Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.

Name: Kaimen Rigor review — Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.
Item: Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.
Rating: 59
Author: Alpha1

Porcari S, Ciccarese C, Heidrich V, Rondinella D, Quaranta G, Severino A, Arduini D, Buti S, Fornarini G, Primi F, Stumbo L, Giannarelli D, Giudice GC, Damassi A, Giron Berríos JR, Punčochář M, Barbazuk TB, Piccinno G, Pinto F, Armanini F, Asnicar F, Schinzari G, Derosa L, Kroemer G, Sanguinetti M, Masucci L, Gasbarrini A, Tortora G, Cammarota G, Zitvogel L, Segata N, Iacovelli R, Ianiro G

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Kaimen Rigor review — 2.75★ (Weak), 0 critical, 5 high issues for “Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.”

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This rigor review was examined and confirmed by Alpha1 Editorial · August 10, 2026

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Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.

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DOI

10.1038/s41591-025-04189-2

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6ac278ad2276514c643b3fb49472171117dc0763e49dd1e07bb6f99f043dd910

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.

Paper source

Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO 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 10, 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

StatisticsStatistic did not reproduce ×3−1.5★
StatisticsPrinted percentage does not match its own count (capped)−0.25★
ReportingBiological variables partially met−0.25★
ReportingKey resources partially met−0.25★

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

Not verified in this report

References were not verified against Crossref/OpenAlex.
The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run on this paper: the pass that reads its reported means did not complete. No reported mean was checked for arithmetic impossibility.

Biggest issues

01Significance claim does not survive recomputation
highOverreachrecomputedFull detail
Recomputed hazard ratio 0.36 (95% CI 0.13–0.99), reported p=0.167
“hazard ratio = 0.36, 95% CI: 0.13–0.99, P = 0.167”
Find in source
02Significance claim does not survive recomputation
highOverreachrecomputedFull detail
Recomputed hazard ratio 0.36 (95% CI 0.13–0.99), reported p=0.146
“hazard ratio = 0.36 (95% CI: 0.13–0.99), P = 0.146”
Find in source
03Significance claim does not survive recomputation
highOverreachrecomputedFull detail
Recomputed HR 0.36 (95% CI 0.13–0.99), reported p=0.146
“HR 0.36, 95% CI 0.13-0.99, p = 0.146”
Find in source
04Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
67% does not match the reported count 33/50
“33 of 50 patients (67%)”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 202OverreachOverstated conclusions 03AuthenticityNone found 204DisclosureReporting gaps 05AvailabilityNone found 06Copyedit3 minor suggestions

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

This is a well-designed randomized double-blind placebo-controlled phase 2a trial with strong reporting, registration, and data availability. Its main weaknesses are incomplete identification of investigational products, missing race/ethnicity and weight/performance-status demographics, and a demonstrable inconsistency in reported p-values for a key hazard ratio.

Two independent reviewer runs were synthesized; they diverged on biological variables (pass vs warn) which we resolved to warn, and both missed the statistical inconsistency found by the verification component, which we incorporated. The statistics component covered only 13 of reported tests; everything not recomputed remains unverified.

Numerical inconsistencies

1 finding · 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

Recomputed 12 tests: 9 consistent, 3 inconsistent (3 change significance at p<.05); 8 recomputed directly from the reported test statistics, 4 via agent-written checks. 1 printed percentage that does not match its own count.

Overstated conclusions

2 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.

Significance claim flips when recomputedRecomputed
Conclusions only partially backed by the presented evidenceAssessed

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

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

Data authenticity concerns

None found

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

Checked — nothing surfaced.

Reporting gaps

2 findings · 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.

Biological variables underreported (sex, age, strain)Assessed
Key resources under-identified (antibodies, cell lines, RRIDs)Assessed

Eight Dimensions6 pass · 2 warn

The introduction cites key studies on ICI efficacy in RCC, the association of gut microbiome with ICI response, and prior FMT trials. It explicitly states that no RCT has evaluated FMT in mRCC, providing a rationale for the study. The limitations of prior work (e.g., lack of RCTs, focus on melanoma) are acknowledged.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 100% conf

The study clearly establishes its scientific foundation by citing prior research on ICI in RCC, the role of the gut microbiome, and FMT, while acknowledging gaps in the literature.

