{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3086-main", "verdict_number": "3086", "title": "Oral thiamine hydrochloride (vitamin B1) × Reduction of persistent fatigue in quiescent inflammatory bowel disease", "view_version": "1.0", "view_created_date": "2026-10-31", "criteria_version": "NGM-v3086-TARIF-IBDF-CROSSOVER-1.0", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-15", "review_scope": { "materials_read": "Stored Korean and English manuscript summaries, case-specific conditions and application records, and stored methodological principles", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "No new reading of external clinical abstracts, full papers, registrations or analysis plans was performed. Historical access levels recorded in the manuscript are distinguished from reading the stored summaries in this work. Unverified does not mean that research or an effect is absent.", "date_meaning": "The date retained material was checked, not the date of a latest clinical-literature search." }, "claim_context": { "population": "Adults with quiescent IBD and persistent fatigue after alternative explanations were excluded; not general wellness or all fatigue disorders", "intervention": "Oral thiamine hydrochloride (vitamin B1)", "dose": "600–1800 mg/day according to sex and weight; research regimen", "comparator": "Oral placebo within the same crossover trial", "endpoint": "Improvement in IBD-F fatigue; distinguish individual response threshold from treatment contrast", "duration": "4 weeks of active treatment; crossover design with 4-week washout", "excluded_extensions": "Do not extend this to general vitality, all fatigue, B2 supplementation, attribution to a single ingredient in a combination, prevention of clinical events, general deficiency treatment, sustained long-term effects, an optimal dose or personal dosing instructions." }, "requirements": [ { "item_id": "N01", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Which population, intervention, comparator, duration and endpoint define this independent comparison?", "needed": "Materials linking the current claim to the actual population, intervention, comparator, time point and IBD-F outcome", "role": "Required", "role_reason": "Needed to keep patient-reported fatigue in quiescent IBD distinct from general vitality or treatment of deficiency.", "application_exception": "The Korean and English versions concern the same claim. Do not create new subclaims from the currently empty list of subclaims.", "criterion": "The source specifies a comparison of single-ingredient oral thiamine hydrochloride versus placebo for IBD-F over a 4-week active period in adults with quiescent IBD and persistent fatigue.", "basis": "C01: M03 §3.1, §3.2.1–3.2.4: principles for clarifying the question; detailed separation rules are this case’s own design / C04: M03 §3.2.1; detailed population conditions are this case’s own design / C05: M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and assays is this case’s own design / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is this case’s own design Adaptation to this IBD-F crossover question: Needed to keep patient-reported fatigue in quiescent IBD distinct from general vitality or treatment of deficiency. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare the question elements in the manuscript and trial materials; separate a changed scope into an independent question and record the reason for the change.", "current_reports": [ "S04", "S05" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The selected original claim concerns reduction of persistent fatigue in quiescent inflammatory bowel disease. It is limited to an IBD-F comparison of single-ingredient oral thiamine hydrochloride and placebo within the same crossover trial.", "condition_status": "Met", "status_reason": "The boundaries of the current independent comparison are verified. This does not establish the clinical magnitude or long-term persistence of fatigue reduction.", "missingness": "There is no gap in the boundary of the independent question; product details, analysis and extensions remain separate conditions.", "uncertainty": "There is no gap in the boundary of the independent question; product details, analysis and extensions remain separate conditions. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Materials linking the current claim to the actual population, intervention, comparator, time point and IBD-F outcome" }, { "item_id": "N02", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Was the actual intervention ingredient and salt form thiamine hydrochloride?", "needed": "Trial methods and product identity records specifying the intervention ingredient and salt form", "role": "Required", "role_reason": "Needed to avoid treating other B1 derivatives or B2 vitamer analyses as the same administered ingredient.", "application_exception": "Do not arbitrarily convert the mass of thiamine hydrochloride into the mass of free thiamine.", "criterion": "The actual trial ingredient is identified as thiamine hydrochloride and attributed to the oral B1 intervention.", "basis": "C05: M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and assays is this case’s own design Adaptation to this IBD-F crossover question: Needed to avoid treating other B1 derivatives or B2 vitamer analyses as the same administered ingredient. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare the trial intervention label with the actual product label to establish differences between salt mass and active amount.", "current_reports": [ "S04", "S05" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The stored structure and the same-TARIF report S05 identify the actual intervention as thiamine hydrochloride. This was not a B2 supplementation trial.", "condition_status": "Met", "status_reason": "The narrow identity of the ingredient and salt is verified. This does not include the detailed dosage form or manufacturing batch.", "missingness": "Product details beyond salt identity are addressed in N03.", "uncertainty": "Product details beyond salt identity are addressed in N03. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Trial methods and product identity records specifying the intervention ingredient and salt form" }, { "item_id": "N03", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are the actual product's dosage form, manufacturer, batch and production origin verified?", "needed": "Trial product specifications, manufacturer and batch records, and salt and active-amount labeling", "role": "Required", "role_reason": "The same ingredient name alone does not establish that all marketed products match the trial product.", "application_exception": "Non-applicability of plant-part classification to a chemical ingredient is distinct from unverified production origin, such as synthesis or fermentation.", "criterion": "The trial product's detailed dosage form, manufacturer, batch and production origin are specified in the materials.", "basis": "C05: M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and assays is this case’s own design Adaptation to this IBD-F crossover question: The same ingredient name alone does not establish that all marketed products match the trial product. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare product specifications with the trial methods and separate results for different dosage forms or production origins.", "current_reports": [ "S05" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "Single-ingredient oral thiamine hydrochloride is identified, but the detailed dosage form, manufacturer and synthetic, fermentation or other production origin are unverified. Plant-part classification does not apply to this chemical intervention.", "condition_status": "Partly verified", "status_reason": "The ingredient and single-ingredient oral intervention are known, but detailed product identity and production origin remain incomplete.", "missingness": "Detailed dosage form, manufacturer, batch, production origin and the basis for conversion to active amount are unavailable.", "uncertainty": "Detailed dosage form, manufacturer, batch, production origin and the basis for conversion to active amount are unavailable. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Trial product specifications, manufacturer and batch records, and salt and active-amount labeling" }, { "item_id": "N04", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Was the actual population selected adults with quiescent IBD and persistent fatigue?", "needed": "Eligibility and exclusion materials covering diagnosis, remission, persistent fatigue and exclusion of alternative causes", "role": "Required", "role_reason": "Needed to avoid transferring results directly to populations with different diseases or fatigue-selection criteria.", "application_exception": "Do not extend the term quiescent to equal effects across all IBD subtypes, active disease or ages.", "criterion": "The population is identified as adults with quiescent IBD and persistent fatigue after alternative explanations were excluded.", "basis": "C04: M03 §3.2.1; detailed population conditions are this case’s own design Adaptation to this IBD-F crossover question: Needed to avoid transferring results directly to populations with different diseases or fatigue-selection criteria. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Review trial eligibility criteria and the fatigue-assessment pathway to compare included and excluded populations.", "current_reports": [ "S04", "S05" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The stored manuscript concerns adults with quiescent IBD and persistent fatigue after other explanations were excluded. It was not a trial of general vitality or all fatigue disorders.", "condition_status": "Met", "status_reason": "This narrow population condition is stated. It does not mean that unverified diagnostic details or effects in other populations have been established.", "missingness": "The current summary does not preserve detailed IBD subtype and diagnostic composition or individual exclusion tests.", "uncertainty": "The current summary does not preserve detailed IBD subtype and diagnostic composition or individual exclusion tests. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Eligibility and exclusion materials covering diagnosis, remission, persistent fatigue and exclusion of alternative causes" }, { "item_id": "N05", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are baseline B1 status and effects within deficiency subgroups verified?", "needed": "Baseline B1 measurements, deficiency definitions, subgroup plans and subgroup comparison results", "role": "Supplementary; required for claims about deficiency subgroups", "role_reason": "Needed to avoid turning the average result in selected IBD fatigue into a general claim about correcting deficiency.", "application_exception": "Even when the value is empty and its information state is recorded as confirmed, do not interpret this as confirmation of all deficiency measurements.", "criterion": "Baseline B1 measurements, the deficiency definition and prespecified subgroup comparisons or interaction results are verified.", "basis": "C04: M03 §3.2.1; detailed population conditions are this case’s own design / E08: M03 §3.2.1–3.2.4; dose, duration and effect-modification details are this case’s own design Adaptation to this IBD-F crossover question: Needed to avoid turning the average result in selected IBD fatigue into a general claim about correcting deficiency. