Oral saffron stigma extract × Cognition in mild-to-moderate Alzheimer's disease

Required evidence, verification status and materials actually read
Item	AVerification status	BReading scope	CReview item	DCurrent findings	EWhy unverified	FRequired materials and conditions	GFurther research
1	Met	Full text not readStored summary read	N01 · Evidence conditionWhich saffron, Alzheimer's disease and cognition comparison is being checked?Required (selected 16-week ADAS-cog comparison)	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. S1 S2 S3	Verification of the question boundary does not establish clinical confirmation or revalidation of the existing grade.	Specific extract, population, 16-week ADAS-cog, placebo and original claim boundary.	Compare candidate material with the exact ingredient, population, comparator, scale and time.
2	Partly verified	Full text not readStored summary read	N02 · Evidence conditionDo the core trial population and medication restrictions match the original question?Required (selected 16-week ADAS-cog comparison)	Retained claim conditions specify age over 55, probable mild-to-moderate AD, MMSE 15–26 and core antidementia-medication restrictions. S1	Detailed selection, representativeness and applicability to all patients receiving concomitant treatment are not established within this retained scope.	Diagnosis, age, MMSE, inclusion/exclusion and antidementia-medication restrictions.	Link selection criteria, baseline tables and medication restrictions to the actual results.
3	Partly verified	Full text not readStored summary read	N03 · Evidence conditionHow far are S1's plant part, extraction specifications, detailed batch, content and manufacturing quality verified?Required (selected 16-week ADAS-cog comparison)	Retained records describe capsules of dried 80% ethanolic extract of dried Crocus sativus stigma and crocin/safranal standardization. S1	Current original-source verification of detailed batch, content and manufacturing quality was not performed.	Stigma, extraction solvent, capsule, standardization and the actual trial product.	Compare product specifications and batch information with the applicability of the trial results.
4	Met	Full text not readStored summary read	N04 · Evidence conditionWere the core trial route and dose linked?Required (selected 16-week ADAS-cog comparison)	Original claim conditions and product facts specify oral 15 mg capsules, 2 times daily, totaling 30 mg/day in the core trial. S1	Actual quantitative adherence and each individual's exposure remain separately unverified.	Oral capsule, amount per 1 administration, frequency, total amount and actual exposure records.	Compare administration specifications, adherence and discontinuation records by group.
5	Met	Full text not readStored summary read	N05 · Evidence conditionDo administration duration and the selected result time match?Required (selected 16-week ADAS-cog comparison)	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. S1 S2 S3	Persistence beyond 16 weeks is outside this verification.	16-week administration, ADAS-cog assessment time and post-discontinuation material.	Separate assessment schedules, end-of-treatment and post-discontinuation follow-up.
6	Partly verified	Full text not readStored summary read	N06 · Evidence conditionWere the core placebo and antidementia-medication restrictions distinguished?Required (selected 16-week ADAS-cog comparison)	Matching-appearance placebo capsules and core antidementia-medication restrictions are recorded. The original review left taste/smell matching and concomitant-treatment deviations unverified. S1	Material fully comparing concurrent treatment, adherence and rescue treatment by group is unavailable in the retained scope.	Comparator product, antidementia-medication restrictions, rescue treatment and changes by group.	Verify comparator specifications, treatment changes and their handling in the analysis of the effect of interest.
7	Met	Full text not readStored summary read	N07 · Evidence conditionIs the donepezil active comparison being turned into placebo-relative efficacy or equivalence?Required (selected 16-week ADAS-cog comparison)	S2 records 54 participants in an active comparison; the abstract's no significant difference is not converted into placebo-relative efficacy, equivalence or noninferiority. S2	S2's completion/analysis details, detailed original text and registration remain separately unverified.	S2's actual comparator, duration, endpoints, design and equivalence plan.	Review the active comparison's advance noninferiority criteria, models and intervals as a separate question.
8	Met	Full text not readStored summary read	N08 · Evidence conditionWere S3's nonsignificant MMSE result and different concomitant-treatment conditions both retained?Required (selected 16-week ADAS-cog comparison)	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. S3	S3's mean difference, 95% CI, full original text and appendices are unverified.	Donepezil co-treatment, 12-week MMSE, denominators, result and role.	First compare whether results address the same question, then acquire separate estimates and intervals.
9	Partly verified	Full text not readStored summary read	N09 · Evidence conditionWere the ADAS-cog definition, direction and version verified?Required (selected 16-week ADAS-cog comparison)	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. S1	Detailed measurement specifications and successful assessor blinding cannot be established.	16-week change, improvement with lower scores, exact version, translation and assessment procedures.	Link scale version, language, assessor training and schedule to the result table.
10	Met	Full text not readStored summary read	N10 · Evidence conditionWere the core change values, SD and direction preserved?Required (selected 16-week ADAS-cog comparison)	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. S1	External original tables were not reread in this work; recorded numbers are treated within preservation of the original verdict.	Group-specific 16-week ADAS-cog mean changes, SD and original location.	Verify original tables, denominators, definitions and rounding before reviewing numerical attribution.
11	Partly verified	Full text not readStored summary read	N11 · Evidence conditionHow far are the reported change-score, repeated-measures and final-value tests and the authors' explanation/correction of the final-value inconsistency verified?Required (selected 16-week ADAS-cog comparison)	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. S1	The historical inconsistency was not resolved through new calculations; the original authors' explanation/correction remains unverified.	Analysis, time, P, t/df and correction records for each test.	Acquire test-specific original tables, models and correction material, comparing each test's meaning.
12	Partly verified	Full text not readStored summary read	N12 · Evidence conditionHow far are endpoint-specific execution, denominators and sensitivity verified for 23/23 allocation and paper-defined ITT/LOCF?Required (selected 16-week ADAS-cog comparison)	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. S1	Endpoint-specific analysis execution, sensitivity and current original-data comparison are unverified.	Randomized, completed and analyzed n, ITT definition, LOCF and effect of interest.	Compare participant flow, actual endpoint-specific analysis sets and missing-data models.
13	Partly verified	Full text not readStored summary read	N13 · Evidence conditionHow far are group-specific dropout/completion records, other missing-data reasons, death handling and sensitivity verified?Required (selected 16-week ADAS-cog comparison)	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. S1	Other missing-data reasons and sensitivity analyses are unverified; no subtraction or rate calculation was performed in this work.	Group-specific dropout, reasons, death and distinction between completion and analysis.	Link group-specific flowcharts, missing-data reasons and death handling to results.
14	Unverified	Full text not readStored summary read	N14 · Evidence conditionWere the validity of LOCF missing-data assumptions and sensitivity to other handling verified?Required (selected 16-week ADAS-cog comparison)	The original review retains LOCF use, dropout, placebo-group death and some concerns, stating that LOCF does not eliminate missing-data uncertainty. S1	The validity of missing-data assumptions and persistence of the effect under other handling are unverified.	Missing-data assumptions, imputation method, reasons by group and sensitivity results.	Compare missing-data and sensitivity analyses appropriate to the effect of interest with randomized results.
15	Met	Full text not readStored summary read	N15 · Evidence conditionWas the arithmetic −7.77-point difference distinguished from an author-adjusted effect?Required (selected 16-week ADAS-cog comparison)	−7.77 points is the retained editorial simple arithmetic difference between mean changes, not an author-reported adjusted effect or an individual improvement probability. S1	The arithmetic record does not replace verification of the authors' adjusted estimate.	Original means, historical arithmetic, estimand definition and adjusted model.	Compare original paper estimates, models and intervals with the existing arithmetic.
16	Partly verified	Full text not readStored summary read	N16 · Evidence conditionHow far are assumptions behind the editorial conditional interval and an author-reported 95% CI for the same endpoint verified?Required (selected 16-week ADAS-cog comparison)	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. S1	The author-reported 95% CI is unverified; the conditional interval does not resolve missingness, reporting bias or clinical importance.	Interval calculator, assumptions, rounding, denominators, LOCF and the original author interval.	Compare original author estimates/intervals, assumptions and missing-data sensitivity for the same endpoint.
17	Unverified	Full text not readStored summary read	N17 · Evidence conditionWas a clinical-importance threshold for this ADAS-cog difference acquired?Required (selected 16-week ADAS-cog comparison)	Existing records leave the applicable clinical-importance threshold unverified and distinguish numerical reconstruction from clinical precision assessment. S1	The previous rationale assigning EX from unverified clinical importance remains under review; no new conclusion is made.	Validated importance criteria and direct clinical outcomes for the diagnosis, scale and duration.	Separately review context-appropriate importance evidence and daily-function material.
18	Partly verified	Full text not readStored summary read	N18 · Evidence conditionWere sequence generation and actual allocation concealment verified?Required (selected 16-week ADAS-cog comparison)	Historical descriptions record a computer-generated random sequence and blinding codes, but separation of responsibilities and actual concealment details are unverified. S1	Original some-concerns assessments are provisional and are not certified as an official RoB2 judgment here.	Sequence generation, recruitment/allocation responsibilities, concealment and baseline balance.	Compare recruitment/allocation procedures, registration, baseline tables and results.
19	Partly verified	Full text not readStored summary read	N19 · Evidence conditionHow far are comparator matching, adherence, assessor training and successful blinding verified?Required (selected 16-week ADAS-cog comparison)	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. S1	Do not turn some verified procedures into a conclusion that no deviation or measurement problems existed.	Appearance, taste/smell, caregiver supervision, assessor training and successful blinding.	Acquire product matching, assessment procedures, exposure by group and success checks.
20	Unverified	Full text not readStored summary read	N20 · Evidence conditionWere prospective registration/SAP and the selected result compared?Required (selected 16-week ADAS-cog comparison)	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. S1 S3	Prospective endpoint specification and analysis selection cannot currently be independently compared.	Time-verified registration, protocol, SAP and scale/time/analysis changes.	Link original registration, timestamps and amendments to the statistical section.
21	Met	Full text not readStored summary read	N21 · Evidence conditionWere the comparisons in the three reports distinguished from independent replication?Required (selected 16-week ADAS-cog comparison)	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. S1 S2 S3	No unique-participant total, definitive independent-family count or new replication certification is provided.	Report identity, comparator, co-treatment, endpoints, times and family links.	Compare report, registry and participant identities to update unique-family links.
22	Met	Full text not readStored summary read	N22 · Evidence conditionWithin which search and review scope is insufficiency described?Required (selected 16-week ADAS-cog comparison)	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. S1 S2 S3	Insufficiency language is limited to the recorded search scope and does not certify absence of all current literature.	Original review date, search methods, registration/unpublished/correction scope and current input.	Record actual queries, dates and inclusion/exclusion within later authorized scope.
23	Partly verified	Full text not readStored summary read	N23 · Evidence conditionHow far are S1's university/company support, material supply, cash shares, employee authorship, patents and separate COI verified?Required (selected 16-week ADAS-cog comparison)	S1 records a joint Tehran university/Green Plants of Life grant and company material supply. S1	Cash shares, employee authorship, patents and separate COI are unverified.	University/company support, material, cash shares, employee authorship, patents and COI.	Compare grant, material-supply, author, patent and COI documents within the same report.
24	Unverified	Full text not readStored summary read	N24 · Evidence conditionHow far are funding, product support, employee authorship, patents and COI verified in S2's own documents?Required (selected 16-week ADAS-cog comparison)	S2's original evidence records funding, product, employee-authorship and patent details as unverified in that review. S2	Details establishing S2's independent funding or presence/absence of interests are not currently determined.	S2-specific funding, products, employment, patents and COI.	Individually compare S2 funding, material supply, author declarations and trial identity.
25	Partly verified	Full text not readStored summary read	N25 · Evidence conditionHow far were S3's support/COI declaration and separate product-supply, employee-authorship and patent verification completed?Required (selected 16-week ADAS-cog comparison)	S3 records Tabriz University Neurosciences Research Center grant 62590 and the authors' declaration of no COI. S3	Separate verification of product supply, employee authorship and patents is incomplete.	Grant 62590, author COI declaration, product supply, employee authorship and patents.	Link support, product, author and patent material by report.
26	Partly verified	Full text not readStored summary read	N26 · Evidence conditionHow far are S1's reported adverse-event/death counts and event definitions, collection completeness and severity verified?Required (selected 16-week ADAS-cog comparison)	S1 records hypomania 2/23 versus 0/23, dry mouth 3/23 versus 1/23 and 1 placebo-group death from myocardial infarction. S1	Complete event definitions, collection completeness, causality and long-term risk are not established.	Event definitions, people denominators by group, duration, severity and collection.	Link original safety tables, denominators, collection procedures and discontinuation reasons.
27	Unverified	Full text not readStored summary read	N27 · Evidence conditionWere harm collection and onset/recovery/discontinuation times acquired?Required (selected 16-week ADAS-cog comparison)	Retained records state short-term events, placebo-group death and some dropouts; event-specific timing, recovery, re-exposure and all collection details are unspecified. S1	Events, times and collection completeness beyond current records cannot be established.	Collection system, event dates, severity, discontinuation, recovery and omissions.	Compare the safety section, event-specific timelines and all dropout reasons.
28	Unverified	Full text not readStored summary read	N28 · Evidence conditionWas direct harm material for concomitant drugs, co-exposures and special populations verified?Supplementary; required for the relevant safety extension	Original records do not establish interactions with other drugs or safety in pregnancy/lactation or major liver/kidney disease. S1	Trial medication restrictions and a small sample are not guarantees of safety for every individual.	Direct harm material for concomitant drugs, co-exposures, pregnancy/lactation and liver/kidney disease.	Separately review population, exposure and follow-up appropriate to the required harm question.
29	Unverified	Full text not readStored summary read	N29 · Evidence conditionWas direct exposure, event, denominator and follow-up material to assess long-term/rare harm beyond 16 weeks verified?Supplementary; required for the relevant long-term harm question	Original records state that small samples cannot exclude rare or long-term risks. S1	Direct material and collection scope for long-term/rare harms are insufficient.	Long-term exposure, rare events, denominators, follow-up and appropriate collection design.	When long-term/rare harm questions are needed, review appropriate follow-up, registry and collection designs.
30	Not applicable	Full text not readStored summary read	N30 · Evidence conditionAre cognitive scores being extended to prevention, slowing progression or medication replacement?Supplementary; required for clinical-event/replacement extensions	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. S1 S2 S3	These separate extensions are not required as mandatory event outcomes for the current narrow cognitive comparison.	Boundary between ADAS-cog and prevention, daily function, caregiving, progression or prescription-drug replacement.	For extensions, separately review the relevant events, daily function, progression and replacement comparisons.
31	Not applicable	Full text not readStored summary read	N31 · Evidence conditionWere optimal dose and persistence after discontinuation verified?Supplementary; required for dose/persistence extensions	Core trial specifications are 30 mg/day for 16 weeks; optimal dose, persistence after stopping and prevention are not established. S1	Because the separate extension was not adopted, it is not required as a mandatory dose comparison for the current result.	Direct dose comparisons, post-discontinuation follow-up, prespecified subgroups and separate estimates.	For extensions, separately review direct dose comparisons, discontinuation and long-term follow-up.
32	Met	Full text not readStored summary read	N32 · Evidence conditionWere the original C46, P correction and EX review status retained?Required (selected 16-week ADAS-cog comparison)	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.	This table does not newly certify the final validity of the existing grade or calculate scores/axes.	Original grade, score, current/previous axes, corrections and unresolved notices.	For a later verdict request, preserve previous values, evidence and change reasons as a separate event.
33	Met	Full text not readStored summary read	N33 · Evidence conditionWere historical access descriptions distinguished from actual reading in this work?Required (selected 16-week ADAS-cog comparison)	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. S1 S2 S3	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.	Bibliographic flags, original locations, original review date, current acquisition/reading and file SHA.	When original material is later acquired, record type, date, location, bytes and actual reading.
34	Met	Full text not readStored summary read	N34 · Evidence conditionAre material acquisition and condition/verdict revisions distinguished as events?Required (selected 16-week ADAS-cog comparison)	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. S1 S2 S3	At the original review, no new material, regrading or public deployment had been performed.	Preservation records for full texts, registration, corrections, numbers, condition versions and previous values.	Record new material identity, reading and locations, review affected rows and freeze condition revisions before application.

