{ "title": "Ordinary thiamine (vitamin B1) × Improvement of cognition in mild cognitive impairment", "criteria_version": "NGM-3087-ORDINARY-B1-MCI-1.0", "criteria_date": "2026-10-05", "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly document the question, eligibility conditions and reasons for changes, and distinguish intervention variants.", "review_level": "Preserved methodological principles, application records and copy hashes were compared. No new external methodology documents were queried and no complete official assessment tool was applied." }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Distinguish and link studies and reports; do not omit studies solely because results are unreported.", "review_level": "Preserved methodological principles, application records and copy hashes were compared. No new external methodology documents were queried and no complete official assessment tool was applied." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Fix the outcome and effect of interest when reviewing randomization, attrition, missing data, measurement and selective reporting.", "review_level": "Preserved methodological principles, application records and copy hashes were compared. No new external methodology documents were queried and no complete official assessment tool was applied." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect values, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "Preserved methodological principles, application records and copy hashes were compared. No new external methodology documents were queried and no complete official assessment tool was applied." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence.", "review_level": "Preserved methodological principles, application records and copy hashes were compared. No new external methodology documents were queried and no complete official assessment tool was applied." } ], "status_dictionary": { "Verified": "Verification of the specified question, identity, attribution and current work scope; separate from establishing clinical efficacy", "Partly verified": "Some actual information about the question is verified, while remaining data for that condition are unverified", "Unverified": "Direct information about the actual condition could not be verified in the current preserved inputs; not 0, no effect or worldwide absence", "Unread": "The external material was not actually read in this work; local-summary reading is separate", "Not applicable": "Nonapplicability limited to extension questions not required by the current fixed claim" }, "schema_version": "chamgap-public-criteria-1.0", "condition_origin": "Chamgap’s own application conditions", "requirements": [ { "item_id": "N01", "question_type": "Independent claim", "question": "Are this table’s question about ordinary B1 alone and cognitive change in MCI, and its exclusions, clear?", "needed": "A boundary record linking the current claim’s wording, question identity, population, endpoint and comparison.", "role": "Required", "role_reason": "This boundary is required to avoid combining cognitive improvement in MCI and dementia treatment into one effect status.", "application_exception": "Unverified scales, doses or durations do not justify inventing combinations as new claims.", "criterion": "Link single-ingredient oral ordinary thiamine, adults with MCI, change on validated cognitive tests and comparison with placebo, no addition or the same usual care; exclude other molecular forms, dementia and deficiency encephalopathy.", "basis": "Common conditions C01, C04, C05, C06 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Before searching for eligible materials or designing a study later, specify this PICO and separate other molecular forms and diagnostic groups into different questions." }, { "item_id": "N02", "question_type": "MCI population", "question": "Can MCI diagnosis, selection and baseline cognition be verified for an actual comparative result on ordinary B1?", "needed": "Eligibility criteria, diagnostic procedures, baseline characteristics and isolated MCI results from an eligible MCI trial.", "role": "Required", "role_reason": "Relabeling an established Alzheimer disease population as MCI because both concern cognition would misapply the population.", "application_exception": "Retain mixed diagnostic populations and examine whether separate MCI results exist. Unverified information does not mean that there is no effect in MCI.", "criterion": "Verify clinical MCI diagnostic criteria, age, baseline cognition, eligibility and MCI-only results; distinguish established dementia and deficiency encephalopathy.", "basis": "Common conditions C04, E08 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Report population flow and results together in a comparative study that clearly selects clinical MCI and records baseline cognition and deficiency status." }, { "item_id": "N03", "question_type": "Distinguishing molecular forms", "question": "Was benfotiamine distinguished from direct MCI evidence for ordinary thiamine?", "needed": "Current source locations supporting S09’s intervention identity and its distinction from ordinary B1.", "role": "Required", "role_reason": "This is required to avoid transferring results from a different molecular form to ordinary B1 simply because it is a related search term.", "application_exception": "This exclusion neither denies benfotiamine efficacy nor establishes equivalence among all B1 derivatives.", "criterion": "Distinguish the original record that S09 used benfotiamine from ordinary