Evidence

paraphrase[Introduction, paragraph 1]

“The introduction references the KEYNOTE-426 trial and discusses evidence linking gut microbiome to ICI response.”

“However, thus far, no randomized controlled trials (RCTs) have demonstrated the efficacy of FMT in mRCC.”

Introduction ¶3Find in source

PASSReviewer 2· 95% conf

The paper establishes a clear scientific foundation, citing prior work on gut microbiome and ICI efficacy, and provides a logical rationale for the study hypothesis.

Evidence

paraphrase[Introduction, paragraph 2]

“The introduction cites studies on antibiotics disrupting gut microbiome and association with worse ICI response, and microbial taxa linked to ICI response.”

“Our phase 2a placebo-controlled RCT aims to evaluate whether FMT from patients with mRCC with complete response to ICIs was effective in improving response to combined first-line therapy with pembrolizumab and axitinib in patients with mRCC.”

IntroductionFind in source

“However, thus far, no randomized controlled trials (RCTs) have demonstrated the efficacy of FMT in mRCC.”

Introduction ¶3Find in source

Randomization was performed using an online random number generator with permuted blocks of size 4, allocation concealed. Blinding was maintained for patients, study staff, and outcome assessors. A power analysis was reported with assumptions. Inclusion/exclusion criteria were detailed, and analysis populations (ITT, FAS, per-protocol, safety) were pre-defined. The primary endpoint was 12-month PFS. The study is registered at ClinicalTrials.gov.

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· 100% conf

The study design is rigorous: randomized, double-blind, placebo-controlled, with a pre-specified sample size calculation and clear inclusion/exclusion criteria.

Evidence

paraphrase[Methods: Randomization and masking]

“An online random number generator software (https://www.sealedenvelope.com) was used to provide random permuted blocks with a block size of four and an equal allocation ratio; the sequence was hidden until the interventions were assigned.”

“A total of 50 patients is required to enter this two-treatment, parallel-design study.”

MethodsFind in source

paraphrase[Methods: Study population]

“Detailed inclusion and exclusion criteria are provided, including metastatic RCC, no prior systemic therapy, and exclusion for recent antibiotic use.”

PASSReviewer 2· 95% conf

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

Evidence

paraphrase[Methods, Randomization and masking]

“To mask treatments to recipients, both infusate bottles and syringes were covered with dark-colored paper before the infusion... Placebo capsules were made of cellulose and were identical in appearance to the FMT capsules... Physicians who evaluated patients at follow-up (clinical outcome assessors) were blinded to administered treatments, as were authors involved in outcome analysis.”

“A total of 50 patients is required to enter this two-treatment, parallel-design study. The probability is 80% that the study detects a treatment difference at a one-sided 5.0% significance level, if the true hazard ratio is 0.436.”

MethodsFind in source

Table 1 reports sex and median age with range. Health status is indicated by IMDC risk class, but weight or performance status (e.g., Karnofsky score) is not tabulated. No race/ethnicity data are reported. For a human study, these are important biological variables.

Sub-criteria

demographicsNOT REPORTED

sex reportedADEQUATE

sex justifiedN/A

age weight healthINADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 100% conf

Patient demographics and baseline characteristics are well-reported, including sex, age, and disease-related variables.

Evidence

“Most participants were male (73%), and the median age at the time of treatment initiation was 62 years (range, 41–79 years).”

Table 1Find in source

paraphrase[Results, Table 1]

“Table 1 includes age, sex, histology, IMDC class, and sites of metastases for both arms.”

WARNReviewer 2· 85% conf

Sex and age are reported, but weight and detailed health status (e.g., ECOG/Karnofsky) are not provided, and race/ethnicity is not reported.

Evidence

paraphrase[Results, Table 1]

“Male sex: 17 (74%) | 16 (73%)”

“the median age at the time of treatment initiation was 62 years (range, 41–79 years)”

Results ¶3Find in source

absence[Whole paper]

Race/ethnicity is not reported.

The study was approved by the institutional review board/ethics committee (ID 2664). All patients gave written informed consent. The study was conducted in accordance with the Declaration of Helsinki and ICH-GCP guidelines. ClinicalTrials.gov registration is provided.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 100% conf

The study obtained ethics approval from a named IRB, all patients provided informed consent, and regulatory compliance is stated.

