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Kaimen Rigor review

Anticoagulation to prevent ischemic stroke and neurocognitive impairment in atrial fibrillation: the BRAIN-AF randomized clinical trial.

Rivard L, Khairy P, Talajic M, Tardif JC, Healey JS, Black SE, Andrade JG, Field TS, Nault I, Bherer L, Massoud F, Nattel S, Lanthier S, Racine N, Roux JF, Greiss I, Macle L, Guerra PG, Tadros R, Mayrand H, Gosselin G, Conen D, Bocti C, Chayer C, Deschaintre Y, Sandhu RK, Manlucu J, Khaykin Y, Verma A, Mondésert B, Dyrda K, Cadrin-Tourigny J, Thibault B, Raymond-Paquin A, Aguilar M, Brouillette J, Roussin A, Robillard A, Tremblay-Gravel M, David LP, Cossette M, Parkash R, Guertin MC, Roy D, BRAIN-AF investigators

DOI: 10.1038/s41591-025-04101-y
Record issued: 2026-08-10
Engine: 7.29.0
Exported: 2026-09-20

Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/fae7681b-034c-46e7-aa8b-bc259d78934f is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

3.75 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ReportingData & code availability partially met−0.25★

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

Findings by category

101ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions 03AuthenticityNone found 104DisclosureReporting 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.

The BRAIN-AF trial is a rigorously designed and transparently reported randomized controlled trial: randomization, blinding, power analysis, ethics approval, demographic reporting, and statistical reporting all meet high standards, and the controlled-access data statement is appropriate for identifiable patient-level data. The primary outcomes are reported with named tests, exact p-values, and effect sizes with CIs, and the statistics verification recomputed all checkable values consistently. The main weaknesses are minor: analysis code is not shared, the reporting checklist is not explicitly named, and two small internal inconsistencies (the primary-analysis denominator count and the stroke event count) are left unexplained.

Both reviewers sampled the same model independently and converged on 7 of 8 dimensions (all pass); they diverged only on data code availability, where I weighed toward warn because the trial's custom SAS analysis code is an applicable, unreported artifact. Statistics coverage is partial (only 3 tests with test-statistic+df or effect+CI were recomputed; threshold-only and resampling/exact p-values were not machine-verified), and the citation check found no retracted or unlocatable references.

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; 3 via agent-written checks.

Agent-written checks— recomputed from reported CIs / ratios by code the agent wrote

CONSISTENTreported p = .460 · recomputed p = .443Reviewer 1
Verify the reported p-value for the primary efficacy outcome (HR=1.10, 95% CI 0.86-1.40) using the confidence interval method.
“hazard ratio of 1.10 (95% confidence interval (CI) 0.86–1.40; P = 0.46 by generalized log-rank test)”
Find in source
Taken as given: The 95% CI is two-sided at the 0.05 level.; The HR is a log-hazard ratio, so log=1 is appropriate.; The CI is not adjusted for multiple comparisons.
Method: pCI is used to compute the two-tailed p-value from the point estimate and 95% confidence interval for a log-scale ratio.
How we recomputed it: pCI(1.10, 0.86, 1.40, 1)
CONSISTENTreported p = .270 · recomputed p = .286Reviewers 1, 2
Verify the reported p-value for major bleeding (HR=0.41, 95% CI 0.08-2.12) using the confidence interval method.
“Major bleeding—no. (%) 2 (0.3) 5 (0.8) 0.41 (0.08, 2.12) 0.27”
Find in source
Taken as given: The 95% CI is two-sided at the 0.05 level.; The HR is a log-hazard ratio, so log=1 is appropriate.; The CI is not adjusted for multiple comparisons.
Method: pCI is used to compute the two-tailed p-value from the point estimate and 95% confidence interval for a log-scale ratio.
How we recomputed it: pCI(0.41, 0.08, 2.12, 1)
CONSISTENTreported p = .460 · recomputed p = .443Reviewer 2
Primary composite outcome: hazard ratio 1.10 (95% CI 0.86–1.40), P = 0.46
“yielding a hazard ratio of 1.10 (95% confidence interval (CI) 0.86–1.40; P = 0.46 by generalized log-rank test”
Find in source
Taken as given: the HR 1.10 and 95% CI 0.86–1.40 are the two-sided estimates for the primary composite outcome; the HR is approximately log-normally distributed; the reported p (0.46) was computed from the interval-censored proportional hazards model, so the CI-derived two-tailed p is an approximation
Method: Two-tailed p derived from the hazard ratio and its 95% confidence interval on the log scale (pCI with log=1).
How we recomputed it: pCI(1.10, 0.86, 1.40, 1)

