{ "schema_version": "chamgap-public-criteria-1.0", "title": "Ordinary thiamine (vitamin B1); the question targets an oral single ingredient, with actual salt/product unverified × Reduction of 12-week HDRS total when added at SSRI initiation in adult MDD inpatients", "criteria_version": "v3120-THIAMINE-MDD-HDRS12-1.1", "criteria_date": "2026-10-05", "condition_origin": "Chamgap application criteria", "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 criteria and reasons for changes, and distinguish variations in the intervention.", "review_level": "Historical reuse of the actual retained HTML copies and SHAs for 1585 and the methodological principles directly reviewed at that time. This is not new reading of full methodological texts, official implementation or clinical certification in this review." }, { "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, and do not omit a study solely because its outcomes are not reported.", "review_level": "Historical reuse of the actual retained HTML copies and SHAs for 1585 and the methodological principles directly reviewed at that time. This is not new reading of full methodological texts, official implementation or clinical certification in this review." }, { "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": "Hold the outcome and effect of interest fixed, then assess randomization, deviations, missing data, measurement and selective reporting.", "review_level": "Historical reuse of the actual retained HTML copies and SHAs for 1585 and the methodological principles directly reviewed at that time. This is not new reading of full methodological texts, official implementation or clinical certification in this review." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "Historical reuse of the actual retained HTML copies and SHAs for 1585 and the methodological principles directly reviewed at that time. This is not new reading of full methodological texts, official implementation or clinical certification in this review." }, { "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": "Questions about harms may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence.", "review_level": "Historical reuse of the actual retained HTML copies and SHAs for 1585 and the methodological principles directly reviewed at that time. This is not new reading of full methodological texts, official implementation or clinical certification in this review." } ], "status_dictionary": { "Met": "The record's identity, boundaries and conditions for preservation/distinction can be explained. This differs from confirmation of treatment efficacy/safety or official certification.", "Partly verified": "Some information for the selected condition is linked, but specific gaps remain.", "Unverified": "Required values/conditions cannot be established within the material currently read. This does not mean no research, an effect of 0 or 0 events.", "Conflicting information": "A specific discrepancy in the level of verification of deficiency statements or in original bibliographic details/reporting/hierarchy. Differences in time points, denominators or designs alone are not automatically designated as conflicts.", "Not applicable": "Used only when there is an actual reason why the selected condition does not apply.", "Not reported": "Limited to a gap at a specific retained location actually read; not extended to nonreporting throughout the external original paper.", "Inaccessible": "Used only when an actual current access attempt has failed. This differs from external access not attempted in this review or historical failures.", "Review incomplete": "An actual pending state of individual table preparation/review, separate from unverified/unread clinical material." }, "requirements": [ { "item_id": "N01", "question_type": "Claim and independent-question boundaries", "question": "Which adults, adjunctive treatment and 12-week outcome does this table address?", "needed": "Original claim, facets and subclaims, and clinical questions excluded from the same page", "role": "Required", "role_reason": "Needed to prevent the question about total depressive symptoms from shifting to general mood, remission or suicide prevention.", "application_exception": "Response, remission, relapse and suicide-related events remain separate questions rather than mandatory outcomes for this total-score question.", "criterion": "Link the original /ko/effect to the population, addition at SSRI initiation and HDRS at 12 weeks, and explain overlap between parent and subordinate questions.", "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are custom-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed; M03 §3.2.4; custom boundaries on extensions", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future research should prespecify HDRS total at 12 weeks and response, remission and suicide-related events as separate outcomes." }, { "item_id": "N02", "question_type": "Current source and identity", "question": "Do the current published source and this summary have the same identity?", "needed": "Current loader-selected path, original SHA, ID/canonical URL, version and actual publication receipt", "role": "Required", "role_reason": "Needed to avoid confusing historical wording about unassigned identifiers and nondeployment with the current ID/URL.", "application_exception": "Historical publication-readiness wording retained in KO is not deleted or reinterpreted as a site-publication event in this review.", "criterion": "Compare the current original and snapshot bytes, ID/canonical URL and reference date.", "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are custom-designed; M04 §4.5–4.6 principles for collecting/selecting materials; the separation of access from reading and the hyperlink contract are custom-designed; M04 §4.5, §4.6.3; limitations of the current material conversion follow the user-defined scope and custom design", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Record identities, dates and publication events separately by version, without creating new research results." }, { "item_id": "N03", "question_type": "Study and report families", "question": "Were the 21 reports kept from being counted repeatedly as unique trials?", "needed": "Original reports, figures, registrations, repositories, a family linkage table and unique-participant identity information", "role": "Required", "role_reason": "Needed to avoid counting figures, repositories, indexes and reviews for the same DOI as independent replications.", "application_exception": "Preserve the bibliography count, but do not estimate unresolved unique-study or participant counts or turn the three candidates into directly eligible trials.", "criterion": "Explain the roles of the S01 series as one family, S03 as a separate candidate and S04 as an indirect family.