Evidence

paraphrase[Methods: Study design and approvals]

“The study was approved by the institutional review board (IRB)/local ethics committee (ID: 2664).”

“All enrolled patients gave their written informed consent to participate in the study.”

MethodsFind in source

paraphrase[Methods: Study design and approvals]

“The study was conducted in accordance with the Declaration of Helsinki and International Conference on the Harmonization of Good Clinical Practice guidelines.”

PASSReviewer 2· 95% conf

The study has clear IRB approval, informed consent, and compliance with ethical guidelines.

Evidence

“The study was approved by the institutional review board (IRB)/local ethics committee (ID: 2664)”

MethodsFind in source

“All enrolled patients gave their written informed consent to participate in the study.”

MethodsFind in source

“The study was conducted in accordance with the Declaration of Helsinki and International Conference on the Harmonization of Good Clinical Practice guidelines”

MethodsFind in source

The drugs pembrolizumab and axitinib are named without manufacturer or lot numbers; the FMT is described but donor identification is limited. Software tools are well-identified with versions. No custom code was shared publicly. According to the scoring rule, the trial's investigational product is a scored resource, and the absence of manufacturer details makes it reported_but_inadequate.

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 90% conf

The investigational products (pembrolizumab, axitinib, FMT) are described but not fully identified with manufacturer information, and no custom code repository is provided.

Evidence

“The combination of pembrolizumab (a programmed cell death protein 1 (PD-1) inhibitor monoclonal antibody) with axitinib (a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor)”

Introduction ¶1Find in source

paraphrase[Methods: Microbiome analysis]

“MetaPhlAn 4 (version 4.1), using the marker genes database vJun23_202307”

absence[Data availability section]

No custom code repository is provided.

WARNReviewer 2· 80% conf

Software tools are well identified, but the investigational products (pembrolizumab, axitinib, FMT) lack full identification details such as manufacturer, dose, and formulation.

Evidence

“we enrolled patients with metastatic, histologically confirmed RCC who were eligible to receive pembrolizumab and axitinib as first-line therapy.”

ResultsFind in source

“IBM-SPSS version 28.0 statistical software, GraphPad Prism version 10, R version 4.4.2 (‘survival’ and ‘survminer’ packages) and Python version 3.10.12 (‘scikit-bio’ and ‘scipy’ packages) were used for the analyses.”

Statistical analysisFind in source

paraphrase[Methods, Assessment of donor strain engraftment]

“The strain engraftment pipeline is described using previously reported methods and improvements, but no public code repository is mentioned.”

The paper reports exact p-values (e.g., P=0.053, P=0.035) and hazard ratios with 95% CIs. Kaplan-Meier curves and box plots are shown with error bars defined. Software is identified. The Cox proportional hazards assumption was checked. No arithmetic inconsistencies were detected in the checked statistics.

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· 100% conf

Statistical tests are named, assumptions verified, exact p-values and effect sizes with CIs are reported, and data presentation is adequate.

Evidence

“hazard ratio = 0.50, 90% CI: 0.27–0.92, P = 0.035”

Figure 2AFind in source

paraphrase[Results, Primary and secondary efficacy outcomes]

“Median PFS with 95% CI and hazard ratio with 90% CI are reported.”

“IBM-SPSS version 28.0 statistical software, GraphPad Prism version 10, R version 4.4.2”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

Statistical tests are named, effect sizes with CIs are reported, software is identified, and data presentation is adequate. Some p-values are reported as thresholds rather than exact values.

Evidence

“70% versus 41% for d-FMT versus p-FMT, respectively, P = 0.053”

ResultsFind in source

“P < 0.001 across all timepoints starting from week 1 follow-up”

ResultsFind in source

“hazard ratio = 0.50, 90% CI: 0.27–0.92, P = 0.035”

ResultsFind in source

The shotgun metagenomic data are available at ENA under PRJEB94043. A data availability statement describes access to patient-level data upon request. Although no custom code repository is provided, the majority of applicable criteria are adequate.

Sub-criteria

code sharingNOT REPORTED

accession numbersADEQUATE

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 100% conf

The metagenomic data are deposited in a public repository with an accession number, and a data availability statement is provided; however, no custom code was shared.

