Antidepressant discontinuation × the claim that depression inevitably relapses: evidence checklist

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	Partly verified	Full text not readStored summary read	N01 · Efficacy comparison and presentation of stored materialWhat is the existing verdict on ‘discontinuation inevitably causes relapse’?Required	The selected existing question is ‘discontinuation inevitably causes relapse’, originally grade D, with a note that 44% of the discontinuation group did not relapse within 52 weeks. Subclaim score, status and axes are absent and separate from the parent's B70 for average relapse reduction. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Subclaim score, status and axes were originally absent; no new verdict is written. Review of existing content remains incomplete.	Distinguishing the subclaim's D grade/note from parent B70 and the absence of score, status and axes	Proposal: Separate source records for the inevitability claim and the parent's average effect are proposed; no new investigation, calculation or trial was conducted.
2	Partly verified	Full text not readStored summary read	N02 · Efficacy comparison and presentation of stored materialWhat period, people and exposure does ‘inevitably’ refer to?Required	The original selected wording is ‘discontinuation inevitably causes relapse’. ANTLER actually compared tapering to placebo in adults with long-term use and remission who were considering stopping, using first-relapse data over 52 weeks. The 52-week period is not extended to a lifetime or every form of discontinuation. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Materials establishing inevitability for every person, period or discontinuation method are absent from this preserved scope. Review of existing content remains incomplete.	Distinguishing an all-person or inevitability claim from the actual 52-week taper-to-placebo conditions	Proposal: Materials separating the claim's time, population and exposure scope are proposed; no new investigation, calculation or trial was conducted.
3	Partly verified	Full text not readStored summary read	N03 · Efficacy comparison and presentation of stored materialIs the 44% without relapse stated directly in the original text?Required	The value that 44% of the discontinuation group did not relapse within 52 weeks is directly stated in the existing reader answer and subclaim note. It was not generated by calculating a new complementary proportion from 56%, and is not changed to absence of relapse over another period. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Individual adherence, restarting, censoring, clinical characteristics and subsequent course among those without relapse remain unverified. Review of existing content remains incomplete.	Preserving the original no-relapse wording, period and unit of the proportion	Proposal: Materials linking observed absence of relapse with individual courses are proposed; no new investigation, calculation or trial was conducted.
4	Partly verified	Full text not readStored summary read	N04 · Efficacy comparison and presentation of stored materialDoes 56% relapse in the discontinuation group mean ‘inevitably’?Required	ANTLER's original discontinuation result of 135/240 (56%), maintenance result of 92/238 (39%) and absolute difference of 17%p are average between-arm comparisons. They are not transferred to relapse in every individual who discontinues; the subclaim's D grade/note is preserved unchanged. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Individual probabilities, outcomes for all people and inevitability over other periods or populations remain unverified. Review of existing content remains incomplete.	Distinguishing original 135/240 (56%), 92/238 (39%) and 17%p from inevitability wording	Proposal: Separate materials on arm comparisons and claims about every person or individual are proposed; no new investigation, calculation or trial was conducted.
5	Partly verified	Full text not readStored summary read	N05 · Efficacy comparison and presentation of stored materialDo the population and recruitment conditions include every patient with depression?Required	Adults from 150 UK general practices felt well enough to consider stopping. They had at least 2 previous episodes or at least 2 years of treatment, with specific study conditions involving long-term use of four drugs. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Exact remission criteria, age, baseline risk, exclusions and the course without relapse under other population conditions remain unverified. Review of existing content remains incomplete.	Conditions involving 150 practices, long-term medication, remission and 2 episodes/2 years	Proposal: Materials linking eligibility conditions with individual outcomes are proposed; no new investigation, calculation or trial was conducted.
6	Partly verified	Full text not readStored summary read	N06 · Efficacy comparison and presentation of stored materialIs study ‘discontinuation’ the same as complete or immediate stopping?Required	The original trial switched users of specified drugs to matching placebo after tapering over 1~2 months. This is not converted into abrupt-stopping exposure, every drug or dose, or outcomes of individuals who completely stopped. Study conditions are not made into tapering or dosing instructions. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Individual actual tapering, exposure, concomitant treatment and stopping or restarting times remain unverified. Review of existing content remains incomplete.	Historical scope of tapering over 1~2 months, switching to placebo and actual exposure	Proposal: Materials linking allocation conditions with actual behavior are proposed; no new investigation, calculation or trial was conducted.
7	Partly verified	Full text not readStored summary read	N07 · Efficacy comparison and presentation of stored materialDo 39% restarting and 52% adherence identify those without relapse?Required	Original values state 52% adherence in the discontinuation group and that 39% restarted a clinician-prescribed antidepressant before the trial ended. These people are not assumed to be the same as the 44% without relapse; no new overlap is calculated. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Individual cross-classification of restarting or adherence with relapse or absence of relapse, timing and reasons remains unverified. Review of existing content remains incomplete.	Relationship between actual exposure or restarting in the discontinuation group and the no-relapse group	Proposal: Materials separating absence of relapse in the allocated group from actual exposure pathways are proposed; no new investigation, calculation or trial was conducted.
8	Partly verified	Full text not readStored summary read	N08 · Efficacy comparison and presentation of stored materialCan individual outcomes after actual stopping be separated from the allocation effect?Required	The allocated comparison of 478 participants and original HR are study results for maintenance versus a taper-followed-by-placebo strategy. No new estimate is made of a pure effect among people who completely stopped, inevitable relapse, or the proportion without relapse and without restarting. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Causal or temporal analysis by actual exposure, crossover, rescue treatment and denominators remains unverified. Review of existing content remains incomplete.	Distinguishing the randomized comparison's estimand from individual and actual-exposure effects	Proposal: Materials distinguishing allocation effects from actual-exposure effects are proposed; no new investigation, calculation or trial was conducted.
9	Partly verified	Full text not readStored summary read	N09 · Efficacy comparison and presentation of stored materialHow does primary first relapse differ from symptom worsening and withdrawal?Required	ANTLER's primary endpoint is time to first depression relapse within 52 weeks, and the parent describes relapse assessed using a symptom scale. Withdrawal symptoms, other transient worsening and recurrent episodes are not merged into the same event as relapse or inevitability. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Details of the relapse instrument, threshold, assessment schedule, withdrawal distinction, first event and censoring remain unverified. Review of existing content remains incomplete.	Event definitions for first relapse within 52 weeks, symptom instruments and withdrawal	Proposal: Materials distinguishing events from symptoms and recurrent outcomes are proposed; no new investigation, calculation or trial was conducted.
10	Partly verified	Full text not readStored summary read	N10 · Efficacy comparison and presentation of stored materialHow are 478 randomized, 468 in time-to-event analysis and 10 with missing timing related?Required	The preserved wording states 478 randomized and 468 in the primary time-to-event analysis, with 10 lacking timing (6 maintenance/4 discontinuation) excluded from the primary analysis but included in absolute relapse counts. Missing-data participants are not newly classified as all having relapsed or all having had no relapse. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Exact timing, reasons for missingness, individual exposure and censoring for the 10 participants, and follow-up details for those without relapse remain unverified. Review of existing content remains incomplete.	238 maintenance/240 discontinuation, missing timing in 6/4, and denominator-specific scope	Proposal: Materials linking relapse or no-relapse observations by denominator are proposed; no new investigation, calculation or trial was conducted.
11	Partly verified	Full text not readStored summary read	N11 · Efficacy comparison and presentation of stored materialDo best- and worst-case missing-data assumptions test relapse in everyone?Required	The original statement that best- and worst-case missing-data analyses remained in the same direction concerns the arm comparison. It is not converted into relapse in everyone, individual discontinuation outcomes, or resolution of all missing-data bias. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Actual values, CIs and denominators under each assumption, pathways without relapse and temporal materials remain unverified. Review of existing content remains incomplete.	Distinguishing the original direction of sensitivity analyses from the inevitability question	Proposal: Separate materials on sensitivity of arm comparisons and individual inevitability are proposed; no new investigation, calculation or trial was conducted.
12	Partly verified	Full text not readStored summary read	N12 · Efficacy comparison and presentation of stored materialIs the discontinuation-versus-maintenance HR 2.06 a probability of inevitability?Required	The original discontinuation-versus-maintenance HR 2.06 (1.56~2.70), P<.001 is a time-to-event comparison. It is not changed into a value meaning 100% probability of relapse or relapse in a particular person. No maintenance-versus-discontinuation reciprocal, new RR or effect is calculated. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Model, censoring, proportional hazards, individual prediction and CIs for absolute outcomes remain unverified. Review of existing content remains incomplete.	Separate units for HR, CI, P, event proportions and individual probabilities	Proposal: Materials linking comparative estimands and individual prediction are proposed; no new investigation, calculation or trial was conducted.
13	Partly verified	Full text not readStored summary read	N13 · Efficacy comparison and presentation of stored materialWhat gaps do withdrawal symptoms and awareness of allocation leave in an inevitability interpretation?Required	The preserved wording gives 12-week DESS means of 3.1 versus 1.3, the original difference of 1.9 (1.5~2.3), and greater awareness of allocation in the discontinuation group. Some withdrawal may have been misclassified as relapse, but the magnitude is undetermined. No new conclusion is made that all relapse was withdrawal. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Misclassified cases, original model and denominators, allocation-guessing figures, and temporal relationships between withdrawal and relapse remain unverified. Review of existing content remains incomplete.	Original scope of 12-week modified DESS, possible misclassification and allocation awareness	Proposal: Materials distinguishing withdrawal from relapse and recording allocation awareness are proposed; no new investigation, calculation or trial was conducted.