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is a custom application; M04 §4.6.1–4.6.2, M15 §15.3.1; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future syntheses should first create study-level outcome tables after comparing registration numbers, authors, recruitment institutions, periods and participant overlap." }, { "item_id": "N04", "question_type": "Actual scope of reading", "question": "What was read in this review, and what was the historical level of access?", "needed": "Retained source/citation, access_level/date/locator, and actual files and reading events", "role": "Required", "role_reason": "Needed to avoid promoting the summary of the current stored summary to reading the original paper, figure or full text.", "application_exception": "Past failures, partial reading and reports of full-text access remain historical records; they are not reused as inaccessibility or full-text reading in this review.", "criterion": "Separate existence, access, acquisition, reading and current/historical dates for each material type.", "basis": "M04 §4.5–4.6 principles for collecting/selecting materials; the separation of access from reading and the hyperlink contract are custom-designed; M04 §4.5, §4.6.3; limitations of the current material conversion follow the user-defined scope and custom design", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "When materials are acquired in the future, record the sections and tables actually read, file SHA and access events separately for each material type." }, { "item_id": "N05", "question_type": "Adult inpatient population", "question": "What are the candidate trial's population and baseline depression severity?", "needed": "Original eligibility criteria, age range, baseline tables by arm, inpatient setting and recruitment flow", "role": "Required", "role_reason": "Needed to avoid applying mood studies in healthy people or other diseases to adult MDD inpatients.", "application_exception": "Do not infer age ranges, arm composition or the status of all participants from mean age or the percentage of women.", "criterion": "Distinguish the reporting level and unverified details of MDD inpatient status, HDRS >24 and means/percentages.", "basis": "M03 §3.2.1; detailed population conditions are custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Specify baseline severity and representativeness in the same inpatient MDD population and present balance between arms." }, { "item_id": "N06", "question_type": "Diagnosis and special populations", "question": "Have the MDD diagnostic framework, episode, treatment resistance and major exclusions been verified?", "needed": "Original diagnostic interview/DSM/ICD, episode/resistance definitions, exclusion criteria and baseline tables by population", "role": "Required", "role_reason": "Needed to avoid interpreting the reported MDD label as verification of a specific diagnostic procedure, treatment resistance or exclusion of bipolar disorder.", "application_exception": "Do not fill in unverified exclusions, such as pregnancy, bipolar disorder or renal/liver disease, as if they had already been applied.", "criterion": "Link diagnosis, episode, treatment resistance, comorbidities and the scope of exclusions to the original methods.", "basis": "M03 §3.2.1; detailed population conditions are custom-designed; M03 §3.2.1–3.2.4; details of dose, persistence and effect modification are custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Prespecify diagnostic procedures and episode/resistance criteria, and analyze applicability to special populations separately." }, { "item_id": "N07", "question_type": "Deficiency, nutrition and alcohol use", "question": "Was the candidate population thiamine-deficient or thiamine-replete?", "needed": "Original baseline thiamine tests/deficiency criteria, dietary/nutritional/alcohol-use records and the review's original citation location", "role": "Required", "role_reason": "Needed to avoid combining correction of deficiency with the effect of additional supplementation in a replete state.", "application_exception": "Do not use the secondary (2nd) review's word deficient to establish the original report's testing, deficiency threshold or replete status.", "criterion": "Separate baseline thiamine markers/thresholds, meals, nutrition and alcohol use from the verification level of secondary (2nd) statements.", "basis": "M03 §3.2.1; detailed population conditions are custom-designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed; M03 §3.2.1–3.2.4; details of dose, persistence and effect modification are custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future research should measure baseline status and assess interaction by prespecified deficiency status." }, { "item_id": "N08", "question_type": "Molecule and single-ingredient composition", "question": "Can ordinary thiamine be distinguished from the actual salt and single-ingredient product?", "needed": "Original trial product name, salt, active/added ingredients, manufacturing/formulation documents and administration records", "role": "Required", "role_reason": "Needed to avoid assigning the identity of derivatives, combinations or other products to the candidate trial.", "application_exception": "Derivatives such as benfotiamine and TTFD, combinations and injections are excluded from the question, but the candidate product is not presumed to have been a single-ingredient preparation.", "criterion": "Show separately the question target and the level of verification of the actual label, salt, source and composition in the original report.", "basis": "M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and tests is custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future direct comparisons should predefine and disclose the salt, product and composition of ordinary thiamine and the control product." }, { "item_id": "N09", "question_type": "Actual route of administration", "question": "Was oral administration verified in the candidate MDD original report?", "needed": "Actual route of administration, product