Evidence

paraphrase[Data availability section]

“The shotgun metagenomic data generated in this study are available at the European Nucleotide Archive under accession number PRJEB94043.”

“PRJEB94043 (http://www.ebi.ac.uk/ena/data/view/PRJEB94043)”

Data availabilityFind in source

absence[Data availability and Methods]

No code repository is mentioned.

PASSReviewer 2· 90% conf

Sequencing data are deposited in ENA with accession number, and a data availability statement describes managed access for clinical data. Custom code is not shared, but this is common for clinical trials.

Evidence

paraphrase[Data availability section]

“The shotgun metagenomic data generated in this study are available at the European Nucleotide Archive under accession number PRJEB94043 (http://www.ebi.ac.uk/ena/data/view/PRJEB94043).”

absence[Whole paper]

No custom code repository is mentioned.

Methods are comprehensive. The trial is registered (NCT04758507) and a CONSORT checklist is provided. All pre-specified primary and secondary outcomes are reported, including negative results. Limitations are discussed (sample size, single donor). Conclusions are proportional to the evidence. Funding and competing interests are disclosed.

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· 100% conf

The manuscript is transparent with detailed methods, trial registration, CONSORT checklist, and complete reporting of outcomes and limitations.

Evidence

“ClinicalTrials.gov identifier: NCT04758507”

AbstractFind in source

paraphrase[Methods: Study design and approvals]

“This study was conducted by following CONSORT guidelines, and a CONSORT checklist is provided in Supplementary Table.”

“This study has some limitations. The sample size was relatively small, with only 45 patients evaluated for the primary endpoint.”

Discussion ¶5Find in source

PASSReviewer 2· 95% conf

The manuscript is well-reported: methods are detailed, trial is registered, CONSORT checklist is provided, all outcomes are reported, limitations are discussed, conclusions are proportional, and funding/COI are disclosed.

Evidence

“ClinicalTrials.gov identifier: NCT04758507”

AbstractFind in source

paraphrase[Methods, Study design and approvals]

“This study was conducted by following CONSORT guidelines, and a CONSORT checklist is provided in Supplementary Table.”

paraphrase[Discussion, paragraph 5]

“The discussion notes the small sample size, baseline imbalances, reliance on a single donor, and treatment delays as limitations.”

Registered (1 ID: ClinicalTrials.gov). Reporting guideline cited: CONSORT.

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.

4 data/code links checked; 4 live.

Copyediting

3 minor

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

No major wording or formatting errors. 3 minor suggestions below.

3 copyedit issues flagged: mostly consistency, other, clarity.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is methodologically robust overall, but the inconsistent p-values for the HR 0.36 (reported 0.167/0.146 vs recomputed 0.0485) constitute a decision error that warrants an erratum or independent re-analysis; readers should weigh this against the otherwise strong design and reporting. Minor gaps in reagent identification and demographics are also worth noting.

1.
HIGHstatistics
In the Results, re-verify the reported p-values for the hazard ratio 0.36 (95% CI 0.13–0.99): reported p=0.167 and p=0.146 differ from the recomputed p=0.0485, which changes the significance decision.
This is a demonstrable statistical error that affects the study's conclusions and warrants a correction or erratum.
2.
HIGHstatistics
Replace threshold-only p-values such as 'P < 0.001' with exact values where available in the Results.
Reviewer 2 noted imprecise reporting; exact values support reproducibility and reader verification.
3.
HIGHother
Add manufacturer, dose, and regimen details for pembrolizumab and axitinib in the Methods section.
Both reviewers flagged incomplete identification of investigational products, which hampers reproducibility.
4.
HIGHother
Provide details of FMT capsule preparation including excipients and storage conditions in the Methods.
Improves reproducibility of the intervention and addresses Reviewer 1's concern.
5.
HIGHreporting
Report race/ethnicity and weight or performance status (e.g., Karnofsky) in Table 1.
Reviewer 2 identified these as missing biological variables; adds completeness for readers.
6.
MEDIUMdata code
Deposit custom analysis code (e.g., strain engraftment pipeline) in a public repository with a persistent identifier.
Both reviewers noted no code repository; increases reproducibility.
7.
MEDIUMreporting
Add a statement on clinical dataset availability under a data use agreement in the Data Availability section.
Reviewer 1 noted that patient-level data access policy could be more explicit.
8.
MEDIUMcopyedit
Add version numbers for the Python packages used in statistical analysis in the Methods.
Copyedit flagged missing package versions, improving reproducibility.
9.
LOWcopyedit
Add a comma after 'guidelines' in the Methods sentence about compliance with the Declaration of Helsinki and ICH-GCP.
Minor readability improvement flagged by copyedit.
10.
LOWcopyedit
Consider harmonizing the reporting of P=0.053 in the Abstract with other sections.
Copyedit noted consistency; already acceptable but could be standardized.