thiamine; do not use its cognitive results as the current effect of B1 alone.", "basis": "Common conditions C05, C08, E02 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "A future comparison of ordinary B1 and benfotiamine would need separately specified molecular interventions and direct comparative results in the same population." }, { "item_id": "N04", "question_type": "Formulation and route", "question": "Can the actual ordinary-B1 salt, formulation and route in an eligible MCI result be verified?", "needed": "Treatment composition, salt/formulation, product specifications, actual administration route and the original report for a comparative ordinary-thiamine MCI study.", "role": "Required", "role_reason": "This is needed to avoid treating the question’s oral route as verification of an actual trial route.", "application_exception": "Do not infer hydrochloride from the name ordinary thiamine or transfer results from another route to oral administration.", "criterion": "Distinguish the question’s single oral ingredient from the actual result’s ingredient, salt, product, formulation and route; link the source identity of the actual report.", "basis": "Common conditions C05, E02 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Specify the single ordinary-B1 product and oral administration procedure; distinguish molecular-form and route effects using a comparator with the same concomitant ingredients." }, { "item_id": "N05", "question_type": "Dose and adherence", "question": "Can the actual ordinary-B1 dose and adherence in MCI be verified?", "needed": "Dose, frequency, actual exposure, adherence and changes or discontinuations in an eligible MCI trial.", "role": "Required", "role_reason": "This condition is needed to attribute cognitive results to actual exposure without substituting doses from other trials.", "application_exception": "Missing adherence information does not prove nonadherence. This table provides no individual dosing instructions.", "criterion": "Verify nominal dose, frequency, actual use, adherence and changes; do not copy doses from other molecular forms or dementia trials into MCI.", "basis": "Common conditions C05, E02, E08 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Collect prescribed and actual doses together and prespecify how adherence and discontinuation will be handled in the analysis. Do not invent an optimal dose or participant count." }, { "item_id": "N06", "question_type": "Duration and timing", "question": "Can actual MCI treatment duration and cognitive-assessment timing be verified?", "needed": "Treatment, discontinuation and cognitive-assessment schedules and outcome-specific timepoints from an eligible MCI trial.", "role": "Required", "role_reason": "This is needed to avoid using the duration of related dementia research as the observation window for the current MCI cognitive-change question.", "application_exception": "Do not prescribe a universal numerical minimum treatment duration or long-term maintenance period.", "criterion": "Link treatment start and end, assessments and follow-up to the relevant cognitive result; do not interpret unknown duration as a long-term effect.", "basis": "Common conditions C05, C06, E08 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Plan cognitive-assessment schedules separately from treatment-exposure duration, and report outcomes and attrition at the relevant timepoints." }, { "item_id": "N07", "question_type": "Baseline B1 status", "question": "Can baseline B1 status and the method for diagnosing deficiency in the MCI population be verified?", "needed": "Baseline B1-status tables, testing/deficiency definitions, exclusion of deficiency encephalopathy and relevant subgroup results for an eligible MCI population.", "role": "Required", "role_reason": "This condition avoids converting responses to treatment of confirmed deficiency into supplementation efficacy in MCI with unknown deficiency status.", "application_exception": "Do not describe nutritional status as normal when deficiency tests are missing. Do not create new effect subgroups based on current deficiency status.", "criterion": "Verify nutritional status, deficiency definitions and baseline B1 values; distinguish treatment results for confirmed deficiency encephalopathy from cognitive effects in general MCI.", "basis": "Common conditions C04, E08 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Measure baseline nutritional status and prespecify hypotheses about effect modification by deficiency, reporting these separately from the main effect." }, { "item_id": "N08", "question_type": "Diet and supplements", "question": "Can total dietary intake and other supplement exposure in each group be verified?", "needed": "Dietary B1, supplement composition, intake, exposure changes and their analytical handling by group.", "role": "Required", "role_reason": "Even when asking about adding a single ingredient, differences in background nutritional exposure matter for interpreting its contribution.", "application_exception": "Do not convert unverified total intake into 0 intake or absence of all supplement use.", "criterion": "Verify total B1 exposure and group distributions or changes in diet and supplements; do not attribute other nutritional differences to ordinary B1 alone.", "basis": "Common conditions C05, E02, H05 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Record diet and supplement use in both groups using the same methods; explicitly address differences and changes in background exposure in the