Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME trial.

Name: Kaimen Rigor review — Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME trial.
Item: Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME trial.
Rating: 100
Author: Alpha1

Marchetti P, Curigliano G, Biffoni M, Lonardi S, Scagnoli S, Fornaro L, Guarneri V, De Giorgi U, Ascierto PA, Blandino G, D'Amati G, Aglietta M, Cremolini C, Conte P, Crimini E, Ceracchi M, Pisegna S, Verkhovskaia S, Bordonaro R, Bracarda S, Butturini G, Del Mastro L, DeCensi A, Fabbri A, Fenocchio E, Gori S, Metro G, Pessino A, Pozzessere D, Puglisi F, Tamberi S, Zambelli A, Marino D, Capoluongo E, Cappuzzo F, Cerbelli B, Giannini G, Malapelle U, Mazzuca F, Nuti M, Pruneri G, Simmaco M, Strigari L, Tonini G, Martini N, Botticelli A, ROME trial investigators consortia

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Kaimen Rigor review — 2.25★ (Weak), 0 critical, 3 high issues for “Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME trial.”

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Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME trial.

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DOI

10.1038/s41591-025-03918-x

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME trial.

Paper source

Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME 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 15, 2026

Kaimen Rigor review

Kaimen Rigor reviewed

2.25 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ClaimsOverstated claim−0.5★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★
LinksDead data/code link−0.25★

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

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary endpoint is ORR, a surrogate for clinical benefit. The paper does not demonstrate target engagement at the tested doses (no PK/PD data) and does not cite validated evidence linking ORR to improved survival or quality of life in this context. The claim of improved outcomes rests on this surrogate without establishing a validated surrogate-to-clinical-outcome link.
“Overall response rate (ORR) was the primary endpoint”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
The primary effect is a modest absolute improvement in ORR of 7.5 percentage points (17.5% vs 10%) and a median PFS improvement of 0.7 months (3.5 vs 2.8 months). These are small fractions of the reference values and are not anchored to a minimal clinically important difference or demonstrated biological meaningfulness. The paper itself describes the ORR improvement as 'modest in magnitude'.
“The improvement in ORR, the primary endpoint of the study, observed in the TT arm compared to the SoC arm within the ITT population (17.5% versus 10%), is clinically relevant and methodologically robust, although modest in magnitude.”
Find in source
03Conclusion reaches beyond the evidence
mediumOverreachreviewer-assessedFull detail
The ROME trial provides the strongest evidence supporting MTB implementation in clinical practice.
“The ROME trial provides, to our knowledge, the strongest evidence supporting MTB implementation in clinical practice, thanks to its agnostic and randomized design.”
DiscussionFind in source
04Declared data/code link does not resolve
mediumAvailabilityrecomputedFull detail
Dead link — nothing to verify.
“https://www.esmo.org/guidelines/esmo-scale-for-clinical-actionability-of-molecular-targets-escat”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 302OverreachOverstated conclusions 03AuthenticityNone found 04DisclosureNone found 105AvailabilityBroken references and links 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.

The ROME trial is a well-designed, randomized phase 2 study with clear scientific premise, rigorous methodology, and transparent reporting. Minor issues include inconsistent crossover rates and a typo, but these do not undermine the core findings.

Both reviewers classified the study as interventional, and no divergence was noted. The evaluation covered the full text, with N/A for non-applicable items (e.g., animal housing, cell lines). The statistics verification covered only a subset of tests (3 recomputed, all consistent); other statistics remain unverified.

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 3 tests: 3 consistent, 0 inconsistent; 1 recomputed directly from the reported test statistics, 2 via agent-written checks.

Overstated conclusions

3 findings · worst high

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.