and prescription records in the candidate original report's Methods", "role": "Required", "role_reason": "Needed to avoid turning an oral-administration question into a fact of actual oral administration.", "application_exception": "The review's oral-administration information is a lead for tracing the original report, not verification of the route in that report.", "criterion": "Distinguish the actual route in the original report from the question's route, and link the route-verification gap to its location.", "basis": "M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and tests is custom-designed; M04 §4.5–4.6 principles for collecting/selecting materials; the separation of access from reading and the hyperlink contract are custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future comparisons should document oral administration and actual intake, and separate these from injection and derivative data." }, { "item_id": "N10", "question_type": "Dose, intake and adherence", "question": "Have the actual prescribed dose and administration regimen in S01 been verified?", "needed": "S01 original prescription/product, daily and per-administration doses, frequency, meal timing, adherence records and handling of deviations", "role": "Required", "role_reason": "Needed to avoid transferring 300 mg/day from another study or review into a verified dose for the candidate trial.", "application_exception": "Do not arbitrarily convert hydrochloride mg or thiamine-equivalent amounts, or fill in unverified frequency, meal timing or adherence.", "criterion": "Distinguish daily/per-administration doses, frequency, meal timing, loading/maintenance and adherence from study duration.", "basis": "M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and tests is custom-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; custom application; M03 §3.2.1–3.2.4; details of dose, persistence and effect modification are custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future research should record actual intake, adherence and changes, and assess dose optimization in separate direct comparisons." }, { "item_id": "N11", "question_type": "Incremental effect at SSRI initiation", "question": "Is this an adjunctive-treatment comparison at initiation of a new SSRI?", "needed": "Records of SSRI initiation timing, drug/dose, maintenance at therapeutic levels and added ingredient/placebo in both arms", "role": "Required", "role_reason": "Needed to avoid turning improvement from the SSRI itself into thiamine monotherapy efficacy or augmentation of a stable dose.", "application_exception": "Newly initiated standard treatment and stable pre-existing treatment are not automatically pooled as the same incremental effect.", "criterion": "Preserve actual background-treatment initiation and maintenance and the structure of the placebo add-on comparison.", "basis": "M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and tests is custom-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; custom application; M08 §8.2.2, M15 §15.3.1; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Compare only the added ingredient on top of the same SSRI initiation, and design augmentation of a stable dose as a separate stratum." }, { "item_id": "N12", "question_type": "Placebo and other treatments", "question": "How were placebo, psychotherapy, other drugs and rescue treatment compared?", "needed": "Placebo composition/appearance, psychotherapy/other psychotropics by arm, rescue treatment and records of changes", "role": "Required", "role_reason": "Needed to avoid mixing differences in concomitant treatment with the selected ingredient's contribution.", "application_exception": "Do not assume that all changes must be identical; examine the actual effect of interest and how changes by arm were handled.", "criterion": "Distinguish the placebo label from actual matching, shared treatment and rescue treatment/psychotherapy by arm.", "basis": "M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and tests is custom-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Adjunctive comparisons should disclose concomitant treatment and rescue use by arm and handle these in a predefined analysis." }, { "item_id": "N13", "question_type": "Allocation and design", "question": "Have the implementation of randomization, allocation concealment and baseline balance been verified?", "needed": "Sequence generation, concealment, unit of allocation, baseline tables by arm and participant flow in the original Methods", "role": "Required", "role_reason": "Needed to avoid stating that allocation issues were resolved merely from the randomized label.", "application_exception": "Do not turn unverified design details into an unsupported Not applicable designation for crossover/cluster considerations.", "criterion": "Link the reported randomized placebo comparison to gaps concerning actual sequence generation, concealment and allocation/baseline details.", "basis": "M08 §8.1–8.2.3; custom application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future trials should predefine allocation and concealment and disclose participant flow and baseline data by arm." }, { "item_id": "N14", "question_type": "Blinding and assessment implementation", "question": "Have assessor blinding and the actual HDRS measurement procedure been verified?", "needed": "Original blinding, unblinding/verification, assessor training/agreement and measurement procedures by arm", "role": "Required", "role_reason": "Needed to distinguish differences in the implementation of clinician assessment from actual differences in symptoms.", "application_exception": "A bibliographic title stating double blind does not establish successful blinding of every party or successful implementation of all assessment procedures.", "criterion": "Link assessor and participant/treatment blinding, timing, training and assessment agreement to the actual methods.", "basis": "M08 Table 8.2.a, M03 §3.2.4; custom application; M08 §8.1–8.2.3; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Define independent assessment procedures using the same scale and time point, and record measurement differences between arms." }, { "item_id": "N15", "question_type": "51 participants and analysis denominators", "question": "Were the total of 51 participants and arm-level randomized, analyzed and completed counts distinguished?", "needed": "Original CONSORT and allocation/completion/withdrawal tables, the HDRS analysis population at 12 weeks and n by arm", "role": "Required", "role_reason": "Needed to avoid turning the abstract's total participant count into the actual analysis denominator at 12 weeks.", "application_exception": "Do not split the odd total participant count between arms or add it to S03 and S04.", "criterion": "Show the label for the reported total count and the unverified arm-level allocation/completion/analysis and principal-time-point denominators.