Alpha¹ by KaimenConfidential

Kaimen Rigor review

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

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

DOI: 10.1056/NEJMoa2400327
Record issued: 2026-08-10
Engine: 7.29.0
Exported: 2026-09-22

Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/d32b5a8a-949f-4606-a723-d968b4f4790b is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

3.5 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern−0.5★
ReportingData & code availability not met−0.5★
ReportingEthical approvals partially met−0.25★
ReportingKey resources partially met−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.29.0Source: full text

Not verified in this report

Declared data/code links were not checked for liveness or content.

Biggest issues

01Data and code not shared
highDisclosurereviewer-assessedFull detail
No data availability statement is present, and no code sharing is mentioned. The trial registration is provided but does not constitute a data availability statement.

Findings by category

101ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions 03AuthenticityNone found 304DisclosureReporting gaps 05AvailabilityNone found · partly checked 06Copyedit1 minor suggestion

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 published paper describes a well-designed Phase 3 randomized controlled trial with a strong scientific premise and robust statistical analysis. Key strengths include detailed methods, clear randomization, and comprehensive reporting of outcomes and limitations. However, significant reporting gaps exist regarding data availability, specific ethical approval details, and full identification of investigational products.

All eight dimensions were evaluated. Reviewers largely agreed on the status and evidence for each dimension. Minor divergences in 'biological variables' and 'statistical analysis' checklists were resolved by weighing the evidence, leading to a 'pass' for both. The statistics component confirmed consistency for one reported test.

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.

Agent-written checks— recomputed from reported CIs / ratios by code the agent wrote

CONSISTENTreported p < .041 · recomputed p = .047Reviewer 1
Hazard ratio for 9BCLLfxZ vs control for time to unfavorable outcome.
“In the 9BCLLfxZ group, time to unfavorable outcome was longer than in the control (hazard ratio=0.48 [95% CI: 0.23-0.98])”
Find in source
Taken as given: The reported hazard ratio and 95% CI correspond to a Cox regression model.; The CI is two-sided 95% and the estimate is 0.48.; The p-value is derived from the CI using the normal approximation: p = pCI(estimate, low, high, log=1) which computes the two-tailed p-value from the CI.
Method: pCI(0.48, 0.23, 0.98, 1) computes the two-tailed p-value from the reported hazard ratio and its 95% CI using the formula for ratio parameters.
How we recomputed it: pCI(0.48, 0.23, 0.98, 1)

lowinternal contradiction
The abstract lists four regimens as non-inferior in the mITT population (9BCLLfxZ, 9BLMZ, 9BDLLfxZ, 9DCMZ) but the conclusion states 'three all oral shortened regimens', creating a minor inconsistency.
In mITT, the control had 80.7% favorable outcomes and 9BCLLfxZ (RD: 9.8% [0.9, 18.7]), 9BLMZ (RD: 8.3% [-0.8, 17.4]), 9BDLLfxZ (RD: 4.6% [-4.9, 14.1]), and 9DCMZ (RD: 2.5% [-7.5, 12.5]) were non-inferior. // Conclusions: Consistent results across all analyses support the non-inferior efficacy of these three all oral shortened regimens.
Discussionreviewer’s wording

Overstated conclusions

1 finding · worst low

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.

