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Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial.

Name: Kaimen Rigor review — Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial.
Item: Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial.
Rating: 59
Author: Alpha1

Trédan O, Pouessel D, Penel N, Chabaud S, Gomez-Roca C, Delord JP, Pannier D, Brahmi M, Fabbro M, Garcia ME, Larrieu-Ciron D, Ray-Coquard I, Viala M, Italiano A, Tosi D, Cassier P, Dufresne A, Attignon V, Boyault S, Treilleux I, Viari A, Pérol D, Blay JY

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Kaimen Rigor review — 3.75★ (Adequate), 0 critical, 3 high issues for “Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial.”

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

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Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial.

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DOI

10.1038/s41591-025-03613-x

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial.

Paper source

Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial.

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Alpha1 Editorial

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

Kaimen Rigor review

Kaimen Rigor reviewed

3.75 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern−0.5★
CitationsUnresolved reference ×2−0.5★
StatisticsPrinted percentage does not match its own count (capped) ×2−0.25★

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

Not verified in this report

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

Biggest issues

01Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
63.3% is unattainable for n=339 (nearest: 63.1, 63.4%)
“214 (63.3%)”
Table 2B
02Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
4.2% is unattainable for n=171 (nearest: 4.1, 4.7%)
“7 (4.2%)”
Table 1

Findings by category

201ArithmeticNumerical inconsistencies 02OverreachNone found 03AuthenticityNone found 04DisclosureNone found 105AvailabilityBroken references and links · partly checked 06Copyedit4 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.

The paper is a well-conducted multicenter randomized controlled trial with rigorous design, clear reporting of ethics, demographics, and statistical methods, and transparent data availability. Minor reporting gaps include the lack of an explicit CONSORT statement and a few copyedit issues such as a duplicate row in Table 1 and unspecified software versions.

Both reviewers classified the study as interventional, which is consistent with the randomized controlled trial design. The evaluation covered all eight dimensions; several sub-criteria were marked not applicable (e.g., animal housing, cell line authentication) due to the human clinical trial context. The statistics verification component checked only a subset of tests, and the two inconsistent findings were not specified, so they were not treated as demonstrable errors.

Numerical inconsistencies

2 findings · worst medium

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.

Printed percentage does not match its own countRecomputed
Internal contradictions in the reported numbersAssessed

Recomputed 2 tests: 2 consistent, 0 inconsistent; 2 via agent-written checks. 2 printed percentages that do not match their own count.

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.

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

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

None found

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.

Checked — nothing surfaced.

Eight Dimensions8 pass

The introduction cites prior work (ProfiLER-01, SHIVA, MPACT, MATCH, 100,000 Genomes Project) and acknowledges limitations such as low MBRT initiation rates and unclear clinical impact of large panels. The rationale for comparing F1CDX (324 genes) versus CTL (87 genes) is clearly stated. The study addresses prior limitations by using a randomized design and paired data from both panels.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise by citing prior genomic profiling programs and trials, and logically links the rationale to the study objective of comparing broader versus limited gene panels.

Evidence

paraphrase[Main, paragraph 1]

“We previously reported the use of next-generation sequencing (NGS) with panels of 59–69 genes and microarray-based comparative genomic hybridization in the ProfiLER-01 study. Molecular profiling in enrolled patients with metastatic cancer allowed proposing MBRTs in 27% of the patients, including 6% in whom an MBRT was initiated.”

“In an attempt to assess this impact, the multicenter prospective randomized study ProfiLER-02 aimed to evaluate the added value of a larger number of screened genomic biomarkers from the gene panel Foundation OneCDX (F1CDX panel, 324 genes) compared to our home-based molecular profiling panel (CTL panel with limited biomarker detection, 87 genes) to identify more MBRTs in patients with advanced cancer.”

Main, paragraph 2Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise by citing prior genomic profiling programs and trials, and logically links the need for larger gene panels to the study objective.