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed; M08 §8.2.2, M15 §15.3.1; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Present the full flow by arm and the analysis n for each outcome, and examine the link between outcomes and attrition." }, { "item_id": "N16", "question_type": "Missing data and analysis populations", "question": "Have attrition, missing data, ITT/PP and the effect analyzed been verified?", "needed": "Original missingness/attrition by arm at 12 weeks, analysis n, SAP, ITT/PP and sensitivity results", "role": "Required", "role_reason": "Needed to identify the material required to examine whether selection of completers/analyzed participants changes the between-group result.", "application_exception": "If the original material does not specify the analysis, do not arbitrarily fill in ITT, PP, LOCF or another method.", "criterion": "Distinguish reasons for attrition, missing data by arm, their handling, analysis populations and the effect of interest.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed; M08 §8.2.2, M15 §15.3.1; custom application; M03 §3.2.3, M08 §8.2.2–8.2.3; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Prespecify the distinction between the effect of assignment and the effect of adherence, and present missing-data assumptions and sensitivity analyses." }, { "item_id": "N17", "question_type": "HDRS version and total score", "question": "What are the actual HDRS version, items, range and direction?", "needed": "Original scale version, items/range, scoring instructions and assessment result tables by arm", "role": "Required", "role_reason": "Needed to avoid treating other depression scales or individual items as the same effect as HDRS total.", "application_exception": "Do not infer 17/21 items or a score range from the HDRS label, or substitute a GHQ subscale.", "criterion": "Separate the recorded clinician-rated total and lower-is-better direction from the unverified version/items/range.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed; M08 Table 8.2.a, M03 §3.2.4; custom application; M03 §3.2.4; custom boundaries on extensions", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future trials should prespecify the exact scale, version, total score and assessor procedures." }, { "item_id": "N18", "question_type": "12 weeks and intermediate visits", "question": "Were the endpoint result at 12 weeks and signals at 3 and 6 weeks distinguished?", "needed": "Original visit schedule, principal time point in the registration/protocol, result tables by time and actual prescribed exposure", "role": "Required", "role_reason": "Needed to avoid substituting a favorable intermediate time point for the selected 12-week question.", "application_exception": "Do not describe the current manuscript's choice of 12 weeks as trial preregistration, or infer the actual daily prescription.", "criterion": "Link the reported 0, 3, 6 and 12 weeks to the manuscript's chosen principal time point and its prespecification status.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed; M08 Table 8.2.a, M04 §4.6.3; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future comparisons should prespecify the principal time point and repeated-measurement plan and disclose all intermediate results." }, { "item_id": "N19", "question_type": "Between-group effects, within-group changes and the original effect", "question": "Has the exact estimate of the between-group effect at 12 weeks been verified?", "needed": "Original arm-level total scores/changes at 12 weeks, adjusted/unadjusted between-group estimates and analysis definitions", "role": "Required", "role_reason": "Needed to avoid turning within-group improvement in both arms into thiamine's incremental contribution.", "application_exception": "Do not reconstruct numerical values from the figure or use the 6-week result or response/remission P values to fill in the total-score result at 12 weeks.", "criterion": "Distinguish the between-group mean difference at 12 weeks from final values/changes and within-group improvement.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed; M08 §8.2.2, M15 §15.3.1; custom application; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Directly estimate the predefined incremental effect at 12 weeks between groups, and present within-group changes separately." }, { "item_id": "N20", "question_type": "Variability, CI and graph", "question": "Can the SD/SE and confidence interval at 12 weeks be interpreted?", "needed": "Original numerical tables at 12 weeks, SD/SE definitions, analysis n by arm, CI and model output", "role": "Required", "role_reason": "Needed to avoid arbitrarily deriving precision from graph bars or sample size.", "application_exception": "Do not use qualitative inspection of the original Fig.1 as digitization or reconstruction of SD/SE or CI.", "criterion": "Show the actual meaning of the reported variability and intervals and the scope of missing values.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed; M15 §15.3.1–15.3.3; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Report uncertainty intervals together with the variability/denominators used, and disclose the source data for the figure." }, { "item_id": "N21", "question_type": "Exact P value and importance", "question": "Have the P value at 12 weeks and the criterion for a clinically important difference been verified?", "needed": "Original exact P value, CI and effect at 12 weeks, and evidence for an important difference appropriate to the HDRS version/population", "role": "Required", "role_reason": "Needed to avoid declaring sufficient effect or precision from significance or participant counts alone.", "application_exception": "Do not fill in unverified P values or MCIDs using conventional thresholds or P values for other outcomes.", "criterion": "Explain whether the exact P value and CI at 12 weeks can be compared with an evidence-based important