14	Partly verified	Full text not readStored summary read	N14 · Efficacy comparison and presentation of stored materialIs 39% relapse during maintenance a different question from inevitability after discontinuation?Required	The parent and related wording that 39% relapsed despite maintenance concerns the complete-prevention question. It is not transferred to the denominator of ‘discontinuation inevitably causes relapse’ or to relapse outcomes for other individuals. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Individual pathways during maintenance or discontinuation and original subgroup prediction materials remain unverified. Review of existing content remains incomplete.	Boundary between the other arm's result and the related complete-prevention question	Proposal: Materials separating average reduction, complete prevention and inevitability claims are proposed; no new investigation, calculation or trial was conducted.
15	Partly verified	Full text not readStored summary read	N15 · Efficacy comparison and presentation of stored materialDoes absence of relapse within 52 weeks certify lifelong freedom from relapse or safe discontinuation?Required	The 44% without relapse is original observational wording within 52 weeks. It is not extended to lifelong freedom from relapse, safe discontinuation for every person or a guarantee of individual treatment choice. The original account states that the trial did not identify who could discontinue safely. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Long-term follow-up, individual risk, withdrawal, restarting and other safety outcomes remain unverified. Review of existing content remains incomplete.	Actual observation period and gaps beyond observation or in individual safety	Proposal: Separate materials on gaps beyond the time or individual scope are proposed; no new investigation, calculation or trial was conducted.
16	Unverified	Full text not readStored summary read	N16 · Efficacy comparison and presentation of stored materialCan those who will remain without relapse be identified beforehand?Required	The preserved wording states that ANTLER reported average relapse reduction and did not distinguish people who could discontinue safely. No individual prediction rule is created from original drug, history or duration conditions alone. S01 S02	The information currently required remains unverified in the preserved summary. Validated individual models, prespecified subgroups and external validation in other populations remain unverified in these authoring materials. Review of existing content remains incomplete.	Distinguishing group comparisons from validated individual prediction and subgroup information	Proposal: Separate materials linking average effects and individual prediction are proposed; no new investigation, calculation or trial was conducted.
17	Partly verified	Full text not readStored summary read	N17 · Efficacy comparison and presentation of stored materialAre the NEJM and HTA citations independent trials?Required	S01 NEJM PMID34587384 and S02 NIHR HTA PMID34842135 report the same ANTLER trial. They share the first evidence record's 478 and 468 participants and withdrawal, adherence and missing-data results. The two reports are not counted as 2 independent trials or two participant populations. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Original tables, analyses and correspondence between the two reports remain externally unread. Review of existing content remains incomplete.	Relationship between the same ANTLER trial, the first evidence record, and the main and detailed reports	Proposal: Materials on multiple-report relationships within the same trial are proposed; no new investigation, calculation or trial was conducted.
18	Partly verified	Full text not readStored summary read	N18 · Efficacy comparison and presentation of stored materialDo average meta-analysis results directly answer ‘inevitably’?Required	Kato's maintenance result of 20.9% versus placebo 39.7%, OR .38 (.33~.43), P<.00001 synthesizes varied maintenance trials. An average relapse difference is not transferred to direct evidence that every person relapses after stopping. The preserved wording that does not count it as an independent replication of ANTLER's primary-care decision is retained. S03	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Periods, populations, events, inclusion denominators, overlap, individual prediction and heterogeneity remain unverified. Review of existing content remains incomplete.	Differences between Kato's 40 trials and 8890 participants, proportions or OR, and the actual original question	Proposal: Materials separating pooled averages from claims about every person or individual are proposed; no new investigation, calculation or trial was conducted.
19	Partly verified	Full text not readStored summary read	N19 · Efficacy comparison and presentation of stored materialDo people and reports overlap across the review, ANTLER and related sheets?Required	This sheet shares the same ANTLER trial and review summary as the 52-week relapse-reduction sheet; NEJM and HTA report the same trial. The 40 trials with 8890 participants, 478 participants and two sheets or reports are not added as independent trials or total participants. S01 S02 S03	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Unique clinical totals and review inclusion or overlap relationships are not established and remain unrecorded. Review of existing content remains incomplete.	Shared preserved summary, two subclaim sheets, and report, trial and synthesis relationships	Proposal: Records of material families and overlap relationships are proposed; no new investigation, calculation or trial was conducted.
20	Partly verified	Full text not readStored summary read	N20 · Efficacy comparison and presentation of stored materialHave registration and prespecified endpoints actually been read?Required	ANTLER's ‘ISRCTN15969819 · EudraCT2015-004210-26’ is preserved unchanged. Kato's ‘Not applicable’ is preserved review wording. Identifiers or wording alone do not establish that registration or plans were read, or that prespecified individual prediction was validated. S01 S02 S03	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Registration amendment history, protocol, SAP, subgroup and missing-data plans remain unread; access was not attempted. Review of existing content remains incomplete.	Original ISRCTN/EudraCT identifiers and unread registration or plans	Proposal: Links between prespecified plans, versions and reports are proposed; no new investigation, calculation or trial was conducted.
21	Partly verified	Full text not readStored summary read	N21 · Efficacy comparison and presentation of stored materialDo public support and unreported product or COI information certify independence?Required	ANTLER's NIHR HTA 13/115/48, PRIMENT core support and UCL sponsor, and Kato's Japanese research grants are preserved unchanged. The historical wording that neither report described donated trial drug or placebo is not changed into actual absence or certification of independence in this work. S01 S02 S03	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Support and product contracts, employee authors, conflicts of interest, study and manuscript roles, and support for included trials in the review remain unverified. Review of existing content remains incomplete.	NIHR, PRIMENT, UCL, product provision, employees, conflicts of interest and review funding	Proposal: Materials on funding, support types and actual roles are proposed; no new investigation, calculation or trial was conducted.
22	Partly verified	Full text not readStored summary read	N22 · Harm-information gaps supplementing the efficacy tableAre withdrawal, serious events and absence of relapse the same safety outcome?Supplementary	Original serious adverse events of 9 maintenance participants (4%)/8 discontinuation participants (3%), 0 deaths or suicide attempts in both groups, and increased withdrawal at 12 weeks are recorded separately. Absence of relapse is not converted into no adverse effects, safe discontinuation or 0 long-term harm. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Event definitions, collection, safety denominators, exposure, follow-up, CIs and long-term or drug-specific harms remain unverified. Review of existing content remains incomplete.	Scope of harm collection, 12-week withdrawal, 9/8 participants and 0 deaths or suicide attempts	Proposal: Materials separating absence of relapse from other harm outcomes are proposed; no new investigation, calculation or trial was conducted.
23	Partly verified	Full text not readStored summary read	N23 · Efficacy comparison and presentation of stored materialDoes this answer questions about other drugs, abrupt stopping or new treatment settings?Required	The original materials' four drugs, specified doses and study taper over 1~2 months are historical exposure. No new verdict is made on inevitability after abrupt stopping, other drugs or doses, acute treatment, other diseases or ages, or every treatment setting. S01 S02	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Direct relapse and safety materials under conditions outside the scope remain unverified. Review of existing content remains incomplete.	Original four drugs, study taper, remission, long-term use and questions outside that scope	Proposal: Separate questions and material scopes by exposure and population are proposed; no new investigation, calculation or trial was conducted.
24	Partly verified	Full text not readStored summary read	N24 · Efficacy comparison and presentation of stored materialWhat preserved summaries and external materials have actually been read?Required	‘Summary read’ means the complete preserved Korean and English texts, original figures, bibliography and subclaims were used for production. External papers, registration, protocol, SAP, support and COI materials remain ‘not read’; historical statements about reading clinical originals or URLs are not inherited as new reading. S01 S02 S03	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. External access, link or click tests and comparison against original external materials were not performed. Review of existing content remains incomplete.	Preserved summary, original NEJM/HTA/Kato URLs and unread external materials	Proposal: Records of acquisition, reading and versions by material are proposed; no new investigation, calculation or trial was conducted.
25	Partly verified	Full text not readStored summary read	N25 · Efficacy comparison and presentation of stored materialAre original subclaim D, parent B70, Korean/English texts, dates and empty values preserved?Required	Selected D grade/note and English wording, parent B70, Caution, Korean and English texts, axes with unrecorded precision, false, 2026-08-26, and empty correction and deliberation values are preserved unchanged. Absent subclaim score, status and axes are not filled from parent values. S01 S02 S03	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. The historical production did not translate the verdict text, create a new verdict or correction, or update external evidence. Review of existing content remains incomplete.	Whole original preservation, absence, unrecorded precision, false values and correction history	Proposal: Links between original versions, dates and the selected subclaim sheet are proposed; no new investigation, calculation or trial was conducted.
26	Partly verified	Full text not readStored summary read	N26 · Efficacy comparison and presentation of stored materialDo applied conditions and completed production mean existing content review is complete?Required	Preservation, freezing and application of conditions, case production and content review are separate records. Existing content review remains incomplete; counts of written records are not totals of unique clinical trials or participants. S01 S02 S03	Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Existing content review remains incomplete. Additional content review, testing, screen checks and link tests were not conducted during the original production. Review of existing content remains incomplete.	Distinguishing preservation, freezing and application of conditions, case production and incomplete content review	Proposal: A history of production versions, conditions and user corrections is proposed; no new investigation, calculation or trial was conducted.

