.

Background Annotation: Critically ill patients rapidly develop muscle wasting resulting in sarcopenia, long-term disability and higher mortality. This protocol explicitly identifies the knowledge gap: clinical evidence on achievement of nutritional goals and influence of bolus nutrition on skeletal muscle metabolism in ICU patients is lacking [34].

Objective Annotation (SMART Framework):

• Primary Objective: To compare the time until the daily protein target (≥1.5 g protein/kg bodyweight/24 h) is achieved within 36 hours between intermittent and continuous enteral feeding.
• Secondary Objectives: To assess tolerance of enteral feeding and evolution of glucose, urea and IGF-1; to evaluate muscle changes via ultrasound and muscle biopsy.

Methods Annotation:

• Study Design: Prospective randomized controlled proof-of-concept trial.
• Participants: 60 critically ill patients recruited during first 48 hours after ICU admission.
• Intervention Groups: Intermittent enteral feeding (30-60 min period) versus continuous enteral feeding.
• Rationale: Bolus nutrition may provide metabolic benefits through increased muscle protein synthesis due to higher leucine peaks [34].

Table: Key Methodological Elements in Nutrition Trial Protocols

Protocol Section	Essential Elements	SPIRIT/TIDieR Alignment
Introduction	Scientific background, rationale, specific hypotheses	SPIRIT Item 2a, 2b
Objectives	Specific, measurable, primary & secondary outcomes	SPIRIT Item 5, 6
Intervention	Detailed description of materials, procedures, timing	TIDieR Items 1-9
Outcomes	Clearly defined primary, secondary outcomes; measurement methods	SPIRIT Item 12
Sample Size	Justification with statistical parameters, power	SPIRIT Item 14
Data Collection	Methods, timing, personnel, blinding procedures	SPIRIT Item 18

Example: Dietary Behavior Modification Trial

Design Framework for Complex Nutrition Interventions

Study Title: Evaluating the effectiveness of a multi-component nutrition education intervention on dietary adherence in prediabetic adults.

Intervention Description Annotation (TIDieR Framework):

• WHAT: Describe both physical materials (food guides, portion tools) and procedures (counseling sessions, cooking demonstrations) in detail.
• WHO: Specify qualifications of interventionists (registered dietitians, health educators).
• HOW: Detail delivery mode (individual vs. group sessions, in-person vs. remote).
• WHERE: Describe intervention settings (clinical, community, home-based).
• WHEN & HOW MUCH: Specify duration, frequency, and intensity of sessions.
• TAILORING: Explain any personalization of the intervention.
• MODIFICATIONS: Document any changes during trial with rationale.

Outcomes Assessment Annotation:

• Primary Outcome: Change in dietary adherence score from validated food frequency questionnaire.
• Secondary Outcomes: Biomarkers (HbA1c, lipid profile), anthropometrics (weight, waist circumference), patient-reported outcomes (quality of life).
• Time Points: Baseline, 3 months, 6 months, 12 months.

Diagram 1: Participant Flow Through Nutrition RCT Stages - This CONSORT-style diagram maps participant progression from assessment to analysis, highlighting potential attrition points critical for validity assessment [35] [36].

Essential Methodological Considerations for Nutrition Protocols

Intervention Implementation Framework

Diagram 2: Nutrition Intervention Implementation Workflow - Systematic approach to ensure consistent intervention delivery and monitoring, addressing common weaknesses in nutrition trial reporting [1].

The Nutrition Researcher's Toolkit

Table: Essential Materials and Methods for Nutrition Trials

Tool Category	Specific Examples	Application in Nutrition Research
Dietary Assessment	Food frequency questionnaires, 24-hour recalls, food diaries, biomarkers	Quantify dietary intake, validate intervention adherence, assess nutritional status
Biological Sampling	Blood, urine, adipose tissue, muscle biopsy	Measure biomarkers, nutrient levels, metabolic responses, genetic markers
Body Composition	DEXA, BIA, anthropometry, MRI/CT	Assess fat/muscle changes, nutritional status, intervention efficacy
Data Collection	Electronic data capture, diet analysis software, mobile health tools	Standardize data collection, enhance quality control, enable real-time monitoring
Intervention Materials	Standardized foods, portion tools, supplement formulations, educational materials	Ensure intervention consistency, enable replication, facilitate adherence

Implementing SPIRIT 2025 and TIDieR in Nutrition Research

The updated SPIRIT 2025 statement incorporates important enhancements for nutrition trial protocols, including new emphasis on open science practices, assessment of harms, detailed description of interventions and comparators, and patient and public involvement in trial design, conduct, and reporting [20].

Key implementation strategies include:

• Use the official SPIRIT 2025 checklist as a protocol writing guide, ensuring all 34 items are adequately addressed [14].

• Integrate TIDieR elements throughout the intervention description, particularly detailing the materials, procedures, and tailoring of nutrition interventions [1].

• Leverage SPIRIT extensions where appropriate (e.g., SPIRIT-Outcomes for patient-reported outcomes, SPIRIT-PRO for patient-centered outcomes) [14].

• Address common weaknesses in nutrition protocols by specifically detailing:

  • Materials used in interventions (only 5.5% adherence) [1]
  • Data collection methods (0% adherence in reviewed protocols) [1]
  • Procedures for monitoring intervention adherence and fidelity

• Engage stakeholders including patients, clinicians, and methodologists in protocol development to enhance relevance and practicality.

By systematically addressing these elements, nutrition researchers can significantly improve the completeness, quality, and ultimate impact of their clinical trial protocols.

Overcoming Common Pitfalls: Optimizing Nutrition RCT Protocols for Real-World Success

The robustness of nutrition science is fundamentally reliant on the quality, transparency, and replicability of its primary evidence, particularly from randomised controlled trials (RCTs). The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement and the TIDieR (Template for Intervention Description and Replication) checklist were developed to provide a framework for complete reporting of trial protocols and interventions, respectively [19] [37]. Adherence to these guidelines ensures that trial methods are meticulously planned and communicated, reducing research waste and enhancing the utility of findings for clinical practice and policy.

However, despite their critical importance, the adoption of these reporting guidelines in the field of nutrition research remains persistently low. A recent meta-research study of 200 nutrition and diet-related RCT protocols revealed that reporting completeness is suboptimal, with protocols failing to fully report over a third of the essential items [2]. This implementation gap undermines the validity and reproducibility of nutrition research, a field characterized by complex interventions and unique methodological challenges. This application note analyzes the root causes of low adoption, presents a quantitative assessment of the current landscape, and provides detailed, actionable protocols to enhance the implementation of SPIRIT and TIDieR guidelines for nutrition RCT protocols.

Quantitative Analysis of Reporting Completeness

Recent empirical evidence highlights specific deficiencies in the reporting of nutrition RCT protocols. The following table synthesizes key findings from a large-scale assessment, pinpointing the areas with the greatest need for improvement.

Table 1: Reporting Completeness of SPIRIT and TIDieR Items in Nutrition RCT Protocols

Reporting Guideline	Specific Item	Reporting Completeness	Key Issue
SPIRIT 2013/2025	Data sharing plans [2]	Very Low	Lack of public access to full protocol, dataset, and statistical code.
	Data management & handling [2]	Very Low	Incomplete description of data entry, coding, security, and storage.
	Study monitoring procedures [2]	Very Low	Insufficient details on frequency and procedures for monitoring trial conduct.
TIDieR	Materials description [2]	Lowest Reported Item	Inadequate details on physical or informational materials used in the intervention.
	Intervention procedures [37]	Often Incomplete	Lack of sufficient detail on procedures, activities, and processes to allow replication.
	Intervention provider expertise [37]	Often Incomplete	Missing descriptions of provider background, expertise, and specific training.

Factors associated with improved reporting include a higher number of authors on the protocol, multicentre trial design, and explicit journal endorsement and requirement of the SPIRIT and TIDieR checklists during the submission process [2]. This quantitative baseline is critical for targeting implementation strategies and measuring future improvement.

Experimental Protocols for Enhanced Guideline Implementation

To address the identified gaps, the following section provides three detailed, executable protocols. These methodologies are designed to be integrated directly into the trial planning and manuscript preparation workflow.

Protocol 1: Integrated SPIRIT-TIDieR Checklist Implementation

This protocol ensures that intervention descriptions within an RCT protocol meet the highest standards of completeness and replicability.

Table 2: Research Reagent Solutions for Protocol Development

Tool / Reagent	Function in Protocol Development
SPIRIT 2025 Checklist [19]	Provides the foundational structure for the entire trial protocol, ensuring all administrative, methodological, and ethical items are addressed.
TIDieR Checklist [37]	Serves as a specialized sub-checklist for the "Intervention and Comparator" section (SPIRIT Item 15), guaranteeing comprehensive description of the intervention.
TIDieR Guide Website (tidierguide.org) [37]	An online authoring tool that guides researchers through completing each TIDieR item, producing a standardized description for inclusion in the protocol.
Digital Adherence Monitoring (e.g., smart bottle caps) [13]	Provides robust, objective data for monitoring adherence to intervention protocols (SPIRIT Item 15c), superior to traditional methods like pill return.

Workflow:

• Foundation: Use the SPIRIT 2025 checklist as the master template for drafting the trial protocol [19].
• Specialization: When drafting Section 15: Intervention and Comparator, do not write free-form text. Instead, complete the 12-item TIDieR checklist first [37].
• Integration: Embed the completed TIDieR description directly into the SPIRIT protocol document under Section 15a. This ensures the intervention is described with sufficient detail to allow replication, including materials, procedures, and tailoring.
• Adherence Strategy: For SPIRIT Item 15c, move beyond "drug tablet return." Specify plans for using digital monitoring technologies where applicable to accurately measure and promote adherence [13].
• Access: For complex interventions, state in TIDieR Item 3 (What-materials) that the full intervention manuals, recipes, or educational materials are available in a supplementary appendix or a publicly accessible repository [2].

Protocol 2: Pre-Submission Peer Review Audit

This protocol uses a structured peer-review process to identify reporting weaknesses before journal submission.

Workflow:

• Checklist Preparation: Distribute the completed protocol draft alongside the official SPIRIT 2025 and TIDieR checklists to internal and external reviewers who were not involved in the drafting process.
• Structured Review: Instruct reviewers to score each checklist item as "Fully Reported," "Partially Reported," or "Not Reported," rather than providing general feedback.
• Gap Analysis: Collate the scores to create a quantitative report of adherence. Focus revision efforts on items most frequently marked as "Partially" or "Not Reported," such as data sharing, monitoring, and intervention materials.
• Contextual Fidelity Assessment: For TIDieR, ensure reviewers comment specifically on Items 9-12 (Tailoring, Modifications, and Fidelity). This captures how the intervention may be adapted while maintaining the core principles of the trial [38].

Protocol 3: Journal-Endorsed Protocol Registry

This protocol leverages trial registries and open science platforms to enforce completeness at the institutional level.

Workflow:

• Mandatory Registration: Institutions and funders should mandate that all RCT protocols are publicly registered before enrolment of the first participant, per SPIRIT Item 4 [19].
• Structured Registry Fields: Trial registries should incorporate key SPIRIT and TIDieR fields as structured, mandatory data entry points, not free text boxes. This includes dedicated fields for:
  • Primary and secondary outcomes with time points (SPIRIT 16).
  • Detailed description of intervention materials and procedures (TIDieR 3 & 4).
  • Data sharing plan (SPIRIT 6).
• Protocol Hosting: The final, approved protocol PDF and statistical analysis plan (SPIRIT Item 5) must be uploaded and linked directly to the trial registration record, making it accessible to reviewers, editors, and the public [19] [11].

Visualization of Implementation Strategy

The following diagram illustrates the integrated workflow and stakeholder interactions required for successful guideline implementation, from protocol development to final publication.

The persistently low adoption of SPIRIT and TIDieR guidelines in nutrition research is a multi-factorial problem requiring a concerted solution. The protocols outlined herein provide a concrete path forward. The integrated checklist protocol directly tackles the most common reporting flaws related to intervention description. The pre-submission audit empowers research teams to proactively improve their work, while the registry-based protocol embeds completeness into the research infrastructure.

Successful implementation, however, ultimately depends on a collective effort. Researchers and trialists must take ownership of applying these guidelines rigorously. Journal editors must move beyond merely "endorsing" guidelines to actively enforcing their use during the peer-review process, potentially employing automated checks for checklist submission. Funders and institutions play a crucial role by making adherence a condition of funding and providing the necessary training and infrastructure for protocol registration and data sharing [2].

The updated SPIRIT 2025 statement, with its enhanced focus on open science, patient involvement, and harms reporting, provides a renewed opportunity to raise the standard of nutrition research [19] [11]. By systematically implementing the strategies described in this application note, the nutrition science community can significantly enhance the transparency, reproducibility, and overall trustworthiness of its evidence base, thereby accelerating the translation of research into effective public health policies and clinical practice.

Managing Protocol Complexity and Avoiding Costly Amendments

Randomized controlled trials (RCTs) in human nutrition present a unique set of methodological challenges that can lead to complex protocols and a high risk of costly amendments. Nutrition research often involves complex behavioral interventions, difficulties with blinding participants, and the need to account for whole-diet approaches rather than single nutrients [39]. These factors increase protocol complexity and the potential for deviations after a trial has begun. The SPIRIT 2025 statement and the TIDieR guideline provide complementary frameworks for enhancing protocol completeness, intervention description, and operational planning, thereby reducing ambiguity that often leads to protocol amendments [25] [22]. Adherence to these guidelines ensures that trial protocols are sufficiently detailed to withstand the complexities of nutrition RCTs while maintaining flexibility for necessary adaptations without requiring formal amendments.

