Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.

Name: Kaimen Rigor review — Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.
Item: Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.
Rating: 96
Author: Alpha1

Cheng Y, Chen J, Zhang W, Xie C, Hu Q, Zhou N, Huang C, Wei S, Sun H, Li X, Yu Y, Lai J, Yang H, Fang H, Chen H, Zhang P, Gu K, Wang Q, Shi J, Yi T, Xu X, Ye X, Wang D, Xie C, Liu C, Zheng Y, Lin D, Zhuang W, Lu P, Yu G, Li J, Gu Y, Li B, Wu R, Jiang O, Wang Z, Wu G, Lin H, Zhong D, Xu Y, Shu Y, Wu D, Chen X, Wang J, Wang M, Yang R

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Kaimen Rigor review — 2.75★ (Weak), 0 critical, 2 high issues for “Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.”

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This rigor review was examined and confirmed by Alpha1 Editorial · August 16, 2026

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Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.

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DOI

10.1038/s41591-024-03132-1

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.

Paper source

Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.

Read full text (PMC)

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Links back to this Kaimen Rigor review.

Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 16, 2026

Kaimen Rigor review

Kaimen Rigor reviewed

2.75 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×4−2★
ReportingData & code availability partially met−0.25★

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

Biggest issues

01Other integrity concern
mediumAuthenticityreviewer-assessedFull detail
Trial NCT04234607 was first submitted to ClinicalTrials.gov on 2020-01-16, after the registered study start date of 2020-01. Retrospective registration means the protocol and outcomes were not on the public record before the study ran, which is what prospective registration exists to establish.
NCT04234607
reviewer’s wording

Findings by category

101ArithmeticNumerical inconsistencies 02OverreachNone found 103AuthenticityData authenticity concerns 104DisclosureReporting gaps 05AvailabilityNone found 06Copyedit6 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 rigorously designed and reported phase 3 randomized controlled trial with strong methodology: comprehensive blinding, adequate power, detailed statistical methods, and transparent reporting of outcomes and limitations. The main weakness is the vague data availability statement, which lacks a concrete access mechanism for de-identified data, and several minor copyedit issues including an incomplete sentence and a percentage typo.

Both reviewers independently scored all eight dimensions and agreed on every status; no divergence required reconciliation. The statistics verification covered only 4 recomputable tests (all consistent), so the broader statistical claims remain unverified. The integrity check flagged retrospective registration (submitted 2020-01-16 after study start 2020-01) as a medium concern, which is a transparency caveat rather than a rigor failure.

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 4 tests: 4 consistent, 0 inconsistent; 4 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.

4 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

1 finding · worst medium

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.

Other integrity concernAssessed

4 integrity concerns flagged (0 high).

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 four prior phase 3 trials (IMpower133, CASPIAN, CAPSTONE-1, ASTRUM-005) and discusses the failure of TIGIT inhibitors, establishing the premise. The rationale for combining anlotinib with PD-L1 inhibition is supported by preclinical and phase 1b data. Limitations of prior work are implicitly addressed by the trial design, though not explicitly framed as such.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study clearly establishes its scientific foundation by citing prior randomized trials and providing a logical rationale for combining anti-angiogenesis with immunochemotherapy.

Evidence

“four randomized, controlled phase 3 studies (IMpower133, CASPIAN, CAPSTONE-1 and ASTRUM-005) have reported significant improvements in median OS on the order of 2–4 months”

Introduction ¶1Find in source

“Anti-angiogenesis is known to augment the efficacy of ICIs in multiple cancer types”

Introduction ¶2Find in source

absence[Introduction]

Limitations of prior research are not explicitly discussed as such.

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise by citing prior randomized trials and providing a logical rationale for combining anti-angiogenesis with immunochemotherapy.

Evidence

“four randomized, controlled phase 3 studies (IMpower133, CASPIAN, CAPSTONE-1 and ASTRUM-005) have reported significant improvements in median OS on the order of 2–4 months”

Introduction ¶1Find in source

“Anti-angiogenesis is known to augment the efficacy of ICIs in multiple cancer types”

Introduction ¶2Find in source

absence[Introduction]

Limitations of prior work are not explicitly discussed as such.