Conclusions only partially backed by the presented evidenceAssessed

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

partialReviewer 1
Consistent results across all analyses support the non-inferior efficacy of three all oral shortened regimens.
The abstract reports four non-inferior regimens in mITT, but the conclusion states three. The evidence supports three regimens being non-inferior across both mITT and PP, but the wording is inconsistent with the abstract listing.
Evidence: Table 2 and Figure 2 show risk differences and CIs for each regimen. The text states that 9DCMZ was not non-inferior in PP, while the other three were.
“Consistent results across all analyses support the non-inferior efficacy of these three all oral shortened regimens.”
ConclusionFind in source
supportedReviewers 1, 2
The endTB trial increases treatment options for MDR/RR-TB.
The trial successfully identified three new all-oral regimens that are non-inferior to the standard of care, thereby expanding the available treatment options.
Evidence: Primary efficacy results show non-inferiority of three regimens in both mITT and PP. Discussion states 'These findings support the use of three new, all-oral, shorter MDR/RR-TB regimens in addition to BPaLM.'
“The endTB trial increases treatment options for MDR/RR-TB.”
DiscussionFind in source
supportedReviewer 1
Three regimens (9BLMZ, 9BCLLfxZ, and 9BDLLfxZ) were non-inferior compared to the standard of care.
The primary and secondary analyses consistently show non-inferiority for these three regimens in both mITT and PP populations.
Evidence: Table 2 shows risk differences and CIs: 9BLMZ RD 8.3% (95% CI -0.8, 17.4), 9BCLLfxZ RD 9.8% (0.9, 18.7), 9BDLLfxZ RD 4.6% (-4.9, 14.1). The lower bounds exceed -12%.
9BLMZ (RD: 8.3% [-0.8, 17.4]), 9BCLLfxZ (RD: 9.8% [0.9, 18.7]), 9BDLLfxZ (RD: 4.6% [-4.9, 14.1])
Table 2reviewer’s wording
supportedReviewer 1
These findings support the use of three new, all-oral, shorter MDR/RR-TB regimens in addition to BPaLM.
The evidence supports the use of these regimens, and the paper appropriately recommends them as additional options.
Evidence: Discussion directly states this recommendation based on the efficacy and safety results.
“These findings support the use of three new, all-oral, shorter MDR/RR-TB regimens in addition to BPaLM.”
DiscussionFind in source
supportedReviewer 1
Two bedaquiline-sparing regimens (9DCMZ and 9DCLLfxZ) were not supported for use.
The results show higher rates of unfavorable outcomes due to positive culture in these regimens, leading to the conclusion that they are not recommended.
Evidence: Table 2 shows 7.5% and 10.2% positive culture in 9DCMZ and 9DCLLfxZ, respectively, compared to 0.8% in control. The discussion states 'the overall assessment of these regimens does not support their use'.
“Two bedaquiline-sparing regimens (9DCMZ and 9DCLLfxZ) were examined: the overall assessment of these regimens does not support their use compared to a control that commonly contained bedaquiline.”
DiscussionFind in source
supportedReviewer 2
Four experimental regimens (9BCLLfxZ, 9BLMZ, 9BDLLfxZ, 9DCMZ) were non-inferior to the control in the mITT population.
The paper provides risk differences and 95% CIs for each comparison, with the lower bounds above -12%.
Evidence: Table 2 and Figure 2 show risk differences and CIs: 9BCLLfxZ RD 9.8% (95%CI 0.9, 18.7), 9BLMZ RD 8.3% (95%CI -0.8, 17.4), etc.
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.
Table 2reviewer’s wording
supportedReviewer 2
Three all-oral shortened regimens (9BLMZ, 9BCLLfxZ, 9BDLLfxZ) are supported by consistent results across all analyses.
The paper states that these three regimens were non-inferior in both mITT and PP analyses, and sensitivity analyses support the findings.
Evidence: Results section and Figure 2 show consistent results across mITT and PP populations for these three regimens.
“Consistent results across all analyses support the non-inferior efficacy of these three all oral shortened regimens.”
DiscussionFind in source
supportedReviewer 2
Bayesian response-adaptive randomization permitted identification of multiple non-inferior TB regimens in a single study.
The paper describes the adaptive randomization and notes that it allowed testing multiple regimens simultaneously, leading to the identification of four non-inferior regimens in mITT.
Evidence: Methods describe the adaptive design, and Results show that multiple regimens were found non-inferior.
“Bayesian response-adaptive randomization permitted identification of multiple non-inferior TB regimens in a single study.”
DiscussionFind in source
supportedReviewer 2
The proportion of participants experiencing grade 3 or higher adverse events was similar across the regimens.
The safety results show that the percentage of participants with at least one grade 3 or higher AE ranged from 54.8% to 62.7%, with overlapping ranges.
Evidence: Table 3 reports the numbers: 54.8% to 62.7% across groups.
“The number with at least one Grade 3 or higher AE ranged from 54.8% (9BLMZ) to 61.4% (9BDLLfxZ) in experimental groups and was 62.7% in the control.”
Table 3Find in source

