Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.

Name: Kaimen Rigor review — Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.
Item: Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.
Rating: 96
Author: Alpha1

Guglielmetti L, Khan U, Velásquez GE, Gouillou M, Abubakirov A, Baudin E, Berikova E, Berry C, Bonnet M, Cellamare M, Chavan V, Cox V, Dakenova Z, de Jong BC, Ferlazzo G, Karabayev A, Kirakosyan O, Kiria N, Kunda M, Lachenal N, Lecca L, McIlleron H, Motta I, Toscano SM, Mushtaque H, Nahid P, Oyewusi L, Panda S, Patil S, Phillips PPJ, Ruiz J, Salahuddin N, Garavito ES, Seung KJ, Ticona E, Trippa L, Vasquez DEV, Wasserman S, Rich ML, Varaine F, Mitnick CD, endTB Clinical Trial Team

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Kaimen Rigor review — 4.25★ (Strong), 0 critical, 2 high issues for “Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.”

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Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 15, 2026

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Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.

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DOI

10.1056/NEJMoa2400327

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.

Paper source

Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.

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Links back to this Kaimen Rigor review.

Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 15, 2026

Kaimen Rigor review

Kaimen Rigor reviewed

4.25 / 5

Strong — minor issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern−0.5★
ReportingData & code availability partially met−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Not verified in this report

No data or code availability links were detected to verify.

Findings by category

101ArithmeticNumerical inconsistencies 02OverreachNone found 03AuthenticityNone found 104DisclosureReporting gaps 05AvailabilityNone found · partly checked 06Copyedit5 minor suggestions

This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This is a well-conducted and well-reported Phase 3 randomized non-inferiority trial with rigorous design, clear statistical methods, and comprehensive reporting of ethics, demographics, and outcomes. The main weakness is the lack of a clear data availability statement and code sharing, which is a common but important transparency gap.

Both reviewers agreed on study type (interventional) and on all dimension statuses except minor differences in checklist sub-items (e.g., limitations addressed, regulatory compliance, data availability statement). The synthesis adopted the more specific evidence where available. Non-applicable sub-criteria (e.g., animal-related, cell lines) were excluded. The statistics verification covered only 1 test (hazard ratio) and found it consistent; other statistics were not machine-verified.

Numerical inconsistencies

1 finding · worst low

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Internal contradictions in the reported numbersAssessed

Recomputed 1 test: 1 consistent, 0 inconsistent; 1 via agent-written checks.

Overstated conclusions

None found

Conclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.

Checked — nothing surfaced.

5 major claims checked against the paper's own evidence: all adequately supported.

Efficacy claim is anchored to an adequate endpoint and a meaningful effect.

Data authenticity concerns

None found

An adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.

Checked — nothing surfaced.

Reporting gaps

1 finding · worst medium

Required detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.

Data/code availability incompleteAssessed

Eight Dimensions7 pass · 1 warn

The introduction cites WHO statistics and historical reliance on expert opinion and observational studies, and it references the launch of endTB and other trials. The rationale for comparing five all-oral regimens to the standard of care is clearly linked to the need for shorter, safer, and more effective treatments. The paper does not explicitly discuss limitations of prior research in detail, but the design addresses the lack of randomized evidence.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise by citing prior observational evidence and the need for randomized trials, and it provides a logical rationale for the study objectives.

Evidence

“Historically, poor response was largely due to the suboptimal 18-to 24-month regimens, which included injected aminoglycosides/polypeptides and caused substantial toxicity. Regimens were devised based on expert opinion and pooled analyses of observational studies because no evidence was available from contemporary randomized, controlled clinical trials.”

Introduction ¶1Find in source

“In 2016-2017, hope of improved evidence and treatment emerged with the launch of endTB and two other multi-country, randomized, controlled trials to examine whether shorter, all-oral regimens of 6- or 9-months duration could safely and efficaciously treat multidrug-resistant (MDR)/RR-TB in adults and adolescents.”

Introduction ¶2Find in source

absence[Introduction]

Limitations of prior research are not explicitly discussed.

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise by citing prior research and explaining the rationale for the trial.

Evidence

Introduction ¶1Find in source

Introduction ¶2Find in source

Randomization used Bayesian response-adaptive randomization with a centralized system. The unit of randomization is the participant. Blinding is described as open-label with a rationale and mitigation strategies. A sample size calculation with power and non-inferiority margin is provided. Inclusion/exclusion criteria are detailed. Outlier handling is addressed through pre-specified analysis populations (mITT and PP). Controls are the standard of care. Independent replication is not applicable for a single pivotal trial.