Randomization method (central stratified randomization) and unit (patient) are described. Blinding is comprehensive, covering patients, investigators, reviewers, statisticians, and sponsor. Power analysis is provided (85% power, HR detection). Inclusion/exclusion criteria are detailed. Outlier handling is addressed through ITT and per-protocol analyses. Controls are appropriate (placebo and active comparator). 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: randomized, double-blind, placebo-controlled, with adequate sample size justification and clear inclusion/exclusion criteria.

Evidence

“Randomization was conducted by the central stratified randomization method, and stratified by ECOG PS (0 versus 1), brain metastases (‘yes’ or ‘no’) and liver metastases (‘yes’ or ‘no’).”

MethodsFind in source

“Patients and their families or guardians, investigators, local and central radiological reviewers, the study statistician, data management personnel who were involved in data cleaning and analysis of the data, and the study sponsor were masked to treatment allocation until the final database was locked.”

MethodsFind in source

“approximately 738 patients (combined sample size for PFS and OS) were needed for 1:1:1 randomization and to provide a power of 85% to detect an HR across treatment groups for disease progression or death at a two-sided significance level of 0.05.”

Statistical analysisFind in source

PASSReviewer 2· 95% conf

The trial design is rigorous with adequate randomization, blinding, power analysis, and inclusion/exclusion criteria.

Evidence

MethodsFind in source

Statistical analysisFind in source

Sex is reported for all groups. Age (median and range) is reported. Demographics include ECOG performance status, smoking status, and disease stage. Species/strain and housing conditions are not applicable. Sex justification is not applicable as both sexes are enrolled.

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

Key demographic and clinical characteristics are reported, including sex, age, and disease stage, which are adequate for a human trial.

Evidence

“Male | 209 (85.0) | 204 (83.3) | 207 (83.8)”

Table 1Find in source

“Median (range) | 62.0 (36–75) | 60.0 (32–75) | 63.0 (30–75)”

Table 1Find in source

paraphrase[Table 1]

“ECOG performance status, n (%) | 0 | 47 (19.1) | 47 (19.2) | 48 (19.4)”

PASSReviewer 2· 90% conf

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

Evidence

“Male | 209 (85.0) | 204 (83.3) | 207 (83.8)”

Table 1Find in source

“Median (range) | 62.0 (36–75) | 60.0 (32–75) | 63.0 (30–75)”

Table 1Find in source

paraphrase[Table 1]

“ECOG performance status, n (%) | 0 | 47 (19.1) | 47 (19.2) | 48 (19.4)”

The ethics statement names the Jinlin Province Cancer Hospital Institutional Review Board with an approval number. Written informed consent is stated. Compliance with Good Clinical Practice and Declaration of Helsinki is declared. This is a human trial, so IACUC is not applicable.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethics approval from a named IRB and informed consent are documented, along with regulatory compliance.

Evidence

“central approval was obtained from the Jinlin Province Cancer Hospital Institutional Review Board (ethics approval no. 201909-053-01).”

EthicsFind in source

“All patients provided written informed consent for participation before enrollment.”

EthicsFind in source

“The trial was conducted per the principles of Good Clinical Practice guidelines and the Declaration of Helsinki.”

EthicsFind in source

PASSReviewer 2· 95% conf

Ethics approval and informed consent are clearly documented.

Evidence

“central approval was obtained from the Jinlin Province Cancer Hospital Institutional Review Board (ethics approval no. 201909-053-01).”

EthicsFind in source

“All patients provided written informed consent for participation before enrollment.”

EthicsFind in source

“The trial was conducted per the principles of Good Clinical Practice guidelines and the Declaration of Helsinki.”

EthicsFind in source

The drugs are named with doses and regimens. The statistical software (SAS 9.4) is identified. Antibodies, cell lines, mycoplasma, and organisms are not applicable as this is a clinical trial without wet-lab assays. Reagents are scored against the investigational products, which are adequately described.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational products (benmelstobart, anlotinib, etoposide, carboplatin) are identified with dosing details, and statistical software is named.

Evidence

“Benmelstobart was given intravenously at a dose of 1,200 mg once daily on day 1 of each cycle. Anlotinib was given orally, once daily, at a dose of 12 mg for 2 weeks followed by 1 week off.”

MethodsFind in source

“The randomization list was generated by an independent statistician using a SAS statistical package (version 9.4, SAS Institute)”

MethodsFind in source

PASSReviewer 2· 85% conf

The investigational products are adequately identified, and statistical software is named.