Key Guideline Updates: SPIRIT 2025 and TIDieR

SPIRIT 2025 Enhancements for Comprehensive Protocol Design

The updated SPIRIT 2025 statement provides an evidence-based checklist of 34 minimum items to address in clinical trial protocols, reflecting methodological advances and feedback from users since the original 2013 version [25]. This update places stronger emphasis on open science practices, harms reporting, and patient and public involvement, all of which are particularly relevant for nutrition trials. Key changes include a new open science section covering trial registration, protocol access, and data sharing; enhanced guidance on describing interventions and comparators; and explicit requirements for planning how patients and the public will be involved in trial design, conduct, and reporting [25] [40]. The harmonization between SPIRIT 2025 and CONSORT 2025 ensures consistent guidance from study conception through results publication, facilitating more complete reporting of nutrition trials [26] [40].

TIDieR for Intervention Replication and Adaptation

The Template for Intervention Description and Replication (TIDieR) checklist and guide addresses the critical problem of incomplete intervention descriptions in research publications [22]. Without complete published descriptions of interventions, clinicians and patients cannot reliably implement interventions that are shown to be useful, and other researchers cannot replicate or build on research findings [22]. The 12-item TIDieR checklist provides a structured approach to describing interventions across multiple dimensions: the rationale, materials, procedures, provider roles, delivery modes, location, timing, tailoring, modifications, and planned/actual fidelity [22]. For complex nutrition interventions, TIDieR has been extended to better capture contextual factors and adaptations during implementation, acknowledging that interventions can evolve over time while maintaining documentation of these changes [41].

Table 1: Core SPIRIT 2025 and TIDieR Checklist Items for Nutrition RCT Protocols

Guideline	Key Section	Application to Nutrition RCTs
SPIRIT 2025	Open Science (Items 4-6)	Registration, protocol access, and data sharing for nutrition-specific data
	Intervention Description (Items 14-16)	Detailed nutritional interventions, comparators, and concomitant care
	Harms Reporting (Item 20)	Nutrition-specific adverse events and monitoring
	Patient Involvement (Item 11)	Participant input on dietary interventions and burden
TIDieR	What: Materials & Procedures	Diet composition, food sources, preparation methods
	Who Provides & How	Qualifications of dietitians, delivery methods
	Where, When & How Much	Intervention setting, duration, intensity, dose
	Tailoring & Modifications	Planned and actual adaptations to individual needs

Experimental Protocols for Guideline Implementation

Protocol for Implementing SPIRIT 2025 in Nutrition RCTs

Objective: To systematically apply SPIRIT 2025 items during nutrition RCT protocol development to minimize ambiguities that lead to amendments.

Methods:

• Stakeholder Engagement: Convene a protocol development team including nutrition scientists, statisticians, registered dietitians, methodologists, and patient representatives at the planning stage to address SPIRIT 2025 Item 11 (patient and public involvement) [25].
• Intervention Mapping: Define all essential elements of the nutritional intervention using TIDieR categories, including specific foods, nutrients, dietary patterns, delivery methods, and quality control measures for both intervention and control groups [22] [41].
• Contextual Assessment: Document the implementation context including food procurement systems, cultural dietary preferences, and seasonal food availability that might influence intervention delivery [41].
• Amendment Triggers: Pre-specify thresholds for protocol modifications versus amendments requiring ethics review, distinguishing between adaptations to maintain feasibility versus fundamental design changes [41].

Expected Outcomes: A comprehensive nutrition RCT protocol with reduced ambiguity in intervention description, clearer contingency plans for common nutrition study challenges, and predefined thresholds for implementation adaptations.

Protocol for Process Evaluation in Complex Nutrition Interventions

Objective: To embed process evaluation within nutrition RCTs to explain variability in intervention effects and identify necessary modifications.

Methods:

• Mixed-Methods Design: Combine quantitative measures of intervention delivery (dose, reach) with qualitative exploration of participant experience and contextual influences, adapting the approach used in the SPIRIT process evaluation [42].
• Multi-Domain Data Collection:
  • Domain 1 (Implementation): Document how the nutritional intervention was actually implemented versus intended, including fidelity to prescribed dietary protocols [42].
  • Domain 2 (Participation and Response): Describe how participants engaged with and responded to the dietary intervention, including barriers and facilitators to adherence [42].
  • Domain 3 (Context): Identify contextual characteristics (social, environmental, organizational) that mediated the relationship between intervention and outcomes [42].
• Developmental Evaluation: Incorporate reflective learning at each stage to adapt evaluation questions and methods as the intervention is implemented in different settings [42].

Expected Outcomes: Detailed understanding of how and why nutrition interventions work in different contexts, informing optimal implementation strategies and distinguishing between necessary protocol amendments versus acceptable adaptations.

Table 2: Nutrition-Specific Protocol Elements to Minimize Amendments

Protocol Area	Common Deficiencies	SPIRIT/TIDieR Enhanced Approach
Intervention Description	Vague dietary prescriptions	Detailed TIDieR description: foods, preparation, delivery, monitoring
Comparator Groups	Inadequate control diet specification	Active comparator with equal attention	Equal intensity control intervention
Adherence Monitoring	Subjective measures only	Multi-method assessment: biomarkers, diet records, compliance checks
Contingency Planning	Unplanned protocol deviations	Pre-specified adaptation strategies for common issues (e.g., food supply problems)
Context Documentation	Ignored or minimally described	Systematic assessment of organizational and environmental factors

Visualization of Guideline Integration

The following diagram illustrates the integrated application of SPIRIT 2025 and TIDieR guidelines throughout the nutrition RCT lifecycle, highlighting key decision points for preventing amendments.

Nutrition RCT Protocol Management Workflow

The Scientist's Toolkit: Research Reagent Solutions

Table 3: Essential Methodological Tools for Nutrition RCT Protocol Development

Tool Category	Specific Resource	Application in Nutrition RCTs
Reporting Guidelines	SPIRIT 2025 Checklist	Protocol completeness for nutrition trials
	TIDieR Checklist & Guide	Detailed dietary intervention description
	CONSORT 2025 Statement	Trial reporting alignment
Methodological Frameworks	Process Evaluation Framework	Understanding context-intervention interaction
	Developmental Evaluation	Adaptive management of complex interventions
Implementation Tools	Fidelity Assessment Tools	Monitoring adherence to dietary protocols
	Context Assessment Tools	Documenting organizational and environmental factors
	Adaptation Tracking System	Recording modifications during implementation

Managing protocol complexity in nutrition RCTs requires a proactive approach to protocol design that anticipates implementation challenges and builds in flexibility where needed while maintaining scientific rigor. The integrated application of SPIRIT 2025 and TIDieR guidelines provides a structured framework for achieving this balance, emphasizing comprehensive intervention description, contextual awareness, and planned adaptation strategies. By adopting these approaches, nutrition researchers can develop more robust protocols that are resistant to the costly amendments that often derail nutrition trials, ultimately advancing the field through more replicable and implementable dietary interventions.

Enhancing Participant Adherence and Retention in Dietary Interventions

Robustly designed and properly executed randomized controlled trials (RCTs) are the cornerstone of evidence-based nutrition science. The scientific integrity and practical utility of a dietary intervention trial hinge on its ability to maintain high participant adherence and minimize attrition. High rates of non-adherence and dropout introduce bias, reduce statistical power, and can compromise the validity of trial conclusions [43]. The updated SPIRIT 2025 statement provides a foundational framework for designing transparent and complete trial protocols, emphasizing that "readers should not have to infer what was probably done; they should be told explicitly" [4] [25]. Furthermore, the TIDieR checklist (Template for Intervention Description and Replication) offers critical guidance for describing interventions in sufficient detail to allow their replication, a particular challenge in complex dietary studies [12]. This document synthesizes these reporting guidelines with empirical evidence to provide detailed application notes and protocols for enhancing participant adherence and retention in dietary intervention trials, framed within the context of advanced nutrition RCT protocol research.

Key Concepts and Evidence Base

Quantitative Evidence on Adherence and Retention

Data from long-term dietary intervention trials reveal specific patterns and challenges in maintaining participant engagement. The DIRECT trial, a two-year dietary intervention study, provides valuable quantitative insights into adherence dynamics and retention challenges [43].

Table 1: Adherence and Retention Patterns from the DIRECT Trial

Metric	Overall Results	Between-Group Differences	Temporal Patterns
Overall Compliance	85% at 24 months	Low-fat: 90%Mediterranean: 85%Low-carbohydrate: 78% (p=.042)	-
Self-Reported Adherence	81% at month-1 to 57% at month-24	Low-carbohydrate diet had significantly higher adherence than low-fat until month-6	Significant decrease during holidays followed by partial rebound
Attrition Predictors	Higher in women (29% vs 14% men, p=.001) and current smokers (25% vs 14%, p=.04)	Higher baseline BMI (OR=1.11; CI:1.03-1.21) and less weight loss at 6 months (OR=1.20; CI:1.1-1.3) predicted dropout	-
Success Predictors	Greater weight loss at 6 months was main predictor of >5% weight loss at 2 years (OR=1.5; CI:1.35-1.67)	-	-

A Cochrane review of 38 studies involving 9,445 participants further contextualizes these findings, noting that while certain interventions like telephone follow-up, video education, and contracting showed promise in improving some adherence outcomes, results were often inconsistent across studies [44]. The review emphasized the need for longer-term, high-quality studies using more standardized adherence measures.

SPIRIT 2025 and TIDieR Framework Integration

The updated SPIRIT 2025 statement consists of an evidence-based checklist of 34 minimum items for trial protocols, with notable changes including enhanced emphasis on open science, assessment of harms, description of interventions and comparators, and a new item on patient and public involvement [4] [20]. These updates align closely with the challenges inherent in dietary intervention research.

The TIDieR guideline complements SPIRIT by providing a detailed framework for intervention description, specifically addressing the "what, how, who, where, and when" of interventions [12]. For dietary trials, this translates to precise documentation of:

• Dietary prescriptions and nutritional composition
• Food provision methods and monitoring approaches
• Behavioral support strategies and counseling techniques
• Delivery personnel qualifications and training
• Intervention settings and temporal patterns

Methodological Protocols for Enhanced Adherence and Retention

Comprehensive Adherence Assessment Protocol

Objective: To implement a multi-dimensional framework for monitoring and assessing participant adherence to dietary interventions throughout the trial lifecycle.

Table 2: Multi-Method Adherence Assessment Framework

Assessment Method	Frequency	Metrics	Implementation Considerations
Dietary Recalls (24-hour)	Baseline, 3, 6, 12, 18, and 24 months	Nutrient intake, food group consumption, adherence score	Use automated analysis tools; train staff in standardized probing techniques
Biological Compliance Biomarkers	Baseline, 6, 12, and 24 months	Fatty acid profiles, urinary sodium, metabolites	Align biomarkers with specific dietary prescriptions; account for analytical variability
Food Provision/Supplement Logs	Weekly for food provision; daily for supplements	Proportion of provided foods consumed; supplement counts	Implement digital tracking systems with reminder functions
Behavioral Adherence Questionnaires	Monthly for first 6 months, then quarterly	Self-rated adherence, situational challenges, motivational factors	Validate instruments for specific dietary approach; ensure cultural appropriateness

This multi-method approach directly addresses SPIRIT 2025's emphasis on comprehensive outcome assessment and TIDieR's requirement for detailed intervention description and monitoring [4] [12]. The protocol should specify procedures for managing missing adherence data, as emphasized in the updated SPIRIT guidelines [40].

Proactive Retention Strategy Protocol

Objective: To implement evidence-based retention strategies targeting high-risk timepoints and participant subgroups.

High-Risk Period Management:

• Holiday Support Packages: Develop specialized meal plans, coping strategies, and enhanced support during holiday periods identified as high-risk for non-adherence [43]
• Early Success Reinforcement: Implement intensive support during the first 6 months, capitalizing on the finding that early weight loss success predicts long-term retention [43]

Tailored Outreach for High-Risk Subgroups:

• Gender-Specific Approaches: Develop women-specific support groups addressing unique barriers identified in the DIRECT trial [43]
• Smoker Cessation Integration: Offer integrated smoking cessation support for current smokers, who demonstrated 25% attrition versus 14% among non-smokers [43]

This protocol operationalizes the SPIRIT 2025 focus on participant-centered trial design and explicit description of trial conduct procedures [20]. It also addresses TIDieR's emphasis on detailing "how" the intervention is tailored and modified [12].