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34 itemsWhat the statuses mean

Assessment scope

Stored-material review date: 2026-10-05
Original evidence review date: 2026-09-14
Scope actually checked: Retained Korean/English summaries and case-specific condition/application records. Full papers, supplements, registrations, plans and original data were not read.
What the dates mean: 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.
Population: Age over 55, probable mild-to-moderate Alzheimer’s disease, MMSE 15–26; core antidementia-medication restrictions
Ingredient, formulation and route: Oral capsules of dried 80% ethanolic extract of dried Crocus sativus stigma; crocin/safranal standardization in retained records
Dose: Trial specification: 15 mg, 2 times per 1 day, totaling 30 mg/day. Actual quantitative adherence and optimal dose are unverified
Comparator: Matching-appearance placebo capsules and core antidementia-medication restrictions. Sensory matching and group-specific concomitant-treatment deviations are unverified
Measured outcome: 16-week ADAS-cog change versus placebo; lower scores indicate improvement. Exact version, training and prespecification are unverified
Duration: The selected direct comparison is at 16 weeks. The 22-week active comparison and 12-week add-on treatment are different comparisons
Questions outside this scope: Retain S1’s 46 participants, 23/23 allocation and paper-defined ITT/LOCF. Changes −3.69±1.69 versus +4.08±1.34 points are mean±SD. −7.77 points is a historical editorial simple difference, not an author-adjusted estimate or individual improvement probability.; The existing conditional interval −8.68~−6.86 points, df44, is an editorial calculation assuming rounded change SD, 23 per group, independent-group equal-variance t and LOCF. The author-reported 95% CI and clinical importance are unverified; calculations were not repeated here.; Change-score P<.0001 and repeated-measures P=.04 concern different tests. The discrepancy between final-value t4.16/df44 reported P<.0001 and historical recalculated P≈.000145 remains separate. Author explanations/corrections are unverified; no new test was performed.; Retain S1 hypomania 2/23 versus 0/23, dry mouth 3/23 versus 1/23 and 1 placebo-group death from myocardial infarction. A small short-term trial does not establish long-term/rare risk or safety in every population.; Retain original C, 46, Caution, the S→P correction and ongoing review of EX, CX and the final grade. Grade revalidation is false and method review is pending. 46 is not an efficacy percentage. Do not extend to tea, food, other extracts, isolated constituents, combinations, prevention, slowing progression, prescription replacement, optimal dose or persistence after stopping.

Evidence and sources

The links below lead to the sources. A link alone does not mean the original source was read or its latest publication status verified.

