{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3081-main", "verdict_number": "3081", "title": "Oral saffron stigma extract × Cognition in mild-to-moderate Alzheimer's disease", "view_version": "1.0", "view_created_date": "2026-10-28", "criteria_version": "1.1", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-14", "review_scope": { "materials_read": "Retained Korean/English summaries and case-specific condition/application records", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "Prepared from retained summaries and condition-application records. External abstracts, full texts, registration, protocols and analysis plans remain unread. Historical review records do not establish current independent clinical validation.", "date_meaning": "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." }, "claim_context": { "population": "Age over 55, probable mild-to-moderate Alzheimer’s disease, MMSE 15–26; core antidementia-medication restrictions", "intervention": "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", "endpoint": "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", "excluded_extensions": [ "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." ] }, "requirements": [ { "item_id": "N01", "question_type": "Evidence condition", "question": "Which saffron, Alzheimer's disease and cognition comparison is being checked?", "needed": "Specific extract, population, 16-week ADAS-cog, placebo and original claim boundary.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid merging all related saffron effects into a single status.", "application_exception": "Active-drug comparisons and add-on trials are not replications of the same placebo question.", "criterion": "Link the specific stigma extract's 16-week ADAS-cog versus placebo question to the retained original.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare candidate material with the exact ingredient, population, comparator, scale and time.", "current_reports": [ "S1", "S2", "S3" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "Verification of the question boundary does not establish clinical confirmation or revalidation of the existing grade.", "missingness": "Verification of the question boundary does not establish clinical confirmation or revalidation of the existing grade.", "uncertainty": "Verification of the question boundary does not establish clinical confirmation or revalidation of the existing grade.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Specific extract, population, 16-week ADAS-cog, placebo and original claim boundary." }, { "item_id": "N02", "question_type": "Evidence condition", "question": "Do the core trial population and medication restrictions match the original question?", "needed": "Diagnosis, age, MMSE, inclusion/exclusion and antidementia-medication restrictions.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid applying the findings to all patients with dementia in routine care.", "application_exception": "Do not extend to MCI, dementia prevention or all patients receiving concomitant drugs.", "criterion": "Distinguish the core population, selection and medication restrictions from unverified representativeness.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link selection criteria, baseline tables and medication restrictions to the actual results.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "Retained claim conditions specify age over 55, probable mild-to-moderate AD, MMSE 15–26 and core antidementia-medication restrictions.", "condition_status": "Partly verified", "status_reason": "Detailed selection, representativeness and applicability to all patients receiving concomitant treatment are not established within this retained scope.", "missingness": "Detailed selection, representativeness and applicability to all patients receiving concomitant treatment are not established within this retained scope.", "uncertainty": "Detailed selection, representativeness and applicability to all patients receiving concomitant treatment are not established within this retained scope.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Diagnosis, age, MMSE, inclusion/exclusion and antidementia-medication restrictions." }, { "item_id": "N03", "question_type": "Evidence condition", "question": "How far are S1's plant part, extraction specifications, detailed batch, content and manufacturing quality verified?", "needed": "Stigma, extraction solvent, capsule, standardization and the actual trial product.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid transferring results to tea, foods or isolated constituents.", "application_exception": "Other extracts, crocin/safranal alone and combination products are separate.", "criterion": "Link the reported stigma, 80% ethanolic dried extract, capsule and standardization specifications, separately assessing original verification of detailed batch, content and manufacturing quality.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare product specifications and batch information with the applicability of the trial results.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "Retained records describe capsules of dried 80% ethanolic extract of dried Crocus sativus stigma and crocin/safranal standardization.", "condition_status": "Partly verified", "status_reason": "Current original-source verification of detailed batch, content and manufacturing quality was not performed.", "missingness": "Current original-source verification of detailed batch, content and manufacturing quality was not performed.", "uncertainty": "Current original-source verification of detailed batch, content and manufacturing quality was not performed.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Stigma, extraction solvent, capsule, standardization and the actual trial product." }, { "item_id": "N04", "question_type": "Evidence condition", "question": "Were the core trial route and dose linked?", "needed": "Oral capsule, amount per 1 administration, frequency, total amount and actual exposure records.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid turning trial specifications into personal dosing instructions.", "application_exception": "Nominal dose does not establish quantitative adherence.", "criterion": "Distinguish the reported oral 15 mg, 2 times daily, from unverified actual exposure.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare administration specifications, adherence and discontinuation records by group.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "Original claim conditions and product facts specify oral 15 mg capsules, 2 times daily, totaling 30 mg/day in the core trial.", "condition_status": "Met", "status_reason": "Actual quantitative adherence and each individual's exposure remain separately unverified.", "missingness": "Actual quantitative adherence and each individual's exposure remain separately unverified.", "uncertainty": "Actual quantitative adherence and each individual's exposure remain separately unverified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Oral capsule, amount per 1 administration, frequency, total amount and actual exposure records." }, { "item_id": "N05", "question_type": "Evidence condition", "question": "Do administration duration and the selected result time match?", "needed": "16-week administration, ADAS-cog assessment time and post-discontinuation material.