Full text (84,385 chars · analyzed ~89%, head + tail)Analyzed: Aug 10, 2026

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Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.

Read full text (PMC)

DOI

10.1038/s41591-025-04189-2

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Record fingerprint

6ac278ad2276514c643b3fb49472171117dc0763e49dd1e07bb6f99f043dd910

Verify via API

Issued Aug 10, 2026Engine 7.29.0

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

StatisticsStatistic did not reproduce ×3−1.5★
StatisticsPrinted percentage does not match its own count (capped)−0.25★
ReportingBiological variables partially met−0.25★
ReportingKey resources partially met−0.25★

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

Not verified in this report

References were not verified against Crossref/OpenAlex.
The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run on this paper: the pass that reads its reported means did not complete. No reported mean was checked for arithmetic impossibility.

Biggest issues

01Significance claim does not survive recomputation
highOverreachrecomputedFull detail
Recomputed hazard ratio 0.36 (95% CI 0.13–0.99), reported p=0.167
“hazard ratio = 0.36, 95% CI: 0.13–0.99, P = 0.167”
Find in source
02Significance claim does not survive recomputation
highOverreachrecomputedFull detail
Recomputed hazard ratio 0.36 (95% CI 0.13–0.99), reported p=0.146
“hazard ratio = 0.36 (95% CI: 0.13–0.99), P = 0.146”
Find in source
03Significance claim does not survive recomputation
highOverreachrecomputedFull detail
Recomputed HR 0.36 (95% CI 0.13–0.99), reported p=0.146
“HR 0.36, 95% CI 0.13-0.99, p = 0.146”
Find in source
04Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
67% does not match the reported count 33/50
“33 of 50 patients (67%)”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 202OverreachOverstated conclusions 03AuthenticityNone found 204DisclosureReporting gaps 05AvailabilityNone found 06Copyedit3 minor suggestions

Numerical inconsistencies

1 finding · worst medium

Printed percentage does not match its own countRecomputed

Overstated conclusions

2 findings · worst high

Significance claim flips when recomputedRecomputed
Conclusions only partially backed by the presented evidenceAssessed

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

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

Data authenticity concerns

None found

Checked — nothing surfaced.

Reporting gaps

2 findings · worst medium

Biological variables underreported (sex, age, strain)Assessed
Key resources under-identified (antibodies, cell lines, RRIDs)Assessed

Eight Dimensions6 pass · 2 warn

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 100% conf

The study clearly establishes its scientific foundation by citing prior research on ICI in RCC, the role of the gut microbiome, and FMT, while acknowledging gaps in the literature.

Evidence

paraphrase[Introduction, paragraph 1]

“The introduction references the KEYNOTE-426 trial and discusses evidence linking gut microbiome to ICI response.”

“However, thus far, no randomized controlled trials (RCTs) have demonstrated the efficacy of FMT in mRCC.”

Introduction ¶3Find in source

PASSReviewer 2· 95% conf

The paper establishes a clear scientific foundation, citing prior work on gut microbiome and ICI efficacy, and provides a logical rationale for the study hypothesis.

Evidence

paraphrase[Introduction, paragraph 2]

“The introduction cites studies on antibiotics disrupting gut microbiome and association with worse ICI response, and microbial taxa linked to ICI response.”

IntroductionFind in source

“However, thus far, no randomized controlled trials (RCTs) have demonstrated the efficacy of FMT in mRCC.”

Introduction ¶3Find 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· 100% conf

The study design is rigorous: randomized, double-blind, placebo-controlled, with a pre-specified sample size calculation and clear inclusion/exclusion criteria.

Evidence

paraphrase[Methods: Randomization and masking]

“A total of 50 patients is required to enter this two-treatment, parallel-design study.”

