Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Cefepime-Taniborbactam in Complicated Urinary Tract Infection.

Name: Kaimen Rigor review — Cefepime-Taniborbactam in Complicated Urinary Tract Infection.
Item: Cefepime-Taniborbactam in Complicated Urinary Tract Infection.
Rating: 96
Author: Alpha1

Wagenlehner FM, Gasink LB, McGovern PC, Moeck G, McLeroth P, Dorr M, Dane A, Henkel T, CERTAIN-1 Study Team

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Kaimen Rigor review — 3.75★ (Adequate), 0 critical, 5 high issues for “Cefepime-Taniborbactam in Complicated Urinary Tract Infection.”

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

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Cefepime-Taniborbactam in Complicated Urinary Tract Infection.

Wagenlehner FM, Gasink LB, McGovern PC, Moeck G, McLeroth P, Dorr M, Dane A, Henkel T, CERTAIN-1 Study Team

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DOI

10.1056/NEJMoa2304748

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d07863954291b5301ff527b5d5a9aa515be7d67a8afd0b34dec37cf552b7abb1

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Issued Aug 16, 2026Engine 7.39.0

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Cefepime-Taniborbactam in Complicated Urinary Tract Infection.

Wagenlehner FM, Gasink LB, McGovern PC, Moeck G, McLeroth P, Dorr M, Dane A, Henkel T, CERTAIN-1 Study Team

Paper source

Cefepime-Taniborbactam in Complicated Urinary Tract Infection.

Read full text

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Links back to this Kaimen Rigor review.

Alpha1 Editorial

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

Kaimen Rigor review

Kaimen Rigor reviewed

3.75 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
CitationsUnresolved reference ×2−0.5★
ReportingData & code availability partially met−0.25★

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

Not verified in this report

No data or code availability links were detected to verify.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary efficacy outcome is a composite of microbiologic and clinical success. Microbiologic success is a surrogate endpoint (reduction of bacteria in urine culture), and while clinical success is a patient-reported outcome, the composite is not a hard clinical outcome. The paper does not provide evidence linking the surrogate (microbiologic eradication) to long-term clinical outcomes, nor does it demonstrate target engagement at the tested dose beyond in vitro activity.
“The primary efficacy outcome was a composite of both microbiologic and clinical success in the microITT population at test of cure on trial days 19 to 23.”
Find in source

Findings by category

01ArithmeticNone found 102OverreachOverstated conclusions 03AuthenticityNone found 104DisclosureReporting gaps 105AvailabilityBroken references and links · partly checked 06CopyeditNone found

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-conducted and well-reported phase 3 randomized controlled trial with rigorous design, clear ethical approvals, and appropriate statistical methods. The main weaknesses are minor reporting gaps: the data sharing statement is not detailed in the text, statistical software is not named, and adherence to a reporting guideline is not explicitly stated.

Both reviewers independently scored all eight dimensions and agreed on every status, so no divergence needed reconciliation. The statistics verification component recomputed only 1 reported test (consistent), so the broader statistical analysis is not fully machine-verified. The citation component flagged 2 references as not found in registry, which are addressed in the action items.

Numerical inconsistencies

None found

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.

Checked — nothing surfaced.

Recomputed 1 test: 1 consistent, 0 inconsistent; 1 via agent-written checks.

Overstated conclusions

1 finding · 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

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

Premise concern: surrogate not validated for clinical benefit.

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

1 finding · worst medium

Required detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.

Data/code availability incompleteAssessed

Eight Dimensions7 pass · 1 warn

The introduction cites multiple prior studies on the threat of resistant organisms and the in vitro/in vivo activity of cefepime–taniborbactam, establishing the scientific need. The rationale linking the drug's mechanism to the trial objective is explicit. Limitations of prior work are implicitly addressed by the phase 3 design, though not explicitly framed as addressing prior limitations.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The premise is well-established with extensive prior work and a clear rationale.