analysis." }, { "item_id": "N09", "question_type": "Actual comparator", "question": "Can an actual comparator differing only in ordinary B1 be verified for an eligible MCI result?", "needed": "Treatment/control composition, shared usual care, background treatment by group and actual results for an eligible MCI comparison.", "role": "Required", "role_reason": "This is needed to avoid presenting the comparison planned in the question as a comparison that was actually performed.", "application_exception": "Absence of placebo alone does not automatically invalidate a result; record the actual comparison and confounding limitations.", "criterion": "Verify the actual placebo, no-addition or identical-usual-care comparator and explain whether ordinary B1 is the only difference between groups.", "basis": "Common conditions C05, E01, E02 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Construct a comparison differing only in the addition of ordinary B1; record usual care and treatment changes in both groups to estimate the between-group effect." }, { "item_id": "N10", "question_type": "Concomitant and rescue treatment", "question": "Can concomitant medicines, rescue treatment and treatment changes that may affect cognition be verified by group?", "needed": "Concomitant medicines and vitamins, rescue treatment, adherence/treatment changes and their analytical handling for an eligible MCI result.", "role": "Required", "role_reason": "This is needed to protect attribution to the selected ingredient without assuming shared treatment in the usual-care question.", "application_exception": "Unknown concomitant details do not mean there was no concomitant treatment; not every change must be identical across groups.", "criterion": "Verify concomitant vitamins, cognitive-disease treatment, rescue treatment and discontinuations or changes; distinguish their contribution from that of ordinary B1.", "basis": "Common conditions E02, E04, H05 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Collect concomitant and rescue treatments in both groups and prespecify how assignment effects and actual-use effects will be distinguished." }, { "item_id": "N11", "question_type": "Patient-function endpoint", "question": "Was the cognitive-function question distinguished from blood vitamers and mechanistic markers?", "needed": "Current source and nutritional-extraction records showing the distinction between the question’s endpoint and biochemical markers.", "role": "Required", "role_reason": "This boundary prevents automatically extending improvements in blood vitamers to improvements in patient cognition.", "application_exception": "Verification that this is a patient-function question does not verify an actual cognitive effect.", "criterion": "Retain the selected endpoint as change on a patient’s cognitive test; do not substitute biochemical, mechanistic or advertising statements for its direct effect.", "basis": "Common conditions C06, E03, E09 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Even if future work collects mechanistic and biochemical markers, report cognitive-test results as a separate endpoint and analyze relationships between markers separately." }, { "item_id": "N12", "question_type": "Scale and measurement", "question": "Can the cognitive scale, direction and measurement procedures for an eligible MCI result be verified?", "needed": "Cognitive-scale specifications, assessment procedures, assessors/blinding and timepoint-specific results in a comparative MCI study.", "role": "Required", "role_reason": "This is needed to avoid combining scores and measurement differences from different cognitive tests into one effect.", "application_exception": "When the specific scale is unverified, do not invent ADAS-Cog, CDR or another scale from adjacent research. Unknown blinding does not establish blinding failure.", "criterion": "Link a validated scale’s name, unit, direction of improvement, assessment timing, assessors/blinding and handling of practice effects to its results.", "basis": "Common conditions C06, E03 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Specify a validated scale suitable for MCI and report results using consistent assessment schedules and procedures while addressing repeat-testing effects." }, { "item_id": "N13", "question_type": "Registration and primary endpoint", "question": "Can registration and the planned primary endpoint of an eligible MCI trial be compared with the actual report?", "needed": "Registration, protocol, analysis plan and original report of the relevant cognitive result for an eligible MCI trial.", "role": "Required", "role_reason": "This is needed to avoid treating an unavailable plan as proof of selective reporting or absence of an eligible trial.", "application_exception": "Freezing this table’s conditions with knowledge of the current materials does not replace clinical-trial preregistration.", "criterion": "Compare primary endpoints, timepoints and analyses in the registration/protocol and analysis plan with actual reports; verify reasons for changes.", "basis": "Common conditions C06, C09, E06 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Specify cognitive endpoints, primary analyses and timepoints before actual data collection; link registration/plans to all results and report reasons for changes." }, { "item_id": "N14", "question_type": "Design and allocation", "question": "Can the actual design, allocation and concealment of an eligible ordinary-B1–MCI comparison be verified?", "needed": "Methods materials on design, randomization/concealment, baseline