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid merging results at different durations as the same effect.", "application_exception": "S2's 22 weeks and S3's 12 weeks do not replace the core 16-week result.", "criterion": "Link core 16-week administration to the ADAS-cog result.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Separate assessment schedules, end-of-treatment and post-discontinuation follow-up.", "current_reports": [ "S1", "S2", "S3" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "Persistence beyond 16 weeks is outside this verification.", "missingness": "Persistence beyond 16 weeks is outside this verification.", "uncertainty": "Persistence beyond 16 weeks is outside this verification.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "16-week administration, ADAS-cog assessment time and post-discontinuation material." }, { "item_id": "N06", "question_type": "Evidence condition", "question": "Were the core placebo and antidementia-medication restrictions distinguished?", "needed": "Comparator product, antidementia-medication restrictions, rescue treatment and changes by group.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid attributing differences in concurrent treatment to saffron.", "application_exception": "Appearance matching does not guarantee taste/smell matching or agreement in all concomitant treatments.", "criterion": "Link the actual placebo and medication restrictions to unverified concomitant-treatment deviations.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Verify comparator specifications, treatment changes and their handling in the analysis of the effect of interest.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "Matching-appearance placebo capsules and core antidementia-medication restrictions are recorded. The original review left taste/smell matching and concomitant-treatment deviations unverified.", "condition_status": "Partly verified", "status_reason": "Material fully comparing concurrent treatment, adherence and rescue treatment by group is unavailable in the retained scope.", "missingness": "Material fully comparing concurrent treatment, adherence and rescue treatment by group is unavailable in the retained scope.", "uncertainty": "Material fully comparing concurrent treatment, adherence and rescue treatment by group is unavailable in the retained scope.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Comparator product, antidementia-medication restrictions, rescue treatment and changes by group." }, { "item_id": "N07", "question_type": "Evidence condition", "question": "Is the donepezil active comparison being turned into placebo-relative efficacy or equivalence?", "needed": "S2's actual comparator, duration, endpoints, design and equivalence plan.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to distinguish no significant difference from equivalence.", "application_exception": "Retain active-comparator material as a different comparison.", "criterion": "S2 is a 22-week donepezil active comparison and does not certify noninferiority or placebo-relative efficacy.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Review the active comparison's advance noninferiority criteria, models and intervals as a separate question.", "current_reports": [ "S2" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "S2 records 54 participants in an active comparison; the abstract's no significant difference is not converted into placebo-relative efficacy, equivalence or noninferiority.", "condition_status": "Met", "status_reason": "S2's completion/analysis details, detailed original text and registration remain separately unverified.", "missingness": "S2's completion/analysis details, detailed original text and registration remain separately unverified.", "uncertainty": "S2's completion/analysis details, detailed original text and registration remain separately unverified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S2's actual comparator, duration, endpoints, design and equivalence plan." }, { "item_id": "N08", "question_type": "Evidence condition", "question": "Were S3's nonsignificant MMSE result and different concomitant-treatment conditions both retained?", "needed": "Donepezil co-treatment, 12-week MMSE, denominators, result and role.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid retaining only favorable direct results.", "application_exception": "Do not turn nonsignificance into an effect of 0 or inflammatory markers into cognitive effects.", "criterion": "Explain the differences between S3 and S1 in co-treatment, scale and time.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "First compare whether results address the same question, then acquire separate estimates and intervals.", "current_reports": [ "S3" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "S3's mean difference, 95% CI, full original text and appendices are unverified.", "missingness": "S3's mean difference, 95% CI, full original text and appendices are unverified.", "uncertainty": "S3's mean difference, 95% CI, full original text and appendices are unverified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Donepezil co-treatment, 12-week MMSE, denominators, result and role." }, { "item_id": "N09", "question_type": "Evidence condition", "question": "Were the ADAS-cog definition, direction and version verified?", "needed": "16-week change, improvement with lower scores, exact version, translation and assessment procedures.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to distinguish the cognitive endpoint itself from other scales and events.", "application_exception": "Do not reclassify it as a biological surrogate merely because it is a test.", "criterion": "Distinguish the direction of the cognitive endpoint from the verified scope of measurement details.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link scale version, language, assessor training and schedule to the result table.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Partly verified", "status_reason": "Detailed measurement specifications and successful assessor blinding cannot be established.", "missingness": "Detailed measurement specifications and successful assessor blinding cannot be established.", "uncertainty": "Detailed measurement specifications and successful assessor blinding cannot be established.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "16-week change, improvement with lower scores, exact version, translation and assessment procedures." }, { "item_id": "N10", "question_type": "Evidence condition", "question": "Were the core change values, SD and direction preserved?", "needed": "Group-specific 16-week ADAS-cog mean changes, SD and original location.