S1 · Saffron versus placebo; 16-week ADAS-cog

Official source

Material type: Retained summary of historical author-uploaded transcription and bibliographic/abstract comparison
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Findings recorded in the stored summary: Retained summary: 46 participants, 23/23 randomized, paper-defined ITT/LOCF, analysis df44. At 16 weeks, changes −3.69±1.69 versus +4.08±1.34 points (SD), change-score P<.0001. The simple difference −7.77 points is a historical editorial calculation. Dropouts 1/23 versus 3/23, total 4/46 and 8.7%, and 22/20 completers are retained records/historical subtraction. Joint Tehran university/Green Plants of Life support and company material supply are recorded; cash shares, employee authorship, patents and separate COI are unverified.
Record level: A direct record for the selected comparison, but original tables, registration and SAP were not read in this work. Retain small-sample, missing-data, reporting-inconsistency and unverified-importance limitations.
Study overlap and 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.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Retained bibliographic/linked summary and historical review record	Internally retained summary	Retained copy acquired; summary read	Stored existing review summary read	The retained summary was acquired and read. This is not an original-byte copy of a clinical full text. Historical manuscript descriptions of transcription, abstract and indexed-excerpt access are retained records. They do not establish external full-text reading, original registry verification or independent clinical certification in this work. The original verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are unrecorded; external access was not attempted in this work.
Existing external link for author-uploaded transcription and bibliographic abstract	Current public availability unverified	External access not attempted; not acquired	Not read	The retained external URL is provided. Access, acquisition and reading were not attempted in this work. Historical manuscript descriptions of transcription, abstract and indexed-excerpt access are retained records. They do not establish external full-text reading, original registry verification or independent clinical certification in this work. The original verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are unrecorded; external access was not attempted in this work.

S2 · Saffron versus donepezil; 22-week active comparison

PubMed

Material type: Historical bibliographic/abstract summary of a randomized double-blind donepezil active-comparator trial
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Findings recorded in the stored summary: Retained summary: 54 participants, 22-week ADAS-cog/CDR-SB, donepezil active comparator rather than placebo. The abstract’s no significant between-group difference establishes neither equivalence, noninferiority nor placebo-relative efficacy. Completion/analysis details and its own funding, products, employee authorship, patents and COI are unverified.
Record level: Retain as active-comparator context without merging it into direct placebo-relative efficacy or replication of the same question.
Study overlap and 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.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Retained bibliographic/linked summary and historical review record	Internally retained summary	Retained copy acquired; summary read	Stored existing review summary read	The retained summary was acquired and read. This is not an original-byte copy of a clinical full text. Historical manuscript descriptions of transcription, abstract and indexed-excerpt access are retained records. They do not establish external full-text reading, original registry verification or independent clinical certification in this work. The original verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are unrecorded; external access was not attempted in this work.
Existing external bibliography/abstract link	Current public availability unverified	External access not attempted; not acquired	Not read	The retained external URL is provided. Access, acquisition and reading were not attempted in this work. Historical manuscript descriptions of transcription, abstract and indexed-excerpt access are retained records. They do not establish external full-text reading, original registry verification or independent clinical certification in this work. The original verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are unrecorded; external access was not attempted in this work.

S3 · Saffron added to donepezil; 12-week MMSE

Official source

Material type: Historical publisher indexed-excerpt summary of a randomized double-blind saffron/placebo add-on trial during donepezil treatment
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Findings recorded in the stored summary: Retained summary: 60 participants, 30/30 randomized, 27/27 analyzed in the excerpt, 12-week MMSE P=.303, saffron 15 mg added 2 times daily. Mean difference and 95% CI are unverified; inflammatory markers are not cognitive effects. Grant 62590 and an author declaration of no COI are recorded, but product supply, employee authorship and patents remain separately unverified. The listed IRCT20190428043409N1 does not establish original registry or timing verification.
Record level: Do not turn nonsignificance into absence of effect. Retain co-treatment/scale differences and unverified estimates together.
Study overlap and 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.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Retained bibliographic/linked summary and historical review record	Internally retained summary	Retained copy acquired; summary read	Stored existing review summary read	The retained summary was acquired and read. This is not an original-byte copy of a clinical full text. Historical manuscript descriptions of transcription, abstract and indexed-excerpt access are retained records. They do not establish external full-text reading, original registry verification or independent clinical certification in this work. The original verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are unrecorded; external access was not attempted in this work.
Existing external publisher indexed-excerpt link	Current public availability unverified	External access not attempted; not acquired	Not read	The retained external URL is provided. Access, acquisition and reading were not attempted in this work. Historical manuscript descriptions of transcription, abstract and indexed-excerpt access are retained records. They do not establish external full-text reading, original registry verification or independent clinical certification in this work. The original verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are unrecorded; external access was not attempted in this work.

Report counts versus independent study counts

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.

Review criteria

Version 1.1 · Criteria record date 2026-10-05. These are Chamgap's own application conditions, informed by the referenced methods. They do not constitute official assessment-tool certification or a new efficacy score.

N01 · Which saffron, Alzheimer's disease and cognition comparison is being checked?

Required materials and conditions: Specific extract, population, 16-week ADAS-cog, placebo and original claim boundary.
Conditions for verification: Link the specific stigma extract's 16-week ADAS-cog versus placebo question to the retained original.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Active-drug comparisons and add-on trials are not replications of the same placebo question.
Why this condition is needed: Needed to avoid merging all related saffron effects into a single status.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N02 · Do the core trial population and medication restrictions match the original question?

Required materials and conditions: Diagnosis, age, MMSE, inclusion/exclusion and antidementia-medication restrictions.
Conditions for verification: Distinguish the core population, selection and medication restrictions from unverified representativeness.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not extend to MCI, dementia prevention or all patients receiving concomitant drugs.
Why this condition is needed: Needed to avoid applying the findings to all patients with dementia in routine care.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N03 · How far are S1's plant part, extraction specifications, detailed batch, content and manufacturing quality verified?

Required materials and conditions: Stigma, extraction solvent, capsule, standardization and the actual trial product.
Conditions for verification: Link the reported stigma, 80% ethanolic dried extract, capsule and standardization specifications, separately assessing original verification of detailed batch, content and manufacturing quality.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Other extracts, crocin/safranal alone and combination products are separate.
Why this condition is needed: Needed to avoid transferring results to tea, foods or isolated constituents.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N04 · Were the core trial route and dose linked?

Required materials and conditions: Oral capsule, amount per 1 administration, frequency, total amount and actual exposure records.
Conditions for verification: Distinguish the reported oral 15 mg, 2 times daily, from unverified actual exposure.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Nominal dose does not establish quantitative adherence.
Why this condition is needed: Needed to avoid turning trial specifications into personal dosing instructions.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N05 · Do administration duration and the selected result time match?

Required materials and conditions: 16-week administration, ADAS-cog assessment time and post-discontinuation material.
Conditions for verification: Link core 16-week administration to the ADAS-cog result.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: S2's 22 weeks and S3's 12 weeks do not replace the core 16-week result.
Why this condition is needed: Needed to avoid merging results at different durations as the same effect.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N06 · Were the core placebo and antidementia-medication restrictions distinguished?

Required materials and conditions: Comparator product, antidementia-medication restrictions, rescue treatment and changes by group.
Conditions for verification: Link the actual placebo and medication restrictions to unverified concomitant-treatment deviations.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Appearance matching does not guarantee taste/smell matching or agreement in all concomitant treatments.
Why this condition is needed: Needed to avoid attributing differences in concurrent treatment to saffron.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N07 · Is the donepezil active comparison being turned into placebo-relative efficacy or equivalence?

Required materials and conditions: S2's actual comparator, duration, endpoints, design and equivalence plan.
Conditions for verification: S2 is a 22-week donepezil active comparison and does not certify noninferiority or placebo-relative efficacy.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Retain active-comparator material as a different comparison.
Why this condition is needed: Needed to distinguish no significant difference from equivalence.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N08 · Were S3's nonsignificant MMSE result and different concomitant-treatment conditions both retained?

Required materials and conditions: Donepezil co-treatment, 12-week MMSE, denominators, result and role.
Conditions for verification: Explain the differences between S3 and S1 in co-treatment, scale and time.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not turn nonsignificance into an effect of 0 or inflammatory markers into cognitive effects.
Why this condition is needed: Needed to avoid retaining only favorable direct results.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N09 · Were the ADAS-cog definition, direction and version verified?

Required materials and conditions: 16-week change, improvement with lower scores, exact version, translation and assessment procedures.
Conditions for verification: Distinguish the direction of the cognitive endpoint from the verified scope of measurement details.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not reclassify it as a biological surrogate merely because it is a test.
Why this condition is needed: Needed to distinguish the cognitive endpoint itself from other scales and events.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N10 · Were the core change values, SD and direction preserved?

Required materials and conditions: Group-specific 16-week ADAS-cog mean changes, SD and original location.
Conditions for verification: Attribute the retained changes −3.69±1.69 versus +4.08±1.34 and SD to the relevant comparison.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not convert mean differences into individual probabilities of improvement.
Why this condition is needed: Needed to distinguish final values, within-group change and between-group effects.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N11 · How far are the reported change-score, repeated-measures and final-value tests and the authors' explanation/correction of the final-value inconsistency verified?

Required materials and conditions: Analysis, time, P, t/df and correction records for each test.
Conditions for verification: Link change-score P<.0001, repeated-measures P=.04 and the historical final-value inconsistency to their respective tests; separately assess original author explanations or corrections.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not call every difference in P a conflict before checking whether it concerns the same question.
Why this condition is needed: Needed to distinguish different tests from actual internal reporting inconsistencies.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N12 · How far are endpoint-specific execution, denominators and sensitivity verified for 23/23 allocation and paper-defined ITT/LOCF?

Required materials and conditions: Randomized, completed and analyzed n, ITT definition, LOCF and effect of interest.
Conditions for verification: Preserve recorded 23/23 allocation, paper-defined ITT/LOCF and analysis df44, assessing endpoint-specific analysis sets, execution, sensitivity and current original-data comparison.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not expand the paper's analysis label into certification of modern complete ITT.
Why this condition is needed: Needed to avoid automatically substituting randomized counts for analysis denominators.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N13 · How far are group-specific dropout/completion records, other missing-data reasons, death handling and sensitivity verified?

Required materials and conditions: Group-specific dropout, reasons, death and distinction between completion and analysis.
Conditions for verification: Retain recorded 1/23 versus 3/23 dropouts and the historical subtraction behind 22/20 completers, assessing other missing-data reasons, death handling and sensitivity analyses.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not calculate new dropout rates or completion counts.
Why this condition is needed: Needed to avoid turning subtraction into an author-observed completion table.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N14 · Were the validity of LOCF missing-data assumptions and sensitivity to other handling verified?