difference.", "basis": "M15 §15.3.1–15.3.3; custom application; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future research should justify the important difference with evidence and disclose the range of effects allowed by the CI." }, { "item_id": "N22", "question_type": "Preserving nonsignificant and positive findings", "question": "Were favorable findings and statements of no difference both retained without exaggeration?", "needed": "All results by time, corrections, analysis definitions and exact original numerical tables", "role": "Required", "role_reason": "Needed to avoid selecting only improvement at 6 weeks to erase the 12-week gap, or turning nonsignificance into an effect of 0.", "application_exception": "Positive findings at other time points, in other populations or on other scales are not automatically treated as conflicts or replications.", "criterion": "Preserve the signal at 6 weeks, nonsignificance at 12 weeks, within-group improvement and positive findings in other studies with their original attribution.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed; M15 §15.3.1–15.3.3; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future research should report all favorable/nonsignificant/unfavorable results according to prespecified time points and analyses." }, { "item_id": "N23", "question_type": "Funding, product provision and COI", "question": "To what level of disclosure has independence been verified?", "needed": "Original funding, internal support, product provision, employee/patent relationships, declared COI and declarations in each report", "role": "Supplementary; required for claims of independence", "role_reason": "Needed to avoid turning unverified funding or a declaration of no external funding into complete independence.", "application_exception": "Do not automatically exclude results because funding/COI exists, or conclude that bias is absent because it does not.", "criterion": "Attribute separately the declarations and internal-support/product gaps in S01, unverified details in S03 and funding in S04.", "basis": "Chamgap's own independence and attribution conditions. The official methodological sections used in this pilot do not validate all details of this item; M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is a custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future research should disclose public, institutional and product support and author relationships item by item, and distinguish them from independent replication." }, { "item_id": "N24", "question_type": "Registration, selective reporting and integrity", "question": "Were the original registration, outcome hierarchy, corrections and scope of unverified information compared?", "needed": "Original registration ID, prospective timing, protocol/SAP, outcome changes, correction/retraction notices and actual access events", "role": "Required", "role_reason": "Needed to avoid turning failure to obtain a registration into confirmed nonregistration or selective reporting, or a guarantee of no retraction.", "application_exception": "Do not retrospectively relabel the current manuscript's principal-time-point selection or historical targeted searches as preregistration or a complete, up-to-date integrity check.", "criterion": "Distinguish the registration/plan gap for S01 from the scope of the correction search at that time.", "basis": "M08 Table 8.2.a, M04 §4.6.3; custom application; M04 §4.5, §4.6.3; limitations of the current material conversion follow the user-defined scope and custom design; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future research should compare plans and results by version and record reasons for changes and unreported outcomes." }, { "item_id": "N25", "question_type": "Secondary (2nd) formulation and dose leads", "question": "What is the evidential level of the oral-administration, dose and SSRI information in the S07 review?", "needed": "Relevant S07 tables/sections and original citations, and the S01 product, route, daily dose and scale Methods", "role": "Required", "role_reason": "Needed to prevent secondary (2nd) information from automatically resolving original-report eligibility gaps.", "application_exception": "The review's tables and descriptions are leads for tracing the original report, not direct verification of the S01 product/route/dose.", "criterion": "Keep the secondary (2nd) information on oral 300 mg/day, fluoxetine 20 mg/day and unspecified formulation distinct as recorded.", "basis": "M04 §4.5–4.6 principles for collecting/selecting materials; the separation of access from reading and the hyperlink contract are custom-designed; M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and tests is custom-designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future material reviews should link each secondary (2nd) claim to a precise location in the original report and compare agreement." }, { "item_id": "N26", "question_type": "A separate controlled MDD signal", "question": "In S03, do the 50 participants, 300 mg/day and P values represent the same 12-week effect?", "needed": "Full S03 Methods/results, n by arm, route/salt, principal time point, analysis attribution of each P value and SSRI/placebo information", "role": "Required", "role_reason": "Needed to avoid combining another controlled MDD study as an exact replication of the placebo comparison at SSRI initiation and 12 weeks.", "application_exception": "Do not arbitrarily assign P=.004/.031/.035 to particular visits, analyses or 12 weeks.", "criterion": "Link the actual S03 population, standard-treatment control, HRSD and denominator/time-point gaps.", "basis": "M03 §3.2.1; detailed population conditions are custom-designed; M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and tests is custom-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed; M04 §4.6.1–4.6.2, M15 §15.3.1; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future syntheses should compare studies after verifying exact PICOT agreement and visit-specific estimates, without automatically creating an average." }, { "item_id": "N27", "question_type": "S03 publication-identity conflict", "question": "Are the date, issue and citation year for S03 consistent?", "needed": "The journal's canonical metadata, corrections to date/issue/citation information and publication events by version", "role": "Supplementary; required for bibliographic identity", "role_reason": "Needed to avoid changing the original record by overwriting different bibliographic years with a single value.", "application_exception": "Do not extend a bibliographic date conflict to a conflict in the clinical results or the entire treatment duration.", "criterion": "Preserve all of the published date 2019-09-24, the 2020 issue and the 2019 citation year.