Visualizing Strategic Frameworks

Dietary Adherence Enhancement Strategy

Participant Retention Workflow

Research Reagent Solutions for Dietary Interventions

Table 3: Essential Methodological Tools for Dietary Intervention Research

Tool Category	Specific Solutions	Research Application	Protocol Integration
Adherence Biomarkers	Erythrocyte fatty acid profiles, Urinary sodium/potassium, Plasma carotenoids, Doubly labeled water	Objective verification of dietary compliance independent of self-report	SPIRIT 2025 Harms Assessment: Document safety monitoring of biomarker collection
Dietary Assessment Platforms	Automated 24-hour recall systems, Digital food photography applications, Blockchain-based food logging	Reduced participant burden and enhanced data quality for adherence monitoring	TIDieR Item 7: Describe "how" adherence is assessed using these tools
Behavioral Support Toolkits	Motivational interviewing protocols, Cognitive behavioral therapy resources, Habit formation guides	Addressing psychological and behavioral barriers to dietary adherence	SPIRIT 2025 Patient Involvement: Detail how patient input shaped support materials
Data Integration Systems	Electronic data capture platforms, API-based biomarker integration, Real-time adherence dashboards	Synthesizing multi-modal adherence data for early intervention	SPIRIT 2025 Data Management: Specify data handling and quality control procedures

Integrating the SPIRIT 2025 and TIDieR frameworks provides a robust methodological foundation for addressing the persistent challenges of participant adherence and retention in dietary intervention trials. The evidence-based strategies outlined in these application notes—including multi-dimensional adherence assessment, proactive retention planning, and systematic intervention description—enable nutrition researchers to design more transparent, reproducible, and ultimately successful clinical trials. By explicitly documenting these elements within trial protocols as mandated by contemporary reporting guidelines, researchers can enhance scientific rigor while generating more clinically meaningful evidence for nutritional science. Future methodological development should focus on validating standardized adherence metrics specific to dietary interventions and exploring novel digital technologies for real-time adherence monitoring and support.

Randomized controlled trials (RCTs) are fundamental to generating evidence for clinical nutrition practice, yet the field faces unique reporting challenges. Nutrition interventions encompass a wide spectrum—from simple supplements and educational programs to complex dietary patterns—each presenting distinct description and replication challenges. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement and the Template for Intervention Description and Replication (TIDieR) checklist provide foundational guidance for protocol development and intervention reporting [12] [45]. However, recent evidence reveals significant gaps in how these guidelines are applied in nutrition science, with overall reporting completeness in nutrition RCT protocols at just 52.0% [1]. This deficiency underscores the urgent need for tailored application notes to improve the transparency, reproducibility, and quality of nutrition intervention research.

The landscape of nutrition research is diverse and expanding. An analysis of 1,068 published nutrition and diet-related RCT protocols revealed that supplementation interventions (37.9%) and nutrition education/counseling (33.1%) represent the most common study types [10]. Each category demands specific reporting considerations that generic guidelines may not adequately address. Furthermore, research transparency practices remain suboptimal, with only a third of journals publishing nutrition protocols endorsing SPIRIT, and fewer than 3% endorsing TIDieR [10]. This article provides detailed application notes and protocols to bridge this gap, offering practical guidance for adapting SPIRIT and TIDieR guidelines to the unique demands of nutrition interventions involving supplements, education, and complex diets.

Quantitative Landscape of Nutrition Intervention Reporting

Current Reporting Completeness and Gaps

Table 1: Reporting Completeness in Nutrition RCT Protocols (n=200)

Reporting Aspect	Completeness Rate (%)	Key Findings
Overall SPIRIT & TIDieR Adherence	52.0 (SD=10.8)	Low overall transparency [1]
Best-reported SPIRIT Item	98.5	Eligibility criteria (n=197) [1]
Poorest-reported SPIRIT Item	0	Data collection methods (n=0) [1]
Best-reported TIDieR Item	98.5	Description of the intervention (n=197) [1]
Poorest-reported TIDieR Item	5.5	Materials used in the intervention (n=11) [1]
Protocols with RCT Registration	94.2	High uptake of registration practices [10]
Protocols with Funding Statements	93.2	Generally well-reported [10]

Factors Associated with Improved Reporting

Table 2: Predictors of Reporting Completeness in Nutrition Protocols

Predictor Variable	Effect on Reporting Completeness (β coefficient)	95% Confidence Interval
Number of Authors	β=0.53	0.28 to 0.78 [1]
Recent Publication Year	β=3.19	0.24 to 6.14 [1]
Journal Requirement of Reporting Guidelines	β=6.50	2.56 to 10.43 [1]
Author Mention of SPIRIT	β=5.15	2.44 to 7.86 [1]

Recent evidence indicates that the number of published nutrition RCT protocols is increasing annually, averaging 103 publications per year between 2012-2022 [10]. This trend reflects growing recognition of protocol publication's importance for research transparency. However, significant opportunities for improvement remain, particularly regarding intervention-specific reporting details essential for replication and synthesis.

Adaptation Protocols for Diverse Nutrition Interventions

Supplemental Interventions

Nutritional supplements represent the most common intervention type in published nutrition RCT protocols (37.9%) [10]. These interventions require precise specification beyond general SPIRIT and TIDieR recommendations to ensure accurate replication and assessment of bioavailability.

Application Notes for SPIRIT Adaptation:

• Item 12 (Outcomes): Beyond specifying primary nutritional biomarkers, precisely define the laboratory methods, assay precision, and timing relative to intervention administration. For nutrients with variable status (e.g., vitamin D), specify seasonal timing considerations.
• Item 11 (Interventions): Detail supplement formulation beyond basic composition: specify chemical forms (e.g., vitamin D3 vs. D2, ferrous sulfate vs. fumarate), delivery matrix (oil-based, powder), excipients that may affect bioavailability, and quality control procedures.
• New Item for Nutrition: Add "Bioavailability Considerations" describing factors that may influence nutrient absorption and metabolism, including participant characteristics (e.g., gastric acidity, genetic polymorphisms) and co-consumption instructions (with/without food, timing relative to other supplements).

TIDieR Adaptation Protocol:

• Materials: Specify manufacturer, batch numbers, quality verification methods, and storage conditions. For natural products, detail standardization methods and biomarker verification.
• Procedures: Describe dosage schedule, administration instructions, compliance assessment methods (pill counts, biomarkers), and procedures for handling missed doses.
• Modifications: Plan for potential formulation changes during the trial with clear protocols for documenting and reporting such changes.

Experimental Protocol for Supplement Interventions:

• Blinding Procedures: Develop matched placebos using identical appearance, taste, and packaging. Document blinding integrity assessment throughout the trial.
• Stability Testing: Conduct ongoing stability testing for sensitive compounds, especially in challenging environmental conditions.
• Bioavailability Assessment: Plan for potential testing of circulating levels, particularly for nutrients with known bioavailability issues (e.g., iron, vitamin B12).
• Adherence Monitoring: Implement multiple adherence measures including self-report, product accountability, and where feasible, biological validation.

Nutrition Education and Counseling Interventions

Group-based nutrition education with behavior change techniques has demonstrated promise for improving healthy eating among community-dwelling older adults [46]. These complex interventions require meticulous description of both content and delivery processes.

Application Notes for SPIRIT Adaptation:

• Item 8 (Trial Design): Specify whether education is delivered individually or in groups, group composition characteristics, and group matching strategies if applicable.
• Item 11 (Interventions): Detail the theoretical framework underlying the intervention (e.g., Social Cognitive Theory, Theory of Planned Behavior) and how it translates to specific educational components.
• Item 5d (Responsibilities): Clearly define educator qualifications, training procedures, and fidelity assessment methods to ensure consistent delivery across providers and sites.

TIDieR Adaptation Protocol:

• Procedures: Document the specific behavior change techniques used (e.g., goal setting, self-monitoring, social support), delivery format (face-to-face, digital, hybrid), session duration and frequency, and interaction style (didactic, facilitative).
• Materials: Describe all educational materials, audiovisual aids, and resources provided to participants. Include information about readability, cultural adaptation, and availability in different languages.
• Tailoring: Specify the extent to which content can be individualized and the protocols for doing so while maintaining intervention integrity.

Experimental Protocol for Education Interventions:

• Standardization Procedures: Develop comprehensive facilitator guides with scripting, timing, and key messaging. Implement train-the-trainer sessions with competency assessments.
• Fidelity Monitoring: Establish systems for direct observation or recording of sessions using structured checklists to assess adherence to protocol.
• Participant Engagement Assessment: Measure attendance, participation levels, homework completion, and qualitative feedback.
• Context Documentation: Record contextual factors that may influence implementation, including setting characteristics and concurrent nutrition initiatives.

Complex Dietary and Whole-Food Interventions

Dietary diversification represents a long-term sustainable strategy for addressing multiple micronutrient deficiencies [47]. These multidimensional interventions present unique replication challenges due to their complexity and contextual dependence.

Application Notes for SPIRIT Adaptation:

• Item 12 (Outcomes): Include both biological outcomes and dietary intake measures using validated assessment methods appropriate for the specific dietary pattern. Specify how dietary adherence will be measured.
• Item 11 (Interventions): Describe the dietary pattern using multiple characterization methods (e.g., food-based guidelines, nutrient composition, dietary indices) and specify allowable individualization.
• Item 7 (Settings): Detail the food provision system (full provision, partial provision, guidance only), food sources, and meal preparation arrangements.

TIDieR Adaptation Protocol:

• Materials: Provide detailed food lists, sample menus, recipes, and meal preparation instructions. Include photographs of portion sizes and meal presentations if relevant.
• Procedures: Describe dietary counseling approaches, monitoring procedures, and strategies for maintaining adherence. Specify handling of special occasions, travel, and individual preferences.
• Modifications: Plan for seasonal food availability changes with predefined substitution protocols.

Experimental Protocol for Complex Dietary Interventions:

• Dietary Assessment: Implement multiple dietary assessment methods (e.g., 24-hour recalls, food frequency questionnaires, food diaries) with appropriate validation.
• Food Provision Standardization: Establish detailed specifications for provided foods, including sourcing, preparation methods, and quality control.
• Adherence Support: Develop comprehensive support strategies including regular counseling, feedback mechanisms, and problem-solving protocols.
• Contamination Prevention: Implement monitoring to detect and document concurrent adoption of other dietary patterns.

Visualization Framework for Guideline Adaptation

Figure 1: Adaptation Framework for Nutrition Intervention Reporting

Table 3: Research Reagent Solutions for Nutrition Intervention Studies

Resource Category	Specific Tools/Resources	Application in Nutrition Research
Reporting Guidelines	SPIRIT Statement, TIDieR Checklist, SPIRIT-Nut Extension (under development) [9]	Ensure comprehensive protocol reporting and intervention description
Dietary Assessment Tools	24-hour recall protocols, Food Frequency Questionnaires, Dietary Diversity Scores [47]	Measure dietary intake and patterns for baseline characterization and outcome assessment
Behavior Change Frameworks	Theoretical Domains Framework, Behavior Change Technique Taxonomy v1 [46]	Design and specify active ingredients in education and counseling interventions
Quality Control Reagents	Certified reference materials, Standard operating procedures for sample handling	Ensure analytical validity of nutritional biomarker assays
Adherence Monitoring Tools	Pill counts, Supplement diaries, Biological compliance biomarkers, Dietary adherence measures	Document intervention fidelity and participant compliance
Data Collection Platforms	Electronic data capture systems, Mobile health applications, Digital dietary assessment tools	Standardize data collection across sites and reduce measurement error

Adapting SPIRIT and TIDieR guidelines for nutrition research requires careful consideration of intervention complexity and context. The protocols and application notes provided here address the most common weaknesses in current nutrition protocol reporting, particularly regarding intervention specification and implementation details. Successful implementation requires attention to several cross-cutting considerations: engaging multidisciplinary teams including nutrition scientists, behavioral psychologists, and dietitians; using validated dietary assessment methods appropriate to the research question; planning for rigorous monitoring of intervention fidelity; and addressing contextual factors that may influence intervention effects. As the field evolves, ongoing development of nutrition-specific reporting extensions, particularly the SPIRIT-Nut guideline currently under development [9], will provide more tailored guidance. By adopting these adapted application notes, nutrition researchers can significantly enhance the transparency, reproducibility, and overall quality of nutrition intervention research, ultimately strengthening the evidence base for dietary recommendations and clinical practice.

Leveraging Technology and AI for Streamlined Protocol Development and Management

The protocol serves as the foundational blueprint for any randomized controlled trial (RCT), guiding study planning, conduct, reporting, and external review. Despite its critical importance, trial protocols frequently suffer from substantial variations in completeness and often fail to adequately address key methodological and ethical elements [4]. This deficiency can lead to avoidable protocol amendments, inconsistent trial conduct, and ultimately, compromised research validity [4]. The recent publication of the SPIRIT 2025 statement marks a significant evolution in protocol guidance, reflecting more than a decade of accumulated evidence and emerging best practices since its initial 2013 release [20] [4]. Simultaneously, the TIDieR (Template for Intervention Description and Replication) checklist provides complementary, detailed guidance for comprehensively describing trial interventions [48].

Within nutritional science, where interventions are often complex and context-dependent, the integration of these guidelines with modern technological tools presents a transformative opportunity. This application note examines how researchers can leverage artificial intelligence (AI) and other digital technologies to enhance adherence to SPIRIT 2025 and TIDieR, thereby streamlining protocol development and management. Such integration is crucial for improving the transparency, reproducibility, and ethical rigor of nutrition research, ensuring that trials provide robust data to inform evidence-based practice and policy [49].