Efficacy rests on an unvalidated surrogate endpointAssessed
Treatment effect not shown to be clinically meaningfulAssessed
Conclusions overstated beyond the evidenceAssessed

6 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

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 multiple prior studies (SHIVA, MOSCATO-01, TAPUR, NCI-MATCH, SAFIR02-BREAST) and frameworks (ESCAT, ETAC-S), acknowledging inconsistent outcomes and gaps. The rationale for the trial—evaluating MTB-guided TT versus SoC in a randomized setting—follows logically from the cited evidence. Limitations of prior research (e.g., lack of randomized evidence, variability in actionability) are explicitly addressed.

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 precision oncology trials and frameworks, and logically motivates the ROME trial.

Evidence

paraphrase[Introduction, paragraph 2]

“For instance, although the SHIVA trial did not show progression-free survival (PFS) benefits for off-label TT compared to standard treatments, the MOSCATO-01 trial achieved its endpoint, underscoring the value of broad genomic testing and targeted drug treatments.”

“The nationwide ROME trial was designed to provide comprehensive genomic profiling and TT for patients with solid tumors across multiple medical oncology units in Italy. This trial aims to evaluate the outcomes of a TT established after discussions in the MTB compared to the standard of care (SoC).”

Introduction ¶4Find in source

“However, definitive evidence demonstrating the superiority of these approaches over standard therapies is lacking, with inconsistent outcomes reported across randomized agnostic precision oncology clinical trials.”

Introduction ¶2Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise by citing prior precision oncology trials and frameworks, and provides a logical rationale for the study.

Evidence

Introduction ¶2Find in source

“The nationwide ROME trial was designed to provide comprehensive genomic profiling and TT for patients with solid tumors across multiple medical oncology units in Italy.”

IntroductionFind in source

paraphrase[Introduction, paragraph 4]

“However, the impact of MTBs on patient outcomes requires further validation, as current evidence is limited and varies based on factors such as drug availability and tumor types treated.”

Randomization method is described (SAS PROC PLAN, independent statistician, 1:1 ratio). Power analysis is detailed with assumptions (20% vs 5% ORR, α=0.10, β=0.20, 86 per stratum, 344 total, 384 with dropout, 400 final). Inclusion/exclusion criteria are extensive and prespecified. Outlier handling is addressed via ITT analysis and predefined SAP. Controls are inherent in the SoC arm. Independent replication is not applicable for a single pivotal trial. Blinding is not reported, but the open-label design is stated; however, no explicit rationale for open-label is given, which is a minor gap.

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsINADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The trial design is rigorous with clear randomization, prespecified endpoints, and a statistical analysis plan, though blinding is not applicable due to open-label design.

Evidence

“The randomization list was generated with a dedicated SAS program using the PROC PLAN procedure by an independent statistician.”

Statistical analysisFind in source

“To detect a 15% difference between the two arms, assuming an α of 0.10 and a β of 0.20 (80% power) and employing a one-sided chi-square test, a total of 86 patients (43 in each arm of the four cohorts) were required.”

MethodsFind in source

“The ROME trial was a multicenter, randomized, open-label phase 2 study comparing tailored treatment (TT) to standard of care (SoC)”

AbstractFind in source

PASSReviewer 2· 85% conf

The trial design is rigorous with clear randomization, blinding (open-label with rationale), power analysis, and predefined inclusion/exclusion criteria.

Evidence

“The randomization list was generated with a dedicated SAS program using the PROC PLAN procedure by an independent statistician.”

Statistical analysisFind in source

MethodsFind in source

“Eligible patients had failed at least one, but no more than two, prior lines of systemic therapy.”

MethodsFind in source

Sex is reported for the ITT population (48% male, 52% female). Age (median 61, range 22-85) and ECOG PS are reported. Demographics include ethnicity breakdown. Species/strain/housing are not applicable for a human trial. 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

Demographic and clinical characteristics are well reported, including age, sex, ethnicity, ECOG PS, and tumor types.

Evidence

“Median (range) | 61 (22–85) | 60 (34–84) | 62 (22–85)”

Table 1Find in source

“Caucasian | 392 (98.1) | 196 (98.0) | 196 (98.0)”

Table 1Find in source

PASSReviewer 2· 90% conf

Demographic and clinical characteristics are well reported, including age, sex, ethnicity, and performance status.