Required materials and conditions: Missing-data assumptions, imputation method, reasons by group and sensitivity results.
Conditions for verification: Retain original LOCF use and missing-data uncertainty, assessing whether reasons by group, assumption validity and sensitivity to alternative handling were verified.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not score LOCF use itself as proven null efficacy or a specified bias magnitude.
Why this condition is needed: Needed to avoid claiming no missing-data problem merely because numerical results are complete.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N15 · Was the arithmetic −7.77-point difference distinguished from an author-adjusted effect?

Required materials and conditions: Original means, historical arithmetic, estimand definition and adjusted model.
Conditions for verification: Identify −7.77 as the historical simple difference between published mean changes.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: No new effect-size calculation is performed in this work.
Why this condition is needed: Needed to avoid turning an existing calculation into a formal between-group effect reported by the authors.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N16 · How far are assumptions behind the editorial conditional interval and an author-reported 95% CI for the same endpoint verified?

Required materials and conditions: Interval calculator, assumptions, rounding, denominators, LOCF and the original author interval.
Conditions for verification: Preserve the existing independent-group equal-variance t conditional interval's calculator, assumptions, rounding, denominators and LOCF; separately assess original verification of an author-reported 95% CI and its analysis assumptions.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not rerun t, SE or CI calculations in this work.
Why this condition is needed: Needed to avoid certifying an original-author interval or clinical precision merely because an interval exists.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N17 · Was a clinical-importance threshold for this ADAS-cog difference acquired?

Required materials and conditions: Validated importance criteria and direct clinical outcomes for the diagnosis, scale and duration.
Conditions for verification: Verify applicable importance criteria and their relationship to the result and uncertainty.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not invent MCID, NNT or efficacy percentages or reconfirm EX.
Why this condition is needed: Needed to distinguish statistical magnitude/significance from clinical importance.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N18 · Were sequence generation and actual allocation concealment verified?

Required materials and conditions: Sequence generation, recruitment/allocation responsibilities, concealment and baseline balance.
Conditions for verification: Distinguish recorded computer-generated sequence/codes from unverified execution details.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not turn unverified details into evidence of improper allocation.
Why this condition is needed: Needed to avoid treating a randomization label as resolution of all allocation issues.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N19 · How far are comparator matching, adherence, assessor training and successful blinding verified?

Required materials and conditions: Appearance, taste/smell, caregiver supervision, assessor training and successful blinding.
Conditions for verification: Link recorded appearance matching, supervision and assessment schedules, assessing verification of taste/smell matching, quantitative adherence, assessor training and blinding success.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not turn a double-blind label into complete verification of actual success.
Why this condition is needed: Needed to preserve distinct verified scopes for intervention and measurement.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N20 · Were prospective registration/SAP and the selected result compared?

Required materials and conditions: Time-verified registration, protocol, SAP and scale/time/analysis changes.
Conditions for verification: Compare the actual plan with 16-week ADAS-cog analysis and reporting.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Unavailable registration is not evidence of nonregistration or manipulated selective reporting.
Why this condition is needed: Needed to avoid mistaking the page-selected endpoint for a registry primary endpoint.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N21 · Were the comparisons in the three reports distinguished from independent replication?

Required materials and conditions: Report identity, comparator, co-treatment, endpoints, times and family links.
Conditions for verification: Explain known relationships among S1 placebo, S2 active and S3 add-on comparisons and unverified unique counts.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not assume the same participant group solely from shared authors or ingredient.
Why this condition is needed: Needed to avoid counting 3 reports as 3 independent replications of the same question.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N22 · Within which search and review scope is insufficiency described?

Required materials and conditions: Original review date, search methods, registration/unpublished/correction scope and current input.
Conditions for verification: Distinguish the original 2026-09-14 review from this retained-material conversion.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: No new search does not mean 0 studies worldwide.
Why this condition is needed: Needed to avoid presenting a retained review as a current exhaustive search.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N23 · How far are S1's university/company support, material supply, cash shares, employee authorship, patents and separate COI verified?

Required materials and conditions: University/company support, material, cash shares, employee authorship, patents and COI.
Conditions for verification: Link stated joint support and company material supply, assessing reporting and original verification of cash shares, employee authorship, patents and separate COI.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Funding institutions and independence of trial replication are separate.
Why this condition is needed: Needed to avoid automatic exclusion or certification of independence based on funding alone.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N24 · How far are funding, product support, employee authorship, patents and COI verified in S2's own documents?

Required materials and conditions: S2-specific funding, products, employment, patents and COI.
Conditions for verification: Without inheriting S1 information, assess the existence and actual verification of funding, product, employment, patent and COI material in S2's own documents.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not copy S1's university/company support as verified S2 information.
Why this condition is needed: Needed to avoid transferring funding information to another comparison with the same authors.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N25 · How far were S3's support/COI declaration and separate product-supply, employee-authorship and patent verification completed?

Required materials and conditions: Grant 62590, author COI declaration, product supply, employee authorship and patents.
Conditions for verification: Link recorded grant 62590 and the authors' no-COI declaration, assessing whether separate product-supply, employee-authorship and patent verification material was confirmed.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: A no-COI declaration does not establish absence of bias.
Why this condition is needed: Needed to distinguish author declarations from complete independence verification.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N26 · How far are S1's reported adverse-event/death counts and event definitions, collection completeness and severity verified?

Required materials and conditions: Event definitions, people denominators by group, duration, severity and collection.
Conditions for verification: Retain hypomania 2/23 versus 0/23, dry mouth 3/23 versus 1/23 and 1 placebo-group death, separately assessing verification of definitions, people denominators, duration, severity and collection completeness.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not calculate new rates, risk ratios or NNT.
Why this condition is needed: Needed to avoid turning small-trial records into a statement that no serious events occurred.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N27 · Were harm collection and onset/recovery/discontinuation times acquired?

Required materials and conditions: Collection system, event dates, severity, discontinuation, recovery and omissions.
Conditions for verification: Link actual event collection and timing/discontinuation details to original material.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not infer unverified times, recovery or re-exposure.
Why this condition is needed: Needed to avoid certifying complete collection or causality from event counts alone.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N28 · Was direct harm material for concomitant drugs, co-exposures and special populations verified?

Required materials and conditions: Direct harm material for concomitant drugs, co-exposures, pregnancy/lactation and liver/kidney disease.
Conditions for verification: Preserve recorded trial medication restrictions while assessing verification and applicability of direct harm material for concomitant drugs, co-exposures, pregnancy/lactation and major liver/kidney disease.
Requirement and applicability: Supplementary; required for the relevant safety extension
Application exceptions: Do not infer absence of events with other drugs or populations.
Why this condition is needed: Needed to avoid extending short-term records in a narrow population to all safety questions.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N29 · Was direct exposure, event, denominator and follow-up material to assess long-term/rare harm beyond 16 weeks verified?

Required materials and conditions: Long-term exposure, rare events, denominators, follow-up and appropriate collection design.
Conditions for verification: Do not extend short-term records to exclusion of long-term/rare risks; assess verification of long-term exposure, rare events, denominators, follow-up and suitable collection material.
Requirement and applicability: Supplementary; required for the relevant long-term harm question
Application exceptions: Do not impose all long-term harm studies as additional mandatory conditions for the original narrow efficacy question.
Why this condition is needed: Needed to avoid excluding rare/long-term risks from small short-term results.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N30 · Are cognitive scores being extended to prevention, slowing progression or medication replacement?

Required materials and conditions: Boundary between ADAS-cog and prevention, daily function, caregiving, progression or prescription-drug replacement.
Conditions for verification: Separate the current 16-week score question from other extensions.
Requirement and applicability: Supplementary; required for clinical-event/replacement extensions
Application exceptions: Do not reclassify the cognitive score itself as a surrogate.
Why this condition is needed: Needed to distinguish the selected cognitive-function endpoint from separate clinical questions.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N31 · Were optimal dose and persistence after discontinuation verified?

Required materials and conditions: Direct dose comparisons, post-discontinuation follow-up, prespecified subgroups and separate estimates.
Conditions for verification: Distinguish nominal 30 mg/day, 16-week results from optimal-dose and persistence questions.
Requirement and applicability: Supplementary; required for dose/persistence extensions
Application exceptions: Do not automatically require every extension for the current 16-week comparison.
Why this condition is needed: Needed to avoid turning a single trial dose into an optimal dose or persistent effect.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N32 · Were the original C46, P correction and EX review status retained?

Required materials and conditions: Original grade, score, current/previous axes, corrections and unresolved notices.
Conditions for verification: Preserve original C46, P, EX/CX, grade-revalidation false and pending method review from the retained original.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not turn the S→P correction into revalidation of other axes or the final grade.
Why this condition is needed: Needed to avoid automatically inheriting original values as efficacy judgments for the new table.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N33 · Were historical access descriptions distinguished from actual reading in this work?

Required materials and conditions: Bibliographic flags, original locations, original review date, current acquisition/reading and file SHA.
Conditions for verification: Separately display actual retained-summary reading, historical descriptions and unread external material.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not infer absent access-level, source-location or individual access-date fields from narrative descriptions.
Why this condition is needed: Needed to avoid turning provision of original links into current full-text reading.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

N34 · Are material acquisition and condition/verdict revisions distinguished as events?

Required materials and conditions: Preservation records for full texts, registration, corrections, numbers, condition versions and previous values.
Conditions for verification: Distinguish current retained scope from material and linked items needed for later updates.
Requirement and applicability: Required (selected 16-week ADAS-cog comparison)
Application exceptions: Do not delete originals, unfavorable results or unverified information.
Why this condition is needed: Needed to avoid automatic condition/verdict changes when new material is acquired.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Referenced methods and the sections actually reviewed

M03 · Cochrane Handbook 6.5 (2024), chapter updated 2023-08

Official methodology · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13

Referenced principle: Clearly record the question, eligibility conditions and reasons for changes; distinguish intervention variants.
Extent of review: Retained method-application records were reused. External originals were not reread and method content was not reassessed.