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The trial design is rigorous with clear randomization, blinding considerations, power analysis, and pre-specified analysis populations.

Evidence

paraphrase[Methods, Randomization and treatment]

“Treatment assignment was made by Bayesian randomization, adapted monthly by interim treatment response: 8-week culture and 39-week efficacy. Assignment occurred through a centralized interactive randomization system.”

“Site trial staff and participants were not blinded to treatment-group assignment because of the treatment-duration difference between experimental and control groups. To mitigate risks of bias, we concealed treatment assignment and randomization probabilities from laboratory staff and central investigators.”

LimitationsFind in source

“A sample size of 750 afforded 80% power for non-inferiority (one-sided type I error rate: 2.5%) of 3 experimental regimens in the mITT and 2 in the PP populations.”

Statistical analysisFind in source

PASSReviewer 2· 95% conf

The trial design is rigorous with clear randomization, blinding considerations, power analysis, and predefined analysis populations.

Evidence

“Treatment assignment was made by Bayesian randomization, adapted monthly by interim treatment response: 8-week culture and 39-week efficacy.”

MethodsFind in source

LimitationsFind in source

“A sample size of 750 afforded 80% power for non-inferiority (one-sided type I error rate: 2.5%) of 3 experimental regimens in the mITT and 2 in the PP populations.”

Statistical analysisFind in source

Sex is reported for all participants (37.8% female). Age is reported with median and range. Health status is captured through HIV, diabetes, hepatitis, and other comorbidities. Demographics are detailed in Table 1. Since both sexes are enrolled, sex_justified is not applicable. Species/strain and housing conditions are not applicable for a human trial.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Demographic and clinical characteristics are well reported, including sex, age, HIV status, and comorbidities.

Evidence

“Overall, 264 (37.8%) participants were female. Median age was 32.0 years, 25 (3.6%) were less than 18 years of age; 98 (14.0%) were living with HIV, 568 (81.3%) had sputum smear results graded 1+ or above, and 57.1% had cavitation on chest radiograph.”

ResultsFind in source

“Female sex – no. (%) | 41 (34.7%) | 37 (32.2%) | 55 (45.1%) | 38 (32.2%) | 45 (42.1%) | 48 (40.3%) | 264 (37.8%)”

Table 1Find in source

PASSReviewer 2· 90% conf

Demographic and clinical characteristics are well reported, including sex, age, and comorbidities.

Evidence

ResultsFind in source

The paper states that the study was approved by institutional/ethics review boards and that all participants provided written informed consent. This satisfies both irb_ethics_statement and informed_consent. Regulatory compliance is implied through adherence to the Declaration of Helsinki and CONSORT guidelines, though not explicitly named.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approval and informed consent are clearly documented.

Evidence

“The study was approved by institutional/ethics review boards that supervise each consortium member and each participating site.”

MethodsFind in source

“All participants provided written informed consent.”

MethodsFind in source

absence[Methods]

Regulatory compliance is not explicitly named.

PASSReviewer 2· 95% conf

Ethical approval and informed consent are clearly documented.

Evidence

“The study was approved by institutional/ethics review boards that supervise each consortium member and each participating site. All participants provided written informed consent.”

MethodsFind in source

The trial uses named drugs (bedaquiline, delamanid, linezolid, levofloxacin, moxifloxacin, clofazimine, pyrazinamide) with dosing regimens described. The control regimen is described as per WHO guidelines. Statistical software (Stata 17.0) is identified. Antibodies, cell lines, and mycoplasma testing are not applicable. Organisms are identified as M. tuberculosis.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedADEQUATE

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The investigational drugs are identified with names and dosing, and statistical software is identified.

Evidence

“Experimental regimens were 39 weeks (9 months) long and contained 4-5 drugs among the following: bedaquiline (B), delamanid (D), clofazimine (C), linezolid (L), levofloxacin (Lfx), moxifloxacin (M), and pyrazinamide (Z).”

MethodsFind in source

“All analyses were performed in Stata version 17.0.”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The investigational drugs are identified, and statistical software is specified.

Evidence

paraphrase[Methods, Randomization and treatment; Statistical Analysis]

The primary analysis uses binomial regression with risk differences and 95% CIs. Cox regression is used for time-to-event. Exact p-values are reported for the hazard ratio (0.48 [95% CI: 0.23-0.98]). Assumptions are addressed via Schoenfeld residuals. Software is identified. Data presentation includes forest plots and tables with per-group n. Mathematical plausibility checks are not applicable for large-N continuous outcomes.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical methods are appropriate and well-described, with exact p-values and confidence intervals reported.