Evidence

“Male | 192 (48.0) | 100 (50.0) | 92 (46.0)”

Table 1Find in source

“Median (range) | 61 (22–85) | 60 (34–84) | 62 (22–85)”

Table 1Find in source

“Caucasian | 392 (98.1) | 196 (98.0) | 196 (98.0)”

Table 1Find in source

The study was approved by the institutional ethics committee of the coordinating center (Sapienza no. rif. C.E. 5575) and by each participating center. AIFA authorized the trial. All patients signed informed consent. Adherence to the Declaration of Helsinki is 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 named committees, informed consent, and regulatory compliance are clearly documented.

Evidence

“The study was approved by the institutional ethics committee of the coordinating center (Sapienza no. rif. C.E. 5575; February 2020) and by the ethics committee of each participating center.”

MethodsFind in source

“All patients signed the specifically conceived informed consent form (ICF).”

MethodsFind in source

“The trial adhered to the principles of the Declaration of Helsinki regarding research involving human subjects.”

MethodsFind in source

PASSReviewer 2· 95% conf

Ethics approval from named committees, informed consent, and regulatory compliance are clearly documented.

Evidence

“The study was approved by the institutional ethics committee of the coordinating center (Sapienza no. rif. C.E. 5575; February 2020) and by the ethics committee of each participating center.”

MethodsFind in source

“All patients signed the specifically conceived informed consent form (ICF).”

MethodsFind in source

“The trial adhered to the principles of the Declaration of Helsinki regarding research involving human subjects.”

MethodsFind in source

The trial uses multiple targeted therapies and immunotherapies; the drugs are named with manufacturers (e.g., Roche, Novartis, Pfizer). NGS tests (FoundationOne CDx and FoundationOne Liquid CDx) are identified with provider. Statistical software (SAS v9.4, R v4.3.3) is identified. Antibodies, cell lines, and mycoplasma testing are not applicable.

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

Investigational products and NGS assays are identified with manufacturers, and software tools are named.

Evidence

“Molecular profiling was performed using FoundationOne CDX and FoundationOne Liquid CDX tests on tissue and liquid biopsies.”

MethodsFind in source

“All analyses were conducted using SAS software (v.9.4).”

Statistical analysisFind in source

“Erlotinib, pertuzumab, vemurafenib, trastuzumab emtansine, alectinib, vismodegib, cobimetinib, atezolizumab, trastuzumab, ipatasertib (GDC-0068), entrectinib and pralsetinib were provided by Roche;”

AcknowledgementsFind in source

PASSReviewer 2· 85% conf

Investigational products and key reagents are identified with sources, and software tools are named.

Evidence

AcknowledgementsFind in source

“Molecular profiling was performed using FoundationOne CDX and FoundationOne Liquid CDX tests on tissue and liquid biopsies.”

MethodsFind in source

“All analyses were conducted using SAS software (v.9.4).”

Statistical analysisFind in source

Tests are named (CMH, chi-square, log-rank, Breslow-Day). Exact p-values are given for primary and key secondary endpoints (e.g., P=0.0294, P=0.0002). Effect sizes with 95% CIs are reported (HR=0.66, 95% CI 0.53-0.82). Software identified (SAS v9.4, R v4.3.3). Data presentation includes Kaplan-Meier curves and forest plots. Mathematical plausibility checks: ORR percentages are consistent with counts (e.g., 17.5% of 200 = 35 patients, matching 6 CR + 29 PR). However, some p-values in figures are reported as thresholds (e.g., P<0.0001), which is acceptable for very small values.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

Statistical methods are well described with named tests, exact p-values, effect sizes with CIs, and software identified; some p-values are reported as thresholds in figures.

Evidence

“The P value from the chi-square test ( P = 0.0294; Extended Data Table ) is nearly identical to the stratified CMH result”

ResultsFind in source

“with a hazard ratio (HR) of 0.66 (95% CI: 0.53–0.82, P = 0.0002; Fig. )”

ResultsFind in source

“All analyses were conducted using SAS software (v.9.4).”

