Single-ingredient riboflavin (vitamin B2) × Reduction of hs-CRP in adults with elevated hs-CRP

Required evidence, verification status and materials actually read
Item	AVerification status	BReading scope	CReview item	DCurrent findings	EWhy unverified	FRequired materials and conditions	GFurther research
1	Met	Full text not readStored summary read	N01 · Separate claimWhich high-sensitivity CRP comparison is being defined?Required (selected hs-CRP comparison)	One main claim was selected: reduction of hs-CRP in adults with elevated hs-CRP. The list of subclaims is empty, and dose/duration remain unverified for the question. S12 S13 S14 S21	Verifying the definition of the question does not mean that a direct effect has been demonstrated.	Definition of the question: a conventional oral B2 single-ingredient preparation, adults with elevated hs-CRP, change in high-sensitivity CRP, and placebo/no additional treatment on top of the same usual care	Compare the population, ingredients, endpoints, and comparison boundaries in the obtained manuscript and candidate studies.
2	Unverified	Full text not readStored summary read	N02 · Molecule and actual routeHas actual oral administration of B2 alone been verified in an eligible result?Required (selected hs-CRP comparison)	The question being judged is defined as riboflavin/oral, but the actual molecule/route values in the preserved study information are empty and unverified, and the list of linked sources is empty. S12 S13 S14 S21	Verifying the direction of the question is separate from obtaining evidence of actual exposure in an eligible result.	Verification of the actual molecule, salt/derivative, route of administration, and single-ingredient composition in the relevant comparison	Link formulation and administration documentation to the population/results tables to verify actual oral exposure to B2 alone.
3	Unverified	Full text not readStored summary read	N03 · Formulation and productAre the release profile, manufacture/purity, and batch of the relevant eligible preparation known?Required (selected hs-CRP comparison)	The question concerns a conventional oral B2 single-ingredient preparation; the manufacturing origin and the release profile of an eligible preparation remain unverified. S14's detailed release formulation has not been directly verified either. S12 S13 S14 S21	Wording about a product name or ingredient in the question alone does not certify its actual specifications.	The exact chemical form, release profile, manufacture/origin, purity, batch, and excipients of the conventional oral single-ingredient preparation	Obtain product/trial-preparation documentation and review differences in applicability between conventional and specialized-release formulations.
4	Partly verified	Full text not readStored summary read	N04 · DoseCan the eligible dose be distinguished from the 10 and 100 mg in related trials?Required (selected hs-CRP comparison)	The records of S12 in older adults at 10 mg/day and S13 in Crohn disease at 100 mg/day are preserved, but the dose for an eligible population with elevated hs-CRP remains unverified. S12 S13	Do not repurpose nominal doses from other populations as actual doses for the current question.	Nominal/actual dose, frequency, adherence, and total exposure in an eligible comparison, and administration records from related studies	Compare administration and actual doses in eligible arms using medication/preparation records and records of concomitant intake.
5	Partly verified	Full text not readStored summary read	N05 · DurationCan the eligible duration be distinguished from the 28 days and 3 weeks in related studies?Required (selected hs-CRP comparison)	The recorded durations of S12 at 28 days and S13 at 3 weeks are verified within that limited scope. Duration and follow-up for an eligible population with elevated hs-CRP remain unverified. S12 S13	Do not extend the 28 days/3 weeks to a directly eligible duration or to long-term effects.	Administration, assessment, and follow-up periods in an eligible study, and the actual time points in candidate studies	Link administration/follow-up and assessment time points using the schedule, assessment plan, and results tables.
6	Unverified	Full text not readStored summary read	N06 · Population selectionHave the selection criteria and underlying diseases for participants with elevated hs-CRP been verified?Required (selected hs-CRP comparison)	Selection for elevated levels has not been verified for S12; S13 is a before-and-after comparison in Crohn disease, and S21 involves healthy participants. Results in a population meeting the fixed question remain unverified. S12 S13 S14 S21	Preserve the distinctions in eligible populations without erasing the existence of related human studies.	The actual threshold for elevated hs-CRP, repeat testing, diagnoses, age, inclusion/exclusion criteria, and baseline distributions	Obtain eligibility criteria, baseline tables, and assay records to compare population concordance and reasons for exclusion for each candidate.
7	Unverified	Full text not readStored summary read	N07 · High-sensitivity assayHave both the high-sensitivity assay and selection for elevated levels been verified?Required (selected hs-CRP comparison)	The original unresolved-items record states that results meeting both the high-sensitivity assay requirement and selection for elevated hs-CRP remain unverified. S12·S13 have assay/selection limitations, while S21 concerns a different endpoint/population. S12 S13 S14 S21	The presence of CRP information does not mean that an hs-CRP effect has been verified.	The hs-CRP assay name, sensitivity, specimen, and units, together with selection for elevated levels in the same population	Compare the original assay methods with baseline assay tables to verify whether a result meets the high-sensitivity criteria.
8	Unverified	Full text not readStored summary read	N08 · Actual comparatorHave placebo/no additional treatment and shared care been verified for an eligible result?Required (selected hs-CRP comparison)	The question specifies placebo/no additional treatment on top of the same usual care. S12's placebo record does not establish eligibility of the population/assay, and S13 has no concurrent randomized comparator. S12 S13 S14 S21	Results from an eligible comparison for the current question cannot be replaced with a related study design.	The composition and schedule of concurrent comparator arms, shared care, and changes by arm	Link comparator/shared-care documentation to the results and review the meaning of the between-group difference.
9	Partly verified	Full text not readStored summary read	N09 · Reports and study familiesHave the distinct studies and outcome relationships underlying the four reports been established?Required (selected hs-CRP comparison)	The four bibliographic records are linked to the stored study identifiers Tavares-riboflavin-2009, RISE-UP, RIBOGUT, and NCT05803811. Direct eligible replication and linkage of the original participants have not been verified. S12 S13 S14 S21	Do not tally the 4 reports as 4 eligible studies, 4 independent replications, or a total number of participants.	Bibliography → trial/study family → endpoint/time point/analysis linkage, and whether there is duplication	Link registry, paper, and study identifiers to review repeated citations of the same result and separate reports.
10	Met	Full text not readStored summary read	N10 · Reading and material typesHas reading the summaries in this work been distinguished from historical access levels?Required (selected hs-CRP comparison)	S12 is a historical record of a publisher abstract; S13, an indexed author abstract/figure legends; S21, an institutional abstract; and S14, a registry shell. Only the preserved summaries were read in this work, with 0 external lookups. S12 S13 S14 S21	The original full texts, registry results, and separate logs/numerical files remain unread. There is no field for individual original-source access dates; the recorded verification date is the original review date for the materials as a whole.	Actual acquisition/reading for each material; historical abstract/figure-legend/institutional-abstract/registry-shell access; locations and dates	If follow-up work is authorized, obtain the original file contents (bytes), source locations, and access dates for each material, and record actual reading histories separately.
11	Met	Full text not readStored summary read	N11 · Cutoff date and search scopeHave the cutoff date and search limitations for the current materials been linked?Required (selected hs-CRP comparison)	The search cutoff in the original revision policy and the recorded verification date are 2026-09-15; there is no top-level evidence-cutoff field. The stated limitation is that the original search was not an exhaustive search of primary databases worldwide. Only this preserved-summary conversion was performed in the current work. S12 S13 S14 S21	Statements of absence mean that eligible results remain unverified within the fixed question and the documents' search scope.	The existing search cutoff and verification date, the current summary-review date, the input scope, and the record that no search was performed	In a separately authorized update, compare the actual search logs and registration/correction status with the original cutoff date.
12	Unverified	Full text not readStored summary read	N12 · Eligible designHas the actual comparative design for the same question been verified?Required (selected hs-CRP comparison)	A placebo trial of conventional CRP, a before-and-after study in Crohn disease, and an analysis in healthy participants exist, but comparative results for an eligible population with elevated hs-CRP have not been verified. S12 S13 S14 S21	Do not turn gaps in design details into a conclusion of poor design or 0 human studies.	The actual parallel, crossover, cluster/randomized design for an eligible population/assay	Review the design and population/assay concordance across the protocol, Methods section, and results tables.
13	Unverified	Full text not readStored summary read	N13 · Allocation and baselineHave sequence generation, allocation concealment, and baseline balance been verified for an eligible comparison?Required (selected hs-CRP comparison)	The currently retained summary does not provide sequence-generation information, allocation concealment, or a baseline table corresponding to an eligible result. The original unused bias assessment axis is also empty. S12 S13 S14 S21	This is unverified within the preserved materials; it does not establish that the entire paper leaves the information unreported or determine the magnitude of bias.	Allocation procedures, sequence generation, concealment, baseline distributions, and linkage to results	Obtain the Methods section, allocation records, and baseline table to review gaps in confounding/allocation information for each outcome.
14	Unverified	Full text not readStored summary read	N14 · Concomitant treatment and concurrent vitaminsHave concurrent treatments and all vitamins in the eligible arms been verified?Required (selected hs-CRP comparison)	The value in the concurrent-vitamin record within the preserved nutrition information is empty and unverified. Details of all concurrent vitamins and treatments by arm for an eligible comparison have not been retained. S12 S13 S14 S21	Do not impose a rule that changes in the two arms must necessarily be identical.	Usual treatment, concurrent vitamins/supplements, medication changes, and rescue treatment by arm	Compare medication, supplementation, and rescue-treatment records with the analysis plan to review the contribution of concomitant treatment and the treatment policies actually compared.
15	Unverified	Full text not readStored summary read	N15 · Total exposure and adherenceHave baseline B2, total dietary intake, actual intake, and adherence been verified?Required (selected hs-CRP comparison)	Values for baseline nutritional status, total dietary/all-supplement exposure, and the eligible dose are empty/unverified; concurrent exposure also remains unverified. S12 S13 S14 S21	Do not fill in actual exposure for an eligible result solely with the nominal amount from a related trial.	Deficiency status/measurement, dietary B2, other supplementary exposure, and actual medication intake/adherence by arm	Obtain baseline nutritional tests and intake/medication records to review gaps in analyses of total exposure and adherence.
16	Met	Full text not readStored summary read	N16 · Endpoint boundariesHave changes in high-sensitivity CRP been distinguished from clinical anti-inflammatory efficacy?Required (selected hs-CRP comparison)	The selected endpoint is change in high-sensitivity CRP concentration. The preserved nutrition information records it as a laboratory surrogate and states that it is not extended to clinical-event prevention. S12 S13 S14 S21	Verification of this boundary does not mean that a direct hs-CRP reduction effect or clinical anti-inflammatory efficacy has been verified.	The actual selected endpoint, units, and direction, and boundaries separating it from other inflammatory markers/clinical events	Link the original outcome definition to clinical results tables to review what belongs to the same question and what belongs to a separate question.
17	Unverified	Full text not readStored summary read	N17 · Measurement proceduresHave sample collection, timing, blinding, and precision for the eligible assay been verified?Required (selected hs-CRP comparison)	Verification of the high-sensitivity assay is still outstanding, and details of the relevant eligible measurement procedures, timing, and blinded assessment have not been verified either. S12 S13 S14 S21	Units in the ordinary-CRP figure were not converted without verification.	The actual hs-CRP assay, specimen/measurement procedures, assessment time points, conditions by arm, and blinding of those taking measurements	Compare the assay SOP, collection time points, and blinding documents with the original results.
18	Unverified	Full text not readStored summary read	N18 · DenominatorsHas the actual analysis denominator for each hs-CRP result been verified?Required (selected hs-CRP comparison)	The summary describes S12 as a study of 42 participants and S13 as a study of 70 participants. The analysis-sample-size record in the preserved study information is empty/unverified, and the preserved source states that assignment counts must not replace unverified outcome-specific counts (n). S12 S13 S14 S21	The total number of participants in a related study and the analysis count (n) for the currently eligible endpoint are separate quantities.	Numbers by arm (n) at recruitment/allocation, administration, measurement, completion, and analysis, and the outcome time points	Use results tables, flow diagrams, and analysis materials to link denominators at each stage to reasons for exclusion.
19	Unverified	Full text not readStored summary read	N19 · Missing data and attritionHave the reasons for missing data and attrition, and the methods used to handle them, been verified for an eligible result?Required (selected hs-CRP comparison)	The current manuscript contains no material that establishes missing data/attrition and handling methods corresponding to an eligible analysis denominator. S12 S13 S14 S21	This is a gap within the currently preserved materials, not confirmation that the entire original paper leaves the information unreported or that it failed.	Losses, exclusions, discontinuations, missing measurements, and analytical handling/sensitivity analyses by arm	Link flow diagrams, plans for handling missing data, and analysis records to review limitations on interpretation of the results.
20	Unverified	Full text not readStored summary read	N20 · Effect of interest and analysisHave the eligible between-group effect and analysis population/adjustment been verified?Required (selected hs-CRP comparison)	S13 is a before-and-after comparison without a concurrent control, and S21 is an association analysis. The analysis population/model/effect for an eligible hs-CRP comparison has not been verified. S12 S13 S14 S21	Do not turn a before-and-after reduction or a correlation into a direct treatment effect versus placebo.	Effects of assignment/adherence, between-group change/final values, ITT/PP, and adjusted/cross analyses	Compare analysis plans, models, and results tables by arm to distinguish the effect of interest from the preserved results.
21	Unverified	Full text not readStored summary read	N21 · Numerical values and unitsHave the effect value and units for the same eligible result been verified?Required (selected hs-CRP comparison)	The effect estimate for the fixed question has not been verified, and the original calculation and numerical-check records are empty lists. Units in the ordinary-CRP figure and numbers in the S14 search overview were not adopted. S12 S13 S14 S21	Do not replace nonsignificance or an empty value with an effect of 0 or a numerical value of 0.	hs-CRP values by arm, changes, units, dispersion, time points, and original results tables	Compare original numerical tables and assay units to record the exact comparison values and what remains unverified.
22	Unverified	Full text not readStored summary read	N22 · Precision and intervalsHave the original CI, dispersion, and denominator for the relevant effect been verified?Required (selected hs-CRP comparison)	The eligible effect and CI have not been verified, and the precision assessment axis is empty. A nonsignificant ordinary-CRP result is not a precisely established null effect for the current question. S12 S13 S14 S21	The original uncalculated precision assessment was not changed into a new CX/E0 or an effect of 0.	The reported CI, dispersion, denominator, and model for the same between-group hs-CRP estimate	Link the estimate, dispersion, interval, and denominator in the relevant results table/model to review the range of effects compatible with them.
23	Unverified	Full text not readStored summary read	N23 · Important differenceIs there a justified criterion for the importance of a change in high-sensitivity CRP?Required (selected hs-CRP comparison)	An eligible effect has not been verified, and this document does not provide a threshold for an important difference or a basis for interpretation for the same comparison. S12 S13 S14 S21	Do not reassess an unverified criterion as an inadequate effect or an unfavorable finding.	The basis for an important difference in the same population/assay and duration, and the corresponding interval	Obtain the basis for clinical/patient importance and interpretation of the surrogate to review the scope of applicability of the results.
24	Unverified	Full text not readStored summary read	N24 · Plans and registrationHave the prospective plans for the eligible primary endpoint, analysis, and time points been cross-checked?Required (selected hs-CRP comparison)	The registered-primary-endpoint record in the preserved study information is empty/unverified, and S14 records a historical basic registry page and failure to render the body. Independent cross-checking of the eligible primary endpoint/plan remains unverified. S14	Do not record endpoints as established or a results body as read solely because the record is labeled as a basic registry page.	Cross-checking official registration, protocol, SAP, and changes against actual results	Link official registration versions, protocols/SAPs, and actual results to review changes and areas that have not been cross-checked.
25	Partly verified	Full text not readStored summary read	N25 · Ordinary CRP in older adultsIs the nonsignificant result in S12 a direct result for this question?Required (selected hs-CRP comparison)	The result that no significant CRP difference was reported in the placebo trial in older adults with 42 participants, 10 mg/day, and 28 days has been preserved. Selection for elevated hs-CRP and a high-sensitivity assay have not been verified. S12	Do not interpret this nonsignificance as an hs-CRP effect of 0, equivalence, or replicated evidence against the effect.	The actual high-sensitivity assay, selection for elevated levels, original result values/intervals, and denominator in S12	Use the original abstract/Methods/results tables to cross-check the assay/selection criteria and the actual scope of the nonsignificant result.
26	Partly verified	Full text not readStored summary read	N26 · Before-and-after comparison in Crohn diseaseIs the CRP result in S13 efficacy established through a concurrent comparison?Required (selected hs-CRP comparison)	S13 is a before-and-after comparison in 70 people with Crohn disease, using 100 mg/day for 3 weeks, with no concurrent randomized control. Some results concern a fecal-calprotectin subgroup. S13	Preserve the before-and-after CRP material without repurposing it as a between-group hs-CRP treatment effect in the same population.	The actual population/assay, comparison, timing, and endpoint/subgroup results in RISE-UP	Link the original abstract/figure captions, Methods, and results tables to review distinctions between before-and-after comparisons, subgroups, and controls.
27	Partly verified	Full text not readStored summary read	N27 · Associations in healthy participantsIs the redox/CRP association in S21 a direct reduction effect?Required (selected hs-CRP comparison)	The redox analysis and correlation with CRP in healthy RIBOGUT participants are not a randomized treatment effect of B2 in a population selected for elevated hs-CRP. S21	Retain differences in population/endpoint/design without deleting the original analysis.	The actual population, administration/design, and definitions of the redox/CRP analyses in RIBOGUT	Compare the institutional abstract with the original analysis/results to review the boundary between an association and a randomized comparison estimate.
28	Unverified	Full text not readStored summary read	N28 · Registry results not obtainedHave the actual population, formulation, and results of NCT05803811 been verified?Required (selected hs-CRP comparison)	The historical S14 record documents the basic registry page at the official study URL and a failure to render the body; the results and detailed release formulation could not be directly verified. Numerical values from the introductory information were not adopted. S14	Do not judge the overall effect or the absence of research from a single original record of inaccessible material.	The body of the official registry record, results tables, release formulation, population/assay, denominator, and linked reports	If follow-up work is permitted, obtain the official version/results and links to papers, and review the formulation, selection criteria, effect, and denominator.
29	Unverified	Full text not readStored summary read	N29 · Funding and independenceHave actual research funding, product provision, and author/institutional interests been verified?Supplementary; required for independence claims	Funding information for the four evidence records is unverified or was not used in this page's grade. The independence assessment axis for the current eligible result also has an empty value. S12 S13 S14 S21	Do not newly fill in the originally undetermined funding information as I1 verification of independence or as confirmed dependence on a manufacturer.	Actual research funding, product provision, author employment/declarations, and independent study-family relationships for each report	Obtain the original funding/conflict-of-interest declarations (Funding/COI) and institutional/study-family information to distinguish funding from relationships between reports and replications.
30	Met	Full text not readStored summary read	N30 · Attribution of the retained original judgmentHave the original ?/empty values and the no-human-study flag with its bounded scope (no_human_study) been preserved exactly?Required (selected hs-CRP comparison)	The original record contains grade ?, an empty score, B/S, and empty values for the remaining unused axes. The true value of the no-human-study flag (no_human_study) is limited to the failure to verify directly eligible results in the document search. No F/E0 was created. S12 S13 S14 S21	Do not turn original empty values into the number 0, absence, or the absence of all related human studies.	The original grade, score, unused assessment axes, eligible scope, and literal wording of the search judgment at that time	If new eligible material becomes available within a separately permitted scope, review it while distinguishing the original judgment/conditions from the new event.
31	Unverified	Full text not readStored summary read	N31 · Additional candidate leadHas the candidate concerning B6–B2 metabolic interactions been verified as a result of B2 administration?Required (selected hs-CRP comparison)	The unresolved additional-lead record (unresolved/additional_lead) records that the original text of the candidate concerning B6–B2 metabolic interactions could not be verified in the earlier review and that the candidate was not adopted as evidence of an effect of B2 administration; the list of linked sources is empty.	The candidate's original text or registry has not been newly read, and no new search has been performed; it is not made into a fifth report.	The actual candidate's bibliographic record, original text, molecule/administration/population/endpoint, and result location	If follow-up work is permitted, establish the identifier and compare the original text with the question to review whether to include it.
32	Unverified	Full text not readStored summary read	N32 · Underlying conditions and subgroupsHave eligible differences by underlying condition or baseline B2 status been compared?Supplementary; required for extensions to conditions/subgroups	The current fixed question does not combine results across underlying conditions. Direct results for eligible comparisons or for modification of the B2 effect by baseline status and condition remain unverified. S12 S13 S14 S21	Do not infer differences in treatment response from contextual results in different populations.	Prespecified subgroups, interactions, separate results, and baseline nutritional status within the same comparison	If follow-up work is permitted, compare prespecified hypotheses and separate results concerning population/baseline differences.
33	Not applicable	Full text not readStored summary read	N33 · Extension to optimal dose and persistenceDoes the selected question include the optimal dose and persistence after discontinuation?Supplementary; required for extensions to optimal dose/maintenance	The current table addresses the fixed question of hs-CRP change; optimal dose and maintenance after discontinuation/long-term persistence are not added as separate mandatory claims. S12 S13 S14 S21	Not applicable is not a judgment that long-term data are absent, that an intervention is safe, or that there is no effect.	Separate extended questions and materials for direct dose comparisons and follow-up after discontinuation/over the long term	If an extension is requested, review direct dose comparisons and treatment-discontinuation/follow-up materials as a separate question.
34	Not applicable	Full text not readStored summary read	N34 · Extension to clinical eventsDoes the hs-CRP question include disease treatment or event prevention?Supplementary; required for extensions to clinical events	The current question concerns the change in hs-CRP concentration itself. Clinical anti-inflammatory effects or event prevention are not additional mandatory claims in this table. S12 S13 S14 S21	This does not mean that clinical effects, anti-inflammatory treatment, or safety have now been verified.	Separate boundaries between clinical anti-inflammatory effects, disease activity, quality of life/events, and the selected change in hs-CRP	If the scope is extended, review direct clinical events and patient-important outcomes as an independent question/sheet.
35	Unverified	Full text not readStored summary read	N35 · SafetyHave harms/discontinuations for the same population, product, and duration been verified?Supplementary; required for safety claims	Safety for the relevant eligible population, product, and duration remains unverified. Short-term tolerability in other populations was not extended to long-term safety, and the original safety status is unknown. S12 S13 S14 S21	Unverified harms do not mean AE 0 or safety.	AE collection, participant/event denominators, discontinuations, duration, concomitant use/vulnerable groups for eligible exposures	Link harm-collection, discontinuation, denominator, and follow-up information to outcomes/exposures to review applicability over the long term and to vulnerable groups.
36	Unverified	Full text not readStored summary read	N36 · Assay interference and drug interactionsHas any separate verification of interference/interactions actually been performed, and within what scope?Supplementary; required for interpreting interference/interactions	In the nutritional extraction record (nutrition_extraction), the assay-interference and drug-interaction fields (assay_interference and drug_interactions) have empty values and are marked as not separately searched. This is a historical record that no separate systematic/comprehensive search was conducted. S12 S13 S14 S21	Only the currently retained summaries were read; do not turn this into a finding of no influence or no drug interactions.	Data on hs-CRP assay interference and interactions involving the relevant exposure/drugs, and the scope of searches performed	If an extension is permitted, separately review interference and interaction data for the actual assay and concomitant exposures.