characteristics by group and blinding for a directly eligible study.", "role": "Required", "role_reason": "This is needed to avoid claiming verified control of confounding in an MCI comparison based only on a trial title or the design of adjacent research.", "application_exception": "Unknown design does not justify marking crossover or cluster conditions not applicable. Retain any nonrandomized evidence with its design and limitations.", "criterion": "Link parallel/crossover/cluster and randomized/nonrandomized design, allocation/concealment and baseline balance to the selected cognitive result.", "basis": "Common conditions E01, E03, E04 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Design a controlled study suited to the cognitive effect of interest and report allocation, concealment, baseline characteristics and measurement blinding. Do not assign a design from currently unverified materials." }, { "item_id": "N15", "question_type": "Denominators and missing data", "question": "Can actual analysis denominators, attrition and missing data for MCI cognitive results be verified?", "needed": "Participant flow, numbers assessed/analyzed at each cognitive timepoint, dropout reasons and missing-data handling in direct MCI research.", "role": "Required", "role_reason": "This is needed to avoid substituting references to separate files or randomized participant counts for actual cognitive-analysis denominators.", "application_exception": "When an adjacent paper’s n field provides no number, do not infer a participant count or 0 dropouts.", "criterion": "Distinguish selection, allocation, completion, measurement and analysis denominators, and missingness reasons/handling; link these to the relevant cognitive result.", "basis": "Common conditions C07, E04, H06 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Disclose flow by group and analysis denominators by outcome; report reasons for missingness, handling and result sensitivity. Do not invent a universal minimum n." }, { "item_id": "N16", "question_type": "Effect of interest and analysis", "question": "Can the definition and analysis of an actual between-group MCI effect be verified?", "needed": "Effect-of-interest definition, analysis population, model, group results and between-group estimates for an eligible MCI comparison.", "role": "Required", "role_reason": "This is needed to avoid transferring cognitive results from related research or within-group improvement to a between-group effect of ordinary B1 in MCI.", "application_exception": "Do not fill an unknown analysis population with ITT; the manuscript’s analysis-attempt records are not actual cognitive effects.", "criterion": "Link assignment/adherence effects, ITT/PP, final values/change scores, between-/within-group definitions, adjustment models and design handling to actual results.", "basis": "Common conditions C06, E04 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Specify the effect of interest and primary analysis; report between-group differences at the same timepoint separately from within-group improvement. Include crossover/cluster handling required by the actual design." }, { "item_id": "N17", "question_type": "Effect, interval and importance", "question": "Can direct cognitive-change effects, variability, CIs and an important difference be verified?", "needed": "Scale-specific between-group effects, variability types, denominators, CIs and evidence for clinical-importance criteria for an eligible MCI result.", "role": "Required", "role_reason": "This is needed to avoid writing an unknown effect as 0 or interpreting ? and null as numerical small-effect or low-precision values.", "application_exception": "Do not estimate new effects from P values or invent universal numerical minimums for duration, sample size, study count or importance.", "criterion": "Distinguish actual scales, between-group effects, SD/SE, denominators and CIs; compare with an evidence-based important difference or record why interpretation is unavailable.", "basis": "Common conditions C07, E05 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Report the main cognitive effect and CI and specify evidence for an important difference, separating uncertainty from clinical meaning. Do not determine sufficiency from significance or study count alone." }, { "item_id": "N18", "question_type": "Adjacent S09 result", "question": "Was S09’s cognitive-trial summary separated from a direct effect of ordinary B1 in MCI?", "needed": "Preserved bibliography, intervention, population/endpoint, exclusion role and result-summary locations for S09.", "role": "Required", "role_reason": "This is needed to preserve the existence of human cognitive trials without inheriting results from other molecular forms or diseases as the current effect.", "application_exception": "This source provides no numerical results, CIs or denominators for S09. No new assessment of the whole paper’s effect direction or precision is made here.", "criterion": "Explain how S09’s benfotiamine/early-Alzheimer-disease endpoint differs from the current question; do not delete the adjacent report or count it as direct replication.", "basis": "Common conditions C04, C05, C06, C08, E07 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "If ordinary B1 in MCI is newly studied, link benfotiamine/dementia findings only as hypothesis background and perform a separate direct comparison with matching intervention and population." }, { "item_id": "N19", "question_type": "Contrary S26 result", "question": "Was the negative ordinary-thiamine