# Oral saffron stigma extract × Cognition in mild-to-moderate Alzheimer's disease Verdict 3081 · Evidence Check Stored-material review date: 2026-10-05 Original evidence review date: 2026-09-14 Review-criteria version: 1.1 Public page/material preparation date: 2026-10-28 Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect. ## Assessment scope - Population: Age over 55, probable mild-to-moderate Alzheimer’s disease, MMSE 15–26; core antidementia-medication restrictions - Ingredient, formulation and route: Oral capsules of dried 80% ethanolic extract of dried Crocus sativus stigma; crocin/safranal standardization in retained records - Dose: Trial specification: 15 mg, 2 times per 1 day, totaling 30 mg/day. Actual quantitative adherence and optimal dose are unverified - Comparator: Matching-appearance placebo capsules and core antidementia-medication restrictions. Sensory matching and group-specific concomitant-treatment deviations are unverified - Measured outcome: 16-week ADAS-cog change versus placebo; lower scores indicate improvement. Exact version, training and prespecification are unverified - Duration: The selected direct comparison is at 16 weeks. The 22-week active comparison and 12-week add-on treatment are different comparisons - Questions outside this scope: Retain S1’s 46 participants, 23/23 allocation and paper-defined ITT/LOCF. Changes −3.69±1.69 versus +4.08±1.34 points are mean±SD. −7.77 points is a historical editorial simple difference, not an author-adjusted estimate or individual improvement probability.; The existing conditional interval −8.68~−6.86 points, df44, is an editorial calculation assuming rounded change SD, 23 per group, independent-group equal-variance t and LOCF. The author-reported 95% CI and clinical importance are unverified; calculations were not repeated here.; Change-score P<.0001 and repeated-measures P=.04 concern different tests. The discrepancy between final-value t4.16/df44 reported P<.0001 and historical recalculated P≈.000145 remains separate. Author explanations/corrections are unverified; no new test was performed.; Retain S1 hypomania 2/23 versus 0/23, dry mouth 3/23 versus 1/23 and 1 placebo-group death from myocardial infarction. A small short-term trial does not establish long-term/rare risk or safety in every population.; Retain original C, 46, Caution, the S→P correction and ongoing review of EX, CX and the final grade. Grade revalidation is false and method review is pending. 46 is not an efficacy percentage. Do not extend to tea, food, other extracts, isolated constituents, combinations, prevention, slowing progression, prescription replacement, optimal dose or persistence after stopping. ## Checklist items ### N01 · Which saffron, Alzheimer's disease and cognition comparison is being checked? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The selected question concerns 16-week ADAS-cog change versus placebo in mild-to-moderate Alzheimer's disease. The subclaim list is empty; S2 and S3's different comparisons are retained as context. - Why unverified: Verification of the question boundary does not establish clinical confirmation or revalidation of the existing grade. - Reason for missing information: Verification of the question boundary does not establish clinical confirmation or revalidation of the existing grade. - Required materials and conditions: Specific extract, population, 16-week ADAS-cog, placebo and original claim boundary. - Materials to obtain first: Specific extract, population, 16-week ADAS-cog, placebo and original claim boundary. - Further research: Compare candidate material with the exact ingredient, population, comparator, scale and time. - Conditions for verification: Link the specific stigma extract's 16-week ADAS-cog versus placebo question to the retained original. - Why this condition is needed: Needed to avoid merging all related saffron effects into a single status. - Application exceptions: Active-drug comparisons and add-on trials are not replications of the same placebo question. - Remaining uncertainty: Verification of the question boundary does not establish clinical confirmation or revalidation of the existing grade. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1, S2, S3 ### N02 · Do the core trial population and medication restrictions match the original question? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Retained claim conditions specify age over 55, probable mild-to-moderate AD, MMSE 15–26 and core antidementia-medication restrictions. - Why unverified: Detailed selection, representativeness and applicability to all patients receiving concomitant treatment are not established within this retained scope. - Reason for missing information: Detailed selection, representativeness and applicability to all patients receiving concomitant treatment are not established within this retained scope. - Required materials and conditions: Diagnosis, age, MMSE, inclusion/exclusion and antidementia-medication restrictions. - Materials to obtain first: Diagnosis, age, MMSE, inclusion/exclusion and antidementia-medication restrictions. - Further research: Link selection criteria, baseline tables and medication restrictions to the actual results. - Conditions for verification: Distinguish the core population, selection and medication restrictions from unverified representativeness. - Why this condition is needed: Needed to avoid applying the findings to all patients with dementia in routine care. - Application exceptions: Do not extend to MCI, dementia prevention or all patients receiving concomitant drugs. - Remaining uncertainty: Detailed selection, representativeness and applicability to all patients receiving concomitant treatment are not established within this retained scope. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N03 · How far are S1's plant part, extraction specifications, detailed batch, content and manufacturing quality verified? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Retained records describe capsules of dried 80% ethanolic extract of dried Crocus sativus stigma and crocin/safranal standardization. - Why unverified: Current original-source verification of detailed batch, content and manufacturing quality was not performed. - Reason for missing information: Current original-source verification of detailed batch, content and manufacturing quality was not performed. - Required materials and conditions: Stigma, extraction solvent, capsule, standardization and the actual trial product. - Materials to obtain first: Stigma, extraction solvent, capsule, standardization and the actual trial product. - Further research: Compare product specifications and batch information with the applicability of the trial results. - Conditions for verification: Link the reported stigma, 80% ethanolic dried extract, capsule and standardization specifications, separately assessing original verification of detailed batch, content and manufacturing quality. - Why this condition is needed: Needed to avoid transferring results to tea, foods or isolated constituents. - Application exceptions: Other extracts, crocin/safranal alone and combination products are separate. - Remaining uncertainty: Current original-source verification of detailed batch, content and manufacturing quality was not performed. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N04 · Were the core trial route and dose linked? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Original claim conditions and product facts specify oral 15 mg capsules, 2 times daily, totaling 30 mg/day in the core trial. - Why unverified: Actual quantitative adherence and each individual's exposure remain separately unverified. - Reason for missing information: Actual quantitative adherence and each individual's exposure remain separately unverified. - Required materials and conditions: Oral capsule, amount per 1 administration, frequency, total amount and actual exposure records. - Materials to obtain first: Oral capsule, amount per 1 administration, frequency, total amount and actual exposure records. - Further research: Compare administration specifications, adherence and discontinuation records by group. - Conditions for verification: Distinguish the reported oral 15 mg, 2 times daily, from unverified actual exposure. - Why this condition is needed: Needed to avoid turning trial specifications into personal dosing instructions. - Application exceptions: Nominal dose does not establish quantitative adherence. - Remaining uncertainty: Actual quantitative adherence and each individual's exposure remain separately unverified. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N05 · Do administration duration and the selected result time match? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The main comparison is at 16 weeks; S2 is a 22-week active comparison and S3 a 12-week add-on trial. Results at these times are not pooled. - Why unverified: Persistence beyond 16 weeks is outside this verification. - Reason for missing information: Persistence beyond 16 weeks is outside this verification. - Required materials and conditions: 16-week administration, ADAS-cog assessment time and post-discontinuation material. - Materials to obtain first: 16-week administration, ADAS-cog assessment time and post-discontinuation material. - Further research: Separate assessment schedules, end-of-treatment and post-discontinuation follow-up. - Conditions for verification: Link core 16-week administration to the ADAS-cog result. - Why this condition is needed: Needed to avoid merging results at different durations as the same effect. - Application exceptions: S2's 22 weeks and S3's 12 weeks do not replace the core 16-week result. - Remaining uncertainty: Persistence beyond 16 weeks is outside this verification. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1, S2, S3 ### N06 · Were the core placebo and antidementia-medication restrictions distinguished? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Matching-appearance placebo capsules and core antidementia-medication restrictions are recorded. The original review left taste/smell matching and concomitant-treatment deviations unverified. - Why unverified: Material fully comparing concurrent treatment, adherence and rescue treatment by group is unavailable in the retained scope. - Reason for missing information: Material fully comparing concurrent treatment, adherence and rescue treatment by group is unavailable in the retained scope. - Required materials and conditions: Comparator product, antidementia-medication restrictions, rescue treatment and changes by group. - Materials to obtain first: Comparator product, antidementia-medication restrictions, rescue treatment and changes by group. - Further research: Verify comparator specifications, treatment changes and their handling in the analysis of the effect of interest. - Conditions for verification: Link the actual placebo and medication restrictions to unverified concomitant-treatment deviations. - Why this condition is needed: Needed to avoid attributing differences in concurrent treatment to saffron. - Application exceptions: Appearance matching does not guarantee taste/smell matching or agreement in all concomitant treatments. - Remaining uncertainty: Material fully comparing concurrent treatment, adherence and rescue treatment by group is unavailable in the retained scope. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N07 · Is the donepezil active comparison being turned into placebo-relative efficacy or equivalence? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: S2 records 54 participants in an active comparison; the abstract's no significant difference is not converted into placebo-relative efficacy, equivalence or noninferiority. - Why unverified: S2's completion/analysis details, detailed original text and registration remain separately unverified. - Reason for missing information: S2's completion/analysis details, detailed original text and registration remain separately unverified. - Required materials and conditions: S2's actual comparator, duration, endpoints, design and equivalence plan. - Materials to obtain first: S2's actual comparator, duration, endpoints, design and equivalence plan. - Further research: Review the active comparison's advance noninferiority criteria, models and intervals as a separate question. - Conditions for verification: S2 is a 22-week donepezil active comparison and does not certify noninferiority or placebo-relative efficacy. - Why this condition is needed: Needed to distinguish no significant difference from equivalence. - Application exceptions: Retain active-comparator material as a different comparison. - Remaining uncertainty: S2's completion/analysis details, detailed original text and registration remain separately unverified. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S2 ### N08 · Were S3's nonsignificant MMSE result and different concomitant-treatment conditions both retained? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: S3 records 60 participants, 30/30 randomized, 27/27 analyzed in the excerpt, and 12-week MMSE P=.303 with donepezil add-on treatment. Do not pool it with S1 or count it as consistent independent replication. - Why unverified: S3's mean difference, 95% CI, full original text and appendices are unverified. - Reason for missing information: S3's mean difference, 95% CI, full original text and appendices are unverified. - Required materials and conditions: Donepezil co-treatment, 12-week MMSE, denominators, result and role. - Materials to obtain first: Donepezil co-treatment, 12-week MMSE, denominators, result and role. - Further research: First compare whether results address the same question, then acquire separate estimates and intervals. - Conditions for verification: Explain the differences between S3 and S1 in co-treatment, scale and time. - Why this condition is needed: Needed to avoid retaining only favorable direct results. - Application exceptions: Do not turn nonsignificance into an effect of 0 or inflammatory markers into cognitive effects. - Remaining uncertainty: S3's mean difference, 95% CI, full original text and appendices are unverified. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S3 ### N09 · Were the ADAS-cog definition, direction and version verified? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: ADAS-cog is the cognitive-function endpoint itself, with lower scores indicating improvement; 16-week change is selected for this page. Exact version, translation and assessor training are unverified. - Why unverified: Detailed measurement specifications and successful assessor blinding cannot be established. - Reason for missing information: Detailed measurement specifications and successful assessor blinding cannot be established. - Required materials and conditions: 16-week change, improvement with lower scores, exact version, translation and assessment procedures. - Materials to obtain first: 16-week change, improvement with lower scores, exact version, translation and assessment procedures. - Further research: Link scale version, language, assessor training and schedule to the result table. - Conditions for verification: Distinguish the direction of the cognitive endpoint from the verified scope of measurement details. - Why this condition is needed: Needed to distinguish the cognitive endpoint itself from other scales and events. - Application exceptions: Do not reclassify it as a biological surrogate merely because it is a test. - Remaining uncertainty: Detailed measurement specifications and successful assessor blinding cannot be established. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N10 · Were the core change values, SD and direction preserved? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: S1 changes are recorded as −3.69±1.69 versus +4.08±1.34 points, mean±SD. The historical location is p4, Results/ADAS-cog, in the author-uploaded version. - Why unverified: External original tables were not reread in this work; recorded numbers are treated within preservation of the original verdict. - Reason for missing information: External original tables were not reread in this work; recorded numbers are treated within preservation of the original verdict. - Required materials and conditions: Group-specific 16-week ADAS-cog mean changes, SD and original location. - Materials to obtain first: Group-specific 16-week ADAS-cog mean changes, SD and original location. - Further research: Verify original tables, denominators, definitions and rounding before reviewing numerical attribution. - Conditions for verification: Attribute the retained changes −3.69±1.69 versus +4.08±1.34 and SD to the relevant comparison. - Why this condition is needed: Needed to distinguish final values, within-group change and between-group effects. - Application exceptions: Do not convert mean differences into individual probabilities of improvement. - Remaining uncertainty: External original tables were not reread in this work; recorded numbers are treated within preservation of the original verdict. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N11 · How far are the reported change-score, repeated-measures and final-value tests and the authors' explanation/correction of the final-value inconsistency verified? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Change-score P<.0001 and abstract P=.04 concern different tests. Separately, the retained bibliographic note records a discrepancy between the reported final-value P for t4.16/df44 and historical recalculated P≈.000145. - Why unverified: The historical inconsistency was not resolved through new calculations; the original authors' explanation/correction remains unverified. - Reason for missing information: The historical inconsistency was not resolved through new calculations; the original authors' explanation/correction remains unverified. - Required materials and conditions: Analysis, time, P, t/df and correction records for each test. - Materials to obtain first: Analysis, time, P, t/df and correction records for each test. - Further research: Acquire test-specific original tables, models and correction material, comparing each test's meaning. - Conditions for verification: Link change-score P<.0001, repeated-measures P=.04 and the historical final-value inconsistency to their respective tests; separately assess original author explanations or corrections. - Why this condition is needed: Needed to distinguish different tests from actual internal reporting inconsistencies. - Application exceptions: Do not call every difference in P a conflict before checking whether it concerns the same question. - Remaining uncertainty: The historical inconsistency was not resolved through new calculations; the original authors' explanation/correction remains unverified. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N12 · How far are endpoint-specific execution, denominators and sensitivity verified for 23/23 allocation and paper-defined ITT/LOCF? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: S1 records 46 participants, 23/23 randomized, paper-defined ITT/LOCF and analysis df44. These labels alone do not resolve missing-data and analysis uncertainty. - Why unverified: Endpoint-specific analysis execution, sensitivity and current original-data comparison are unverified. - Reason for missing information: Endpoint-specific analysis execution, sensitivity and current original-data comparison are unverified. - Required materials and conditions: Randomized, completed and analyzed n, ITT definition, LOCF and effect of interest. - Materials to obtain first: Randomized, completed and analyzed n, ITT definition, LOCF and effect of interest. - Further research: Compare participant flow, actual endpoint-specific analysis sets and missing-data models. - Conditions for verification: Preserve recorded 23/23 allocation, paper-defined ITT/LOCF and analysis df44, assessing endpoint-specific analysis sets, execution, sensitivity and current original-data comparison. - Why this condition is needed: Needed to avoid automatically substituting randomized counts for analysis denominators. - Application exceptions: Do not expand the paper's analysis label into certification of modern complete ITT. - Remaining uncertainty: Endpoint-specific analysis execution, sensitivity and current original-data comparison are unverified. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N13 · How far are group-specific dropout/completion records, other missing-data reasons, death handling and sensitivity verified? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Dropouts of 1/23 versus 3/23, total 4/46 and 8.7%, and 22/20 completers are retained records and historical calculations. A placebo-group death is also recorded. - Why unverified: Other missing-data reasons and sensitivity analyses are unverified; no subtraction or rate calculation was performed in this work. - Reason for missing information: Other missing-data reasons and sensitivity analyses are unverified; no subtraction or rate calculation was performed in this work. - Required materials and conditions: Group-specific dropout, reasons, death and distinction between completion and analysis. - Materials to obtain first: Group-specific dropout, reasons, death and distinction between completion and analysis. - Further research: Link group-specific flowcharts, missing-data reasons and death handling to results. - Conditions for verification: Retain recorded 1/23 versus 3/23 dropouts and the historical subtraction behind 22/20 completers, assessing other missing-data reasons, death handling and sensitivity analyses. - Why this condition is needed: Needed to avoid turning subtraction into an author-observed completion table. - Application exceptions: Do not calculate new dropout rates or completion counts. - Remaining uncertainty: Other missing-data reasons and sensitivity analyses are unverified; no subtraction or rate calculation was performed in this work. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N14 · Were the validity of LOCF missing-data assumptions and sensitivity to other handling verified? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The original review retains LOCF use, dropout, placebo-group death and some concerns, stating that LOCF does not eliminate missing-data uncertainty. - Why unverified: The validity of missing-data assumptions and persistence of the effect under other handling are unverified. - Reason for missing information: The validity of missing-data assumptions and persistence of the effect under other handling are unverified. - Required materials and conditions: Missing-data assumptions, imputation method, reasons by group and sensitivity results. - Materials to obtain first: Missing-data assumptions, imputation method, reasons by group and sensitivity results. - Further research: Compare missing-data and sensitivity analyses appropriate to the effect of interest with randomized results. - Conditions for verification: Retain original LOCF use and missing-data uncertainty, assessing whether reasons by group, assumption validity and sensitivity to alternative handling were verified. - Why this condition is needed: Needed to avoid claiming no missing-data problem merely because numerical results are complete. - Application exceptions: Do not score LOCF use itself as proven null efficacy or a specified bias magnitude. - Remaining uncertainty: The validity of missing-data assumptions and persistence of the effect under other handling are unverified. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N15 · Was the arithmetic −7.77-point difference distinguished from an author-adjusted effect? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: −7.77 points is the retained editorial simple arithmetic difference between mean changes, not an author-reported adjusted effect or an individual improvement probability. - Why unverified: The arithmetic record does not replace verification of the authors' adjusted estimate. - Reason for missing information: The arithmetic record does not replace verification of the authors' adjusted estimate. - Required materials and conditions: Original means, historical arithmetic, estimand definition and adjusted model. - Materials to obtain first: Original means, historical arithmetic, estimand definition and adjusted model. - Further research: Compare original paper estimates, models and intervals with the existing arithmetic. - Conditions for verification: Identify −7.77 as the historical simple difference between published mean changes. - Why this condition is needed: Needed to avoid turning an existing calculation into a formal between-group effect reported by the authors. - Application exceptions: No new effect-size calculation is performed in this work. - Remaining uncertainty: The arithmetic record does not replace verification of the authors' adjusted estimate. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N16 · How far are assumptions behind the editorial conditional interval and an author-reported 95% CI for the same endpoint verified? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The existing −8.68~−6.86-point interval (df44) is an editorial calculation assuming rounded change SD, 23 participants per group and LOCF. Exact original calculation values and assumptions are retained. - Why unverified: The author-reported 95% CI is unverified; the conditional interval does not resolve missingness, reporting bias or clinical importance. - Reason for missing information: The author-reported 95% CI is unverified; the conditional interval does not resolve missingness, reporting bias or clinical importance. - Required materials and conditions: Interval calculator, assumptions, rounding, denominators, LOCF and the original author interval. - Materials to obtain first: Interval calculator, assumptions, rounding, denominators, LOCF and the original author interval. - Further research: Compare original author estimates/intervals, assumptions and missing-data sensitivity for the same endpoint. - Conditions for verification: Preserve the existing independent-group equal-variance t conditional interval's calculator, assumptions, rounding, denominators and LOCF; separately assess original verification of an author-reported 95% CI and its analysis assumptions. - Why this condition is needed: Needed to avoid certifying an original-author interval or clinical precision merely because an interval exists. - Application exceptions: Do not rerun t, SE or CI calculations in this work. - Remaining uncertainty: The author-reported 95% CI is unverified; the conditional interval does not resolve missingness, reporting bias or clinical importance. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N17 · Was a clinical-importance threshold for this ADAS-cog difference acquired? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Existing records leave the applicable clinical-importance threshold unverified and distinguish numerical reconstruction from clinical precision assessment. - Why unverified: The previous rationale assigning EX from unverified clinical importance remains under review; no new conclusion is made. - Reason for missing information: The previous rationale assigning EX from unverified clinical importance remains under review; no new conclusion is made. - Required materials and conditions: Validated importance criteria and direct clinical outcomes for the diagnosis, scale and duration. - Materials to obtain first: Validated importance criteria and direct clinical outcomes for the diagnosis, scale and duration. - Further research: Separately review context-appropriate importance evidence and daily-function material. - Conditions for verification: Verify applicable importance criteria and their relationship to the result and uncertainty. - Why this condition is needed: Needed to distinguish statistical magnitude/significance from clinical importance. - Application exceptions: Do not invent MCID, NNT or efficacy percentages or reconfirm EX. - Remaining uncertainty: The previous rationale assigning EX from unverified clinical importance remains under review; no new conclusion is made. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N18 · Were sequence generation and actual allocation concealment verified? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Historical descriptions record a computer-generated random sequence and blinding codes, but separation of responsibilities and actual concealment details are unverified. - Why unverified: Original some-concerns assessments are provisional and are not certified as an official RoB2 judgment here. - Reason for missing information: Original some-concerns assessments are provisional and are not certified as an official RoB2 judgment here. - Required materials and conditions: Sequence generation, recruitment/allocation responsibilities, concealment and baseline balance. - Materials to obtain first: Sequence generation, recruitment/allocation responsibilities, concealment and baseline balance. - Further research: Compare recruitment/allocation procedures, registration, baseline tables and results. - Conditions for verification: Distinguish recorded computer-generated sequence/codes from unverified execution details. - Why this condition is needed: Needed to avoid treating a randomization label as resolution of all allocation issues. - Application exceptions: Do not turn unverified details into evidence of improper allocation. - Remaining uncertainty: Original some-concerns assessments are provisional and are not certified as an official RoB2 judgment here. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N19 · How far are comparator matching, adherence, assessor training and successful blinding verified? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Double blinding, matching appearance, caregiver supervision and the same ADAS-cog schedule are recorded; taste/smell, quantitative adherence, assessor training and successful blinding are unverified. - Why unverified: Do not turn some verified procedures into a conclusion that no deviation or measurement problems existed. - Reason for missing information: Do not turn some verified procedures into a conclusion that no deviation or measurement problems existed. - Required materials and conditions: Appearance, taste/smell, caregiver supervision, assessor training and successful blinding. - Materials to obtain first: Appearance, taste/smell, caregiver supervision, assessor training and successful blinding. - Further research: Acquire product matching, assessment procedures, exposure by group and success checks. - Conditions for verification: Link recorded appearance matching, supervision and assessment schedules, assessing verification of taste/smell matching, quantitative adherence, assessor training and blinding success. - Why this condition is needed: Needed to preserve distinct verified scopes for intervention and measurement. - Application exceptions: Do not turn a double-blind label into complete verification of actual success. - Remaining uncertainty: Do not turn some verified procedures into a conclusion that no deviation or measurement problems existed. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N20 · Were prospective registration/SAP and the selected result compared? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The paper describes a 16-week change-score test but contains multiple scales/analyses; core timestamped registration/SAP were not acquired. S3's listed IRCT identifier also differs from verification of the actual registry and timing. - Why unverified: Prospective endpoint specification and analysis selection cannot currently be independently compared. - Reason for missing information: Prospective endpoint specification and analysis selection cannot currently be independently compared. - Required materials and conditions: Time-verified registration, protocol, SAP and scale/time/analysis changes. - Materials to obtain first: Time-verified registration, protocol, SAP and scale/time/analysis changes. - Further research: Link original registration, timestamps and amendments to the statistical section. - Conditions for verification: Compare the actual plan with 16-week ADAS-cog analysis and reporting. - Why this condition is needed: Needed to avoid mistaking the page-selected endpoint for a registry primary endpoint. - Application exceptions: Unavailable registration is not evidence of nonregistration or manipulated selective reporting. - Remaining uncertainty: Prospective endpoint specification and analysis selection cannot currently be independently compared. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1, S3 ### N21 · Were the comparisons in the three reports distinguished from independent replication? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The retained reports differ in comparator, co-treatment, scale and duration. Original records identify S1 as a direct placebo trial and leave independent replication under the same conditions unverified. - Why unverified: No unique-participant total, definitive independent-family count or new replication certification is provided. - Reason for missing information: No unique-participant total, definitive independent-family count or new replication certification is provided. - Required materials and conditions: Report identity, comparator, co-treatment, endpoints, times and family links. - Materials to obtain first: Report identity, comparator, co-treatment, endpoints, times and family links. - Further research: Compare report, registry and participant identities to update unique-family links. - Conditions for verification: Explain known relationships among S1 placebo, S2 active and S3 add-on comparisons and unverified unique counts. - Why this condition is needed: Needed to avoid counting 3 reports as 3 independent replications of the same question. - Application exceptions: Do not assume the same participant group solely from shared authors or ingredient. - Remaining uncertainty: No unique-participant total, definitive independent-family count or new replication certification is provided. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1, S2, S3 ### N22 · Within which search and review scope is insufficiency described? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Original records describe 56 submitted web-search queries and core comparisons as of 2026-09-14. This was not a complete database search, systematic review or exhaustive unpublished-registry survey; no new clinical search was performed here. - Why unverified: Insufficiency language is limited to the recorded search scope and does not certify absence of all current literature. - Reason for missing information: Insufficiency language is limited to the recorded search scope and does not certify absence of all current literature. - Required materials and conditions: Original review date, search methods, registration/unpublished/correction scope and current input. - Materials to obtain first: Original review date, search methods, registration/unpublished/correction scope and current input. - Further research: Record actual queries, dates and inclusion/exclusion within later authorized scope. - Conditions for verification: Distinguish the original 2026-09-14 review from this retained-material conversion. - Why this condition is needed: Needed to avoid presenting a retained review as a current exhaustive search. - Application exceptions: No new search does not mean 0 studies worldwide. - Remaining uncertainty: Insufficiency language is limited to the recorded search scope and does not certify absence of all current literature. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1, S2, S3 ### N23 · How far are S1's university/company support, material supply, cash shares, employee authorship, patents and separate COI verified? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: S1 records a joint Tehran university/Green Plants of Life grant and company material supply. - Why unverified: Cash shares, employee authorship, patents and separate COI are unverified. - Reason for missing information: Cash shares, employee authorship, patents and separate COI are unverified. - Required materials and conditions: University/company support, material, cash shares, employee authorship, patents and COI. - Materials to obtain first: University/company support, material, cash shares, employee authorship, patents and COI. - Further research: Compare grant, material-supply, author, patent and COI documents within the same report. - Conditions for verification: Link stated joint support and company material supply, assessing reporting and original verification of cash shares, employee authorship, patents and separate COI. - Why this condition is needed: Needed to avoid automatic exclusion or certification of independence based on funding alone. - Application exceptions: Funding institutions and independence of trial replication are separate. - Remaining uncertainty: Cash shares, employee authorship, patents and separate COI are unverified. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N24 · How far are funding, product support, employee authorship, patents and COI verified in S2's own documents? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: S2's original evidence records funding, product, employee-authorship and patent details as unverified in that review. - Why unverified: Details establishing S2's independent funding or presence/absence of interests are not currently determined. - Reason for missing information: Details establishing S2's independent funding or presence/absence of interests are not currently determined. - Required materials and conditions: S2-specific funding, products, employment, patents and COI. - Materials to obtain first: S2-specific funding, products, employment, patents and COI. - Further research: Individually compare S2 funding, material supply, author declarations and trial identity. - Conditions for verification: Without inheriting S1 information, assess the existence and actual verification of funding, product, employment, patent and COI material in S2's own documents. - Why this condition is needed: Needed to avoid transferring funding information to another comparison with the same authors. - Application exceptions: Do not copy S1's university/company support as verified S2 information. - Remaining uncertainty: Details establishing S2's independent funding or presence/absence of interests are not currently determined. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S2 ### N25 · How far were S3's support/COI declaration and separate product-supply, employee-authorship and patent verification completed? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: S3 records Tabriz University Neurosciences Research Center grant 62590 and the authors' declaration of no COI. - Why unverified: Separate verification of product supply, employee authorship and patents is incomplete. - Reason for missing information: Separate verification of product supply, employee authorship and patents is incomplete. - Required materials and conditions: Grant 62590, author COI declaration, product supply, employee authorship and patents. - Materials to obtain first: Grant 62590, author COI declaration, product supply, employee authorship and patents. - Further research: Link support, product, author and patent material by report. - Conditions for verification: Link recorded grant 62590 and the authors' no-COI declaration, assessing whether separate product-supply, employee-authorship and patent verification material was confirmed. - Why this condition is needed: Needed to distinguish author declarations from complete independence verification. - Application exceptions: A no-COI declaration does not establish absence of bias. - Remaining uncertainty: Separate verification of product supply, employee authorship and patents is incomplete. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S3 ### N26 · How far are S1's reported adverse-event/death counts and event definitions, collection completeness and severity verified? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: S1 records hypomania 2/23 versus 0/23, dry mouth 3/23 versus 1/23 and 1 placebo-group death from myocardial infarction. - Why unverified: Complete event definitions, collection completeness, causality and long-term risk are not established. - Reason for missing information: Complete event definitions, collection completeness, causality and long-term risk are not established. - Required materials and conditions: Event definitions, people denominators by group, duration, severity and collection. - Materials to obtain first: Event definitions, people denominators by group, duration, severity and collection. - Further research: Link original safety tables, denominators, collection procedures and discontinuation reasons. - Conditions for verification: Retain hypomania 2/23 versus 0/23, dry mouth 3/23 versus 1/23 and 1 placebo-group death, separately assessing verification of definitions, people denominators, duration, severity and collection completeness. - Why this condition is needed: Needed to avoid turning small-trial records into a statement that no serious events occurred. - Application exceptions: Do not calculate new rates, risk ratios or NNT. - Remaining uncertainty: Complete event definitions, collection completeness, causality and long-term risk are not established. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N27 · Were harm collection and onset/recovery/discontinuation times acquired? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Retained records state short-term events, placebo-group death and some dropouts; event-specific timing, recovery, re-exposure and all collection details are unspecified. - Why unverified: Events, times and collection completeness beyond current records cannot be established. - Reason for missing information: Events, times and collection completeness beyond current records cannot be established. - Required materials and conditions: Collection system, event dates, severity, discontinuation, recovery and omissions. - Materials to obtain first: Collection system, event dates, severity, discontinuation, recovery and omissions. - Further research: Compare the safety section, event-specific timelines and all dropout reasons. - Conditions for verification: Link actual event collection and timing/discontinuation details to original material. - Why this condition is needed: Needed to avoid certifying complete collection or causality from event counts alone. - Application exceptions: Do not infer unverified times, recovery or re-exposure. - Remaining uncertainty: Events, times and collection completeness beyond current records cannot be established. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N28 · Was direct harm material for concomitant drugs, co-exposures and special populations verified? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Original records do not establish interactions with other drugs or safety in pregnancy/lactation or major liver/kidney disease. - Why unverified: Trial medication restrictions and a small sample are not guarantees of safety for every individual. - Reason for missing information: Trial medication restrictions and a small sample are not guarantees of safety for every individual. - Required materials and conditions: Direct harm material for concomitant drugs, co-exposures, pregnancy/lactation and liver/kidney disease. - Materials to obtain first: Direct harm material for concomitant drugs, co-exposures, pregnancy/lactation and liver/kidney disease. - Further research: Separately review population, exposure and follow-up appropriate to the required harm question. - Conditions for verification: Preserve recorded trial medication restrictions while assessing verification and applicability of direct harm material for concomitant drugs, co-exposures, pregnancy/lactation and major liver/kidney disease. - Why this condition is needed: Needed to avoid extending short-term records in a narrow population to all safety questions. - Application exceptions: Do not infer absence of events with other drugs or populations. - Remaining uncertainty: Trial medication restrictions and a small sample are not guarantees of safety for every individual. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N29 · Was direct exposure, event, denominator and follow-up material to assess long-term/rare harm beyond 16 weeks verified? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Original records state that small samples cannot exclude rare or long-term risks. - Why unverified: Direct material and collection scope for long-term/rare harms are insufficient. - Reason for missing information: Direct material and collection scope for long-term/rare harms are insufficient. - Required materials and conditions: Long-term exposure, rare events, denominators, follow-up and appropriate collection design. - Materials to obtain first: Long-term exposure, rare events, denominators, follow-up and appropriate collection design. - Further research: When long-term/rare harm questions are needed, review appropriate follow-up, registry and collection designs. - Conditions for verification: Do not extend short-term records to exclusion of long-term/rare risks; assess verification of long-term exposure, rare events, denominators, follow-up and suitable collection material. - Why this condition is needed: Needed to avoid excluding rare/long-term risks from small short-term results. - Application exceptions: Do not impose all long-term harm studies as additional mandatory conditions for the original narrow efficacy question. - Remaining uncertainty: Direct material and collection scope for long-term/rare harms are insufficient. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N30 · Are cognitive scores being extended to prevention, slowing progression or medication replacement? Verification status: Not applicable Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The current question concerns 16-week ADAS-cog change. The retained original does not establish dementia prevention, slowing progression, standard-drug replacement or long-term function. - Why unverified: These separate extensions are not required as mandatory event outcomes for the current narrow cognitive comparison. - Reason for missing information: These separate extensions are not required as mandatory event outcomes for the current narrow cognitive comparison. - Required materials and conditions: Boundary between ADAS-cog and prevention, daily function, caregiving, progression or prescription-drug replacement. - Materials to obtain first: Boundary between ADAS-cog and prevention, daily function, caregiving, progression or prescription-drug replacement. - Further research: For extensions, separately review the relevant events, daily function, progression and replacement comparisons. - Conditions for verification: Separate the current 16-week score question from other extensions. - Why this condition is needed: Needed to distinguish the selected cognitive-function endpoint from separate clinical questions. - Application exceptions: Do not reclassify the cognitive score itself as a surrogate. - Remaining uncertainty: These separate extensions are not required as mandatory event outcomes for the current narrow cognitive comparison. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1, S2, S3 ### N31 · Were optimal dose and persistence after discontinuation verified? Verification status: Not applicable Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Core trial specifications are 30 mg/day for 16 weeks; optimal dose, persistence after stopping and prevention are not established. - Why unverified: Because the separate extension was not adopted, it is not required as a mandatory dose comparison for the current result. - Reason for missing information: Because the separate extension was not adopted, it is not required as a mandatory dose comparison for the current result. - Required materials and conditions: Direct dose comparisons, post-discontinuation follow-up, prespecified subgroups and separate estimates. - Materials to obtain first: Direct dose comparisons, post-discontinuation follow-up, prespecified subgroups and separate estimates. - Further research: For extensions, separately review direct dose comparisons, discontinuation and long-term follow-up. - Conditions for verification: Distinguish nominal 30 mg/day, 16-week results from optimal-dose and persistence questions. - Why this condition is needed: Needed to avoid turning a single trial dose into an optimal dose or persistent effect. - Application exceptions: Do not automatically require every extension for the current 16-week comparison. - Remaining uncertainty: Because the separate extension was not adopted, it is not required as a mandatory dose comparison for the current result. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1 ### N32 · Were the original C46, P correction and EX review status retained? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Original C46 is a retained value; endpoint S→P was corrected. EX rationale, statistics versus clinical importance, CX and the final grade remain under review; grade revalidation is false. - Why unverified: This table does not newly certify the final validity of the existing grade or calculate scores/axes. - Reason for missing information: This table does not newly certify the final validity of the existing grade or calculate scores/axes. - Required materials and conditions: Original grade, score, current/previous axes, corrections and unresolved notices. - Materials to obtain first: Original grade, score, current/previous axes, corrections and unresolved notices. - Further research: For a later verdict request, preserve previous values, evidence and change reasons as a separate event. - Conditions for verification: Preserve original C46, P, EX/CX, grade-revalidation false and pending method review from the retained original. - Why this condition is needed: Needed to avoid automatically inheriting original values as efficacy judgments for the new table. - Application exceptions: Do not turn the S→P correction into revalidation of other axes or the final grade. - Remaining uncertainty: This table does not newly certify the final validity of the existing grade or calculate scores/axes. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: ### N33 · Were historical access descriptions distinguished from actual reading in this work? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: What was actually read is the current retained summary. Historical descriptions of S1 author-uploaded transcription/bibliographic abstract, S2 bibliographic abstract and S3 indexed excerpt remain in bibliographic notes. - Why unverified: External originals, registration, SAP, publisher PDF and original bytes are unread/unacquired in this work. Individual structured access-level fields are absent in the original. - Reason for missing information: External originals, registration, SAP, publisher PDF and original bytes are unread/unacquired in this work. Individual structured access-level fields are absent in the original. - Required materials and conditions: Bibliographic flags, original locations, original review date, current acquisition/reading and file SHA. - Materials to obtain first: Bibliographic flags, original locations, original review date, current acquisition/reading and file SHA. - Further research: When original material is later acquired, record type, date, location, bytes and actual reading. - Conditions for verification: Separately display actual retained-summary reading, historical descriptions and unread external material. - Why this condition is needed: Needed to avoid turning provision of original links into current full-text reading. - Application exceptions: Do not infer absent access-level, source-location or individual access-date fields from narrative descriptions. - Remaining uncertainty: External originals, registration, SAP, publisher PDF and original bytes are unread/unacquired in this work. Individual structured access-level fields are absent in the original. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1, S2, S3 ### N34 · Are material acquisition and condition/verdict revisions distinguished as events? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Retain original corrections/unresolved status, S2/S3 context, historical calculations and access limitations. Registration, SAP, author estimates, importance, measurement, safety and funding details are later verification targets. - Why unverified: At the original review, no new material, regrading or public deployment had been performed. - Reason for missing information: At the original review, no new material, regrading or public deployment had been performed. - Required materials and conditions: Preservation records for full texts, registration, corrections, numbers, condition versions and previous values. - Materials to obtain first: Preservation records for full texts, registration, corrections, numbers, condition versions and previous values. - Further research: Record new material identity, reading and locations, review affected rows and freeze condition revisions before application. - Conditions for verification: Distinguish current retained scope from material and linked items needed for later updates. - Why this condition is needed: Needed to avoid automatic condition/verdict changes when new material is acquired. - Application exceptions: Do not delete originals, unfavorable results or unverified information. - Remaining uncertainty: At the original review, no new material, regrading or public deployment had been performed. - Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S1, S2, S3 ## Evidence and sources ### S1 Saffron versus placebo; 16-week ADAS-cog [Official source](https://www.researchgate.net/publication/46218185_ORIGINAL_ARTICLE_Saffron_in_the_treatment_of_patients_with_mild_to_moderate_Alzheimer%27s_disease_a_16-week_randomized_and_placebo-controlled_trial) Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. Findings recorded in the summary: Retained summary: 46 participants, 23/23 randomized, paper-defined ITT/LOCF, analysis df44. At 16 weeks, changes −3.69±1.69 versus +4.08±1.34 points (SD), change-score P<.0001. The simple difference −7.77 points is a historical editorial calculation. Dropouts 1/23 versus 3/23, total 4/46 and 8.7%, and 22/20 completers are retained records/historical subtraction. Joint Tehran university/Green Plants of Life support and company material supply are recorded; cash shares, employee authorship, patents and separate COI are unverified. Record level: A direct record for the selected comparison, but original tables, registration and SAP were not read in this work. Retain small-sample, missing-data, reporting-inconsistency and unverified-importance limitations. Independent replication: S1’s placebo 16-week ADAS-cog, S2’s donepezil active comparison at 22 weeks and S3’s donepezil add-on 12-week MMSE address different questions. Do not count 3 reports as 3 independent replications of the same question or sum participants. Definitive unique-family and participant totals are not provided. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained bibliographic/linked summary and historical review record | Internally retained summary | Retained copy acquired; summary read | Stored existing review summary read | The retained summary was acquired and read. This is not an original-byte copy of a clinical full text. Historical manuscript descriptions of transcription, abstract and indexed-excerpt access are retained records. They do not establish external full-text reading, original registry verification or independent clinical certification in this work. The original verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are unrecorded; external access was not attempted in this work. | | Existing external link for author-uploaded transcription and bibliographic abstract | Current public availability unverified | External access not attempted; not acquired | Not read | The retained external URL is provided. Access, acquisition and reading were not attempted in this work. Historical manuscript descriptions of transcription, abstract and indexed-excerpt access are retained records. They do not establish external full-text reading, original registry verification or independent clinical certification in this work. The original verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are unrecorded; external access was not attempted in this work. | ### S2 Saffron versus donepezil; 22-week active comparison [PubMed](https://pubmed.ncbi.nlm.nih.gov/19838862/) Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. Findings recorded in the summary: Retained summary: 54 participants, 22-week ADAS-cog/CDR-SB, donepezil active comparator rather than placebo. The abstract’s no significant between-group difference establishes neither equivalence, noninferiority nor placebo-relative efficacy. Completion/analysis details and its own funding, products, employee authorship, patents and COI are unverified. Record level: Retain as active-comparator context without merging it into direct placebo-relative efficacy or replication of the same question. Independent replication: S1’s placebo 16-week ADAS-cog, S2’s donepezil active comparison at 22 weeks and S3’s donepezil add-on 12-week MMSE address different questions. Do not count 3 reports as 3 independent replications of the same question or sum participants. Definitive unique-family and participant totals are not provided. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained bibliographic/linked summary and historical review record | Internally retained summary | Retained copy acquired; summary read | Stored existing review summary read | The retained summary was acquired and read. This is not an original-byte copy of a clinical full text. Historical manuscript descriptions of transcription, abstract and indexed-excerpt access are retained records. They do not establish external full-text reading, original registry verification or independent clinical certification in this work. The original verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are unrecorded; external access was not attempted in this work. | | Existing external bibliography/abstract link | Current public availability unverified | External access not attempted; not acquired | Not read | The retained external URL is provided. Access, acquisition and reading were not attempted in this work. Historical manuscript descriptions of transcription, abstract and indexed-excerpt access are retained records. They do not establish external full-text reading, original registry verification or independent clinical certification in this work. The original verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are unrecorded; external access was not attempted in this work. | ### S3 Saffron added to donepezil; 12-week MMSE [Official source](https://www.sciencedirect.com/science/article/pii/S2210803322000434) Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. Findings recorded in the summary: Retained summary: 60 participants, 30/30 randomized, 27/27 analyzed in the excerpt, 12-week MMSE P=.303, saffron 15 mg added 2 times daily. Mean difference and 95% CI are unverified; inflammatory markers are not cognitive effects. Grant 62590 and an author declaration of no COI are recorded, but product supply, employee authorship and patents remain separately unverified. The listed IRCT20190428043409N1 does not establish original registry or timing verification. Record level: Do not turn nonsignificance into absence of effect. Retain co-treatment/scale differences and unverified estimates together. Independent replication: S1’s placebo 16-week ADAS-cog, S2’s donepezil active comparison at 22 weeks and S3’s donepezil add-on 12-week MMSE address different questions. Do not count 3 reports as 3 independent replications of the same question or sum participants. Definitive unique-family and participant totals are not provided. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained bibliographic/linked summary and historical review record | Internally retained summary | Retained copy acquired; summary read | Stored existing review summary read | The retained summary was acquired and read. This is not an original-byte copy of a clinical full text. Historical manuscript descriptions of transcription, abstract and indexed-excerpt access are retained records. They do not establish external full-text reading, original registry verification or independent clinical certification in this work. The original verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are unrecorded; external access was not attempted in this work. | | Existing external publisher indexed-excerpt link | Current public availability unverified | External access not attempted; not acquired | Not read | The retained external URL is provided. Access, acquisition and reading were not attempted in this work. Historical manuscript descriptions of transcription, abstract and indexed-excerpt access are retained records. They do not establish external full-text reading, original registry verification or independent clinical certification in this work. The original verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are unrecorded; external access was not attempted in this work. | ## Review criteria and methods These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score. - M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility conditions and reasons for changes; distinguish intervention variants. · Retained method-application records were reused. External originals were not reread and method content was not reassessed. - M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Link studies and reports separately; do not omit studies solely because results are unreported. · Retained method-application records were reused. External originals were not reread and method content was not reassessed. - M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Fix the result and effect of interest when examining randomization, deviations, missingness, measurement and selective reporting. · Retained method-application records were reused. External originals were not reread and method content was not reassessed. - M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision. · Retained method-application records were reused. External originals were not reread and method content was not reassessed. - M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence. · Retained method-application records were reused. External originals were not reread and method content was not reassessed. ## What the statuses mean - Partly verified: Some retained information and the remaining required material are displayed together. - Unverified: The specified condition cannot be established within the retained scope; this means neither an effect of 0, 0 studies worldwide nor established safety. - Review incomplete: Original-material comparison/search was not performed within the authorized scope. - Not reported: A scope-limited status meaning that an item is not reported in the specific material/section actually read. - Inaccessible: Used only for material actually accessed unsuccessfully. Not assigned to clinical material in this work. - Insufficient evidence matching the conditions: Used only after reviewing relevant research within a defined scope and finding insufficient evidence to answer the condition. Not applied universally here. - Not applicable: Separate events, optimal dose and long-term extensions are not additional mandatory conditions for the selected 16-week cognitive comparison. - Conflicting data: Used when material addressing the same question, time and analysis is difficult to reconcile. Different numbers in reviews alone do not qualify. - Met: The stated retained content, boundary and attribution are verified; this is not clinical confirmation, external full-text reading or revalidation of the original verdict. ## Change history 2026-10-28 · Public page/materials 1.0. The public view and materials were prepared from the existing 34 items. No new clinical search, verification-state change or scoring was performed.