MethodsFind in source

paraphrase[Methods: Study population]

“Detailed inclusion and exclusion criteria are provided, including metastatic RCC, no prior systemic therapy, and exclusion for recent antibiotic use.”

PASSReviewer 2· 95% conf

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

Evidence

paraphrase[Methods, Randomization and masking]

MethodsFind in source

Sub-criteria

demographicsNOT REPORTED

sex reportedADEQUATE

sex justifiedN/A

age weight healthINADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 100% conf

Patient demographics and baseline characteristics are well-reported, including sex, age, and disease-related variables.

Evidence

“Most participants were male (73%), and the median age at the time of treatment initiation was 62 years (range, 41–79 years).”

Table 1Find in source

paraphrase[Results, Table 1]

“Table 1 includes age, sex, histology, IMDC class, and sites of metastases for both arms.”

WARNReviewer 2· 85% conf

Sex and age are reported, but weight and detailed health status (e.g., ECOG/Karnofsky) are not provided, and race/ethnicity is not reported.

Evidence

paraphrase[Results, Table 1]

“Male sex: 17 (74%) | 16 (73%)”

“the median age at the time of treatment initiation was 62 years (range, 41–79 years)”

Results ¶3Find in source

absence[Whole paper]

Race/ethnicity is not reported.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 100% conf

The study obtained ethics approval from a named IRB, all patients provided informed consent, and regulatory compliance is stated.

Evidence

paraphrase[Methods: Study design and approvals]

“The study was approved by the institutional review board (IRB)/local ethics committee (ID: 2664).”

“All enrolled patients gave their written informed consent to participate in the study.”

MethodsFind in source

paraphrase[Methods: Study design and approvals]

“The study was conducted in accordance with the Declaration of Helsinki and International Conference on the Harmonization of Good Clinical Practice guidelines.”

PASSReviewer 2· 95% conf

The study has clear IRB approval, informed consent, and compliance with ethical guidelines.

Evidence

“The study was approved by the institutional review board (IRB)/local ethics committee (ID: 2664)”

MethodsFind in source

“All enrolled patients gave their written informed consent to participate in the study.”

MethodsFind in source

“The study was conducted in accordance with the Declaration of Helsinki and International Conference on the Harmonization of Good Clinical Practice guidelines”

MethodsFind in source

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 90% conf

The investigational products (pembrolizumab, axitinib, FMT) are described but not fully identified with manufacturer information, and no custom code repository is provided.

Evidence

Introduction ¶1Find in source

paraphrase[Methods: Microbiome analysis]

“MetaPhlAn 4 (version 4.1), using the marker genes database vJun23_202307”

absence[Data availability section]

No custom code repository is provided.

WARNReviewer 2· 80% conf

Software tools are well identified, but the investigational products (pembrolizumab, axitinib, FMT) lack full identification details such as manufacturer, dose, and formulation.

Evidence

“we enrolled patients with metastatic, histologically confirmed RCC who were eligible to receive pembrolizumab and axitinib as first-line therapy.”

ResultsFind in source

Statistical analysisFind in source

paraphrase[Methods, Assessment of donor strain engraftment]

“The strain engraftment pipeline is described using previously reported methods and improvements, but no public code repository is mentioned.”

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· 100% conf

Statistical tests are named, assumptions verified, exact p-values and effect sizes with CIs are reported, and data presentation is adequate.

Evidence

“hazard ratio = 0.50, 90% CI: 0.27–0.92, P = 0.035”

Figure 2AFind in source

paraphrase[Results, Primary and secondary efficacy outcomes]

“Median PFS with 95% CI and hazard ratio with 90% CI are reported.”

“IBM-SPSS version 28.0 statistical software, GraphPad Prism version 10, R version 4.4.2”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

Statistical tests are named, effect sizes with CIs are reported, software is identified, and data presentation is adequate. Some p-values are reported as thresholds rather than exact values.

Evidence

“70% versus 41% for d-FMT versus p-FMT, respectively, P = 0.053”

ResultsFind in source

“P < 0.001 across all timepoints starting from week 1 follow-up”

ResultsFind in source

“hazard ratio = 0.50, 90% CI: 0.27–0.92, P = 0.035”

ResultsFind in source

Sub-criteria

code sharingNOT REPORTED

accession numbersADEQUATE

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 100% conf

The metagenomic data are deposited in a public repository with an accession number, and a data availability statement is provided; however, no custom code was shared.