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to distinguish final values, within-group change and between-group effects.", "application_exception": "Do not convert mean differences into individual probabilities of improvement.", "criterion": "Attribute the retained changes −3.69±1.69 versus +4.08±1.34 and SD to the relevant comparison.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Verify original tables, denominators, definitions and rounding before reviewing numerical attribution.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "External original tables were not reread in this work; recorded numbers are treated within preservation of the original verdict.", "missingness": "External original tables were not reread in this work; recorded numbers are treated within preservation of the original verdict.", "uncertainty": "External original tables were not reread in this work; recorded numbers are treated within preservation of the original verdict.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Group-specific 16-week ADAS-cog mean changes, SD and original location." }, { "item_id": "N11", "question_type": "Evidence condition", "question": "How far are the reported change-score, repeated-measures and final-value tests and the authors' explanation/correction of the final-value inconsistency verified?", "needed": "Analysis, time, P, t/df and correction records for each test.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to distinguish different tests from actual internal reporting inconsistencies.", "application_exception": "Do not call every difference in P a conflict before checking whether it concerns the same question.", "criterion": "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.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Acquire test-specific original tables, models and correction material, comparing each test's meaning.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The historical inconsistency was not resolved through new calculations; the original authors' explanation/correction remains unverified.", "missingness": "The historical inconsistency was not resolved through new calculations; the original authors' explanation/correction remains unverified.", "uncertainty": "The historical inconsistency was not resolved through new calculations; the original authors' explanation/correction remains unverified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Analysis, time, P, t/df and correction records for each test." }, { "item_id": "N12", "question_type": "Evidence condition", "question": "How far are endpoint-specific execution, denominators and sensitivity verified for 23/23 allocation and paper-defined ITT/LOCF?", "needed": "Randomized, completed and analyzed n, ITT definition, LOCF and effect of interest.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid automatically substituting randomized counts for analysis denominators.", "application_exception": "Do not expand the paper's analysis label into certification of modern complete ITT.", "criterion": "Preserve recorded 23/23 allocation, paper-defined ITT/LOCF and analysis df44, assessing endpoint-specific analysis sets, execution, sensitivity and current original-data comparison.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare participant flow, actual endpoint-specific analysis sets and missing-data models.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Partly verified", "status_reason": "Endpoint-specific analysis execution, sensitivity and current original-data comparison are unverified.", "missingness": "Endpoint-specific analysis execution, sensitivity and current original-data comparison are unverified.", "uncertainty": "Endpoint-specific analysis execution, sensitivity and current original-data comparison are unverified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Randomized, completed and analyzed n, ITT definition, LOCF and effect of interest." }, { "item_id": "N13", "question_type": "Evidence condition", "question": "How far are group-specific dropout/completion records, other missing-data reasons, death handling and sensitivity verified?", "needed": "Group-specific dropout, reasons, death and distinction between completion and analysis.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid turning subtraction into an author-observed completion table.", "application_exception": "Do not calculate new dropout rates or completion counts.", "criterion": "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.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link group-specific flowcharts, missing-data reasons and death handling to results.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Partly verified", "status_reason": "Other missing-data reasons and sensitivity analyses are unverified; no subtraction or rate calculation was performed in this work.", "missingness": "Other missing-data reasons and sensitivity analyses are unverified; no subtraction or rate calculation was performed in this work.", "uncertainty": "Other missing-data reasons and sensitivity analyses are unverified; no subtraction or rate calculation was performed in this work.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Group-specific dropout, reasons, death and distinction between completion and analysis." }, { "item_id": "N14", "question_type": "Evidence condition", "question": "Were the validity of LOCF missing-data assumptions and sensitivity to other handling verified?", "needed": "Missing-data assumptions, imputation method, reasons by group and sensitivity results.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid claiming no missing-data problem merely because numerical results are complete.", "application_exception": "Do not score LOCF use itself as proven null efficacy or a specified bias magnitude.", "criterion": "Retain original LOCF use and missing-data uncertainty, assessing whether reasons by group, assumption validity and sensitivity to alternative handling were verified.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare missing-data and sensitivity analyses appropriate to the effect of interest with randomized results.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "The original review retains LOCF use, dropout, placebo-group death and some concerns, stating that LOCF does not eliminate missing-data uncertainty.", "condition_status": "Unverified", "status_reason": "The validity of missing-data assumptions and persistence of the effect under other handling are unverified.", "missingness": "The validity of missing-data assumptions and persistence of the effect under other handling are unverified.", "uncertainty": "The validity of missing-data assumptions and persistence of the effect under other handling are unverified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Missing-data assumptions, imputation method, reasons by group and sensitivity results." }, { "item_id": "N15", "question_type": "Evidence condition", "question": "Was the arithmetic −7.77-point difference distinguished from an author-adjusted effect?", "needed": "Original means, historical arithmetic, estimand definition and adjusted model.