Evidence

paraphrase[Methods, Statistical Analysis]

“Risk differences were estimated using a binomial regression model (generalized linear model for a binomial outcome with an identity link function). Cox regression was used to estimate crude hazard ratios for time from randomization to unfavorable outcome and 95% confidence intervals (CI) for each experimental group.”

paraphrase[Results, Efficacy results]

“In the 9BCLLfxZ group, time to unfavorable outcome was longer than in the control (hazard ratio=0.48 [95% CI: 0.23-0.98]).”

“Schoenfeld residuals were used to test the proportional hazards assumption.”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

Statistical methods are appropriate and well-described, with effect sizes and confidence intervals reported.

Evidence

“Risk differences (RD) were: 9.8% (95%CI, 0.9 to 18.7) for 9BCLLfxZ, 8.3% (95%CI, -0.8 to 17.4) for 9BLMZ, 4.6% (95%CI, -4.9 to 14.1) for 9BDLLfxZ, and 2.5% (95%CI, -7.5 to 12.5) for 9DCMZ”

ResultsFind in source

The paper states that the protocol is available at NEJM.org and that data are available from the corresponding author on reasonable request, but no repository or accession numbers are provided. Since this is a clinical trial with patient data, managed access is acceptable, but the statement lacks a concrete mechanism or timeframe. No custom code is mentioned.

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositN/A

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

A data availability statement is present but vague, and no code is shared.

Evidence

“All authors vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol (available at nejm.org).”

MethodsFind in source

absence[Entire paper]

No code sharing is mentioned.

WARNReviewer 2· 80% conf

Data availability is not explicitly stated; the paper mentions supplementary material but no repository or access mechanism.

Evidence

absence[Entire paper]

No data availability statement

The trial is registered at ClinicalTrials.gov (NCT02754765). The CONSORT extension for adaptive designs is referenced. All pre-specified outcomes are reported, including negative results. Limitations are discussed in detail. Conclusions are proportional to the evidence. Funding sources and disclosure forms are provided.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The trial is registered, follows CONSORT, reports all outcomes, discusses limitations, and provides funding and COI statements.

Evidence

“ClinicalTrials.gov (http://ClinicalTrials.gov) : NCT02754765”

AbstractFind in source

“The Consolidated Standards of Reporting Trials extension for adaptive design trials guided this trial report.”

MethodsFind in source

“Site trial staff and participants were not blinded to treatment-group assignment because of the treatment-duration difference between experimental and control groups.”

LimitationsFind in source

PASSReviewer 2· 90% conf

The trial is registered, reporting guidelines are followed, and limitations are discussed.

Evidence

paraphrase[Abstract; Methods, Design and oversight]

“ClinicalTrials.gov (http://ClinicalTrials.gov) : NCT02754765 ; The Consolidated Standards of Reporting Trials extension for adaptive design trials guided this trial report.”

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

Broken references and links

None found · partly checked

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.

Checked 39 references by DOI: 32 verified — 7 no DOI (shown, not verified).

Copyediting

5 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 5 minor suggestions below.

5 copyedit issues flagged: mostly consistency, clarity, typo.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is robust and well-reported; an informed reader should weigh the minor transparency gap in data availability and the lack of code sharing. No erratum is warranted based on the integrity checks, but the authors should consider providing a clearer data access mechanism and sharing analysis code to enhance reproducibility.

1.
HIGHdata code
Add a detailed data availability statement in the Methods or a dedicated section, specifying a managed-access platform (e.g., YODA, Vivli) or a data-access committee with conditions and timeframe.
The current statement is vague and does not provide a concrete mechanism for accessing de-identified participant data, which is a transparency gap for a data-driven clinical trial.
2.
HIGHdata code
Deposit the statistical analysis code (e.g., Stata do-files) in a public repository (e.g., GitHub, Zenodo) with a DOI and reference it in the paper.
Sharing analysis code enhances reproducibility and is expected for clinical trials; the paper currently mentions no code sharing.
3.
MEDIUMreporting
Explicitly state compliance with the Declaration of Helsinki or ICH-GCP in the Methods to strengthen regulatory compliance reporting.
Reviewer 1 noted that regulatory compliance is not explicitly named; adding this statement would fully satisfy the ethical approvals dimension.
4.
MEDIUMreporting
Clarify in the data availability statement that the full protocol and statistical analysis plan are available at NEJM.org, as currently only implied.
This would make the availability of key trial documents explicit and improve transparency.
5.
MEDIUMcopyedit
Standardize confidence interval formatting throughout the paper (e.g., '95% CI' with a space and consistent use of 'to' vs. comma).
The copyedit pass flagged inconsistent spacing and formatting in CI notation, which is a minor but noticeable consistency issue.
6.
MEDIUMcopyedit
Rephrase the safety results sentence to 'The percentage of participants with at least one Grade 3 or higher AE ranged...' for clarity.
The copyedit pass noted a minor clarity improvement in the safety results section.
7.
LOWcopyedit
Specify the test used for proportional hazards assumption (e.g., based on scaled Schoenfeld residuals) in the Methods.
The copyedit pass suggested this minor clarity improvement.
8.
LOWreporting
Add a note on the availability of the statistical analysis plan or protocol amendments to enhance transparency.
This would further strengthen the reporting transparency dimension.