lowinternal contradiction
The text reports 13 strokes among the 256 primary-outcome events, whereas Table 2 lists 9 + 7 = 16 stroke events; the discrepancy is partly explained by the table footnote that some participants experienced more than one component, but the first-event classification (13) versus all-events count (16) is not reconciled in the text.
stroke for 13 (5.1%) and TIA for 9 (3.5%) ... | Stroke | 9 (1.5) | 7 (1.1) |
Table 2reviewer’s wording
lowinternal contradiction
The primary-efficacy analysis denominators (610 and 623) sum to 1,233, two fewer than the 1,235 participants stated as randomized, with no stated reason for the two exclusions in the provided text.
“the primary outcome occurred in 130 of 610 participants (21.3%), compared with 126 of 623 participants (20.2%)”
ResultsFind in source

Overstated conclusions

1 finding · worst low

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.

Conclusions only partially backed by the presented evidenceAssessed

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

partialReviewers 1, 2
The results provide the strongest evidence to date in support of current guidelines that do not recommend anticoagulation in patients without conventional risk factors for stroke.
The trial's null result supports the guideline position in this low-risk population, but 'strongest evidence to date' is a comparative claim about the broader literature that the paper itself does not substantiate.
Evidence: Null primary outcome and low stroke/TIA rate (<0.7% per year).
“This low rate, combined with the lack of efficacy of rivaroxaban in improving cognitive outcomes, provides the strongest evidence to date in support of current guidelines that do not recommend anticoagulation in patients without conventional risk factors for stroke.”
DiscussionFind in source
supportedReviewer 1
No benefit of anticoagulation was observed across sensitivity analyses.
The primary result (HR 1.10, 95% CI 0.86-1.40, p=0.46) shows no statistically significant benefit, and the sensitivity analyses (censored and on-treatment) are consistent, with overlapping confidence intervals and similar p-values.
Evidence: Primary efficacy outcome: HR 1.10 (0.86-1.40), p=0.46; Censored analysis: HR not explicitly given but p=0.44; On-treatment analysis: p=0.41.
“No benefit of anticoagulation was observed across sensitivity analyses (censored and on-treatment analyses) or in any predefined subgroup.”
Figure 2Find in source
supportedReviewer 1
The trial was terminated early due to futility.
The conditional power analysis showing a 1.2% probability of achieving statistical significance under the original alternative hypothesis, and the DSMB recommendation based on the pre-specified futility boundary, support this claim.
Evidence: Conditional power analysis: 1.2% probability of a statistically significant treatment effect if continued.
“The conditional power analysis based on the alternative hypothesis underlying the sample size calculation indicated a 1.2% probability of achieving a statistically significant treatment effect had the trial been continued to its planned completion.”
ResultsFind in source
supportedReviewer 1
Despite the high incidence of cognitive decline, the BRAIN-AF trial was stopped early for futility.
The paper reports a high incidence of cognitive decline (20.7% primary outcome, 6.4% annual rate in placebo) and the early stopping for futility, which is consistent with the results.
Evidence: Primary outcome occurred in 20.7% of participants; annual rate 6.4% in placebo; trial stopped for futility after interim analysis.
“Despite the high incidence of cognitive decline observed among patients with AF and low stroke risk, the BRAIN-AF trial, which tested a low dose of rivaroxaban to prevent stroke, transient ischemic attack and cognitive decline in patients with prior AF, was stopped early due to futility.”
DiscussionFind in source
supportedReviewer 1
The lack of rivaroxaban's superiority was not attributable to an insufficient event rate.
The observed event rate in the placebo group (6.4% per year) aligned with the assumptions used in the sample size calculation, so the null result is not due to a lower-than-expected event rate.
Evidence: Annualized rate in placebo: 6.4%; trial design assumed 6% per year. The primary outcome occurred in 20.7% of participants.
“In the BRAIN-AF trial, the primary outcome occurred in more than 20% of participants, with an annual incidence of 6.4% in the placebo group, aligning with the trial’s sample size and power calculations. The lack of rivaroxaban’s superiority was, therefore, not attributable to an insufficient event rate.”
Discussion ¶3Find in source
supportedReviewer 2
Treatment with rivaroxaban showed no benefit in reducing cognitive decline, stroke or transient ischemic attack compared to placebo.
The presented primary result (HR 1.10, 95% CI 0.86–1.40, P=0.46) and consistent sensitivity and subgroup analyses directly support the null conclusion.
Evidence: HR 1.10 (0.86–1.40), P=0.46; consistent censored (P=0.44) and on-treatment (P=0.41) analyses; no subgroup interaction significant.
“treatment with the anticoagulant rivaroxaban showed no benefit in reducing cognitive decline, stroke or transient ischemic attack when compared to placebo”
AbstractFind in source
supportedReviewer 2
The trial was stopped early due to futility with a low conditional probability of success had it continued.
The DSMB recommendation, the 256 of 410 events at termination, and the stated 1.2% conditional power directly back the futility claim.
Evidence: Conditional power analysis indicated a 1.2% probability of achieving a statistically significant treatment effect if continued.
“Conditional power analysis indicated a 1.2% probability of achieving a statistically significant treatment effect if the trial had been continued to its planned total of 410 events.”
AbstractFind in source
supportedReviewer 2
The lack of rivaroxaban superiority was not attributable to an insufficient event rate.
The observed placebo event rate (6.4% per year) aligned with the sample-size assumption (6% per year), supporting that the null result was not due to too few events.
Evidence: Primary outcome annual rate 6.4% in placebo vs the assumed 6%; 256 events occurred by termination.
The lack of rivaroxaban's superiority was, therefore, not attributable to an insufficient event rate.
Discussionreviewer’s wording
supportedReviewer 2
BRAIN-AF is the largest randomized controlled trial designed to determine whether oral anticoagulation could prevent cognitive decline in patients with AF.
This is a framing claim about trial scope; the paper presents a 1,235-participant randomized trial designed for this purpose, consistent with the statement.
Evidence: 1,235 participants randomized across 53 sites; composite cognitive endpoint.
“BRAIN-AF is the largest randomized controlled trial designed to determine whether oral anticoagulation could prevent cognitive decline in patients with AF.”
DiscussionFind in source