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36 itemsWhat the statuses mean

Assessment scope

Stored-material review date: 2026-10-05
Original evidence date: 2026-09-15
Scope actually checked: Preserved Korean and English manuscripts and case-specific records of criteria and their application. Full papers, supplements, registrations, plans and original data were not read.
What the dates mean: This is the date the preserved materials were reviewed, not the date of a new search of the clinical literature.
Population: Adults defined by elevated hs-CRP; results for different underlying diseases are not combined
Ingredient, formulation and route: The question concerns a conventional oral B2 single-ingredient preparation; it is not automatically combined with a specialized colonic-release formulation
Dose: The dose in an eligible trial involving participants with elevated hs-CRP remains unverified
Comparator: Question: placebo/no additional treatment on top of the same usual care; comparative results for the relevant population and assay remain unverified
Measured outcome: Change in high-sensitivity CRP concentration; distinguished from conventional CRP, other inflammatory markers, and clinical anti-inflammatory efficacy
Duration: The duration of an eligible trial involving participants with elevated hs-CRP remains unverified
Questions outside this scope: Conventional CRP, other inflammatory/redox markers, clinical anti-inflammatory efficacy/events, specialized colonic-release formulations, combinations/B1, acute exercise recovery, IBD fatigue 3090, correction of confirmed deficiency, and optimal dose/long-term effects are separate questions. The existing 374/1456 are reused IDs in the original metadata; their individual manuscripts were not read in this work.