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid turning an existing calculation into a formal between-group effect reported by the authors.", "application_exception": "No new effect-size calculation is performed in this work.", "criterion": "Identify −7.77 as the historical simple difference between published mean changes.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare original paper estimates, models and intervals with the existing arithmetic.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "−7.77 points is the retained editorial simple arithmetic difference between mean changes, not an author-reported adjusted effect or an individual improvement probability.", "condition_status": "Met", "status_reason": "The arithmetic record does not replace verification of the authors' adjusted estimate.", "missingness": "The arithmetic record does not replace verification of the authors' adjusted estimate.", "uncertainty": "The arithmetic record does not replace verification of the authors' adjusted estimate.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original means, historical arithmetic, estimand definition and adjusted model." }, { "item_id": "N16", "question_type": "Evidence condition", "question": "How far are assumptions behind the editorial conditional interval and an author-reported 95% CI for the same endpoint verified?", "needed": "Interval calculator, assumptions, rounding, denominators, LOCF and the original author interval.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid certifying an original-author interval or clinical precision merely because an interval exists.", "application_exception": "Do not rerun t, SE or CI calculations in this work.", "criterion": "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.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare original author estimates/intervals, assumptions and missing-data sensitivity for the same endpoint.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The author-reported 95% CI is unverified; the conditional interval does not resolve missingness, reporting bias or clinical importance.", "missingness": "The author-reported 95% CI is unverified; the conditional interval does not resolve missingness, reporting bias or clinical importance.", "uncertainty": "The author-reported 95% CI is unverified; the conditional interval does not resolve missingness, reporting bias or clinical importance.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Interval calculator, assumptions, rounding, denominators, LOCF and the original author interval." }, { "item_id": "N17", "question_type": "Evidence condition", "question": "Was a clinical-importance threshold for this ADAS-cog difference acquired?", "needed": "Validated importance criteria and direct clinical outcomes for the diagnosis, scale and duration.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to distinguish statistical magnitude/significance from clinical importance.", "application_exception": "Do not invent MCID, NNT or efficacy percentages or reconfirm EX.", "criterion": "Verify applicable importance criteria and their relationship to the result and uncertainty.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Separately review context-appropriate importance evidence and daily-function material.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "Existing records leave the applicable clinical-importance threshold unverified and distinguish numerical reconstruction from clinical precision assessment.", "condition_status": "Unverified", "status_reason": "The previous rationale assigning EX from unverified clinical importance remains under review; no new conclusion is made.", "missingness": "The previous rationale assigning EX from unverified clinical importance remains under review; no new conclusion is made.", "uncertainty": "The previous rationale assigning EX from unverified clinical importance remains under review; no new conclusion is made.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Validated importance criteria and direct clinical outcomes for the diagnosis, scale and duration." }, { "item_id": "N18", "question_type": "Evidence condition", "question": "Were sequence generation and actual allocation concealment verified?", "needed": "Sequence generation, recruitment/allocation responsibilities, concealment and baseline balance.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid treating a randomization label as resolution of all allocation issues.", "application_exception": "Do not turn unverified details into evidence of improper allocation.", "criterion": "Distinguish recorded computer-generated sequence/codes from unverified execution details.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare recruitment/allocation procedures, registration, baseline tables and results.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "Historical descriptions record a computer-generated random sequence and blinding codes, but separation of responsibilities and actual concealment details are unverified.", "condition_status": "Partly verified", "status_reason": "Original some-concerns assessments are provisional and are not certified as an official RoB2 judgment here.", "missingness": "Original some-concerns assessments are provisional and are not certified as an official RoB2 judgment here.", "uncertainty": "Original some-concerns assessments are provisional and are not certified as an official RoB2 judgment here.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Sequence generation, recruitment/allocation responsibilities, concealment and baseline balance." }, { "item_id": "N19", "question_type": "Evidence condition", "question": "How far are comparator matching, adherence, assessor training and successful blinding verified?", "needed": "Appearance, taste/smell, caregiver supervision, assessor training and successful blinding.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to preserve distinct verified scopes for intervention and measurement.", "application_exception": "Do not turn a double-blind label into complete verification of actual success.", "criterion": "Link recorded appearance matching, supervision and assessment schedules, assessing verification of taste/smell matching, quantitative adherence, assessor training and blinding success.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Acquire product matching, assessment procedures, exposure by group and success checks.