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is a custom application; M04 §4.5–4.6 principles for collecting/selecting materials; the separation of access from reading and the hyperlink contract are custom-designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Record changes in bibliographic identity together with the original values; this is not an efficacy experiment." }, { "item_id": "N28", "question_type": "Indirect PCOS/IVF population", "question": "Is S04 a direct result for MDD inpatients at SSRI initiation?", "needed": "Actual S04 eligibility, scale, duration, product, depression-subgroup data and original plan", "role": "Required", "role_reason": "Needed to avoid transferring results for other populations, scales or time points to the selected effect merely because the trial used oral B1.", "application_exception": "Retain the indirect study's original data, but do not turn exclusion of psychological disorders and the absence of a depression entry threshold into an MDD sample.", "criterion": "Show the difference between PCOS/IVF at ages 18–40 years with GHQ at 4 weeks and MDD with HDRS at 12 weeks.", "basis": "M03 §3.2.1; detailed population conditions are custom-designed; M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and tests is custom-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed; M04 §4.6.1–4.6.2, M15 §15.3.1; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "To answer the MDD question, separately design a direct comparison in the same MDD/SSRI-initiation setting with HDRS at 12 weeks." }, { "item_id": "N29", "question_type": "PCOS denominators, numerical values and SD", "question": "Were S04 denominators and positive results correctly attributed?", "needed": "S04 original Tables 2–3, CONSORT, analysis n, actual depression-subgroup results and missing-data handling", "role": "Supplementary; required for describing indirect results", "role_reason": "Needed to avoid confusing the 70 participants randomized with the 64 participants analyzed, or SD with total-score/subgroup results.", "application_exception": "Do not convert means on another scale into an HDRS effect or calculate new between-group differences/changes.", "criterion": "Separately preserve the 35/35 randomized and 32/32 analyzed counts and the original GHQ means/SDs and P value.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Indirect studies should separate overall/subgroup populations and randomized/completed counts, and present scale-specific estimates and intervals." }, { "item_id": "N30", "question_type": "S04 reporting and plan gaps", "question": "How were S04 thresholds, percentages, outcome hierarchy and registration retained?", "needed": "S04 table/text corrections, protocol, original IRCT registration/versions, CONSORT and raw data", "role": "Supplementary; required for accuracy of indirect material", "role_reason": "Needed to avoid resolving original reporting inconsistencies and failure to obtain registration in a favorable direction.", "application_exception": "Do not silently correct original percentages or infer prospective timing from the digits in the IRCT identifier.", "criterion": "Preserve historical quality notes, gaps in the original registration record and differences in scale thresholds/hierarchy.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed; M08 Table 8.2.a, M04 §4.6.3; custom application; M04 §4.5–4.6 principles for collecting/selecting materials; the separation of access from reading and the hyperlink contract are custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future material comparisons should disclose the original definitions of thresholds, denominators and hierarchy and reasons for changes, and check sensitivity." }, { "item_id": "N31", "question_type": "Healthy participants, observational studies and deficiency case reports", "question": "Do the results in S16–18 directly answer the selected adjunctive-efficacy question?", "needed": "Population, design, exposure/route, endpoint and comparator in each original report, and directness to the selected MDD question", "role": "Supplementary; required to prevent extensions", "role_reason": "Needed to avoid combining mood in healthy people, nutritional-status associations and deficiency case reports into a placebo-controlled adjunctive effect in MDD.", "application_exception": "Do not delete indirect material, but do not invent numerical values for results that were not extracted.", "criterion": "Show separately the differences among healthy young women, observations in older Chinese adults and a deficiency case treated by parenteral→oral administration.", "basis": "M03 §3.2.1; detailed population conditions are custom-designed; M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and tests is custom-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed; M04 §4.6.1–4.6.2, M15 §15.3.1; custom application; M03 §3.2.4; custom boundaries on extensions", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Design questions about healthy people, correction of deficiency and observational associations separately, and distinguish them from the exact MDD adjunctive-treatment trial." }, { "item_id": "N32", "question_type": "Combinations, fatigue and other endpoints", "question": "Are S19–21 HDRS results for ordinary thiamine alone?", "needed": "Ingredients, populations, screening scales, endpoints/times and ingredient-specific direct comparisons in each original report", "role": "Supplementary; required to prevent extensions", "role_reason": "Needed to avoid attributing results for combinations, pregnancy or fatigue to the selected ingredient/total score.", "application_exception": "Do not decompose the contribution of B1+B2 or multiple micronutrients into B1 alone.", "criterion": "Explain the actual screening roles of combination/pregnancy studies, anxiety/stress/sleep and PBC fatigue.", "basis": "M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and tests is custom-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed; M03 §3.2.1; detailed population conditions are custom-designed; M04 §4.6.1–4.6.2, M15 §15.3.1; custom