Evidence and sources

The links below lead to the sources. A link alone does not mean the original source was read or its latest publication status verified.

S12 · Tavares et al. — riboflavin, homocysteine and C-reactive protein in older adults (2009)

Official source

Material type: Abstract record of a contextual placebo trial of ordinary CRP in older adults
Materials actually read: The bibliographic information and summaries in the currently retained materials were actually read; external original materials remain unread
Findings recorded in the stored summary: The placebo-controlled trial in older adults involved 42 participants, B2 10 mg/day, and 28 days; it did not report a significant difference in CRP. Selection for elevated hs-CRP and use of a high-sensitivity assay were not verified.
Record level: The explicitly stated scope of the retained summaries; not current verification of external results
Study overlap and independent replication: The distinction concerns 4 bibliographic records and 4 stored study identifiers (study_id); it does not certify 4 directly eligible studies, a unique participant count, or independent replication.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Bibliographic information, linked summaries, and historical records in the retained summaries	Preserved locally	Obtained	Summary read	Exact locations and values/SHA; not the bytes of the original clinical full text
External entry point for article/publisher abstracts or full texts	Unverified (current external lookups: 0)	Access not attempted	Unread	An external entry point is provided, but the material is currently unread. Historical records concerning abstracts/figure captions/institutional abstracts/basic registry pages and historical failures to access results are not treated as current access history.

S13 · von Martels et al. — RISE-UP riboflavin study in Crohn disease (2020)

Official source

Material type: Abstract/figure-caption record of a contextual uncontrolled before-and-after study in Crohn disease
Materials actually read: The bibliographic information and summaries in the currently retained materials were actually read; external original materials remain unread
Findings recorded in the stored summary: RISE-UP is a before-and-after comparison in 70 participants with Crohn disease who received B2 100 mg/day for 3 weeks. There was no concurrent randomized control group, and some results were for fecal calprotectin subgroups.
Record level: The explicitly stated scope of the retained summaries; not current verification of external results
Study overlap and independent replication: The distinction concerns 4 bibliographic records and 4 stored study identifiers (study_id); it does not certify 4 directly eligible studies, a unique participant count, or independent replication.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Bibliographic information, linked summaries, and historical records in the retained summaries	Preserved locally	Obtained	Summary read	Exact locations and values/SHA; not the bytes of the original clinical full text
External entry point for the article or PubMed abstract/full text	Unverified (current external lookups: 0)	Access not attempted	Unread	An external entry point is provided, but the material is currently unread. Historical records concerning abstracts/figure captions/institutional abstracts/basic registry pages and historical failures to access results are not treated as current access history.

S14 · Clinical trial record NCT05803811

Official source

Material type: Historical record of the basic registry page and failed access to the results body
Materials actually read: The bibliographic information and summaries in the currently retained materials were actually read; external original materials remain unread
Findings recorded in the stored summary: According to the historical record, the registry results and detailed release formulation could not be directly verified. Numerical values from the search overview were not adopted.
Record level: The explicitly stated scope of the retained summaries; not current verification of external results
Study overlap and independent replication: The distinction concerns 4 bibliographic records and 4 stored study identifiers (study_id); it does not certify 4 directly eligible studies, a unique participant count, or independent replication.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Bibliographic information, linked summaries, and historical records in the retained summaries	Preserved locally	Obtained	Summary read	Exact locations and values/SHA; not the bytes of the original clinical full text
ClinicalTrials.gov registry webpage and unobtained results body	Unverified (current external lookups: 0)	Access not attempted	Unread	An external entry point is provided, but the material is currently unread. Historical records concerning abstracts/figure captions/institutional abstracts/basic registry pages and historical failures to access results are not treated as current access history.

S21 · Bourgonje et al. — riboflavin and systemic redox status (2022)

Official source

Material type: Institutional abstract record of an analysis of redox/CRP associations in healthy participants
Materials actually read: The bibliographic information and summaries in the currently retained materials were actually read; external original materials remain unread
Findings recorded in the stored summary: RIBOGUT's redox analysis and CRP correlations in healthy participants do not constitute a randomized treatment effect of B2 in a group with elevated hs-CRP.
Record level: The explicitly stated scope of the retained summaries; not current verification of external results
Study overlap and independent replication: The distinction concerns 4 bibliographic records and 4 stored study identifiers (study_id); it does not certify 4 directly eligible studies, a unique participant count, or independent replication.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Bibliographic information, linked summaries, and historical records in the retained summaries	Preserved locally	Obtained	Summary read	Exact locations and values/SHA; not the bytes of the original clinical full text
Institutional article-abstract webpage and linked full text	Unverified (current external lookups: 0)	Access not attempted	Unread	An external entry point is provided, but the material is currently unread. Historical records concerning abstracts/figure captions/institutional abstracts/basic registry pages and historical failures to access results are not treated as current access history.

Report counts versus independent study counts

The four bibliographic records and four stored study identifiers (study_id) do not certify four directly eligible studies, independent replication, or a unique participant count.

Review criteria

Version NGM-v3089-ORAL-RIBOFLAVIN-ELEVATED-HSCRP-1.0 · Criteria record date 2026-10-05. These are Chamgap's own application conditions, informed by the referenced methods. They do not constitute official assessment-tool certification or a new efficacy score.

N01 · Which high-sensitivity CRP comparison is being defined?

Required materials and conditions: Definition of the question: a conventional oral B2 single-ingredient preparation, adults with elevated hs-CRP, change in high-sensitivity CRP, and placebo/no additional treatment on top of the same usual care
Conditions for verification: Link the original effect wording and the actual scope of inclusion and exclusion to the same source location.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Conventional CRP, redox associations, clinical anti-inflammatory efficacy, and IBD fatigue are separate questions.
Why this condition is needed: This is needed to avoid mixing general discussion of CRP with a single comparison question.
Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed

N02 · Has actual oral administration of B2 alone been verified in an eligible result?

Required materials and conditions: Verification of the actual molecule, salt/derivative, route of administration, and single-ingredient composition in the relevant comparison
Conditions for verification: Verify the actual molecule and route for an eligible result using administration documentation.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not turn B1, B-vitamin combinations, or associations with blood vitamers into evidence of B2 administration.
Why this condition is needed: This is needed to avoid mistaking B2 as specified in the question for an actual administration record from an eligible study.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application

N03 · Are the release profile, manufacture/purity, and batch of the relevant eligible preparation known?

Required materials and conditions: The exact chemical form, release profile, manufacture/origin, purity, batch, and excipients of the conventional oral single-ingredient preparation
Conditions for verification: Verify the specifications of the preparation actually used for an eligible result.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Plant-part classification is not applicable, but this does not remove the unverified status of manufacture and formulation.
Why this condition is needed: This is needed to avoid automatically combining results for specialized colonic-release preparations with those for conventional B2.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed

N04 · Can the eligible dose be distinguished from the 10 and 100 mg in related trials?

Required materials and conditions: Nominal/actual dose, frequency, adherence, and total exposure in an eligible comparison, and administration records from related studies
Conditions for verification: Verify actual exposure in the relevant eligible arms separately from nominal doses in related studies.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: 10 mg/day and 100 mg/day are records from related studies, not an optimal-dose comparison.
Why this condition is needed: This is needed to avoid using doses from other populations as demonstrated or recommended doses for participants with elevated hs-CRP.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed

N05 · Can the eligible duration be distinguished from the 28 days and 3 weeks in related studies?

Required materials and conditions: Administration, assessment, and follow-up periods in an eligible study, and the actual time points in candidate studies
Conditions for verification: Verify the administration/assessment periods for each outcome in an eligible comparison.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not newly set a common minimum number of weeks or participants.
Why this condition is needed: This is needed to avoid fixing the short duration of another study as the appropriate duration for the selected question.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed

N06 · Have the selection criteria and underlying diseases for participants with elevated hs-CRP been verified?

Required materials and conditions: The actual threshold for elevated hs-CRP, repeat testing, diagnoses, age, inclusion/exclusion criteria, and baseline distributions
Conditions for verification: Verify the criteria for the actual comparison population selected for elevated levels using a high-sensitivity assay.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not combine results from different underlying diseases into a single population for application.
Why this condition is needed: This is needed to avoid equating general older-adult, Crohn disease, or healthy populations with a population selected for elevated levels.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed

N07 · Have both the high-sensitivity assay and selection for elevated levels been verified?

Required materials and conditions: The hs-CRP assay name, sensitivity, specimen, and units, together with selection for elevated levels in the same population
Conditions for verification: Link the actual assay and population selection to the same study/result.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not infer units or high-sensitivity status from figures or product names.
Why this condition is needed: This is needed to avoid arbitrarily substituting high-sensitivity CRP for conventional CRP.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application

N08 · Have placebo/no additional treatment and shared care been verified for an eligible result?

Required materials and conditions: The composition and schedule of concurrent comparator arms, shared care, and changes by arm
Conditions for verification: Verify the actual comparator content and differences in care for the selected population/assay.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not turn an uncontrolled before-and-after study into a concurrently assigned placebo comparison.
Why this condition is needed: This is needed to avoid confusing the comparison specified by the question with the actual comparator.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application

N09 · Have the distinct studies and outcome relationships underlying the four reports been established?

Required materials and conditions: Bibliography → trial/study family → endpoint/time point/analysis linkage, and whether there is duplication
Conditions for verification: Compare actual identifiers to distinguish verified study-family relationships from those that remain undetermined.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not create counts of unique participants or independent studies when they remain undetermined.
Why this condition is needed: This is needed to avoid turning the number of stored source identifiers/bibliographic records into the number of independent direct replications.
Referenced methods: M04 §4.6.1–4.6.2 on distinguishing studies from reports; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application

N10 · Has reading the summaries in this work been distinguished from historical access levels?

Required materials and conditions: Actual acquisition/reading for each material; historical abstract/figure-legend/institutional-abstract/registry-shell access; locations and dates
Conditions for verification: Link the records while distinguishing reading the currently preserved summaries from the fact that access to each external original material has not been attempted and the material has not been read in this work.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not re-record a historical failure to access registry results as a failed access attempt in this work.
Why this condition is needed: This is needed to avoid promoting a link or the originally recorded access level into a claim that the full text was read in this work.
Referenced methods: Material-collection/selection principles in M04 §4.5–4.6; the distinction between access and reading and the hyperlink rules are internally designed; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and are internally designed

N11 · Have the cutoff date and search limitations for the current materials been linked?

Required materials and conditions: The existing search cutoff and verification date, the current summary-review date, the input scope, and the record that no search was performed
Conditions for verification: Separate the original dates and the documents' search scope from the scope of work actually performed now.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not identify the merely named tasks/R01-007/ or historical search records as files actually read in this work.
Why this condition is needed: This is needed to avoid exaggerating the preservation conversion as an up-to-date, exhaustive literature search.
Referenced methods: M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and are internally designed

N12 · Has the actual comparative design for the same question been verified?

Required materials and conditions: The actual parallel, crossover, cluster/randomized design for an eligible population/assay
Conditions for verification: Directly link the design in the methods to the relevant eligible result.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not assign a not-applicable status to crossover/cluster designs because the design is unverified.
Why this condition is needed: This is needed to avoid substituting the design label of a related trial for an eligible causal comparison.
Referenced methods: M08 §8.1–8.2.3; internal application

N13 · Have sequence generation, allocation concealment, and baseline balance been verified for an eligible comparison?

Required materials and conditions: Allocation procedures, sequence generation, concealment, baseline distributions, and linkage to results
Conditions for verification: Verify whether allocation/baseline documentation for an eligible comparison supports each result.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not fill gaps in information from the original Methods by inventing a conclusion that bias has been established.
Why this condition is needed: This is needed to avoid certifying the adequacy of allocation solely from the label placebo.
Referenced methods: M08 §8.1–8.2.3; internal application

N14 · Have concurrent treatments and all vitamins in the eligible arms been verified?

Required materials and conditions: Usual treatment, concurrent vitamins/supplements, medication changes, and rescue treatment by arm
Conditions for verification: Link concomitant treatment/changes by arm in the eligible comparison to the effect of interest.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not fill unverified concurrent-vitamin information with an exposure value of 0.
Why this condition is needed: Needed to avoid mistaking differences in shared care for the contribution of B2 alone.
Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application

N15 · Have baseline B2, total dietary intake, actual intake, and adherence been verified?