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26 itemsWhat the statuses mean

Assessment scope

Stored-material review date: Not recorded
Original evidence cut-off: 2026-08-26
Scope actually checked: Existing review summaries and stored records of methodological application. Full papers, supplements, registrations, plans and original data were not read.
What the dates mean: This is the date the stored materials were checked, not the date of a new search of the clinical literature.
Population: Adults in UK primary care with remission and long-term use who were considering stopping; not extended to every individual or setting
Ingredient, formulation and route: Original ANTLER allocation strategy of tapering to placebo; actual restarting and adherence distinguished from complete discontinuation
Dose: Not recorded
Comparator: Original arm results for maintenance versus tapering to placebo; individual inevitability is a separate question
Measured outcome: Existing question ‘discontinuation inevitably causes relapse’, original wording on 44% without relapse within 52 weeks, and the gap in individual prediction
Duration: Original observation over 52 weeks; not extended to lifelong freedom from relapse or safe discontinuation for an individual
Questions outside this scope: Extending the original reduction in relapse within 52 weeks to complete prevention for every person or period, or inevitable relapse on discontinuation; Extending the original 44% without relapse to lifelong freedom from relapse, safe discontinuation for an individual, or complete discontinuation without restarting; Calculating correspondence or overlap by assuming the discontinuation group's 52% adherence, 39% restarting and 44% without relapse refer to the same people; Calculating new exclusion proportions, denominators, events or individual classifications from 478 randomized, 468 in the time-to-event analysis and 10 with missing timing (6/4); Recalculating or converting the original 92/238, 135/240, 39%/56%, 17%p, HR 2.06/CI/P or DESS means and difference into reciprocals, NNT or individual probabilities; Double-counting NEJM and HTA as independent trials, or adding participants across the two sheets, arms, time points or the 478/8890 participant figures; Using the 40-study meta-analysis as a new independent replication under ANTLER conditions, or certification of inevitability or individual prediction; Treating possible withdrawal misclassification or awareness of allocation as the cause of all results, a newly quantified bias, or invalidation of the trial; Extending 9/8 participants with serious events and 0 deaths or suicide attempts to zero risk, long-term safety or drug selection; Treating the absence of reported company donations in the original account as absence of support, employee authors or conflicts of interest, or certification of independence; Inheriting the parent's B70, axes, historical cross-checking, public funding or original-material review statements as subclaim values, review of content in this work or external reading; New searches or numerical calculations; hypothetical quantitative examples; new effects, CIs, grades or certification of independence; guidance on maintenance, discontinuation, tapering, dosing, drug changes or treatment

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.

S01 · Lewis G, Marston L, Duffy L, et al. Maintenance or Discontinuation of Antidepressants in Primary Care. N Engl J Med. 2021;385:1257-1267. PMID: 34587384. DOI: 10.1056/NEJMoa2106356.

Publisher · PubMed

Material type: Multicenter double-blind placebo-controlled superiority RCT
Materials actually read: Summary read; external material unread
Findings recorded in the stored summary: Relapse: 92/238 (39%) versus 135/240 (56%); discontinuation versus maintenance HR 2.06 (95% CI 1.56~2.70), P<0.001; absolute difference 17%p. The existing reader answer and subclaim state that 44% of the discontinuation group had no relapse within 52 weeks and that 39% of the maintenance group relapsed. The 10 participants with missing timing were excluded from the primary analysis but included in absolute counts. Adherence of 70%/52%, restarting in 39% of the discontinuation group, and 12-week DESS means of 3.1/1.3 with the original difference of 1.9 (CI 1.5~2.3) are preserved separately. No new proportions, differences, individual probabilities, reciprocals, effects, CIs or grades are calculated.
Record level: Outcome wording in the stored summary
Study overlap and independent replication: S01 NEJM/Lewis2021 PMID34587384 is the main ANTLER report. The first record in the existing evidence list describes both reports together. They share 478 randomized participants (238 maintenance/240 taper followed by placebo), 468 in the time-to-event analysis, 10 with missing timing (6/4), absolute relapse counts, withdrawal, adherence and restarting. Reports, related sheets, arms, time points and people are not added as new independent trials or participants. Counts of report or material slots are not totals of unique clinical trials, participants or independent replications. Unique clinical totals remain unrecorded. S02 NIHR HTA/Duffy2021 PMID34842135 is a detailed report of the same ANTLER trial. The first record in the existing evidence list describes both reports together. They share 478 randomized participants (238 maintenance/240 taper followed by placebo), 468 in the time-to-event analysis, 10 with missing timing (6/4), absolute relapse counts, withdrawal, adherence and restarting. Reports, related sheets, arms, time points and people are not added as new independent trials or participants. Counts of report or material slots are not totals of unique clinical trials, participants or independent replications. Unique clinical totals remain unrecorded. S03 Kato2021 PMID32704061 is a meta-analysis of 40 trials with 8,890 participants comparing maintenance with switching to placebo after various acute treatments. The original wording that does not count it as an independent replication of ANTLER's long-term primary-care discontinuation decision is preserved. Inclusion, overlap, timing and unique trial totals remain unverified; participants in the review, ANTLER and related sheets are not added together. Counts of report or material slots are not totals of unique clinical trials, participants or independent replications. Unique clinical totals remain unrecorded.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Stored summary	Stored file	Stored summary	Summary read	Only the stored JSON summary and bibliography were used for production. This does not constitute external verification or completed content review.
External paper	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.
Registration material	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.
Protocol	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.
Statistical analysis plan	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.
Funding, product-support and COI material	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.

S02 · Duffy L, Clarke CS, Lewis G, et al. Antidepressant medication to prevent depression relapse in primary care: the ANTLER RCT. Health Technol Assess. 2021;25(69):1-62. PMID: 34842135. DOI: 10.3310/hta25690.

Publisher · PubMed

Material type: Multicenter double-blind placebo-controlled superiority RCT
Materials actually read: Summary read; external material unread
Findings recorded in the stored summary: Relapse: 92/238 (39%) versus 135/240 (56%); discontinuation versus maintenance HR 2.06 (95% CI 1.56~2.70), P<0.001; absolute difference 17%p. The existing reader answer and subclaim state that 44% of the discontinuation group had no relapse within 52 weeks and that 39% of the maintenance group relapsed. The 10 participants with missing timing were excluded from the primary analysis but included in absolute counts. Adherence of 70%/52%, restarting in 39% of the discontinuation group, and 12-week DESS means of 3.1/1.3 with the original difference of 1.9 (CI 1.5~2.3) are preserved separately. No new proportions, differences, individual probabilities, reciprocals, effects, CIs or grades are calculated.
Record level: Outcome wording in the stored summary
Study overlap and independent replication: S01 NEJM/Lewis2021 PMID34587384 is the main ANTLER report. The first record in the existing evidence list describes both reports together. They share 478 randomized participants (238 maintenance/240 taper followed by placebo), 468 in the time-to-event analysis, 10 with missing timing (6/4), absolute relapse counts, withdrawal, adherence and restarting. Reports, related sheets, arms, time points and people are not added as new independent trials or participants. Counts of report or material slots are not totals of unique clinical trials, participants or independent replications. Unique clinical totals remain unrecorded. S02 NIHR HTA/Duffy2021 PMID34842135 is a detailed report of the same ANTLER trial. The first record in the existing evidence list describes both reports together. They share 478 randomized participants (238 maintenance/240 taper followed by placebo), 468 in the time-to-event analysis, 10 with missing timing (6/4), absolute relapse counts, withdrawal, adherence and restarting. Reports, related sheets, arms, time points and people are not added as new independent trials or participants. Counts of report or material slots are not totals of unique clinical trials, participants or independent replications. Unique clinical totals remain unrecorded. S03 Kato2021 PMID32704061 is a meta-analysis of 40 trials with 8,890 participants comparing maintenance with switching to placebo after various acute treatments. The original wording that does not count it as an independent replication of ANTLER's long-term primary-care discontinuation decision is preserved. Inclusion, overlap, timing and unique trial totals remain unverified; participants in the review, ANTLER and related sheets are not added together. Counts of report or material slots are not totals of unique clinical trials, participants or independent replications. Unique clinical totals remain unrecorded.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Stored summary	Stored file	Stored summary	Summary read	Only the stored JSON summary and bibliography were used for production. This does not constitute external verification or completed content review.
External paper	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.
Registration material	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.
Protocol	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.
Statistical analysis plan	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.
Funding, product-support and COI material	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.

S03 · Kato M, Hori H, Inoue T, et al. Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: a systematic review and meta-analysis. Mol Psychiatry. 2021;26:118-133. PMID: 32704061. DOI: 10.1038/s41380-020-0843-0.

Publisher · PubMed

Material type: Meta-analysis of 40 trials of antidepressant maintenance versus switching to placebo
Materials actually read: Summary read; external material unread
Findings recorded in the stored summary: Maintenance 20.9% versus switching to placebo 39.7%, OR 0.38 (95% CI 0.33~0.43), P<0.00001. The original proportions, OR and direction are preserved within the scope of this synthesis. This estimand differs from the ANTLER HR and 17%p; no new reciprocal, pooled effect, period-specific incidence, total participant count or individual prediction is generated.
Record level: Outcome wording in the stored summary
Study overlap and independent replication: S01 NEJM/Lewis2021 PMID34587384 is the main ANTLER report. The first record in the existing evidence list describes both reports together. They share 478 randomized participants (238 maintenance/240 taper followed by placebo), 468 in the time-to-event analysis, 10 with missing timing (6/4), absolute relapse counts, withdrawal, adherence and restarting. Reports, related sheets, arms, time points and people are not added as new independent trials or participants. Counts of report or material slots are not totals of unique clinical trials, participants or independent replications. Unique clinical totals remain unrecorded. S02 NIHR HTA/Duffy2021 PMID34842135 is a detailed report of the same ANTLER trial. The first record in the existing evidence list describes both reports together. They share 478 randomized participants (238 maintenance/240 taper followed by placebo), 468 in the time-to-event analysis, 10 with missing timing (6/4), absolute relapse counts, withdrawal, adherence and restarting. Reports, related sheets, arms, time points and people are not added as new independent trials or participants. Counts of report or material slots are not totals of unique clinical trials, participants or independent replications. Unique clinical totals remain unrecorded. S03 Kato2021 PMID32704061 is a meta-analysis of 40 trials with 8,890 participants comparing maintenance with switching to placebo after various acute treatments. The original wording that does not count it as an independent replication of ANTLER's long-term primary-care discontinuation decision is preserved. Inclusion, overlap, timing and unique trial totals remain unverified; participants in the review, ANTLER and related sheets are not added together. Counts of report or material slots are not totals of unique clinical trials, participants or independent replications. Unique clinical totals remain unrecorded.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Stored summary	Stored file	Stored summary	Summary read	Only the stored JSON summary and bibliography were used for production. This does not constitute external verification or completed content review.
External paper	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.
Registration material	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.
Protocol	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.
Statistical analysis plan	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.
Funding, product-support and COI material	Public availability unverified; only bibliography links preserved	Unread; access not attempted	Not read	No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status.