Key Updates in Guideline Frameworks

SPIRIT 2025: Enhanced Protocol Requirements

The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2025 update is the product of a systematic, evidence-based process involving a scoping review, a Delphi survey with 317 participants, and a consensus meeting of 30 international experts [20] [4]. This process led to substantive modifications from the 2013 version, including the addition of two new items, revision of five items, and deletion or merger of five others [4]. The updated statement now consists of a 34-item checklist and a diagram illustrating the schedule of enrolment, interventions, and assessments [4]. Notable enhancements particularly relevant to nutrition research include:

• Open Science Integration: A new dedicated section consolidates items critical to promoting research transparency, including trial registration; sharing of full protocols, statistical analysis plans, and de-identified participant-level data; and disclosure of funding sources and conflicts of interest [4] [40].
• Patient and Public Involvement (PPI): A new item requires protocols to detail how patients and the public will be involved in trial design, conduct, and reporting [4] [49]. This is especially valuable in nutrition research for ensuring the relevance and practicality of dietary interventions.
• Harm Assessment: Enhanced emphasis on the assessment and reporting of harms, integrating key recommendations from the CONSORT Harms 2022 extension [4]. This is crucial for nutritional trials where adverse events, though often minor, must be systematically captured.
• Intervention Description: Strengthened guidance on the description of interventions and comparators, aligning with TIDieR principles to ensure comprehensive replication [4].

TIDieR: Comprehensive Intervention Description

The TIDieR checklist provides a structured framework to improve the completeness of intervention reporting, which is frequently inadequate in trial publications [48]. Its items can be summed to create a summary score (range 0-24) that assesses the completeness of reporting, though its low internal consistency suggests it is best used to discriminate between the least and most detailed reports rather than for fine-grained comparisons [48]. For nutrition RCTs, TIDieR is invaluable for capturing the necessary details of often complex dietary interventions, including:

• The physical or informational materials used
• The procedures, activities, and processes involved
• The qualifications of intervention providers
• The modes, settings, and intensities of delivery

Table 1: Key Updates in SPIRIT 2025 Relevant to Nutrition RCTs

Update Category	Specific Changes	Implications for Nutrition Research
Open Science	New section on data sharing, protocol accessibility, and funding disclosure	Facilitates meta-analyses, reproducibility, and research synthesis in nutrition
Patient Involvement	New item on PPI in design, conduct, and reporting	Enhances relevance and practicality of dietary interventions and outcome measures
Harm Reporting	Enhanced emphasis on harms assessment	Improves safety monitoring of nutritional interventions and supplements
Intervention Description	Strengthened description of interventions and comparators	Aligns with TIDieR for better replication of complex dietary interventions
Ethical Considerations	Integration with 2024 Declaration of Helsinki principles	Strengthens ethical standards, especially for non-physician investigators

Technological Solutions for Protocol Development

AI-Assisted Protocol Authoring and Compliance Checking

Artificial intelligence tools, particularly large language models (LLMs), can significantly accelerate the initial drafting of trial protocols while ensuring comprehensive coverage of SPIRIT 2025 items. AI-powered systems can be trained to:

• Generate protocol templates pre-populated with SPIRIT 2025 section headers and prompts for required information
• Identify omissions or ambiguities in draft protocols against the SPIRIT checklist
• Suggest appropriate methodological language for complex trial designs common in nutrition research
• Flag inconsistencies between different protocol sections (e.g., between sample size justification and statistical analysis plan)

However, recent evidence suggests a note of caution regarding AI productivity claims. A randomized controlled trial examining AI's impact on software development found that experienced developers actually took 19% longer to complete tasks when using AI tools, despite predicting a 24% time savings [50] [51]. This slowdown was attributed to factors including time spent editing and debugging AI-generated code [51]. This finding highlights that while AI tools offer significant potential, their implementation requires thoughtful integration into workflows and consideration of the learning curve, especially for complex, nuanced tasks like protocol development.

Structured Data Capture and Management Systems

Modern electronic data capture (EDC) systems can be configured to directly align with SPIRIT 2025 requirements, creating a seamless pipeline from protocol planning to trial execution. For nutrition RCTs, this might include:

• Dietary Assessment Modules: Digital integration of 24-hour recalls, food frequency questionnaires, or photographic food records that link directly to nutrient analysis databases
• Adherence Monitoring Tools: Component for tracking participant compliance with dietary interventions through mobile apps, biometric sensors, or biomarker collection
• Blinding Preservation: Systems that maintain allocation concealment while allowing for appropriate monitoring of intervention fidelity
• Adverse Event Integration: Automated capture of safety data aligned with SPIRIT 2025's enhanced harms reporting requirements

Table 2: Digital Tools for SPIRIT 2025-Compliant Protocol Management

Technology Tool	Primary Function	SPIRIT 2025 Alignment
AI-Powered Authoring Platforms	Protocol drafting, consistency checking, omission identification	Ensures comprehensive coverage of all 34 checklist items
Electronic Data Capture (EDC) Systems	Structured data collection, management, and storage	Facilitates detailed description of data management plans (Item 19)
Trial Master File (TMF) Systems	Centralized protocol and amendment version control	Maintains audit trail of protocol changes (Item 34)
Agent Interoperability Protocols (A2A)	Enables AI agents to communicate across platforms	Supports complex workflow automation for multi-site nutrition trials

Agent Interoperability for Complex Workflow Management

The emerging Agent2Agent (A2A) protocol, developed by Google with numerous technology partners, provides a standardized framework for AI agents to communicate and collaborate across different platforms and applications [52]. For complex nutrition RCTs, this interoperability could enable:

• Automated Ethics Compliance: AI agents that automatically populate ethics application forms based on protocol content
• Multi-Site Coordination: Synchronization of protocol amendments and implementation processes across different trial sites
• Regulatory Reporting: Automated generation of regulatory documents and submissions based on protocol information
• Participant Engagement: Coordinated communication between systems managing participant recruitment, intervention delivery, and data collection

The A2A protocol is designed to be secure by default, support long-running tasks, and handle multiple modalities—all essential features for the extended duration and complexity of many nutrition trials [52].

Experimental Protocols for Technology Evaluation

Protocol for Evaluating AI-Assisted Protocol Development

Objective: To quantitatively assess the impact of AI tools on the efficiency and quality of nutrition RCT protocol development.

Design: Randomized controlled trial with protocol developers assigned to AI-assisted or standard protocol development groups.

Participants: Experienced clinical trial methodologies and nutrition researchers (n=40).

Intervention: The AI-assisted group uses an AI tool trained on SPIRIT 2025, TIDieR, and nutrition-specific reporting guidelines to develop a protocol for a standardized nutrition RCT scenario. The control group uses standard software and guideline documents.

Primary Outcome: Time to complete a SPIRIT 2025-compliant protocol draft.

Secondary Outcomes:

• Completeness score (percentage of SPIRIT 2025 items adequately addressed)
• TIDieR adherence score (0-24 point scale) [48]
• Quality rating by independent methodology experts
• Participant satisfaction with the development process

Statistical Analysis: Intention-to-treat analysis comparing primary and secondary outcomes between groups using linear regression models adjusted for prior experience with AI tools.

Protocol for Evaluating Digital TIDieR Implementation

Objective: To determine whether a digital TIDieR template improves the completeness of dietary intervention descriptions in trial protocols.

Design: Crossover trial where researchers complete two protocol development tasks with and without the digital template.

Participants: Nutrition researchers with active protocol development responsibilities (n=30).

Intervention: A digital TIDieR template integrated into protocol development software that provides:

• Structured fields for each TIDieR item
• Nutrition-specific examples and prompts
• Automated completeness checking
• Export functionality for inclusion in full protocols

Primary Outcome: TIDieR summary score (0-24) for the intervention description [48].

Secondary Outcomes:

• Time to complete intervention description
• Investigator-rated usability (System Usability Scale)
• Accuracy of intervention replication based on blinded methodological review

Analysis: Paired t-tests to compare TIDieR scores between intervention and control conditions, with thematic analysis of researcher feedback on the digital template.

The Scientist's Toolkit: Research Reagent Solutions

Table 3: Essential Technology Solutions for Modern Protocol Development

Tool Category	Specific Solutions	Primary Application in Protocol Development
AI-Powered Writing Assistants	Custom-trained LLMs on SPIRIT/TIDieR, Grammar checkers with methodology focus	Drafting protocol content, ensuring comprehensive item coverage, consistency checking
Structured Data Platforms	Electronic Trial Master File (eTMF) systems, Protocol templating software	Version control of protocols, structured data capture for key protocol elements
Collaboration Platforms	Shared document workspaces with commenting, Multi-site coordination tools	Facilitating patient and public involvement, team review of protocol drafts
Reference Management	Citation managers with guideline integration, Automated reference checking	Ensuring citation of appropriate methodology references, SPIRIT 2025 papers
Interoperability Protocols	Agent2Agent (A2A) protocol, API integrations	Connecting different systems used in protocol development and management

Implementation Workflow and Integration Framework

Successful implementation of technology for protocol development requires a systematic approach that integrates both human and technical components. The following workflow visualization illustrates the key stages in developing a SPIRIT 2025 and TIDieR-compliant nutrition RCT protocol using modern technological tools:

This workflow emphasizes the iterative nature of protocol development and the points where technology can provide the greatest efficiency gains. Particular attention should be paid to the integration of TIDieR-specific detailing for nutrition interventions, which often require precise description of dietary components, delivery methods, and compliance assessment techniques that differ substantially from pharmaceutical interventions.

The integration of SPIRIT 2025, TIDieR, and modern technology represents a powerful approach to enhancing the quality and efficiency of nutrition RCT protocol development. While AI tools show significant promise, their implementation must be evidence-based and mindful of potential productivity paradoxes, as demonstrated in recent randomized trials [50] [51]. The most effective approach combines the structured guidance of reporting standards like SPIRIT 2025 and TIDieR with appropriately selected technological tools that streamline the authoring, review, and compliance checking processes.

For nutrition researchers, this integration offers the specific advantage of better handling the complexity of dietary interventions through structured digital templates, improved collaboration capabilities for multi-disciplinary teams, and enhanced transparency through open science practices. By adopting these tools and methodologies, the nutrition research community can significantly advance the robustness, reproducibility, and clinical relevance of trial findings, ultimately contributing to more evidence-based nutritional recommendations and public health policies.

Ensuring Excellence: Validating Your Protocol and Demonstrating Regulatory Readiness

For researchers in the field of nutrition science, developing a robust randomized controlled trial (RCT) protocol is the foundational step that determines a study's rigor, reproducibility, and ultimate impact. The protocol serves as the detailed blueprint for study planning, conduct, and reporting, providing the basis for ethical and scientific review. Despite this critical role, studies consistently show that trial protocols often lack completeness, failing to address key elements of design and conduct [4]. This article provides a structured framework for benchmarking your nutrition RCT protocol against the latest international standards, primarily the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement and the TIDieR (Template for Intervention Description and Replication) checklist, to enhance transparency and methodological quality.

The Current Landscape of Nutrition Trial Protocols

Recent metaresearch investigating the scope and methods of nutrition- and diet-related RCT protocols reveals both progress and persistent challenges. An analysis of 1,068 protocols published between 2012 and 2022 shows a promising annual increase in published protocols, supporting growing awareness of research transparency [10]. However, the adoption of reporting guidelines remains suboptimal:

• Only 33.8% of journals publishing these protocols endorsed the SPIRIT guideline.
• Just 32.1% of protocols mentioned using SPIRIT during development.
• The TIDieR checklist was endorsed by only 2.7% of journals and mentioned in a mere 1.9% of protocols [10].

This insufficient adoption of reporting guidelines has tangible consequences. Evaluations of nutritional interventions have found major reporting gaps in materials, procedures, personalization, and modifications of interventions [53]. Such omissions hinder the replication of studies, the accurate assessment of bias, and the effective translation of research findings into clinical practice or public health policy.

SPIRIT 2025: The Updated Gold Standard for Protocols

The SPIRIT statement, first published in 2013, was updated in 2025 through an evidence-based process involving a scoping review, a Delphi survey with 317 participants, and a consensus meeting of 30 international experts [4]. The SPIRIT 2025 statement provides a checklist of 34 minimum items that should be addressed in any clinical trial protocol [54] [4].

Key Updates in SPIRIT 2025

Substantive changes in the 2025 update reflect evolving best practices in clinical trials [4]:

• New Open Science Section: Consolidates items on trial registration, sharing of full protocols, statistical analysis plans, and de-identified data.
• Enhanced Patient and Public Involvement: A new item specifically addresses how patients and the public will be involved in trial design, conduct, and reporting.
• Greater Emphasis on Harms: Strengthened reporting on the assessment and monitoring of adverse events.
• Improved Intervention Description: Offers more detailed guidance on describing interventions and comparators.

Core SPIRIT 2025 Checklist for Nutrition Protocols

Table 1: Key SPIRIT 2025 Sections for Nutrition RCT Protocol Benchmarking

Section	Key Items to Address	Nutrition-Specific Considerations
Administrative	Title, trial registration, version, funding, roles	Declare conflicts of interest with food/ supplement industry [53].
Introduction	Background, rationale, objectives, trial design	Justify choice of comparator (placebo, usual care, active control).
Methods	Study setting, eligibility, interventions, outcomes	Detail intervention composition, delivery, background diet controls.
Statistics	Sample size, blinding, analysis methods	Define statistical approach for complex designs (e.g., crossover).
Ethics	Informed consent, confidentiality, post-trial care	Plan for monitoring nutritional deficiencies or excesses.
Open Science	Data sharing, dissemination policy	Commit to publishing full protocol and sharing data [4].

The TIDieR Checklist: Ensuring Comprehensive Intervention Reporting

For nutrition trials, the TIDieR checklist provides indispensable, granular guidance for describing interventions—an area where reporting is often inadequate [53]. TIDieR complements SPIRIT by focusing specifically on the "what, how, where, and when" of the interventions being studied.