dementia result kept from becoming a conclusion of no effect in MCI?", "needed": "S26 population/endpoint, ordinary-B1 identity, preserved results and original body-text locations addressing the negative result.", "role": "Required", "role_reason": "This is needed to retain unfavorable adjacent findings while respecting applicability limits arising from differences in the actual question.", "application_exception": "The source provides no actual S26 numerical results, P values/CIs or denominators; do not invent statistical no-difference findings or effect sizes.", "criterion": "Preserve both S26’s established-Alzheimer-dementia population and the manuscript’s negative-result statement; do not transfer these to an MCI effect of 0, equivalence or repeated refutation.", "basis": "Common conditions C04, C08, E07 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Obtain results by directly comparing ordinary B1 in MCI; interpret differences from dementia evidence separately by population and disease stage." }, { "item_id": "N20", "question_type": "Bibliographic identity and corrections", "question": "Were the benfotiamine paper’s identifier correction and both reports’ bibliographic links preserved accurately?", "needed": "Exact original wording of current citation/evidence records and the PMID/DOI linkage correction.", "role": "Required", "role_reason": "This is needed to avoid mixing a potentially mislinked paper identifier with different effect evidence.", "application_exception": "Do not interpret a publisher URL’s existence or its /fullarticle path as successful full-text reading.", "criterion": "Link the original correction’s PMID/DOI to citation/evidence identity without labeling this as a current external identity check or full-text verification.", "basis": "Common conditions C02, C03, C09 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "When obtaining materials later, compare PMID, DOI, authors/year and intervention identity; preserve before/after identifiers and the grounds for any correction." }, { "item_id": "N21", "question_type": "Reports and trial families", "question": "Were the two adjacent reports kept from being counted as independent replications of direct MCI trials?", "needed": "Study identifiers, bibliography and roles for both reports, plus family-linkage materials for additional registrations or related reports.", "role": "Required", "role_reason": "This is needed to avoid counting two different citations as 2 direct MCI replications or 2 independent refutations.", "application_exception": "Identifiers alone do not fully verify institutional or participant independence across studies. Leave undetermined direct-trial and participant counts null.", "criterion": "Link bibliographic/study identifiers and exclusion roles; distinguish report counts from unique directly eligible trial and participant counts.", "basis": "Common conditions C02, E07 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "When collecting materials, link reports to unique trial families and manage follow-ups, repeat citations and subgroup analyses of the same trial as one family." }, { "item_id": "N22", "question_type": "Actual reading scope", "question": "Were current local-summary reading and historical publisher-abstract access distinguished for each material?", "needed": "Exact locations, values and hashes in the preserved materials, original access levels and source locations for both reports, and material-specific reading records.", "role": "Required", "role_reason": "This display condition is required to avoid upgrading a link or historical abstract access to current full-text reading.", "application_exception": "Not attempted does not mean access failed. When a citation record lacks an individual access date, leave it null; do not copy the original review date into the access date.", "criterion": "Separate actual reading of the current preserved manuscript summaries from both external abstracts/full texts being unattempted and unread; preserve historical publisher-abstract access, source locations and null individual dates.", "basis": "Common conditions C03, C09 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "If external materials are actually obtained later, separately record timing, access/acquisition/reading locations by material type and compare full-text results with the current summaries." }, { "item_id": "N23", "question_type": "Search and selection scope", "question": "Can the original search’s databases, strategies and selection scope be traced in the current inputs?", "needed": "Actual search sources, strategies, timing, selection/exclusion flow and coverage of unpublished/registered materials and corrections in the historical search record.", "role": "Required", "role_reason": "This is needed to avoid extending absence statements in the preserved summaries to absence from all current literature.", "application_exception": "No new clinical search is performed here, and the separate historical-search-record path is not claimed to have been opened. Incomplete searching is not displayed as 0 studies.", "criterion": "Preserve the evidence cut-off and bounded search conclusion; distinguish whether actual search strategies, databases and exclusion flow have been obtained.", "basis": "Common conditions C09, E06 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "When a subsequent update is authorized, reproducibly record question-specific search sources, strategies, selection and links to registered/unpublished materials; state whether the search was