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

ADEQUATESurrogate endpoint
The primary endpoint is a composite clinical/microbiologic outcome (favorable outcome at week 73 based on negative sputum cultures and clinical/radiologic evolution, with death and treatment failure considered unfavorable), which is a standard hard outcome for TB treatment trials.
“The primary outcome was favorable outcome at week 73 defined by two negative sputum culture results or by favorable bacteriologic, clinical, and radiologic evolution.”
Find in source
ADEQUATEEffect size
The experimental regimens produced favorable outcomes in 85-90% of participants, with risk differences vs control of +9.8, +8.3, +4.6, and +2.5 percentage points against a non-inferiority margin of -12 percentage points; the authors anchor this to clinical meaningfulness by comparing to global averages and the BPaLM regimen.
“These three regimens each produced favorable outcomes in more than 85% of participants at week 73; this represents an improvement over global averages and is comparable to trial results with the BPaLM regimen (88%).”
Find in source

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

3 findings · worst high

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 and code not sharedAssessed
Ethics/consent reporting incompleteAssessed
Key resources under-identified (antibodies, cell lines, RRIDs)Assessed

Eight Dimensions5 pass · 2 warn · 1 fail

The introduction cites the global burden of RR-TB, historical poor treatment outcomes, and prior observational studies and trials (STREAM 2, TB-PRACTECAL). It acknowledges the limitations of previous evidence (e.g., 'poor treatment options and low-quality evidence plagued care') and explains how the trial addresses these gaps through a randomized, concurrently controlled design. The hypothesis follows logically from the cited evidence.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper clearly establishes the scientific foundation, citing prior research on MDR/RR-TB treatment and the need for randomized controlled trials, and provides a logical rationale for the study.

Evidence

“For decades, poor treatment options and low-quality evidence plagued care for multidrug/rifampin-resistant tuberculosis (MDR/RR-TB). The advent of new anti-TB drugs and enhanced funding now permit randomized controlled trials of shortened, all-oral treatment for MDR/RR-TB.”

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 ¶3Find in source

paraphrase[Methods, Design and oversight]

“The paper describes a randomized, controlled, internally controlled design, which is essential for high-certainty evidence, thus addressing the limitation of prior observational studies.”

PASSReviewer 2· 95% conf

The paper establishes a clear scientific foundation by citing prior observational studies and the need for RCT evidence, and provides a logical rationale linking the premise to the trial objectives.

Evidence

“For decades, poor treatment options and low-quality evidence plagued care for multidrug/rifampin-resistant tuberculosis (MDR/RR-TB).”

Introduction ¶1Find in source

“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 ¶2Find in source

paraphrase[Introduction, paragraph 3]

“The endTB (Evaluating Newly Approved Drugs for Multidrug-resistant Tuberculosis) trial (ClinicalTrials.gov identifier NCT02754765), reported here, evaluated the efficacy and safety of five 9-month, all-oral treatment regimens compared to the evolving standard of care for fluoroquinolone-susceptible RR-TB.”

Randomization method (Bayesian response-adaptive randomization with monthly updates) is detailed. The unit of randomization is the individual participant. The open-label design is justified by the treatment duration difference between groups. A power analysis with sample size of 750 provides 80% power for non-inferiority. Inclusion/exclusion criteria are listed. Pre-specified analysis populations (mITT, PP) handle missing data and exclusions. Other criteria (replicate_distinction, controls, independent_replication) are not applicable for a human RCT.

Sub-criteria

controlsN/A

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 study design is rigorous: randomization method is described (Bayesian response-adaptive randomization with centralized system), sample size calculation is provided, and inclusion/exclusion criteria are clearly defined. The open-label design is justified.

Evidence

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

MethodsFind 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

paraphrase[Methods, Participants]

PASSReviewer 2· 95% conf

The study design is rigorous for a Phase 3 non-inferiority trial, with clear randomization, sample size justification, inclusion/exclusion criteria, and handling of 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

“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

paraphrase[Methods, Participants]

“Individuals aged 15 years or older who had fluoroquinolone-susceptible, pulmonary RR-TB confirmed by WHO-endorsed rapid tests were enrolled... The trial excluded persons with baseline: pregnancy; elevated liver enzymes; uncorrectable electrolyte disorders; QT interval corrected by the Fridericia formula (QTcF) ≥450 msec; resistance or prior exposure (≥30 days) to bedaquiline, delamanid, clofazimine, or linezolid; and ≥15 days treatment with any second-line anti-tuberculosis drug during the current TB episode.”