Evidence

“Benmelstobart was given intravenously at a dose of 1,200 mg once daily on day 1 of each cycle. Anlotinib was given orally, once daily, at a dose of 12 mg for 2 weeks followed by 1 week off.”

MethodsFind in source

“The randomization list was generated by an independent statistician using a SAS statistical package (version 9.4, SAS Institute)”

MethodsFind in source

Tests are named (stratified log-rank, Cox model, Cochran–Mantel–Haenszel). Assumptions are handled by design (stratified analyses). Exact p-values are reported (e.g., P = 0.0002). Effect sizes with 95% CIs are provided. Software is identified. Data presentation includes Kaplan-Meier curves and forest plots. Mathematical plausibility checks were not performed due to large N and 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 effect sizes with confidence intervals.

Evidence

“Survival data were estimated with the Kaplan–Meier method and compared using the stratified log-rank test. HRs and associated 95% CIs were assessed using a stratified Cox proportional-hazards model”

Statistical analysisFind in source

paraphrase[Results, Primary endpoint of OS]

“HR, 0.61 (95% CI 0.47–0.79); P = 0.0002”

“median OS was greater in the benmelstobart and anlotinib plus EC group compared with the EC alone group (19.3 months (95% CI 14.2 to not estimable) versus 11.9 months (95% CI 10.7–13.4); hazard ratio (HR), 0.61 (95% CI 0.47–0.79); P = 0.0002)”

ResultsFind in source

PASSReviewer 2· 90% conf

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

Evidence

Statistical analysisFind in source

“hazard ratio 0.61; P = 0.0002”

ResultsFind in source

paraphrase[Results, Primary endpoint of OS]

“HR, 0.61 (95% CI 0.47–0.79)”

The data availability statement says all data required to interpret the claims are included in the article or uploaded, but does not specify a repository or access mechanism. Individual deidentified participant data are not shared due to reidentification risk. This is a controlled-access situation, but the statement lacks a concrete mechanism or platform, making it inadequate. Repository deposit and accession numbers are not applicable for patient-level data. Code sharing is not applicable as no bespoke code is mentioned.

Sub-criteria

code sharingN/A

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 exists but is vague, stating data are included in the article or supplementary, and individual participant data cannot be shared.

Evidence

“All data required to interpret, verify or build new research on the published claims are included in the article or uploaded in . We cannot share individual deidentified participant data owing to the risk of reidentification and loss of patient confidentiality.”

Data availabilityFind in source

WARNReviewer 2· 80% conf

A data availability statement exists but is vague, lacking a concrete access mechanism.

Evidence

Data availabilityFind in source

The trial is registered (NCT04234607). Methods are detailed. All primary and secondary endpoints are reported, including negative results (anlotinib plus EC OS). Limitations are discussed. Conclusions are proportional. Funding and competing interests are declared. Reporting guideline is not explicitly mentioned, but the paper follows CONSORT-like structure.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The manuscript is transparent: registered, reports all outcomes, discusses limitations, and provides funding and COI statements.

Evidence

“ClinicalTrials.gov identifier: NCT04234607”

AbstractFind in source

“Several limitations should be acknowledged. This study provided no direct comparison with the current standard-of-care immunochemotherapy.”

Discussion ¶8Find in source

paraphrase[Acknowledgements and Competing interests]

“This study was sponsored by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. ... We declare that none of the authors has competing financial or nonfinancial interests”

PASSReviewer 2· 90% conf

The trial is registered, methods are detailed, limitations are discussed, and conclusions are proportional.

Evidence

“ClinicalTrials.gov identifier: NCT04234607”

AbstractFind in source

“Several limitations should be acknowledged. This study provided no direct comparison with the current standard-of-care immunochemotherapy.”

Discussion ¶8Find in source

paraphrase[Acknowledgements and Competing interests]

“This study was sponsored by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. ... We declare that none of the authors has competing financial or nonfinancial interests”

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

Broken references and links

None found

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.

Checked — nothing surfaced.

Checked 29 references by DOI: 28 verified — 1 no DOI (shown, not verified).

2 data/code links checked; 2 live.

Copyediting

6 minor

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

No major wording or formatting errors. 6 minor suggestions below.