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare measurements and interaction analyses for prespecified deficiency subgroups, keeping them distinct from the overall effect.", "current_reports": [ "S05" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The selected scope of quiescent IBD after exclusion of other fatigue explanations is known, but effects across all B1-deficiency subgroups are unverified. The structured baseline-status value is empty.", "condition_status": "Unverified", "status_reason": "The currently stored scope lacks materials verifying deficiency definitions, measurements and subgroup effects.", "missingness": "Baseline B1 measurements, assay methods, deficiency thresholds, prespecified subgroups and interaction estimates are unverified.", "uncertainty": "Baseline B1 measurements, assay methods, deficiency thresholds, prespecified subgroups and interaction estimates are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Baseline B1 measurements, deficiency definitions, subgroup plans and subgroup comparison results" }, { "item_id": "N06", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are the actual doses and dosing frequency specified by sex and weight?", "needed": "Dose schedules by sex and weight, dosing frequency, tablet counts and actual exposure records", "role": "Required", "role_reason": "Needed to avoid turning the research dose range into a uniform dose for every participant or a recommended dose.", "application_exception": "Do not present the range of 600–1800 mg/day as an optimal dose or an instruction for self-dosing.", "criterion": "The dose by sex and weight criteria, units, salt labeling and actual dosing frequency are specified.", "basis": "C05: M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and assays is this case’s own design / E08: M03 §3.2.1–3.2.4; dose, duration and effect-modification details are this case’s own design Adaptation to this IBD-F crossover question: Needed to avoid turning the research dose range into a uniform dose for every participant or a recommended dose. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare dose-allocation schedules with actual dosing records; examine dose effects separately using direct comparisons.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "S04 records a research regimen of 600–1800 mg/day according to sex and weight. The thresholds, actual participant-level doses and dosing frequency are not specified in the currently stored materials.", "condition_status": "Partly verified", "status_reason": "The research range and dose-allocation criteria are known, but the actual intervention within each stratum is not fully verified.", "missingness": "Sex and weight thresholds, stratum-specific doses, dosing frequency, tablet counts and actual amounts taken are unverified.", "uncertainty": "Sex and weight thresholds, stratum-specific doses, dosing frequency, tablet counts and actual amounts taken are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Dose schedules by sex and weight, dosing frequency, tablet counts and actual exposure records" }, { "item_id": "N07", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Was the actual administration route oral?", "needed": "The actual administration route specified in the trial methods", "role": "Required", "role_reason": "Needed to align the claimed route with the actual study route.", "application_exception": "Do not turn verification of an oral route into equivalence with injections, other derivatives or other dosage forms.", "criterion": "The actual TARIF intervention route is verified as oral.", "basis": "C05: M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and assays is this case’s own design Adaptation to this IBD-F crossover question: Needed to align the claimed route with the actual study route. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare the claimed route with the actual route in the study methods and separate other routes.", "current_reports": [ "S04", "S05" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The stored study information and linked records in S04 and S05 identify the actual administration route as oral.", "condition_status": "Met", "status_reason": "The actual oral study route is verified. Equivalence of detailed dosage forms and bioavailability is a separate question.", "missingness": "There is no gap in this narrow route item.", "uncertainty": "There is no gap in this narrow route item. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "The actual administration route specified in the trial methods" }, { "item_id": "N08", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Is the planned sequence of active treatment, washout and alternate treatment periods verified?", "needed": "The protocol and trial methods specifying crossover sequences and each treatment and washout period", "role": "Required", "role_reason": "Needed to avoid extending the 4-week active result to long-term observation or persistence after treatment stops.", "application_exception": "A planned 4-week washout does not itself demonstrate absence of carryover or an adequate washout.", "criterion": "The source specifies a crossover plan of 4 weeks of active treatment, a 4-week washout and 4 weeks of the alternate treatment.", "basis": "C05: M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and assays is this case’s own design / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is this case’s own design / E01: M08 §8.1–8.2.3; this case’s own application Adaptation to this IBD-F crossover question: Needed to avoid extending the 4-week active result to long-term observation or persistence after treatment stops. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare the planned periods with actual visit and treatment schedules, linking effects to each period.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The stored citation for S04 specifies 4 weeks of treatment, a 4-week washout and then 4 weeks of the alternate treatment. The main question concerns a 4-week active period.", "condition_status": "Met", "status_reason": "The narrow planned duration can be verified. Actual completion by sequence and carryover are addressed separately in N12 and N13.", "missingness": "Actual deviations from scheduled visits and completion by sequence are unverified.", "uncertainty": "Actual deviations from scheduled visits and completion by sequence are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "The protocol and trial methods specifying crossover sequences and each treatment and washout period" }, { "item_id": "N09", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are the actual placebo composition and period-specific differences in concomitant and background treatment verified?", "needed": "Placebo specifications and records of background treatment, concomitant vitamins, diet and changes by period", "role": "Required", "role_reason": "The label placebo-controlled alone does not establish that all differences in concomitant treatment, diet and therapy were controlled.", "application_exception": "Do not interpret the manuscript's single-ingredient B1 intervention as meaning there were no concomitant vitamins or medications.", "criterion": "The oral placebo composition, concomitant vitamins, diet, IBD treatment by period and handling of changes are verified.", "basis": "C05: M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and assays is this case’s own design / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; this case’s own application Adaptation to this IBD-F crossover question: The label placebo-controlled alone does not establish that all differences in concomitant treatment, diet and therapy were controlled. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare placebo and background-treatment records by period and sequence, analyzing them alongside differences in the selected intervention.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "An oral placebo comparison within the same crossover trial is verified. Total dietary intake, all supplement exposure and arm-level details of concomitant vitamins are unverified.", "condition_status": "Partly verified", "status_reason": "The comparator type is known, but the actual placebo composition and all shared or concomitant interventions are not verified.", "missingness": "Placebo composition and period-specific diet, supplements, medications, rescue treatment and changes in IBD therapy are unverified.", "uncertainty": "Placebo composition and period-specific diet, supplements, medications, rescue treatment and changes in IBD therapy are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Placebo specifications and records of background treatment, concomitant vitamins, diet and changes by period" }, { "item_id": "N10", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are the actual methods of crossover randomization, concealment and blinding verified?", "needed": "Trial methods covering sequence generation, allocation concealment, blinding and baseline balance", "role": "Required", "role_reason": "The label randomized double-blind alone cannot establish absence of allocation or measurement bias.", "application_exception": "Do not turn unverified methods into confirmed failure of allocation or blinding.", "criterion": "The actual methods for generating and concealing crossover sequences and blinding participants and assessors are verified.", "basis": "E01: M08 §8.1–8.2.3; this case’s own application / E03: M08 Table 8.2.a, M03 §3.2.4; this case’s own application Adaptation to this IBD-F crossover question: The label randomized double-blind alone cannot establish absence of allocation or measurement bias. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare sequence generation, allocation and blinding by outcome in the original methods section, distinguishing unverified information from verified problems.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "S04 is described as a randomized double-blind placebo-controlled crossover trial. The current summary cannot verify implementation details of sequence generation, allocation concealment or blinding.", "condition_status": "Partly verified", "status_reason": "The design label is verified, but the actual conduct of allocation and blinding has not been fully checked.", "missingness": "Details of sequence generation, allocation concealment, implementation and assessment of blinding, and baseline balance are unverified.", "uncertainty": "Details of sequence generation, allocation concealment, implementation and assessment of blinding, and baseline balance are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Trial methods covering sequence generation, allocation concealment, blinding and baseline balance" }, { "item_id": "N11", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are enrollment and the actual analysis denominator for the IBD-F crossover comparison separately identified and verified?", "needed": "Participant flow, numbers measured and completing each period, and the paired IBD-F analysis denominator", "role": "Required", "role_reason": "Needed to avoid substituting the 40 enrolled participants for the endpoint analysis population or the denominator of each independent arm.", "application_exception": "Do not sum crossover participants as independent groups.", "criterion": "Enrollment, treatment and completion numbers and the actual paired IBD-F analysis denominator are verified and linked to each outcome.", "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is this case’s own design / E04: M08 §8.2.2, M15 §15.3.1; this case’s own application Adaptation to this IBD-F crossover question: Needed to avoid substituting the 40 enrolled participants for the endpoint analysis population or the denominator of each independent arm. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare participant flow and analysis populations by period and sequence to verify the actual endpoint denominator.