M04 · Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03

Official methodology · §4.5, §4.6.1–4.6.3, MECIR C42

Referenced principle: Link studies and reports separately; do not omit studies solely because results are unreported.
Extent of review: Retained method-application records were reused. External originals were not reread and method content was not reassessed.

M08 · Cochrane Handbook 6.5 (2024), chapter updated 2019-10

Official methodology · §8.1–8.2.3, Table 8.2.a

Referenced principle: Fix the result and effect of interest when examining randomization, deviations, missingness, measurement and selective reporting.
Extent of review: Retained method-application records were reused. External originals were not reread and method content was not reassessed.

M15 · Cochrane Handbook 6.5 (2024), chapter updated 2023-08

Official methodology · §15.2.4, §15.3.1–15.3.3

Referenced principle: Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.
Extent of review: Retained method-application records were reused. External originals were not reread and method content was not reassessed.

M19 · Cochrane Handbook 6.5 (2024), chapter updated 2019-10

Official methodology · §19.1.2, §19.2.1–19.2.4

Referenced principle: Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence.
Extent of review: Retained method-application records were reused. External originals were not reread and method content was not reassessed.

What the statuses mean

Partly verified: Some retained information and the remaining required material are displayed together.
Unverified: The specified condition cannot be established within the retained scope; this means neither an effect of 0, 0 studies worldwide nor established safety.
Review incomplete: Original-material comparison/search was not performed within the authorized scope.
Not reported: A scope-limited status meaning that an item is not reported in the specific material/section actually read.
Inaccessible: Used only for material actually accessed unsuccessfully. Not assigned to clinical material in this work.
Insufficient evidence matching the conditions: Used only after reviewing relevant research within a defined scope and finding insufficient evidence to answer the condition. Not applied universally here.
Not applicable: Separate events, optimal dose and long-term extensions are not additional mandatory conditions for the selected 16-week cognitive comparison.
Conflicting data: Used when material addressing the same question, time and analysis is difficult to reconcile. Different numbers in reviews alone do not qualify.
Met: The stated retained content, boundary and attribution are verified; this is not clinical confirmation, external full-text reading or revalidation of the original verdict.

Change history

2026-10-28 · Public page/material version 1.0

The public view and materials were prepared from the existing 34 items. No new clinical search, verification-state change or scoring was performed.

The stored-material review date (2026-10-05) and original evidence review date (2026-09-14) were retained unchanged.

Researcher downloads

These materials provide the same evidence, scope and verification status as this page.

View all item details

N01 · Which saffron, Alzheimer's disease and cognition comparison is being checked?

Current findings: The selected question concerns 16-week ADAS-cog change versus placebo in mild-to-moderate Alzheimer's disease. The subclaim list is empty; S2 and S3's different comparisons are retained as context.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Verification of the question boundary does not establish clinical confirmation or revalidation of the existing grade.
Reason for missing information: Verification of the question boundary does not establish clinical confirmation or revalidation of the existing grade.
Required materials and conditions: Specific extract, population, 16-week ADAS-cog, placebo and original claim boundary.
Materials to obtain first: Specific extract, population, 16-week ADAS-cog, placebo and original claim boundary.
Further research: Compare candidate material with the exact ingredient, population, comparator, scale and time.
Remaining uncertainty: Verification of the question boundary does not establish clinical confirmation or revalidation of the existing grade.
Conditions for verification: Link the specific stigma extract's 16-week ADAS-cog versus placebo question to the retained original.
Why this condition is needed: Needed to avoid merging all related saffron effects into a single status.
Application exceptions: Active-drug comparisons and add-on trials are not replications of the same placebo question.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1 S2 S3

N02 · Do the core trial population and medication restrictions match the original question?

Current findings: Retained claim conditions specify age over 55, probable mild-to-moderate AD, MMSE 15–26 and core antidementia-medication restrictions.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Detailed selection, representativeness and applicability to all patients receiving concomitant treatment are not established within this retained scope.
Reason for missing information: Detailed selection, representativeness and applicability to all patients receiving concomitant treatment are not established within this retained scope.
Required materials and conditions: Diagnosis, age, MMSE, inclusion/exclusion and antidementia-medication restrictions.
Materials to obtain first: Diagnosis, age, MMSE, inclusion/exclusion and antidementia-medication restrictions.
Further research: Link selection criteria, baseline tables and medication restrictions to the actual results.
Remaining uncertainty: Detailed selection, representativeness and applicability to all patients receiving concomitant treatment are not established within this retained scope.
Conditions for verification: Distinguish the core population, selection and medication restrictions from unverified representativeness.
Why this condition is needed: Needed to avoid applying the findings to all patients with dementia in routine care.
Application exceptions: Do not extend to MCI, dementia prevention or all patients receiving concomitant drugs.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N03 · How far are S1's plant part, extraction specifications, detailed batch, content and manufacturing quality verified?

Current findings: Retained records describe capsules of dried 80% ethanolic extract of dried Crocus sativus stigma and crocin/safranal standardization.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Current original-source verification of detailed batch, content and manufacturing quality was not performed.
Reason for missing information: Current original-source verification of detailed batch, content and manufacturing quality was not performed.
Required materials and conditions: Stigma, extraction solvent, capsule, standardization and the actual trial product.
Materials to obtain first: Stigma, extraction solvent, capsule, standardization and the actual trial product.
Further research: Compare product specifications and batch information with the applicability of the trial results.
Remaining uncertainty: Current original-source verification of detailed batch, content and manufacturing quality was not performed.
Conditions for verification: Link the reported stigma, 80% ethanolic dried extract, capsule and standardization specifications, separately assessing original verification of detailed batch, content and manufacturing quality.
Why this condition is needed: Needed to avoid transferring results to tea, foods or isolated constituents.
Application exceptions: Other extracts, crocin/safranal alone and combination products are separate.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N04 · Were the core trial route and dose linked?

Current findings: Original claim conditions and product facts specify oral 15 mg capsules, 2 times daily, totaling 30 mg/day in the core trial.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Actual quantitative adherence and each individual's exposure remain separately unverified.
Reason for missing information: Actual quantitative adherence and each individual's exposure remain separately unverified.
Required materials and conditions: Oral capsule, amount per 1 administration, frequency, total amount and actual exposure records.
Materials to obtain first: Oral capsule, amount per 1 administration, frequency, total amount and actual exposure records.
Further research: Compare administration specifications, adherence and discontinuation records by group.
Remaining uncertainty: Actual quantitative adherence and each individual's exposure remain separately unverified.
Conditions for verification: Distinguish the reported oral 15 mg, 2 times daily, from unverified actual exposure.
Why this condition is needed: Needed to avoid turning trial specifications into personal dosing instructions.
Application exceptions: Nominal dose does not establish quantitative adherence.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N05 · Do administration duration and the selected result time match?

Current findings: The main comparison is at 16 weeks; S2 is a 22-week active comparison and S3 a 12-week add-on trial. Results at these times are not pooled.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Persistence beyond 16 weeks is outside this verification.
Reason for missing information: Persistence beyond 16 weeks is outside this verification.
Required materials and conditions: 16-week administration, ADAS-cog assessment time and post-discontinuation material.
Materials to obtain first: 16-week administration, ADAS-cog assessment time and post-discontinuation material.
Further research: Separate assessment schedules, end-of-treatment and post-discontinuation follow-up.
Remaining uncertainty: Persistence beyond 16 weeks is outside this verification.
Conditions for verification: Link core 16-week administration to the ADAS-cog result.
Why this condition is needed: Needed to avoid merging results at different durations as the same effect.
Application exceptions: S2's 22 weeks and S3's 12 weeks do not replace the core 16-week result.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1 S2 S3

N06 · Were the core placebo and antidementia-medication restrictions distinguished?

Current findings: Matching-appearance placebo capsules and core antidementia-medication restrictions are recorded. The original review left taste/smell matching and concomitant-treatment deviations unverified.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Material fully comparing concurrent treatment, adherence and rescue treatment by group is unavailable in the retained scope.
Reason for missing information: Material fully comparing concurrent treatment, adherence and rescue treatment by group is unavailable in the retained scope.
Required materials and conditions: Comparator product, antidementia-medication restrictions, rescue treatment and changes by group.
Materials to obtain first: Comparator product, antidementia-medication restrictions, rescue treatment and changes by group.
Further research: Verify comparator specifications, treatment changes and their handling in the analysis of the effect of interest.
Remaining uncertainty: Material fully comparing concurrent treatment, adherence and rescue treatment by group is unavailable in the retained scope.
Conditions for verification: Link the actual placebo and medication restrictions to unverified concomitant-treatment deviations.
Why this condition is needed: Needed to avoid attributing differences in concurrent treatment to saffron.
Application exceptions: Appearance matching does not guarantee taste/smell matching or agreement in all concomitant treatments.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N07 · Is the donepezil active comparison being turned into placebo-relative efficacy or equivalence?

Current findings: S2 records 54 participants in an active comparison; the abstract's no significant difference is not converted into placebo-relative efficacy, equivalence or noninferiority.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: S2's completion/analysis details, detailed original text and registration remain separately unverified.
Reason for missing information: S2's completion/analysis details, detailed original text and registration remain separately unverified.
Required materials and conditions: S2's actual comparator, duration, endpoints, design and equivalence plan.
Materials to obtain first: S2's actual comparator, duration, endpoints, design and equivalence plan.
Further research: Review the active comparison's advance noninferiority criteria, models and intervals as a separate question.
Remaining uncertainty: S2's completion/analysis details, detailed original text and registration remain separately unverified.
Conditions for verification: S2 is a 22-week donepezil active comparison and does not certify noninferiority or placebo-relative efficacy.
Why this condition is needed: Needed to distinguish no significant difference from equivalence.
Application exceptions: Retain active-comparator material as a different comparison.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S2

N08 · Were S3's nonsignificant MMSE result and different concomitant-treatment conditions both retained?