Full text (43,130 chars)Analyzed: Aug 15, 2026

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Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.

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DOI

10.1056/NEJMoa2400327

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b0d7488b5ab28eba4f1d2dd3a987c06aa51e82e755b4dffb3a18620d3d0be2fe

Verify via API

Issued Aug 15, 2026Engine 7.39.0

Alpha1 assesses methodological rigor, not the importance of the findings. See how we calibrate →

Kaimen Rigor review

Kaimen Rigor reviewed

4.25 / 5

Strong — minor issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern−0.5★
ReportingData & code availability partially met−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Not verified in this report

No data or code availability links were detected to verify.

Findings by category

101ArithmeticNumerical inconsistencies 02OverreachNone found 03AuthenticityNone found 104DisclosureReporting gaps 05AvailabilityNone found · partly checked 06Copyedit5 minor suggestions

Numerical inconsistencies

1 finding · worst low

Internal contradictions in the reported numbersAssessed

Recomputed 1 test: 1 consistent, 0 inconsistent; 1 via agent-written checks.

Overstated conclusions

None found

Checked — nothing surfaced.

5 major claims checked against the paper's own evidence: all adequately supported.

Efficacy claim is anchored to an adequate endpoint and a meaningful effect.

Data authenticity concerns

None found

Checked — nothing surfaced.

Reporting gaps

1 finding · worst medium

Data/code availability incompleteAssessed

Eight Dimensions7 pass · 1 warn

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise by citing prior observational evidence and the need for randomized trials, and it provides a logical rationale for the study objectives.

Evidence

Introduction ¶1Find in source

Introduction ¶2Find in source

absence[Introduction]

Limitations of prior research are not explicitly discussed.

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise by citing prior research and explaining the rationale for the trial.

Evidence

Introduction ¶1Find in source

Introduction ¶2Find in source

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The trial design is rigorous with clear randomization, blinding considerations, power analysis, and pre-specified analysis populations.

Evidence

paraphrase[Methods, Randomization and treatment]

LimitationsFind in source

“A sample size of 750 afforded 80% power for non-inferiority (one-sided type I error rate: 2.5%) of 3 experimental regimens in the mITT and 2 in the PP populations.”

Statistical analysisFind in source

PASSReviewer 2· 95% conf

The trial design is rigorous with clear randomization, blinding considerations, power analysis, and predefined analysis populations.

Evidence

“Treatment assignment was made by Bayesian randomization, adapted monthly by interim treatment response: 8-week culture and 39-week efficacy.”

MethodsFind in source

LimitationsFind in source

“A sample size of 750 afforded 80% power for non-inferiority (one-sided type I error rate: 2.5%) of 3 experimental regimens in the mITT and 2 in the PP populations.”

Statistical analysisFind in source

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Demographic and clinical characteristics are well reported, including sex, age, HIV status, and comorbidities.

Evidence

ResultsFind in source

“Female sex – no. (%) | 41 (34.7%) | 37 (32.2%) | 55 (45.1%) | 38 (32.2%) | 45 (42.1%) | 48 (40.3%) | 264 (37.8%)”

Table 1Find in source

PASSReviewer 2· 90% conf

Demographic and clinical characteristics are well reported, including sex, age, and comorbidities.

Evidence

ResultsFind in source

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approval and informed consent are clearly documented.

Evidence

“The study was approved by institutional/ethics review boards that supervise each consortium member and each participating site.”

MethodsFind in source

“All participants provided written informed consent.”

MethodsFind in source

absence[Methods]

Regulatory compliance is not explicitly named.

PASSReviewer 2· 95% conf

Ethical approval and informed consent are clearly documented.

Evidence

“The study was approved by institutional/ethics review boards that supervise each consortium member and each participating site. All participants provided written informed consent.”

MethodsFind in source

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedADEQUATE

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The investigational drugs are identified with names and dosing, and statistical software is identified.