Required materials and conditions: Deficiency status/measurement, dietary B2, other supplementary exposure, and actual medication intake/adherence by arm
Conditions for verification: Link the population's baseline status, total intake, and actual amount to administration records.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not combine results from a confirmed-deficiency population outside the question as effects of additional supplementation.
Why this condition is needed: Needed to avoid turning the nominal B2 amount into total exposure or an effect of correcting deficiency.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application

N16 · Have changes in high-sensitivity CRP been distinguished from clinical anti-inflammatory efficacy?

Required materials and conditions: The actual selected endpoint, units, and direction, and boundaries separating it from other inflammatory markers/clinical events
Conditions for verification: State the distinction between the selected hs-CRP change and ordinary CRP/other markers/clinical outcomes.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: The original B/S describes the endpoint of the fixed question; it is not certification of an observed eligible clinical trial.
Why this condition is needed: Needed to avoid extending a laboratory surrogate to disease treatment or event prevention.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M03 §3.2.4; internally defined limits on extensions

N17 · Have sample collection, timing, blinding, and precision for the eligible assay been verified?

Required materials and conditions: The actual hs-CRP assay, specimen/measurement procedures, assessment time points, conditions by arm, and blinding of those taking measurements
Conditions for verification: Verify the actual measurement conditions and differences between arms for the selected result.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not automatically judge unverified blinding as failed or adequate.
Why this condition is needed: Needed to distinguish measurement differences from intervention differences.
Referenced methods: M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed

N18 · Has the actual analysis denominator for each hs-CRP result been verified?

Required materials and conditions: Numbers by arm (n) at recruitment/allocation, administration, measurement, completion, and analysis, and the outcome time points
Conditions for verification: Verify the analysis denominators by arm corresponding to the selected result.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not turn a historical numerical record merely named in the preserved source into material with available values by opening it in this work.
Why this condition is needed: Needed to avoid repurposing 42·70 as eligible analysis denominators.
Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application

N19 · Have the reasons for missing data and attrition, and the methods used to handle them, been verified for an eligible result?

Required materials and conditions: Losses, exclusions, discontinuations, missing measurements, and analytical handling/sensitivity analyses by arm
Conditions for verification: Verify information on observation losses and their analytical handling for the relevant result.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not calculate the number of dropouts, their reasons, or their impact from the existing sample size.
Why this condition is needed: Needed to avoid turning unverified information into complete follow-up or an absence of events.
Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application

N20 · Have the eligible between-group effect and analysis population/adjustment been verified?

Required materials and conditions: Effects of assignment/adherence, between-group change/final values, ITT/PP, and adjusted/cross analyses
Conditions for verification: Link the effect definition and actual analysis for the same question to the result.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not fill in ITT, an adjustment model, or dispersion from names alone.
Why this condition is needed: Needed to avoid using uncontrolled before-and-after change and a between-group causal effect as the same value.
Referenced methods: M08 §8.2.2, M15 §15.3.1; internal application

N21 · Have the effect value and units for the same eligible result been verified?

Required materials and conditions: hs-CRP values by arm, changes, units, dispersion, time points, and original results tables
Conditions for verification: Attribute only verified original values to their corresponding population, assay, comparison, and time point.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not perform new effect calculations/unit conversions or reverse calculations from rounded values.
Why this condition is needed: Needed to avoid arbitrarily repurposing ordinary-CRP values or numbers from search overviews.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application

N22 · Have the original CI, dispersion, and denominator for the relevant effect been verified?

Required materials and conditions: The reported CI, dispersion, denominator, and model for the same between-group hs-CRP estimate
Conditions for verification: Verify the original reported interval and its basis corresponding to the same estimate.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not reconstruct intervals from P values, assignment counts, or the SD for a different endpoint.
Why this condition is needed: Needed to avoid declaring a precisely estimated null effect or treatment effect from significance and sample size alone.
Referenced methods: M15 §15.3.1–15.3.3; internal application

N23 · Is there a justified criterion for the importance of a change in high-sensitivity CRP?

Required materials and conditions: The basis for an important difference in the same population/assay and duration, and the corresponding interval
Conditions for verification: Verify the relationship between the original basis for importance and the interval for the same comparison.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not propose an arbitrary hs-CRP reduction, minimum n, or duration.
Why this condition is needed: Needed to avoid automatically interpreting a significant difference as a clinically meaningful anti-inflammatory effect.
Referenced methods: M15 §15.3.1–15.3.3; internal application; M03 §3.2.4; internally defined limits on extensions

N24 · Have the prospective plans for the eligible primary endpoint, analysis, and time points been cross-checked?

Required materials and conditions: Cross-checking official registration, protocol, SAP, and changes against actual results
Conditions for verification: Compare the same eligible result with the primary endpoint, analysis, and time points in the original plan.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Material not obtained does not establish nonregistration or selective reporting.
Why this condition is needed: Needed to avoid treating a basic registry page as a plan with verified planned/actual endpoints.
Referenced methods: M08 Table 8.2.a, M04 §4.6.3; internal application; material-collection and selection principles in M04 §4.5–4.6; separation of access from reading and the rules governing hyperlinks are internally designed

N25 · Is the nonsignificant result in S12 a direct result for this question?

Required materials and conditions: The actual high-sensitivity assay, selection for elevated levels, original result values/intervals, and denominator in S12
Conditions for verification: Verify whether the original population/assay/results in S12 meet the fixed eligibility criteria.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: The ordinary-CRP record for 42 participants, a 10 mg dose, and 28 days is not direct evidence of efficacy for the current question.
Why this condition is needed: Needed to avoid hiding a related result showing no significant difference or transferring it to a precisely established null effect on hs-CRP.
Referenced methods: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application

N26 · Is the CRP result in S13 efficacy established through a concurrent comparison?

Required materials and conditions: The actual population/assay, comparison, timing, and endpoint/subgroup results in RISE-UP
Conditions for verification: Verify the extent to which the actual design/population/assay answers the selected question.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not automatically adopt the record of 70 participants, 100 mg, and 3 weeks as an eligible randomized comparison or analysis denominator.
Why this condition is needed: Needed to avoid turning uncontrolled before-and-after changes and a fecal-calprotectin subgroup into an hs-CRP effect.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application

N27 · Is the redox/CRP association in S21 a direct reduction effect?

Required materials and conditions: The actual population, administration/design, and definitions of the redox/CRP analyses in RIBOGUT
Conditions for verification: Verify whether the direction, endpoint, and population of the actual analysis match the causal question posed by the comparison.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not generate a new hs-CRP reduction value from an association or mechanism.
Why this condition is needed: Needed to avoid reversing a correlation in healthy participants into a treatment effect in a population with elevated levels.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application

N28 · Have the actual population, formulation, and results of NCT05803811 been verified?

Required materials and conditions: The body of the official registry record, results tables, release formulation, population/assay, denominator, and linked reports
Conditions for verification: Verify the registry's exact results and their eligibility for the fixed question using the actual documents.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not turn a historical record of failed access into an absence of research or a failed access attempt in the current work.
Why this condition is needed: This is needed to avoid presenting search-result snippets or a registry address as evidence that actual results were obtained.
Referenced methods: Data-collection and selection principles in M04 §4.5–4.6; the distinction between access and reading and the rules governing hyperlinks were designed for this assessment; M08 Table 8.2.a, M04 §4.6.3; application for this assessment; M04 §4.6.3, M15 §15.3.1–15.3.3; distinctions between statuses were designed for this assessment

N29 · Have actual research funding, product provision, and author/institutional interests been verified?

Required materials and conditions: Actual research funding, product provision, author employment/declarations, and independent study-family relationships for each report
Conditions for verification: Compare the original declarations/funding for each material with the scope in which research independence has been verified.
Requirement and applicability: Supplementary; required for independence claims
Application exceptions: Do not automatically exclude results merely because funding was provided.
Why this condition is needed: This is needed to avoid upgrading unverified funding to a finding of independence or absence of bias.
Referenced methods: Chamgap's own conditions for independence and attribution. The official methods sections used in this pilot do not endorse all of these detailed items; M04 §4.6.1–4.6.2, M15 §15.3.1; application for this assessment

N30 · Have the original ?/empty values and the no-human-study flag with its bounded scope (no_human_study) been preserved exactly?

Required materials and conditions: The original grade, score, unused assessment axes, eligible scope, and literal wording of the search judgment at that time
Conditions for verification: Preserve ?, empty values in the retained summaries, Boolean values/empty strings, and the bounded scope at their original locations and in their original bytes.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not upgrade the historical judgment in the original verdict into a new scoring result in the current work.
Why this condition is needed: This is needed to avoid turning an uncalculated value into no effect, 0 studies worldwide, or a condition-fulfillment rate for the new table.
Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules were designed for this assessment; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and were designed for this assessment

N31 · Has the candidate concerning B6–B2 metabolic interactions been verified as a result of B2 administration?

Required materials and conditions: The actual candidate's bibliographic record, original text, molecule/administration/population/endpoint, and result location
Conditions for verification: Use the candidate's actual original text to verify whether it concerns an effect of B2 administration.
Requirement and applicability: Required (selected hs-CRP comparison)
Application exceptions: Do not invent a source identifier (source_id), number, or paper for the empty list of linked sources.
Why this condition is needed: This is needed to avoid counting a merely identified, unverified candidate as a new human efficacy study.
Referenced methods: The distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/result linkage is an application for this assessment; data-collection and selection principles in M04 §4.5–4.6; the distinction between access and reading and the rules governing hyperlinks were designed for this assessment; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and were designed for this assessment

N32 · Have eligible differences by underlying condition or baseline B2 status been compared?

Required materials and conditions: Prespecified subgroups, interactions, separate results, and baseline nutritional status within the same comparison
Conditions for verification: Check whether direct evidence from separate subgroup results or interaction analyses supports the extended claim.
Requirement and applicability: Supplementary; required for extensions to conditions/subgroups
Application exceptions: Do not impose all subgroup studies as mandatory requirements for the principal question.
Why this condition is needed: This is needed to avoid using differences between older adults, people with Crohn disease, and healthy participants as verification of subgroups in response to B2.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed

N33 · Does the selected question include the optimal dose and persistence after discontinuation?

Required materials and conditions: Separate extended questions and materials for direct dose comparisons and follow-up after discontinuation/over the long term
Conditions for verification: Distinguish whether separate claims about optimal dose/maintenance fall within this table's question scope.
Requirement and applicability: Supplementary; required for extensions to optimal dose/maintenance
Application exceptions: Do not present the unverified original duration as though the optimal duration or long-term effects have already been verified.
Why this condition is needed: This is needed to avoid imposing all extension studies as additional mandatory requirements for the narrow hs-CRP comparison.
Referenced methods: M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification were designed for this assessment

N34 · Does the hs-CRP question include disease treatment or event prevention?

Required materials and conditions: Separate boundaries between clinical anti-inflammatory effects, disease activity, quality of life/events, and the selected change in hs-CRP
Conditions for verification: State whether the fixed question concerns a change in a numerical value or a separate clinical effect.
Requirement and applicability: Supplementary; required for extensions to clinical events
Application exceptions: Do not remove the current question or extend it to clinical effects merely because it concerns a surrogate marker.
Why this condition is needed: This is needed to avoid unconditionally imposing a clinical-event trial as a requirement for a change in a surrogate marker.
Referenced methods: M03 §3.2.4; extension boundaries developed for this assessment

N35 · Have harms/discontinuations for the same population, product, and duration been verified?

Required materials and conditions: AE collection, participant/event denominators, discontinuations, duration, concomitant use/vulnerable groups for eligible exposures
Conditions for verification: Verify the actual harm data and scope of collection for the same population/product/duration.
Requirement and applicability: Supplementary; required for safety claims
Application exceptions: Do not change the original unknown safety status and short-term contextual materials into a new safety grade.
Why this condition is needed: This is needed to avoid turning tolerability in a short trial in another population into long-term safety.
Referenced methods: M19 §19.1.2–19.2.4; application for this assessment; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for individual study designs were designed for this assessment

N36 · Has any separate verification of interference/interactions actually been performed, and within what scope?