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

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is methodologically robust and the reported results are internally consistent for the tests that could be recomputed. An informed reader should weigh the retrospective registration timing and the lack of a concrete data-sharing mechanism as transparency limitations, but neither undermines the core findings. The minor copyedit issues (incomplete data-availability sentence, percentage typo) are cosmetic and do not warrant a correction on their own, though the authors may consider a correction for the data-availability statement.

1.
HIGHdata code
In the Data availability section, replace the incomplete sentence 'uploaded in .' with a concrete statement naming the repository or supplementary file, and specify a managed-access mechanism (e.g., Vivli, a data access committee with contact details and conditions) for any de-identified data that could be shared.
The current statement is vague and incomplete, failing to provide readers any route to access or verify the data, which is a transparency gap in a data-driven trial.
2.
HIGHreporting
In the Methods or a reporting summary, explicitly state adherence to CONSORT guidelines for this randomized trial.
Reporting guideline adherence is not stated in the manuscript, and explicit mention would strengthen transparency and reproducibility.
3.
MEDIUMcopyedit
In Table 1, correct the stage II percentage from '1 (0.04%)' to '1 (0.4%)' to match the group size.
The percentage is internally inconsistent with the N=247 group size and is a clear typo that could mislead readers.
4.
MEDIUMcopyedit
In the Abstract, fix the typo 'hereafter to referred to as' to 'hereafter referred to as'.
This is a grammatical error that detracts from the manuscript's professionalism.
5.
MEDIUMcopyedit
In the Discussion, clarify that the median OS of 19.3 months refers specifically to the benmelstobart+anlotinib+EC arm, not the overall trial.
The current wording could be misinterpreted as the overall trial median OS, which would be misleading.
6.
MEDIUMreporting
In the Data availability section, add a statement clarifying that no custom code was used, or provide access to any analysis code if applicable.
This addresses the code-sharing sub-criterion and removes ambiguity about reproducibility.
7.
MEDIUMreporting
In the Acknowledgements or Competing interests, clarify the specific role of the funder (Chia Tai Tianqing Pharmaceutical Group) in study design, data collection, analysis, and manuscript preparation.
Transparency about funder involvement is important for assessing potential conflicts of interest.
8.
LOWcopyedit
In the Results, add a reference to the CONSORT flow diagram (Fig. 1) when describing the 1,005 assessed and 738 randomized patients.
This clarifies the patient flow and aligns with reporting guidelines.
9.
LOWcopyedit
In the Abstract and Results, ensure the distinction between TRAE (93.1%, 94.3%, 87.0%) and TEAE (94.3%, 95.9%, 89.0%) rates is clearly labeled to avoid confusion.
The close numbers for different metrics could be misread as a contradiction; explicit labeling prevents misinterpretation.

Full text (52,618 chars)Analyzed: Aug 16, 2026

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Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.

Read full text (PMC)

DOI

10.1038/s41591-024-03132-1

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Record fingerprint

fcfede2d97b870f087d226d4c19160062c758f00b2997c509dd24c6f94cb46f9

Verify via API

Issued Aug 16, 2026Engine 7.39.0

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

Kaimen Rigor review

Kaimen Rigor reviewed

2.75 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×4−2★
ReportingData & code availability partially met−0.25★

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

Biggest issues

01Other integrity concern
mediumAuthenticityreviewer-assessedFull detail
Trial NCT04234607 was first submitted to ClinicalTrials.gov on 2020-01-16, after the registered study start date of 2020-01. Retrospective registration means the protocol and outcomes were not on the public record before the study ran, which is what prospective registration exists to establish.
NCT04234607
reviewer’s wording

Findings by category

101ArithmeticNumerical inconsistencies 02OverreachNone found 103AuthenticityData authenticity concerns 104DisclosureReporting gaps 05AvailabilityNone found 06Copyedit6 minor suggestions

Numerical inconsistencies

1 finding · worst low

Internal contradictions in the reported numbersAssessed

Recomputed 4 tests: 4 consistent, 0 inconsistent; 4 via agent-written checks.

Overstated conclusions

None found

Checked — nothing surfaced.

4 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

1 finding · worst medium

Other integrity concernAssessed

4 integrity concerns flagged (0 high).

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 study clearly establishes its scientific foundation by citing prior randomized trials and providing a logical rationale for combining anti-angiogenesis with immunochemotherapy.