Statistical analysisFind in source

PASSReviewer 2· 80% conf

Statistical tests are named, effect sizes with CIs are reported, and the analysis is appropriate for a clinical trial.

Evidence

“The primary endpoint analysis conducted using the stratified analysis by Cochran–Mantel–Haenszel (CMH) test demonstrated a significant difference in ORR between groups ( P = 0.0285; Extended Data Table ).”

ResultsFind in source

“PFS was significantly improved in the TT arm (median 3.5 months, 95% CI: 3.0–4.8) compared to the SoC arm (2.8 months, 95% CI: 2.5–3.2), with a hazard ratio (HR) of 0.66 (95% CI: 0.53–0.82, P = 0.0002; Fig. ).”

ResultsFind in source

“Kaplan–Meier survival analysis, accompanied by the log-rank test, was employed to compare OS and PFS across arms and subgroups.”

Statistical analysisFind in source

The data availability statement describes a managed-access process: requests reviewed by steering committee, data access agreement, secure platform, within 4-8 weeks, considered within 12 months. This is reported_and_adequate. Repository deposit and accession numbers are not applicable for identifiable patient data. Code sharing is not applicable as no custom code is mentioned (only standard software).

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Data availability statement provides a concrete managed-access route with conditions and timeframe; code sharing is not applicable as no bespoke code is mentioned.

Evidence

“Individual deidentified participant data generated during the current study are available upon reasonable request from academic or qualified clinical researchers affiliated with recognized institutions, strictly for the purpose of conducting non-commercial, ethically approvable research aligned with the original scope of the trial.”

Data availabilityFind in source

“Data will be shared via a secure data-sharing platform within 4–8 weeks of approval, contingent upon data volume and complexity. Data requests will be considered within 12 months of manuscript publication.”

Data availabilityFind in source

PASSReviewer 2· 90% conf

Data availability statement provides a concrete managed-access route, and trial registration is public.

Evidence

Data availabilityFind in source

“The trial registration, study protocol and methodological details are publicly accessible through ClinicalTrials.gov (accession identifier NCT04591431”

Data availabilityFind in source

Trial registration is provided (NCT04591431, EudraCT 2018-002190-21). CONSORT checklist is mentioned in supplementary. All outcomes are reported, including negative OS result. Limitations are discussed (crossover, subgroup sizes, TMB variability). Conclusions are proportional, acknowledging exploratory nature of subgroups. Funding sources and COI are detailed.

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· 90% conf

The manuscript is transparent with trial registration, CONSORT checklist, limitations discussion, proportional conclusions, and funding/COI statements.

Evidence

“The trial is registered on ClinicalTrials.gov with identifier NCT04591431”

MethodsFind in source

“Supplementary Table 1: Type of previous treatments received by patients in the ITT population; Supplementary Table 2: Crossover rate; Supplementary Table 3: Reasons for patients not undergoing crossover (SoC arm); Supplementary Table 4: Extension of tumor primary site listed as ‘Other’ in Table 1; Protocol V4; Protocol Appendix 2; and CONSORT checklist.”

Supplementary materialFind in source

“The substantial crossover rate (58.8%) from the SoC arm to the TT arm after disease progression, although ethically appropriate, likely contributed to this lack of OS benefit.”

Discussion ¶4Find in source

PASSReviewer 2· 90% conf

The manuscript is transparent with complete methods, trial registration, CONSORT checklist, and limitations discussed.

Evidence

“The trial is registered on ClinicalTrials.gov with identifier NCT04591431”

MethodsFind in source

Supplementary materialFind in source

“The substantial crossover rate (58.8%) from the SoC arm to the TT arm after disease progression, although ethically appropriate, likely contributed to this lack of OS benefit.”

Discussion ¶4Find in source

Registered (3 IDs: ClinicalTrials.gov, EudraCT). Reporting guideline cited: CONSORT.

Broken references and links

1 finding · worst medium

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.

