{ "title": "Single-ingredient riboflavin (vitamin B2) × Reduction of persistent fatigue in quiescent inflammatory bowel disease", "criteria_version": "NGM-3090-ORAL-B2-QUIESCENT-IBD-FATIGUE-1.0", "criteria_date": "2026-10-05", "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly document the question, eligibility conditions, and reasons for changes, and distinguish intervention variants.", "review_level": "Actual copies and hashes of the original methodological text from 1585 were reused. The model for this work read the preserved principles defining the families; it did not read the methodological HTML body, browse new web material, or apply the official method in full." }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Distinguish and link studies and reports; do not omit studies solely because results are unreported.", "review_level": "Actual copies and hashes of the original methodological text from 1585 were reused. The model for this work read the preserved principles defining the families; it did not read the methodological HTML body, browse new web material, or apply the official method in full." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Fix the outcome and effect of interest when reviewing randomization, deviations, missing data, measurement, and selective reporting.", "review_level": "Actual copies and hashes of the original methodological text from 1585 were reused. The model for this work read the preserved principles defining the families; it did not read the methodological HTML body, browse new web material, or apply the official method in full." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect values, intervals, importance, and applicability. Sample size alone does not determine precision.", "review_level": "Actual copies and hashes of the original methodological text from 1585 were reused. The model for this work read the preserved principles defining the families; it did not read the methodological HTML body, browse new web material, or apply the official method in full." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Harm questions may require different designs, populations, and follow-up from efficacy questions. Case reports do not establish incidence.", "review_level": "Actual copies and hashes of the original methodological text from 1585 were reused. The model for this work read the preserved principles defining the families; it did not read the methodological HTML body, browse new web material, or apply the official method in full." } ], "status_dictionary": { "Verified": "Verification of the specified question, materials, attribution, or original records. Separate from establishing a clinical effect.", "Partly verified": "Some actual information has been verified, but the materials and results needed for the entire condition remain unverified.", "Unverified": "Direct information for judging the condition has not been verified in the current input. This does not mean 0, absence, or no effect.", "Unread": "The material itself was not actually read in this work. Separate from reading a summary.", "Not applicable": "A decision that an extension outside the specified current question scope does not apply." }, "schema_version": "chamgap-public-criteria-1.0", "condition_origin": "Chamgap’s own application conditions", "requirements": [ { "item_id": "N01", "question_type": "Question boundaries", "question": "What question about administration of B2 alone and persistent fatigue is being reviewed?", "needed": "Persistent fatigue in adults with quiescent IBD, addition of ordinary oral riboflavin alone, a comparator under the same usual care, the fatigue scale, and the boundaries stated in the original manuscript.", "role": "Required", "role_reason": "Even when an ingredient name or the word fatigue is the same, a different intervention or patient state means a different question.", "application_exception": "Details of eligible administration that remain unverified are left as part of the question. Doses or endpoints from related studies are not used to fill them in.", "criterion": "Distinguish the comparative effect of B2 administration from B1 administration, vitamer associations, combination products, and exercise recovery, and link it to a single independent question.", "basis": "The meanings of the existing family templates C01, C05 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "First state these boundaries as eligibility criteria, then individually compare whether the ingredient, population, and endpoint in each actual study all match." }, { "item_id": "N02", "question_type": "Population and remission", "question": "Does the population in the actual B2 material consist of adults with quiescent IBD?", "needed": "IBD diagnosis/type, the definition and assessment timing of remission, age and eligibility criteria, and a characteristics table for the actual population receiving B2.", "role": "Required", "role_reason": "Remission status affects the causes of persistent fatigue and applicability to the current population.", "application_exception": "The presence of a population in remission in a B1 trial does not mean that the population in the material on B2 alone has also been verified.", "criterion": "Verify remission status in the actual eligible B2 population, distinguishing it from a general-fatigue population or active disease.", "basis": "The meanings of the existing family templates C04, E07 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Prespecify the definition of remission and recruitment criteria, and report the population's B2 comparative results separately." }, { "item_id": "N03", "question_type": "Persistent