Required materials and conditions: Data on hs-CRP assay interference and interactions involving the relevant exposure/drugs, and the scope of searches performed
Conditions for verification: Check whether the actual materials and review scope support statements about interference/interactions.
Requirement and applicability: Supplementary; required for interpreting interference/interactions
Application exceptions: Do not turn the question into one about assay bias itself or record an area not searched as failed access.
Why this condition is needed: This is needed to avoid interpreting the absence of a separate search as absence of an influence.
Referenced methods: M08 Table 8.2.a, M03 §3.2.4; application for this assessment; M19 §19.1.2–19.2.4; application for this assessment; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and were designed for this assessment

Referenced methods and the sections actually reviewed

M03 · Cochrane Handbook 6.5 (2024), chapter updated 2023-08

Official methodology · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13

Referenced principle: Clearly document the question, eligibility conditions, and reasons for changes, and distinguish intervention variants.
Extent of review: Reuse of the methodological principles/versions preserved for 1585 and 5 actual HTML copies; no new reading of the full methodological text or execution of an official tool

M04 · Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03

Official methodology · §4.5, §4.6.1–4.6.3, MECIR C42

Referenced principle: Distinguish and link studies and reports; do not omit studies solely because results are unreported.
Extent of review: Reuse of the methodological principles/versions preserved for 1585 and 5 actual HTML copies; no new reading of the full methodological text or execution of an official tool

M08 · Cochrane Handbook 6.5 (2024), chapter updated 2019-10

Official methodology · §8.1–8.2.3, Table 8.2.a

Referenced principle: Fix the outcome and effect of interest when reviewing randomization, attrition, missing data, measurement, and selective reporting.
Extent of review: Reuse of the methodological principles/versions preserved for 1585 and 5 actual HTML copies; no new reading of the full methodological text or execution of an official tool

M15 · Cochrane Handbook 6.5 (2024), chapter updated 2023-08

Official methodology · §15.2.4, §15.3.1–15.3.3

Referenced principle: Distinguish effect values, intervals, importance, and applicability. Sample size alone does not determine precision.
Extent of review: Reuse of the methodological principles/versions preserved for 1585 and 5 actual HTML copies; no new reading of the full methodological text or execution of an official tool

M19 · Cochrane Handbook 6.5 (2024), chapter updated 2019-10

Official methodology · §19.1.2, §19.2.1–19.2.4

Referenced principle: Harm questions may require different designs, populations, and follow-up from efficacy questions. Case reports do not establish incidence.
Extent of review: Reuse of the methodological principles/versions preserved for 1585 and 5 actual HTML copies; no new reading of the full methodological text or execution of an official tool

What the statuses mean

Partly verified: Some information in the retained summaries is verified, but gaps remain regarding the eligible population, assay, preparation, and results
Unverified: The specified necessary materials could not be established within the currently preserved scope; this does not mean an effect of 0, 0 studies worldwide, or safety
Review incomplete: The original sources were not cross-checked or searched within the permitted scope
Not reported: A scope-limited status indicating that the item was not stated in the specific material/section that was read
Inaccessible: Used only for materials that could not be accessed despite an actual attempt. Not assigned to clinical materials in this work
Insufficient evidence meeting the criteria: Used only when related studies within the defined scope have been reviewed and the evidence is insufficient to answer the criterion. It is not applied across the board in this work
Not applicable: Separate clinical-event/optimal-dose/long-term extensions are not imposed as additional mandatory requirements for the selected hs-CRP change question
Conflicting data: Used when materials that are difficult to reconcile for the same question, time point, and analysis have been compared. Not assigned merely because numerical values in reviews differ
Met: The specified question/scope/attribution/preservation linkage has been verified; distinguished from certification of direct hs-CRP efficacy or full-text reading

Change history

2026-11-01 · Public page/material version 1.0

A public display and data were created from the existing 36 items. No new clinical search, change to verification status, or scoring was performed.

The stored-material review date (2026-10-05) and original evidence cut-off (2026-09-15) were retained unchanged.

Researcher downloads

These materials provide the same evidence, scope and verification status as this page.

View all item details

N01 · Which high-sensitivity CRP comparison is being defined?

Current findings: One main claim was selected: reduction of hs-CRP in adults with elevated hs-CRP. The list of subclaims is empty, and dose/duration remain unverified for the question.
Verification status: Met
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Verifying the definition of the question does not mean that a direct effect has been demonstrated.
Reason for missing information: Verifying the definition of the question does not mean that a direct effect has been demonstrated.
Required materials and conditions: Definition of the question: a conventional oral B2 single-ingredient preparation, adults with elevated hs-CRP, change in high-sensitivity CRP, and placebo/no additional treatment on top of the same usual care
Materials to obtain first: Definition of the question: a conventional oral B2 single-ingredient preparation, adults with elevated hs-CRP, change in high-sensitivity CRP, and placebo/no additional treatment on top of the same usual care
Further research: Compare the population, ingredients, endpoints, and comparison boundaries in the obtained manuscript and candidate studies.
Remaining uncertainty: Verifying the definition of the question does not mean that a direct effect has been demonstrated.
Conditions for verification: Link the original effect wording and the actual scope of inclusion and exclusion to the same source location.
Why this condition is needed: This is needed to avoid mixing general discussion of CRP with a single comparison question.
Application exceptions: Conventional CRP, redox associations, clinical anti-inflammatory efficacy, and IBD fatigue are separate questions.
Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed

Related sources S12 S13 S14 S21

N02 · Has actual oral administration of B2 alone been verified in an eligible result?

Current findings: The question being judged is defined as riboflavin/oral, but the actual molecule/route values in the preserved study information are empty and unverified, and the list of linked sources is empty.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Verifying the direction of the question is separate from obtaining evidence of actual exposure in an eligible result.
Reason for missing information: Verifying the direction of the question is separate from obtaining evidence of actual exposure in an eligible result.
Required materials and conditions: Verification of the actual molecule, salt/derivative, route of administration, and single-ingredient composition in the relevant comparison
Materials to obtain first: Verification of the actual molecule, salt/derivative, route of administration, and single-ingredient composition in the relevant comparison
Further research: Link formulation and administration documentation to the population/results tables to verify actual oral exposure to B2 alone.
Remaining uncertainty: Verifying the direction of the question is separate from obtaining evidence of actual exposure in an eligible result.
Conditions for verification: Verify the actual molecule and route for an eligible result using administration documentation.
Why this condition is needed: This is needed to avoid mistaking B2 as specified in the question for an actual administration record from an eligible study.
Application exceptions: Do not turn B1, B-vitamin combinations, or associations with blood vitamers into evidence of B2 administration.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application

Related sources S12 S13 S14 S21

N03 · Are the release profile, manufacture/purity, and batch of the relevant eligible preparation known?

Current findings: The question concerns a conventional oral B2 single-ingredient preparation; the manufacturing origin and the release profile of an eligible preparation remain unverified. S14's detailed release formulation has not been directly verified either.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Wording about a product name or ingredient in the question alone does not certify its actual specifications.
Reason for missing information: Wording about a product name or ingredient in the question alone does not certify its actual specifications.
Required materials and conditions: The exact chemical form, release profile, manufacture/origin, purity, batch, and excipients of the conventional oral single-ingredient preparation
Materials to obtain first: The exact chemical form, release profile, manufacture/origin, purity, batch, and excipients of the conventional oral single-ingredient preparation
Further research: Obtain product/trial-preparation documentation and review differences in applicability between conventional and specialized-release formulations.
Remaining uncertainty: Wording about a product name or ingredient in the question alone does not certify its actual specifications.
Conditions for verification: Verify the specifications of the preparation actually used for an eligible result.
Why this condition is needed: This is needed to avoid automatically combining results for specialized colonic-release preparations with those for conventional B2.
Application exceptions: Plant-part classification is not applicable, but this does not remove the unverified status of manufacture and formulation.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed

Related sources S12 S13 S14 S21

N04 · Can the eligible dose be distinguished from the 10 and 100 mg in related trials?

Current findings: The records of S12 in older adults at 10 mg/day and S13 in Crohn disease at 100 mg/day are preserved, but the dose for an eligible population with elevated hs-CRP remains unverified.
Verification status: Partly verified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not repurpose nominal doses from other populations as actual doses for the current question.
Reason for missing information: Do not repurpose nominal doses from other populations as actual doses for the current question.
Required materials and conditions: Nominal/actual dose, frequency, adherence, and total exposure in an eligible comparison, and administration records from related studies
Materials to obtain first: Nominal/actual dose, frequency, adherence, and total exposure in an eligible comparison, and administration records from related studies
Further research: Compare administration and actual doses in eligible arms using medication/preparation records and records of concomitant intake.
Remaining uncertainty: Do not repurpose nominal doses from other populations as actual doses for the current question.
Conditions for verification: Verify actual exposure in the relevant eligible arms separately from nominal doses in related studies.
Why this condition is needed: This is needed to avoid using doses from other populations as demonstrated or recommended doses for participants with elevated hs-CRP.
Application exceptions: 10 mg/day and 100 mg/day are records from related studies, not an optimal-dose comparison.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed

Related sources S12 S13

N05 · Can the eligible duration be distinguished from the 28 days and 3 weeks in related studies?

Current findings: The recorded durations of S12 at 28 days and S13 at 3 weeks are verified within that limited scope. Duration and follow-up for an eligible population with elevated hs-CRP remain unverified.
Verification status: Partly verified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not extend the 28 days/3 weeks to a directly eligible duration or to long-term effects.
Reason for missing information: Do not extend the 28 days/3 weeks to a directly eligible duration or to long-term effects.
Required materials and conditions: Administration, assessment, and follow-up periods in an eligible study, and the actual time points in candidate studies
Materials to obtain first: Administration, assessment, and follow-up periods in an eligible study, and the actual time points in candidate studies
Further research: Link administration/follow-up and assessment time points using the schedule, assessment plan, and results tables.
Remaining uncertainty: Do not extend the 28 days/3 weeks to a directly eligible duration or to long-term effects.
Conditions for verification: Verify the administration/assessment periods for each outcome in an eligible comparison.
Why this condition is needed: This is needed to avoid fixing the short duration of another study as the appropriate duration for the selected question.
Application exceptions: Do not newly set a common minimum number of weeks or participants.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed

Related sources S12 S13

N06 · Have the selection criteria and underlying diseases for participants with elevated hs-CRP been verified?

Current findings: Selection for elevated levels has not been verified for S12; S13 is a before-and-after comparison in Crohn disease, and S21 involves healthy participants. Results in a population meeting the fixed question remain unverified.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Preserve the distinctions in eligible populations without erasing the existence of related human studies.
Reason for missing information: Preserve the distinctions in eligible populations without erasing the existence of related human studies.
Required materials and conditions: The actual threshold for elevated hs-CRP, repeat testing, diagnoses, age, inclusion/exclusion criteria, and baseline distributions
Materials to obtain first: The actual threshold for elevated hs-CRP, repeat testing, diagnoses, age, inclusion/exclusion criteria, and baseline distributions
Further research: Obtain eligibility criteria, baseline tables, and assay records to compare population concordance and reasons for exclusion for each candidate.
Remaining uncertainty: Preserve the distinctions in eligible populations without erasing the existence of related human studies.
Conditions for verification: Verify the criteria for the actual comparison population selected for elevated levels using a high-sensitivity assay.
Why this condition is needed: This is needed to avoid equating general older-adult, Crohn disease, or healthy populations with a population selected for elevated levels.
Application exceptions: Do not combine results from different underlying diseases into a single population for application.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed

Related sources S12 S13 S14 S21

N07 · Have both the high-sensitivity assay and selection for elevated levels been verified?

Current findings: The original unresolved-items record states that results meeting both the high-sensitivity assay requirement and selection for elevated hs-CRP remain unverified. S12·S13 have assay/selection limitations, while S21 concerns a different endpoint/population.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: The presence of CRP information does not mean that an hs-CRP effect has been verified.
Reason for missing information: The presence of CRP information does not mean that an hs-CRP effect has been verified.
Required materials and conditions: The hs-CRP assay name, sensitivity, specimen, and units, together with selection for elevated levels in the same population
Materials to obtain first: The hs-CRP assay name, sensitivity, specimen, and units, together with selection for elevated levels in the same population
Further research: Compare the original assay methods with baseline assay tables to verify whether a result meets the high-sensitivity criteria.
Remaining uncertainty: The presence of CRP information does not mean that an hs-CRP effect has been verified.
Conditions for verification: Link the actual assay and population selection to the same study/result.
Why this condition is needed: This is needed to avoid arbitrarily substituting high-sensitivity CRP for conventional CRP.
Application exceptions: Do not infer units or high-sensitivity status from figures or product names.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application

Related sources S12 S13 S14 S21

N08 · Have placebo/no additional treatment and shared care been verified for an eligible result?