Evidence

“four randomized, controlled phase 3 studies (IMpower133, CASPIAN, CAPSTONE-1 and ASTRUM-005) have reported significant improvements in median OS on the order of 2–4 months”

Introduction ¶1Find in source

“Anti-angiogenesis is known to augment the efficacy of ICIs in multiple cancer types”

Introduction ¶2Find in source

absence[Introduction]

Limitations of prior research are not explicitly discussed as such.

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise by citing prior randomized trials and providing a logical rationale for combining anti-angiogenesis with immunochemotherapy.

Evidence

“four randomized, controlled phase 3 studies (IMpower133, CASPIAN, CAPSTONE-1 and ASTRUM-005) have reported significant improvements in median OS on the order of 2–4 months”

Introduction ¶1Find in source

“Anti-angiogenesis is known to augment the efficacy of ICIs in multiple cancer types”

Introduction ¶2Find in source

absence[Introduction]

Limitations of prior work are not explicitly discussed as such.

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: randomized, double-blind, placebo-controlled, with adequate sample size justification and clear inclusion/exclusion criteria.

Evidence

MethodsFind in source

Statistical analysisFind in source

PASSReviewer 2· 95% conf

The trial design is rigorous with adequate randomization, blinding, power analysis, and inclusion/exclusion criteria.

Evidence

MethodsFind in source

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

Key demographic and clinical characteristics are reported, including sex, age, and disease stage, which are adequate for a human trial.

Evidence

“Male | 209 (85.0) | 204 (83.3) | 207 (83.8)”

Table 1Find in source

“Median (range) | 62.0 (36–75) | 60.0 (32–75) | 63.0 (30–75)”

Table 1Find in source

paraphrase[Table 1]

“ECOG performance status, n (%) | 0 | 47 (19.1) | 47 (19.2) | 48 (19.4)”

PASSReviewer 2· 90% conf

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

Evidence

“Male | 209 (85.0) | 204 (83.3) | 207 (83.8)”

Table 1Find in source

“Median (range) | 62.0 (36–75) | 60.0 (32–75) | 63.0 (30–75)”

Table 1Find in source

paraphrase[Table 1]

“ECOG performance status, n (%) | 0 | 47 (19.1) | 47 (19.2) | 48 (19.4)”

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethics approval from a named IRB and informed consent are documented, along with regulatory compliance.

Evidence

“central approval was obtained from the Jinlin Province Cancer Hospital Institutional Review Board (ethics approval no. 201909-053-01).”

EthicsFind in source

“All patients provided written informed consent for participation before enrollment.”

EthicsFind in source

“The trial was conducted per the principles of Good Clinical Practice guidelines and the Declaration of Helsinki.”

EthicsFind in source

PASSReviewer 2· 95% conf

Ethics approval and informed consent are clearly documented.

Evidence

“central approval was obtained from the Jinlin Province Cancer Hospital Institutional Review Board (ethics approval no. 201909-053-01).”

EthicsFind in source

“All patients provided written informed consent for participation before enrollment.”

EthicsFind in source

“The trial was conducted per the principles of Good Clinical Practice guidelines and the Declaration of Helsinki.”

EthicsFind in source

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational products (benmelstobart, anlotinib, etoposide, carboplatin) are identified with dosing details, and statistical software is named.

Evidence

“Benmelstobart was given intravenously at a dose of 1,200 mg once daily on day 1 of each cycle. Anlotinib was given orally, once daily, at a dose of 12 mg for 2 weeks followed by 1 week off.”

MethodsFind in source

“The randomization list was generated by an independent statistician using a SAS statistical package (version 9.4, SAS Institute)”

MethodsFind in source

PASSReviewer 2· 85% conf

The investigational products are adequately identified, and statistical software is named.

Evidence

“Benmelstobart was given intravenously at a dose of 1,200 mg once daily on day 1 of each cycle. Anlotinib was given orally, once daily, at a dose of 12 mg for 2 weeks followed by 1 week off.”

MethodsFind in source

“The randomization list was generated by an independent statistician using a SAS statistical package (version 9.4, SAS Institute)”

MethodsFind in source

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 effect sizes with confidence intervals.