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "S04 records 40 enrolled participants, but the effective denominator for the crossover analysis is unverified. The analysis-denominator value and its linked source list are empty.", "condition_status": "Partly verified", "status_reason": "Only enrollment is verified; the actual analysis denominator for the selected outcome is not established.", "missingness": "Numbers measured, completing treatment and included in paired analyses by treatment and period, and definitions of analysis populations, are unverified.", "uncertainty": "Numbers measured, completing treatment and included in paired analyses by treatment and period, and definitions of analysis populations, are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Participant flow, numbers measured and completing each period, and the paired IBD-F analysis denominator" }, { "item_id": "N12", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are period-specific adherence, withdrawals, missing data and analysis handling verified?", "needed": "Records of adherence, withdrawals, reasons for missing data, actual analysis populations and handling by period and sequence", "role": "Required", "role_reason": "Knowing enrollment does not establish how missing data and deviations from treatment affected the comparison.", "application_exception": "Do not calculate withdrawal or missing-data rates from enrollment alone, or interpret unverified withdrawals as 0 withdrawals.", "criterion": "Adherence, losses and their reasons in each period and sequence, and ITT/PP or missing-data handling, are verified.", "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is this case’s own design / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; this case’s own application / E04: M08 §8.2.2, M15 §15.3.1; this case’s own application Adaptation to this IBD-F crossover question: Knowing enrollment does not establish how missing data and deviations from treatment affected the comparison. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare period-specific measurement losses and treatment deviations with the analysis plan and examine the implications of handling assumptions.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The current manuscript states that effective analysis numbers were not fully verified. The stored summary does not specify period-specific adherence, withdrawals, missing data or actual analysis handling.", "condition_status": "Unverified", "status_reason": "Materials on losses, deviations and analysis handling for the selected crossover comparison have not been obtained.", "missingness": "Period-specific adherence, withdrawal and missing-data numbers and reasons, ITT/PP and imputation procedures are unverified.", "uncertainty": "Period-specific adherence, withdrawal and missing-data numbers and reasons, ITT/PP and imputation procedures are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Records of adherence, withdrawals, reasons for missing data, actual analysis populations and handling by period and sequence" }, { "item_id": "N13", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Is a crossover model addressing sequence, period and carryover effects verified?", "needed": "Crossover sequence data, checks for period and carryover effects, and statistical model specifications", "role": "Required", "role_reason": "Needed to avoid replacing self-controlled data with a comparison that ignores dependence and period effects.", "application_exception": "Do not assume that a 4-week washout eliminates carryover or treat the crossover design as inapplicable.", "criterion": "Actual checks for sequence, period and carryover effects and their handling in the crossover model are verified.", "basis": "E01: M08 §8.1–8.2.3; this case’s own application / E04: M08 §8.2.2, M15 §15.3.1; this case’s own application Adaptation to this IBD-F crossover question: Needed to avoid replacing self-controlled data with a comparison that ignores dependence and period effects. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare the handling of period, sequence and carryover effects with the selected estimand in the original statistical section.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "A 4-week washout is planned, but the formal crossover model is unverified. How sequence, period and carryover effects were examined and handled cannot be established.", "condition_status": "Unverified", "status_reason": "The currently stored scope lacks actual specifications of the model and carryover handling required for this crossover design.", "missingness": "Sequence-specific results, examination of period and carryover effects, and the adjusted model are unverified.", "uncertainty": "Sequence-specific results, examination of period and carryover effects, and the adjusted model are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Crossover sequence data, checks for period and carryover effects, and statistical model specifications" }, { "item_id": "N14", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are the IBD-F version, scale direction, assessment times and measurement conditions verified?", "needed": "Materials on the IBD-F version, scoring, assessment times, collection procedures and measurement conditions", "role": "Required", "role_reason": "Needed to avoid replacing patient-reported fatigue changes with other functional, vitamer or clinical-event outcomes.", "application_exception": "Do not dismiss an outcome merely because it is patient-reported or use the double-blind label as complete verification of measurement.", "criterion": "The IBD-F version, score direction, assessment times, collection procedures and blinding conditions are verified.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is this case’s own design / E03: M08 Table 8.2.a, M03 §3.2.4; this case’s own application Adaptation to this IBD-F crossover question: Needed to avoid replacing patient-reported fatigue changes with other functional, vitamer or clinical-event outcomes. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Review how the scale and assessment schedule were actually used and connect measurement differences or unverified details to the outcome.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The selected endpoint is improvement in patient-reported IBD-F fatigue, and the directions of mean reduction and placebo increase are retained. The scale version, scoring range and detailed assessment schedule are unverified.", "condition_status": "Partly verified", "status_reason": "The endpoint and direction are known, but the complete measurement conditions are not verified.", "missingness": "The IBD-F version and scoring range, detailed assessment times and collection conditions are unverified.", "uncertainty": "The IBD-F version and scoring range, detailed assessment times and collection conditions are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Materials on the IBD-F version, scoring, assessment times, collection procedures and measurement conditions" }, { "item_id": "N15", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Does the paper identify IBD-F improvement as its primary endpoint?", "needed": "Materials linking the paper-defined primary endpoint to the page endpoint", "role": "Required", "role_reason": "Needed to distinguish verification of the paper-stated primary endpoint from a separate registry comparison.", "application_exception": "Do not interpret an empty value as absence of the paper-stated primary-endpoint description. Registry concordance is examined separately in N16.", "criterion": "The manuscript explicitly records IBD-F improvement as the paper-stated primary endpoint.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is this case’s own design / E06: M08 Table 8.2.a, M04 §4.6.3; this case’s own application Adaptation to this IBD-F crossover question: Needed to distinguish verification of the paper-stated primary endpoint from a separate registry comparison. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare the paper-stated primary-endpoint definition with the page outcome, keeping this distinct from comparison against the registry and plans.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The primary-endpoint classification value is empty, but its description explicitly confirms IBD-F improvement as the paper-stated primary endpoint.", "condition_status": "Met", "status_reason": "This narrow attribution to the paper-stated primary endpoint is verified. Concordance with the registry or analysis plan was not verified.", "missingness": "Independent comparison with registration and plans remains unverified in N16.", "uncertainty": "Independent comparison with registration and plans remains unverified in N16. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Materials linking the paper-defined primary endpoint to the page endpoint" }, { "item_id": "N16", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Do endpoints, time points and analyses agree across registration, protocol, analysis plan and results?", "needed": "The actual registration versions, protocol, analysis plan and results report for NCT03634735", "role": "Required", "role_reason": "A registration identifier alone cannot establish concordance between prespecified plans and reporting.", "application_exception": "Do not turn an unchecked registry comparison into confirmed non-registration or selective reporting.", "criterion": "The original registration, protocol and analysis plan are compared with reported endpoints, time points, analyses and reasons for changes.", "basis": "E06: M08 Table 8.2.a, M04 §4.6.3; this case’s own application / C09: M04 §4.5, §4.6.3; limits on converting the current materials follow the user’s scope and this case’s own design Adaptation to this IBD-F crossover question: A registration identifier alone cannot establish concordance between prespecified plans and reporting. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare registration-version timing, endpoints and analyses with the paper to identify prespecified plans and changes.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "S04 has the identifier NCT03634735, but the registered-primary-endpoint value is empty and independent registry-to-primary-endpoint concordance is unverified. The actual registration record was not read in this work.", "condition_status": "Unverified", "status_reason": "The identifier and paper-stated primary-endpoint description alone cannot establish concordance with registration and plans.", "missingness": "The actual registration versions, protocol and analysis plan, timing and reasons for changes, and their comparison with reporting are unverified.", "uncertainty": "The actual registration versions, protocol and analysis plan, timing and reasons for changes, and their comparison with reporting are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "The actual registration versions, protocol, analysis plan and results report for NCT03634735" }, { "item_id": "N17", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are the units, directions and treatment attribution of the reported mean changes verified?", "needed": "Original results containing treatment-specific IBD-F mean changes, units and directions", "role": "Required", "role_reason": "Needed to avoid reversing symptom improvement and placebo worsening or interpreting changes as final scores.", "application_exception": "Do not use descriptive mean changes as an adjusted crossover effect or confidence interval.", "criterion": "A mean fatigue reduction of 4.5 points and placebo increase of 0.75 points are attributed to the respective treatment-specific IBD-F changes.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is this case’s own design / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separating verification states is this case’s own design / E04: M08 §8.2.2, M15 §15.3.1; this case’s own application Adaptation to this IBD-F crossover question: Needed to avoid reversing symptom improvement and placebo worsening or interpreting changes as final scores. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare directions, changes, units and time points in the results table, reporting them separately from adjusted estimates.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The stored S04 result records a mean fatigue reduction of 4.5 points on thiamine and an increase of 0.75 points on placebo. These are treatment-specific mean changes, not an interval for a formal adjusted contrast.", "condition_status": "Met", "status_reason": "The directions, units and attribution of the two descriptive values are stated in the current manuscript. The external original table was not independently verified in this work.", "missingness": "Adjusted effects, dispersion, denominators and intervals remain unverified in N18–N20.", "uncertainty": "Adjusted effects, dispersion, denominators and intervals remain unverified in N18–N20. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Original results containing treatment-specific IBD-F mean changes, units and directions" }, { "item_id": "N18", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are the actual effect of interest and adjusted crossover estimate verified?", "needed": "Analysis population, effect of interest, adjusted model specifications and the formal treatment-contrast estimate", "role": "Required", "role_reason": "Needed to avoid turning arithmetic on mean changes into an effect of assignment, an effect of adherence or an adjusted self-controlled contrast.", "application_exception": "Do not invent ITT, PP or adjusted models, or extend the manuscript's verification limits to a claim that the entire paper lacks data.", "criterion": "The actual analysis population, effect of interest, adjusted crossover model and estimate for the selected contrast are verified.", "basis": "E04: M08 §8.2.2, M15 §15.3.1; this case’s own application / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is this case’s own design Adaptation to this IBD-F crossover question: Needed to avoid turning arithmetic on mean changes into an effect of assignment, an effect of adherence or an adjusted self-controlled contrast. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare the actual effect of interest in the statistical section and results, distinguishing descriptive changes from model estimates.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The current manuscript states that the adjusted crossover effect was not fully verified. The retained arithmetic value of −5.25 points is not an adjusted treatment estimate.", "condition_status": "Unverified", "status_reason": "Statistical materials verifying the formal analysis population and adjusted treatment contrast have not been obtained.", "missingness": "The effect of interest, ITT/PP, adjustment variables, crossover model and formal effect estimate are unverified.", "uncertainty": "The effect of interest, ITT/PP, adjustment variables, crossover model and formal effect estimate are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Analysis population, effect of interest, adjusted model specifications and the formal treatment-contrast estimate" }, { "item_id": "N19", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are paired dispersion, SD/SE and actual analysis numbers for the selected contrast verified?", "needed": "Variance of paired differences, SD/SE, analysis numbers and original analysis specifications", "role": "Required", "role_reason": "Needed to avoid ignoring within-participant crossover correlation or generating an effect size from assumed dispersion or denominators.", "application_exception": "Do not approximate Cohen d or SE using the 40 enrolled participants, P values or unverified SD.", "criterion": "Paired dispersion, SD/SE and the effective analysis denominator appropriate to the selected crossover contrast are verified together.", "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is this case’s own design / E04: M08 §8.2.2, M15 §15.3.1; this case’s own application / E05: M15 §15.3.1–15.3.3; this case’s own application Adaptation to this IBD-F crossover question: Needed to avoid ignoring within-participant crossover correlation or generating an effect size from assumed dispersion or denominators. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare the original tables and model to establish which contrast and analysis population produced the dispersion estimate.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The manuscript records that paired dispersion and effective analysis numbers were not fully verified. Its attempt to use means, standard deviations and analysis numbers lacked complete verified inputs, so no assumed SD or analysis population size was used.", "condition_status": "Unverified", "status_reason": "Paired dispersion and the actual denominator for the selected crossover contrast were not verified.", "missingness": "Paired SD/SE, correlation, effective analysis n and their connection to the model are unverified.", "uncertainty": "Paired SD/SE, correlation, effective analysis n and their connection to the model are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Variance of paired differences, SD/SE, analysis numbers and original analysis specifications" }, { "item_id": "N20", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are the confidence interval and precision of the formal treatment contrast verified?", "needed": "The CI for the formal crossover effect, estimation method, units and connection to the model", "role": "Required", "role_reason": "Statistical significance, trial counts or enrollment alone cannot establish that a difference is precise or important.", "application_exception": "When the original interval is unverified, do not approximate it from P values or substitute an individual response threshold.", "criterion": "The confidence interval, units and model for the selected formal crossover treatment contrast are verified.", "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is this case’s own design / E05: M15 §15.3.1–15.3.3; this case’s own application Adaptation to this IBD-F crossover question: Statistical significance, trial counts or enrollment alone cannot establish that a difference is precise or important. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "After verifying the original interval, examine the range of compatible effects and distinguish its relationship to an importance threshold.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The effect interval for the actual paired treatment contrast is unverified. The reported mean changes and arithmetic difference of −5.25 points are not described as its confidence interval.", "condition_status": "Unverified", "status_reason": "Without a verified formal contrast interval, precision and the range of clinically possible effects cannot be assessed.", "missingness": "The CI, SE, model and interval level for the selected contrast are unverified.", "uncertainty": "The CI, SE, model and interval level for the selected contrast are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "The CI for the formal crossover effect, estimation method, units and connection to the model" }, { "item_id": "N21", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Is −5.25 points attributed only to the retained descriptive arithmetic?", "needed": "Materials linking the retained arithmetic record, its purpose and the correction history", "role": "Required", "role_reason": "Needed to avoid promoting the historical arithmetic value into a new calculation or an adjusted crossover effect.", "application_exception": "Do not recalculate the original formula or restore assumption-dependent standardized effect sizes in this work.", "criterion": "The retained arithmetic record links the string −5.25 to its purpose as descriptive arithmetic rather than an adjusted crossover effect.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is this case’s own design / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separating verification states is this case’s own design / E04: M08 §8.2.2, M15 §15.3.1; this case’s own application Adaptation to this IBD-F crossover question: Needed to avoid promoting the historical arithmetic value into a new calculation or an adjusted crossover effect. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare the value, units and purpose of the existing record with the original result, displaying it separately from the formal estimand.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The retained arithmetic record preserves −5.25 points as a string with the direction of fatigue change aligned, explicitly identifying it as descriptive arithmetic rather than an adjusted crossover effect. The correction history records removal of assumption-dependent standardized effect sizes.", "condition_status": "Met", "status_reason": "The narrow attribution and purpose of this retained value are stated. Arithmetic verification was not repeated as a new clinical effect calculation.", "missingness": "The formal adjusted effect is unverified and is not filled in with this arithmetic value.", "uncertainty": "The formal adjusted effect is unverified and is not filled in with this arithmetic value. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Materials linking the retained arithmetic record, its purpose and the correction history" }, { "item_id": "N22", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Is the within-person 3-point improvement threshold identified as an individual response criterion?", "needed": "Materials defining the individual response threshold, its unit of application and its distinction from between-group importance", "role": "Required", "role_reason": "Needed to avoid turning an individual response threshold into a clinical-importance threshold for a between-group mean difference.", "application_exception": "Do not use 3 points as a between-group MCID, a response-rate denominator or a new NNT.", "criterion": "The manuscript identifies the 3-point improvement threshold as a within-person response criterion.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is this case’s own design / E05: M15 §15.3.1–15.3.3; this case’s own application Adaptation to this IBD-F crossover question: Needed to avoid turning an individual response threshold into a clinical-importance threshold for a between-group mean difference. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare the response definition and its target of application, examining continuous changes, response rates and between-group thresholds separately.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The stored Korean manuscript explicitly states that the within-person 3-point improvement threshold was not used as a between-group MCID. Interpretation of the response criterion is separated from that of between-group change.", "condition_status": "Met", "status_reason": "Its application to an individual response is verified. Actual responder numbers, proportions and the between-group MCID were not verified.", "missingness": "Individual responder numbers, denominators and between-group importance in this setting remain separately unverified.", "uncertainty": "Individual responder numbers, denominators and between-group importance in this setting remain separately unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Materials defining the individual response threshold, its unit of application and its distinction from between-group importance" }, { "item_id": "N23", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Is a validated between-group MCID applicable to this IBD-F crossover comparison verified?", "needed": "Evidence for an MCID applicable to this population, IBD-F version and between-group contrast", "role": "Required for interpretation of clinical importance", "role_reason": "Needed to distinguish the direction of mean change from a between-group difference important to patients.", "application_exception": "Do not borrow the individual 3-point threshold or thresholds from other diseases or scales.", "criterion": "A validated MCID and supporting evidence appropriate to the relevant IBD-F between-group contrast in quiescent IBD are verified.", "basis": "E05: M15 §15.3.1–15.3.3; this case’s own application / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is this case’s own design Adaptation to this IBD-F crossover question: Needed to distinguish the direction of mean change from a between-group difference important to patients. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare the validation population, scale and unit of application of the importance threshold, examining it alongside the formal effect interval.