Evidence

paraphrase[Introduction, paragraph 1]

“The cefepime–taniborbactam combination is active in vitro against most isolates of carbapenem-resistant Enterobacterales species, multidrug-resistant Pseudomonas aeruginosa, and Enterobacterales species and P. aeruginosa organisms that are resistant to both ceftolozane–tazobactam and ceftazidime–avibactam.”

paraphrase[Introduction, paragraph 2]

“We performed the Cefepime Rescue with Taniborbactam in Complicated UTI (CERTAIN-1) phase 3 trial to evaluate the safety and efficacy of cefepime–taniborbactam as compared with meropenem.”

absence[Introduction]

Limitations of prior research are not explicitly discussed.

PASSReviewer 2· 95% conf

The paper establishes a clear scientific premise with extensive prior work and a logical rationale for the trial.

Evidence

paraphrase[Introduction, paragraphs 1-3]

“Carbapenem-resistant Enterobacterales species and multidrug-resistant Pseudomonas aeruginosa are global health threats. Cefepime–taniborbactam is an investigational β-lactam and β-lactamase inhibitor combination with activity against Enterobacterales species and P. aeruginosa expressing serine- and metallo-β-lactamases.”

paraphrase[Introduction, last paragraph]

“We performed the Cefepime Rescue with Taniborbactam in Complicated UTI (CERTAIN-1) phase 3 trial to evaluate the safety and efficacy of cefepime–taniborbactam as compared with meropenem (a preferred treatment option for infections caused by ESBL-producing gram-negative pathogens) in hospitalized patients with complicated UTI.”

absence[Introduction]

Limitations of prior research are not explicitly discussed as such.

Randomization method (central computer-generated sequence, block size 6, stratified) and unit (patient) are reported. Blinding is described (double-blind, double-dummy, with unblinded pharmacy staff). Power analysis is provided (≥396 microITT patients, >90% power). Inclusion/exclusion criteria are detailed. Outlier handling is addressed via missing-data imputation (counted as failures). Controls are inherent in the active-comparator design. Independent replication is not applicable for a single pivotal trial.

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The trial design is rigorous with adequate randomization, blinding, power analysis, and pre-specified populations.

Evidence

“An interactive-response system was used for randomization with a central computer-generated sequence and a block size of 6.”

MethodsFind in source

“The trial sponsor, investigators, site staff members who were participating in patient care or clinical evaluations, and patients were not aware of treatment assignments.”

MethodsFind in source

paraphrase[Methods, Statistical Analysis]

“We determined that the enrollment of at least 396 patients in the microITT population would provide the trial with more than 90% power for the assessment of the primary outcome.”

PASSReviewer 2· 95% conf

The trial design is rigorous with adequate randomization, blinding, power analysis, and pre-specified populations.

Evidence

paraphrase[Methods, Randomization and Treatment]

“An interactive-response system was used for randomization with a central computer-generated sequence and a block size of 6. Randomization was stratified according to infection type (complicated UTI or acute pyelonephritis only) and region (North America and Western Europe, Eastern Europe, or rest of the world).”

“The trial sponsor, investigators, site staff members who were participating in patient care or clinical evaluations, and patients were not aware of treatment assignments.”

MethodsFind in source

paraphrase[Methods, Statistical Analysis]

“We determined that the enrollment of at least 396 patients in the microITT population would provide the trial with more than 90% power for the assessment of the primary outcome, assuming that 75% of the patients in the two treatment groups had composite success.”

Sex, age, race/ethnicity, BMI, renal function, infection type, and comorbidities are reported in Table 1. Both sexes are enrolled, so sex justification is not applicable. Age and health status are reported. Species/strain and housing 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· 95% conf

Demographic and clinical characteristics are comprehensively reported.

Evidence

“Female sex — no. (%) 161 (54.9) 69 (48.3)”

Table 1Find in source

“Age Mean 56.5±17.6 55.8±17.9”

Table 1Find in source

PASSReviewer 2· 95% conf

Demographic and clinical characteristics are well reported for the human trial.