fatigue", "question": "What criteria were used to select for persistent fatigue?", "needed": "Eligibility criteria concerning fatigue persistence, severity, and assessment tools, and selection records for the actual B2 population.", "role": "Required", "role_reason": "Chronic fatigue in patients and acute exercise recovery cannot be combined as the same effect.", "application_exception": "Do not assign arbitrary numerical values to a duration or scale threshold absent from the original text.", "criterion": "Verify selection for persistent fatigue and actual measurement of patient symptoms, distinguishing these from discomfort after acute exercise.", "basis": "The meanings of the existing family templates C04, C06, E03 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Select a definition of persistent fatigue and assessment tools appropriate to the clinical context, and record fatigue status at recruitment." }, { "item_id": "N04", "question_type": "Deficiency status", "question": "Are baseline B2 status and the population requiring correction of deficiency distinguished?", "needed": "Measurement of B2 status, deficiency-assessment methods, baseline distributions, and whether the actual treated population has deficiency.", "role": "Required", "role_reason": "This is needed to avoid confusing associations involving vitamer levels with the application of deficiency treatment.", "application_exception": "Do not use the presence of fatigue or measurement of FMN alone to diagnose B2 deficiency.", "criterion": "Distinguish general persistent fatigue in quiescent IBD from correction of confirmed B2 deficiency, and verify actual baseline status.", "basis": "The meanings of the existing family templates C04, E08 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Record baseline status and assessment methods, and plan analyses by deficiency status in advance if they are needed." }, { "item_id": "N05", "question_type": "Preparation identity", "question": "Is the actual administered preparation riboflavin alone?", "needed": "The ingredient's molecular form and salt, formulation, product composition, manufacturing origin and batch, and materials verifying actual administration.", "role": "Required", "role_reason": "If the identity of the pharmacological exposure differs, a contribution cannot be attributed to B2 alone.", "application_exception": "Naming B2 alone in the question does not replace verification of the actual trial product. Classification by plant part used does not apply.", "criterion": "Distinguish administration of riboflavin alone from B1, combination products, and analysis of circulating FMN, and verify the identity of the actual product.", "basis": "The meanings of the existing family templates C05, E02 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Compare product composition and molecular form with administration records, and record every active ingredient by arm." }, { "item_id": "N06", "question_type": "Actual route", "question": "Is the actual administration route in an eligible B2 result oral?", "needed": "Sections and administration records specifying the method and route of administration in an eligible trial.", "role": "Required", "role_reason": "This is needed to avoid turning verification of oral B1 administration into verification of the actual route of B2 administration.", "application_exception": "Do not replace the null entry (no value) in the observation record with the oral route specified by the question.", "criterion": "Link the oral route specified by the question separately from the route verified in actual eligible material.", "basis": "The meaning of the existing family template C05 was adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "After verifying actual administration methods, classify materials involving different routes separately." }, { "item_id": "N07", "question_type": "Dose", "question": "What are the nominal and actual doses in an eligible B2 comparison?", "needed": "The nominal dose, frequency, actual intake, changes, and adherence records for B2 alone.", "role": "Required", "role_reason": "Doses from related B1 or exercise trials cannot establish the effect or safety range for persistent fatigue in IBD.", "application_exception": "Do not present an unverified actual dose as 0 mg or as no effect at any dose.", "criterion": "Verify the actual B2 dose for the eligible population and endpoint, without repurposing doses from related studies.", "basis": "The meanings of the existing family templates C05, E02, E08 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "In a subsequent comparison, specify a dosing strategy supported by evidence and track actual exposure and changes by arm." }, { "item_id": "N08", "question_type": "Duration", "question": "Are the periods of administration, fatigue assessment, and follow-up after discontinuation distinguished?", "needed": "The duration of eligible B2 administration, the fatigue-assessment schedule, the time of discontinuation, and subsequent follow-up records.", "role": "Required", "role_reason": "Different durations cannot be interpreted as the same effect on fatigue or the same persistent effect.", "application_exception": "Do not specify a common minimum number of weeks or a length of long-term follow-up without original source material.", "criterion": "Verify the actual administration period and outcome-measurement time points; do not turn a short-term recovery interval into a duration of persistent fatigue.", "basis": "The meanings of the existing family templates C06, E08 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Justify an assessment schedule appropriate to the time course of