Current findings: S3 records 60 participants, 30/30 randomized, 27/27 analyzed in the excerpt, and 12-week MMSE P=.303 with donepezil add-on treatment. Do not pool it with S1 or count it as consistent independent replication.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: S3's mean difference, 95% CI, full original text and appendices are unverified.
Reason for missing information: S3's mean difference, 95% CI, full original text and appendices are unverified.
Required materials and conditions: Donepezil co-treatment, 12-week MMSE, denominators, result and role.
Materials to obtain first: Donepezil co-treatment, 12-week MMSE, denominators, result and role.
Further research: First compare whether results address the same question, then acquire separate estimates and intervals.
Remaining uncertainty: S3's mean difference, 95% CI, full original text and appendices are unverified.
Conditions for verification: Explain the differences between S3 and S1 in co-treatment, scale and time.
Why this condition is needed: Needed to avoid retaining only favorable direct results.
Application exceptions: Do not turn nonsignificance into an effect of 0 or inflammatory markers into cognitive effects.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S3

N09 · Were the ADAS-cog definition, direction and version verified?

Current findings: ADAS-cog is the cognitive-function endpoint itself, with lower scores indicating improvement; 16-week change is selected for this page. Exact version, translation and assessor training are unverified.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Detailed measurement specifications and successful assessor blinding cannot be established.
Reason for missing information: Detailed measurement specifications and successful assessor blinding cannot be established.
Required materials and conditions: 16-week change, improvement with lower scores, exact version, translation and assessment procedures.
Materials to obtain first: 16-week change, improvement with lower scores, exact version, translation and assessment procedures.
Further research: Link scale version, language, assessor training and schedule to the result table.
Remaining uncertainty: Detailed measurement specifications and successful assessor blinding cannot be established.
Conditions for verification: Distinguish the direction of the cognitive endpoint from the verified scope of measurement details.
Why this condition is needed: Needed to distinguish the cognitive endpoint itself from other scales and events.
Application exceptions: Do not reclassify it as a biological surrogate merely because it is a test.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N10 · Were the core change values, SD and direction preserved?

Current findings: S1 changes are recorded as −3.69±1.69 versus +4.08±1.34 points, mean±SD. The historical location is p4, Results/ADAS-cog, in the author-uploaded version.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: External original tables were not reread in this work; recorded numbers are treated within preservation of the original verdict.
Reason for missing information: External original tables were not reread in this work; recorded numbers are treated within preservation of the original verdict.
Required materials and conditions: Group-specific 16-week ADAS-cog mean changes, SD and original location.
Materials to obtain first: Group-specific 16-week ADAS-cog mean changes, SD and original location.
Further research: Verify original tables, denominators, definitions and rounding before reviewing numerical attribution.
Remaining uncertainty: External original tables were not reread in this work; recorded numbers are treated within preservation of the original verdict.
Conditions for verification: Attribute the retained changes −3.69±1.69 versus +4.08±1.34 and SD to the relevant comparison.
Why this condition is needed: Needed to distinguish final values, within-group change and between-group effects.
Application exceptions: Do not convert mean differences into individual probabilities of improvement.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N11 · How far are the reported change-score, repeated-measures and final-value tests and the authors' explanation/correction of the final-value inconsistency verified?

Current findings: Change-score P<.0001 and abstract P=.04 concern different tests. Separately, the retained bibliographic note records a discrepancy between the reported final-value P for t4.16/df44 and historical recalculated P≈.000145.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The historical inconsistency was not resolved through new calculations; the original authors' explanation/correction remains unverified.
Reason for missing information: The historical inconsistency was not resolved through new calculations; the original authors' explanation/correction remains unverified.
Required materials and conditions: Analysis, time, P, t/df and correction records for each test.
Materials to obtain first: Analysis, time, P, t/df and correction records for each test.
Further research: Acquire test-specific original tables, models and correction material, comparing each test's meaning.
Remaining uncertainty: The historical inconsistency was not resolved through new calculations; the original authors' explanation/correction remains unverified.
Conditions for verification: Link change-score P<.0001, repeated-measures P=.04 and the historical final-value inconsistency to their respective tests; separately assess original author explanations or corrections.
Why this condition is needed: Needed to distinguish different tests from actual internal reporting inconsistencies.
Application exceptions: Do not call every difference in P a conflict before checking whether it concerns the same question.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N12 · How far are endpoint-specific execution, denominators and sensitivity verified for 23/23 allocation and paper-defined ITT/LOCF?

Current findings: S1 records 46 participants, 23/23 randomized, paper-defined ITT/LOCF and analysis df44. These labels alone do not resolve missing-data and analysis uncertainty.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Endpoint-specific analysis execution, sensitivity and current original-data comparison are unverified.
Reason for missing information: Endpoint-specific analysis execution, sensitivity and current original-data comparison are unverified.
Required materials and conditions: Randomized, completed and analyzed n, ITT definition, LOCF and effect of interest.
Materials to obtain first: Randomized, completed and analyzed n, ITT definition, LOCF and effect of interest.
Further research: Compare participant flow, actual endpoint-specific analysis sets and missing-data models.
Remaining uncertainty: Endpoint-specific analysis execution, sensitivity and current original-data comparison are unverified.
Conditions for verification: Preserve recorded 23/23 allocation, paper-defined ITT/LOCF and analysis df44, assessing endpoint-specific analysis sets, execution, sensitivity and current original-data comparison.
Why this condition is needed: Needed to avoid automatically substituting randomized counts for analysis denominators.
Application exceptions: Do not expand the paper's analysis label into certification of modern complete ITT.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N13 · How far are group-specific dropout/completion records, other missing-data reasons, death handling and sensitivity verified?

Current findings: Dropouts of 1/23 versus 3/23, total 4/46 and 8.7%, and 22/20 completers are retained records and historical calculations. A placebo-group death is also recorded.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Other missing-data reasons and sensitivity analyses are unverified; no subtraction or rate calculation was performed in this work.
Reason for missing information: Other missing-data reasons and sensitivity analyses are unverified; no subtraction or rate calculation was performed in this work.
Required materials and conditions: Group-specific dropout, reasons, death and distinction between completion and analysis.
Materials to obtain first: Group-specific dropout, reasons, death and distinction between completion and analysis.
Further research: Link group-specific flowcharts, missing-data reasons and death handling to results.
Remaining uncertainty: Other missing-data reasons and sensitivity analyses are unverified; no subtraction or rate calculation was performed in this work.
Conditions for verification: Retain recorded 1/23 versus 3/23 dropouts and the historical subtraction behind 22/20 completers, assessing other missing-data reasons, death handling and sensitivity analyses.
Why this condition is needed: Needed to avoid turning subtraction into an author-observed completion table.
Application exceptions: Do not calculate new dropout rates or completion counts.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N14 · Were the validity of LOCF missing-data assumptions and sensitivity to other handling verified?

Current findings: The original review retains LOCF use, dropout, placebo-group death and some concerns, stating that LOCF does not eliminate missing-data uncertainty.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The validity of missing-data assumptions and persistence of the effect under other handling are unverified.
Reason for missing information: The validity of missing-data assumptions and persistence of the effect under other handling are unverified.
Required materials and conditions: Missing-data assumptions, imputation method, reasons by group and sensitivity results.
Materials to obtain first: Missing-data assumptions, imputation method, reasons by group and sensitivity results.
Further research: Compare missing-data and sensitivity analyses appropriate to the effect of interest with randomized results.
Remaining uncertainty: The validity of missing-data assumptions and persistence of the effect under other handling are unverified.
Conditions for verification: Retain original LOCF use and missing-data uncertainty, assessing whether reasons by group, assumption validity and sensitivity to alternative handling were verified.
Why this condition is needed: Needed to avoid claiming no missing-data problem merely because numerical results are complete.
Application exceptions: Do not score LOCF use itself as proven null efficacy or a specified bias magnitude.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N15 · Was the arithmetic −7.77-point difference distinguished from an author-adjusted effect?

Current findings: −7.77 points is the retained editorial simple arithmetic difference between mean changes, not an author-reported adjusted effect or an individual improvement probability.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The arithmetic record does not replace verification of the authors' adjusted estimate.
Reason for missing information: The arithmetic record does not replace verification of the authors' adjusted estimate.
Required materials and conditions: Original means, historical arithmetic, estimand definition and adjusted model.
Materials to obtain first: Original means, historical arithmetic, estimand definition and adjusted model.
Further research: Compare original paper estimates, models and intervals with the existing arithmetic.
Remaining uncertainty: The arithmetic record does not replace verification of the authors' adjusted estimate.
Conditions for verification: Identify −7.77 as the historical simple difference between published mean changes.
Why this condition is needed: Needed to avoid turning an existing calculation into a formal between-group effect reported by the authors.
Application exceptions: No new effect-size calculation is performed in this work.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N16 · How far are assumptions behind the editorial conditional interval and an author-reported 95% CI for the same endpoint verified?