Evidence

“Female sex — no. (%) 161 (54.9) 69 (48.3)”

Table 1Find in source

“Age Mean 56.5±17.6 55.8±17.9”

Table 1Find in source

The trial was conducted in accordance with ICH-GCP and the Declaration of Helsinki, with approval by an independent ethics committee at each site. Written informed consent was obtained from all patients. 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 and informed consent are adequately documented.

Evidence

paraphrase[Methods, Trial Design and Oversight]

“The protocol and its amendments ... were approved by an independent ethics committee at each participating site.”

“All the patients provided written informed consent.”

MethodsFind in source

paraphrase[Methods, Trial Design and Oversight]

“The trial was designed and conducted by Venatorx Pharmaceuticals in accordance with the Good Clinical Practice guidelines of the International Council for Harmonisation and the ethical principles of the Declaration of Helsinki.”

PASSReviewer 2· 95% conf

Ethical approvals and consent are adequately documented.

Evidence

paraphrase[Methods, Trial Design and Oversight]

“The protocol and its amendments (available with the full text of this article at NEJM.org) were approved by an independent ethics committee at each participating site.”

“All the patients provided written informed consent.”

MethodsFind in source

paraphrase[Methods, Trial Design and Oversight]

Cefepime–taniborbactam and meropenem are named with doses and regimens. The manufacturer (Venatorx) is implied. No bench reagents or software are used, so other criteria are not applicable.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The investigational products are adequately identified.

Evidence

paraphrase[Methods, Randomization and Treatment]

“cefepime–taniborbactam (at a dose of 2.5 g; 2 g of cefepime and 0.5 g of taniborbactam) ... or meropenem (at a dose of 1 g)”

PASSReviewer 2· 90% conf

The investigational drugs are adequately identified, and statistical software is identified.

Evidence

paraphrase[Methods, Randomization and Treatment]

“Patients were randomly assigned in a 2:1 ratio to receive cefepime–taniborbactam (at a dose of 2.5 g; 2 g of cefepime and 0.5 g of taniborbactam) intravenously over a 2-hour period every 8 hours plus meropenem placebo or meropenem (at a dose of 1 g) intravenously over a 30-minute period every 8 hours plus cefepime–taniborbactam placebo for 7 days”

absence[Methods, Statistical Analysis]

Statistical software is not explicitly named.

The primary analysis uses a two-sided 95% CI for the difference in proportions (Miettinen and Nurminen method) and a two-sided P value. Effect sizes are reported with CIs. Missing data are handled as treatment failures. Software is not explicitly named, but the analysis is standard. Data presentation includes forest plots and tables with per-group n. Mathematical plausibility checks are not applicable for large-N continuous outcomes.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedNOT REPORTED

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical methods are appropriate and well-reported, with effect sizes and CIs.

Evidence

paraphrase[Methods, Statistical Analysis]

“The difference in success between treatments ... was calculated with the 95% confidence interval of between-group differences according to the Miettinen and Nurminen method.”

paraphrase[Results, Efficacy Outcomes]

“P = 0.009”

“12.6 (3.1 to 22.2)”

Table 2Find in source

PASSReviewer 2· 90% conf

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

Evidence

“The difference in success between treatments (cefepime–taniborbactam minus meropenem) was calculated with the 95% confidence interval of between-group differences according to the Miettinen and Nurminen method.”

Statistical analysisFind in source

“with a treatment difference of 12.6 percentage points (95% confidence interval [CI], 3.1 to 22.2; P = 0.009)”

ResultsFind in source

“12.6 (3.1 to 22.2)”

Table 2Find in source

The paper states 'A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.' This is vague and does not specify the access mechanism. For a clinical trial, managed access is acceptable, but the statement is not concrete. No code is shared.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

A data sharing statement is mentioned but not detailed in the provided text.

Evidence

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

AcknowledgementsFind in source

WARNReviewer 2· 85% conf

A data sharing statement is mentioned but not detailed in the text; no repository or accession numbers are provided.