application; M03 §3.2.4; custom boundaries on extensions", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "If the contribution of B1 alone is needed, design a separate direct comparison with the other ingredients/treatments matched." }, { "item_id": "N33", "question_type": "Youth registration candidate", "question": "Were controlled adult results verified in NCT07793071?", "needed": "The official registration's identity, population, ingredient, route, design, time points, results, versions and actual acquisition events", "role": "Supplementary; required for interpreting registration", "role_reason": "Needed to avoid promoting an indexed title, app shell or API failure into actual adult results.", "application_exception": "Do not use details from a 3rd-party mirror as the original registration, or equate youth with an adult population.", "criterion": "Separate discovery of a candidate registration title from unverified original content/results.", "basis": "M04 §4.5–4.6 principles for collecting/selecting materials; the separation of access from reading and the hyperlink contract are custom-designed; M04 §4.5, §4.6.3; limitations of the current material conversion follow the user-defined scope and custom design; M08 Table 8.2.a, M04 §4.6.3; custom application; M03 §3.2.1; detailed population conditions are custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "After actually obtaining the registration content, compare population/design eligibility and separately track unpublished results as well." }, { "item_id": "N34", "question_type": "Harm statements in the candidate trial", "question": "Does S01's statement of no adverse effects mean 0 events per arm?", "needed": "S01 event/person counts by arm, exposure/follow-up n, duration, AE definitions/collection and reasons for discontinuation", "role": "Supplementary; required for safety statements", "role_reason": "Needed to avoid turning the abstract's absence statement into complete ascertainment or an incidence of 0.", "application_exception": "Do not arbitrarily use the total of 51 participants or 12 weeks as an exact exposure denominator or ascertainment scope.", "criterion": "Separate the original wording from unverified event/person counts, exposure n, discontinuations and ascertainment.", "basis": "M19 §19.1.2–19.2.4; custom application; M19 §19.1.2–19.2.4; detailed distinctions are custom-designed; M19 §19.1.2–19.2.4, M04 §4.6.3; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future trials should report systematic harm ascertainment and arm-level people/events, exposure and discontinuations separately from efficacy." }, { "item_id": "N35", "question_type": "Psychiatric events and long-term harms", "question": "Were suicide-related events, manic switch, worsening and long-term safety assessed?", "needed": "Psychiatric-event definitions, systematic ascertainment, arm-level n/duration, worsening/mania/suicide and long-term follow-up data", "role": "Supplementary; required for those safety extensions", "role_reason": "Needed to avoid extending a general AE statement in a short-term abstract to psychiatric events or overall safety.", "application_exception": "Do not turn unverified suicide/mania/worsening into absence of events or a causal finding of worsening.", "criterion": "Check the scope of separate psychiatric ascertainment, exposure time and long-term/special-population information.", "basis": "M19 §19.1.2–19.2.4; detailed distinctions are custom-designed; M19 §19.2 design-specific harm questions; details of temporal relationships are custom-designed; M19 §19.1.2–19.2.4; custom application; Chamgap's own interpretive boundaries. Informed by M19 principles, not an official causality-tool implementation", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Collect psychiatric events using separate prespecified definitions and appropriate follow-up/surveillance, and separate them from efficacy total scores." }, { "item_id": "N36", "question_type": "Harms in other candidates", "question": "How are the nausea/adverse-effect statements in S03 and S04 attributed?", "needed": "S03/S04 original events/people by arm, ascertainment, exposure/duration, discontinuations, products and CONSORT data", "role": "Supplementary; required for safety interpretation of other materials", "role_reason": "Needed to avoid adding events from other studies to harms in S01 or counting them as replications for the same product.", "application_exception": "Do not create event counts, exposure denominators or 0 events from descriptions of nausea or no important AEs.", "criterion": "Distinguish populations, products and durations from the corresponding reports' harm statements and denominator gaps.", "basis": "M19 §19.1.2–19.2.4; custom application; M19 §19.1.2–19.2.4; detailed distinctions are custom-designed; M04 §4.6.1–4.6.2; adaptation for harm data is custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Safety syntheses should compare identities, populations, products and ascertainment, then separate unique events from frequencies." }, { "item_id": "N37", "question_type": "Separate oral-product SmPC", "question": "Does the Flamingo product information establish the candidate product and its harms?", "needed": "Documentation linking the candidate trial product to this product, and the actual SmPC/version and original harm data for the oral product", "role": "Supplementary; required for interpreting product safety", "role_reason": "Needed to avoid assigning a separate hydrochloride product's identity to the candidate trial's actual product/route.", "application_exception": "Do not transfer the frequency of hypersensitivity reported mainly with parenteral use into incidence in an oral trial.", "criterion": "Separate the 100 mg oral product, historical version and unknown gastrointestinal/hypersensitivity frequencies from the unverified candidate product.", "basis": "M03 §3.2.2–3.2.3; adaptation for reverse-direction markers and tests is custom-designed; M04 §4.5–4.6 principles for collecting/selecting materials; the separation of access from reading and the hyperlink contract are custom-designed; M19 §19.2.2–19.2.4, M03 §3.2.3; custom application; M19 §19.1.2–19.2.4; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Product-specific harm reviews should directly compare matched routes, products, exposed populations and event-occurrence/reporting systems." }, { "item_id": "N38", "question_type": "Nutritional upper