Dead data/code linksRecomputed

Checked 39 references by DOI: 39 verified.

7 data/code links checked; 6 live, 1 dead.

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.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is robust and well-reported. An informed reader should weigh the minor internal inconsistencies (crossover rate, p-value discrepancy) and the overstated claim of 'strongest evidence' when interpreting the results. No erratum is strictly required, but correcting these inconsistencies would improve clarity.

1.
HIGHreporting
Reconcile the crossover rate across the abstract (52%), results (59%), and discussion (58.8%) to a single consistent value.
Inconsistent reporting of a key trial metric undermines reader trust and could be flagged as an internal contradiction.
2.
HIGHreporting
Reconcile the PFS p-value discrepancy: text reports P=0.0002 while Figure 2a legend reports P=0.002 for the same comparison.
A mismatch between text and figure for a primary endpoint p-value is a factual inconsistency that should be corrected.
3.
HIGHreporting
Temper the claim 'The ROME trial provides the strongest evidence supporting MTB implementation in clinical practice' to reflect that it is one of several randomized trials, not necessarily the strongest.
The claim is overstated given the lack of a comparative analysis across all MTB studies; over-claiming is a common reviewer objection.
4.
MEDIUMcopyedit
Fix the typo 'snd' to 'and' in the Competing interests section.
Typographical errors in a published manuscript are unprofessional and easily corrected.
5.
MEDIUMreporting
Add a rationale for the open-label design in the Methods (e.g., impracticality of blinding due to different treatment modalities).
Providing a rationale for the lack of blinding strengthens the study design reporting.
6.
MEDIUMstatistics
Clarify how the assumptions of the CMH test and log-rank test were verified (e.g., proportional hazards) in the Statistical analysis section.
Explicitly addressing assumption verification enhances the statistical rigor and reproducibility.
7.
MEDIUMreporting
Provide exact p-values in figures (e.g., Fig. 2) instead of thresholds like P<0.0001 where feasible.
Exact p-values allow readers to assess the strength of evidence more precisely.
8.
MEDIUMdata code
Specify the name of the secure data-sharing platform in the Data availability statement.
Naming the platform makes the data access route more concrete and actionable.
9.
MEDIUMreporting
Consider making the full statistical analysis plan (SAP) publicly available rather than only upon reasonable request.
Public SAP increases transparency and reduces concerns about post hoc analyses.
10.
MEDIUMreporting
Discuss the potential implications of the higher proportion of women in the TT arm on the results.
Addressing baseline imbalances, even if not statistically significant, preempts reader concerns about confounding.
11.
MEDIUMreporting
Clarify how the protocol amendment in 2024 (adding drugs) affected the predefined statistical analysis plan.
Transparency about protocol changes is essential for interpreting the results as prespecified.
12.
MEDIUMreporting
Report the number of patients who received each specific targeted therapy in the TT arm.
Granular treatment data improves interpretability and reproducibility.
13.
MEDIUMstatistics
Perform a sensitivity analysis adjusting for crossover to assess the robustness of the OS result.
Given the high crossover rate, a sensitivity analysis would strengthen the OS conclusion.
14.
LOWreporting
Provide exact p-values for all secondary endpoints in the text, not just thresholds like '<0.0001'.
Exact p-values for secondary endpoints improve transparency and allow readers to assess evidence strength.
15.
LOWreporting
Consider moving the CONSORT flow diagram into the main text for easier access.
A CONSORT diagram in the main text improves readability and adherence to reporting guidelines.

Full text (82,707 chars · analyzed ~91%, head + tail)Analyzed: Aug 15, 2026

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Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME trial.