Evidence

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

End of articleFind in source

The trial is registered (NCT03840148). Methods are detailed. Reporting guideline adherence is implied by NEJM standards but not explicitly stated. All outcomes are reported, including negative results. Limitations are discussed in the Discussion. Conclusions are proportional. Funding and COI are disclosed.

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· 95% conf

The trial is registered, methods are complete, and limitations are discussed.

Evidence

“CERTAIN-1 ClinicalTrials.gov number, NCT03840148.”

AbstractFind in source

paraphrase[Discussion, paragraph 4]

“However, the lack of oral step-down antibiotics, the fixed duration of intravenous therapy, and the requirement for inpatient participation may not reflect clinical practice in all regions of the world.”

paraphrase[Funding and acknowledgments]

“Supported by Venatorx Pharmaceuticals ... Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.”

PASSReviewer 2· 95% conf

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

Evidence

“CERTAIN-1 ClinicalTrials.gov number, NCT03840148.”

AbstractFind in source

paraphrase[Discussion, paragraph 4]

paraphrase[End of article]

“Supported by Venatorx Pharmaceuticals, which received funding from the Department of Health and Human Services; ... Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.”

Registered (1 ID: 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 38 references by DOI: 28 verified — 2 DOI unresolved, 8 no DOI (shown, not verified).

Copyediting

None found

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

Checked — nothing surfaced.

No copyedit issues found.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published paper is methodologically robust and transparent, with only minor reporting gaps that do not undermine its conclusions. An informed reader should weigh the minor omissions (data sharing details, software identification, explicit CONSORT adherence) and the two references that could not be located in registries, but these do not warrant retraction or major correction.

1.
HIGHdata code
In the Data Availability section, specify the exact access mechanism and conditions for the data sharing statement, e.g., 'available upon request to the corresponding author after approval of a proposal and with a data access agreement'.
The current statement is vague and does not provide readers with a concrete path to access the data, which is a common expectation for clinical trials.
2.
HIGHreporting
In the Methods, explicitly state adherence to a reporting guideline such as CONSORT, and mention that the CONSORT checklist is provided as supplementary material.
Explicitly naming the reporting guideline improves transparency and helps readers verify that all CONSORT items are addressed.
3.
HIGHstatistics
In the Statistical Analysis section, name the statistical software and version used (e.g., SAS version 9.4) to improve reproducibility.
Naming the software is a standard reproducibility requirement and was flagged by both reviewers as a minor omission.
4.
HIGHother
Verify the reference 'Effect of meropenem-vaborbactam vs piperacillin-tazobactam on clinical cure or improvement and microbial eradication in complicated urinary tract infection: the TANGO I randomized clinical trial' (DOI 10.1001/jama.2018.0439) — it was not found in Crossref/OpenAlex; correct the DOI or citation details if erroneous.
A reference that cannot be located in any registry may be fabricated or contain an incorrect DOI, which is an integrity concern.
5.
HIGHother
Verify the reference 'Cefepime/enmetazobactam for complicated urinary tract infections' (DOI 10.1001/jama.2022.17035) — it was not found in Crossref/OpenAlex; correct the DOI or citation details if erroneous.
A reference that cannot be located in any registry may be fabricated or contain an incorrect DOI, which is an integrity concern.
6.
MEDIUMreporting
In the Discussion, explicitly acknowledge the limitation that the trial was not powered for subgroup analyses and that multiplicity was not controlled for secondary outcomes.
This is a common reviewer expectation and improves the transparency of the interpretation of secondary and subgroup results.
7.
MEDIUMreporting
In the Results, consider reporting the number of patients with missing data for the primary outcome and how they were handled beyond the general statement.
Providing specific missing-data counts helps readers assess the robustness of the primary analysis.
8.
MEDIUMreporting
In the Methods, provide more detail on the randomization sequence generation and allocation concealment to fully meet CONSORT requirements.
While the current description is adequate, more detail would fully satisfy CONSORT and enhance reproducibility.
9.
MEDIUMreporting
In the Discussion, address the potential impact of the high proportion of patients from Eastern Europe on generalizability more explicitly.
Geographic imbalance can affect generalizability, and explicitly discussing it strengthens the limitations section.
10.
MEDIUMreporting
In the Results, report the exact number of patients with each adverse event leading to discontinuation, as currently only percentages are given.
Providing exact counts improves transparency and allows readers to assess the clinical significance of adverse events.
11.
MEDIUMstatistics
In the Methods, clarify whether the analysis of the primary outcome was adjusted for stratification factors, as this is a common expectation.
Clarifying adjustment for stratification factors helps readers understand the analysis and its potential biases.
12.
LOWdata code
Provide the data sharing statement content in the main text or supplement, rather than only referencing it as available at NEJM.org.
Including the full statement improves accessibility and transparency for readers who may not access the NEJM platform.
13.
LOWdata code
Consider including a statement on the availability of the statistical analysis plan or protocol in a public repository.
Public availability of the protocol and SAP enhances transparency and allows independent verification of the analysis.