Report counts versus independent study counts

S01 NEJM/Lewis2021 PMID34587384 is the main ANTLER report. The first record in the existing evidence list describes both reports together. They share 478 randomized participants (238 maintenance/240 taper followed by placebo), 468 in the time-to-event analysis, 10 with missing timing (6/4), absolute relapse counts, withdrawal, adherence and restarting. Reports, related sheets, arms, time points and people are not added as new independent trials or participants. Counts of report or material slots are not totals of unique clinical trials, participants or independent replications. Unique clinical totals remain unrecorded. S02 NIHR HTA/Duffy2021 PMID34842135 is a detailed report of the same ANTLER trial. The first record in the existing evidence list describes both reports together. They share 478 randomized participants (238 maintenance/240 taper followed by placebo), 468 in the time-to-event analysis, 10 with missing timing (6/4), absolute relapse counts, withdrawal, adherence and restarting. Reports, related sheets, arms, time points and people are not added as new independent trials or participants. Counts of report or material slots are not totals of unique clinical trials, participants or independent replications. Unique clinical totals remain unrecorded. S03 Kato2021 PMID32704061 is a meta-analysis of 40 trials with 8,890 participants comparing maintenance with switching to placebo after various acute treatments. The original wording that does not count it as an independent replication of ANTLER's long-term primary-care discontinuation decision is preserved. Inclusion, overlap, timing and unique trial totals remain unverified; participants in the review, ANTLER and related sheets are not added together. Counts of report or material slots are not totals of unique clinical trials, participants or independent replications. Unique clinical totals remain unrecorded.

Review criteria

Version 1.0 · Criteria record date 2026-10-06. 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 · What is the existing verdict on ‘discontinuation inevitably causes relapse’?

Required materials and conditions: Distinguishing the subclaim's D grade/note from parent B70 and the absence of score, status and axes
Conditions for verification: Relevant original materials and analysis scope for Distinguishing the subclaim's D grade/note from parent B70 and the absence of score, status and axes must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Distinguishing the subclaim's D grade/note from parent B70 and the absence of score, status and axes and link the materials required for the selected question to currently available materials.
Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are our own design

N02 · What period, people and exposure does ‘inevitably’ refer to?

Required materials and conditions: Distinguishing an all-person or inevitability claim from the actual 52-week taper-to-placebo conditions
Conditions for verification: Relevant original materials and analysis scope for Distinguishing an all-person or inevitability claim from the actual 52-week taper-to-placebo conditions must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Distinguishing an all-person or inevitability claim from the actual 52-week taper-to-placebo conditions and link the materials required for the selected question to currently available materials.
Referenced methods: M03 §3.1, §3.2.1–3.2.4: principles for clarifying the question; detailed separation rules are Chamgap's own design; M03 §3.2.1; detailed population conditions are Chamgap's own design; M03 §3.2.2–3.2.3; reverse labeling and test adaptations are Chamgap's own design; M03 §3.2.1–3.2.4; dose, duration and effect-modification details are Chamgap's own design

N03 · Is the 44% without relapse stated directly in the original text?

Required materials and conditions: Preserving the original no-relapse wording, period and unit of the proportion
Conditions for verification: Relevant original materials and analysis scope for Preserving the original no-relapse wording, period and unit of the proportion must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Preserving the original no-relapse wording, period and unit of the proportion and link the materials required for the selected question to currently available materials.
Referenced methods: M03 §3.2.4 and M15 §15.3.1–15.3.3; Question-specific outcome adaptation is Chamgap design; M08 Table 8.2.a, M15 §15.3 and M19 §19.1.2–19.2.4; Design-specific adaptation is Chamgap design; M03 §3.2.1–3.2.4; Dose, duration and effect-modifier details are Chamgap design

N04 · Does 56% relapse in the discontinuation group mean ‘inevitably’?

Required materials and conditions: Distinguishing original 135/240 (56%), 92/238 (39%) and 17%p from inevitability wording
Conditions for verification: Relevant original materials and analysis scope for Distinguishing original 135/240 (56%), 92/238 (39%) and 17%p from inevitability wording must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Distinguishing original 135/240 (56%), 92/238 (39%) and 17%p from inevitability wording and link the materials required for the selected question to currently available materials.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are Chamgap's own design; M03 §3.2.4; Chamgap's own limits on extension

N05 · Do the population and recruitment conditions include every patient with depression?

Required materials and conditions: Conditions involving 150 practices, long-term medication, remission and 2 episodes/2 years
Conditions for verification: Relevant original materials and analysis scope for Conditions involving 150 practices, long-term medication, remission and 2 episodes/2 years must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Conditions involving 150 practices, long-term medication, remission and 2 episodes/2 years and link the materials required for the selected question to currently available materials.
Referenced methods: M03 §3.2.1; Detailed population conditions are Chamgap design; M03 §3.2.1–3.2.4; Dose, duration and effect-modifier details are Chamgap design

N06 · Is study ‘discontinuation’ the same as complete or immediate stopping?

Required materials and conditions: Historical scope of tapering over 1~2 months, switching to placebo and actual exposure
Conditions for verification: Relevant original materials and analysis scope for Historical scope of tapering over 1~2 months, switching to placebo and actual exposure must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Historical scope of tapering over 1~2 months, switching to placebo and actual exposure and link the materials required for the selected question to currently available materials.
Referenced methods: M03 §3.2.2–3.2.3; Reverse-direction labels and assessment adaptation are Chamgap design; M03 §3.2.3 and M08 §8.2.2–8.2.3; Chamgap application

N07 · Do 39% restarting and 52% adherence identify those without relapse?

Required materials and conditions: Relationship between actual exposure or restarting in the discontinuation group and the no-relapse group
Conditions for verification: Relevant original materials and analysis scope for Relationship between actual exposure or restarting in the discontinuation group and the no-relapse group must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Relationship between actual exposure or restarting in the discontinuation group and the no-relapse group and link the materials required for the selected question to currently available materials.
Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed

N08 · Can individual outcomes after actual stopping be separated from the allocation effect?

Required materials and conditions: Distinguishing the randomized comparison's estimand from individual and actual-exposure effects
Conditions for verification: Relevant original materials and analysis scope for Distinguishing the randomized comparison's estimand from individual and actual-exposure effects must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Distinguishing the randomized comparison's estimand from individual and actual-exposure effects and link the materials required for the selected question to currently available materials.
Referenced methods: M08 §8.2.2, M15 §15.3.1; our own application; M03 §3.2.3, M08 §8.2.2–8.2.3; our own application

N09 · How does primary first relapse differ from symptom worsening and withdrawal?

Required materials and conditions: Event definitions for first relapse within 52 weeks, symptom instruments and withdrawal
Conditions for verification: Relevant original materials and analysis scope for Event definitions for first relapse within 52 weeks, symptom instruments and withdrawal must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Event definitions for first relapse within 52 weeks, symptom instruments and withdrawal and link the materials required for the selected question to currently available materials.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptation to each question is internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M08 Table 8.2.a, M04 §4.6.3; internal application

N10 · How are 478 randomized, 468 in time-to-event analysis and 10 with missing timing related?

Required materials and conditions: 238 maintenance/240 discontinuation, missing timing in 6/4, and denominator-specific scope
Conditions for verification: Relevant original materials and analysis scope for 238 maintenance/240 discontinuation, missing timing in 6/4, and denominator-specific scope must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish 238 maintenance/240 discontinuation, missing timing in 6/4, and denominator-specific scope and link the materials required for the selected question to currently available materials.
Referenced methods: M08 Table 8.2.a, M15 §15.3 and M19 §19.1.2–19.2.4; Design-specific adaptation is Chamgap design; M08 §8.2.2 and M15 §15.3.1; Chamgap application

N11 · Do best- and worst-case missing-data assumptions test relapse in everyone?

Required materials and conditions: Distinguishing the original direction of sensitivity analyses from the inevitability question
Conditions for verification: Relevant original materials and analysis scope for Distinguishing the original direction of sensitivity analyses from the inevitability question must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Distinguishing the original direction of sensitivity analyses from the inevitability question and link the materials required for the selected question to currently available materials.
Referenced methods: M08 Table 8.2.a, M15 §15.3 and M19 §19.1.2–19.2.4; Design-specific adaptation is Chamgap design; M08 §8.2.2 and M15 §15.3.1; Chamgap application; M15 §15.3.1–15.3.3; Chamgap application

N12 · Is the discontinuation-versus-maintenance HR 2.06 a probability of inevitability?

Required materials and conditions: Separate units for HR, CI, P, event proportions and individual probabilities
Conditions for verification: Relevant original materials and analysis scope for Separate units for HR, CI, P, event proportions and individual probabilities must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Separate units for HR, CI, P, event proportions and individual probabilities and link the materials required for the selected question to currently available materials.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are Chamgap's own design; M08 §8.2.2, M15 §15.3.1; Chamgap's own application; M15 §15.3.1–15.3.3; Chamgap's own application

N13 · What gaps do withdrawal symptoms and awareness of allocation leave in an inevitability interpretation?

Required materials and conditions: Original scope of 12-week modified DESS, possible misclassification and allocation awareness
Conditions for verification: Relevant original materials and analysis scope for Original scope of 12-week modified DESS, possible misclassification and allocation awareness must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Original scope of 12-week modified DESS, possible misclassification and allocation awareness and link the materials required for the selected question to currently available materials.
Referenced methods: M08 Table 8.2.a, M03 §3.2.4; internal application; M19 §19.1.2–19.2.4; finer distinctions are internally designed; design-specific harm questions in M19 §19.2; details of temporal relationships are internally designed

N14 · Is 39% relapse during maintenance a different question from inevitability after discontinuation?