fatigue, and distinguish administration, assessment, and follow-up after discontinuation." }, { "item_id": "N09", "question_type": "Comparator", "question": "Has the actual comparator for B2 under the same usual IBD care been verified?", "needed": "The actual placebo arm or arm with no additional treatment, placebo composition, usual-care policy, and actual treatment by arm.", "role": "Required", "role_reason": "To interpret the intervention's contribution, it is necessary to know what was compared with the arm receiving additional B2.", "application_exception": "Do not describe the placebo/no-additional-treatment comparison in the question as a comparator actually implemented.", "criterion": "Verify the comparison policy in the question and the actual B2 comparison; do not repurpose the control arm from a B1 trial.", "basis": "The meanings of the existing family templates C05, E01, E02 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Design a comparison under the same usual-care policy, and disclose placebo composition, actual treatment, and changes." }, { "item_id": "N10", "question_type": "Concurrent exposure", "question": "Are concurrent vitamins, diet, and IBD treatment distinguished from the contribution of B2?", "needed": "IBD treatment, rescue treatment, concurrent vitamins, total dietary intake, changes, and adherence materials by arm.", "role": "Required", "role_reason": "This is needed to avoid attributing a B-vitamin combination or dietary differences to the effect of B2 alone.", "application_exception": "Do not impose a requirement that actual changes in every arm must be the same. Compare the effect of interest with the permitted policies.", "criterion": "Record actual concomitant use and changes, and examine whether other ingredients or differences in usual care are mixed with the contribution of B2.", "basis": "The meanings of the existing family templates C05, E02, H05 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Record all relevant exposures and changes by arm, and prespecify the effect of interest and handling methods for the strategy of adding B2." }, { "item_id": "N11", "question_type": "Measurement tools", "question": "Have the fatigue scale, units, direction, and measurement time points been verified?", "needed": "The fatigue instrument, version, score direction, units, measurement time points, and basis for validity in an actual B2 trial.", "role": "Required", "role_reason": "If scales or directions differ, numerical increases and decreases cannot be treated as the same improvement.", "application_exception": "Do not turn the question's requirement for a validated scale into a fact that the instrument actually used has been validated.", "criterion": "Attribute actual measurements of the selected endpoint to patients' persistent fatigue, keeping them separate from circulating vitamers and exercise performance.", "basis": "The meanings of the existing family templates C06, E03 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Justify a fatigue instrument and measurement schedule appropriate to the population, and disclose the score direction and definition of change." }, { "item_id": "N12", "question_type": "Assessment procedures", "question": "What are the blinding and collection procedures and measurement limitations for fatigue assessment?", "needed": "Actual fatigue assessors, self-report procedures, collection by arm, assessment blinding, and records of missing data.", "role": "Required", "role_reason": "This is needed to distinguish differences in expectations and data collection from differences in patients' symptoms.", "application_exception": "Do not automatically score unverified or infeasible blinding as a flaw.", "criterion": "Verify the actual procedures and differences between arms in subjective fatigue measurement, and do not assume that unknown methods were adequate or failed.", "basis": "The content of the existing family template E03 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Standardize fatigue-data collection procedures and document feasible blinding, differences in assessment, and limitations." }, { "item_id": "N13", "question_type": "Denominators", "question": "Can allocation, measurement, and analysis denominators for the actual fatigue endpoint be distinguished?", "needed": "Recruitment, allocation, exposure, measurement, completion, and analysis flow in an eligible B2 trial, and participant counts for each endpoint.", "role": "Required", "role_reason": "Confusing the total participant count with the fatigue-analysis denominator changes the interpretation of the effect and the extent of missing data.", "application_exception": "Do not treat a string referring to a historical numerical record as a number that has been read. Do not estimate denominators from rounding or other reports.", "criterion": "Verify the actual number analyzed for each endpoint in the original material, and do not replace it with the total participant count from a trial of another ingredient.", "basis": "The content of the existing family templates C07, E04 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Make participant flow and endpoint-analysis counts by arm available, and link reasons for exclusion to the results." }, { "item_id": "N14", "question_type": "Allocation and analysis", "question": "Can the design, allocation, and effect of interest in an eligible B2 comparison be verified?", "needed": "The actual design, such as parallel or crossover; allocation, concealment, and baseline balance; and the analysis population, model, and between-group contrast.", "role": "Required", "role_reason": "Observational associations and effects of