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Partly verified", "status_reason": "Do not turn some verified procedures into a conclusion that no deviation or measurement problems existed.", "missingness": "Do not turn some verified procedures into a conclusion that no deviation or measurement problems existed.", "uncertainty": "Do not turn some verified procedures into a conclusion that no deviation or measurement problems existed.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Appearance, taste/smell, caregiver supervision, assessor training and successful blinding." }, { "item_id": "N20", "question_type": "Evidence condition", "question": "Were prospective registration/SAP and the selected result compared?", "needed": "Time-verified registration, protocol, SAP and scale/time/analysis changes.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid mistaking the page-selected endpoint for a registry primary endpoint.", "application_exception": "Unavailable registration is not evidence of nonregistration or manipulated selective reporting.", "criterion": "Compare the actual plan with 16-week ADAS-cog analysis and reporting.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link original registration, timestamps and amendments to the statistical section.", "current_reports": [ "S1", "S3" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "Prospective endpoint specification and analysis selection cannot currently be independently compared.", "missingness": "Prospective endpoint specification and analysis selection cannot currently be independently compared.", "uncertainty": "Prospective endpoint specification and analysis selection cannot currently be independently compared.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Time-verified registration, protocol, SAP and scale/time/analysis changes." }, { "item_id": "N21", "question_type": "Evidence condition", "question": "Were the comparisons in the three reports distinguished from independent replication?", "needed": "Report identity, comparator, co-treatment, endpoints, times and family links.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid counting 3 reports as 3 independent replications of the same question.", "application_exception": "Do not assume the same participant group solely from shared authors or ingredient.", "criterion": "Explain known relationships among S1 placebo, S2 active and S3 add-on comparisons and unverified unique counts.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare report, registry and participant identities to update unique-family links.", "current_reports": [ "S1", "S2", "S3" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "No unique-participant total, definitive independent-family count or new replication certification is provided.", "missingness": "No unique-participant total, definitive independent-family count or new replication certification is provided.", "uncertainty": "No unique-participant total, definitive independent-family count or new replication certification is provided.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Report identity, comparator, co-treatment, endpoints, times and family links." }, { "item_id": "N22", "question_type": "Evidence condition", "question": "Within which search and review scope is insufficiency described?", "needed": "Original review date, search methods, registration/unpublished/correction scope and current input.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid presenting a retained review as a current exhaustive search.", "application_exception": "No new search does not mean 0 studies worldwide.", "criterion": "Distinguish the original 2026-09-14 review from this retained-material conversion.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Record actual queries, dates and inclusion/exclusion within later authorized scope.", "current_reports": [ "S1", "S2", "S3" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "Insufficiency language is limited to the recorded search scope and does not certify absence of all current literature.", "missingness": "Insufficiency language is limited to the recorded search scope and does not certify absence of all current literature.", "uncertainty": "Insufficiency language is limited to the recorded search scope and does not certify absence of all current literature.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original review date, search methods, registration/unpublished/correction scope and current input." }, { "item_id": "N23", "question_type": "Evidence condition", "question": "How far are S1's university/company support, material supply, cash shares, employee authorship, patents and separate COI verified?", "needed": "University/company support, material, cash shares, employee authorship, patents and COI.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid automatic exclusion or certification of independence based on funding alone.", "application_exception": "Funding institutions and independence of trial replication are separate.", "criterion": "Link stated joint support and company material supply, assessing reporting and original verification of cash shares, employee authorship, patents and separate COI.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare grant, material-supply, author, patent and COI documents within the same report.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "S1 records a joint Tehran university/Green Plants of Life grant and company material supply.", "condition_status": "Partly verified", "status_reason": "Cash shares, employee authorship, patents and separate COI are unverified.", "missingness": "Cash shares, employee authorship, patents and separate COI are unverified.", "uncertainty": "Cash shares, employee authorship, patents and separate COI are unverified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "University/company support, material, cash shares, employee authorship, patents and COI." }, { "item_id": "N24", "question_type": "Evidence condition", "question": "How far are funding, product support, employee authorship, patents and COI verified in S2's own documents?", "needed": "S2-specific funding, products, employment, patents and COI.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid transferring funding information to another comparison with the same authors.", "application_exception": "Do not copy S1's university/company support as verified S2 information.", "criterion": "Without inheriting S1 information, assess the existence and actual verification of funding, product, employment, patent and COI material in S2's own documents.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Individually compare S2 funding, material supply, author declarations and trial identity.", "current_reports": [ "S2" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "S2's original evidence records funding, product, employee-authorship and patent details as unverified in that review.", "condition_status": "Unverified", "status_reason": "Details establishing S2's independent funding or presence/absence of interests are not currently determined.", "missingness": "Details establishing S2's independent funding or presence/absence of interests are not currently determined.", "uncertainty": "Details establishing S2's independent funding or presence/absence of interests are not currently determined.