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 observational studies and reviews that establish the link between AF and cognitive decline, and the potential benefit of anticoagulation. It acknowledges the limitations of prior work (observational, not randomized) and explicitly states that the trial aims to address this gap. The hypothesis follows logically from the cited evidence.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper establishes a strong scientific foundation by citing prior observational studies linking AF to cognitive decline and the potential for anticoagulation to mitigate this risk, with a clear rationale for the trial.

Evidence

“Observational studies suggest that anticoagulation may reduce the risk of cognitive decline in patients with AF and elevated thromboembolic risk, implicating subclinical cerebral emboli as a potential mechanistic link.”

Introduction ¶1Find in source

paraphrase[Introduction, paragraph 2]

“We, therefore, conducted the BRAIN-AF trial to determine whether a low dose of rivaroxaban (15 mg once daily) reduces a composite endpoint of cognitive decline, stroke or transient ischemic attack (TIA) compared to placebo in participants with AF who have no established indication for thromboprophylaxis.”

paraphrase[Methods, Trial design and ethical approval]

“The BRAIN-AF trial (NCT02387229) was a multicenter randomized double-blind placebo-controlled trial”

PASSReviewer 2· 90% conf

The introduction firmly establishes the scientific premise with cited observational evidence linking AF to cognitive decline and anticoagulation to reduced dementia risk, and frames the residual uncertainty motivating the trial.

Evidence

“Observational studies and real-world healthcare data further suggest that anticoagulation may reduce cognitive decline and dementia risk in AF patients at high stroke risk”

IntroductionFind in source

Randomization was performed via an interactive web response system using permuted blocks, with double-blinding (patients and investigators). An a priori sample size calculation was provided (1,424 participants, 85% power, alpha=0.05). Detailed inclusion and exclusion criteria are listed. Pre-specified outlier handling (ITT, on-treatment, censored analyses) is described. Independent replication is not applicable for a single pivotal trial.