Evidence

MethodsFind in source

“All analyses were performed in Stata version 17.0.”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The investigational drugs are identified, and statistical software is specified.

Evidence

paraphrase[Methods, Randomization and treatment; Statistical Analysis]

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical methods are appropriate and well-described, with exact p-values and confidence intervals reported.

Evidence

paraphrase[Methods, Statistical Analysis]

paraphrase[Results, Efficacy results]

“In the 9BCLLfxZ group, time to unfavorable outcome was longer than in the control (hazard ratio=0.48 [95% CI: 0.23-0.98]).”

“Schoenfeld residuals were used to test the proportional hazards assumption.”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

Statistical methods are appropriate and well-described, with effect sizes and confidence intervals reported.

Evidence

“Risk differences (RD) were: 9.8% (95%CI, 0.9 to 18.7) for 9BCLLfxZ, 8.3% (95%CI, -0.8 to 17.4) for 9BLMZ, 4.6% (95%CI, -4.9 to 14.1) for 9BDLLfxZ, and 2.5% (95%CI, -7.5 to 12.5) for 9DCMZ”

ResultsFind in source

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositN/A

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

A data availability statement is present but vague, and no code is shared.

Evidence

“All authors vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol (available at nejm.org).”

MethodsFind in source

absence[Entire paper]

No code sharing is mentioned.

WARNReviewer 2· 80% conf

Data availability is not explicitly stated; the paper mentions supplementary material but no repository or access mechanism.

Evidence

absence[Entire paper]

No data availability statement

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The trial is registered, follows CONSORT, reports all outcomes, discusses limitations, and provides funding and COI statements.

Evidence

“ClinicalTrials.gov (http://ClinicalTrials.gov) : NCT02754765”

AbstractFind in source

“The Consolidated Standards of Reporting Trials extension for adaptive design trials guided this trial report.”

MethodsFind in source

“Site trial staff and participants were not blinded to treatment-group assignment because of the treatment-duration difference between experimental and control groups.”

LimitationsFind in source

PASSReviewer 2· 90% conf

The trial is registered, reporting guidelines are followed, and limitations are discussed.

Evidence

paraphrase[Abstract; Methods, Design and oversight]

“ClinicalTrials.gov (http://ClinicalTrials.gov) : NCT02754765 ; The Consolidated Standards of Reporting Trials extension for adaptive design trials guided this trial report.”

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

Broken references and links

None found · partly checked

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.

Checked 39 references by DOI: 32 verified — 7 no DOI (shown, not verified).

Copyediting

5 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 5 minor suggestions below.

5 copyedit issues flagged: mostly consistency, clarity, typo.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
HIGHdata code
Add a detailed data availability statement in the Methods or a dedicated section, specifying a managed-access platform (e.g., YODA, Vivli) or a data-access committee with conditions and timeframe.
The current statement is vague and does not provide a concrete mechanism for accessing de-identified participant data, which is a transparency gap for a data-driven clinical trial.
2.
HIGHdata code
Deposit the statistical analysis code (e.g., Stata do-files) in a public repository (e.g., GitHub, Zenodo) with a DOI and reference it in the paper.
Sharing analysis code enhances reproducibility and is expected for clinical trials; the paper currently mentions no code sharing.
3.
MEDIUMreporting
Explicitly state compliance with the Declaration of Helsinki or ICH-GCP in the Methods to strengthen regulatory compliance reporting.
Reviewer 1 noted that regulatory compliance is not explicitly named; adding this statement would fully satisfy the ethical approvals dimension.
4.
MEDIUMreporting
Clarify in the data availability statement that the full protocol and statistical analysis plan are available at NEJM.org, as currently only implied.
This would make the availability of key trial documents explicit and improve transparency.
5.
MEDIUMcopyedit
Standardize confidence interval formatting throughout the paper (e.g., '95% CI' with a space and consistent use of 'to' vs. comma).
The copyedit pass flagged inconsistent spacing and formatting in CI notation, which is a minor but noticeable consistency issue.
6.
MEDIUMcopyedit
Rephrase the safety results sentence to 'The percentage of participants with at least one Grade 3 or higher AE ranged...' for clarity.
The copyedit pass noted a minor clarity improvement in the safety results section.
7.
LOWcopyedit
Specify the test used for proportional hazards assumption (e.g., based on scaled Schoenfeld residuals) in the Methods.
The copyedit pass suggested this minor clarity improvement.
8.
LOWreporting
Add a note on the availability of the statistical analysis plan or protocol amendments to enhance transparency.
This would further strengthen the reporting transparency dimension.

Full text (43,130 chars)Analyzed: Aug 15, 2026