Required materials and conditions: Boundary between the other arm's result and the related complete-prevention question
Conditions for verification: Relevant original materials and analysis scope for Boundary between the other arm's result and the related complete-prevention question must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Boundary between the other arm's result and the related complete-prevention question and link the materials required for the selected question to currently available materials.
Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed

N15 · Does absence of relapse within 52 weeks certify lifelong freedom from relapse or safe discontinuation?

Required materials and conditions: Actual observation period and gaps beyond observation or in individual safety
Conditions for verification: Relevant original materials and analysis scope for Actual observation period and gaps beyond observation or in individual safety must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Actual observation period and gaps beyond observation or in individual safety and link the materials required for the selected question to currently available materials.
Referenced methods: M03 §3.2.1–3.2.4; dose, duration and effect-modification details are our own design; M19 §19.1.2–19.2.4; own application

N16 · Can those who will remain without relapse be identified beforehand?

Required materials and conditions: Distinguishing group comparisons from validated individual prediction and subgroup information
Conditions for verification: Relevant original materials and analysis scope for Distinguishing group comparisons from validated individual prediction and subgroup information must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Distinguishing group comparisons from validated individual prediction and subgroup information and link the materials required for the selected question to currently available materials.
Referenced methods: M03 §3.2.1–3.2.4; dose, duration and effect-modification details are our own design

N17 · Are the NEJM and HTA citations independent trials?

Required materials and conditions: Relationship between the same ANTLER trial, the first evidence record, and the main and detailed reports
Conditions for verification: Relevant original materials and analysis scope for Relationship between the same ANTLER trial, the first evidence record, and the main and detailed reports must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Relationship between the same ANTLER trial, the first evidence record, and the main and detailed reports and link the materials required for the selected question to currently available materials.
Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application; data collection and selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are internally designed

N18 · Do average meta-analysis results directly answer ‘inevitably’?

Required materials and conditions: Differences between Kato's 40 trials and 8890 participants, proportions or OR, and the actual original question
Conditions for verification: Relevant original materials and analysis scope for Differences between Kato's 40 trials and 8890 participants, proportions or OR, and the actual original question must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Differences between Kato's 40 trials and 8890 participants, proportions or OR, and the actual original question and link the materials required for the selected question to currently available materials.
Referenced methods: M03 §3.2.4 and M15 §15.3.1–15.3.3: question-specific outcome adaptation is in-house; M04 §4.6.1–4.6.2 and M15 §15.3.1: in-house application; M03 §3.2.4: in-house extension boundaries.

N19 · Do people and reports overlap across the review, ANTLER and related sheets?

Required materials and conditions: Shared preserved summary, two subclaim sheets, and report, trial and synthesis relationships
Conditions for verification: Relevant original materials and analysis scope for Shared preserved summary, two subclaim sheets, and report, trial and synthesis relationships must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Shared preserved summary, two subclaim sheets, and report, trial and synthesis relationships and link the materials required for the selected question to currently available materials.
Referenced methods: Study/report distinction in M04 §4.6.1–4.6.2; Cohort/outcome linkage is Chamgap application; M04 §4.6.1–4.6.2 and M15 §15.3.1; Chamgap application

N20 · Have registration and prespecified endpoints actually been read?

Required materials and conditions: Original ISRCTN/EudraCT identifiers and unread registration or plans
Conditions for verification: Relevant original materials and analysis scope for Original ISRCTN/EudraCT identifiers and unread registration or plans must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Original ISRCTN/EudraCT identifiers and unread registration or plans and link the materials required for the selected question to currently available materials.
Referenced methods: M04 §4.5–4.6 material collection/selection principles; acquisition/reading separation and hyperlink specifications are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application

N21 · Do public support and unreported product or COI information certify independence?

Required materials and conditions: NIHR, PRIMENT, UCL, product provision, employees, conflicts of interest and review funding
Conditions for verification: Relevant original materials and analysis scope for NIHR, PRIMENT, UCL, product provision, employees, conflicts of interest and review funding must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish NIHR, PRIMENT, UCL, product provision, employees, conflicts of interest and review funding and link the materials required for the selected question to currently available materials.
Referenced methods: Chamgap's own conditions for independence and attribution. The official methodological sections used in this example do not validate every detail of these items.

N22 · Are withdrawal, serious events and absence of relapse the same safety outcome?

Required materials and conditions: Scope of harm collection, 12-week withdrawal, 9/8 participants and 0 deaths or suicide attempts
Conditions for verification: Relevant original materials and analysis scope for Scope of harm collection, 12-week withdrawal, 9/8 participants and 0 deaths or suicide attempts must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Supplementary
Application exceptions: Addresses gaps in withdrawal and safety materials for the selected relapse question. Relapse, absence of relapse or original safety wording is not used to assess overall safety or an individual's ability to discontinue, or to generate harm incidence or guidance on maintenance, discontinuation, tapering, dosing or treatment.
Why this condition is needed: Production item to distinguish Scope of harm collection, 12-week withdrawal, 9/8 participants and 0 deaths or suicide attempts and link the materials required for the selected question to currently available materials.
Referenced methods: M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; finer distinctions are internally designed; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretation boundary. M19 principles are referenced; no official causality tool was executed

N23 · Does this answer questions about other drugs, abrupt stopping or new treatment settings?

Required materials and conditions: Original four drugs, study taper, remission, long-term use and questions outside that scope
Conditions for verification: Relevant original materials and analysis scope for Original four drugs, study taper, remission, long-term use and questions outside that scope must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Original four drugs, study taper, remission, long-term use and questions outside that scope and link the materials required for the selected question to currently available materials.
Referenced methods: M03 §3.2.1; detailed population conditions are our own design; M03 §3.2.2–3.2.3; reverse-direction labels and test adaptations are our own design; M03 §3.2.1–3.2.4; dose, duration and effect-modification details are our own design

N24 · What preserved summaries and external materials have actually been read?

Required materials and conditions: Preserved summary, original NEJM/HTA/Kato URLs and unread external materials
Conditions for verification: Relevant original materials and analysis scope for Preserved summary, original NEJM/HTA/Kato URLs and unread external materials must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Preserved summary, original NEJM/HTA/Kato URLs and unread external materials and link the materials required for the selected question to currently available materials.
Referenced methods: M04 §4.5–4.6 material collection/selection principles; acquisition/reading separation and hyperlink specifications are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design

N25 · Are original subclaim D, parent B70, Korean/English texts, dates and empty values preserved?

Required materials and conditions: Whole original preservation, absence, unrecorded precision, false values and correction history
Conditions for verification: Relevant original materials and analysis scope for Whole original preservation, absence, unrecorded precision, false values and correction history must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Whole original preservation, absence, unrecorded precision, false values and correction history and link the materials required for the selected question to currently available materials.
Referenced methods: M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design

N26 · Do applied conditions and completed production mean existing content review is complete?

Required materials and conditions: Distinguishing preservation, freezing and application of conditions, case production and incomplete content review
Conditions for verification: Relevant original materials and analysis scope for Distinguishing preservation, freezing and application of conditions, case production and incomplete content review must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Requirement and applicability: Required
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Why this condition is needed: Production item to distinguish Distinguishing preservation, freezing and application of conditions, case production and incomplete content review and link the materials required for the selected question to currently available materials.
Referenced methods: M04 §4.5–4.6 material collection/selection principles; acquisition/reading separation and hyperlink specifications are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design

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, and distinguish variations in interventions.
Extent of review: Preserved method HTML copies; no current method-content re-review or official tool execution

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: Distinguish studies from reports and link them; do not omit a study solely because results are unreported.
Extent of review: Preserved method HTML copies; no current method-content re-review or official tool execution

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

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

Referenced principle: Define the outcome and effect of interest, then examine randomization, deviations, missing data, measurement and selective reporting.
Extent of review: Preserved method HTML copies; no current method-content re-review or official tool execution

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: Preserved method HTML copies; no current method-content re-review or official tool execution

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 rates.
Extent of review: Preserved method HTML copies; no current method-content re-review or official tool execution

What the statuses mean

Met: Status for necessary evidence confirmed after existing content review. No completion is declared in the current presentation.
Partly verified: Some information in the stored summary is linked into the table. External comparison/content review is not complete.
Unverified: The article leaves this unverified, or required material is absent from the current stored summary. This is distinct from zero, absence or safety.
Review incomplete: Existing content review incomplete.
Not reported: Not reported within the stored material actually read; not extended to the entire primary paper.
Inaccessible: Means an actual access failure. Access not attempted here is not assigned this state.
Not applicable: Not used as a substitute for an evidence gap.
Conflicting data: Requires an observed disagreement under the same comparison criteria; not automatically judged in this production.
Insufficient evidence for the conditions: Marks a gap in additional material required by the selected conditions; not a new efficacy grade.

Change history

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

The reader view and materials were prepared from the existing 26 items. No new clinical search, verification-status changes or scoring were performed.

The stored-material review date (Not recorded) and original evidence cut-off (2026-08-26) were retained unchanged.

Researcher downloads

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

View all item details

N01 · What is the existing verdict on ‘discontinuation inevitably causes relapse’?

Current findings: The selected existing question is ‘discontinuation inevitably causes relapse’, originally grade D, with a note that 44% of the discontinuation group did not relapse within 52 weeks. Subclaim score, status and axes are absent and separate from the parent's B70 for average relapse reduction.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Subclaim score, status and axes were originally absent; no new verdict is written. Review of existing content remains incomplete.
Reason for missing information: Subclaim score, status and axes were originally absent; no new verdict is written.
Required materials and conditions: Distinguishing the subclaim's D grade/note from parent B70 and the absence of score, status and axes
Materials to obtain first: Additional materials for the selected question or user feedback
Further research: Proposal: Separate source records for the inevitability claim and the parent's average effect are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Distinguishing the subclaim's D grade/note from parent B70 and the absence of score, status and axes must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Distinguishing the subclaim's D grade/note from parent B70 and the absence of score, status and axes and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are our own design

Related sources S01 S02

N02 · What period, people and exposure does ‘inevitably’ refer to?