Evidence

paraphrase[Data availability section]

“The shotgun metagenomic data generated in this study are available at the European Nucleotide Archive under accession number PRJEB94043.”

“PRJEB94043 (http://www.ebi.ac.uk/ena/data/view/PRJEB94043)”

Data availabilityFind in source

absence[Data availability and Methods]

No code repository is mentioned.

PASSReviewer 2· 90% conf

Evidence

paraphrase[Data availability section]

“The shotgun metagenomic data generated in this study are available at the European Nucleotide Archive under accession number PRJEB94043 (http://www.ebi.ac.uk/ena/data/view/PRJEB94043).”

absence[Whole paper]

No custom code repository is mentioned.

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· 100% conf

The manuscript is transparent with detailed methods, trial registration, CONSORT checklist, and complete reporting of outcomes and limitations.

Evidence

“ClinicalTrials.gov identifier: NCT04758507”

AbstractFind in source

paraphrase[Methods: Study design and approvals]

“This study was conducted by following CONSORT guidelines, and a CONSORT checklist is provided in Supplementary Table.”

“This study has some limitations. The sample size was relatively small, with only 45 patients evaluated for the primary endpoint.”

Discussion ¶5Find in source

PASSReviewer 2· 95% conf

Evidence

“ClinicalTrials.gov identifier: NCT04758507”

AbstractFind in source

paraphrase[Methods, Study design and approvals]

“This study was conducted by following CONSORT guidelines, and a CONSORT checklist is provided in Supplementary Table.”

paraphrase[Discussion, paragraph 5]

“The discussion notes the small sample size, baseline imbalances, reliance on a single donor, and treatment delays as limitations.”

Registered (1 ID: ClinicalTrials.gov). Reporting guideline cited: CONSORT.

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.

4 data/code links checked; 4 live.

Copyediting

3 minor

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

No major wording or formatting errors. 3 minor suggestions below.

3 copyedit issues flagged: mostly consistency, other, clarity.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
HIGHstatistics
In the Results, re-verify the reported p-values for the hazard ratio 0.36 (95% CI 0.13–0.99): reported p=0.167 and p=0.146 differ from the recomputed p=0.0485, which changes the significance decision.
This is a demonstrable statistical error that affects the study's conclusions and warrants a correction or erratum.
2.
HIGHstatistics
Replace threshold-only p-values such as 'P < 0.001' with exact values where available in the Results.
Reviewer 2 noted imprecise reporting; exact values support reproducibility and reader verification.
3.
HIGHother
Add manufacturer, dose, and regimen details for pembrolizumab and axitinib in the Methods section.
Both reviewers flagged incomplete identification of investigational products, which hampers reproducibility.
4.
HIGHother
Provide details of FMT capsule preparation including excipients and storage conditions in the Methods.
Improves reproducibility of the intervention and addresses Reviewer 1's concern.
5.
HIGHreporting
Report race/ethnicity and weight or performance status (e.g., Karnofsky) in Table 1.
Reviewer 2 identified these as missing biological variables; adds completeness for readers.
6.
MEDIUMdata code
Deposit custom analysis code (e.g., strain engraftment pipeline) in a public repository with a persistent identifier.
Both reviewers noted no code repository; increases reproducibility.
7.
MEDIUMreporting
Add a statement on clinical dataset availability under a data use agreement in the Data Availability section.
Reviewer 1 noted that patient-level data access policy could be more explicit.
8.
MEDIUMcopyedit
Add version numbers for the Python packages used in statistical analysis in the Methods.
Copyedit flagged missing package versions, improving reproducibility.
9.
LOWcopyedit
Add a comma after 'guidelines' in the Methods sentence about compliance with the Declaration of Helsinki and ICH-GCP.
Minor readability improvement flagged by copyedit.
10.
LOWcopyedit
Consider harmonizing the reporting of P=0.053 in the Abstract with other sections.
Copyedit noted consistency; already acceptable but could be standardized.

Full text (84,385 chars · analyzed ~89%, head + tail)Analyzed: Aug 10, 2026