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· 95% conf

The study design is rigorously described, with appropriate randomization, blinding, power analysis, inclusion/exclusion criteria, and pre-specified sensitivity analyses.

Evidence

paraphrase[Methods, Interventions]

“Patients with an MMSE score ≥25 were then randomized in a 1:1 ratio to receive either rivaroxaban 15 mg once daily orally or a matching placebo through an interactive web response system (IWRS) using a permuted block randomization method. Patients and investigators remained blinded to treatment assignments until data analysis.”

“Based on these assumptions, a sample size of 1,424 patients was required to detect a relative risk reduction of 30% with a power of 85% and a two-sided significance level of 0.05.”

Statistical analysisFind in source

“Efficacy outcomes were analyzed based on the original randomization groups for all participants, including those who discontinued the trial early or switched to open-label anticoagulant therapy after developing a new clinical indication for oral anticoagulation post-randomization.”

Statistical analysisFind in source

PASSReviewer 2· 95% conf

Core design elements for a human RCT — randomization method and unit, double-blinding, a priori power calculation, pre-specified inclusion/exclusion criteria and ITT analysis population — are all reported adequately.

Evidence

“randomized in a 1:1 ratio to receive either rivaroxaban 15 mg once daily orally or a matching placebo through an interactive web response system (IWRS) using a permuted block randomization method”

MethodsFind in source

“a sample size of 1,424 patients was required to detect a relative risk reduction of 30% with a power of 85% and a two-sided significance level of 0.05”

Statistical analysisFind in source

“Patients and investigators remained blinded to treatment assignments until data analysis”

MethodsFind in source

Sex is reported (25.6% female), and both sexes are included, so sex justification is not applicable. Age, weight (BMI), and health status (e.g., CHA2DS2-VA score, LVEF, creatinine clearance) are reported in Table 1. Demographics include age, sex, race, education, depression, alcohol use, etc. The species/strain and housing criteria are not applicable for a human study.

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 baseline clinical characteristics are reported in detail, including sex, age, race, education, and comorbidities, with balance across groups.

Evidence

paraphrase[Table 1]

“Female sex—no. (%) 316 (25.6) | Age—years 53.4 ± 7.3”

paraphrase[Table 1]

“Caucasian 1,181 (95.6) | Level of education—years of schooling 15.2 ± 3.3 | Left ventricular ejection fraction—% 59.8 ± 5.6”

PASSReviewer 2· 90% conf

Sex, age, health status, race/ethnicity, education and depression are all reported in Table 1; both sexes were enrolled, so a single-sex justification is not applicable.

Evidence

“Female sex—no. (%) | 316 (25.6) | 163 (26.7) | 153 (24.5)”

Table 1Find in source

“Race or ethnic group—no. (%) a | | Caucasian | 1,181 (95.6)”

Table 1Find in source

The study was approved by the institutional review board of the Montreal Heart Institute (MP-33-2014-1559) and each participating center. All patients provided written informed consent. Compliance with 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

Ethical approval from named institutional review boards, written informed consent, and compliance with the Declaration of Helsinki are explicitly stated.

Evidence

“The study was authorized by Health Canada and the institutional review boards of the Montreal Heart Institute (MP-33-2014-1559) and each participating center”

EthicsFind in source

“All patients provided written, informed consent before any trial activities.”

MethodsFind in source

“conducted in accordance with the principles of the Declaration of Helsinki.”

EthicsFind in source

PASSReviewer 2· 95% conf

A named research ethics board with a protocol number, Health Canada authorization, Declaration of Helsinki compliance and written informed consent are all explicitly stated.

Evidence

“the study was authorized by Health Canada and the institutional review boards of the Montreal Heart Institute (MP-33-2014-1559) and each participating center and was conducted in accordance with the principles of the Declaration of Helsinki”

EthicsFind in source

“All patients provided written informed consent to participate.”