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S2-specific funding, products, employment, patents and COI." }, { "item_id": "N25", "question_type": "Evidence condition", "question": "How far were S3's support/COI declaration and separate product-supply, employee-authorship and patent verification completed?", "needed": "Grant 62590, author COI declaration, product supply, employee authorship and patents.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to distinguish author declarations from complete independence verification.", "application_exception": "A no-COI declaration does not establish absence of bias.", "criterion": "Link recorded grant 62590 and the authors' no-COI declaration, assessing whether separate product-supply, employee-authorship and patent verification material was confirmed.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link support, product, author and patent material by report.", "current_reports": [ "S3" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "S3 records Tabriz University Neurosciences Research Center grant 62590 and the authors' declaration of no COI.", "condition_status": "Partly verified", "status_reason": "Separate verification of product supply, employee authorship and patents is incomplete.", "missingness": "Separate verification of product supply, employee authorship and patents is incomplete.", "uncertainty": "Separate verification of product supply, employee authorship and patents is incomplete.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Grant 62590, author COI declaration, product supply, employee authorship and patents." }, { "item_id": "N26", "question_type": "Evidence condition", "question": "How far are S1's reported adverse-event/death counts and event definitions, collection completeness and severity verified?", "needed": "Event definitions, people denominators by group, duration, severity and collection.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid turning small-trial records into a statement that no serious events occurred.", "application_exception": "Do not calculate new rates, risk ratios or NNT.", "criterion": "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.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link original safety tables, denominators, collection procedures and discontinuation reasons.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "S1 records hypomania 2/23 versus 0/23, dry mouth 3/23 versus 1/23 and 1 placebo-group death from myocardial infarction.", "condition_status": "Partly verified", "status_reason": "Complete event definitions, collection completeness, causality and long-term risk are not established.", "missingness": "Complete event definitions, collection completeness, causality and long-term risk are not established.", "uncertainty": "Complete event definitions, collection completeness, causality and long-term risk are not established.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Event definitions, people denominators by group, duration, severity and collection." }, { "item_id": "N27", "question_type": "Evidence condition", "question": "Were harm collection and onset/recovery/discontinuation times acquired?", "needed": "Collection system, event dates, severity, discontinuation, recovery and omissions.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid certifying complete collection or causality from event counts alone.", "application_exception": "Do not infer unverified times, recovery or re-exposure.", "criterion": "Link actual event collection and timing/discontinuation details to original material.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare the safety section, event-specific timelines and all dropout reasons.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "Retained records state short-term events, placebo-group death and some dropouts; event-specific timing, recovery, re-exposure and all collection details are unspecified.", "condition_status": "Unverified", "status_reason": "Events, times and collection completeness beyond current records cannot be established.", "missingness": "Events, times and collection completeness beyond current records cannot be established.", "uncertainty": "Events, times and collection completeness beyond current records cannot be established.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Collection system, event dates, severity, discontinuation, recovery and omissions." }, { "item_id": "N28", "question_type": "Evidence condition", "question": "Was direct harm material for concomitant drugs, co-exposures and special populations verified?", "needed": "Direct harm material for concomitant drugs, co-exposures, pregnancy/lactation and liver/kidney disease.", "role": "Supplementary; required for the relevant safety extension", "role_reason": "Needed to avoid extending short-term records in a narrow population to all safety questions.", "application_exception": "Do not infer absence of events with other drugs or populations.", "criterion": "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.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Separately review population, exposure and follow-up appropriate to the required harm question.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "Original records do not establish interactions with other drugs or safety in pregnancy/lactation or major liver/kidney disease.", "condition_status": "Unverified", "status_reason": "Trial medication restrictions and a small sample are not guarantees of safety for every individual.", "missingness": "Trial medication restrictions and a small sample are not guarantees of safety for every individual.", "uncertainty": "Trial medication restrictions and a small sample are not guarantees of safety for every individual.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Direct harm material for concomitant drugs, co-exposures, pregnancy/lactation and liver/kidney disease." }, { "item_id": "N29", "question_type": "Evidence condition", "question": "Was direct exposure, event, denominator and follow-up material to assess long-term/rare harm beyond 16 weeks verified?", "needed": "Long-term exposure, rare events, denominators, follow-up and appropriate collection design.", "role": "Supplementary; required for the relevant long-term harm question", "role_reason": "Needed to avoid excluding rare/long-term risks from small short-term results.", "application_exception": "Do not impose all long-term harm studies as additional mandatory conditions for the original narrow efficacy question.", "criterion": "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.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "When long-term/rare harm questions are needed, review appropriate follow-up, registry and collection designs.