administration, and within-group changes and between-group contrasts, have different causal interpretations.", "application_exception": "Do not fill an unverified eligible design with an assertion of nonrandomization or an ITT analysis. Do not arbitrarily assign not applicable (NA) to a crossover design either.", "criterion": "Verify the effect of assignment or adherence and the between-group analysis for the actual B2 intervention, distinguishing them from observational vitamer analyses.", "basis": "The content of the existing family templates E01, E04 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Conduct a direct B2 comparison with the effect of interest and design specified and allocation, analysis populations, and handling methods documented." }, { "item_id": "N15", "question_type": "Missing data and attrition", "question": "Were missing fatigue outcomes, dropouts, and treatment changes reflected in the analysis?", "needed": "Materials on missing fatigue measurements and reasons for dropout by arm, treatment changes, handling of missing data, and sensitivity analyses.", "role": "Required", "role_reason": "This is needed to avoid presenting an analysis restricted to people with available results as the overall effect of adding B2.", "application_exception": "Do not classify unverified missing data as 0 dropouts or as an established large bias.", "criterion": "Verify the extent of actual missing endpoint data and the handling methods, distinguishing missing values from no change.", "basis": "The content of the existing family templates C07, E02, E04, H06 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Record missing data, dropouts, and treatment changes by arm, and link prespecified handling and sensitivity analyses to the actual fatigue contrast." }, { "item_id": "N16", "question_type": "Effects and intervals", "question": "Is there a between-group estimate and interval for fatigue change with B2 alone?", "needed": "The between-group effect value, units, dispersion, denominator, CI, and analysis definition for the actual fatigue endpoint.", "role": "Required", "role_reason": "Correlations or significance alone cannot establish the direction, magnitude, or precision of the effect of B2 administration.", "application_exception": "Do not turn an unverified effect into 0, equivalence, or an inadequate effect. Do not calculate a new no-effect grade.", "criterion": "Link only reported between-group estimates and intervals for the same population, endpoint, and time point; do not reconstruct values from P values or other studies.", "basis": "The content of the existing family templates C06, C07, E04, E05 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Report the between-group fatigue estimate, dispersion, denominator, and CI together in a direct comparison, and state what the estimate represents." }, { "item_id": "N17", "question_type": "Clinical importance", "question": "Is there a basis for judging a fatigue difference that patients would consider important?", "needed": "The basis for an important difference appropriate to the actual fatigue instrument and population, the source of the criterion, and the reported effect interval.", "role": "Required", "role_reason": "Statistical associations must be distinguished from symptom improvement that matters to patients.", "application_exception": "Do not arbitrarily set a common minimum sample size, duration, or difference on the scale. An unverified criterion does not mean no effect.", "criterion": "Compare a justified criterion for fatigue importance with the effect and interval from the same analysis, or record why a judgment cannot be made.", "basis": "The content of the existing family template E05 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Establish the basis for an important difference for each population and fatigue instrument, and compare the criterion set at the planning stage with the actual interval." }, { "item_id": "N18", "question_type": "Registration and hierarchy", "question": "Can the prospective plan for the B2 fatigue endpoint be compared with the actual report?", "needed": "Eligible B2 registration, protocol, and analysis plan, and records of changes to the primary endpoint, time points, and analyses.", "role": "Required", "role_reason": "Concordance between the endpoint named by a paper and the preregistered endpoint must be verified separately.", "application_exception": "Do not turn unverified registration concordance into an established finding of nonregistration or selective reporting.", "criterion": "Compare the actual B2 plan and report, without repurposing the B1 TARIF registration identity as a B2 plan.", "basis": "The content of the existing family templates C09, E06 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Compare planning materials and reports for an eligible B2 study, and retain changes to endpoints, timing, and analyses and the reasons for them." }, { "item_id": "N19", "question_type": "TARIF intervention", "question": "Was the substance actually administered in TARIF B2 or B1?", "needed": "Records showing the ingredient, molecular form, and route actually administered in S05, and the role of the relevant result.", "role": "Required", "role_reason": "A shared B-vitamin label or a population with fatigue alone does not establish that the ingredient is the same.", "application_exception": "Exclude it from direct evidence of a B2 effect because the intervention does not match, while preserving the related observational information.", "criterion": "Do not turn actual B1 administration into a B2 intervention; distinguish whether the intervention is eligible for this