limit and general context", "question": "What do an unset UL and general nutritional/medication context mean?", "needed": "Original official nutrition/excess-intake, vulnerable-population and interaction documents, and direct harm data matching the population and exposure", "role": "Supplementary; required for general safety extensions", "role_reason": "Needed to avoid using the absence of a UL or deficiency context as evidence of unlimited safety or MDD efficacy.", "application_exception": "Do not derive personal recommendations or MDD treatment effects from general information about intake/medication relationships.", "criterion": "Link the unset UL and excessive-intake warning in S05 to its role as context rather than efficacy evidence.", "basis": "M19 §19.1.2–19.2.4; custom application; Chamgap's own interpretive boundaries. Informed by M19 principles, not an official causality-tool implementation; M03 §3.2.1; detailed population conditions are custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Assess concomitant-medication/excess-intake risks in the selected MDD population using separate actual exposure data." }, { "item_id": "N39", "question_type": "Extensions to persistence, dose and remission", "question": "Does the total score at 12 weeks also answer questions about optimal dose, maintenance, response/remission and prevention?", "needed": "Direct dose comparisons, follow-up after discontinuation, prespecified subgroups/interactions and response/remission/relapse/suicide-event data", "role": "Supplementary; required for those extension claims", "role_reason": "Needed to avoid extending a narrow symptom comparison to dose selection, persistence or clinical events.", "application_exception": "Do not require every extension trial as a mandatory condition for constructing this table's direct 12-week question.", "criterion": "Clearly distinguish the selected total score from unverified extension questions.", "basis": "M03 §3.2.1–3.2.4; details of dose, persistence and effect modification are custom-designed; M03 §3.2.4; custom boundaries on extensions; M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Address each extension question in a separate study with a prespecified direct comparison, definition, time point and denominator." }, { "item_id": "N40", "question_type": "Additional material and new research", "question": "Were original materials needed to fill current gaps distinguished from methods for future trials?", "needed": "S01 original Methods/product, HDRS version, arm-level tables/CI at 12 weeks, flow, registration/SAP, safety and corrections", "role": "Required", "role_reason": "Needed to avoid presenting acquisition of a full text and conduct of new research as the same action.", "application_exception": "Do not adopt a new minimum sample size, number of trials, dose or MCID without justification.", "criterion": "Distinguish obtaining current original reports/plans from proposals for eligible direct comparisons and analysis/reporting.", "basis": "M04 §4.5, §4.6.3; limitations of the current material conversion follow the user-defined scope and custom design; M08 §8.1–8.2.3; custom application; M03 §3.2.3, M08 §8.2.2–8.2.3; custom application; M08 Table 8.2.a, M03 §3.2.4; custom application; M08 §8.2.2, M15 §15.3.1; custom application; M15 §15.3.1–15.3.3; custom application; M08 Table 8.2.a, M04 §4.6.3; custom application", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "In a direct randomized placebo comparison that clearly defines the product/route, MDD criteria and SSRI initiation, prespecify HDRS at 12 weeks, arm-level n/missing data, CI, an important difference and harms, and disclose all results." }, { "item_id": "N41", "question_type": "Reference dates, original verdict and exception", "question": "Were the existing ?/null and calculator exception kept from being inherited as the new table's status?", "needed": "Original calculation inputs/errors, current-value exception, verification records and authoritative records of new evidence/condition-change events", "role": "Required", "role_reason": "Needed to avoid turning an uncalculated value into no effect, no human research or a score of 0 points.", "application_exception": "Do not adopt the historical calculator's validation error/pre-validation B as a new valid grade, or rerun the calculator.", "criterion": "Preserve the original cutoff and review dates, original grade/score, axes, exception and historical self-review.", "basis": "M04 §4.5, §4.6.3; limitations of the current material conversion follow the user-defined scope and custom design; M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are custom-designed; M04 §4.5–4.6 principles for collecting/selecting materials; the separation of access from reading and the hyperlink contract are custom-designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "If eligibility or the representation of rules is updated, separate the event, conditions and adjudication procedure, and preserve the entire previous original text." }, { "item_id": "N42", "question_type": "Repeated visits and statistical model", "question": "How were analyses across multiple visits/scales and the adjusted model prespecified?", "needed": "Original protocol/SAP, analysis model, covariates, repeated-visit/multiplicity handling, effect of interest at 12 weeks and reasons for changes", "role": "Required", "role_reason": "Needed to avoid mixing comparisons at 3, 6 and 12 weeks and selection of favorable analyses into the same 12-week estimate.", "application_exception": "Without the original SAP, do not infer repeated-measures methods, multiplicity adjustments or covariate models.", "criterion": "Explain the actual adjusted/unadjusted effect of interest, handling of multiple time points/endpoints and unverified plans.", "basis": "M08 §8.2.2, M15 §15.3.1; custom application; M08 Table 8.2.a, M04 §4.6.3; custom application; M15 §15.3.1–15.3.3; custom application; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed", "condition_origin": "Designed for a known development case after actually reading the current stored materials individually. This was not blinded, clinically preregistered, or an official tool implementation/certification.", "proposed_research": "Future direct comparisons should prespecify the effect of interest at 12 weeks, primary endpoint, visit-specific comparisons, covariates, multiplicity handling and sensitivity to missing data." } ] }