Current findings: The existing −8.68~−6.86-point interval (df44) is an editorial calculation assuming rounded change SD, 23 participants per group and LOCF. Exact original calculation values and assumptions are retained.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The author-reported 95% CI is unverified; the conditional interval does not resolve missingness, reporting bias or clinical importance.
Reason for missing information: The author-reported 95% CI is unverified; the conditional interval does not resolve missingness, reporting bias or clinical importance.
Required materials and conditions: Interval calculator, assumptions, rounding, denominators, LOCF and the original author interval.
Materials to obtain first: Interval calculator, assumptions, rounding, denominators, LOCF and the original author interval.
Further research: Compare original author estimates/intervals, assumptions and missing-data sensitivity for the same endpoint.
Remaining uncertainty: The author-reported 95% CI is unverified; the conditional interval does not resolve missingness, reporting bias or clinical importance.
Conditions for verification: Preserve the existing independent-group equal-variance t conditional interval's calculator, assumptions, rounding, denominators and LOCF; separately assess original verification of an author-reported 95% CI and its analysis assumptions.
Why this condition is needed: Needed to avoid certifying an original-author interval or clinical precision merely because an interval exists.
Application exceptions: Do not rerun t, SE or CI calculations in this work.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N17 · Was a clinical-importance threshold for this ADAS-cog difference acquired?

Current findings: Existing records leave the applicable clinical-importance threshold unverified and distinguish numerical reconstruction from clinical precision assessment.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The previous rationale assigning EX from unverified clinical importance remains under review; no new conclusion is made.
Reason for missing information: The previous rationale assigning EX from unverified clinical importance remains under review; no new conclusion is made.
Required materials and conditions: Validated importance criteria and direct clinical outcomes for the diagnosis, scale and duration.
Materials to obtain first: Validated importance criteria and direct clinical outcomes for the diagnosis, scale and duration.
Further research: Separately review context-appropriate importance evidence and daily-function material.
Remaining uncertainty: The previous rationale assigning EX from unverified clinical importance remains under review; no new conclusion is made.
Conditions for verification: Verify applicable importance criteria and their relationship to the result and uncertainty.
Why this condition is needed: Needed to distinguish statistical magnitude/significance from clinical importance.
Application exceptions: Do not invent MCID, NNT or efficacy percentages or reconfirm EX.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N18 · Were sequence generation and actual allocation concealment verified?

Current findings: Historical descriptions record a computer-generated random sequence and blinding codes, but separation of responsibilities and actual concealment details are unverified.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Original some-concerns assessments are provisional and are not certified as an official RoB2 judgment here.
Reason for missing information: Original some-concerns assessments are provisional and are not certified as an official RoB2 judgment here.
Required materials and conditions: Sequence generation, recruitment/allocation responsibilities, concealment and baseline balance.
Materials to obtain first: Sequence generation, recruitment/allocation responsibilities, concealment and baseline balance.
Further research: Compare recruitment/allocation procedures, registration, baseline tables and results.
Remaining uncertainty: Original some-concerns assessments are provisional and are not certified as an official RoB2 judgment here.
Conditions for verification: Distinguish recorded computer-generated sequence/codes from unverified execution details.
Why this condition is needed: Needed to avoid treating a randomization label as resolution of all allocation issues.
Application exceptions: Do not turn unverified details into evidence of improper allocation.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N19 · How far are comparator matching, adherence, assessor training and successful blinding verified?

Current findings: Double blinding, matching appearance, caregiver supervision and the same ADAS-cog schedule are recorded; taste/smell, quantitative adherence, assessor training and successful blinding are unverified.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Do not turn some verified procedures into a conclusion that no deviation or measurement problems existed.
Reason for missing information: Do not turn some verified procedures into a conclusion that no deviation or measurement problems existed.
Required materials and conditions: Appearance, taste/smell, caregiver supervision, assessor training and successful blinding.
Materials to obtain first: Appearance, taste/smell, caregiver supervision, assessor training and successful blinding.
Further research: Acquire product matching, assessment procedures, exposure by group and success checks.
Remaining uncertainty: Do not turn some verified procedures into a conclusion that no deviation or measurement problems existed.
Conditions for verification: Link recorded appearance matching, supervision and assessment schedules, assessing verification of taste/smell matching, quantitative adherence, assessor training and blinding success.
Why this condition is needed: Needed to preserve distinct verified scopes for intervention and measurement.
Application exceptions: Do not turn a double-blind label into complete verification of actual success.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N20 · Were prospective registration/SAP and the selected result compared?

Current findings: The paper describes a 16-week change-score test but contains multiple scales/analyses; core timestamped registration/SAP were not acquired. S3's listed IRCT identifier also differs from verification of the actual registry and timing.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Prospective endpoint specification and analysis selection cannot currently be independently compared.
Reason for missing information: Prospective endpoint specification and analysis selection cannot currently be independently compared.
Required materials and conditions: Time-verified registration, protocol, SAP and scale/time/analysis changes.
Materials to obtain first: Time-verified registration, protocol, SAP and scale/time/analysis changes.
Further research: Link original registration, timestamps and amendments to the statistical section.
Remaining uncertainty: Prospective endpoint specification and analysis selection cannot currently be independently compared.
Conditions for verification: Compare the actual plan with 16-week ADAS-cog analysis and reporting.
Why this condition is needed: Needed to avoid mistaking the page-selected endpoint for a registry primary endpoint.
Application exceptions: Unavailable registration is not evidence of nonregistration or manipulated selective reporting.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1 S3

N21 · Were the comparisons in the three reports distinguished from independent replication?

Current findings: The retained reports differ in comparator, co-treatment, scale and duration. Original records identify S1 as a direct placebo trial and leave independent replication under the same conditions unverified.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: No unique-participant total, definitive independent-family count or new replication certification is provided.
Reason for missing information: No unique-participant total, definitive independent-family count or new replication certification is provided.
Required materials and conditions: Report identity, comparator, co-treatment, endpoints, times and family links.
Materials to obtain first: Report identity, comparator, co-treatment, endpoints, times and family links.
Further research: Compare report, registry and participant identities to update unique-family links.
Remaining uncertainty: No unique-participant total, definitive independent-family count or new replication certification is provided.
Conditions for verification: Explain known relationships among S1 placebo, S2 active and S3 add-on comparisons and unverified unique counts.
Why this condition is needed: Needed to avoid counting 3 reports as 3 independent replications of the same question.
Application exceptions: Do not assume the same participant group solely from shared authors or ingredient.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1 S2 S3

N22 · Within which search and review scope is insufficiency described?

Current findings: Original records describe 56 submitted web-search queries and core comparisons as of 2026-09-14. This was not a complete database search, systematic review or exhaustive unpublished-registry survey; no new clinical search was performed here.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Insufficiency language is limited to the recorded search scope and does not certify absence of all current literature.
Reason for missing information: Insufficiency language is limited to the recorded search scope and does not certify absence of all current literature.
Required materials and conditions: Original review date, search methods, registration/unpublished/correction scope and current input.
Materials to obtain first: Original review date, search methods, registration/unpublished/correction scope and current input.
Further research: Record actual queries, dates and inclusion/exclusion within later authorized scope.
Remaining uncertainty: Insufficiency language is limited to the recorded search scope and does not certify absence of all current literature.
Conditions for verification: Distinguish the original 2026-09-14 review from this retained-material conversion.
Why this condition is needed: Needed to avoid presenting a retained review as a current exhaustive search.
Application exceptions: No new search does not mean 0 studies worldwide.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1 S2 S3

N23 · How far are S1's university/company support, material supply, cash shares, employee authorship, patents and separate COI verified?

Current findings: S1 records a joint Tehran university/Green Plants of Life grant and company material supply.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Cash shares, employee authorship, patents and separate COI are unverified.
Reason for missing information: Cash shares, employee authorship, patents and separate COI are unverified.
Required materials and conditions: University/company support, material, cash shares, employee authorship, patents and COI.
Materials to obtain first: University/company support, material, cash shares, employee authorship, patents and COI.
Further research: Compare grant, material-supply, author, patent and COI documents within the same report.
Remaining uncertainty: Cash shares, employee authorship, patents and separate COI are unverified.
Conditions for verification: Link stated joint support and company material supply, assessing reporting and original verification of cash shares, employee authorship, patents and separate COI.
Why this condition is needed: Needed to avoid automatic exclusion or certification of independence based on funding alone.
Application exceptions: Funding institutions and independence of trial replication are separate.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N24 · How far are funding, product support, employee authorship, patents and COI verified in S2's own documents?

Current findings: S2's original evidence records funding, product, employee-authorship and patent details as unverified in that review.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Details establishing S2's independent funding or presence/absence of interests are not currently determined.
Reason for missing information: Details establishing S2's independent funding or presence/absence of interests are not currently determined.
Required materials and conditions: S2-specific funding, products, employment, patents and COI.
Materials to obtain first: S2-specific funding, products, employment, patents and COI.
Further research: Individually compare S2 funding, material supply, author declarations and trial identity.
Remaining uncertainty: Details establishing S2's independent funding or presence/absence of interests are not currently determined.
Conditions for verification: Without inheriting S1 information, assess the existence and actual verification of funding, product, employment, patent and COI material in S2's own documents.
Why this condition is needed: Needed to avoid transferring funding information to another comparison with the same authors.
Application exceptions: Do not copy S1's university/company support as verified S2 information.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S2

N25 · How far were S3's support/COI declaration and separate product-supply, employee-authorship and patent verification completed?

Current findings: S3 records Tabriz University Neurosciences Research Center grant 62590 and the authors' declaration of no COI.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Separate verification of product supply, employee authorship and patents is incomplete.
Reason for missing information: Separate verification of product supply, employee authorship and patents is incomplete.
Required materials and conditions: Grant 62590, author COI declaration, product supply, employee authorship and patents.
Materials to obtain first: Grant 62590, author COI declaration, product supply, employee authorship and patents.
Further research: Link support, product, author and patent material by report.
Remaining uncertainty: Separate verification of product supply, employee authorship and patents is incomplete.
Conditions for verification: Link recorded grant 62590 and the authors' no-COI declaration, assessing whether separate product-supply, employee-authorship and patent verification material was confirmed.
Why this condition is needed: Needed to distinguish author declarations from complete independence verification.
Application exceptions: A no-COI declaration does not establish absence of bias.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S3

N26 · How far are S1's reported adverse-event/death counts and event definitions, collection completeness and severity verified?