Evidence

paraphrase[Main, paragraph 1]

Main, paragraph 1Find in source

Randomization used an IWRS with permuted block design, and the randomization list was generated by a statistician. Blinding was maintained for study collaborators except biologists. A sample size calculation was performed with 98% power. Inclusion/exclusion criteria are detailed. The analysis population (ITT and per-protocol) is defined. Outlier handling is addressed through the ITT principle and sensitivity analysis.

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· 90% conf

The trial design is rigorous with clear randomization, blinding, sample size calculation, and pre-specified inclusion/exclusion criteria.

Evidence

“Registration and randomization used an interactive web response system (IWRS, Ennov) with a permuted block design. A statistician was in charge of generating the randomization list.”

MethodsFind in source

“At randomization request, the IWRS automatically sent an email with the NGS panel assigned at MTB#1 to biologists only. Other study collaborators remained blinded.”

MethodsFind in source

paraphrase[Methods, Statistics and reproducibility, Sample size calculation]

“A total of 289 patients with results achieved using both panels (pairs) were needed to detect with 98% power a 10% difference in proportions, with 20% discordant pairs in proportions using a McNemar test of equality of paired proportions at a 5% two-sided significance level.”

PASSReviewer 2· 95% conf

The trial design is rigorous with clear randomization, blinding, sample size calculation, and pre-specified inclusion/exclusion criteria.

Evidence

“Registration and randomization used an interactive web response system (IWRS, Ennov) with a permuted block design. A statistician was in charge of generating the randomization list.”

MethodsFind in source

“At randomization request, the IWRS automatically sent an email with the NGS panel assigned at MTB#1 to biologists only. Other study collaborators remained blinded.”

MethodsFind in source

paraphrase[Methods, Statistics and reproducibility, Sample size calculation]

Sex is reported (54.9% female), age (median 57 years), metastatic status, and tumor types are detailed in Table 1. Since both sexes are enrolled, sex_justified is not applicable. Demographics are adequately reported. 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

Patient demographics and clinical characteristics are well reported, including sex, age, metastatic status, and tumor types.

Evidence

“In the ITT population, female patients ( n = 186) accounted for 54.9% of the population. At inclusion, the median age was 57 (19–85) years and 222 (65.5%) patients had metastasis.”

ResultsFind in source

PASSReviewer 2· 90% conf

Patient demographics and clinical characteristics are well reported, including sex, age, and tumor types.

Evidence

“In the ITT population, female patients ( n = 186) accounted for 54.9% of the population. At inclusion, the median age was 57 (19–85) years and 222 (65.5%) patients had metastasis.”

ResultsFind in source

The study obtained approval from the Ethics Committee of Lyon Sud-Est IV on 23 May 2017 and authorization from the national competent authority. All patients provided written informed consent. The study was conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. Regulatory compliance is explicitly stated.

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 committee, informed consent, and regulatory compliance are all clearly documented.

Evidence

“This multicenter randomized prospective study, ProfiLER-02, was performed in 12 institutions after obtaining approval from the Ethics Committee of Lyon Sud-Est IV on 23 May 2017 and after receiving authorization from the national competent authority on 15 May 2017.”

MethodsFind in source

“All patients provided written informed consent.”

MethodsFind in source

“This study was conducted in accordance with the Good Clinical Practice guidelines of the International Conference on Harmonization and the Declaration of Helsinki, as well as relevant French and European laws and directives.”

MethodsFind in source

PASSReviewer 2· 95% conf

Ethics approval from a named committee, informed consent, and regulatory compliance are all reported.

Evidence

MethodsFind in source

“All patients provided written informed consent.”

MethodsFind in source

The F1CDX panel is identified as provided by Foundation Medicine. The CTL panel is described with its gene list and the kit used (Forma Pure RNA kit, Beckman Coulter, # C19158). Sequencing platforms and software versions are specified (e.g., FastQC v0.11.5, SAMtools v1.3.1, R v3.5.3, Annovar v02-2016, VEP release 92). Antibodies, cell lines, and mycoplasma testing are not applicable for this clinical trial.