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "Original records state that small samples cannot exclude rare or long-term risks.", "condition_status": "Unverified", "status_reason": "Direct material and collection scope for long-term/rare harms are insufficient.", "missingness": "Direct material and collection scope for long-term/rare harms are insufficient.", "uncertainty": "Direct material and collection scope for long-term/rare harms are insufficient.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Long-term exposure, rare events, denominators, follow-up and appropriate collection design." }, { "item_id": "N30", "question_type": "Evidence condition", "question": "Are cognitive scores being extended to prevention, slowing progression or medication replacement?", "needed": "Boundary between ADAS-cog and prevention, daily function, caregiving, progression or prescription-drug replacement.", "role": "Supplementary; required for clinical-event/replacement extensions", "role_reason": "Needed to distinguish the selected cognitive-function endpoint from separate clinical questions.", "application_exception": "Do not reclassify the cognitive score itself as a surrogate.", "criterion": "Separate the current 16-week score question from other extensions.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "For extensions, separately review the relevant events, daily function, progression and replacement comparisons.", "current_reports": [ "S1", "S2", "S3" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Not applicable", "status_reason": "These separate extensions are not required as mandatory event outcomes for the current narrow cognitive comparison.", "missingness": "These separate extensions are not required as mandatory event outcomes for the current narrow cognitive comparison.", "uncertainty": "These separate extensions are not required as mandatory event outcomes for the current narrow cognitive comparison.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Boundary between ADAS-cog and prevention, daily function, caregiving, progression or prescription-drug replacement." }, { "item_id": "N31", "question_type": "Evidence condition", "question": "Were optimal dose and persistence after discontinuation verified?", "needed": "Direct dose comparisons, post-discontinuation follow-up, prespecified subgroups and separate estimates.", "role": "Supplementary; required for dose/persistence extensions", "role_reason": "Needed to avoid turning a single trial dose into an optimal dose or persistent effect.", "application_exception": "Do not automatically require every extension for the current 16-week comparison.", "criterion": "Distinguish nominal 30 mg/day, 16-week results from optimal-dose and persistence questions.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "For extensions, separately review direct dose comparisons, discontinuation and long-term follow-up.", "current_reports": [ "S1" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "Core trial specifications are 30 mg/day for 16 weeks; optimal dose, persistence after stopping and prevention are not established.", "condition_status": "Not applicable", "status_reason": "Because the separate extension was not adopted, it is not required as a mandatory dose comparison for the current result.", "missingness": "Because the separate extension was not adopted, it is not required as a mandatory dose comparison for the current result.", "uncertainty": "Because the separate extension was not adopted, it is not required as a mandatory dose comparison for the current result.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Direct dose comparisons, post-discontinuation follow-up, prespecified subgroups and separate estimates." }, { "item_id": "N32", "question_type": "Evidence condition", "question": "Were the original C46, P correction and EX review status retained?", "needed": "Original grade, score, current/previous axes, corrections and unresolved notices.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid automatically inheriting original values as efficacy judgments for the new table.", "application_exception": "Do not turn the S→P correction into revalidation of other axes or the final grade.", "criterion": "Preserve original C46, P, EX/CX, grade-revalidation false and pending method review from the retained original.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "For a later verdict request, preserve previous values, evidence and change reasons as a separate event.", "current_reports": [], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "This table does not newly certify the final validity of the existing grade or calculate scores/axes.", "missingness": "This table does not newly certify the final validity of the existing grade or calculate scores/axes.", "uncertainty": "This table does not newly certify the final validity of the existing grade or calculate scores/axes.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original grade, score, current/previous axes, corrections and unresolved notices." }, { "item_id": "N33", "question_type": "Evidence condition", "question": "Were historical access descriptions distinguished from actual reading in this work?", "needed": "Bibliographic flags, original locations, original review date, current acquisition/reading and file SHA.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid turning provision of original links into current full-text reading.", "application_exception": "Do not infer absent access-level, source-location or individual access-date fields from narrative descriptions.", "criterion": "Separately display actual retained-summary reading, historical descriptions and unread external material.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "When original material is later acquired, record type, date, location, bytes and actual reading.", "current_reports": [ "S1", "S2", "S3" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "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.", "missingness": "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.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Bibliographic flags, original locations, original review date, current acquisition/reading and file SHA." }, { "item_id": "N34", "question_type": "Evidence condition", "question": "Are material acquisition and condition/verdict revisions distinguished as events?", "needed": "Preservation records for full texts, registration, corrections, numbers, condition versions and previous values.", "role": "Required (selected 16-week ADAS-cog comparison)", "role_reason": "Needed to avoid automatic condition/verdict changes when new material is acquired.", "application_exception": "Do not delete originals, unfavorable results or unverified information.", "criterion": "Distinguish current retained scope from material and linked items needed for later updates.", "basis": "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.", "condition_origin": "Conditions for the specific saffron stigma extract, Alzheimer’s disease, 16-week ADAS-cog and placebo comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Record new material identity, reading and locations, review affected rows and freeze condition revisions before application.", "current_reports": [ "S1", "S2", "S3" ], "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "At the original review, no new material, regrading or public deployment had been performed.", "missingness": "At the original review, no new material, regrading or public deployment had been performed.", "uncertainty": "At the original review, no new material, regrading or public deployment had been performed.