Table 1 reports sex, median age, BMI, HIV status, hepatitis, diabetes, smear grade, cavitation, and TB extent. Both sexes are included (37.8% female), so sex_justified is not applicable. Age and weight (BMI) are reported. Health status (ECOG, comorbidities) is detailed. Demographics include country and TB history. The study is human, so species/strain/housing criteria are not applicable.

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· 95% conf

Biological variables are well-reported: sex, age, BMI, health status (HIV, comorbidities), and demographics (country, TB severity) are provided in baseline table.

Evidence

paraphrase[Table 1]

“Female sex – no. (%) | 264 (37.8%) | Median age, years (IQR) [range] | 32.0 (23.0;44.0) [15.0;71.0]”

paraphrase[Table 1]

“HIV, positive – no. (%) | 98 (14.0%) | Cavitation – no. (%) | 399 (57.1%)”

PASSReviewer 2· 85% conf

Sex, age, weight (via BMI), and health status are reported. Race/ethnicity is not explicitly reported, but comorbidities and country-level demographics are provided.

Evidence

“Overall, 264 (37.8%) participants were female.”

ResultsFind in source

“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

paraphrase[Table 1, Baseline characteristics]

“Study country – no. (%) ... Georgia 2 (1.7%), India 8 (6.8%), ...”

The ethics statement mentions 'institutional/ethics review boards that supervise each consortium member and each participating site' but does not name the boards or give protocol numbers, which is reported_but_inadequate per the grading criteria. Written informed consent is reported adequately. Regulatory compliance (e.g., Declaration of Helsinki) is not explicitly stated, making it not_reported. Lacking the named IRB and regulatory compliance statement, the dimension does not meet 'all applicable adequate' for a pass.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementINADEQUATE

regulatory complianceNOT REPORTED

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 90% conf

The paper states that the study was approved by institutional/ethics review boards and that written informed consent was obtained, but it does not name the specific IRB or provide protocol numbers, and does not explicitly state compliance with a recognized regulatory framework.

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, Design and oversight]

Regulatory compliance statement is absent.

WARNReviewer 2· 90% conf

Informed consent is adequately reported, but the ethics approval statement is vague and does not name a specific reviewing body or provide a protocol number, and no explicit regulatory compliance statement is included.

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, Design and oversight; Discussion]

No regulatory compliance statement is found.

The paper names the drugs (bedaquiline, delamanid, etc.) but does not provide manufacturer, formulation, strength, or specific dose regimen for each drug. The software (Stata 17.0) is identified. Antibodies, cell lines, mycoplasma testing, and organisms are not applicable as this is a clinical trial without wet-lab components. Since the investigational product is not fully identified (only names), reagents_identified is reported_but_inadequate. Software is adequate. Thus 1 of 2 applicable criteria are adequate, resulting in a warn.

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

The investigational drugs are named but not fully identified (manufacturer, formulation, dose), and statistical software is identified. Other resource criteria are not applicable.

Evidence

paraphrase[Methods, Randomization and treatment]

“Regimen combinations were: 9BLMZ, 9BCLLfxZ, 9BDLLfxZ, 9DCLLfxZ, and 9DCMZ.”

“All analyses were performed in Stata version 17.0.”

Statistical analysisFind in source

WARNReviewer 2· 80% conf

The investigational drugs are named but not identified with manufacturer, formulation, or dose regimen. The statistical software is adequately 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

absence[Methods, Randomization and treatment]

Dose regimens are not reported in the main text.

The primary analysis uses binomial regression with identity link to estimate risk differences and 95% CIs, consistent with non-inferiority testing. Cox regression is used for time-to-event analysis with proportional hazards assumption tested via Schoenfeld residuals. Effect sizes are reported with CIs (e.g., RD: 9.8% [95%CI: 0.9, 18.7]). Software is Stata 17.0. Data presentation includes per-group counts and percentages in tables, and forest plots. No arithmetic errors were detected in the provided tables. Since the analysis is estimation-based, exact_p_values is not applicable.

Sub-criteria

tests namedADEQUATE

exact p valuesN/A

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Statistical methods are well-described: tests are named (binomial regression, Cox regression), assumptions are partially verified (proportional hazards tested), effect sizes are reported with 95% CIs, and software is identified. p-values are not used as primary inference (CI-based non-inferiority), so exact_p_values is not applicable. Data presentation is adequate with tables, figures, and per-group n.