Current findings: S1 records hypomania 2/23 versus 0/23, dry mouth 3/23 versus 1/23 and 1 placebo-group death from myocardial infarction.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Complete event definitions, collection completeness, causality and long-term risk are not established.
Reason for missing information: Complete event definitions, collection completeness, causality and long-term risk are not established.
Required materials and conditions: Event definitions, people denominators by group, duration, severity and collection.
Materials to obtain first: Event definitions, people denominators by group, duration, severity and collection.
Further research: Link original safety tables, denominators, collection procedures and discontinuation reasons.
Remaining uncertainty: Complete event definitions, collection completeness, causality and long-term risk are not established.
Conditions for verification: Retain hypomania 2/23 versus 0/23, dry mouth 3/23 versus 1/23 and 1 placebo-group death, separately assessing verification of definitions, people denominators, duration, severity and collection completeness.
Why this condition is needed: Needed to avoid turning small-trial records into a statement that no serious events occurred.
Application exceptions: Do not calculate new rates, risk ratios or NNT.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N27 · Were harm collection and onset/recovery/discontinuation times acquired?

Current findings: Retained records state short-term events, placebo-group death and some dropouts; event-specific timing, recovery, re-exposure and all collection details are unspecified.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Events, times and collection completeness beyond current records cannot be established.
Reason for missing information: Events, times and collection completeness beyond current records cannot be established.
Required materials and conditions: Collection system, event dates, severity, discontinuation, recovery and omissions.
Materials to obtain first: Collection system, event dates, severity, discontinuation, recovery and omissions.
Further research: Compare the safety section, event-specific timelines and all dropout reasons.
Remaining uncertainty: Events, times and collection completeness beyond current records cannot be established.
Conditions for verification: Link actual event collection and timing/discontinuation details to original material.
Why this condition is needed: Needed to avoid certifying complete collection or causality from event counts alone.
Application exceptions: Do not infer unverified times, recovery or re-exposure.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N28 · Was direct harm material for concomitant drugs, co-exposures and special populations verified?

Current findings: Original records do not establish interactions with other drugs or safety in pregnancy/lactation or major liver/kidney disease.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Trial medication restrictions and a small sample are not guarantees of safety for every individual.
Reason for missing information: Trial medication restrictions and a small sample are not guarantees of safety for every individual.
Required materials and conditions: Direct harm material for concomitant drugs, co-exposures, pregnancy/lactation and liver/kidney disease.
Materials to obtain first: Direct harm material for concomitant drugs, co-exposures, pregnancy/lactation and liver/kidney disease.
Further research: Separately review population, exposure and follow-up appropriate to the required harm question.
Remaining uncertainty: Trial medication restrictions and a small sample are not guarantees of safety for every individual.
Conditions for verification: Preserve recorded trial medication restrictions while assessing verification and applicability of direct harm material for concomitant drugs, co-exposures, pregnancy/lactation and major liver/kidney disease.
Why this condition is needed: Needed to avoid extending short-term records in a narrow population to all safety questions.
Application exceptions: Do not infer absence of events with other drugs or populations.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N29 · Was direct exposure, event, denominator and follow-up material to assess long-term/rare harm beyond 16 weeks verified?

Current findings: Original records state that small samples cannot exclude rare or long-term risks.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Direct material and collection scope for long-term/rare harms are insufficient.
Reason for missing information: Direct material and collection scope for long-term/rare harms are insufficient.
Required materials and conditions: Long-term exposure, rare events, denominators, follow-up and appropriate collection design.
Materials to obtain first: Long-term exposure, rare events, denominators, follow-up and appropriate collection design.
Further research: When long-term/rare harm questions are needed, review appropriate follow-up, registry and collection designs.
Remaining uncertainty: Direct material and collection scope for long-term/rare harms are insufficient.
Conditions for verification: Do not extend short-term records to exclusion of long-term/rare risks; assess verification of long-term exposure, rare events, denominators, follow-up and suitable collection material.
Why this condition is needed: Needed to avoid excluding rare/long-term risks from small short-term results.
Application exceptions: Do not impose all long-term harm studies as additional mandatory conditions for the original narrow efficacy question.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N30 · Are cognitive scores being extended to prevention, slowing progression or medication replacement?

Current findings: The current question concerns 16-week ADAS-cog change. The retained original does not establish dementia prevention, slowing progression, standard-drug replacement or long-term function.
Verification status: Not applicable
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: These separate extensions are not required as mandatory event outcomes for the current narrow cognitive comparison.
Reason for missing information: These separate extensions are not required as mandatory event outcomes for the current narrow cognitive comparison.
Required materials and conditions: Boundary between ADAS-cog and prevention, daily function, caregiving, progression or prescription-drug replacement.
Materials to obtain first: Boundary between ADAS-cog and prevention, daily function, caregiving, progression or prescription-drug replacement.
Further research: For extensions, separately review the relevant events, daily function, progression and replacement comparisons.
Remaining uncertainty: These separate extensions are not required as mandatory event outcomes for the current narrow cognitive comparison.
Conditions for verification: Separate the current 16-week score question from other extensions.
Why this condition is needed: Needed to distinguish the selected cognitive-function endpoint from separate clinical questions.
Application exceptions: Do not reclassify the cognitive score itself as a surrogate.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1 S2 S3

N31 · Were optimal dose and persistence after discontinuation verified?

Current findings: Core trial specifications are 30 mg/day for 16 weeks; optimal dose, persistence after stopping and prevention are not established.
Verification status: Not applicable
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Because the separate extension was not adopted, it is not required as a mandatory dose comparison for the current result.
Reason for missing information: Because the separate extension was not adopted, it is not required as a mandatory dose comparison for the current result.
Required materials and conditions: Direct dose comparisons, post-discontinuation follow-up, prespecified subgroups and separate estimates.
Materials to obtain first: Direct dose comparisons, post-discontinuation follow-up, prespecified subgroups and separate estimates.
Further research: For extensions, separately review direct dose comparisons, discontinuation and long-term follow-up.
Remaining uncertainty: Because the separate extension was not adopted, it is not required as a mandatory dose comparison for the current result.
Conditions for verification: Distinguish nominal 30 mg/day, 16-week results from optimal-dose and persistence questions.
Why this condition is needed: Needed to avoid turning a single trial dose into an optimal dose or persistent effect.
Application exceptions: Do not automatically require every extension for the current 16-week comparison.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1

N32 · Were the original C46, P correction and EX review status retained?

Current findings: Original C46 is a retained value; endpoint S→P was corrected. EX rationale, statistics versus clinical importance, CX and the final grade remain under review; grade revalidation is false.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: This table does not newly certify the final validity of the existing grade or calculate scores/axes.
Reason for missing information: This table does not newly certify the final validity of the existing grade or calculate scores/axes.
Required materials and conditions: Original grade, score, current/previous axes, corrections and unresolved notices.
Materials to obtain first: Original grade, score, current/previous axes, corrections and unresolved notices.
Further research: For a later verdict request, preserve previous values, evidence and change reasons as a separate event.
Remaining uncertainty: This table does not newly certify the final validity of the existing grade or calculate scores/axes.
Conditions for verification: Preserve original C46, P, EX/CX, grade-revalidation false and pending method review from the retained original.
Why this condition is needed: Needed to avoid automatically inheriting original values as efficacy judgments for the new table.
Application exceptions: Do not turn the S→P correction into revalidation of other axes or the final grade.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources

N33 · Were historical access descriptions distinguished from actual reading in this work?

Current findings: What was actually read is the current retained summary. Historical descriptions of S1 author-uploaded transcription/bibliographic abstract, S2 bibliographic abstract and S3 indexed excerpt remain in bibliographic notes.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: External originals, registration, SAP, publisher PDF and original bytes are unread/unacquired in this work. Individual structured access-level fields are absent in the original.
Reason for missing information: External originals, registration, SAP, publisher PDF and original bytes are unread/unacquired in this work. Individual structured access-level fields are absent in the original.
Required materials and conditions: Bibliographic flags, original locations, original review date, current acquisition/reading and file SHA.
Materials to obtain first: Bibliographic flags, original locations, original review date, current acquisition/reading and file SHA.
Further research: When original material is later acquired, record type, date, location, bytes and actual reading.
Remaining uncertainty: External originals, registration, SAP, publisher PDF and original bytes are unread/unacquired in this work. Individual structured access-level fields are absent in the original.
Conditions for verification: Separately display actual retained-summary reading, historical descriptions and unread external material.
Why this condition is needed: Needed to avoid turning provision of original links into current full-text reading.
Application exceptions: Do not infer absent access-level, source-location or individual access-date fields from narrative descriptions.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1 S2 S3

N34 · Are material acquisition and condition/verdict revisions distinguished as events?

Current findings: Retain original corrections/unresolved status, S2/S3 context, historical calculations and access limitations. Registration, SAP, author estimates, importance, measurement, safety and funding details are later verification targets.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: At the original review, no new material, regrading or public deployment had been performed.
Reason for missing information: At the original review, no new material, regrading or public deployment had been performed.
Required materials and conditions: Preservation records for full texts, registration, corrections, numbers, condition versions and previous values.
Materials to obtain first: Preservation records for full texts, registration, corrections, numbers, condition versions and previous values.
Further research: Record new material identity, reading and locations, review affected rows and freeze condition revisions before application.
Remaining uncertainty: At the original review, no new material, regrading or public deployment had been performed.
Conditions for verification: Distinguish current retained scope from material and linked items needed for later updates.
Why this condition is needed: Needed to avoid automatic condition/verdict changes when new material is acquired.
Application exceptions: Do not delete originals, unfavorable results or unverified information.
Referenced methods: Existing method principles distinguish population, formulation, dose, duration, comparator, cognition measurement, denominators, missingness, between-group analysis, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S1 S2 S3