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Preservation records for full texts, registration, corrections, numbers, condition versions and previous values." } ], "reports": [ { "report_id": "S1", "title": "Saffron versus placebo; 16-week ADAS-cog", "url": "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", "report_type": "Retained summary of historical author-uploaded transcription and bibliographic/abstract comparison", "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "study_family": "Local link for the selected direct placebo comparison. Independent replication and overall participant overlap were not newly certified.", "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.", "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-14", "materials": [ { "material_type": "Retained bibliographic/linked summary and historical review record", "public_status": "Internally retained summary", "access_status": "Retained copy acquired; summary read", "acquired": true, "actually_read": "Stored existing review summary read", "as_of": "2026-10-05", "qualification": "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." }, { "material_type": "Existing external link for author-uploaded transcription and bibliographic abstract", "public_status": "Current public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "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." } ], "links": [ { "label": "Official source", "url": "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" } ] }, { "report_id": "S2", "title": "Saffron versus donepezil; 22-week active comparison", "url": "https://pubmed.ncbi.nlm.nih.gov/19838862/", "report_type": "Historical bibliographic/abstract summary of a randomized double-blind donepezil active-comparator trial", "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "study_family": "Context report under a different comparison. Shared authors or ingredient alone do not establish independent replication or identical participants.", "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.", "observed_result": "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.", "result_level": "Retain as active-comparator context without merging it into direct placebo-relative efficacy or replication of the same question.", "source_evidence_date": "2026-09-14", "materials": [ { "material_type": "Retained bibliographic/linked summary and historical review record", "public_status": "Internally retained summary", "access_status": "Retained copy acquired; summary read", "acquired": true, "actually_read": "Stored existing review summary read", "as_of": "2026-10-05", "qualification": "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." }, { "material_type": "Existing external bibliography/abstract link", "public_status": "Current public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "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." } ], "links": [ { "label": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/19838862/" } ] }, { "report_id": "S3", "title": "Saffron added to donepezil; 12-week MMSE", "url": "https://www.sciencedirect.com/science/article/pii/S2210803322000434", "report_type": "Historical publisher indexed-excerpt summary of a randomized double-blind saffron/placebo add-on trial during donepezil treatment", "existence": "Retained bilingual research and bibliographic summaries exist. Current existence, public availability, acquisition and reading of external papers, registration, plans and original product, funding and harm material have not been separately established.", "acquired_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.", "study_family": "A context report with different co-treatment, scale and time; not newly certified as independent replication of the direct placebo comparison.", "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.", "observed_result": "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.", "result_level": "Do not turn nonsignificance into absence of effect. Retain co-treatment/scale differences and unverified estimates together.", "source_evidence_date": "2026-09-14", "materials": [ { "material_type": "Retained bibliographic/linked summary and historical review record", "public_status": "Internally retained summary", "access_status": "Retained copy acquired; summary read", "acquired": true, "actually_read": "Stored existing review summary read", "as_of": "2026-10-05", "qualification": "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." }, { "material_type": "Existing external publisher indexed-excerpt link", "public_status": "Current public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "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." } ], "links": [ { "label": "Official source", "url": "https://www.sciencedirect.com/science/article/pii/S2210803322000434" } ] } ], "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly record the question, eligibility conditions and reasons for changes; distinguish intervention variants.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "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": "Link studies and reports separately; do not omit studies solely because results are unreported.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "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 result and effect of interest when examining randomization, deviations, missingness, measurement and selective reporting.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "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": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." } ], "status_dictionary": { "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." }, "study_overlap": { "state": "Unverified", "unique_trial_count": null, "unique_participant_count": null, "reason": "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." }, "history": [ { "date": "2026-10-28", "kind": "Separation of public-facing pages and materials", "view_version": "1.0", "change": "The public view and materials were prepared from the existing 34 items. No new clinical search, verification-state change or scoring was performed." } ], "language": "en", "translation_date": "2026-10-28" }