Evidence

“Risk differences were estimated using a binomial regression model (generalized linear model for a binomial outcome with an identity link function).”

Statistical analysisFind in source

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

Statistical analysisFind in source

paraphrase[Results, Efficacy results]

“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.”

PASSReviewer 2· 85% conf

Statistical tests are named, effect sizes with CIs are reported, software is identified, and data presentation is adequate. No p-values are reported (estimation-based), and assumptions verification is partially addressed. No arithmetic errors are detected.

Evidence

“Risk differences were estimated using a binomial regression model (generalized linear model for a binomial outcome with an identity link function).”

Statistical analysisFind in source

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

Statistical analysisFind in source

paraphrase[Results, Efficacy results]

“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.”

The paper does not include a data availability statement. It mentions ClinicalTrials.gov identifier NCT02754765 for trial registration, but no statement about where individual patient data or aggregated data can be accessed. Code sharing is not mentioned. For a clinical trial, a data availability statement is required; its absence results in a fail. Repository deposit and accession numbers are not applicable (patient-level data, no sequencing data).

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositN/A

data availability statementNOT REPORTED

Per reviewer (2) — the votes behind the verdict

FAILReviewer 1· 95% conf

No data availability statement is present, and no code sharing is mentioned. The trial registration is provided but does not constitute a data availability statement.

Evidence

absence[Entire paper]

No data availability statement found.

absence[Entire paper]

No code sharing mentioned.

FAILReviewer 2· 90% conf

No data availability statement is provided in the paper, and no repository deposit or code sharing is mentioned.

Evidence

absence[Entire paper]

No data availability statement is present.

absence[Entire paper]

No repository deposit or accession numbers are provided.

absence[Entire paper]

No code sharing is mentioned.

Methods are comprehensive, including design, participants, randomization, procedures, outcomes, and analysis. Trial registration number (NCT02754765) is given. The paper states it follows the CONSORT extension for adaptive designs. Primary and secondary outcomes are reported in tables and text, including negative results (e.g., 9DCLLfxZ not non-inferior). Limitations (open-label, WHO guideline changes) are discussed. Conclusions are appropriate to the evidence. Funding sources and a disclosure statement 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 manuscript is well-reported: methods are detailed, trial registration is provided, CONSORT extension for adaptive designs is referenced, all outcomes are reported, limitations are discussed, conclusions are proportional, and funding/COI are disclosed.

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

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

DiscussionFind in source

PASSReviewer 2· 95% conf

The manuscript provides detailed methods, trial registration, a reporting guideline, reports all outcomes, discusses limitations, draws proportional conclusions, and includes funding and conflict of interest 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

DiscussionFind in source

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

ClinicalTrials.gov

NCT02754765

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).

NO DOI
Global tuberculosis report 2023
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
WHO Treatment guidelines for drug-resistant tuberculosis – 2016 update
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Rapid Communication: Key changes to the treatment of drug-resistant tuberculosis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
WHO consolidated guidelines on tuberculosis. Module 4: treatment - drug-resistant tuberculosis treatment, 2022 update
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Clinical and Research Information on Drug-Induced Liver Injury: Linezolid
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Consolidated guidelines on tuberculosis Module 5: management of tuberculosis in children and adolescents
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Management of Drug-Resistant Tuberculosis in Pregnant and Peripartum People: A Field Guide
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

Copyediting

1 minor

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

No major wording or formatting errors. 1 minor suggestion below.

1 copyedit issue flagged: mostly consistency.

MINORconsistencyAbstract vs. Conclusions
“In mITT, the control had 80.7% favorable outcomes and 9BCLLfxZ (RD: 9.8% [0.9, 18.7]), 9BLMZ (RD: 8.3% [-0.8, 17.4]), 9BDLLfxZ (RD: 4.6% [-4.9, 14.1]), and 9DCMZ (RD: 2.5% [-7.5, 12.5]) were non-inferior. // Conclusions: Consistent results across all analyses support the non-inferior efficacy of these three all oral shortened regimens.”
→ Harmonize the number: either clarify that three regimens were non-inferior in both mITT and PP (excluding 9DCMZ), or adjust the abstract to list four and explain that 9DCMZ was not supported in PP.
The abstract lists four non-inferior regimens in mITT, but the conclusion says 'three'. This inconsistency could confuse readers.