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· 90% conf

The investigational product (F1CDX panel) and key reagents/software are adequately identified.

Evidence

paraphrase[Methods, Procedures]

“Genomic molecular profiles were determined concomitantly using NGS and two different gene panels: (1) a panel of 324 cancer-related genes (F1CDX) provided by Foundation Medicine and (2) a panel of 87 cancer-related genes (CTL) routinely used at Centre Léon Bérard.”

paraphrase[Methods, Procedures]

“CTL used genomic DNA extracted from FFPE tissues using the Forma Pure RNA kit (Beckman Coulter, # C19158) following the manufacturer’s instructions.”

“Statistical analyses were performed using R v3.5.3 (R Foundation for Statistical Computing). Mutations were annotated with Annovar (v02-2016) and VEP (release 92).”

MethodsFind in source

PASSReviewer 2· 85% conf

The investigational products (gene panels) are identified, and software tools are named with versions.

Evidence

paraphrase[Methods, Procedures]

“CTL used genomic DNA extracted from FFPE tissues using the Forma Pure RNA kit (Beckman Coulter, # C19158) following the manufacturer’s instructions.”

“The quality of sequencing data was checked using FastQC (v0.11.5) and SAMtools (v1.3.1) for DNA and FastQC and RSeQC for RNA. Statistical analyses were performed using R v3.5.3 (R Foundation for Statistical Computing).”

MethodsFind in source

The primary analysis used McNemar test for paired proportions, and p-values are reported exactly (P < 0.001). Effect sizes are reported as percentage point differences with 95% CIs for PFS. Statistical software is identified (SAS v9.4). Data presentation includes Kaplan-Meier curves and per-group n. Mathematical plausibility checks were not applicable 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

“corresponding to a significant increase in MBRT identification of 14.8 percentage points using F1CDX versus CTL (McNemar test: P < 0.001)”

ResultsFind in source

paraphrase[Results, Progression-free survival]

“The median progression-free survival (PFS) ... was 1.4 (95% confidence interval (CI) 0.0–2.1) months in patients allocated to the F1CDX panel first and 0 (95% CI 0–1.4) months in those allocated to the CTL panel first ( P = 0.3409)”

“Statistical analyses were performed using SAS software v9.4 or later.”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

Statistical tests are named, exact p-values are reported, effect sizes with CIs are provided, and software is identified.

Evidence

“corresponding to a significant increase in MBRT identification of 14.8 percentage points using F1CDX versus CTL (McNemar test: P < 0.001)”

ResultsFind in source

paraphrase[Results, Progression-free survival]

“Statistical analyses were performed using SAS software v9.4 or later.”

Statistical analysisFind in source

The data availability statement provides a specific repository (Zenodo) and DOI (10.5281/zenodo.14794347). Since the data are anonymized individual-level data, repository_deposit and accession_numbers are applicable and adequate. Code sharing is not applicable as no bespoke code is mentioned.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Anonymized individual data are deposited in Zenodo with a DOI, and the data availability statement is concrete.

Evidence

“Anonymized individual data, including selected actionable gene alterations, detailed alterations, ESCAT class, pharmaceutical class proposed by the MTB and initiated, and MBRTs initiated, are available via Zenodo at 10.5281/zenodo.14794347 (ref. ).”

Data availabilityFind in source

PASSReviewer 2· 95% conf

Anonymized individual data are deposited in Zenodo with a DOI, and a data availability statement is present.

Evidence

Data availabilityFind in source

The trial is registered at ClinicalTrials.gov (NCT03163732). Methods are comprehensive. Limitations are explicitly discussed, including the small number of MBRT initiations and the overrepresentation of certain tumor types. Conclusions appropriately state that no differences in clinical outcomes were observed. Funding and COI statements are provided.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

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

Evidence

“ClinicalTrials.gov registration: NCT03163732”

AbstractFind in source

“Some limitations have to be underlined. These results should be interpreted with caution considering the small number of patients in whom an MBRT was initiated (the main limitation resulting from the critical lack of accessibility of MBRTs) and the aggressiveness of most of the included cancers (gliomas and sarcomas).”