Current findings: The question specifies placebo/no additional treatment on top of the same usual care. S12's placebo record does not establish eligibility of the population/assay, and S13 has no concurrent randomized comparator.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Results from an eligible comparison for the current question cannot be replaced with a related study design.
Reason for missing information: Results from an eligible comparison for the current question cannot be replaced with a related study design.
Required materials and conditions: The composition and schedule of concurrent comparator arms, shared care, and changes by arm
Materials to obtain first: The composition and schedule of concurrent comparator arms, shared care, and changes by arm
Further research: Link comparator/shared-care documentation to the results and review the meaning of the between-group difference.
Remaining uncertainty: Results from an eligible comparison for the current question cannot be replaced with a related study design.
Conditions for verification: Verify the actual comparator content and differences in care for the selected population/assay.
Why this condition is needed: This is needed to avoid confusing the comparison specified by the question with the actual comparator.
Application exceptions: Do not turn an uncontrolled before-and-after study into a concurrently assigned placebo comparison.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application

Related sources S12 S13 S14 S21

N09 · Have the distinct studies and outcome relationships underlying the four reports been established?

Current findings: The four bibliographic records are linked to the stored study identifiers Tavares-riboflavin-2009, RISE-UP, RIBOGUT, and NCT05803811. Direct eligible replication and linkage of the original participants have not been verified.
Verification status: Partly verified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not tally the 4 reports as 4 eligible studies, 4 independent replications, or a total number of participants.
Reason for missing information: Do not tally the 4 reports as 4 eligible studies, 4 independent replications, or a total number of participants.
Required materials and conditions: Bibliography → trial/study family → endpoint/time point/analysis linkage, and whether there is duplication
Materials to obtain first: Bibliography → trial/study family → endpoint/time point/analysis linkage, and whether there is duplication
Further research: Link registry, paper, and study identifiers to review repeated citations of the same result and separate reports.
Remaining uncertainty: Do not tally the 4 reports as 4 eligible studies, 4 independent replications, or a total number of participants.
Conditions for verification: Compare actual identifiers to distinguish verified study-family relationships from those that remain undetermined.
Why this condition is needed: This is needed to avoid turning the number of stored source identifiers/bibliographic records into the number of independent direct replications.
Application exceptions: Do not create counts of unique participants or independent studies when they remain undetermined.
Referenced methods: M04 §4.6.1–4.6.2 on distinguishing studies from reports; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application

Related sources S12 S13 S14 S21

N10 · Has reading the summaries in this work been distinguished from historical access levels?

Current findings: S12 is a historical record of a publisher abstract; S13, an indexed author abstract/figure legends; S21, an institutional abstract; and S14, a registry shell. Only the preserved summaries were read in this work, with 0 external lookups.
Verification status: Met
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: The original full texts, registry results, and separate logs/numerical files remain unread. There is no field for individual original-source access dates; the recorded verification date is the original review date for the materials as a whole.
Reason for missing information: The original full texts, registry results, and separate logs/numerical files remain unread. There is no field for individual original-source access dates; the recorded verification date is the original review date for the materials as a whole.
Required materials and conditions: Actual acquisition/reading for each material; historical abstract/figure-legend/institutional-abstract/registry-shell access; locations and dates
Materials to obtain first: Actual acquisition/reading for each material; historical abstract/figure-legend/institutional-abstract/registry-shell access; locations and dates
Further research: If follow-up work is authorized, obtain the original file contents (bytes), source locations, and access dates for each material, and record actual reading histories separately.
Remaining uncertainty: The original full texts, registry results, and separate logs/numerical files remain unread. There is no field for individual original-source access dates; the recorded verification date is the original review date for the materials as a whole.
Conditions for verification: Link the records while distinguishing reading the currently preserved summaries from the fact that access to each external original material has not been attempted and the material has not been read in this work.
Why this condition is needed: This is needed to avoid promoting a link or the originally recorded access level into a claim that the full text was read in this work.
Application exceptions: Do not re-record a historical failure to access registry results as a failed access attempt in this work.
Referenced methods: Material-collection/selection principles in M04 §4.5–4.6; the distinction between access and reading and the hyperlink rules are internally designed; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and are internally designed

Related sources S12 S13 S14 S21

N11 · Have the cutoff date and search limitations for the current materials been linked?

Current findings: The search cutoff in the original revision policy and the recorded verification date are 2026-09-15; there is no top-level evidence-cutoff field. The stated limitation is that the original search was not an exhaustive search of primary databases worldwide. Only this preserved-summary conversion was performed in the current work.
Verification status: Met
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Statements of absence mean that eligible results remain unverified within the fixed question and the documents' search scope.
Reason for missing information: Statements of absence mean that eligible results remain unverified within the fixed question and the documents' search scope.
Required materials and conditions: The existing search cutoff and verification date, the current summary-review date, the input scope, and the record that no search was performed
Materials to obtain first: The existing search cutoff and verification date, the current summary-review date, the input scope, and the record that no search was performed
Further research: In a separately authorized update, compare the actual search logs and registration/correction status with the original cutoff date.
Remaining uncertainty: Statements of absence mean that eligible results remain unverified within the fixed question and the documents' search scope.
Conditions for verification: Separate the original dates and the documents' search scope from the scope of work actually performed now.
Why this condition is needed: This is needed to avoid exaggerating the preservation conversion as an up-to-date, exhaustive literature search.
Application exceptions: Do not identify the merely named tasks/R01-007/ or historical search records as files actually read in this work.
Referenced methods: M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and are internally designed

Related sources S12 S13 S14 S21

N12 · Has the actual comparative design for the same question been verified?

Current findings: A placebo trial of conventional CRP, a before-and-after study in Crohn disease, and an analysis in healthy participants exist, but comparative results for an eligible population with elevated hs-CRP have not been verified.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not turn gaps in design details into a conclusion of poor design or 0 human studies.
Reason for missing information: Do not turn gaps in design details into a conclusion of poor design or 0 human studies.
Required materials and conditions: The actual parallel, crossover, cluster/randomized design for an eligible population/assay
Materials to obtain first: The actual parallel, crossover, cluster/randomized design for an eligible population/assay
Further research: Review the design and population/assay concordance across the protocol, Methods section, and results tables.
Remaining uncertainty: Do not turn gaps in design details into a conclusion of poor design or 0 human studies.
Conditions for verification: Directly link the design in the methods to the relevant eligible result.
Why this condition is needed: This is needed to avoid substituting the design label of a related trial for an eligible causal comparison.
Application exceptions: Do not assign a not-applicable status to crossover/cluster designs because the design is unverified.
Referenced methods: M08 §8.1–8.2.3; internal application

Related sources S12 S13 S14 S21

N13 · Have sequence generation, allocation concealment, and baseline balance been verified for an eligible comparison?

Current findings: The currently retained summary does not provide sequence-generation information, allocation concealment, or a baseline table corresponding to an eligible result. The original unused bias assessment axis is also empty.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: This is unverified within the preserved materials; it does not establish that the entire paper leaves the information unreported or determine the magnitude of bias.
Reason for missing information: This is unverified within the preserved materials; it does not establish that the entire paper leaves the information unreported or determine the magnitude of bias.
Required materials and conditions: Allocation procedures, sequence generation, concealment, baseline distributions, and linkage to results
Materials to obtain first: Allocation procedures, sequence generation, concealment, baseline distributions, and linkage to results
Further research: Obtain the Methods section, allocation records, and baseline table to review gaps in confounding/allocation information for each outcome.
Remaining uncertainty: This is unverified within the preserved materials; it does not establish that the entire paper leaves the information unreported or determine the magnitude of bias.
Conditions for verification: Verify whether allocation/baseline documentation for an eligible comparison supports each result.
Why this condition is needed: This is needed to avoid certifying the adequacy of allocation solely from the label placebo.
Application exceptions: Do not fill gaps in information from the original Methods by inventing a conclusion that bias has been established.
Referenced methods: M08 §8.1–8.2.3; internal application

Related sources S12 S13 S14 S21

N14 · Have concurrent treatments and all vitamins in the eligible arms been verified?

Current findings: The value in the concurrent-vitamin record within the preserved nutrition information is empty and unverified. Details of all concurrent vitamins and treatments by arm for an eligible comparison have not been retained.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not impose a rule that changes in the two arms must necessarily be identical.
Reason for missing information: Do not impose a rule that changes in the two arms must necessarily be identical.
Required materials and conditions: Usual treatment, concurrent vitamins/supplements, medication changes, and rescue treatment by arm
Materials to obtain first: Usual treatment, concurrent vitamins/supplements, medication changes, and rescue treatment by arm
Further research: Compare medication, supplementation, and rescue-treatment records with the analysis plan to review the contribution of concomitant treatment and the treatment policies actually compared.
Remaining uncertainty: Do not impose a rule that changes in the two arms must necessarily be identical.
Conditions for verification: Link concomitant treatment/changes by arm in the eligible comparison to the effect of interest.
Why this condition is needed: Needed to avoid mistaking differences in shared care for the contribution of B2 alone.
Application exceptions: Do not fill unverified concurrent-vitamin information with an exposure value of 0.
Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application

Related sources S12 S13 S14 S21

N15 · Have baseline B2, total dietary intake, actual intake, and adherence been verified?

Current findings: Values for baseline nutritional status, total dietary/all-supplement exposure, and the eligible dose are empty/unverified; concurrent exposure also remains unverified.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not fill in actual exposure for an eligible result solely with the nominal amount from a related trial.
Reason for missing information: Do not fill in actual exposure for an eligible result solely with the nominal amount from a related trial.
Required materials and conditions: Deficiency status/measurement, dietary B2, other supplementary exposure, and actual medication intake/adherence by arm
Materials to obtain first: Deficiency status/measurement, dietary B2, other supplementary exposure, and actual medication intake/adherence by arm
Further research: Obtain baseline nutritional tests and intake/medication records to review gaps in analyses of total exposure and adherence.
Remaining uncertainty: Do not fill in actual exposure for an eligible result solely with the nominal amount from a related trial.
Conditions for verification: Link the population's baseline status, total intake, and actual amount to administration records.
Why this condition is needed: Needed to avoid turning the nominal B2 amount into total exposure or an effect of correcting deficiency.
Application exceptions: Do not combine results from a confirmed-deficiency population outside the question as effects of additional supplementation.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application

Related sources S12 S13 S14 S21

N16 · Have changes in high-sensitivity CRP been distinguished from clinical anti-inflammatory efficacy?

Current findings: The selected endpoint is change in high-sensitivity CRP concentration. The preserved nutrition information records it as a laboratory surrogate and states that it is not extended to clinical-event prevention.
Verification status: Met
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Verification of this boundary does not mean that a direct hs-CRP reduction effect or clinical anti-inflammatory efficacy has been verified.
Reason for missing information: Verification of this boundary does not mean that a direct hs-CRP reduction effect or clinical anti-inflammatory efficacy has been verified.
Required materials and conditions: The actual selected endpoint, units, and direction, and boundaries separating it from other inflammatory markers/clinical events
Materials to obtain first: The actual selected endpoint, units, and direction, and boundaries separating it from other inflammatory markers/clinical events
Further research: Link the original outcome definition to clinical results tables to review what belongs to the same question and what belongs to a separate question.
Remaining uncertainty: Verification of this boundary does not mean that a direct hs-CRP reduction effect or clinical anti-inflammatory efficacy has been verified.
Conditions for verification: State the distinction between the selected hs-CRP change and ordinary CRP/other markers/clinical outcomes.
Why this condition is needed: Needed to avoid extending a laboratory surrogate to disease treatment or event prevention.
Application exceptions: The original B/S describes the endpoint of the fixed question; it is not certification of an observed eligible clinical trial.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M03 §3.2.4; internally defined limits on extensions

Related sources S12 S13 S14 S21

N17 · Have sample collection, timing, blinding, and precision for the eligible assay been verified?

Current findings: Verification of the high-sensitivity assay is still outstanding, and details of the relevant eligible measurement procedures, timing, and blinded assessment have not been verified either.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Units in the ordinary-CRP figure were not converted without verification.
Reason for missing information: Units in the ordinary-CRP figure were not converted without verification.
Required materials and conditions: The actual hs-CRP assay, specimen/measurement procedures, assessment time points, conditions by arm, and blinding of those taking measurements
Materials to obtain first: The actual hs-CRP assay, specimen/measurement procedures, assessment time points, conditions by arm, and blinding of those taking measurements
Further research: Compare the assay SOP, collection time points, and blinding documents with the original results.
Remaining uncertainty: Units in the ordinary-CRP figure were not converted without verification.
Conditions for verification: Verify the actual measurement conditions and differences between arms for the selected result.
Why this condition is needed: Needed to distinguish measurement differences from intervention differences.
Application exceptions: Do not automatically judge unverified blinding as failed or adequate.
Referenced methods: M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed

Related sources S12 S13 S14 S21

N18 · Has the actual analysis denominator for each hs-CRP result been verified?