Kaimen Rigor Action ItemsFinal pass before journal submission

This published work demonstrates strong methodological rigor but has notable reporting deficiencies that an informed reader should consider. The absence of a data availability statement is a significant concern for reproducibility and transparency. Additionally, the lack of specific ethical approval details and full drug identification could warrant a correction or erratum to enhance the paper's robustness and utility.

1.
HIGHdata code
Add a data availability statement in the Methods or a separate section, specifying a concrete access route for the trial data (e.g., a managed-access platform or a data access committee) with conditions and timeframe.
The absence of a data availability statement is a critical reporting gap for a clinical trial, hindering reproducibility and transparency.
2.
HIGHethics
In the Methods section, state the name of the specific institutional review board that approved the study and include the protocol number for each ethics committee approval.
Specific identification of IRBs and protocol numbers is essential for ethical transparency and verification of oversight.
3.
HIGHethics
Include an explicit statement of compliance with a recognized regulatory framework (e.g., Declaration of Helsinki, ICH-GCP) in the Ethics section.
Explicitly stating regulatory compliance ensures adherence to international ethical standards for human research.
4.
HIGHrigor
In the Methods section, specify the manufacturer, formulation, strength, and dose regimen for each investigational drug (e.g., bedaquiline 400 mg daily, linezolid 600 mg daily).
Full identification of investigational products is crucial for reproducibility and understanding the exact intervention studied.
5.
HIGHcopyedit
Harmonize the number of non-inferior regimens mentioned in the Abstract and the Conclusions section.
Inconsistent reporting of key findings can confuse readers and undermine confidence in the results.
6.
MEDIUMreporting
Consider adding a code sharing statement, even if no custom code was used, to confirm that analyses were performed with standard software packages.
A code sharing statement enhances transparency regarding the analytical process, even for standard software.
7.
MEDIUMreporting
Provide the dosing details for the control group regimens (e.g., drug names, doses, durations) in the main text or supplement, made more accessible.
Detailed information on control group regimens is necessary for a complete understanding of the study design and comparability.
8.
MEDIUMreporting
Include a CONSORT flow diagram in the main manuscript (currently referenced in supplement) to improve transparency of participant flow.
A CONSORT flow diagram in the main text provides immediate clarity on participant recruitment, allocation, and follow-up.
9.
LOWrigor
In the statistical analysis section, add a brief statement on the verification of assumptions for the binomial regression model (e.g., linearity, independence) or note that robust standard errors were used.
Explicitly addressing assumptions for all statistical models enhances the rigor and transparency of the analysis.
10.
LOWrigor
Report race/ethnicity of participants if collected, or justify its omission, in the demographics table.
Reporting race/ethnicity, or explaining its absence, contributes to a more complete demographic characterization of the study population.

Full text (43,130 chars)Analyzed: Aug 10, 2026

RigorReviewer 1

RigorReviewer 2

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

PreregistrationDeterministic check· no model (rule-based)

The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”

How stars are deducted

Reporting — 8 dimensionseach dimension that fully fails−½★
each dimension partially met−¼★
Statistics · Integrity · Claimseach serious problem−1★
each medium problem−½★
Citationseach retracted or unverifiable reference−¼★
Copyeditonly when the manuscript needs a full edit−½★

The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.

The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.

The eight reporting dimensions

Scientific PremisePrior work, rationale, and how it addresses gaps.

Study Design & RigorRandomization, blinding, power, controls, replication.

Biological VariablesSex, age, species/strain, housing, demographics.

Ethical ApprovalsIRB/IACUC approval, informed consent, regulatory compliance.

Key ResourcesAntibodies, cell lines, organisms, software — identified with persistent IDs.

Statistical ReportingNamed tests, exact p-values, effect sizes, plausible summary stats.

Data & Code AvailabilityAvailability statements, repositories, accession numbers, shared code.

Reporting TransparencyMethods, registration, guidelines, outcomes, limitations, funding/COI.

Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.

This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.

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

DOI

10.1056/NEJMoa2400327

Record issued

2026-08-10

Engine

7.29.0

Exported

2026-09-22