Evidence

Statistical analysisFind in source

paraphrase[Results, Primary endpoint of OS]

“HR, 0.61 (95% CI 0.47–0.79); P = 0.0002”

ResultsFind in source

PASSReviewer 2· 90% conf

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

Evidence

Statistical analysisFind in source

“hazard ratio 0.61; P = 0.0002”

ResultsFind in source

paraphrase[Results, Primary endpoint of OS]

“HR, 0.61 (95% CI 0.47–0.79)”

Sub-criteria

code sharingN/A

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 exists but is vague, stating data are included in the article or supplementary, and individual participant data cannot be shared.

Evidence

Data availabilityFind in source

WARNReviewer 2· 80% conf

A data availability statement exists but is vague, lacking a concrete access mechanism.

Evidence

Data availabilityFind in source

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The manuscript is transparent: registered, reports all outcomes, discusses limitations, and provides funding and COI statements.

Evidence

“ClinicalTrials.gov identifier: NCT04234607”

AbstractFind in source

“Several limitations should be acknowledged. This study provided no direct comparison with the current standard-of-care immunochemotherapy.”

Discussion ¶8Find in source

paraphrase[Acknowledgements and Competing interests]

“This study was sponsored by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. ... We declare that none of the authors has competing financial or nonfinancial interests”

PASSReviewer 2· 90% conf

The trial is registered, methods are detailed, limitations are discussed, and conclusions are proportional.

Evidence

“ClinicalTrials.gov identifier: NCT04234607”

AbstractFind in source

“Several limitations should be acknowledged. This study provided no direct comparison with the current standard-of-care immunochemotherapy.”

Discussion ¶8Find in source

paraphrase[Acknowledgements and Competing interests]

“This study was sponsored by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. ... We declare that none of the authors has competing financial or nonfinancial interests”

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

Broken references and links

None found

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.

Checked — nothing surfaced.

Checked 29 references by DOI: 28 verified — 1 no DOI (shown, not verified).

2 data/code links checked; 2 live.

Copyediting

6 minor

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

No major wording or formatting errors. 6 minor suggestions below.

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

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
HIGHdata code
In the Data availability section, replace the incomplete sentence 'uploaded in .' with a concrete statement naming the repository or supplementary file, and specify a managed-access mechanism (e.g., Vivli, a data access committee with contact details and conditions) for any de-identified data that could be shared.
The current statement is vague and incomplete, failing to provide readers any route to access or verify the data, which is a transparency gap in a data-driven trial.
2.
HIGHreporting
In the Methods or a reporting summary, explicitly state adherence to CONSORT guidelines for this randomized trial.
Reporting guideline adherence is not stated in the manuscript, and explicit mention would strengthen transparency and reproducibility.
3.
MEDIUMcopyedit
In Table 1, correct the stage II percentage from '1 (0.04%)' to '1 (0.4%)' to match the group size.
The percentage is internally inconsistent with the N=247 group size and is a clear typo that could mislead readers.
4.
MEDIUMcopyedit
In the Abstract, fix the typo 'hereafter to referred to as' to 'hereafter referred to as'.
This is a grammatical error that detracts from the manuscript's professionalism.
5.
MEDIUMcopyedit
In the Discussion, clarify that the median OS of 19.3 months refers specifically to the benmelstobart+anlotinib+EC arm, not the overall trial.
The current wording could be misinterpreted as the overall trial median OS, which would be misleading.
6.
MEDIUMreporting
In the Data availability section, add a statement clarifying that no custom code was used, or provide access to any analysis code if applicable.
This addresses the code-sharing sub-criterion and removes ambiguity about reproducibility.
7.
MEDIUMreporting
In the Acknowledgements or Competing interests, clarify the specific role of the funder (Chia Tai Tianqing Pharmaceutical Group) in study design, data collection, analysis, and manuscript preparation.
Transparency about funder involvement is important for assessing potential conflicts of interest.
8.
LOWcopyedit
In the Results, add a reference to the CONSORT flow diagram (Fig. 1) when describing the 1,005 assessed and 738 randomized patients.
This clarifies the patient flow and aligns with reporting guidelines.
9.
LOWcopyedit
In the Abstract and Results, ensure the distinction between TRAE (93.1%, 94.3%, 87.0%) and TEAE (94.3%, 95.9%, 89.0%) rates is clearly labeled to avoid confusion.
The close numbers for different metrics could be misread as a contradiction; explicit labeling prevents misinterpretation.

Full text (52,618 chars)Analyzed: Aug 16, 2026