Current findings: The original selected wording is ‘discontinuation inevitably causes relapse’. ANTLER actually compared tapering to placebo in adults with long-term use and remission who were considering stopping, using first-relapse data over 52 weeks. The 52-week period is not extended to a lifetime or every form of discontinuation.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Materials establishing inevitability for every person, period or discontinuation method are absent from this preserved scope. Review of existing content remains incomplete.
Reason for missing information: Materials establishing inevitability for every person, period or discontinuation method are absent from this preserved scope.
Required materials and conditions: Distinguishing an all-person or inevitability claim from the actual 52-week taper-to-placebo conditions
Materials to obtain first: Direct materials specifying period, population and actual exposure, if supplied
Further research: Proposal: Materials separating the claim's time, population and exposure scope are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Distinguishing an all-person or inevitability claim from the actual 52-week taper-to-placebo conditions must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Distinguishing an all-person or inevitability claim from the actual 52-week taper-to-placebo conditions and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M03 §3.1, §3.2.1–3.2.4: principles for clarifying the question; detailed separation rules are Chamgap's own design; M03 §3.2.1; detailed population conditions are Chamgap's own design; M03 §3.2.2–3.2.3; reverse labeling and test adaptations are Chamgap's own design; M03 §3.2.1–3.2.4; dose, duration and effect-modification details are Chamgap's own design

Related sources S01 S02

N03 · Is the 44% without relapse stated directly in the original text?

Current findings: The value that 44% of the discontinuation group did not relapse within 52 weeks is directly stated in the existing reader answer and subclaim note. It was not generated by calculating a new complementary proportion from 56%, and is not changed to absence of relapse over another period.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Individual adherence, restarting, censoring, clinical characteristics and subsequent course among those without relapse remain unverified. Review of existing content remains incomplete.
Reason for missing information: Individual adherence, restarting, censoring, clinical characteristics and subsequent course among those without relapse remain unverified.
Required materials and conditions: Preserving the original no-relapse wording, period and unit of the proportion
Materials to obtain first: Materials on the no-relapse group, follow-up, actual exposure and timing
Further research: Proposal: Materials linking observed absence of relapse with individual courses are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Preserving the original no-relapse wording, period and unit of the proportion must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Preserving the original no-relapse wording, period and unit of the proportion and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M03 §3.2.4 and M15 §15.3.1–15.3.3; Question-specific outcome adaptation is Chamgap design; M08 Table 8.2.a, M15 §15.3 and M19 §19.1.2–19.2.4; Design-specific adaptation is Chamgap design; M03 §3.2.1–3.2.4; Dose, duration and effect-modifier details are Chamgap design

Related sources S01 S02

N04 · Does 56% relapse in the discontinuation group mean ‘inevitably’?

Current findings: ANTLER's original discontinuation result of 135/240 (56%), maintenance result of 92/238 (39%) and absolute difference of 17%p are average between-arm comparisons. They are not transferred to relapse in every individual who discontinues; the subclaim's D grade/note is preserved unchanged.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Individual probabilities, outcomes for all people and inevitability over other periods or populations remain unverified. Review of existing content remains incomplete.
Reason for missing information: Individual probabilities, outcomes for all people and inevitability over other periods or populations remain unverified.
Required materials and conditions: Distinguishing original 135/240 (56%), 92/238 (39%) and 17%p from inevitability wording
Materials to obtain first: Individual follow-up or prediction, or corresponding direct materials
Further research: Proposal: Separate materials on arm comparisons and claims about every person or individual are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Distinguishing original 135/240 (56%), 92/238 (39%) and 17%p from inevitability wording must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Distinguishing original 135/240 (56%), 92/238 (39%) and 17%p from inevitability wording and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are Chamgap's own design; M03 §3.2.4; Chamgap's own limits on extension

Related sources S01 S02

N05 · Do the population and recruitment conditions include every patient with depression?

Current findings: Adults from 150 UK general practices felt well enough to consider stopping. They had at least 2 previous episodes or at least 2 years of treatment, with specific study conditions involving long-term use of four drugs.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Exact remission criteria, age, baseline risk, exclusions and the course without relapse under other population conditions remain unverified. Review of existing content remains incomplete.
Reason for missing information: Exact remission criteria, age, baseline risk, exclusions and the course without relapse under other population conditions remain unverified.
Required materials and conditions: Conditions involving 150 practices, long-term medication, remission and 2 episodes/2 years
Materials to obtain first: Eligibility, exclusions, baseline tables and direct materials under other conditions
Further research: Proposal: Materials linking eligibility conditions with individual outcomes are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Conditions involving 150 practices, long-term medication, remission and 2 episodes/2 years must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Conditions involving 150 practices, long-term medication, remission and 2 episodes/2 years and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M03 §3.2.1; Detailed population conditions are Chamgap design; M03 §3.2.1–3.2.4; Dose, duration and effect-modifier details are Chamgap design

Related sources S01 S02

N06 · Is study ‘discontinuation’ the same as complete or immediate stopping?

Current findings: The original trial switched users of specified drugs to matching placebo after tapering over 1~2 months. This is not converted into abrupt-stopping exposure, every drug or dose, or outcomes of individuals who completely stopped. Study conditions are not made into tapering or dosing instructions.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Individual actual tapering, exposure, concomitant treatment and stopping or restarting times remain unverified. Review of existing content remains incomplete.
Reason for missing information: Individual actual tapering, exposure, concomitant treatment and stopping or restarting times remain unverified.
Required materials and conditions: Historical scope of tapering over 1~2 months, switching to placebo and actual exposure
Materials to obtain first: Records of actual exposure, tapering and concomitant treatment
Further research: Proposal: Materials linking allocation conditions with actual behavior are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Historical scope of tapering over 1~2 months, switching to placebo and actual exposure must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Historical scope of tapering over 1~2 months, switching to placebo and actual exposure and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M03 §3.2.2–3.2.3; Reverse-direction labels and assessment adaptation are Chamgap design; M03 §3.2.3 and M08 §8.2.2–8.2.3; Chamgap application

Related sources S01 S02

N07 · Do 39% restarting and 52% adherence identify those without relapse?

Current findings: Original values state 52% adherence in the discontinuation group and that 39% restarted a clinician-prescribed antidepressant before the trial ended. These people are not assumed to be the same as the 44% without relapse; no new overlap is calculated.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Individual cross-classification of restarting or adherence with relapse or absence of relapse, timing and reasons remains unverified. Review of existing content remains incomplete.
Reason for missing information: Individual cross-classification of restarting or adherence with relapse or absence of relapse, timing and reasons remains unverified.
Required materials and conditions: Relationship between actual exposure or restarting in the discontinuation group and the no-relapse group
Materials to obtain first: Individual linked materials on relapse, restarting, adherence and time
Further research: Proposal: Materials separating absence of relapse in the allocated group from actual exposure pathways are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Relationship between actual exposure or restarting in the discontinuation group and the no-relapse group must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Relationship between actual exposure or restarting in the discontinuation group and the no-relapse group and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed

Related sources S01 S02

N08 · Can individual outcomes after actual stopping be separated from the allocation effect?

Current findings: The allocated comparison of 478 participants and original HR are study results for maintenance versus a taper-followed-by-placebo strategy. No new estimate is made of a pure effect among people who completely stopped, inevitable relapse, or the proportion without relapse and without restarting.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Causal or temporal analysis by actual exposure, crossover, rescue treatment and denominators remains unverified. Review of existing content remains incomplete.
Reason for missing information: Causal or temporal analysis by actual exposure, crossover, rescue treatment and denominators remains unverified.
Required materials and conditions: Distinguishing the randomized comparison's estimand from individual and actual-exposure effects
Materials to obtain first: Materials on exposure, crossover and event timing, and the prespecified analysis plan
Further research: Proposal: Materials distinguishing allocation effects from actual-exposure effects are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Distinguishing the randomized comparison's estimand from individual and actual-exposure effects must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Distinguishing the randomized comparison's estimand from individual and actual-exposure effects and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M08 §8.2.2, M15 §15.3.1; our own application; M03 §3.2.3, M08 §8.2.2–8.2.3; our own application

Related sources S01 S02

N09 · How does primary first relapse differ from symptom worsening and withdrawal?

Current findings: ANTLER's primary endpoint is time to first depression relapse within 52 weeks, and the parent describes relapse assessed using a symptom scale. Withdrawal symptoms, other transient worsening and recurrent episodes are not merged into the same event as relapse or inevitability.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Details of the relapse instrument, threshold, assessment schedule, withdrawal distinction, first event and censoring remain unverified. Review of existing content remains incomplete.
Reason for missing information: Details of the relapse instrument, threshold, assessment schedule, withdrawal distinction, first event and censoring remain unverified.
Required materials and conditions: Event definitions for first relapse within 52 weeks, symptom instruments and withdrawal
Materials to obtain first: Relapse and withdrawal definitions, assessment and adjudication materials, and SAP
Further research: Proposal: Materials distinguishing events from symptoms and recurrent outcomes are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Event definitions for first relapse within 52 weeks, symptom instruments and withdrawal must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Event definitions for first relapse within 52 weeks, symptom instruments and withdrawal and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptation to each question is internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M08 Table 8.2.a, M04 §4.6.3; internal application

Related sources S01 S02

N10 · How are 478 randomized, 468 in time-to-event analysis and 10 with missing timing related?