Applying TIDieR to Nutrition Interventions

Table 2: TIDieR Checklist Application for Nutrition RCTs

TIDieR Item	Application to Nutrition Interventions
1. Brief Name	Provide a specific, descriptive name (e.g., "Mediterranean Diet with Enhanced Polyphenols").
2. Why	Describe the rationale and theory behind the intervention's components.
3. What	List all materials (foods, supplements, educational content) and their sources.
4. Procedures	Detail the preparation, delivery, and administration of the intervention.
5. Who	Specify the credentials and expertise of intervention providers.
6. How	Describe the mode of delivery (individual, group, remote).
7. Where	State the location and context (clinic, free-living, controlled lab).
8. When/How Much	Define the duration, intensity, and timing of intervention sessions.
9. Tailoring	Explain if, how, and why the intervention was personalized.
10. Modifications	Document any changes during the trial and the reasons.
11. Fidelity	Plan for assessing and maintaining adherence to the protocol.

Research indicates that nutritional interventions adjacent to bariatric surgery, for instance, were poorly reported, with particular deficiencies in detailing materials, procedures, and intervention modifications [53]. Using TIDieR ensures these critical elements are not overlooked.

A Practical Benchmarking Methodology

This section provides an experimental protocol for systematically evaluating your nutrition RCT protocol against SPIRIT and TIDieR standards.

Phase 1: Document Preparation and Initial Audit

• Compile Documents: Gather the current protocol draft, any related statistical analysis plans, and the approved trial registry entry.
• Conduct Item-Level Audit: Create a spreadsheet with each item from the SPIRIT 2025 and TIDieR checklists. For each item, mark as "Fully Addressed," "Partially Addressed," or "Not Addressed."
• Identify Critical Gaps: Flag items related to primary outcomes, sample size justification, intervention description, randomization, blinding, and analysis plans as high priority.

Phase 2: In-Depth Quality Assessment

• Evaluate Intervention Description: Use TIDieR to assess if another researcher could replicate the intervention exactly. Pay special attention to:
  • Materials: Brand, formulation, and dosage of supplements; recipes for provided meals.
  • Procedures: Step-by-step delivery of dietary counseling or education.
  • Tailoring: How personalization (e.g., calorie levels based on weight) is managed and recorded.
• Assess Outcome Measurement: Ensure primary and secondary outcomes are completely defined, including the specific tool, scale, or assay used, the time point of collection, and the method of aggregation (e.g., change from baseline, final value).
• Review Statistical Rigor: Confirm that the statistical analysis plan includes methods for handling missing data, adherence, and any planned subgroup or sensitivity analyses.

Phase 3: Scoring and Action Plan

• Calculate Completeness Scores:
  • SPIRIT Score = (Number of "Fully Addressed" SPIRIT items / 34) * 100
  • TIDieR Score = (Number of "Fully Addressed" TIDieR items / 12) * 100
• Develop Improvement Plan: For each item not fully addressed, draft a specific revision. Prioritize changes based on their potential impact on the trial's validity, feasibility, and ethical conduct.

The following workflow diagram visualizes this benchmarking process.

The Researcher's Toolkit for Protocol Development

Table 3: Essential Research Reagent Solutions for Nutrition RCT Protocols

Tool / Resource	Primary Function	Access Information
SPIRIT 2025 Checklist	Provides the definitive minimum list of items to include in a trial protocol.	Available via the EQUATOR Network and consort-spirit.org [14].
SPIRIT 2025 E&E Document	Offers detailed explanations, rationale, and examples of good reporting for each checklist item [4].	Published simultaneously in multiple journals (e.g., BMJ, JAMA).
TIDieR Checklist & Guide	Ensures comprehensive description of interventions for replication and application [53].	Available via the EQUATOR Network.
Clinical Trial Registry	Fulfills ethical and journal requirements; establishes trial existence and key dates (e.g., ClinicalTrials.gov).	Multiple international registries available (WHO ICTRP).
CONSORT-Nut Extension (forthcoming)	Will provide nutrition-specific reporting guidance for completed trials, informing protocol design [55].	Expected publication in 2026 [55].

Benchmarking your nutrition RCT protocol against the SPIRIT and TIDieR guidelines is not a mere bureaucratic exercise. It is a critical scientific process that enhances the transparency, reproducibility, and overall quality of your research. The consistent application of these tools addresses the identified weaknesses in current nutrition trial reporting, particularly in the detailed description of complex interventions. As the nutrition science community moves toward higher standards, with active development of a dedicated CONSORT extension for nutrition trials [55], adopting these evidence-based frameworks will ensure your research is methodologically sound, ethically robust, and positioned to make a meaningful contribution to the field.

The Role of Reporting Guidelines in Regulatory and Ethics Committee Submissions

The conduct of human nutrition randomized controlled trials (RCTs) operates within a complex regulatory ecosystem where incomplete protocol documentation can jeopardize both scientific validity and ethical compliance. Reporting guidelines such as SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and TIDieR (Template for Intervention Description and Replication) provide critical frameworks for ensuring comprehensive protocol reporting [5] [12]. These guidelines address unique methodological challenges in nutrition research, including difficulties in blinding interventions, controlling for background diet, and selecting appropriate comparators [8] [55]. The standardized application of these guidelines strengthens both scientific rigor and regulatory compliance by ensuring protocols contain all necessary elements for proper review by institutional review boards (IRBs), data safety and monitoring boards (DSMBs), and regulatory agencies like the US Food and Drug Administration (FDA) [8].

Nutrition RCTs present distinctive regulatory considerations as diet-related interventions span a spectrum from isolated nutrients to whole dietary patterns, each carrying different regulatory implications [8]. The US FDA regulates products based on intent of use, classifying as drugs "articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease" [8]. This definition extends to clinical investigations, creating potential regulatory complexities for nutrition researchers. Proper protocol documentation using SPIRIT and TIDieR frameworks helps establish whether nutrition interventions require Investigational New Drug (IND) applications or qualify for exemptions, particularly for studies evaluating nutritional structure/function effects or disease risk reduction claims [8].

Current Landscape of Nutrition RCT Protocol Reporting

Quantitative Assessment of Reporting Practices

Recent metaresearch reveals significant gaps in the reporting completeness of nutrition and diet-related RCT protocols. A comprehensive analysis of 1,068 protocols published between 2012 and 2022 found that while the annual number of published protocols is increasing, support and mention of relevant reporting guidelines by journals and researchers remains suboptimal [10] [56]. Only 33.8% of journals publishing these protocols endorsed SPIRIT, while 75.3% endorsed CONSORT (Consolidated Standards of Reporting Trials) [10]. Among researchers, just 32.1% of protocols mentioned SPIRIT and a mere 1.9% referenced TIDieR [10].

A separate assessment of 200 diet or nutrition-related RCT protocols found an overall reporting completeness of only 52.0% when evaluated against SPIRIT and TIDieR checklists [1]. Adherence to individual items varied substantially, with eligibility criteria reported in 98.5% of protocols but data collection methods described in 0% [1]. For TIDieR items, while 98.5% provided some description of the intervention, only 5.5% documented materials used in the intervention [1], creating significant barriers to replication and regulatory assessment.

Table 1: Reporting Completeness in Nutrition RCT Protocols

Reporting Aspect	Current Adherence	Key Deficiencies
SPIRIT Mention	32.1% of protocols [10]	Limited awareness among researchers
TIDieR Mention	1.9% of protocols [10]	Rarely used despite relevance to nutrition interventions
Overall Completeness	52.0% (SD = 10.8%) [1]	Inconsistent across protocol sections
Intervention Materials	5.5% of protocols [1]	Critical gap for replicability and safety assessment
Data Collection Methods	0% of protocols [1]	Fundamental methodology missing

Factors Influencing Reporting Quality

Multivariable regression analysis has identified several factors significantly associated with improved reporting completeness in nutrition RCT protocols. Protocols with a higher number of authors [β = 0.53], more recent publication year [β = 3.19], journal requirement of reporting guideline checklists during submission [β = 6.50], and author mention of SPIRIT [β = 5.15] all demonstrated substantially higher reporting completeness scores [1]. These findings suggest that both editorial policies and researcher education are crucial drivers of reporting quality.

SPIRIT and TIDieR Guidelines: Application to Nutrition Research

SPIRIT 2025 Updates and Nutrition-Specific Considerations

The updated SPIRIT 2025 statement provides an evidence-based checklist of 34 minimum items for trial protocols, incorporating key enhancements relevant to nutrition research [5]. Notable changes include a new open science section, emphasis on harm assessment, detailed description of interventions and comparators, and patient involvement in trial design [5]. For nutrition RCTs, these elements address longstanding weaknesses in protocol reporting, particularly regarding intervention specificity and safety monitoring.

The unique complexities of nutrition RCTs necessitate special attention to several SPIRIT items:

• Item 12a: Description of Interventions - Requires detailed specification of dietary interventions, including source, composition, and preparation of foods or supplements [8] [55]
• Item 20: Harms - Essential for monitoring unintended consequences of dietary changes, including nutrient interactions and gastrointestinal effects [57]
• Item 20a: Data Safety and Monitoring Board (DSMB) - Particularly crucial for controlled feeding trials with potentially significant metabolic impacts [8]

TIDieR Checklist for Nutrition Intervention Replication

The TIDieR checklist provides critical guidance for describing nutrition interventions with sufficient detail to enable replication—a common failure in current nutrition research [12]. Key TIDieR items with particular relevance to nutrition science include:

• Materials: Precise specification of food sources, nutrient compositions, and supplement formulations [8]
• Procedures: Detailed protocols for intervention delivery, including feeding environment, supervision, and compliance monitoring [8]
• Modifications: Documentation of any adjustments to interventions during trials, common in long-term dietary studies [12]
• Fidelity: Strategies to ensure adherence to dietary interventions, such as biomarker monitoring and dietary assessment methods [57]

Regulatory and Ethics Submission Framework

Protocol Documentation for Institutional Review Boards

IRB submissions for nutrition RCTs require careful attention to unique ethical considerations arising from dietary interventions. The Common Rule (45 CFR 46 Subpart A) governs federally funded research, but nutrition studies often present distinct challenges in risk assessment [8]. SPIRIT-aligned protocols facilitate comprehensive IRB review by ensuring:

• Risk-Benefit Analysis: Clear documentation of potential risks associated with dietary changes, including nutrient deficiencies, interactions, and metabolic effects [8]
• Participant Safety: Detailed safety monitoring plans, including appropriate biochemical and clinical parameters for specific nutritional interventions [57]
• Informed Consent: Transparent communication of intervention specifics, including food sources, preparation methods, and potential discomforts [8]

Table 2: Essential Protocol Elements for Ethics Committee Approval

Ethical Consideration	SPIRIT/TIDieR Alignment	Documentation Requirements
Risk Assessment	SPIRIT Item 20 (Harms)	Nutrient-specific safety profiles, contraindications, interaction potentials
Intervention Specificity	TIDieR Items 3-8 (Intervention details)	Food sources, compositions, preparation methods, stability data
Safety Monitoring	SPIRIT Item 20a (DSMB)	Biochemical monitoring schedule, adverse event reporting procedures
Participant Burden	TIDieR Item 8 (Procedure details)	Time requirements, dietary restrictions, sample collection demands
Confidentiality	SPIRIT Item 31 (Confidentiality)	Data handling procedures for sensitive dietary and health information

FDA Regulatory Compliance and IND Determinations

Nutrition RCT protocols must establish whether interventions require Investigational New Drug applications under FDA regulations [8]. The FDA's 2013 guidance clarified that studies investigating foods or dietary supplements for disease diagnosis, cure, mitigation, treatment, or prevention generally require INDs, though certain exemptions exist [8]. SPIRIT and TIDieR facilitate regulatory determinations by ensuring protocols contain sufficient information regarding:

• Intervention Characterization: Complete compositional analysis and safety data for dietary components [8]
• Intent of Use: Clear statement of research objectives relative to disease prevention or management [8]
• Target Population: Specific inclusion/exclusion criteria affecting risk assessment [8]

Current exemptions from IND requirements include clinical studies designed to evaluate whether conventional foods or dietary supplements may reduce disease risk (for health claim petitions) and studies assessing nutritional structure/function effects [8]. However, consultation with the FDA is advised when uncertainty exists regarding regulatory status [8].