question.", "basis": "The content of the existing family templates C05, E02, E07 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Compare the intervention section of the original report with the subanalysis, and separately verify whether a B2-administration comparison exists." }, { "item_id": "N20", "question_type": "Vitamer associations", "question": "Does an association between circulating B2 vitamers and fatigue establish an effect of administration?", "needed": "Vitamer measurements and observational analyses in S05, the ingredient actually administered, and information on the direction of the association and adjustment.", "role": "Required", "role_reason": "Recasting a biomarker association as a treatment effect changes the causal direction.", "application_exception": "Preserve observational associations as leads for further research, without presenting them as between-group results from actual B2 administration.", "criterion": "Distinguish associations involving circulating markers from changes in patients' fatigue following riboflavin administration.", "basis": "The content of the existing family templates C06, E04, E09 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Review exposures and adjustment in the observational analysis separately from comparisons of B2 administration, and design the direct comparison needed." }, { "item_id": "N21", "question_type": "Study-family overlap", "question": "Is the TARIF vitamer analysis being counted as a separate replication for B2?", "needed": "Study-family links among TARIF registration, the main report, the vitamer subanalysis, participants, and outcomes.", "role": "Required", "role_reason": "This is needed to distinguish the number of reports from the number of unique studies and to avoid using a family of studies on another intervention as replication for B2.", "application_exception": "Do not infer original report contents or unique participant counts that are absent from the current input.", "criterion": "Do not count a subanalysis from the same TARIF family as an independent B2 trial or replication.", "basis": "The content of the existing family templates C02, E07 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Check the linkage table for registration, the main report, and the subanalysis, and indicate overlap by endpoint and analysis." }, { "item_id": "N22", "question_type": "Combination-product composition", "question": "Does the IBD combination product in S08 contain B2?", "needed": "All active ingredients in S08, the composition by arm, and whether individual ingredients were compared separately.", "role": "Required", "role_reason": "This is needed to avoid assuming that a product contains B2 solely because it is called a general B-vitamin complex.", "application_exception": "Do not delete the combination-product results, but do not present them as an effect of B2 or an isolated effect of B1.", "criterion": "Verify the B1·B6·B12·magnesium composition, and do not attribute results from a combination product without B2 to B2.", "basis": "The content of the existing family templates C05, E02, E07 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Compare the product composition with the actual intervention section, and link only a separable B2 comparison to the B2-alone question." }, { "item_id": "N23", "question_type": "Exercise recovery", "question": "Is acute exercise recovery in S25 the same outcome as persistent fatigue in IBD?", "needed": "A comparison table of the ultramarathon study's population, acute endpoints, and timing against the IBD fatigue question.", "role": "Required", "role_reason": "Matching the B2 ingredient alone cannot remove differences in disease, endpoint, and timing.", "application_exception": "Do not combine exercise outcomes with persistent-fatigue outcomes in IBD, whether the exercise findings are favorable or unfavorable.", "criterion": "Distinguish acute muscle soreness and recovery performance from patients' persistent fatigue, without repurposing samples or effects.", "basis": "The content of the existing family templates C04, C06, E07, E08 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Verify the population, endpoint, and timing at actual locations in the original text, and find a separate direct B2 comparison that meets the question." }, { "item_id": "N24", "question_type": "Funding and independence", "question": "Can funding and independent replication for direct B2 evidence be verified?", "needed": "Research funding, product provision, author conflicts of interest, and independent study-family information for eligible B2 reports.", "role": "Supplementary; required for independence claims", "role_reason": "Even when there are several related reports, independent replication of the same question requires separate verification.", "application_exception": "Do not automatically exclude material because a conflict of interest exists. A statement that funding was not used in grading does not mean there was no funding.", "criterion": "Explain independence only on the basis of verified funding and study families, and do not turn unverified information into independent funding or absence of bias.", "basis": "The content of the existing family templates C10, C02, E07 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Verify declarations, product provision, and study-family identity for each eligible report, and cross-check whether replication is independent." }, { "item_id": "N25", "question_type": "Direction of results", "question": "Are the direction and no-difference findings in related materials distinguished from direct B2 results?", "needed": "The actual endpoints, analyses, direction