MethodsFind in source

Rivaroxaban 15 mg daily is the investigational product, with in-kind support from Bayer Inc. Placebo is matching but not further described, which is acceptable. Software (SAS version 9.4) is identified. Antibodies, cell lines, organisms, 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· 90% conf

The investigational drug (rivaroxaban) is identified with dose and manufacturer, and the statistical software (SAS 9.4) is specified. No other biological or chemical resources are used, so other criteria are not applicable.

Evidence

“rivaroxaban 15 mg once daily orally”

MethodsFind in source

“All statistical analyses were conducted using SAS software version 9.4.”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The investigational product (rivaroxaban 15 mg, Bayer) with matching placebo and aspirin double-dummy is identified with dose and regimen, and the analysis software (SAS 9.4) is named; wet-lab sub-criteria are not applicable.

Evidence

“rivaroxaban 15 mg once daily orally or a matching placebo”

AcknowledgementsFind in source

“All statistical analyses were conducted using SAS software version 9.4.”

Statistical analysisFind in source

The primary analysis uses a generalized log-rank test and proportional hazards model for interval-censored data, both clearly named. Exact p-values (e.g., P=0.46) and 95% CIs are reported. SAS 9.4 is identified. Data presentation includes Kaplan-Meier curves, forest plots, and per-group event counts. Assumptions are not explicitly tested but handled by standard methods. Mathematical plausibility checks revealed no inconsistencies; percentages sum to ~100% with rounding noted.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical tests are named, exact p-values and effect sizes with confidence intervals are reported, software is identified, and data presentation follows clinical trial standards. No arithmetic errors were detected.

Evidence

paraphrase[Results, Efficacy outcomes]

“hazard ratio of 1.10 (95% confidence interval (CI) 0.86–1.40; P = 0.46 by generalized log-rank test)”

paraphrase[Table 2]

“Hazard ratio (95% CI) 1.10 (0.86, 1.40)”

“All statistical analyses were conducted using SAS software version 9.4.”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

Statistical methods are fully reported for the clinical-trial idiom: named tests, exact p-values, HRs with 95% CIs, SAS 9.4, per-group n and figures; reported proportions and denominators were checked and are arithmetically plausible.

Evidence

“yielding a hazard ratio of 1.10 (95% confidence interval (CI) 0.86–1.40; P = 0.46 by generalized log-rank test”

ResultsFind in source

paraphrase[Results, Participants and follow-up]

“Of the 410 primary outcome events prespecified in the trial's sample size and power calculations, 256 (62.4%) had occurred at the time of study termination.”

The data availability statement describes a concrete route for controlled access to deidentified individual-level data, which is adequate for patient-level data. However, no code repository is provided for the statistical analysis code, which limits reproducibility. Repository deposit and accession numbers are not applicable for the patient-level data.

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 90% conf

A data availability statement is provided with a controlled-access mechanism, but custom analysis code is not shared, which is a common gap for clinical trials.

Evidence

paraphrase[Data availability section]

“Deidentified data underlying the results reported in this article are stored in a secure research environment at SERIANT... Qualified academic investigators may request controlled on-site access to analyze these data after completion of all prespecified primary and secondary analyses and beginning 12 months after publication, for a period of 36 months.”

absence[Data availability section and Methods]

No code sharing mentioned.

PASSReviewer 2· 90% conf

A concrete managed/controlled-access data statement is provided (SERIANT secure environment, embargo and request conditions), which is the appropriate standard for identifiable patient-level data; repository/accession and code-sharing sub-criteria are n/a.

Evidence

“Qualified academic investigators may request controlled on-site access to analyze these data after completion of all prespecified primary and secondary analyses and beginning 12 months after publication, for a period of 36 months.”

Data availabilityFind in source

Methods are thorough and replicable. The trial is registered at ClinicalTrials.gov (NCT02387229). A reporting summary is linked. All pre-specified outcomes are reported, including negative and null results. Limitations are discussed extensively. Conclusions are proportional to the evidence. Funding sources and competing interests are fully 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· 95% conf

The manuscript provides detailed methods, trial registration, a reporting summary, transparent reporting of all outcomes, a balanced discussion of limitations, proportional conclusions, and full funding/COI disclosures.