Experimental Protocols for Guideline Implementation

Protocol Development Workflow for Nutrition RCTs

Diagram 1: Nutrition RCT Protocol Development Workflow

Nutrition-Specific Methodology Documentation

Controlled feeding trials represent some of the most methodologically complex nutrition studies, requiring exceptional detail in protocol documentation. The following experimental protocol outlines key methodological considerations aligned with SPIRIT and TIDieR guidelines:

Protocol Title: Controlled Feeding Trial to Assess [Nutritional Intervention] Effects on [Health Outcomes]

Objectives and Endpoints:

• Primary Objective: To determine the effect of [specific dietary intervention] on [primary endpoint]
• Secondary Objectives: To assess impacts on [secondary endpoints] and evaluate safety/tolerability

Study Design:

• Randomized, [parallel/crossover], [single/multi]-center design
• [Superiority/equivalence/non-inferiority] framework with [duration] intervention period
• [Blinding procedure] with appropriate control intervention

Intervention Description (TIDieR-compliant):

• Materials: [Detailed specification of food sources, compositions, and preparation methods]
• Procedures: [Feeding environment, supervision, compliance monitoring, and contingency plans]
• Modifications: [Criteria and procedures for intervention adjustments during trial]
• Fidelity: [Strategies to maintain intervention integrity throughout study duration]

Participant Safety Monitoring:

• Schedule of safety assessments: [Biochemical, clinical, and anthropometric measures]
• Adverse event reporting procedures: [Documentation, grading, and reporting protocols]
• DSMB charter: [Composition, responsibilities, and stopping guidelines]

Table 3: Essential Resources for Nutrition RCT Protocol Development

Resource Type	Specific Tools	Application in Nutrition RCTs
Reporting Guidelines	SPIRIT 2025 Checklist [5], TIDieR Checklist [12]	Protocol structure and intervention description standardization
Regulatory Guidance	FDA IND Determination Guidance [8], Common Rule (45 CFR 46) [8]	Regulatory compliance and ethics approval
Methodological Resources	CONSORT-Nutrition Extension (in development) [55], Nutrition-Specific SOPs [8]	Nutrition-specific trial design and conduct
Documentation Templates	Controlled Feeding Protocols [8], Supplement Formulation Specs [8]	Standardized documentation of intervention details
Training Modules	Good Documentation Practice Training [8], CITI Program Research Ethics [58]	Staff training for protocol adherence

The systematic implementation of SPIRIT and TIDieR guidelines in nutrition RCT protocols addresses critical gaps in research transparency and regulatory compliance. As the field moves toward specialized reporting guidance with the ongoing development of a CONSORT-Nutrition extension [55], researchers have an unprecedented opportunity to enhance the methodological rigor and credibility of nutrition science. The integration of these frameworks into regulatory and ethics submissions represents not merely a bureaucratic exercise, but a fundamental component of scientific quality that strengthens evidence-based nutrition policy and clinical practice.

The integrity of clinical research is fundamentally rooted in the quality of its foundational document: the study protocol. High-quality protocols, characterized by their completeness and transparency, are crucial for ensuring research reproducibility, ethical conduct, and the eventual reliability of trial results. Within nutrition science, where interventions are often complex and context-dependent, rigorous protocols are especially critical. This document provides application notes and detailed methodologies for systematically measuring the quality of nutrition and diet-related randomized controlled trial (RCT) protocols, framed specifically within the context of adherence to SPIRIT 2025 and TIDieR guidelines.

The recent update to the SPIRIT standard introduces key changes, including a new Open Science section, greater emphasis on harm assessment, and detailed guidance on intervention description and patient involvement [59] [4]. Concurrently, meta-research reveals that despite growing awareness, the adoption and mention of these essential reporting guidelines in nutrition research remain far from ideal [60] [10]. This creates an urgent need for standardized metrics and practical tools to quantify and improve protocol quality, thereby addressing the "credibility crisis" in nutritional science.

Quantitative Landscape of Nutrition RCT Protocol Reporting

Recent empirical studies provide a benchmark for the current state of protocol reporting completeness in nutrition research. A meta-research study of 1,068 published nutrition and diet-related RCT protocols revealed critical insights into transparency practices and guideline adoption [60] [10].

Table 1: Research Transparency Practices in Nutrition RCT Protocols (2012-2022)

Transparency Practice	Frequency (n)	Percentage (%)
Reported RCT registration number	1,006	94.2%
Included funding statement	994	93.2%
Included conflicts of interest statement	952	89.1%
Mentioned SPIRIT guideline	343	32.1%
Mentioned CONSORT guideline	297	27.8%
Mentioned TIDieR guideline	20	1.9%

Furthermore, an in-depth assessment of a random sample of 200 protocols published in 2019 and 2021 measured adherence directly to SPIRIT and TIDieR item-level requirements [1]. The overall average reporting completeness was found to be 52.0% (SD = 10.8%), indicating significant room for improvement. Adherence to specific items varied dramatically:

Table 2: Adherence to SPIRIT and TIDieR Items in Nutrition RCT Protocols

Reporting Guideline Item	Adherence (%)	Frequency (n=200)
SPIRIT: Eligibility criteria	98.5%	197
TIDieR: Intervention description	98.5%	197
TIDieR: Materials used in intervention	5.5%	11
SPIRIT: Data collection methods	0%	0

Multivariable regression analysis from this study identified several factors positively associated with higher reporting completeness scores [1]:

• Higher number of authors (β = 0.53)
• More recent year of publication (β = 3.19)
• Journal requirement of reporting guidelines during submission (β = 6.50)
• Author mention of SPIRIT adherence (β = 5.15)

Core Metrics for Measuring Completeness and Transparency

Assessing protocol quality requires operationalizing abstract concepts into measurable units. The framework below adapts universal data quality dimensions specifically for evaluating clinical trial protocols [61] [62].

Primary Quality Dimensions and Metrics

Table 3: Core Metrics for Protocol Quality Assessment

Quality Dimension	Definition	Quantification Method
Completeness	Degree to which all SPIRIT/TIDieR required data is present.	Percentage of checklist items fully addressed (0-100%).
Consistency	Alignment of information across protocol sections.	Number of internal contradictions (e.g., differing sample sizes).
Validity	Adherence to predefined rules, formats, and standards.	Count of entries violating defined formats or value ranges.
Timeliness	Protocol availability relative to trial commencement.	Time between final protocol approval and first participant enrollment.
Usability	Ease with which information can be understood and applied.	Readability scores, clarity ratings from independent reviewers.

The Assessment Workflow

The following diagram visualizes the systematic workflow for conducting a protocol quality assessment, from initial preparation to final reporting:

Experimental Protocol: Measuring Adherence to SPIRIT 2025 and TIDieR

This section provides a detailed, step-by-step methodology for conducting a systematic assessment of a nutrition RCT protocol's adherence to contemporary reporting guidelines.

Research Reagent Solutions: Essential Materials for Protocol Assessment

Table 4: Essential Tools for Protocol Quality Assessment

Tool Category	Specific Resource	Function in Assessment
Reporting Guidelines	SPIRIT 2025 Checklist (34 items) [4]	Reference standard for minimum protocol content.
Reporting Guidelines	TIDieR Checklist & Guide [12]	Standard for comprehensive intervention description.
Data Extraction Tool	Custom REDCap electronic form [10]	Structured data capture during protocol review.
Statistical Software	R or Python with pandas	Quantitative analysis of completeness scores and metrics.
Reference Management	EndNote, Rayyan [10]	Organizing protocols and facilitating screening.

Step-by-Step Methodology

Step 1: Preparation and Tool Development

• Obtain the official SPIRIT 2025 Checklist (34 items) and the TIDieR Checklist [12] [4].
• Create a data extraction form, ideally using an electronic data capture platform like REDCap, that lists every item from both checklists as a discrete field [10]. For each item, include fields for:
  • Yes/No/Partial response for adherence.
  • A text field for quoting the relevant protocol section.
  • Notes on the quality of reporting.

Step 2: Pilot Testing and Calibration

• Select a random sample of 5-10 nutrition RCT protocols for pilot review.
• Have at least two independent reviewers assess the pilot protocols using the extraction form.
• Calculate inter-rater reliability (e.g., Cohen's kappa) to ensure consistent interpretation of checklist items. A concordance rate >90% is desirable, as achieved in prior meta-research [10].
• Resolve discrepancies through discussion and refine the extraction form and guidance notes accordingly.

Step 3: Systematic Data Extraction

• For each protocol under review, the reviewer systematically goes through the entire document.
• For every SPIRIT and TIDieR item, the reviewer records:
  • Completeness: Whether the item is fully reported (Yes), partially reported (Partial), or not reported (No).
  • Location: The page and section number where the information is located.
  • Direct Quote: The exact text from the protocol that addresses the item.

Step 4: Quantitative Metric Calculation

• Calculate the primary outcome: Overall Completeness Score.
  • Score = (Number of Yes responses + 0.5 * Number of Partial responses) / Total Number of Applicable Items.
  • Multiply by 100 to express as a percentage [1].
• Calculate dimension-specific scores (e.g., Methodology Completeness, Intervention Description Completeness) using the same formula for relevant item subsets.
• Record the frequency of specific, commonly missed items (e.g., "materials used in the intervention") to identify areas for targeted improvement.

Step 5: Analysis and Reporting

• Use descriptive statistics (means, standard deviations, frequencies) to summarize the data.
• Employ linear regression analyses, if comparing multiple protocols, to explore associations between protocol characteristics (e.g., number of authors, journal endorsement of guidelines) and overall completeness scores [1].
• Report findings structured around the SPIRIT 2025 and TIDieR checklists, highlighting both strengths and consistent weaknesses.

Conceptual Framework for High-Quality Nutrition Protocols

The following diagram illustrates the interconnected components and logical flow that underpin a high-quality nutrition RCT protocol, integrating the core principles of SPIRIT 2025 and TIDieR:

Systematically measuring the completeness and transparency of nutrition RCT protocols using SPIRIT 2025 and TIDieR metrics provides an evidence-based pathway to enhance research rigor and reliability. The quantitative data and experimental protocols detailed in these application notes offer researchers, funders, and journals a practical toolkit for elevating protocol quality. Widespread adoption of these assessment practices will strengthen the foundation of nutrition science, ensuring that trial protocols fulfill their role as robust blueprints for generating reliable evidence to inform clinical practice and public health policy.

The Impact of Guideline Adherence on Future Trial Reporting and Publication Success

Within the field of nutritional science, the reliability of evidence generated by Randomized Controlled Trials (RCTs) is foundational for informing clinical practice and public health policy. The protocol phase of an RCT represents a critical juncture where methodological rigor and transparency are established, profoundly influencing the trial's eventual utility and publication success. Adherence to established reporting guidelines such as SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and TIDieR (Template for Intervention Description and Replication) is not merely an administrative formality but a significant determinant of research quality [2] [63]. This application note explores the quantifiable impact of SPIRIT and TIDieR adherence on the reporting completeness and publication outcomes of nutrition RCTs, providing evidence-based protocols for researchers.

Nutrition research faces unique complexities, including the influence of background diet, difficulties in blinding dietary interventions, and the lack of true placebo comparators in many studies [55]. These challenges make comprehensive protocol reporting especially vital. Recent meta-research reveals that nutrition and diet-related RCT protocols suffer from substantial reporting gaps, with an average overall reporting completeness of only 52% when evaluated against SPIRIT and TIDieR standards [3] [2]. This analysis synthesizes current evidence to demonstrate how strict adherence to these guidelines can enhance research transparency, facilitate subsequent publication, and increase the eventual impact of nutritional science.

Quantitative Landscape of Reporting Completeness in Nutrition RCTs

Understanding the current state of reporting completeness provides a crucial baseline for quality improvement initiatives. A meta-research study of 200 nutrition or diet-related RCT protocols published in 2019 and 2021 revealed a concerning landscape of reporting transparency, with significant variations across different aspects of trial design and conduct [3] [2].

Table 1: Overall Reporting Completeness in Nutrition RCT Protocols (n=200)

Reporting Aspect	Average Completeness	Key Findings
Overall SPIRIT/TIDieR Adherence	52.0% (±10.8%)	Majority of protocols miss nearly half of recommended items [3]
Best Reported SPIRIT Items	Up to 98.5%	Item 10 (Objectives) was most consistently reported [3]
Poorest Reported SPIRIT Items	As low as 0%	Item 18a (Data handling and management) was most frequently missing [3]
TIDieR Intervention Description	35.5% - 98.5%	Materials used for intervention was the most incompletely reported TIDieR item [2]

Further analysis reveals that reporting quality is not uniform across all types of nutritional interventions. The complexity and nature of the intervention appear to influence how completely researchers describe their methodological approach.

Table 2: Reporting Completeness by Intervention Type in Nutrition RCTs

Intervention Category	Reporting Completeness	Notable Characteristics
Foods	62.2% (±9.2%)	Highest reporting completeness among intervention types [3]
Supplementation	48.0% prevalence	Most common intervention type in nutrition RCTs [3]
Nutrition Education	51.9% (±9.2%)	Lower reporting completeness despite behavioral complexity [3]

The data indicates that protocols focusing on whole foods interventions achieved superior reporting completeness compared to those investigating nutritional supplements or educational approaches [3]. This discrepancy may reflect the more tangible nature of food interventions or potentially greater methodological rigor in these trials.

Factors Influencing Guideline Adherence and Its Impact on Reporting Quality

Multiple factors significantly influence the degree to which nutrition RCT protocols adhere to SPIRIT and TIDieR guidelines. Understanding these factors helps identify strategic opportunities for improving reporting practices across the research community.

Table 3: Factors Associated with Improved Reporting Completeness in Nutrition RCT Protocols

Influencing Factor	Impact on Reporting Completeness	Statistical Evidence
Protocol Registration	58.1% (with registration) vs. 49.3% (without)	8.8 percentage point increase [3]
Self-Declared SPIRIT Adherence	62.5% (with declaration) vs. 54.7% (without)	7.8 percentage point increase [3]
Journal Mandated Checklist	Significantly higher completeness	Journals requiring guidelines improved reporting [2]
Number of Authors	Positive correlation	More authors associated with better reporting [2]
Year of Publication	59.9% (2021) vs. 56.3% (2019)	3.6 percentage point improvement over time [3]

The most poorly reported items consistently relate to data handling, study monitoring, and accessibility of research materials [2]. Specifically, fewer than 20% of protocols provided information on public access to the full protocol document, dataset, or statistical code [2]. This represents a critical transparency gap that hinders reproducibility and secondary analysis of nutrition research.