Read full text (PMC)

DOI

10.1038/s41591-025-03918-x

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Record fingerprint

e6513aa58ea7f67b8fe7098d6702438bb71aa85616f8daf21e736d67d6da0350

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

2.25 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ClaimsOverstated claim−0.5★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★
LinksDead data/code link−0.25★

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

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary endpoint is ORR, a surrogate for clinical benefit. The paper does not demonstrate target engagement at the tested doses (no PK/PD data) and does not cite validated evidence linking ORR to improved survival or quality of life in this context. The claim of improved outcomes rests on this surrogate without establishing a validated surrogate-to-clinical-outcome link.
“Overall response rate (ORR) was the primary endpoint”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
The primary effect is a modest absolute improvement in ORR of 7.5 percentage points (17.5% vs 10%) and a median PFS improvement of 0.7 months (3.5 vs 2.8 months). These are small fractions of the reference values and are not anchored to a minimal clinically important difference or demonstrated biological meaningfulness. The paper itself describes the ORR improvement as 'modest in magnitude'.
“The improvement in ORR, the primary endpoint of the study, observed in the TT arm compared to the SoC arm within the ITT population (17.5% versus 10%), is clinically relevant and methodologically robust, although modest in magnitude.”
Find in source
03Conclusion reaches beyond the evidence
mediumOverreachreviewer-assessedFull detail
The ROME trial provides the strongest evidence supporting MTB implementation in clinical practice.
“The ROME trial provides, to our knowledge, the strongest evidence supporting MTB implementation in clinical practice, thanks to its agnostic and randomized design.”
DiscussionFind in source
04Declared data/code link does not resolve
mediumAvailabilityrecomputedFull detail
Dead link — nothing to verify.
“https://www.esmo.org/guidelines/esmo-scale-for-clinical-actionability-of-molecular-targets-escat”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 302OverreachOverstated conclusions 03AuthenticityNone found 04DisclosureNone found 105AvailabilityBroken references and links 06Copyedit6 minor suggestions

Numerical inconsistencies

1 finding · worst low

Internal contradictions in the reported numbersAssessed

Recomputed 3 tests: 3 consistent, 0 inconsistent; 1 recomputed directly from the reported test statistics, 2 via agent-written checks.

Overstated conclusions

3 findings · worst high

Efficacy rests on an unvalidated surrogate endpointAssessed
Treatment effect not shown to be clinically meaningfulAssessed
Conclusions overstated beyond the evidenceAssessed

6 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

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

The paper establishes a clear scientific premise by citing prior precision oncology trials and frameworks, and logically motivates the ROME trial.

Evidence

paraphrase[Introduction, paragraph 2]

Introduction ¶4Find in source

Introduction ¶2Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise by citing prior precision oncology trials and frameworks, and provides a logical rationale for the study.

Evidence

Introduction ¶2Find in source

“The nationwide ROME trial was designed to provide comprehensive genomic profiling and TT for patients with solid tumors across multiple medical oncology units in Italy.”

IntroductionFind in source

paraphrase[Introduction, paragraph 4]

“However, the impact of MTBs on patient outcomes requires further validation, as current evidence is limited and varies based on factors such as drug availability and tumor types treated.”

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsINADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The trial design is rigorous with clear randomization, prespecified endpoints, and a statistical analysis plan, though blinding is not applicable due to open-label design.

Evidence

“The randomization list was generated with a dedicated SAS program using the PROC PLAN procedure by an independent statistician.”

Statistical analysisFind in source

MethodsFind in source

“The ROME trial was a multicenter, randomized, open-label phase 2 study comparing tailored treatment (TT) to standard of care (SoC)”

AbstractFind in source

PASSReviewer 2· 85% conf

The trial design is rigorous with clear randomization, blinding (open-label with rationale), power analysis, and predefined inclusion/exclusion criteria.

Evidence

“The randomization list was generated with a dedicated SAS program using the PROC PLAN procedure by an independent statistician.”

Statistical analysisFind in source

MethodsFind in source

“Eligible patients had failed at least one, but no more than two, prior lines of systemic therapy.”

MethodsFind in source

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Demographic and clinical characteristics are well reported, including age, sex, ethnicity, ECOG PS, and tumor types.

Evidence

“Median (range) | 61 (22–85) | 60 (34–84) | 62 (22–85)”

Table 1Find in source

“Caucasian | 392 (98.1) | 196 (98.0) | 196 (98.0)”

Table 1Find in source

PASSReviewer 2· 90% conf

Demographic and clinical characteristics are well reported, including age, sex, ethnicity, and performance status.