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Cefepime-Taniborbactam in Complicated Urinary Tract Infection.

Wagenlehner FM, Gasink LB, McGovern PC, Moeck G, McLeroth P, Dorr M, Dane A, Henkel T, CERTAIN-1 Study Team

Read full text

DOI

10.1056/NEJMoa2304748

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Record fingerprint

d07863954291b5301ff527b5d5a9aa515be7d67a8afd0b34dec37cf552b7abb1

Verify via API

Issued Aug 16, 2026Engine 7.39.0

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

Kaimen Rigor review

Kaimen Rigor reviewed

3.75 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
CitationsUnresolved reference ×2−0.5★
ReportingData & code availability partially met−0.25★

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

Not verified in this report

No data or code availability links were detected to verify.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary efficacy outcome is a composite of microbiologic and clinical success. Microbiologic success is a surrogate endpoint (reduction of bacteria in urine culture), and while clinical success is a patient-reported outcome, the composite is not a hard clinical outcome. The paper does not provide evidence linking the surrogate (microbiologic eradication) to long-term clinical outcomes, nor does it demonstrate target engagement at the tested dose beyond in vitro activity.
“The primary efficacy outcome was a composite of both microbiologic and clinical success in the microITT population at test of cure on trial days 19 to 23.”
Find in source

Findings by category

01ArithmeticNone found 102OverreachOverstated conclusions 03AuthenticityNone found 104DisclosureReporting gaps 105AvailabilityBroken references and links · partly checked 06CopyeditNone found

Numerical inconsistencies

None found

Checked — nothing surfaced.

Recomputed 1 test: 1 consistent, 0 inconsistent; 1 via agent-written checks.

Overstated conclusions

1 finding · worst high

Efficacy rests on an unvalidated surrogate endpointAssessed

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

Premise concern: surrogate not validated for clinical benefit.

Data authenticity concerns

None found

Checked — nothing surfaced.

Reporting gaps

1 finding · worst medium

Data/code availability incompleteAssessed

Eight Dimensions7 pass · 1 warn

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The premise is well-established with extensive prior work and a clear rationale.

Evidence

paraphrase[Introduction, paragraph 1]

paraphrase[Introduction, paragraph 2]

“We performed the Cefepime Rescue with Taniborbactam in Complicated UTI (CERTAIN-1) phase 3 trial to evaluate the safety and efficacy of cefepime–taniborbactam as compared with meropenem.”

absence[Introduction]

Limitations of prior research are not explicitly discussed.

PASSReviewer 2· 95% conf

The paper establishes a clear scientific premise with extensive prior work and a logical rationale for the trial.

Evidence

paraphrase[Introduction, paragraphs 1-3]

paraphrase[Introduction, last paragraph]

absence[Introduction]

Limitations of prior research are not explicitly discussed as such.

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The trial design is rigorous with adequate randomization, blinding, power analysis, and pre-specified populations.

Evidence

“An interactive-response system was used for randomization with a central computer-generated sequence and a block size of 6.”