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The original unresolved-information record states that a validated between-group MCID in this setting is unverified. It is not replaced with the within-person 3-point improvement threshold.", "condition_status": "Unverified", "status_reason": "Materials verifying an importance threshold appropriate to the between-group comparison are unavailable.", "missingness": "The between-group MCID in this setting and its validation method are unverified.", "uncertainty": "The between-group MCID in this setting and its validation method are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Evidence for an MCID applicable to this population, IBD-F version and between-group contrast" }, { "item_id": "N24", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Do S04, S05 and S06 belong to the same TARIF trial family?", "needed": "Trial identifiers and materials linking each report's recruitment, endpoints, time points and analyses", "role": "Required", "role_reason": "Needed to avoid counting the primary result, vitamer secondary analysis and follow-up observation as three independent replications.", "application_exception": "Report counts describe the presence of reports, not numbers of independent studies or participants.", "criterion": "The three reports share the study identifier TARIF-NCT03634735, and their different roles are stated.", "basis": "C02: M04 §4.6.1–4.6.2: distinguishing studies from reports; cohort/outcome linkage is this case’s own application / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; this case’s own application Adaptation to this IBD-F crossover question: Needed to avoid counting the primary result, vitamer secondary analysis and follow-up observation as three independent replications. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Link reports by registration, cohort, endpoint and time point to distinguish shared participants from independent recruitment.", "current_reports": [ "S04", "S05", "S06" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "S04, S05 and S06 all have the study identifier TARIF-NCT03634735. They are recorded respectively as the direct crossover trial, vitamer support from the same trial, and a follow-up contextual report from the same family.", "condition_status": "Met", "status_reason": "The shared family identity and each report's role are verified in the currently stored materials. No new count of independent replications or unique total participants is calculated.", "missingness": "Detailed participant overlap between reports is unverified and is not converted into a new total.", "uncertainty": "Detailed participant overlap between reports is unverified and is not converted into a new total. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Trial identifiers and materials linking each report's recruitment, endpoints, time points and analyses" }, { "item_id": "N25", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are the follow-up report's actual dose, duration, design and results verified?", "needed": "Original materials on the actual methods, denominators, dose, duration and results of the S06 follow-up report", "role": "Supplementary; required for claims about persistence or follow-up effects", "role_reason": "The existence of a follow-up citation alone cannot verify long-term persistence of the 4-week crossover effect or independent replication.", "application_exception": "Do not label historical numerical records as files read in this work or adopt unverified follow-up values.", "criterion": "The follow-up report's actual dose, duration, observational design, denominator and results are specifically verified.", "basis": "C02: M04 §4.6.1–4.6.2: distinguishing studies from reports; cohort/outcome linkage is this case’s own application / E08: M03 §3.2.1–3.2.4; dose, duration and effect-modification details are this case’s own design Adaptation to this IBD-F crossover question: The existence of a follow-up citation alone cannot verify long-term persistence of the 4-week crossover effect or independent replication. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare exposure, design and follow-up with the main crossover trial, distinguishing persistence of effect from observational context.", "current_reports": [ "S06" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "S06 retains only its role as a report with different dosing, duration and observational design within the same family. Earlier bibliography and access records are reused; no new effect values are adopted.", "condition_status": "Partly verified", "status_reason": "The family and the difference in follow-up context are known, but specific doses, duration, denominators and effects are unverified.", "missingness": "Follow-up dosing, duration, completion and analysis numbers, and actual results are unverified.", "uncertainty": "Follow-up dosing, duration, completion and analysis numbers, and actual results are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Original materials on the actual methods, denominators, dose, duration and results of the S06 follow-up report" }, { "item_id": "N26", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Do the populations and interventions in S07 and S08 differ from the selected direct comparison?", "needed": "Materials linking other reports' populations and intervention composition to eligibility for the original question", "role": "Required", "role_reason": "Needed to avoid combining results from other diseases and combination products as repeated refutation or independent replication of single-ingredient B1 in IBD.", "application_exception": "Exclusion on eligibility grounds is not a judgment that a study is invalid or that it found no effect.", "criterion": "The actual differences are verified: S07 concerns primary biliary cholangitis, and S08 uses a combination of B1, B6, B12 and magnesium.", "basis": "C02: M04 §4.6.1–4.6.2: distinguishing studies from reports; cohort/outcome linkage is this case’s own application / C04: M03 §3.2.1; detailed population conditions are this case’s own design / C05: M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and assays is this case’s own design / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separating verification states is this case’s own design / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; this case’s own application Adaptation to this IBD-F crossover question: Needed to avoid combining results from other diseases and combination products as repeated refutation or independent replication of single-ingredient B1 in IBD. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare disease, ingredients, comparators and endpoints to assess direct comparability, preserving findings on other questions in their respective roles.", "current_reports": [ "S07", "S08" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "S07 concerns fatigue in primary biliary cholangitis; S08 uses B1, B6, B12 and magnesium in combination. Neither is attributed as independent replication of an isolated B1 or B2 supplementation comparison in IBD.", "condition_status": "Met", "status_reason": "The population and intervention differences and their exclusion roles are stated in the current materials. No positive, non-significant or harm values absent from this manuscript are invented.", "missingness": "Detailed effects and denominators for these other questions were not verified beyond the current manuscript's scope.", "uncertainty": "Detailed effects and denominators for these other questions were not verified beyond the current manuscript's scope. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Materials linking other reports' populations and intervention composition to eligibility for the original question" }, { "item_id": "N27", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are public or nonprofit funding, funder roles, product provision and author relationships actually verified?", "needed": "Original disclosures of funding sources, product provision, funder roles and author conflicts of interest", "role": "Supplementary; required for independence claims", "role_reason": "Needed to avoid treating a public or nonprofit funding label as absence of all conflicts or bias.", "application_exception": "The original I2 and score of 50 are historical judgments, not inherited as fulfillment of the current condition or a new independence certification.", "criterion": "The disclosed scope of actual funding sources, funder roles, product provision and author conflicts is verified.", "basis": "C10: Chamgap’s own independence and attribution conditions. The official methodology sections referenced in this pilot do not endorse all of these detailed items Adaptation to this IBD-F crossover question: Needed to avoid treating a public or nonprofit funding label as absence of all conflicts or bias. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare disclosures with support documents to distinguish verified funding and roles from unverified conflicts.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "S04 records verification of disclosed public or nonprofit support. The English assessment identifies public or nonprofit foundations and records that no funder role was reported. The stored summary lacks full details of funding lists, product provision and author disclosures.", "condition_status": "Partly verified", "status_reason": "Funding type was historically verified, but the current materials cannot fully check actual support, product provision and author relationships.", "missingness": "Individual funding lists, contracts, product provision, complete author disclosures and the actual scope of verification of funder influence are unverified.", "uncertainty": "Individual funding lists, contracts, product provision, complete author disclosures and the actual scope of verification of funder influence are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Original disclosures of funding sources, product provision, funder roles and author conflicts of interest" }, { "item_id": "N28", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are materials available to reproduce the historical search, selection and correction-check scope for the exact question?", "needed": "Historical search and selection logs, the scope of checks for registrations, unpublished evidence and corrections, and date records", "role": "Required", "role_reason": "Needed to avoid extending the presence of currently stored direct evidence into an exhaustive check of the latest worldwide literature.", "application_exception": "Do not claim to have read actual search logs merely from their file paths or interpret absence of a new search as absence of research.", "criterion": "Historical search strategies, databases, dates, selection, registration and correction-check scope are compared with original records.", "basis": "C09: M04 §4.5, §4.6.3; limits on converting the current materials follow the user’s scope and this case’s own design / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separating verification states is this case’s own design Adaptation to this IBD-F crossover question: Needed to avoid extending the presence of currently stored direct evidence into an exhaustive check of the latest worldwide literature. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Within an authorized follow-up scope, review search and selection records to reproduce coverage of omissions and corrections, distinguishing the evidence cutoff.", "current_reports": [], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The fixed-question record that an eligible human result was identified and the search cutoff of 2026-09-15 are retained. The original historical search record was not read in this work, and the manuscript states that not every native database worldwide was searched exhaustively.", "condition_status": "Partly verified", "status_reason": "The cutoff and limited verification scope are known, but the complete actual search and selection records were not reproduced and checked.", "missingness": "Current comparison of historical search strategies, original logs and the full scope of registration, unpublished-evidence and correction searches is unverified.", "uncertainty": "Current comparison of historical search strategies, original logs and the full scope of registration, unpublished-evidence and correction searches is unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Historical search and selection logs, the scope of checks for registrations, unpublished evidence and corrections, and date records" }, { "item_id": "N29", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are persistence of fatigue improvement and effects after stopping treatment beyond 4 weeks directly verified?", "needed": "Comparative results after treatment stops or during long-term follow-up, actual exposure and IBD-F analysis denominators", "role": "Supplementary; required for claims of sustained effects", "role_reason": "Needed to avoid extending a short active-treatment result into long-term persistence of benefit.", "application_exception": "Do not use a washout period or the existence of follow-up citations as direct proof of sustained effects.", "criterion": "Post-treatment or long-term comparative IBD-F estimates and follow-up denominators for the selected intervention are verified.", "basis": "E08: M03 §3.2.1–3.2.4; dose, duration and effect-modification details are this case’s own design Adaptation to this IBD-F crossover question: Needed to avoid extending a short active-treatment result into long-term persistence of benefit. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Link follow-up times with actual exposure and comparators, examining short-term findings separately from sustained effects.", "current_reports": [ "S04", "S06" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The main trial's active treatment lasted 4 weeks. S06 is a follow-up contextual report, but no new effect estimate is adopted and long-term persistence is not established.", "condition_status": "Unverified", "status_reason": "Materials verifying long-term or post-treatment comparative results and denominators for this question are unavailable.", "missingness": "Duration of persistence, actual exposure, follow-up denominators, long-term comparative effects and intervals are unverified.", "uncertainty": "Duration of persistence, actual exposure, follow-up denominators, long-term comparative effects and intervals are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Comparative results after treatment stops or during long-term follow-up, actual exposure and IBD-F analysis denominators" }, { "item_id": "N30", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are direct dose comparisons, an optimal dose and effects by sex and weight verified?", "needed": "Prespecified dose and subgroup plans, direct comparisons, interaction results and denominators", "role": "Supplementary; required for claims about dose or effect modification", "role_reason": "Needed to avoid interpreting a dose-allocation range as a dose-response relationship or superiority in a particular stratum.", "application_exception": "Do not impose new fixed minimum sample sizes or durations, or perform new dose-response calculations.", "criterion": "Direct results from prespecified dose comparisons, sex or weight subgroups and interaction analyses are verified.", "basis": "E08: M03 §3.2.1–3.2.4; dose, duration and effect-modification details are this case’s own design / C05: M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and assays is this case’s own design Adaptation to this IBD-F crossover question: Needed to avoid interpreting a dose-allocation range as a dose-response relationship or superiority in a particular stratum. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Distinguish dose allocation from effect comparison and check direct estimates and interactions for prespecified subgroups.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The research allocation of 600–1800 mg/day according to sex and weight is known, but the current manuscript has no verified values for direct dose comparisons, an optimal dose or effects by sex and weight.", "condition_status": "Unverified", "status_reason": "Dose-allocation information alone cannot verify effect modification or an optimal dose.", "missingness": "Prespecified dose-comparison and subgroup plans, actual stratum-specific effects, denominators and interactions are unverified.", "uncertainty": "Prespecified dose-comparison and subgroup plans, actual stratum-specific effects, denominators and interactions are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Prespecified dose and subgroup plans, direct comparisons, interaction results and denominators" }, { "item_id": "N31", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are vitamer analyses distinguished from patient fatigue and clinical-event outcomes?", "needed": "Materials linking vitamer analyses, actual interventions, patient fatigue and separate clinical-event outcomes", "role": "Required for outcome attribution", "role_reason": "Needed to avoid turning vitamer associations in the same cohort into B2 supplementation effects or prevention of IBD events.", "application_exception": "The current question concerns patient-reported fatigue; clinical-event trials are not imposed as an invariably required condition for this numerical outcome.", "criterion": "The distinction is verified: S05 is a secondary vitamer analysis of participants in a B1 trial, and the selected outcome is patient-reported IBD-F.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is this case’s own design / E09: M03 §3.2.4; this case’s own limits on extension / C02: M04 §4.6.1–4.6.2: distinguishing studies from reports; cohort/outcome linkage is this case’s own application Adaptation to this IBD-F crossover question: Needed to avoid turning vitamer associations in the same cohort into B2 supplementation effects or prevention of IBD events. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare the intervention and measurement targets, separating vitamer associations, symptom changes and event prevention into independent questions.", "current_reports": [ "S05" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The B2-related vitamer analysis in S05 is an observational secondary analysis from the same TARIF family receiving a B1 intervention. The selected question concerns patient symptoms and function rather than circulating vitamers and does not answer prevention of clinical events.", "condition_status": "Met", "status_reason": "The actual intervention, analysis and endpoint categories are distinguished. This does not establish mechanistic causation or prevention of events.", "missingness": "This table did not verify mechanistic causation involving vitamers or direct comparisons of clinical events.", "uncertainty": "This table did not verify mechanistic causation involving vitamers or direct comparisons of clinical events. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Materials linking vitamer analyses, actual interventions, patient fatigue and separate clinical-event outcomes" }, { "item_id": "N32", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are adverse-event collection methods, event and participant counts by arm, and discontinuations verified?", "needed": "Adverse-event definitions, collection, event and participant counts by arm or period, exposure denominators and discontinuations", "role": "Supplementary; required for comparative harms and safety", "role_reason": "Needed to avoid turning a summary statement of mild side effects into low incidence or overall safety.", "application_exception": "Do not impose event-rate conditions on the continuous IBD-F endpoint; examine separate collection methods and denominators for harms.", "criterion": "Adverse-event definitions, collection methods, severity, event and participant counts, denominators and discontinuations by period and sequence are verified.", "basis": "E10: M19 §19.1.2–19.2.4; this case’s own application / H01: M19 §19.1.2–19.2.4; detailed discrimination is this case’s own design / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; this case’s own application / H04: M19 §19.1.2–19.2.4; this case’s own application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; this case’s own application Adaptation to this IBD-F crossover question: Needed to avoid turning a summary statement of mild side effects into low incidence or overall safety. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare harm collection with actual exposure, distinguishing event counts, participant counts, comparative risks and reporting limitations.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The historically accessed abstract is recorded as reporting only mild side effects. Arm-level event counts and long-term safety are unverified, and the structured adverse-event value is empty.", "condition_status": "Partly verified", "status_reason": "There is a historical description of mild side effects, but actual collection systems, denominators, discontinuations and comparative risks are unverified.", "missingness": "Event definitions, systematic collection, severity, participant and event counts, period-specific denominators, discontinuations and comparative estimates are unverified.", "uncertainty": "Event definitions, systematic collection, severity, participant and event counts, period-specific denominators, discontinuations and comparative estimates are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Adverse-event definitions, collection, event and participant counts by arm or period, exposure denominators and discontinuations" }, { "item_id": "N33", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are actual materials investigating drug interactions and assay interference verified?", "needed": "Evidence on interactions and interference for each concomitant medication and assay, with records of verification scope", "role": "Supplementary; required for interaction claims and interpretation of assays", "role_reason": "Needed to avoid turning the original not-searched status into absence of interactions or effects on assays.", "application_exception": "Do not conduct new safety searches or issue personal instructions to take, stop or withhold supplements or tests in this work.", "criterion": "Actual materials investigating interactions and interference between the selected intervention and dose, concomitant drugs and assay methods are verified.", "basis": "E10: M19 §19.1.2–19.2.4; this case’s own application / H05: M19 §19.2.2–19.2.4: design considerations; detailed confounding records are this case’s own design / H08: M19 §19.1.2–19.2.4; this case’s own application Adaptation to this IBD-F crossover question: Needed to avoid turning the original not-searched status into absence of interactions or effects on assays. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare evidence appropriate to concomitant exposure and assay methods separately, distinguishing absence of investigation from absence of effects.", "current_reports": [], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "Drug-interaction and assay-interference values are empty, and no separate search is recorded. No separate comprehensive search was performed; this does not mean there is no effect.", "condition_status": "Unverified", "status_reason": "Actual investigative materials for this separate question are currently unverified.", "missingness": "The scope of verification of interactions and interference across concomitant drugs and assay methods is unverified.", "uncertainty": "The scope of verification of interactions and interference across concomitant drugs and assay methods is unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Evidence on interactions and interference for each concomitant medication and assay, with records of verification scope" }, { "item_id": "N34", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Is direct evidence available for pregnancy, children, active IBD or other fatigue disorders?", "needed": "Actual diagnosis, exposure, comparator, fatigue, harm and follow-up materials for each population extension", "role": "Supplementary; required for population and safety extensions", "role_reason": "Needed to avoid extending a short high-dose study in quiescent IBD to efficacy and safety in every population.", "application_exception": "Do not turn insufficient direct evidence into instructions to delay treatment or self-administer high doses.", "criterion": "Direct evidence on the relevant intervention, exposure, comparator, fatigue and harms is verified for each population extension.", "basis": "C04: M03 §3.2.1; detailed population conditions are this case’s own design / E08: M03 §3.2.1–3.2.4; dose, duration and effect-modification details are this case’s own design / E10: M19 §19.1.2–19.2.4; this case’s own application / H08: M19 §19.1.2–19.2.4; this case’s own application / H09: Chamgap’s own interpretation boundaries. M19 principles are referenced; no official causality tool was applied Adaptation to this IBD-F crossover question: Needed to avoid extending a short high-dose study in quiescent IBD to efficacy and safety in every population. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Define each population as an independent question and review eligibility of direct evidence and limits of applicability and harm assessment.", "current_reports": [ "S04" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The original safety explanation explicitly avoids direct application to pregnancy, children, acute exacerbation or other diseases, and does not present a high-dose study as a self-dosing instruction. Direct evidence for these groups is currently unverified.", "condition_status": "Unverified", "status_reason": "Direct efficacy and harm evidence outside the selected quiescent-IBD population was not verified.", "missingness": "Direct comparisons in special populations, active disease and other conditions, and long-term or rare harms, are unverified.", "uncertainty": "Direct comparisons in special populations, active disease and other conditions, and long-term or rare harms, are unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Actual diagnosis, exposure, comparator, fatigue, harm and follow-up materials for each population extension" }, { "item_id": "N35", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are the stored summaries read in this work distinguished from external materials and historical access levels?", "needed": "Records of each material's existence, access, acquisition and reading status, with exact source locations and hashes", "role": "Required for reading records", "role_reason": "Needed to avoid promoting a summary link or historical full-text access into external reading in this work.", "application_exception": "Do not label the historical failure to obtain the full S04 statistical text as a current access failure. External access was not attempted in this work.", "criterion": "The exact locations read in the stored manuscript are recorded separately from each material's historical access and current external access not attempted or material not read.", "basis": "C03: M04 §4.5–4.6: principles for collecting and selecting materials; separating access from reading and the hyperlink requirements are this case’s own design / C09: M04 §4.5, §4.6.3; limits on converting the current materials follow the user’s scope and this case’s own design Adaptation to this IBD-F crossover question: Needed to avoid promoting a summary link or historical full-text access into external reading in this work. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare material types with actual action receipts, distinguishing a summary reader from the reading status of an external link.", "current_reports": [ "S04", "S05", "S06", "S07", "S08" ], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The complete Korean and English text, structure, 5 evidence records and 5 citations in the currently stored summary were read. S04 historically had publisher-abstract and funding access; S05, S07 and S08 had HTML full-text access; S06 had a provided-abstract-extraction record. External materials were neither accessed nor read in this work.", "condition_status": "Met", "status_reason": "The recording condition separating current local-summary review from material-specific historical access is met. This is not current verification of full clinical papers.", "missingness": "The original full statistical text and supplement for S04 and all linked external materials were not checked in this work.", "uncertainty": "The original full statistical text and supplement for S04 and all linked external materials were not checked in this work. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Records of each material's existence, access, acquisition and reading status, with exact source locations and hashes" }, { "item_id": "N36", "question_type": "Crossover comparison of IBD-F fatigue", "question": "Are the evidence cutoff, material-specific access dates, review dates, original judgment and correction history distinguished?", "needed": "The current manuscript, versions, dates, original judgment, corrections, revision records and input hashes", "role": "Required for version and date attribution", "role_reason": "Needed to avoid substituting a global original-review date for material-specific access dates or using C50 as a new condition score.", "application_exception": "Do not invent separate fields or lists absent from the manuscript; preserve the empty subclaim list and original empty values.", "criterion": "The search cutoff and original review date of 2026-09-15, unverified material-specific access dates and new review date are distinguished, while original grades, scores, axes and corrections are preserved byte for byte.", "basis": "C09: M04 §4.5, §4.6.3; limits on converting the current materials follow the user’s scope and this case’s own design / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separating verification states is this case’s own design Adaptation to this IBD-F crossover question: Needed to avoid substituting a global original-review date for material-specific access dates or using C50 as a new condition score. Roles, exceptions and criteria are this case’s own design; no new clinical assessment was performed.", "condition_origin": "These are case-specific conditions for a known development case whose stored materials had already been read. They do not represent automatic copying, blinding, clinical preregistration or official methodological certification.", "proposed_research": "Compare actual version and date fields; after a change, preserve the complete earlier version, reasons and separate freezing and application of new conditions.", "current_reports": [], "existence": "Limited to the specified locations in the currently stored materials.", "acquired_read": "The relevant locations in the stored review summary were read. Clinical source materials and external full texts were not read for this work.", "observation": "The revision-policy search cutoff and original review date are 2026-09-15. Citations lack material-specific access-date fields, so historical access dates remain empty. Original C50, B/P/R1/I2/EX/B2/CX and the two corrections are retained as historical values.", "condition_status": "Met", "status_reason": "This narrow record of dates, original values and version attribution is linked to actual fields and hashes. It is not a new clinical grade or official methodological certification.", "missingness": "Actual material-specific access dates are absent from the manuscript and remain unverified.", "uncertainty": "Actual material-specific access dates are absent from the manuscript and remain unverified. No new effect sizes, CIs, incidence rates or grades are calculated or reassessed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "The current manuscript, versions, dates, original judgment, corrections, revision records and input hashes" } ], "reports": [ { "report_id": "S04", "title": "Bager et al. — oral thiamine and fatigue in quiescent IBD (2021)", "url": "https://onlinelibrary.wiley.com/doi/10.1111/apt.16166", "report_type": "Publisher article abstract and funding-information page (historical access)", "existence": "The stored bibliography, linked URLs and result summaries were checked. The current public availability of external materials was not newly queried.", "acquired_read": "Stored manuscript summaries and condition-application records were read. External abstracts, full papers, registrations and analysis plans were not attempted, acquired or read in this work.", "study_family": "TARIF-NCT03634735", "independent_replication": "This is a direct report from the same TARIF trial. Other reports from the same family are not summed as independent replications.", "observed_result": "Recorded at preservation: TARIF was a randomized double-blind placebo-controlled crossover trial with 40 enrolled participants; the actual paired IBD-F analysis denominator is unverified. Thiamine 600–1800 mg/day was allocated by sex and weight for 4 weeks, followed by a 4-week washout and 4 weeks of the alternate intervention. A mean fatigue reduction of 4.5 points versus a placebo increase of 0.75 points is recorded; the retained −5.25 points is descriptive arithmetic, not an adjusted crossover effect or CI. The within-person 3-point improvement threshold is distinguished from a between-group MCID. Public or nonprofit support was historically verified, but the complete statistical section and supplement were not obtained at that time.", "result_level": "The original review's summary and attribution are retained. This is not new reading or regrading of external clinical originals.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Stored summary of bibliography, evidence and manuscript", "public_status": "Stored material", "access_status": "Stored summary accessed and read", "acquired": true, "actually_read": "Stored summary read", "as_of": "2026-10-31", "qualification": "This is the stored summary read in this work. It does not inherit the external paper's full-text reading record.", "material_id": "S04-M1", "url": null }, { "material_type": "Publisher article abstract and funding-information page (historical access)", "public_status": "Current public availability unverified", "access_status": "External access not attempted in this work", "acquired": false, "actually_read": "Not read in this work", "as_of": null, "qualification": "Historical recorded access level: publisher abstract and funding information. Material-specific access dates are unverified; external access, acquisition and reading were not performed in this work.", "material_id": "S04-M2", "url": "https://onlinelibrary.wiley.com/doi/10.1111/apt.16166" } ], "links": [ { "label": "Official source", "url": "https://onlinelibrary.wiley.com/doi/10.1111/apt.16166" } ] }, { "report_id": "S05", "title": "B-vitamins and metabolites in quiescent IBD with fatigue treated with oral thiamine (2023)", "url": "https://link.springer.com/article/10.1186/s10020-023-00741-3", "report_type": "Original article HTML full text (historical access)", "existence": "The stored bibliography, linked URLs and result summaries were checked. The current public availability of external materials was not newly queried.", "acquired_read": "Stored manuscript summaries and condition-application records were read. External abstracts, full papers, registrations and analysis plans were not attempted, acquired or read in this work.", "study_family": "TARIF-NCT03634735", "independent_replication": "This is a secondary vitamer analysis from the same TARIF trial family, not independent replication.", "observed_result": "Recorded at preservation: the actual trial intervention was oral thiamine hydrochloride. B2-related vitamer analyses were observational secondary analyses in the same TARIF family, not a B2 supplementation trial or independent replication. The actual denominator for the relevant result is not specified as verified in this manuscript, and historical numerical records were not read in this work.", "result_level": "The original review's summary and attribution are retained. This is not new reading or regrading of external clinical originals.