Evidence

“Male | 192 (48.0) | 100 (50.0) | 92 (46.0)”

Table 1Find in source

“Median (range) | 61 (22–85) | 60 (34–84) | 62 (22–85)”

Table 1Find in source

“Caucasian | 392 (98.1) | 196 (98.0) | 196 (98.0)”

Table 1Find 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 named committees, informed consent, and regulatory compliance are clearly documented.

Evidence

“The study was approved by the institutional ethics committee of the coordinating center (Sapienza no. rif. C.E. 5575; February 2020) and by the ethics committee of each participating center.”

MethodsFind in source

“All patients signed the specifically conceived informed consent form (ICF).”

MethodsFind in source

“The trial adhered to the principles of the Declaration of Helsinki regarding research involving human subjects.”

MethodsFind in source

PASSReviewer 2· 95% conf

Ethics approval from named committees, informed consent, and regulatory compliance are clearly documented.

Evidence

“The study was approved by the institutional ethics committee of the coordinating center (Sapienza no. rif. C.E. 5575; February 2020) and by the ethics committee of each participating center.”

MethodsFind in source

“All patients signed the specifically conceived informed consent form (ICF).”

MethodsFind in source

“The trial adhered to the principles of the Declaration of Helsinki regarding research involving human subjects.”

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· 85% conf

Investigational products and NGS assays are identified with manufacturers, and software tools are named.

Evidence

“Molecular profiling was performed using FoundationOne CDX and FoundationOne Liquid CDX tests on tissue and liquid biopsies.”

MethodsFind in source

“All analyses were conducted using SAS software (v.9.4).”

Statistical analysisFind in source

AcknowledgementsFind in source

PASSReviewer 2· 85% conf

Investigational products and key reagents are identified with sources, and software tools are named.

Evidence

AcknowledgementsFind in source

“Molecular profiling was performed using FoundationOne CDX and FoundationOne Liquid CDX tests on tissue and liquid biopsies.”

MethodsFind in source

“All analyses were conducted using SAS software (v.9.4).”

Statistical analysisFind in source

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

Statistical methods are well described with named tests, exact p-values, effect sizes with CIs, and software identified; some p-values are reported as thresholds in figures.

Evidence

“The P value from the chi-square test ( P = 0.0294; Extended Data Table ) is nearly identical to the stratified CMH result”

ResultsFind in source

“with a hazard ratio (HR) of 0.66 (95% CI: 0.53–0.82, P = 0.0002; Fig. )”

ResultsFind in source

“All analyses were conducted using SAS software (v.9.4).”

Statistical analysisFind in source

PASSReviewer 2· 80% conf

Statistical tests are named, effect sizes with CIs are reported, and the analysis is appropriate for a clinical trial.

Evidence

ResultsFind in source

“Kaplan–Meier survival analysis, accompanied by the log-rank test, was employed to compare OS and PFS across arms and subgroups.”

Statistical analysisFind in source

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Data availability statement provides a concrete managed-access route with conditions and timeframe; code sharing is not applicable as no bespoke code is mentioned.

Evidence

Data availabilityFind in source

PASSReviewer 2· 90% conf

Data availability statement provides a concrete managed-access route, and trial registration is public.

Evidence

Data availabilityFind in source

“The trial registration, study protocol and methodological details are publicly accessible through ClinicalTrials.gov (accession identifier NCT04591431”

Data availabilityFind in source

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· 90% conf

The manuscript is transparent with trial registration, CONSORT checklist, limitations discussion, proportional conclusions, and funding/COI statements.

Evidence

“The trial is registered on ClinicalTrials.gov with identifier NCT04591431”

MethodsFind in source

Supplementary materialFind in source

“The substantial crossover rate (58.8%) from the SoC arm to the TT arm after disease progression, although ethically appropriate, likely contributed to this lack of OS benefit.”