Current findings: The summary describes S12 as a study of 42 participants and S13 as a study of 70 participants. The analysis-sample-size record in the preserved study information is empty/unverified, and the preserved source states that assignment counts must not replace unverified outcome-specific counts (n).
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: The total number of participants in a related study and the analysis count (n) for the currently eligible endpoint are separate quantities.
Reason for missing information: The total number of participants in a related study and the analysis count (n) for the currently eligible endpoint are separate quantities.
Required materials and conditions: Numbers by arm (n) at recruitment/allocation, administration, measurement, completion, and analysis, and the outcome time points
Materials to obtain first: Numbers by arm (n) at recruitment/allocation, administration, measurement, completion, and analysis, and the outcome time points
Further research: Use results tables, flow diagrams, and analysis materials to link denominators at each stage to reasons for exclusion.
Remaining uncertainty: The total number of participants in a related study and the analysis count (n) for the currently eligible endpoint are separate quantities.
Conditions for verification: Verify the analysis denominators by arm corresponding to the selected result.
Why this condition is needed: Needed to avoid repurposing 42·70 as eligible analysis denominators.
Application exceptions: Do not turn a historical numerical record merely named in the preserved source into material with available values by opening it in this work.
Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application

Related sources S12 S13 S14 S21

N19 · Have the reasons for missing data and attrition, and the methods used to handle them, been verified for an eligible result?

Current findings: The current manuscript contains no material that establishes missing data/attrition and handling methods corresponding to an eligible analysis denominator.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: This is a gap within the currently preserved materials, not confirmation that the entire original paper leaves the information unreported or that it failed.
Reason for missing information: This is a gap within the currently preserved materials, not confirmation that the entire original paper leaves the information unreported or that it failed.
Required materials and conditions: Losses, exclusions, discontinuations, missing measurements, and analytical handling/sensitivity analyses by arm
Materials to obtain first: Losses, exclusions, discontinuations, missing measurements, and analytical handling/sensitivity analyses by arm
Further research: Link flow diagrams, plans for handling missing data, and analysis records to review limitations on interpretation of the results.
Remaining uncertainty: This is a gap within the currently preserved materials, not confirmation that the entire original paper leaves the information unreported or that it failed.
Conditions for verification: Verify information on observation losses and their analytical handling for the relevant result.
Why this condition is needed: Needed to avoid turning unverified information into complete follow-up or an absence of events.
Application exceptions: Do not calculate the number of dropouts, their reasons, or their impact from the existing sample size.
Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application

Related sources S12 S13 S14 S21

N20 · Have the eligible between-group effect and analysis population/adjustment been verified?

Current findings: S13 is a before-and-after comparison without a concurrent control, and S21 is an association analysis. The analysis population/model/effect for an eligible hs-CRP comparison has not been verified.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not turn a before-and-after reduction or a correlation into a direct treatment effect versus placebo.
Reason for missing information: Do not turn a before-and-after reduction or a correlation into a direct treatment effect versus placebo.
Required materials and conditions: Effects of assignment/adherence, between-group change/final values, ITT/PP, and adjusted/cross analyses
Materials to obtain first: Effects of assignment/adherence, between-group change/final values, ITT/PP, and adjusted/cross analyses
Further research: Compare analysis plans, models, and results tables by arm to distinguish the effect of interest from the preserved results.
Remaining uncertainty: Do not turn a before-and-after reduction or a correlation into a direct treatment effect versus placebo.
Conditions for verification: Link the effect definition and actual analysis for the same question to the result.
Why this condition is needed: Needed to avoid using uncontrolled before-and-after change and a between-group causal effect as the same value.
Application exceptions: Do not fill in ITT, an adjustment model, or dispersion from names alone.
Referenced methods: M08 §8.2.2, M15 §15.3.1; internal application

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N21 · Have the effect value and units for the same eligible result been verified?

Current findings: The effect estimate for the fixed question has not been verified, and the original calculation and numerical-check records are empty lists. Units in the ordinary-CRP figure and numbers in the S14 search overview were not adopted.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not replace nonsignificance or an empty value with an effect of 0 or a numerical value of 0.
Reason for missing information: Do not replace nonsignificance or an empty value with an effect of 0 or a numerical value of 0.
Required materials and conditions: hs-CRP values by arm, changes, units, dispersion, time points, and original results tables
Materials to obtain first: hs-CRP values by arm, changes, units, dispersion, time points, and original results tables
Further research: Compare original numerical tables and assay units to record the exact comparison values and what remains unverified.
Remaining uncertainty: Do not replace nonsignificance or an empty value with an effect of 0 or a numerical value of 0.
Conditions for verification: Attribute only verified original values to their corresponding population, assay, comparison, and time point.
Why this condition is needed: Needed to avoid arbitrarily repurposing ordinary-CRP values or numbers from search overviews.
Application exceptions: Do not perform new effect calculations/unit conversions or reverse calculations from rounded values.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application

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N22 · Have the original CI, dispersion, and denominator for the relevant effect been verified?

Current findings: The eligible effect and CI have not been verified, and the precision assessment axis is empty. A nonsignificant ordinary-CRP result is not a precisely established null effect for the current question.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: The original uncalculated precision assessment was not changed into a new CX/E0 or an effect of 0.
Reason for missing information: The original uncalculated precision assessment was not changed into a new CX/E0 or an effect of 0.
Required materials and conditions: The reported CI, dispersion, denominator, and model for the same between-group hs-CRP estimate
Materials to obtain first: The reported CI, dispersion, denominator, and model for the same between-group hs-CRP estimate
Further research: Link the estimate, dispersion, interval, and denominator in the relevant results table/model to review the range of effects compatible with them.
Remaining uncertainty: The original uncalculated precision assessment was not changed into a new CX/E0 or an effect of 0.
Conditions for verification: Verify the original reported interval and its basis corresponding to the same estimate.
Why this condition is needed: Needed to avoid declaring a precisely estimated null effect or treatment effect from significance and sample size alone.
Application exceptions: Do not reconstruct intervals from P values, assignment counts, or the SD for a different endpoint.
Referenced methods: M15 §15.3.1–15.3.3; internal application

Related sources S12 S13 S14 S21

N23 · Is there a justified criterion for the importance of a change in high-sensitivity CRP?

Current findings: An eligible effect has not been verified, and this document does not provide a threshold for an important difference or a basis for interpretation for the same comparison.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not reassess an unverified criterion as an inadequate effect or an unfavorable finding.
Reason for missing information: Do not reassess an unverified criterion as an inadequate effect or an unfavorable finding.
Required materials and conditions: The basis for an important difference in the same population/assay and duration, and the corresponding interval
Materials to obtain first: The basis for an important difference in the same population/assay and duration, and the corresponding interval
Further research: Obtain the basis for clinical/patient importance and interpretation of the surrogate to review the scope of applicability of the results.
Remaining uncertainty: Do not reassess an unverified criterion as an inadequate effect or an unfavorable finding.
Conditions for verification: Verify the relationship between the original basis for importance and the interval for the same comparison.
Why this condition is needed: Needed to avoid automatically interpreting a significant difference as a clinically meaningful anti-inflammatory effect.
Application exceptions: Do not propose an arbitrary hs-CRP reduction, minimum n, or duration.
Referenced methods: M15 §15.3.1–15.3.3; internal application; M03 §3.2.4; internally defined limits on extensions

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N24 · Have the prospective plans for the eligible primary endpoint, analysis, and time points been cross-checked?

Current findings: The registered-primary-endpoint record in the preserved study information is empty/unverified, and S14 records a historical basic registry page and failure to render the body. Independent cross-checking of the eligible primary endpoint/plan remains unverified.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not record endpoints as established or a results body as read solely because the record is labeled as a basic registry page.
Reason for missing information: Do not record endpoints as established or a results body as read solely because the record is labeled as a basic registry page.
Required materials and conditions: Cross-checking official registration, protocol, SAP, and changes against actual results
Materials to obtain first: Cross-checking official registration, protocol, SAP, and changes against actual results
Further research: Link official registration versions, protocols/SAPs, and actual results to review changes and areas that have not been cross-checked.
Remaining uncertainty: Do not record endpoints as established or a results body as read solely because the record is labeled as a basic registry page.
Conditions for verification: Compare the same eligible result with the primary endpoint, analysis, and time points in the original plan.
Why this condition is needed: Needed to avoid treating a basic registry page as a plan with verified planned/actual endpoints.
Application exceptions: Material not obtained does not establish nonregistration or selective reporting.
Referenced methods: M08 Table 8.2.a, M04 §4.6.3; internal application; material-collection and selection principles in M04 §4.5–4.6; separation of access from reading and the rules governing hyperlinks are internally designed

Related sources S14

N25 · Is the nonsignificant result in S12 a direct result for this question?

Current findings: The result that no significant CRP difference was reported in the placebo trial in older adults with 42 participants, 10 mg/day, and 28 days has been preserved. Selection for elevated hs-CRP and a high-sensitivity assay have not been verified.
Verification status: Partly verified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not interpret this nonsignificance as an hs-CRP effect of 0, equivalence, or replicated evidence against the effect.
Reason for missing information: Do not interpret this nonsignificance as an hs-CRP effect of 0, equivalence, or replicated evidence against the effect.
Required materials and conditions: The actual high-sensitivity assay, selection for elevated levels, original result values/intervals, and denominator in S12
Materials to obtain first: The actual high-sensitivity assay, selection for elevated levels, original result values/intervals, and denominator in S12
Further research: Use the original abstract/Methods/results tables to cross-check the assay/selection criteria and the actual scope of the nonsignificant result.
Remaining uncertainty: Do not interpret this nonsignificance as an hs-CRP effect of 0, equivalence, or replicated evidence against the effect.
Conditions for verification: Verify whether the original population/assay/results in S12 meet the fixed eligibility criteria.
Why this condition is needed: Needed to avoid hiding a related result showing no significant difference or transferring it to a precisely established null effect on hs-CRP.
Application exceptions: The ordinary-CRP record for 42 participants, a 10 mg dose, and 28 days is not direct evidence of efficacy for the current question.
Referenced methods: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application

Related sources S12

N26 · Is the CRP result in S13 efficacy established through a concurrent comparison?

Current findings: S13 is a before-and-after comparison in 70 people with Crohn disease, using 100 mg/day for 3 weeks, with no concurrent randomized control. Some results concern a fecal-calprotectin subgroup.
Verification status: Partly verified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Preserve the before-and-after CRP material without repurposing it as a between-group hs-CRP treatment effect in the same population.
Reason for missing information: Preserve the before-and-after CRP material without repurposing it as a between-group hs-CRP treatment effect in the same population.
Required materials and conditions: The actual population/assay, comparison, timing, and endpoint/subgroup results in RISE-UP
Materials to obtain first: The actual population/assay, comparison, timing, and endpoint/subgroup results in RISE-UP
Further research: Link the original abstract/figure captions, Methods, and results tables to review distinctions between before-and-after comparisons, subgroups, and controls.
Remaining uncertainty: Preserve the before-and-after CRP material without repurposing it as a between-group hs-CRP treatment effect in the same population.
Conditions for verification: Verify the extent to which the actual design/population/assay answers the selected question.
Why this condition is needed: Needed to avoid turning uncontrolled before-and-after changes and a fecal-calprotectin subgroup into an hs-CRP effect.
Application exceptions: Do not automatically adopt the record of 70 participants, 100 mg, and 3 weeks as an eligible randomized comparison or analysis denominator.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application

Related sources S13

N27 · Is the redox/CRP association in S21 a direct reduction effect?

Current findings: The redox analysis and correlation with CRP in healthy RIBOGUT participants are not a randomized treatment effect of B2 in a population selected for elevated hs-CRP.
Verification status: Partly verified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Retain differences in population/endpoint/design without deleting the original analysis.
Reason for missing information: Retain differences in population/endpoint/design without deleting the original analysis.
Required materials and conditions: The actual population, administration/design, and definitions of the redox/CRP analyses in RIBOGUT
Materials to obtain first: The actual population, administration/design, and definitions of the redox/CRP analyses in RIBOGUT
Further research: Compare the institutional abstract with the original analysis/results to review the boundary between an association and a randomized comparison estimate.
Remaining uncertainty: Retain differences in population/endpoint/design without deleting the original analysis.
Conditions for verification: Verify whether the direction, endpoint, and population of the actual analysis match the causal question posed by the comparison.
Why this condition is needed: Needed to avoid reversing a correlation in healthy participants into a treatment effect in a population with elevated levels.
Application exceptions: Do not generate a new hs-CRP reduction value from an association or mechanism.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application

Related sources S21

N28 · Have the actual population, formulation, and results of NCT05803811 been verified?