Adherence to reporting guidelines shows a clear positive correlation with overall reporting quality. Protocols that explicitly mentioned SPIRIT adherence demonstrated significantly higher completeness scores (62.5%) compared to those that did not (54.7%) [3]. This relationship underscores the value of guideline awareness and implementation for enhancing protocol quality. Furthermore, the temporal improvement between 2019 and 2021 suggests a positive trend toward embracing reporting standards in nutritional science [3].

SPIRIT 2025 Updates: Implications for Nutrition Trial Protocols

The recent update to the SPIRIT guidelines introduces important changes that specifically address some historical weaknesses in trial protocol reporting. The SPIRIT 2025 statement incorporates 34 checklist items, including new sections on open science practices and enhanced emphasis on intervention description and harm assessment [59] [19].

A notable advancement in SPIRIT 2025 is the strengthened focus on intervention and comparator description (Item 15), though some experts have raised concerns about potential softening of adherence monitoring compared to the 2013 version [13]. The updated guidance references "strategies to improve adherence to intervention/comparator protocols" but has removed specific mention of laboratory tests as a monitoring method, focusing instead on drug tablet return and session attendance [13]. For nutrition trials, this highlights the need for researchers to proactively implement and report robust, field-appropriate adherence monitoring strategies, such as biomarker verification for nutritional interventions.

The updated guidelines also introduce a dedicated open science section encompassing trial registration, protocol and statistical analysis plan accessibility, data sharing policies, and dissemination plans [19]. This formalizes expectations for transparency practices that were previously inconsistently addressed in nutrition trial protocols. Given the abysmally low reporting of data sharing statements in current nutrition protocols (under 20%), this represents a significant area for improvement [2].

Experimental Protocols for Assessing and Implementing Guideline Adherence

Protocol 1: Assessment of Reporting Completeness in Nutrition RCT Protocols

Objective: To systematically evaluate adherence to SPIRIT and TIDieR guidelines in a sample of nutrition and diet-related RCT protocols.

Materials and Methods:

• Sample Collection: Identify 200 nutrition or diet-related RCT protocols published within a specified timeframe using databases such as PubMed, Embase, CINAHL, Web of Science, PsycINFO, and the Global Health Database [2].
• Data Extraction Form: Develop a standardized extraction form incorporating all 34 items from the SPIRIT 2025 checklist and 12 items from the TIDieR guideline [2] [63].
• Assessment Procedure: Two independent reviewers assess each protocol, recording whether each checklist item is completely, partially, or not reported. Discrepancies are resolved through consensus or third-party adjudication [3].
• Completeness Scoring: Calculate a proportional reporting completeness score for each protocol: (Number of items reported / Total applicable items) × 100 [3].
• Statistical Analysis: Conduct univariate and multivariate analyses to identify factors associated with reporting completeness, including year of publication, journal type, author numbers, funding source, and stated guideline adherence [2].

Protocol 2: Implementation of SPIRIT 2025 and TIDieR in New Nutrition RCT Protocols

Objective: To ensure comprehensive adherence to SPIRIT 2025 and TIDieR guidelines when developing new nutrition RCT protocols.

Materials and Methods:

• Guideline Resources: Access the official SPIRIT 2025 checklist (34 items) and TIDieR checklist (12 items) from the EQUATOR Network website [14].
• Structured Protocol Development:
  • Administrative Framework: Include all administrative items (Title, protocol version, roles and responsibilities) as per SPIRIT 2025 Items 1-3 [19].
  • Open Science Integration: Implement the open science section (SPIRIT 2025 Items 4-8) including trial registration before participant enrollment, data sharing plans, and dissemination policies [19].
  • Intervention Specification: Utilize TIDieR to describe interventions in complete detail, including materials, procedures, providers, modes of delivery, and adherence monitoring strategies specific to nutrition interventions [63].
  • Methodological Rigor: Clearly describe trial design, eligibility criteria, outcomes, sample size justification, and statistical methods aligned with SPIRIT 2025 Items 12-18 [19].
  • Ethics and Oversight: Detail research ethics approval, monitoring plans, and protocol amendment procedures as per SPIRIT 2025 Items 19-23 [19].
• Quality Assurance: Implement a checklist verification process before protocol finalization, ensuring each SPIRIT and TIDieR item is adequately addressed [2].

The following workflow diagram illustrates the strategic implementation of these guidelines throughout the trial protocol development process:

Table 4: Essential Research Reagents and Resources for Nutrition RCT Protocol Development

Resource Category	Specific Tool/Guideline	Application in Nutrition RCTs
Primary Reporting Guidelines	SPIRIT 2025 Statement (34 items) [19]	Foundation for comprehensive trial protocol structure and content
Intervention Reporting	TIDieR Checklist (12 items) [63]	Detailed description of nutrition interventions for replicability
Field-Specific Extensions	CONSORT-Nut (Under development) [55] [32]	Adaptation for nuances of nutrition trials (e.g., background diet)
Digital Adherence Tools	Smart bottle caps, electronic monitoring [13]	Objective measurement of intervention adherence in supplementation trials
Trial Registration	ClinicalTrials.gov, WHO registries [19]	Public prospect registration to reduce selective reporting bias
Data Sharing Platforms	OSF, ClinicalStudyDataRequest.com [2]	Archive for sharing de-identified data, statistical code, and materials

Adherence to SPIRIT and TIDieR guidelines exerts a substantial and measurable impact on the quality and completeness of nutrition RCT protocols, with cascading benefits for subsequent publication success and research utility. The evidence demonstrates that protocols adhering to these guidelines show significantly higher reporting completeness (62.5% for SPIRIT-declaring protocols versus 54.7% for non-declaring) [3], directly addressing the current inadequacies in nutrition trial reporting where average completeness remains just 52% [2].

The recent SPIRIT 2025 update provides an opportunity to reinforce comprehensive reporting practices, particularly in critical areas such as open science, intervention description, and adherence monitoring [19]. For the nutrition research community, the ongoing development of the CONSORT-Nut extension promises field-specific guidance that addresses unique methodological challenges [55] [32]. By systematically implementing the protocols and resources outlined in this application note, researchers can significantly enhance the transparency, reproducibility, and overall impact of nutrition science, ultimately strengthening the evidence base for dietary recommendations and clinical practice.

The integrity of clinical nutrition research hinges on the quality and transparency of its foundational plans. Randomized Controlled Trials (RCTs) provide the highest quality evidence for validating nutrition and lifestyle interventions [64]. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement provides a structured framework for protocol development, while the TIDieR (Template for Intervention Description and Replication) checklist ensures interventions are described with sufficient detail for replication and clinical application [2]. This case study analyzes the application of these guidelines within nutrition research, a field where interventions are often complex and difficult to blind. Recent evidence indicates that the reporting completeness of nutrition and diet-related RCT protocols remains low, with an average adherence of only 52.0% to combined SPIRIT and TIDieR items [1] [2]. This analysis will dissect the essential components of a high-quality protocol, identify common reporting shortcomings, and provide a blueprint for designing nutrition RCTs that meet contemporary standards of transparency and scientific rigor.

Background: The Need for Reporting Guidelines in Nutrition Research

Nutrition RCT protocols face unique challenges that necessitate rigorous reporting standards. Unlike pharmaceutical trials, nutrition interventions often involve whole foods, complex dietary patterns, and behavioral components, making them difficult to standardize, blind, and replicate [64] [65]. The baseline nutritional status of participants, carry-over effects of interventions, and interactions with the individual's gut microbiota introduce additional layers of complexity that must be meticulously documented in the protocol [65].

Despite the availability of the SPIRIT statement since 2013, key elements of trial protocols are frequently under-reported. A meta-research study of 200 nutrition RCT protocols found that items related to data handling, study monitoring, and public access to the protocol and datasets were most often missing [2]. Similarly, TIDieR items concerning the materials used in the intervention and the procedures for its delivery were reported in only a small minority of protocols [1] [2]. This lack of detail impedes the critical appraisal of trial methods, the replication of interventions in research, and the translation of effective interventions into clinical practice.

Recognizing these specific challenges, extensions to existing guidelines are being developed. The SPIRIT-Nut and CONSORT-Nut extensions are currently under development to provide tailored, consensus-driven guidance for nutritional intervention trials [9] [32]. These efforts aim to consolidate existing guidance and address the unique aspects of nutritional interventions, such as the characterization of the intervention composition, stability, and bioavailability.

Analysis of Current Reporting Quality

Table 1: Reporting Completeness of Nutrition RCT Protocols for SPIRIT and TIDieR Items

Reporting Aspect	Adherence Rate	Key Findings from Meta-Research
Overall Reporting Completeness	52.0% (SD = 10.8%) [1]	Based on 200 diet or nutrition-related RCT protocols.
Best Reported SPIRIT Item	98.5% for eligibility criteria [1]	Most protocols adequately describe who is eligible for the trial.
Poorest Reported SPIRIT Items	0% for data collection methods [1]	Methods for collecting data are consistently omitted.
Best Reported TIDieR Item	98.5% for intervention description [1]	The 'what' of the intervention is usually stated.
Poorest Reported TIDieR Item	5.5% for materials used in the intervention [1]	Specific brands, ingredients, and dosages are rarely provided.
Factors for Better Reporting	Higher author numbers, journal endorsement of guidelines, mention of SPIRIT by authors [1]	These factors are positively associated with reporting completeness.

Table 2: TIDieR Application in Specific Nutrition Intervention Fields

Field of Research	Average TIDieR Items Reported	Commonly Missed Intervention Details
Perioperative Bariatric Surgery Interventions [66]	70.4% of items	Adherence (51.3%), mode of delivery (42.1%), provider (38.3%), fidelity assessment (23.7%)
Nutrition-Focused Weight Management [53]	6.6 out of 12 items fully reported	Materials, procedures, personalization, intervention modifications
General Diet or Nutrition RCTs [2]	Varies widely by item	Materials, procedures for tailoring, intervention fidelity

The empirical data reveals a significant gap between current reporting practices and the ideal of transparent, replicable science. The failure to document the materials comprising a nutritional intervention—such as the specific brand, chemical composition, or supplier of a supplement or food product—makes it impossible to replicate the study [1] [2]. Furthermore, the procedures for tailoring the intervention to individual participants and plans for assessing and maintaining intervention fidelity are among the least reported items, despite being critical for interpreting trial outcomes and translating the research into real-world settings [53] [66].

This reporting inadequacy is not static. Studies have shown that the quality of reporting has not significantly improved since the publication of the TIDieR guidelines, indicating that passive dissemination of checklists is insufficient [53]. Active endorsement by journals, explicit commitment by authors to adhere to guidelines, and adequate space in publications for detailed methods descriptions are necessary to drive improvement.

Detailed Methodology for a High-Quality Nutrition RCT Protocol

Core Study Design and Registration

A high-quality protocol begins with a clear, concise title that incorporates the PICOT (Population, Intervention, Comparator, Outcome, Time frame) format [64]. The hypothesis and objectives should follow the SMART (Specific, Measurable, Attainable, Relevant, Time-bound) criteria. The primary objective, for which the sample size is calculated, must be clearly distinguished from secondary objectives [64].

The protocol must pre-specify the trial design (parallel, crossover, or factorial), justifying its choice in the context of the research question. For instance, a crossover design may be efficient for stable outcomes but is unsuitable where carry-over effects are likely, as in some weight loss or bone turnover studies [64] [65]. The protocol must also detail the trial's registration number and the name of the public trial registry, as prospective registration is a cornerstone of research transparency and is mandated by many journals [67].

Participant Selection and Ethical Considerations

The eligibility criteria should strike a balance between scientific rigor and generalizability. Overly strict criteria can hinder recruitment and limit the applicability of the findings. The protocol should describe recruitment strategies, procedures for obtaining informed consent, and plans for maintaining participant confidentiality [64] [67]. It must name the ethics committee that approved the study and include the committee’s reference number [67].

A statistically sound sample size calculation, with all its parameters (including alpha, power, and the minimally important clinical difference), must be provided. This calculation should be based on the primary outcome and justify the feasibility of recruiting the target number of participants within the planned timeline [64].

Intervention and Comparator: Applying TIDieR

This section is the heart of a nutrition RCT protocol and must be described with utmost precision to satisfy TIDieR criteria.

• What (Materials): Provide a complete description of the intervention and comparator. For a whole food intervention (e.g., blueberries), this includes the botanical name, cultivar, growing conditions, processing method (e.g., freeze-drying), and storage conditions [65]. For supplements, specify the chemical form, manufacturer, and batch-to-batch verification of active compound concentration. The stability of the intervention over the study period should be confirmed and reported [65].
• Who, How, and Where: Define the credentials of the intervention providers (e.g., registered dietitians, trained staff). Describe the mode of delivery (e.g., individual counseling, group sessions, provision of food) and the setting (e.g., research clinic, participant's home) [66] [67].
• Tailoring and Modifications: Document if and how the intervention will be tailored to individuals and the predefined rules for any allowed modifications during the study [53].
• Blinding: Acknowledge the challenges of blinding in nutrition trials and detail the strategies used to maximize blinding where possible. This can include using a placebo or comparator product matched for taste, appearance, and energy content, and having research kitchen staff code the products so that outcome assessors and data analysts are blinded [65].

Outcomes, Data Management, and Analysis

Define a limited number of primary and secondary outcomes, specifying how, when, and by whom they will be measured [64]. The protocol must include a detailed statistical analysis plan (SAP) that is finalized before unmasking the data. This plan should cover the principles for handling missing data, the primary statistical model, and any planned subgroup or sensitivity analyses [1] [2]. A data management section should outline data collection methods, quality control procedures, and plans for data sharing, including where the final dataset will be archived [67] [2].