Discussion ¶4Find in source

PASSReviewer 2· 90% conf

The manuscript is transparent with complete methods, trial registration, CONSORT checklist, and limitations discussed.

Evidence

“The trial is registered on ClinicalTrials.gov with identifier NCT04591431”

MethodsFind in source

Supplementary materialFind in source

“The substantial crossover rate (58.8%) from the SoC arm to the TT arm after disease progression, although ethically appropriate, likely contributed to this lack of OS benefit.”

Discussion ¶4Find in source

Registered (3 IDs: ClinicalTrials.gov, EudraCT). Reporting guideline cited: CONSORT.

Broken references and links

1 finding · worst medium

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.

Dead data/code linksRecomputed

Checked 39 references by DOI: 39 verified.

7 data/code links checked; 6 live, 1 dead.

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.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
HIGHreporting
Reconcile the crossover rate across the abstract (52%), results (59%), and discussion (58.8%) to a single consistent value.
Inconsistent reporting of a key trial metric undermines reader trust and could be flagged as an internal contradiction.
2.
HIGHreporting
Reconcile the PFS p-value discrepancy: text reports P=0.0002 while Figure 2a legend reports P=0.002 for the same comparison.
A mismatch between text and figure for a primary endpoint p-value is a factual inconsistency that should be corrected.
3.
HIGHreporting
Temper the claim 'The ROME trial provides the strongest evidence supporting MTB implementation in clinical practice' to reflect that it is one of several randomized trials, not necessarily the strongest.
The claim is overstated given the lack of a comparative analysis across all MTB studies; over-claiming is a common reviewer objection.
4.
MEDIUMcopyedit
Fix the typo 'snd' to 'and' in the Competing interests section.
Typographical errors in a published manuscript are unprofessional and easily corrected.
5.
MEDIUMreporting
Add a rationale for the open-label design in the Methods (e.g., impracticality of blinding due to different treatment modalities).
Providing a rationale for the lack of blinding strengthens the study design reporting.
6.
MEDIUMstatistics
Clarify how the assumptions of the CMH test and log-rank test were verified (e.g., proportional hazards) in the Statistical analysis section.
Explicitly addressing assumption verification enhances the statistical rigor and reproducibility.
7.
MEDIUMreporting
Provide exact p-values in figures (e.g., Fig. 2) instead of thresholds like P<0.0001 where feasible.
Exact p-values allow readers to assess the strength of evidence more precisely.
8.
MEDIUMdata code
Specify the name of the secure data-sharing platform in the Data availability statement.
Naming the platform makes the data access route more concrete and actionable.
9.
MEDIUMreporting
Consider making the full statistical analysis plan (SAP) publicly available rather than only upon reasonable request.
Public SAP increases transparency and reduces concerns about post hoc analyses.
10.
MEDIUMreporting
Discuss the potential implications of the higher proportion of women in the TT arm on the results.
Addressing baseline imbalances, even if not statistically significant, preempts reader concerns about confounding.
11.
MEDIUMreporting
Clarify how the protocol amendment in 2024 (adding drugs) affected the predefined statistical analysis plan.
Transparency about protocol changes is essential for interpreting the results as prespecified.
12.
MEDIUMreporting
Report the number of patients who received each specific targeted therapy in the TT arm.
Granular treatment data improves interpretability and reproducibility.
13.
MEDIUMstatistics
Perform a sensitivity analysis adjusting for crossover to assess the robustness of the OS result.
Given the high crossover rate, a sensitivity analysis would strengthen the OS conclusion.
14.
LOWreporting
Provide exact p-values for all secondary endpoints in the text, not just thresholds like '<0.0001'.
Exact p-values for secondary endpoints improve transparency and allow readers to assess evidence strength.
15.
LOWreporting
Consider moving the CONSORT flow diagram into the main text for easier access.
A CONSORT diagram in the main text improves readability and adherence to reporting guidelines.

Full text (82,707 chars · analyzed ~91%, head + tail)Analyzed: Aug 15, 2026