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Stored summary of bibliography, evidence and manuscript", "public_status": "Stored material", "access_status": "Stored summary accessed and read", "acquired": true, "actually_read": "Stored summary read", "as_of": "2026-10-31", "qualification": "This is the stored summary read in this work. It does not inherit the external paper's full-text reading record.", "material_id": "S05-M1", "url": null }, { "material_type": "Original article HTML full text (historical access)", "public_status": "Current public availability unverified", "access_status": "External access not attempted in this work", "acquired": false, "actually_read": "Not read in this work", "as_of": null, "qualification": "Historical recorded access level: article HTML full text. Material-specific access dates are unverified; external access, acquisition and reading were not performed in this work.", "material_id": "S05-M2", "url": "https://link.springer.com/article/10.1186/s10020-023-00741-3" } ], "links": [ { "label": "Official source", "url": "https://link.springer.com/article/10.1186/s10020-023-00741-3" } ] }, { "report_id": "S06", "title": "Thiamine follow-up in patients with quiescent IBD and fatigue", "url": "https://pubmed.ncbi.nlm.nih.gov/34592862/", "report_type": "PubMed bibliography and abstract index; record of provided abstract extraction (historical reuse)", "existence": "The stored bibliography, linked URLs and result summaries were checked. The current public availability of external materials was not newly queried.", "acquired_read": "Stored manuscript summaries and condition-application records were read. External abstracts, full papers, registrations and analysis plans were not attempted, acquired or read in this work.", "study_family": "TARIF-NCT03634735", "independent_replication": "This is a follow-up contextual report from the same TARIF trial family, not independent replication.", "observed_result": "Recorded at preservation: follow-up context concerns different doses, durations and observational designs within the same TARIF family. Only prior bibliography and access records are reused; this does not verify new effect values in the current work. Actual follow-up doses, durations and denominators are not specified in the current manuscript.", "result_level": "The original review's summary and attribution are retained. This is not new reading or regrading of external clinical originals.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Stored summary of bibliography, evidence and manuscript", "public_status": "Stored material", "access_status": "Stored summary accessed and read", "acquired": true, "actually_read": "Stored summary read", "as_of": "2026-10-31", "qualification": "This is the stored summary read in this work. It does not inherit the external paper's full-text reading record.", "material_id": "S06-M1", "url": null }, { "material_type": "PubMed bibliography and abstract index; record of provided abstract extraction (historical reuse)", "public_status": "Current public availability unverified", "access_status": "External access not attempted in this work", "acquired": false, "actually_read": "Not read in this work", "as_of": null, "qualification": "This records a historically provided abstract extraction. The actual historical access level of the PubMed page itself and material-specific access dates are unverified. External access, acquisition and reading were not performed in this work.", "material_id": "S06-M2", "url": "https://pubmed.ncbi.nlm.nih.gov/34592862/" } ], "links": [ { "label": "Official source", "url": "https://pubmed.ncbi.nlm.nih.gov/34592862/" } ] }, { "report_id": "S07", "title": "High-dose oral thiamine and fatigue in primary biliary cholangitis (2024)", "url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0301354", "report_type": "Original article HTML full text (historical access)", "existence": "The stored bibliography, linked URLs and result summaries were checked. The current public availability of external materials was not newly queried.", "acquired_read": "Stored manuscript summaries and condition-application records were read. External abstracts, full papers, registrations and analysis plans were not attempted, acquired or read in this work.", "study_family": "PBC-thiamine-2024", "independent_replication": "The population has a different disease, so this is not counted as independent replication or repeated refutation for the selected IBD-fatigue question.", "observed_result": "Recorded at preservation: this fatigue trial concerned primary biliary cholangitis, a disease distinct from IBD. It was not counted as independent replication or repeated refutation of single-ingredient B1 for IBD fatigue. No detailed effect values or actual analysis denominators were newly adopted in this manuscript.", "result_level": "The original review's summary and attribution are retained. This is not new reading or regrading of external clinical originals.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Stored summary of bibliography, evidence and manuscript", "public_status": "Stored material", "access_status": "Stored summary accessed and read", "acquired": true, "actually_read": "Stored summary read", "as_of": "2026-10-31", "qualification": "This is the stored summary read in this work. It does not inherit the external paper's full-text reading record.", "material_id": "S07-M1", "url": null }, { "material_type": "Original article HTML full text (historical access)", "public_status": "Current public availability unverified", "access_status": "External access not attempted in this work", "acquired": false, "actually_read": "Not read in this work", "as_of": null, "qualification": "Historical recorded access level: article HTML full text. Material-specific access dates are unverified; external access, acquisition and reading were not performed in this work.", "material_id": "S07-M2", "url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0301354" } ], "links": [ { "label": "Official source", "url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0301354" } ] }, { "report_id": "S08", "title": "Vitamin B complex plus magnesium and fatigue in IBD (2026)", "url": "https://www.nature.com/articles/s41598-026-49880-7", "report_type": "Original article HTML full text (historical access)", "existence": "The stored bibliography, linked URLs and result summaries were checked. The current public availability of external materials was not newly queried.", "acquired_read": "Stored manuscript summaries and condition-application records were read. External abstracts, full papers, registrations and analysis plans were not attempted, acquired or read in this work.", "study_family": "IBD-Bcomplex-Mg-2026", "independent_replication": "As a combination intervention, this is not included as independent replication of an isolated B1 effect.", "observed_result": "Recorded at preservation: the IBD-fatigue intervention combined B1, B6, B12 and magnesium. Its findings were not attributed to B2 or isolated B1, or counted as independent replication of a single-ingredient thiamine-hydrochloride comparison. Detailed doses, results and denominators are not specified as verified in this manuscript.", "result_level": "The original review's summary and attribution are retained. This is not new reading or regrading of external clinical originals.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Stored summary of bibliography, evidence and manuscript", "public_status": "Stored material", "access_status": "Stored summary accessed and read", "acquired": true, "actually_read": "Stored summary read", "as_of": "2026-10-31", "qualification": "This is the stored summary read in this work. It does not inherit the external paper's full-text reading record.", "material_id": "S08-M1", "url": null }, { "material_type": "Original article HTML full text (historical access)", "public_status": "Current public availability unverified", "access_status": "External access not attempted in this work", "acquired": false, "actually_read": "Not read in this work", "as_of": null, "qualification": "Historical recorded access level: article HTML full text. Material-specific access dates are unverified; external access, acquisition and reading were not performed in this work.", "material_id": "S08-M2", "url": "https://www.nature.com/articles/s41598-026-49880-7" } ], "links": [ { "label": "Official source", "url": "https://www.nature.com/articles/s41598-026-49880-7" } ] } ], "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly record the question, eligibility conditions and reasons for changes; distinguish intervention variants.", "review_level": "Stored method principles, application records and copy hashes were checked. No new retrieval of external methods documents or execution of an entire official assessment tool was performed." }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Distinguish and link studies and reports; do not omit studies solely because outcomes are unreported.", "review_level": "Stored method principles, application records and copy hashes were checked. No new retrieval of external methods documents or execution of an entire official assessment tool was performed." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Fix the outcome and effect of interest, then review randomization, deviations, missing data, measurement and selective reporting.", "review_level": "Stored method principles, application records and copy hashes were checked. No new retrieval of external methods documents or execution of an entire official assessment tool was performed." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effects, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "Stored method principles, application records and copy hashes were checked. No new retrieval of external methods documents or execution of an entire official assessment tool was performed." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Harm questions may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence.", "review_level": "Stored method principles, application records and copy hashes were checked. No new retrieval of external methods documents or execution of an entire official assessment tool was performed." } ], "status_dictionary": { "Met": "The relevant narrow identity, attribution of original values, outcome category or explicit recording condition is verified. This does not certify overall clinical efficacy or safety.", "Partly verified": "Some of the actual information required by the question is verified, but product, measurement, denominator or analysis details remain incomplete.", "Unverified": "The relevant actual facts or analyses cannot be established within the currently stored scope. This does not mean an effect of 0, absence of research worldwide or an access failure in this work.", "Conflicting information": "Actual reports of the same fact disagree. This is distinct from successful preservation of a record.", "Not reported": "Limited to explicitly identified materials or sections actually read. It does not indicate absence of information throughout an unread full paper.", "Not applicable": "Used only with a specific reason why the question's applicability conditions are not met; not a substitute for unread material.", "Inaccessible": "Distinguishes historical access failures from failures of an actual current attempt. It is not assigned when external access was not attempted in this work.", "Review incomplete": "Limited to the absence of comparison with external original materials in this work. This is distinct from the completed local stored-summary review." }, "study_overlap": { "state": "Family linkage verified; total unique participant count unverified", "unique_trial_count": null, "unique_participant_count": null, "reason": "S04, S05 and S06 report direct results, a secondary vitamer analysis and follow-up context from the same TARIF trial family. Report counts are not summed as independent replications or unique participants. S07 concerns primary biliary cholangitis, a different population; S08 is a combination intervention. Detailed participant overlap and the total unique participant count are unverified." }, "history": [ { "date": "2026-10-31", "kind": "Public reader/material separation", "view_version": "1.0", "change": "Public pages and materials were prepared from the existing 36 items. No new clinical search, verification-status changes or scoring were performed." } ], "language": "en", "translation_date": "2026-10-31" }