Discussion ¶8Find in source

“However, no differences in clinical outcomes were observed in this population of patients with advanced and/or metastatic cancer in need of treatment beyond standard genomic alterations.”

Discussion ¶9Find in source

PASSReviewer 2· 90% conf

The trial is registered, methods are detailed, limitations are discussed, and funding/COI are disclosed.

Evidence

“ClinicalTrials.gov registration: NCT03163732”

AbstractFind in source

DiscussionFind in source

“This work received partial funding from Roche Pharma AG. The F1CDX panel was provided for free by Foundation Medicine.”

AcknowledgementsFind in source

Registered (3 IDs: ClinicalTrials.gov). No reporting guideline cited.

Broken references and links

1 finding · worst low

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.

References not resolvable to a published paperRecomputed

Checked 26 references by DOI: 24 verified — 2 DOI unresolved.

Copyediting

4 minor

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

No major wording or formatting errors. 4 minor suggestions below.

4 copyedit issues flagged: mostly consistency, clarity.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is robust and well-reported; an informed reader should weigh the minor reporting gaps (missing CONSORT statement, duplicate Table 1 row, unspecified RSeQC version) and the unverified subset of statistical tests. No erratum is warranted for the core findings, but the authors should consider issuing a correction for the Table 1 duplication and clarifying the death counts.

1.
HIGHcopyedit
In Table 1, remove the duplicate 'Pancreatic' row and verify the correct counts for pancreatic cancer, ensuring consistency with the text.
The duplicate row with conflicting numbers is an internal contradiction that could confuse readers and undermine data integrity.
2.
HIGHreporting
In the Methods or Reporting Summary, explicitly state that the study followed the CONSORT reporting guideline and provide the checklist as supplementary material.
The absence of an explicit CONSORT statement is a reporting gap that reviewers and readers expect for a randomized trial.
3.
HIGHstatistics
In the Results, report the exact p-values for secondary endpoints (e.g., PFS) rather than only thresholds, and clarify the handling of missing data for the primary endpoint.
Exact p-values and missing-data handling improve statistical transparency and reproducibility.
4.
MEDIUMcopyedit
In Methods, Procedures, specify the version of RSeQC used for RNA quality checking.
Providing software versions for all tools enhances reproducibility.
5.
MEDIUMcopyedit
In Results, Description of the cohort, clarify whether the 233 deaths include the 17 during screening and 58 after randomization.
The ambiguity in death counts could lead to misinterpretation of the survival analysis.
6.
MEDIUMdata code
In the Data Availability section, consider also depositing the analysis code (e.g., SAS scripts) used for statistical analyses in a public repository.
Sharing analysis code enhances reproducibility, even though it is not strictly required.
7.
MEDIUMreporting
In the Discussion, add a brief note on the generalizability of the findings given the overrepresentation of gliomas and sarcomas and the underrepresentation of common cancers.
This would help readers interpret the applicability of the results to broader patient populations.
8.
LOWother
Verify the two references flagged as not found in the registry (the cancer genomes analysis and the Zenodo dataset) and correct or replace them if they are erroneous.
Unresolved references may indicate fabrication or citation errors that need correction.

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Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial.

Read full text (PMC)

DOI

10.1038/s41591-025-03613-x

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Record fingerprint

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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

3.75 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern−0.5★
CitationsUnresolved reference ×2−0.5★
StatisticsPrinted percentage does not match its own count (capped) ×2−0.25★

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

Not verified in this report

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

Biggest issues

01Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
63.3% is unattainable for n=339 (nearest: 63.1, 63.4%)
“214 (63.3%)”
Table 2B
02Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
4.2% is unattainable for n=171 (nearest: 4.1, 4.7%)
“7 (4.2%)”
Table 1

Findings by category

201ArithmeticNumerical inconsistencies 02OverreachNone found 03AuthenticityNone found 04DisclosureNone found 105AvailabilityBroken references and links · partly checked 06Copyedit4 minor suggestions

Numerical inconsistencies

2 findings · worst medium

Printed percentage does not match its own countRecomputed
Internal contradictions in the reported numbersAssessed

Recomputed 2 tests: 2 consistent, 0 inconsistent; 2 via agent-written checks. 2 printed percentages that do not match their own count.