of results, and eligibility of the three related reports, and direct B2 comparison results.", "role": "Required", "role_reason": "Reasons for exclusion and effect direction are separate dimensions; positive evidence must not be selectively chosen.", "application_exception": "Do not supply detailed directions, P values, or effect values absent from the current retained summary by guessing what the original paper says.", "criterion": "Preserve positive, no-difference, and unfavorable findings according to their roles, without aggregating results for other questions as confirmation or refutation of B2.", "basis": "The content of the existing family templates C08, E07 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Compare direct and related materials by endpoint and analysis, and report all available results together, regardless of their direction." }, { "item_id": "N26", "question_type": "Materials and reading", "question": "Which materials were actually read in this work, and what historical full-text access is recorded?", "needed": "A list distinguishing retained summaries, citation locations, original-source access levels, individual dates, and reading records for this work for each material.", "role": "Required", "role_reason": "Copying a historical declaration of access to a paper's full-text HTML as verification of the full text in this work would create a false reading record.", "application_exception": "If individual historical access dates are absent, leave them as null values and distinguish them from the original review date, 2026-09-15.", "criterion": "Distinguish reading the retained summaries in full in this work from the fact that access to external clinical full texts was not attempted and they were not read; do not label a link as reading the original text.", "basis": "The meanings of the existing family templates C03, C09 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "If obtaining further materials is permitted, record actual access events, full-text locations, and dates, and compare them with the current summaries." }, { "item_id": "N27", "question_type": "Search scope", "question": "To what verification scope is the lack of verified directly eligible results limited?", "needed": "The original evidence cutoff, scope of the documented search, selection reasons, unverified areas, and whether a new search was performed in this work.", "role": "Required", "role_reason": "This is needed to align the scope of clinical conclusions with the search scope.", "application_exception": "Because the referenced historical search records were not actually read, do not describe this as complete verification of search strategies or databases.", "criterion": "Do not extend the original record's lack of verified eligible results to an absence of all human research worldwide or an effect of 0.", "basis": "The meaning of the existing family template C09 was adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "In a subsequently permitted investigation, document the scope of searches, registrations, unpublished material, and corrections, and select each item using the current eligibility conditions." }, { "item_id": "N28", "question_type": "Original judgment", "question": "How should the original ?, null values, and unused axes be interpreted?", "needed": "The original text showing the original grade, score, B/P axes, null values, empty and false values, and their bounded meanings.", "role": "Required", "role_reason": "Unverified information and 0, empty strings and null values, and the clinical endpoint of the question and an actual effect value have different meanings.", "application_exception": "Do not present document quality A or technical confidence in identity assignment as clinical efficacy grades either.", "criterion": "Preserve the original judgment and data types without carrying them over as verification statuses, efficacy probabilities, or new scores in the new table.", "basis": "The meanings of the existing family templates C01, C09 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "When updating evidence, preserve the original values and distinguish actual new evidence and condition changes from an event in which the original judgment is reconsidered." }, { "item_id": "N29", "question_type": "Safety data collection", "question": "How were adverse events collected for the same exposure to B2 alone in IBD?", "needed": "Adverse-event definitions, occurrence/worsening, collection, discontinuations, severity, and exposure denominators for the same population, dose, and duration.", "role": "Supplementary; required for safety claims", "role_reason": "An efficacy summary or the essential nutritional role of a nutrient is not evidence of the safety of high-dose treatment.", "application_exception": "Do not present unverified adverse-event information as no events or safety. Keep gaps in efficacy and harms separate.", "criterion": "Verify events, denominators, duration, and the scope of collection in direct B2 safety data; do not inherit safety findings from other ingredients.", "basis": "The meanings of the existing family templates E10, H01, H02, H03, H04, H06, H09 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Define and systematically collect events under the same conditions as the eligible exposure, and report the number of people with events, the number of events, exposure denominators, and discontinuations." }, { "item_id": "N30", "question_type": "Interactions", "question": "Have interactions between IBD medications or other exposures and B2 been verified?", "needed": "Medications and concurrent exposures in the same population, the scope of interaction