MethodsFind in source

“The trial sponsor, investigators, site staff members who were participating in patient care or clinical evaluations, and patients were not aware of treatment assignments.”

MethodsFind in source

paraphrase[Methods, Statistical Analysis]

“We determined that the enrollment of at least 396 patients in the microITT population would provide the trial with more than 90% power for the assessment of the primary outcome.”

PASSReviewer 2· 95% conf

The trial design is rigorous with adequate randomization, blinding, power analysis, and pre-specified populations.

Evidence

paraphrase[Methods, Randomization and Treatment]

“The trial sponsor, investigators, site staff members who were participating in patient care or clinical evaluations, and patients were not aware of treatment assignments.”

MethodsFind in source

paraphrase[Methods, Statistical Analysis]

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Demographic and clinical characteristics are comprehensively reported.

Evidence

“Female sex — no. (%) 161 (54.9) 69 (48.3)”

Table 1Find in source

“Age Mean 56.5±17.6 55.8±17.9”

Table 1Find in source

PASSReviewer 2· 95% conf

Demographic and clinical characteristics are well reported for the human trial.

Evidence

“Female sex — no. (%) 161 (54.9) 69 (48.3)”

Table 1Find in source

“Age Mean 56.5±17.6 55.8±17.9”

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 and informed consent are adequately documented.

Evidence

paraphrase[Methods, Trial Design and Oversight]

“The protocol and its amendments ... were approved by an independent ethics committee at each participating site.”

“All the patients provided written informed consent.”

MethodsFind in source

paraphrase[Methods, Trial Design and Oversight]

PASSReviewer 2· 95% conf

Ethical approvals and consent are adequately documented.

Evidence

paraphrase[Methods, Trial Design and Oversight]

“The protocol and its amendments (available with the full text of this article at NEJM.org) were approved by an independent ethics committee at each participating site.”

“All the patients provided written informed consent.”

MethodsFind in source

paraphrase[Methods, Trial Design and Oversight]

Cefepime–taniborbactam and meropenem are named with doses and regimens. The manufacturer (Venatorx) is implied. No bench reagents or software are used, so other criteria are not applicable.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The investigational products are adequately identified.

Evidence

paraphrase[Methods, Randomization and Treatment]

“cefepime–taniborbactam (at a dose of 2.5 g; 2 g of cefepime and 0.5 g of taniborbactam) ... or meropenem (at a dose of 1 g)”

PASSReviewer 2· 90% conf

The investigational drugs are adequately identified, and statistical software is identified.

Evidence

paraphrase[Methods, Randomization and Treatment]

absence[Methods, Statistical Analysis]

Statistical software is not explicitly named.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedNOT REPORTED

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical methods are appropriate and well-reported, with effect sizes and CIs.

Evidence

paraphrase[Methods, Statistical Analysis]

“The difference in success between treatments ... was calculated with the 95% confidence interval of between-group differences according to the Miettinen and Nurminen method.”

paraphrase[Results, Efficacy Outcomes]

“P = 0.009”

“12.6 (3.1 to 22.2)”

Table 2Find in source

PASSReviewer 2· 90% conf

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

Evidence

Statistical analysisFind in source

“with a treatment difference of 12.6 percentage points (95% confidence interval [CI], 3.1 to 22.2; P = 0.009)”

ResultsFind in source

“12.6 (3.1 to 22.2)”

Table 2Find in source

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

A data sharing statement is mentioned but not detailed in the provided text.

Evidence

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

AcknowledgementsFind in source

WARNReviewer 2· 85% conf

A data sharing statement is mentioned but not detailed in the text; no repository or accession numbers are provided.

Evidence

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

End of articleFind 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· 95% conf

The trial is registered, methods are complete, and limitations are discussed.

Evidence

“CERTAIN-1 ClinicalTrials.gov number, NCT03840148.”

AbstractFind in source

paraphrase[Discussion, paragraph 4]

paraphrase[Funding and acknowledgments]

“Supported by Venatorx Pharmaceuticals ... Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.”