exhaustive." }, { "item_id": "N24", "question_type": "Preserving original ? and null", "question": "Were the original ?, absent score, unused axes and bounded no-eligible-human-result marker preserved unchanged?", "needed": "Exact wording of the original grade, score, assessment axes, human-research existence and eligible-result flags, calculation records and bounded unverified interpretation.", "role": "Required", "role_reason": "This meaning boundary is required to prevent reading the original ? as total absence of human research, no effect or E0/RX/F.", "application_exception": "The original absent score and null unused axes are not 0. Passing current structural checks is separate from assessing clinical efficacy.", "criterion": "Preserve the original grade/score, B/P, null unused axes, false and empty arrays, and the bounded no-eligible-human-result meaning; do not convert these into new efficacy/safety scores or an effect of 0.", "basis": "Common conditions C01, C08, C09, E05 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "If eligible materials are verified later, record previous status, dates and evidence separately from the new decision event. Do not derive clinical scores from row counts or verification rates in this table." }, { "item_id": "N25", "question_type": "Funding and interests", "question": "Can research funding, product provision and conflicts of interest for direct MCI evidence be verified?", "needed": "Funding, conflicts of interest, product provision, author/institution materials and related trial-family records for direct MCI reports.", "role": "Supplementary; required for independence claims", "role_reason": "This is needed to avoid treating unknown funding in adjacent reports or the original null independence axis as evidence of independent funding or replication.", "application_exception": "Do not automatically exclude evidence because of conflicts or infer absence of bias because no conflict is reported. Do not assign a new independence axis when direct results are unavailable.", "criterion": "Verify actual funding, product provision, author employment/patents, declared interests and study families; do not interpret unknown information as independent funding.", "basis": "Common conditions C10, C02 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Future research should disclose funding, product provision and author relationships; link families of replication studies and conflicts separately for interpretation." }, { "item_id": "N26", "question_type": "Harm events and denominators", "question": "Can adverse-event definitions, collection and denominators be verified under the same ordinary-B1–MCI exposure?", "needed": "Adverse-event definitions, collection methods, events/exposure denominators by group, severity and discontinuations in ordinary-B1 MCI research.", "role": "Supplementary; required for safety claims", "role_reason": "This is needed to avoid turning the existence of a cognitive trial or summary into a claim of safety or 0 adverse events.", "application_exception": "Do not transfer tolerability from other molecular forms or dementia trials as equivalent. Do not calculate incidence without denominators.", "criterion": "Link actual dose, duration, event definitions/severity, collection methods, affected-person/event counts and exposure denominators.", "basis": "Common conditions E10, H01, H04, H09, C07 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Systematically collect harms in the same population/exposure separately from efficacy outcomes; disclose affected-person counts, event counts, denominators and duration together." }, { "item_id": "N27", "question_type": "Harm timing and comparisons", "question": "Can exposure timing, comparisons and follow-up losses for harms be verified in the same MCI materials?", "needed": "Event timelines, discontinuation/recovery, group comparisons, follow-up losses and completeness of event disclosure under the same ordinary-B1 MCI exposure.", "role": "Supplementary; required for comparative safety", "role_reason": "This is needed to avoid upgrading harms unseen in short or incomplete summaries to safety, causality or total incidence.", "application_exception": "Do not infer improvement after discontinuation or re-exposure when these are absent. Unverified information also does not mean a harm event occurred.", "criterion": "Link exposure start/stop, event onset/recovery, follow-up, comparators and attrition/detection by group; temporal sequence alone does not establish causality.", "basis": "Common conditions H02, H03, H06, H08, H09, E10 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Use the same safety follow-up procedures in both groups; collect exposure, onset/recovery and attrition, and report limitations of comparative risk." }, { "item_id": "N28", "question_type": "Interaction coverage", "question": "Was drug-interaction information for ordinary B1 in MCI sufficiently verified?", "needed": "Actual concomitant medicines, dose, timing and materials/search coverage and results for specific interactions.", "role": "Supplementary; required for interaction claims", "role_reason": "This is needed to avoid extending the efficacy manuscript’s scope into a guarantee of individual safety with all medicines.", "application_exception": "Failure to perform a comprehensive search alone establishes neither presence nor absence of interactions. Do not create individual dosing instructions.", "criterion": "Distinguish drug-interaction search/verification coverage from actual concomitant exposure; do not interpret absence of a