The Scientist's Toolkit: Essential Reagents and Materials

Table 3: Key Research Reagent Solutions for Nutrition RCTs

Reagent/Material	Function in Nutrition RCT	Critical Reporting Details
Standardized Food/Supplement	The active intervention being tested.	Botanical name/chemical form, cultivar, processing, supplier, batch number, concentration of active compounds, stability data. [65]
Placebo/Comparator Product	Controls for placebo effect and allows blinding.	Matched for energy, macronutrients, taste, appearance, and texture. Composition must be fully disclosed. [65]
Calibrated Measurement Devices	Ensures accurate and consistent data collection.	Type, model, calibration schedule (e.g., for DXA scanners, bioimpedance scales, blood pressure monitors).
Biomarker Assay Kits	Quantifies biochemical outcomes from biological samples.	Manufacturer, catalog number, assay precision (intra- and inter-assay CV), sensitivity, and validation for the study population.
Dietary Assessment Tools	Measures background diet and compliance.	Validated food frequency questionnaire, 24-hour recall software, or diet diary protocol.
Data Management System	Securely stores and manages trial data.	Electronic data capture (EDC) system, audit trail functionality, and data backup procedures.

Visualizing the Protocol Development Workflow

The following diagram illustrates the logical workflow and key decision points for developing a high-quality nutrition RCT protocol, integrating the requirements of SPIRIT and TIDieR.

A high-quality nutrition RCT protocol is more than an administrative requirement; it is the blueprint for scientific rigor and a contract for transparency. This analysis demonstrates that while the tools for excellent protocol development—namely the SPIRIT and TIDieR guidelines—are available, their application in nutrition science is inconsistent. The consequence of incomplete reporting is a less trustworthy evidence base, which ultimately hinders the development of effective public health nutrition policies and clinical guidelines. Researchers, funders, and journal editors share the responsibility to champion the adoption of these reporting guidelines. By meticulously detailing the materials, procedures, and theoretical rationale for nutrition interventions, the scientific community can ensure that its findings are replicable, evaluable, and primed for meaningful translation into practice. The ongoing development of the SPIRIT-Nut extension promises future, field-specific guidance to further support this critical endeavor [9].

Conclusion

The integration of SPIRIT 2025 and TIDieR guidelines is no longer optional but essential for producing high-quality, transparent, and reproducible nutrition RCT protocols. By adhering to these frameworks, researchers can navigate the increasing complexity of modern trials, reduce costly amendments, and build trust in nutrition science. The future of nutrition research will be shaped by greater protocol standardization, increased patient involvement, and the intelligent application of technology, all guided by these evidence-based reporting standards. Widespread adoption will not only enhance the scientific rigor of individual studies but also strengthen the entire evidence base for dietary recommendations and interventions.

References

• 1. Reporting completeness of nutrition and diet-related randomised ... [https://pubmed.ncbi.nlm.nih.gov/38795681/]
• 2. Reporting completeness of nutrition and diet-related randomised controlled trials protocols - ScienceDirect [https://www.sciencedirect.com/science/article/abs/pii/S0261561424001456]
• 3. P065/S2-P1 reporting completeness in nutrition or diet-related... [https://www.alanrevista.org/ediciones/2023/suplemento-1/art-168/]
• 4. SPIRIT 2025 statement: updated guideline for protocols of randomized trials | Nature Medicine [https://www.nature.com/articles/s41591-025-03668-w]
• 5. SPIRIT 2025 statement: updated guideline for protocols of randomised trials - PubMed [https://pubmed.ncbi.nlm.nih.gov/40294953/]
• 6. SPIRIT 2025 statement: Updated guideline for protocols of randomised trials | PLOS Medicine [https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004589]
• 7. Perspective: Guidelines Needed for the Conduct of Human Nutrition Randomized Controlled Trials - PMC [https://pmc.ncbi.nlm.nih.gov/articles/PMC7850095/]
• 8. Perspective: US Documentation and Regulation of Human Nutrition Randomized Controlled Trials - PMC [https://pmc.ncbi.nlm.nih.gov/articles/PMC7850145/]
• 9. Reporting guidelines under development for... | EQUATOR Network [https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-clinical-trials-protocols/]
• 10. and diet-related randomized controlled trials: metaresearch ... [https://pmc.ncbi.nlm.nih.gov/articles/PMC12002212/]
• 11. SPIRIT 2025 explanation and elaboration: updated guideline ... [https://pmc.ncbi.nlm.nih.gov/articles/PMC12128891/]
• 12. template for intervention description and replication (TIDieR) [https://www.equator-network.org/reporting-guidelines/tidier/]
• 13. SPIRIT 2025: Trial Protocols & Adherence Gaps [https://aardexgroup.com/revisiting-adherence-in-spirit-2025-guidelines/]
• 14. SPIRIT 2025 Statement: Defining standard protocol items ... [https://www.equator-network.org/reporting-guidelines/spirit-2013-statement-defining-standard-protocol-items-for-clinical-trials/]
• 15. Completeness of Reporting in Diet- and Nutrition -Related Randomized... [https://www.researchprotocols.org/2023/1/e43537]
• 16. and Transparency Practices in a Sample of Reproducibility ... Nutrition [https://www.mdpi.com/2504-3900/91/1/62]
• 17. in Reproducibility Research Nutrition [https://www.numberanalytics.com/blog/reproducibility-in-nutrition-research-methods]
• 18. Statistical analysis of continuous outcomes from parallel-arm... [https://www.nature.com/articles/s41430-020-00750-z?error=cookies_not_supported&code=0fce3ac9-65da-43f5-b96a-288601286f05]
• 19. SPIRIT 2025 statement: updated guideline for protocols of ... [https://pmc.ncbi.nlm.nih.gov/articles/PMC12035670/]
• 20. Updated guideline for protocols of randomised trials [https://pubmed.ncbi.nlm.nih.gov/40294521/]
• 21. Study protocol for the randomized controlled trial of ... [https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2025.1555222/full]
• 22. template for intervention description and replication ... [https://pubmed.ncbi.nlm.nih.gov/24609605/]
• 23. Use of the TIDieR checklist to describe an online structured ... [https://pmc.ncbi.nlm.nih.gov/articles/PMC7708660/]
• 24. consort-spirit.org: Home [https://www.consort-spirit.org/]
• 25. statement: Updated SPIRIT for protocols of... 2025 guideline [https://pmc.ncbi.nlm.nih.gov/articles/PMC12037212/]
• 26. Published statements | consort- spirit .org [https://www.consort-spirit.org/published-statements]
• 27. Frontiers | Oral nutritional supplementation with dietary counseling improves linear catch-up growth and health outcomes in children with or at risk of undernutrition: a randomized controlled trial [https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1341963/full]
• 28. Reporting completeness of nutrition and diet-related randomised ... [https://www.ndorms.ox.ac.uk/publications/1995090]
• 29. [Interpretation and Examples: Key Updates in SPIRIT Statement] 2025 [https://pubmed.ncbi.nlm.nih.gov/40964111/]
• 30. Methods used to develop the SPIRIT 2024 and CONSORT 2024 Statements - ScienceDirect [https://www.sciencedirect.com/science/article/pii/S0895435624000647]
• 31. Improving the completeness and transparency of protocols and reports... [https://ora.ox.ac.uk/objects/uuid:9fbc93e6-5ff4-4b4a-9d0a-fc1173079506]
• 32. Reporting guidelines under development for... | EQUATOR Network [https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-clinical-trials/]
• 33. Protocol Writing in Clinical Research - PMC [https://pmc.ncbi.nlm.nih.gov/articles/PMC5198475/]
• 34. Protein delivery in intermittent and continuous enteral nutrition with... [https://pubmed.ncbi.nlm.nih.gov/32843075/]
• 35. Reporting of participant flow diagrams in published reports of randomized trials | Trials | Full Text [https://trialsjournal.biomedcentral.com/articles/10.1186/1745-6215-12-253]
• 36. How to interpret figures in reports of clinical trials - PMC [https://pmc.ncbi.nlm.nih.gov/articles/PMC2394578/]
• 37. The Template for Intervention Description and Replication ... [https://pmc.ncbi.nlm.nih.gov/articles/PMC9957771/]
• 38. Getting messier with TIDieR: embracing context and ... [https://pmc.ncbi.nlm.nih.gov/articles/PMC5774137/]
• 39. Perspective: Randomized Controlled Trials Are Not a Panacea for Diet-Related Research - PMC [https://pmc.ncbi.nlm.nih.gov/articles/PMC4863268/]
• 40. New CONSORT & SPIRIT Published | MRC Clinical... 2025 Guidelines [https://www.mrcctu.ucl.ac.uk/news/news-stories/2025/june/new-consort-spirit-2025-guidelines-published/]
• 41. Getting messier with TIDieR: embracing context and complexity in intervention reporting | BMC Medical Research Methodology | Full Text [https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-017-0461-y]
• 42. for the process evaluation of a Protocol intervention... complex [https://implementationscience.biomedcentral.com/articles/10.1186/s13012-014-0113-0]
• 43. Adherence and success in long-term weight loss diets: the dietary intervention randomized controlled trial (DIRECT) - PubMed [https://pubmed.ncbi.nlm.nih.gov/19828901/]
• 44. Interventions to enhance adherence to dietary advice for preventing and managing chronic diseases in adults - PubMed [https://pubmed.ncbi.nlm.nih.gov/23450587/]
• 45. The SPIRIT Checklist—lessons from the experience of SPIRIT protocol editors | Trials | Full Text [https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06316-7]
• 46. Group-based nutrition interventions to promote healthy eating and mobility in community-dwelling older adults: a systematic review - PMC [https://pmc.ncbi.nlm.nih.gov/articles/PMC9991860/]
• 47. Food-Based Interventions to Modify Diet Quality and Diversity to Address Multiple Micronutrient Deficiency - PMC [https://pmc.ncbi.nlm.nih.gov/articles/PMC4700276/]
• 48. The Template for Intervention Description and Replication ( TIDieR )... [https://pedro.org.au/english/the-template-for-intervention-description-and-replication-tidier-checklist-can-be-summed-to-create-a-score/]
• 49. SPIRIT 2025 and CONSORT 2025 Statements: Guidance Tools to Ensure Clinical Trial Transparency | Archivos de Bronconeumología [https://www.archbronconeumol.org/es-spirit-2025-consort-2025-statements-avance-S0300289625001899]
• 50. Measuring the Impact of Early-2025 AI on Experienced Open-Source Developer Productivity - METR [https://metr.org/blog/2025-07-10-early-2025-ai-experienced-os-dev-study/]
• 51. [2507.09089] Measuring the Impact of Early-2025 AI on Experienced Open-Source Developer Productivity [https://arxiv.org/abs/2507.09089]
• 52. Announcing the Agent2Agent Protocol (A2A) - Google Developers Blog [https://developers.googleblog.com/en/a2a-a-new-era-of-agent-interoperability/]
• 53. Completeness of intervention reporting of nutrition-focused weight management interventions adjunct to metabolic and bariatric surgery: effect of the TIDieR checklist | International Journal of Obesity [https://www.nature.com/articles/s41366-024-01506-6]
• 54. statement: updated SPIRIT for protocols of randomised... 2025 guideline [https://ora.ox.ac.uk/objects/uuid:b2c8b331-3dcd-4350-8309-04baf4f947d9]
• 55. Progress towards a nutrition extension of the CONSORT reporting... [https://fensnutrition.org/2025/07/progress-towards-a-nutrition-extension-of-the-consort-reporting-guidelines-for-rcts/]
• 56. Describing the landscape of nutrition- and diet-related randomized controlled trials: metaresearch study of protocols published between 2012 and 2022 - PubMed [https://pubmed.ncbi.nlm.nih.gov/39864593/]
• 57. Users' Nutrition : Guides Part 2 - structured RCTs for... guide [https://pubmed.ncbi.nlm.nih.gov/39882290/]
• 58. Perspective: Guidelines Needed for the Conduct of Human Nutrition Randomized Controlled Trials - PubMed [https://pubmed.ncbi.nlm.nih.gov/33200180/]
• 59. Improving the completeness and transparency of protocols and... [https://pubmed.ncbi.nlm.nih.gov/40252855/]
• 60. Describing the landscape of nutrition - and diet-related... | CoLab [https://colab.ws/articles/10.1016%2Fj.ajcnut.2025.01.016]
• 61. 9 Key Data Quality Metrics You Need to Know in 2025 [https://atlan.com/data-quality-metrics/]
• 62. 12 Data Quality Metrics to Measure Data Quality in 2025 [https://lakefs.io/data-quality/data-quality-metrics/]
• 63. Completeness of Reporting in Diet- and Nutrition -Related... [https://pmc.ncbi.nlm.nih.gov/articles/PMC10131600/]
• 64. Designing and Conducting Randomized Controlled Trials: Basic Concepts for Educating Early Researchers in the Field of Clinical Nutrition - PMC [https://pmc.ncbi.nlm.nih.gov/articles/PMC8425776/]
• 65. Frontiers | Designing, Conducting, and Documenting Human Nutrition ... [https://www.frontiersin.org/articles/10.3389/fnut.2021.782703/full]
• 66. Perioperative lifestyle and nutritional interventions' details reporting in... [https://pubmed.ncbi.nlm.nih.gov/39706722/]
• 67. International Journal of Behavioral Nutrition and Physical Activity [https://ijbnpa.biomedcentral.com/submission-guidelines/preparing-your-manuscript/research]