PASSReviewer 2· 95% conf

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

Evidence

“CERTAIN-1 ClinicalTrials.gov number, NCT03840148.”

AbstractFind in source

paraphrase[Discussion, paragraph 4]

paraphrase[End of article]

Registered (1 ID: 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 38 references by DOI: 28 verified — 2 DOI unresolved, 8 no DOI (shown, not verified).

Copyediting

None found

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

Checked — nothing surfaced.

No copyedit issues found.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
HIGHdata code
In the Data Availability section, specify the exact access mechanism and conditions for the data sharing statement, e.g., 'available upon request to the corresponding author after approval of a proposal and with a data access agreement'.
The current statement is vague and does not provide readers with a concrete path to access the data, which is a common expectation for clinical trials.
2.
HIGHreporting
In the Methods, explicitly state adherence to a reporting guideline such as CONSORT, and mention that the CONSORT checklist is provided as supplementary material.
Explicitly naming the reporting guideline improves transparency and helps readers verify that all CONSORT items are addressed.
3.
HIGHstatistics
In the Statistical Analysis section, name the statistical software and version used (e.g., SAS version 9.4) to improve reproducibility.
Naming the software is a standard reproducibility requirement and was flagged by both reviewers as a minor omission.
4.
HIGHother
Verify the reference 'Effect of meropenem-vaborbactam vs piperacillin-tazobactam on clinical cure or improvement and microbial eradication in complicated urinary tract infection: the TANGO I randomized clinical trial' (DOI 10.1001/jama.2018.0439) — it was not found in Crossref/OpenAlex; correct the DOI or citation details if erroneous.
A reference that cannot be located in any registry may be fabricated or contain an incorrect DOI, which is an integrity concern.
5.
HIGHother
Verify the reference 'Cefepime/enmetazobactam for complicated urinary tract infections' (DOI 10.1001/jama.2022.17035) — it was not found in Crossref/OpenAlex; correct the DOI or citation details if erroneous.
A reference that cannot be located in any registry may be fabricated or contain an incorrect DOI, which is an integrity concern.
6.
MEDIUMreporting
In the Discussion, explicitly acknowledge the limitation that the trial was not powered for subgroup analyses and that multiplicity was not controlled for secondary outcomes.
This is a common reviewer expectation and improves the transparency of the interpretation of secondary and subgroup results.
7.
MEDIUMreporting
In the Results, consider reporting the number of patients with missing data for the primary outcome and how they were handled beyond the general statement.
Providing specific missing-data counts helps readers assess the robustness of the primary analysis.
8.
MEDIUMreporting
In the Methods, provide more detail on the randomization sequence generation and allocation concealment to fully meet CONSORT requirements.
While the current description is adequate, more detail would fully satisfy CONSORT and enhance reproducibility.
9.
MEDIUMreporting
In the Discussion, address the potential impact of the high proportion of patients from Eastern Europe on generalizability more explicitly.
Geographic imbalance can affect generalizability, and explicitly discussing it strengthens the limitations section.
10.
MEDIUMreporting
In the Results, report the exact number of patients with each adverse event leading to discontinuation, as currently only percentages are given.
Providing exact counts improves transparency and allows readers to assess the clinical significance of adverse events.
11.
MEDIUMstatistics
In the Methods, clarify whether the analysis of the primary outcome was adjusted for stratification factors, as this is a common expectation.
Clarifying adjustment for stratification factors helps readers understand the analysis and its potential biases.
12.
LOWdata code
Provide the data sharing statement content in the main text or supplement, rather than only referencing it as available at NEJM.org.
Including the full statement improves accessibility and transparency for readers who may not access the NEJM platform.
13.
LOWdata code
Consider including a statement on the availability of the statistical analysis plan or protocol in a public repository.
Public availability of the protocol and SAP enhances transparency and allows independent verification of the analysis.

Full text (44,755 chars)Analyzed: Aug 16, 2026