Current findings: The preserved wording states 478 randomized and 468 in the primary time-to-event analysis, with 10 lacking timing (6 maintenance/4 discontinuation) excluded from the primary analysis but included in absolute relapse counts. Missing-data participants are not newly classified as all having relapsed or all having had no relapse.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Exact timing, reasons for missingness, individual exposure and censoring for the 10 participants, and follow-up details for those without relapse remain unverified. Review of existing content remains incomplete.
Reason for missing information: Exact timing, reasons for missingness, individual exposure and censoring for the 10 participants, and follow-up details for those without relapse remain unverified.
Required materials and conditions: 238 maintenance/240 discontinuation, missing timing in 6/4, and denominator-specific scope
Materials to obtain first: Flow diagram and records of events, missing timing and follow-up
Further research: Proposal: Materials linking relapse or no-relapse observations by denominator are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for 238 maintenance/240 discontinuation, missing timing in 6/4, and denominator-specific scope must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish 238 maintenance/240 discontinuation, missing timing in 6/4, and denominator-specific scope and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M08 Table 8.2.a, M15 §15.3 and M19 §19.1.2–19.2.4; Design-specific adaptation is Chamgap design; M08 §8.2.2 and M15 §15.3.1; Chamgap application

Related sources S01 S02

N11 · Do best- and worst-case missing-data assumptions test relapse in everyone?

Current findings: The original statement that best- and worst-case missing-data analyses remained in the same direction concerns the arm comparison. It is not converted into relapse in everyone, individual discontinuation outcomes, or resolution of all missing-data bias.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Actual values, CIs and denominators under each assumption, pathways without relapse and temporal materials remain unverified. Review of existing content remains incomplete.
Reason for missing information: Actual values, CIs and denominators under each assumption, pathways without relapse and temporal materials remain unverified.
Required materials and conditions: Distinguishing the original direction of sensitivity analyses from the inevitability question
Materials to obtain first: Sensitivity tables, assumptions and prespecified plan
Further research: Proposal: Separate materials on sensitivity of arm comparisons and individual inevitability are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Distinguishing the original direction of sensitivity analyses from the inevitability question must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Distinguishing the original direction of sensitivity analyses from the inevitability question and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M08 Table 8.2.a, M15 §15.3 and M19 §19.1.2–19.2.4; Design-specific adaptation is Chamgap design; M08 §8.2.2 and M15 §15.3.1; Chamgap application; M15 §15.3.1–15.3.3; Chamgap application

Related sources S01 S02

N12 · Is the discontinuation-versus-maintenance HR 2.06 a probability of inevitability?

Current findings: The original discontinuation-versus-maintenance HR 2.06 (1.56~2.70), P<.001 is a time-to-event comparison. It is not changed into a value meaning 100% probability of relapse or relapse in a particular person. No maintenance-versus-discontinuation reciprocal, new RR or effect is calculated.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Model, censoring, proportional hazards, individual prediction and CIs for absolute outcomes remain unverified. Review of existing content remains incomplete.
Reason for missing information: Model, censoring, proportional hazards, individual prediction and CIs for absolute outcomes remain unverified.
Required materials and conditions: Separate units for HR, CI, P, event proportions and individual probabilities
Materials to obtain first: Original HR model and SAP, and individual prediction materials
Further research: Proposal: Materials linking comparative estimands and individual prediction are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Separate units for HR, CI, P, event proportions and individual probabilities must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Separate units for HR, CI, P, event proportions and individual probabilities and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are Chamgap's own design; M08 §8.2.2, M15 §15.3.1; Chamgap's own application; M15 §15.3.1–15.3.3; Chamgap's own application

Related sources S01 S02

N13 · What gaps do withdrawal symptoms and awareness of allocation leave in an inevitability interpretation?

Current findings: The preserved wording gives 12-week DESS means of 3.1 versus 1.3, the original difference of 1.9 (1.5~2.3), and greater awareness of allocation in the discontinuation group. Some withdrawal may have been misclassified as relapse, but the magnitude is undetermined. No new conclusion is made that all relapse was withdrawal.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Misclassified cases, original model and denominators, allocation-guessing figures, and temporal relationships between withdrawal and relapse remain unverified. Review of existing content remains incomplete.
Reason for missing information: Misclassified cases, original model and denominators, allocation-guessing figures, and temporal relationships between withdrawal and relapse remain unverified.
Required materials and conditions: Original scope of 12-week modified DESS, possible misclassification and allocation awareness
Materials to obtain first: Withdrawal and relapse items, original tables, masking and adjudication records
Further research: Proposal: Materials distinguishing withdrawal from relapse and recording allocation awareness are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Original scope of 12-week modified DESS, possible misclassification and allocation awareness must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Original scope of 12-week modified DESS, possible misclassification and allocation awareness and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M08 Table 8.2.a, M03 §3.2.4; internal application; M19 §19.1.2–19.2.4; finer distinctions are internally designed; design-specific harm questions in M19 §19.2; details of temporal relationships are internally designed

Related sources S01 S02

N14 · Is 39% relapse during maintenance a different question from inevitability after discontinuation?

Current findings: The parent and related wording that 39% relapsed despite maintenance concerns the complete-prevention question. It is not transferred to the denominator of ‘discontinuation inevitably causes relapse’ or to relapse outcomes for other individuals.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Individual pathways during maintenance or discontinuation and original subgroup prediction materials remain unverified. Review of existing content remains incomplete.
Reason for missing information: Individual pathways during maintenance or discontinuation and original subgroup prediction materials remain unverified.
Required materials and conditions: Boundary between the other arm's result and the related complete-prevention question
Materials to obtain first: Individual courses by arm and direct materials for the separate question
Further research: Proposal: Materials separating average reduction, complete prevention and inevitability claims are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Boundary between the other arm's result and the related complete-prevention question must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Boundary between the other arm's result and the related complete-prevention question and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed

Related sources S01 S02

N15 · Does absence of relapse within 52 weeks certify lifelong freedom from relapse or safe discontinuation?

Current findings: The 44% without relapse is original observational wording within 52 weeks. It is not extended to lifelong freedom from relapse, safe discontinuation for every person or a guarantee of individual treatment choice. The original account states that the trial did not identify who could discontinue safely.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Long-term follow-up, individual risk, withdrawal, restarting and other safety outcomes remain unverified. Review of existing content remains incomplete.
Reason for missing information: Long-term follow-up, individual risk, withdrawal, restarting and other safety outcomes remain unverified.
Required materials and conditions: Actual observation period and gaps beyond observation or in individual safety
Materials to obtain first: Follow-up beyond observation and individual prediction or safety materials
Further research: Proposal: Separate materials on gaps beyond the time or individual scope are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Actual observation period and gaps beyond observation or in individual safety must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Actual observation period and gaps beyond observation or in individual safety and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M03 §3.2.1–3.2.4; dose, duration and effect-modification details are our own design; M19 §19.1.2–19.2.4; own application

Related sources S01 S02

N16 · Can those who will remain without relapse be identified beforehand?

Current findings: The preserved wording states that ANTLER reported average relapse reduction and did not distinguish people who could discontinue safely. No individual prediction rule is created from original drug, history or duration conditions alone.
Verification status: Unverified
Materials actually read: Summary read; external material unread
Why unverified: The information currently required remains unverified in the preserved summary. Validated individual models, prespecified subgroups and external validation in other populations remain unverified in these authoring materials. Review of existing content remains incomplete.
Reason for missing information: Validated individual models, prespecified subgroups and external validation in other populations remain unverified in these authoring materials.
Required materials and conditions: Distinguishing group comparisons from validated individual prediction and subgroup information
Materials to obtain first: Individual prediction, prespecified subgroup or external-population materials, if supplied
Further research: Proposal: Separate materials linking average effects and individual prediction are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Distinguishing group comparisons from validated individual prediction and subgroup information must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Distinguishing group comparisons from validated individual prediction and subgroup information and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M03 §3.2.1–3.2.4; dose, duration and effect-modification details are our own design

Related sources S01 S02

N17 · Are the NEJM and HTA citations independent trials?

Current findings: S01 NEJM PMID34587384 and S02 NIHR HTA PMID34842135 report the same ANTLER trial. They share the first evidence record's 478 and 468 participants and withdrawal, adherence and missing-data results. The two reports are not counted as 2 independent trials or two participant populations.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Original tables, analyses and correspondence between the two reports remain externally unread. Review of existing content remains incomplete.
Reason for missing information: Original tables, analyses and correspondence between the two reports remain externally unread.
Required materials and conditions: Relationship between the same ANTLER trial, the first evidence record, and the main and detailed reports
Materials to obtain first: Linkage table for shared results and trial registration across the two reports
Further research: Proposal: Materials on multiple-report relationships within the same trial are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Relationship between the same ANTLER trial, the first evidence record, and the main and detailed reports must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Relationship between the same ANTLER trial, the first evidence record, and the main and detailed reports and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application; data collection and selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are internally designed

Related sources S01 S02

N18 · Do average meta-analysis results directly answer ‘inevitably’?

Current findings: Kato's maintenance result of 20.9% versus placebo 39.7%, OR .38 (.33~.43), P<.00001 synthesizes varied maintenance trials. An average relapse difference is not transferred to direct evidence that every person relapses after stopping. The preserved wording that does not count it as an independent replication of ANTLER's primary-care decision is retained.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Periods, populations, events, inclusion denominators, overlap, individual prediction and heterogeneity remain unverified. Review of existing content remains incomplete.
Reason for missing information: Periods, populations, events, inclusion denominators, overlap, individual prediction and heterogeneity remain unverified.
Required materials and conditions: Differences between Kato's 40 trials and 8890 participants, proportions or OR, and the actual original question
Materials to obtain first: Inclusion and exclusion tables, trial characteristics, periods, denominators and individual materials
Further research: Proposal: Materials separating pooled averages from claims about every person or individual are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Differences between Kato's 40 trials and 8890 participants, proportions or OR, and the actual original question must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Differences between Kato's 40 trials and 8890 participants, proportions or OR, and the actual original question and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M03 §3.2.4 and M15 §15.3.1–15.3.3: question-specific outcome adaptation is in-house; M04 §4.6.1–4.6.2 and M15 §15.3.1: in-house application; M03 §3.2.4: in-house extension boundaries.