Current findings: The historical S14 record documents the basic registry page at the official study URL and a failure to render the body; the results and detailed release formulation could not be directly verified. Numerical values from the introductory information were not adopted.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not judge the overall effect or the absence of research from a single original record of inaccessible material.
Reason for missing information: Do not judge the overall effect or the absence of research from a single original record of inaccessible material.
Required materials and conditions: The body of the official registry record, results tables, release formulation, population/assay, denominator, and linked reports
Materials to obtain first: The body of the official registry record, results tables, release formulation, population/assay, denominator, and linked reports
Further research: If follow-up work is permitted, obtain the official version/results and links to papers, and review the formulation, selection criteria, effect, and denominator.
Remaining uncertainty: Do not judge the overall effect or the absence of research from a single original record of inaccessible material.
Conditions for verification: Verify the registry's exact results and their eligibility for the fixed question using the actual documents.
Why this condition is needed: This is needed to avoid presenting search-result snippets or a registry address as evidence that actual results were obtained.
Application exceptions: Do not turn a historical record of failed access into an absence of research or a failed access attempt in the current work.
Referenced methods: Data-collection and selection principles in M04 §4.5–4.6; the distinction between access and reading and the rules governing hyperlinks were designed for this assessment; M08 Table 8.2.a, M04 §4.6.3; application for this assessment; M04 §4.6.3, M15 §15.3.1–15.3.3; distinctions between statuses were designed for this assessment

Related sources S14

N29 · Have actual research funding, product provision, and author/institutional interests been verified?

Current findings: Funding information for the four evidence records is unverified or was not used in this page's grade. The independence assessment axis for the current eligible result also has an empty value.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not newly fill in the originally undetermined funding information as I1 verification of independence or as confirmed dependence on a manufacturer.
Reason for missing information: Do not newly fill in the originally undetermined funding information as I1 verification of independence or as confirmed dependence on a manufacturer.
Required materials and conditions: Actual research funding, product provision, author employment/declarations, and independent study-family relationships for each report
Materials to obtain first: Actual research funding, product provision, author employment/declarations, and independent study-family relationships for each report
Further research: Obtain the original funding/conflict-of-interest declarations (Funding/COI) and institutional/study-family information to distinguish funding from relationships between reports and replications.
Remaining uncertainty: Do not newly fill in the originally undetermined funding information as I1 verification of independence or as confirmed dependence on a manufacturer.
Conditions for verification: Compare the original declarations/funding for each material with the scope in which research independence has been verified.
Why this condition is needed: This is needed to avoid upgrading unverified funding to a finding of independence or absence of bias.
Application exceptions: Do not automatically exclude results merely because funding was provided.
Referenced methods: Chamgap's own conditions for independence and attribution. The official methods sections used in this pilot do not endorse all of these detailed items; M04 §4.6.1–4.6.2, M15 §15.3.1; application for this assessment

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N30 · Have the original ?/empty values and the no-human-study flag with its bounded scope (no_human_study) been preserved exactly?

Current findings: The original record contains grade ?, an empty score, B/S, and empty values for the remaining unused axes. The true value of the no-human-study flag (no_human_study) is limited to the failure to verify directly eligible results in the document search. No F/E0 was created.
Verification status: Met
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not turn original empty values into the number 0, absence, or the absence of all related human studies.
Reason for missing information: Do not turn original empty values into the number 0, absence, or the absence of all related human studies.
Required materials and conditions: The original grade, score, unused assessment axes, eligible scope, and literal wording of the search judgment at that time
Materials to obtain first: The original grade, score, unused assessment axes, eligible scope, and literal wording of the search judgment at that time
Further research: If new eligible material becomes available within a separately permitted scope, review it while distinguishing the original judgment/conditions from the new event.
Remaining uncertainty: Do not turn original empty values into the number 0, absence, or the absence of all related human studies.
Conditions for verification: Preserve ?, empty values in the retained summaries, Boolean values/empty strings, and the bounded scope at their original locations and in their original bytes.
Why this condition is needed: This is needed to avoid turning an uncalculated value into no effect, 0 studies worldwide, or a condition-fulfillment rate for the new table.
Application exceptions: Do not upgrade the historical judgment in the original verdict into a new scoring result in the current work.
Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules were designed for this assessment; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and were designed for this assessment

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N31 · Has the candidate concerning B6–B2 metabolic interactions been verified as a result of B2 administration?

Current findings: The unresolved additional-lead record (unresolved/additional_lead) records that the original text of the candidate concerning B6–B2 metabolic interactions could not be verified in the earlier review and that the candidate was not adopted as evidence of an effect of B2 administration; the list of linked sources is empty.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: The candidate's original text or registry has not been newly read, and no new search has been performed; it is not made into a fifth report.
Reason for missing information: The candidate's original text or registry has not been newly read, and no new search has been performed; it is not made into a fifth report.
Required materials and conditions: The actual candidate's bibliographic record, original text, molecule/administration/population/endpoint, and result location
Materials to obtain first: The actual candidate's bibliographic record, original text, molecule/administration/population/endpoint, and result location
Further research: If follow-up work is permitted, establish the identifier and compare the original text with the question to review whether to include it.
Remaining uncertainty: The candidate's original text or registry has not been newly read, and no new search has been performed; it is not made into a fifth report.
Conditions for verification: Use the candidate's actual original text to verify whether it concerns an effect of B2 administration.
Why this condition is needed: This is needed to avoid counting a merely identified, unverified candidate as a new human efficacy study.
Application exceptions: Do not invent a source identifier (source_id), number, or paper for the empty list of linked sources.
Referenced methods: The distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/result linkage is an application for this assessment; data-collection and selection principles in M04 §4.5–4.6; the distinction between access and reading and the rules governing hyperlinks were designed for this assessment; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and were designed for this assessment

Related sources

N32 · Have eligible differences by underlying condition or baseline B2 status been compared?

Current findings: The current fixed question does not combine results across underlying conditions. Direct results for eligible comparisons or for modification of the B2 effect by baseline status and condition remain unverified.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Do not infer differences in treatment response from contextual results in different populations.
Reason for missing information: Do not infer differences in treatment response from contextual results in different populations.
Required materials and conditions: Prespecified subgroups, interactions, separate results, and baseline nutritional status within the same comparison
Materials to obtain first: Prespecified subgroups, interactions, separate results, and baseline nutritional status within the same comparison
Further research: If follow-up work is permitted, compare prespecified hypotheses and separate results concerning population/baseline differences.
Remaining uncertainty: Do not infer differences in treatment response from contextual results in different populations.
Conditions for verification: Check whether direct evidence from separate subgroup results or interaction analyses supports the extended claim.
Why this condition is needed: This is needed to avoid using differences between older adults, people with Crohn disease, and healthy participants as verification of subgroups in response to B2.
Application exceptions: Do not impose all subgroup studies as mandatory requirements for the principal question.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed

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N33 · Does the selected question include the optimal dose and persistence after discontinuation?

Current findings: The current table addresses the fixed question of hs-CRP change; optimal dose and maintenance after discontinuation/long-term persistence are not added as separate mandatory claims.
Verification status: Not applicable
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Not applicable is not a judgment that long-term data are absent, that an intervention is safe, or that there is no effect.
Reason for missing information: Not applicable is not a judgment that long-term data are absent, that an intervention is safe, or that there is no effect.
Required materials and conditions: Separate extended questions and materials for direct dose comparisons and follow-up after discontinuation/over the long term
Materials to obtain first: Separate extended questions and materials for direct dose comparisons and follow-up after discontinuation/over the long term
Further research: If an extension is requested, review direct dose comparisons and treatment-discontinuation/follow-up materials as a separate question.
Remaining uncertainty: Not applicable is not a judgment that long-term data are absent, that an intervention is safe, or that there is no effect.
Conditions for verification: Distinguish whether separate claims about optimal dose/maintenance fall within this table's question scope.
Why this condition is needed: This is needed to avoid imposing all extension studies as additional mandatory requirements for the narrow hs-CRP comparison.
Application exceptions: Do not present the unverified original duration as though the optimal duration or long-term effects have already been verified.
Referenced methods: M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification were designed for this assessment

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N34 · Does the hs-CRP question include disease treatment or event prevention?

Current findings: The current question concerns the change in hs-CRP concentration itself. Clinical anti-inflammatory effects or event prevention are not additional mandatory claims in this table.
Verification status: Not applicable
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: This does not mean that clinical effects, anti-inflammatory treatment, or safety have now been verified.
Reason for missing information: This does not mean that clinical effects, anti-inflammatory treatment, or safety have now been verified.
Required materials and conditions: Separate boundaries between clinical anti-inflammatory effects, disease activity, quality of life/events, and the selected change in hs-CRP
Materials to obtain first: Separate boundaries between clinical anti-inflammatory effects, disease activity, quality of life/events, and the selected change in hs-CRP
Further research: If the scope is extended, review direct clinical events and patient-important outcomes as an independent question/sheet.
Remaining uncertainty: This does not mean that clinical effects, anti-inflammatory treatment, or safety have now been verified.
Conditions for verification: State whether the fixed question concerns a change in a numerical value or a separate clinical effect.
Why this condition is needed: This is needed to avoid unconditionally imposing a clinical-event trial as a requirement for a change in a surrogate marker.
Application exceptions: Do not remove the current question or extend it to clinical effects merely because it concerns a surrogate marker.
Referenced methods: M03 §3.2.4; extension boundaries developed for this assessment

Related sources S12 S13 S14 S21

N35 · Have harms/discontinuations for the same population, product, and duration been verified?

Current findings: Safety for the relevant eligible population, product, and duration remains unverified. Short-term tolerability in other populations was not extended to long-term safety, and the original safety status is unknown.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Unverified harms do not mean AE 0 or safety.
Reason for missing information: Unverified harms do not mean AE 0 or safety.
Required materials and conditions: AE collection, participant/event denominators, discontinuations, duration, concomitant use/vulnerable groups for eligible exposures
Materials to obtain first: AE collection, participant/event denominators, discontinuations, duration, concomitant use/vulnerable groups for eligible exposures
Further research: Link harm-collection, discontinuation, denominator, and follow-up information to outcomes/exposures to review applicability over the long term and to vulnerable groups.
Remaining uncertainty: Unverified harms do not mean AE 0 or safety.
Conditions for verification: Verify the actual harm data and scope of collection for the same population/product/duration.
Why this condition is needed: This is needed to avoid turning tolerability in a short trial in another population into long-term safety.
Application exceptions: Do not change the original unknown safety status and short-term contextual materials into a new safety grade.
Referenced methods: M19 §19.1.2–19.2.4; application for this assessment; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for individual study designs were designed for this assessment

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N36 · Has any separate verification of interference/interactions actually been performed, and within what scope?

Current findings: In the nutritional extraction record (nutrition_extraction), the assay-interference and drug-interaction fields (assay_interference and drug_interactions) have empty values and are marked as not separately searched. This is a historical record that no separate systematic/comprehensive search was conducted.
Verification status: Unverified
Materials actually read: The exact preserved summary was actually read; original source materials/external full texts were not read in this work
Why unverified: Only the currently retained summaries were read; do not turn this into a finding of no influence or no drug interactions.
Reason for missing information: Only the currently retained summaries were read; do not turn this into a finding of no influence or no drug interactions.
Required materials and conditions: Data on hs-CRP assay interference and interactions involving the relevant exposure/drugs, and the scope of searches performed
Materials to obtain first: Data on hs-CRP assay interference and interactions involving the relevant exposure/drugs, and the scope of searches performed
Further research: If an extension is permitted, separately review interference and interaction data for the actual assay and concomitant exposures.
Remaining uncertainty: Only the currently retained summaries were read; do not turn this into a finding of no influence or no drug interactions.
Conditions for verification: Check whether the actual materials and review scope support statements about interference/interactions.
Why this condition is needed: This is needed to avoid interpreting the absence of a separate search as absence of an influence.
Application exceptions: Do not turn the question into one about assay bias itself or record an area not searched as failed access.
Referenced methods: M08 Table 8.2.a, M03 §3.2.4; application for this assessment; M19 §19.1.2–19.2.4; application for this assessment; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and were designed for this assessment

Related sources S12 S13 S14 S21