investigations, events, and temporal relationships.", "role": "Supplementary; required for interaction claims", "role_reason": "This is needed to avoid attributing events due to IBD medications or other causes solely to B2.", "application_exception": "Do not newly list interactions or conclude that there is no risk.", "criterion": "Record the distinction between no comprehensive search being performed and no known interactions, and actually verify information on concurrent exposures.", "basis": "The meanings of the existing family templates E10, H05, H08, H09 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "In a subsequent safety investigation, record actual medications, exposures, timing, and alternative causes together, and design the necessary comparisons." }, { "item_id": "N31", "question_type": "Assay interference", "question": "Does the assessment distinguish whether assay interference was investigated from whether there was an effect on fatigue?", "needed": "The scope of investigations of interference in B2/vitamer assays, the actual measurement methods, and materials verifying interference.", "role": "Supplementary; required for vitamer interpretation", "role_reason": "Limitations of vitamer measurement must not automatically be converted into a clinical effect on fatigue or a diagnosis of deficiency.", "application_exception": "Do not impose assay-interference research uniformly as a mandatory efficacy condition for a patient-symptom question.", "criterion": "Do not present the absence of a separate search as absence of interference or as actual detection of interference.", "basis": "The meanings of the existing family templates C06, E03 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "When interpreting biochemical markers, separately verify the actual assay and whether interference is present, and distinguish them from clinical fatigue." }, { "item_id": "N32", "question_type": "Persistence and subgroups", "question": "Can questions about optimal dose, persistence of effects, and subgroups also be answered directly?", "needed": "Direct B2 dose comparisons, follow-up after discontinuation, and separate estimates for prespecified subgroups and interactions.", "role": "Supplementary; required for the relevant extended claim", "role_reason": "When the principal effect remains unverified, the dose, particular patient groups, and maintenance of effects cannot be established.", "application_exception": "Do not impose all extension studies as mandatory conditions for the initial narrow question. Do not recommend unsupported doses or durations.", "criterion": "Distinguish direct materials for the narrow persistent-fatigue question from extensions to optimal dose, persistence, and subgroups.", "basis": "The meanings of the existing family templates E08, H08 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "If the extended question is needed, separately design prespecified dose contrasts, follow-up, subgroup hypotheses, and appropriate interaction analyses." }, { "item_id": "N33", "question_type": "Clinical extensions", "question": "Does the fatigue question also include IBD relapse, hospitalization, and improvement in disease activity?", "needed": "The boundary distinguishing the fatigue scope of the original question from separate questions about disease activity, events, and quality of life.", "role": "Supplementary; required for clinical-event extensions", "role_reason": "This is needed to prevent endpoint expansion, but it does not impose all event trials on the current fatigue question.", "application_exception": "The current table reviews only the persistent-fatigue question. Direct event evidence is required only when making a separate claim about clinical events.", "criterion": "Do not extend changes in a scale of persistent fatigue in patients to improvement in other IBD clinical events.", "basis": "The meanings of the existing family templates C01, C06, E09 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "If a separate event question is added, review event definitions, denominators, duration, and comparisons separately under new boundaries and conditions." }, { "item_id": "N34", "question_type": "Evidence for updates", "question": "What materials, if obtained, would prompt reconsideration of the gaps in the fatigue question?", "needed": "A list of updates linked to the current conditions: direct B2 evidence, full texts, registry results, and corrections to numerical values, units, or identities.", "role": "Required", "role_reason": "The current unverified state must not be treated as permanently established, and the mere existence of new material must not be treated as satisfying the conditions.", "application_exception": "The original empty list of publication prerequisites (publication_prerequisites) or historical publication status does not constitute authorization for distribution or evidence of completion in this work.", "criterion": "Distinguish addition of new evidence, revision of the question or conditions, modification of the original judgment, and publication events, preserving previous values and reasons.", "basis": "The meanings of the existing family templates C09, C01 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed.", "condition_origin": "Chamgap's own conditions, developed for a case with prior knowledge of the retained materials; not preregistered, blinded, or officially certified as a method", "proposed_research": "Apply the precise identity, results, and date of new material to the existing conditions again; if the boundary changes, revise and freeze the conditions first." } ], "language": "en", "translation_date": "2026-11-01" }