Related sources S03

N19 · Do people and reports overlap across the review, ANTLER and related sheets?

Current findings: This sheet shares the same ANTLER trial and review summary as the 52-week relapse-reduction sheet; NEJM and HTA report the same trial. The 40 trials with 8890 participants, 478 participants and two sheets or reports are not added as independent trials or total participants.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Unique clinical totals and review inclusion or overlap relationships are not established and remain unrecorded. Review of existing content remains incomplete.
Reason for missing information: Unique clinical totals and review inclusion or overlap relationships are not established and remain unrecorded.
Required materials and conditions: Shared preserved summary, two subclaim sheets, and report, trial and synthesis relationships
Materials to obtain first: Trial, report, population and review inclusion lists, if supplied
Further research: Proposal: Records of material families and overlap relationships are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Shared preserved summary, two subclaim sheets, and report, trial and synthesis relationships must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Shared preserved summary, two subclaim sheets, and report, trial and synthesis relationships and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: Study/report distinction in M04 §4.6.1–4.6.2; Cohort/outcome linkage is Chamgap application; M04 §4.6.1–4.6.2 and M15 §15.3.1; Chamgap application

Related sources S01 S02 S03

N20 · Have registration and prespecified endpoints actually been read?

Current findings: ANTLER's ‘ISRCTN15969819 · EudraCT2015-004210-26’ is preserved unchanged. Kato's ‘Not applicable’ is preserved review wording. Identifiers or wording alone do not establish that registration or plans were read, or that prespecified individual prediction was validated.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Registration amendment history, protocol, SAP, subgroup and missing-data plans remain unread; access was not attempted. Review of existing content remains incomplete.
Reason for missing information: Registration amendment history, protocol, SAP, subgroup and missing-data plans remain unread; access was not attempted.
Required materials and conditions: Original ISRCTN/EudraCT identifiers and unread registration or plans
Materials to obtain first: Registration or plan copies, or user-supplied materials
Further research: Proposal: Links between prespecified plans, versions and reports are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Original ISRCTN/EudraCT identifiers and unread registration or plans must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Original ISRCTN/EudraCT identifiers and unread registration or plans and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M04 §4.5–4.6 material collection/selection principles; acquisition/reading separation and hyperlink specifications are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application

Related sources S01 S02 S03

N21 · Do public support and unreported product or COI information certify independence?

Current findings: ANTLER's NIHR HTA 13/115/48, PRIMENT core support and UCL sponsor, and Kato's Japanese research grants are preserved unchanged. The historical wording that neither report described donated trial drug or placebo is not changed into actual absence or certification of independence in this work.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Support and product contracts, employee authors, conflicts of interest, study and manuscript roles, and support for included trials in the review remain unverified. Review of existing content remains incomplete.
Reason for missing information: Support and product contracts, employee authors, conflicts of interest, study and manuscript roles, and support for included trials in the review remain unverified.
Required materials and conditions: NIHR, PRIMENT, UCL, product provision, employees, conflicts of interest and review funding
Materials to obtain first: Original materials on support, provision, authors, contributions and conflicts of interest
Further research: Proposal: Materials on funding, support types and actual roles are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for NIHR, PRIMENT, UCL, product provision, employees, conflicts of interest and review funding must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish NIHR, PRIMENT, UCL, product provision, employees, conflicts of interest and review funding and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: Chamgap's own conditions for independence and attribution. The official methodological sections used in this example do not validate every detail of these items.

Related sources S01 S02 S03

N22 · Are withdrawal, serious events and absence of relapse the same safety outcome?

Current findings: Original serious adverse events of 9 maintenance participants (4%)/8 discontinuation participants (3%), 0 deaths or suicide attempts in both groups, and increased withdrawal at 12 weeks are recorded separately. Absence of relapse is not converted into no adverse effects, safe discontinuation or 0 long-term harm.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Event definitions, collection, safety denominators, exposure, follow-up, CIs and long-term or drug-specific harms remain unverified. Review of existing content remains incomplete.
Reason for missing information: Event definitions, collection, safety denominators, exposure, follow-up, CIs and long-term or drug-specific harms remain unverified.
Required materials and conditions: Scope of harm collection, 12-week withdrawal, 9/8 participants and 0 deaths or suicide attempts
Materials to obtain first: Endpoint-specific safety, withdrawal, exposure, denominator and follow-up materials
Further research: Proposal: Materials separating absence of relapse from other harm outcomes are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Scope of harm collection, 12-week withdrawal, 9/8 participants and 0 deaths or suicide attempts must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Scope of harm collection, 12-week withdrawal, 9/8 participants and 0 deaths or suicide attempts and link the materials required for the selected question to currently available materials.
Application exceptions: Addresses gaps in withdrawal and safety materials for the selected relapse question. Relapse, absence of relapse or original safety wording is not used to assess overall safety or an individual's ability to discontinue, or to generate harm incidence or guidance on maintenance, discontinuation, tapering, dosing or treatment.
Referenced methods: M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; finer distinctions are internally designed; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretation boundary. M19 principles are referenced; no official causality tool was executed

Related sources S01 S02

N23 · Does this answer questions about other drugs, abrupt stopping or new treatment settings?

Current findings: The original materials' four drugs, specified doses and study taper over 1~2 months are historical exposure. No new verdict is made on inevitability after abrupt stopping, other drugs or doses, acute treatment, other diseases or ages, or every treatment setting.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Direct relapse and safety materials under conditions outside the scope remain unverified. Review of existing content remains incomplete.
Reason for missing information: Direct relapse and safety materials under conditions outside the scope remain unverified.
Required materials and conditions: Original four drugs, study taper, remission, long-term use and questions outside that scope
Materials to obtain first: Direct materials under separate conditions, if supplied
Further research: Proposal: Separate questions and material scopes by exposure and population are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Original four drugs, study taper, remission, long-term use and questions outside that scope must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Original four drugs, study taper, remission, long-term use and questions outside that scope and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M03 §3.2.1; detailed population conditions are our own design; M03 §3.2.2–3.2.3; reverse-direction labels and test adaptations are our own design; M03 §3.2.1–3.2.4; dose, duration and effect-modification details are our own design

Related sources S01 S02

N24 · What preserved summaries and external materials have actually been read?

Current findings: ‘Summary read’ means the complete preserved Korean and English texts, original figures, bibliography and subclaims were used for production. External papers, registration, protocol, SAP, support and COI materials remain ‘not read’; historical statements about reading clinical originals or URLs are not inherited as new reading.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. External access, link or click tests and comparison against original external materials were not performed. Review of existing content remains incomplete.
Reason for missing information: External access, link or click tests and comparison against original external materials were not performed.
Required materials and conditions: Preserved summary, original NEJM/HTA/Kato URLs and unread external materials
Materials to obtain first: User-provided original materials and actual reading records.
Further research: Proposal: Records of acquisition, reading and versions by material are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Preserved summary, original NEJM/HTA/Kato URLs and unread external materials must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Preserved summary, original NEJM/HTA/Kato URLs and unread external materials and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M04 §4.5–4.6 material collection/selection principles; acquisition/reading separation and hyperlink specifications are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design

Related sources S01 S02 S03

N25 · Are original subclaim D, parent B70, Korean/English texts, dates and empty values preserved?

Current findings: Selected D grade/note and English wording, parent B70, Caution, Korean and English texts, axes with unrecorded precision, false, 2026-08-26, and empty correction and deliberation values are preserved unchanged. Absent subclaim score, status and axes are not filled from parent values.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. The historical production did not translate the verdict text, create a new verdict or correction, or update external evidence. Review of existing content remains incomplete.
Reason for missing information: The historical production did not translate the verdict text, create a new verdict or correction, or update external evidence.
Required materials and conditions: Whole original preservation, absence, unrecorded precision, false values and correction history
Materials to obtain first: Correction originals or user comments
Further research: Proposal: Links between original versions, dates and the selected subclaim sheet are proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Whole original preservation, absence, unrecorded precision, false values and correction history must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Whole original preservation, absence, unrecorded precision, false values and correction history and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design

Related sources S01 S02 S03

N26 · Do applied conditions and completed production mean existing content review is complete?

Current findings: Preservation, freezing and application of conditions, case production and content review are separate records. Existing content review remains incomplete; counts of written records are not totals of unique clinical trials or participants.
Verification status: Partly verified
Materials actually read: Summary read; external material unread
Why unverified: Only relevant preserved-summary information has been recorded; detailed original materials remain unread and existing content review is incomplete. Existing content review remains incomplete. Additional content review, testing, screen checks and link tests were not conducted during the original production. Review of existing content remains incomplete.
Reason for missing information: Existing content review remains incomplete. Additional content review, testing, screen checks and link tests were not conducted during the original production.
Required materials and conditions: Distinguishing preservation, freezing and application of conditions, case production and incomplete content review
Materials to obtain first: Comments on existing content review and additional preserved materials
Further research: Proposal: A history of production versions, conditions and user corrections is proposed; no new investigation, calculation or trial was conducted.
Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
Conditions for verification: Relevant original materials and analysis scope for Distinguishing preservation, freezing and application of conditions, case production and incomplete content review must be supplied and unverified matters distinguished. Preserved wording is linked during this work; review of existing content remains incomplete.
Why this condition is needed: Production item to distinguish Distinguishing preservation, freezing and application of conditions, case production and incomplete content review and link the materials required for the selected question to currently available materials.
Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
Referenced methods: M04 §4.5–4.6 material collection/selection principles; acquisition/reading separation and hyperlink specifications are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design

Related sources S01 S02 S03