separate search as absence of interactions.", "basis": "Common conditions C09, E10, H05, H08 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "Subsequent safety assessments should record actual concomitant medicines and review suitable exposure/outcome materials for each specified interaction question." }, { "item_id": "N29", "question_type": "Dose and long-term extensions", "question": "Does the current table claim an optimal dose, persistence after discontinuation or long-term cognitive effects?", "needed": "Direct dose comparisons, discontinuation/long-term follow-up and exposure/timepoint-specific results if an extension question is newly addressed.", "role": "Supplementary; required for extension claims", "role_reason": "This supplementary boundary prevents extending an unverified main effect to a specific regimen or long-term effect.", "application_exception": "Do not require all dose and long-term studies for the current narrow cognitive-change question. Original dose/duration uncertainty remains in other rows.", "criterion": "Separate the fixed comparative cognitive-change question from optimal-dose or long-term-maintenance extensions, and do not claim those extensions.", "basis": "Common conditions E08, H08 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "If an extension is needed, separately plan dose comparisons and discontinuation/long-term follow-up; report direct estimates and safety information." }, { "item_id": "N30", "question_type": "Dementia-prevention extension", "question": "Is cognitive-test change extended to dementia prevention, quality of life or mortality effects?", "needed": "Population, denominators, duration and comparative results directly measuring dementia incidence/clinical function, quality of life or survival if an extension question is addressed.", "role": "Supplementary; required for clinical-event extensions", "role_reason": "This condition avoids automatically extending a cognitive-test question to dementia prevention or every improvement in patients’ lives.", "application_exception": "Do not require an event trial for a numerical-change question. Unverified direct cognitive effects do not establish an event effect of 0.", "criterion": "Separate cognitive-test change itself from clinical events, quality of life and survival; do not use the current results as evidence for those separate questions.", "basis": "Common conditions C06, E09 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "To evaluate clinical events or quality of life, plan separate research with clear event definitions and appropriate follow-up/denominators, and report independently of cognitive scores." }, { "item_id": "N31", "question_type": "Assay-interference coverage", "question": "Can presence or absence of interference be judged within the original assay-interference verification scope?", "needed": "Materials on specific assays, actual B1 exposure and interference/errors, plus separate search/verification coverage.", "role": "Supplementary; required for assay-interference claims", "role_reason": "This supplementary condition avoids extending an unsearched interference question to error-free assessment tools or biochemical-assay safety.", "application_exception": "The current cognitive-change question does not itself claim assay interference. Absence of a separate search does not establish that cognitive-trial measurement errors occurred either.", "criterion": "Do not convert absence of a separate assay-interference search into absence of interference; limit relevance to cognitive assessment or separate biochemical tests to the verified scope.", "basis": "Common conditions C06, C09, E03 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "For a subsequent question, specify the assay actually used, compare exposure and sampling/assessment timing with assay principles, and perform the necessary validation." }, { "item_id": "N32", "question_type": "Updates and reference scope", "question": "Were the original update conditions and the separate records not opened here clearly documented?", "needed": "Original update policy, editorial references and identities, dates and scope of subsequent materials/corrections, with before/after records.", "role": "Required", "role_reason": "This is needed to avoid presenting reference paths and historical self-checks as current reinvestigation or automatic verification.", "application_exception": "Only reference strings for historical search records, historical numerical records, the calculator, earlier 162 and supporting examples were read; their individual sources were not opened. The possibility of an update does not establish that a result currently exists.", "criterion": "Distinguish new-evidence, full-text/registration acquisition, numerical/identity correction and retraction events from manuscript/condition revisions; do not upgrade unread referenced files into the actual reading scope.", "basis": "Common conditions C03, C09, E06 were individually adapted to the ordinary-B1-alone MCI question. These are case-specific conditions referencing preserved methodological principles, not official methodological certification.", "condition_origin": "Case-specific conditions developed with knowledge of the preserved manuscript; neither blinded nor clinical preregistration", "proposed_research": "In later updates, preserve actual new materials, dates and reading levels together with previous values and change reasons; separately review linked rows and whether conditions need revision." } ], "language": "en", "translation_date": "2026-10-31" }