Overstated conclusions

None found

Checked — nothing surfaced.

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

Data authenticity concerns

None found

Checked — nothing surfaced.

Reporting gaps

None found

Checked — nothing surfaced.

Eight Dimensions8 pass

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Evidence

paraphrase[Main, paragraph 1]

Main, paragraph 2Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise by citing prior genomic profiling programs and trials, and logically links the need for larger gene panels to the study objective.

Evidence

paraphrase[Main, paragraph 1]

Main, paragraph 1Find in source

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· 90% conf

The trial design is rigorous with clear randomization, blinding, sample size calculation, and pre-specified inclusion/exclusion criteria.

Evidence

“Registration and randomization used an interactive web response system (IWRS, Ennov) with a permuted block design. A statistician was in charge of generating the randomization list.”

MethodsFind in source

“At randomization request, the IWRS automatically sent an email with the NGS panel assigned at MTB#1 to biologists only. Other study collaborators remained blinded.”

MethodsFind in source

paraphrase[Methods, Statistics and reproducibility, Sample size calculation]

PASSReviewer 2· 95% conf

The trial design is rigorous with clear randomization, blinding, sample size calculation, and pre-specified inclusion/exclusion criteria.

Evidence

“Registration and randomization used an interactive web response system (IWRS, Ennov) with a permuted block design. A statistician was in charge of generating the randomization list.”

MethodsFind in source

“At randomization request, the IWRS automatically sent an email with the NGS panel assigned at MTB#1 to biologists only. Other study collaborators remained blinded.”

MethodsFind in source

paraphrase[Methods, Statistics and reproducibility, Sample size calculation]

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

Patient demographics and clinical characteristics are well reported, including sex, age, metastatic status, and tumor types.

Evidence

“In the ITT population, female patients ( n = 186) accounted for 54.9% of the population. At inclusion, the median age was 57 (19–85) years and 222 (65.5%) patients had metastasis.”

ResultsFind in source

PASSReviewer 2· 90% conf

Patient demographics and clinical characteristics are well reported, including sex, age, and tumor types.

Evidence

“In the ITT population, female patients ( n = 186) accounted for 54.9% of the population. At inclusion, the median age was 57 (19–85) years and 222 (65.5%) patients had metastasis.”

ResultsFind in source

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 committee, informed consent, and regulatory compliance are all clearly documented.

Evidence

MethodsFind in source

“All patients provided written informed consent.”

MethodsFind in source

PASSReviewer 2· 95% conf

Ethics approval from a named committee, informed consent, and regulatory compliance are all reported.

Evidence

MethodsFind in source

“All patients provided written informed consent.”

MethodsFind 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· 90% conf

The investigational product (F1CDX panel) and key reagents/software are adequately identified.

Evidence

paraphrase[Methods, Procedures]

“CTL used genomic DNA extracted from FFPE tissues using the Forma Pure RNA kit (Beckman Coulter, # C19158) following the manufacturer’s instructions.”

“Statistical analyses were performed using R v3.5.3 (R Foundation for Statistical Computing). Mutations were annotated with Annovar (v02-2016) and VEP (release 92).”

MethodsFind in source

PASSReviewer 2· 85% conf

The investigational products (gene panels) are identified, and software tools are named with versions.

Evidence

paraphrase[Methods, Procedures]

“CTL used genomic DNA extracted from FFPE tissues using the Forma Pure RNA kit (Beckman Coulter, # C19158) following the manufacturer’s instructions.”

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

“corresponding to a significant increase in MBRT identification of 14.8 percentage points using F1CDX versus CTL (McNemar test: P < 0.001)”

ResultsFind in source

paraphrase[Results, Progression-free survival]

“Statistical analyses were performed using SAS software v9.4 or later.”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

Statistical tests are named, exact p-values are reported, effect sizes with CIs are provided, and software is identified.

Evidence

“corresponding to a significant increase in MBRT identification of 14.8 percentage points using F1CDX versus CTL (McNemar test: P < 0.001)”

ResultsFind in source

paraphrase[Results, Progression-free survival]

“Statistical analyses were performed using SAS software v9.4 or later.”

Statistical analysisFind in source

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Anonymized individual data are deposited in Zenodo with a DOI, and the data availability statement is concrete.

Evidence

Data availabilityFind in source

PASSReviewer 2· 95% conf

Anonymized individual data are deposited in Zenodo with a DOI, and a data availability statement is present.

Evidence

Data availabilityFind in source

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

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

Evidence

“ClinicalTrials.gov registration: NCT03163732”

AbstractFind in source

Discussion ¶8Find in source

“However, no differences in clinical outcomes were observed in this population of patients with advanced and/or metastatic cancer in need of treatment beyond standard genomic alterations.”

Discussion ¶9Find in source

PASSReviewer 2· 90% conf

The trial is registered, methods are detailed, limitations are discussed, and funding/COI are disclosed.

Evidence

“ClinicalTrials.gov registration: NCT03163732”

AbstractFind in source

DiscussionFind in source

“This work received partial funding from Roche Pharma AG. The F1CDX panel was provided for free by Foundation Medicine.”

AcknowledgementsFind in source

Registered (3 IDs: ClinicalTrials.gov). No reporting guideline cited.

Broken references and links

1 finding · worst low

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.

References not resolvable to a published paperRecomputed

Checked 26 references by DOI: 24 verified — 2 DOI unresolved.

Copyediting

4 minor

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

No major wording or formatting errors. 4 minor suggestions below.

4 copyedit issues flagged: mostly consistency, clarity.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
HIGHcopyedit
In Table 1, remove the duplicate 'Pancreatic' row and verify the correct counts for pancreatic cancer, ensuring consistency with the text.
The duplicate row with conflicting numbers is an internal contradiction that could confuse readers and undermine data integrity.
2.
HIGHreporting
In the Methods or Reporting Summary, explicitly state that the study followed the CONSORT reporting guideline and provide the checklist as supplementary material.
The absence of an explicit CONSORT statement is a reporting gap that reviewers and readers expect for a randomized trial.
3.
HIGHstatistics
In the Results, report the exact p-values for secondary endpoints (e.g., PFS) rather than only thresholds, and clarify the handling of missing data for the primary endpoint.
Exact p-values and missing-data handling improve statistical transparency and reproducibility.
4.
MEDIUMcopyedit
In Methods, Procedures, specify the version of RSeQC used for RNA quality checking.
Providing software versions for all tools enhances reproducibility.
5.
MEDIUMcopyedit
In Results, Description of the cohort, clarify whether the 233 deaths include the 17 during screening and 58 after randomization.
The ambiguity in death counts could lead to misinterpretation of the survival analysis.
6.
MEDIUMdata code
In the Data Availability section, consider also depositing the analysis code (e.g., SAS scripts) used for statistical analyses in a public repository.
Sharing analysis code enhances reproducibility, even though it is not strictly required.
7.
MEDIUMreporting
In the Discussion, add a brief note on the generalizability of the findings given the overrepresentation of gliomas and sarcomas and the underrepresentation of common cancers.
This would help readers interpret the applicability of the results to broader patient populations.
8.
LOWother
Verify the two references flagged as not found in the registry (the cancer genomes analysis and the Zenodo dataset) and correct or replace them if they are erroneous.
Unresolved references may indicate fabrication or citation errors that need correction.

Full text (61,069 chars)Analyzed: Aug 15, 2026