Evidence

“ClinicalTrials.gov registration: NCT02387229 (https://clinicaltrials.gov/study/NCT02387229)”

AbstractFind in source

paraphrase[Discussion, paragraph 5-7]

“A few methodological aspects merit consideration. First, by design, the primary outcome was heavily driven by cognitive decline...”

“This trial was funded by the Canadian Institutes of Health Research (CIHR, grant no. PJT-175207, L.R.), Canadian Stroke Prevention Network (CSPIN, L.R.), Montreal Heart Institute Foundation (L.R.) and BAYER Inc”

AcknowledgementsFind in source

PASSReviewer 2· 85% conf

Registration, methods completeness, outcome reporting, limitations, proportional conclusions, funding and COI are all adequate; the only minor gap is that the reporting checklist (e.g., CONSORT) is referenced only generically as a 'Reporting summary' rather than named explicitly.

Evidence

“ClinicalTrials.gov registration: NCT02387229”

AbstractFind in source

“Further information on research design is available in the linked to this article.”

AbstractFind in source

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

ClinicalTrials.gov

NCT02387229

Broken references and links

None found

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Checked — nothing surfaced.

Checked 50 references by DOI: 49 verified — 1 no DOI (shown, not verified).

NO DOI
Beck Depression Inventory: Manual
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

2 data/code links checked; 2 live.

datahttps://clinicaltrials.gov/study/NCT02387229LIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttps://clinicaltrials.gov/ct2/show/NCT02387229LIVEHTTP 200
Resolves, but the content could not be matched to the paper.

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 clarity, consistency.

MINORclarityTable 1
“Body mass index—m kg − 2”
→ Use standard units 'kg/m²' for BMI.
Likely a conversion artifact; the value column is correct but the unit string reads as 'm kg − 2'.
MINORclarityTable 1
“Left atrial volume—ml m − 2”
→ Use standard units 'ml/m²' for the indexed left atrial volume.
Same unit-formatting artifact as BMI row.
MINORconsistencyResults, Efficacy outcomes
“the primary outcome occurred in 130 of 610 participants (21.3%), compared with 126 of 623 participants (20.2%)”
→ Explain why the primary-analysis denominators (610 and 623) total 1,233 rather than the 1,235 randomized (e.g., two participants without post-baseline data).
Appears in abstract-derived text and Results; not contradicted elsewhere but left unexplained.

Kaimen Rigor Action ItemsFinal pass before journal submission

This is a robust published trial: an informed reader can rely on its core rigor dimensions, and no evidence of fabrication, retracted citations, or invalid statistics was found. The two low-severity internal inconsistencies (primary-analysis denominators summing to 1,233 vs. 1,235 randomized, and text reporting 13 strokes vs. Table 2 listing 16 stroke events) warrant a correction/clarification from the authors and should be weighed when interpreting the primary analysis, as should the absence of shared analysis code.

1.
HIGHrigor
Clarify in the Results/figure-1 flow diagram why the primary-efficacy denominators (610 and 623, summing to 1,233) differ from the 1,235 randomized participants, e.g., state that two participants were excluded for lack of post-baseline cognitive assessment.
The unexplained two-participant discrepancy was independently flagged by a reviewer, the copyedit pass, and the integrity check, so a reader cannot reconcile the reported analysis population without a stated reason.
2.
HIGHrigor
Reconcile the stroke event count discrepancy between the text (13 strokes among the 256 primary-outcome events) and Table 2 (9 + 7 = 16 stroke events), clarifying the first-event classification versus the all-events count.
The integrity check flagged this internal contradiction; although partly explained by the table footnote that some participants had more than one component, the text does not reconcile the 13 vs. 16 figures.
3.
MEDIUMreporting
Name the CONSORT 2010 reporting checklist explicitly (with completion status) in the Reporting summary section instead of only referencing the generic 'Reporting summary'.
Reviewer 2 flagged that the reporting guideline is referenced only generically, and naming the checklist is the expected standard for a randomized trial.
4.
MEDIUMdata code
Deposit the custom SAS 9.4 analysis code in a public repository (e.g., GitHub) or describe it in the Methods to complement the controlled-access data statement.
The trial's SAS analyses are an applicable artifact whose absence limits reproducibility; this was the sole basis for the warn on data_code_availability.
5.
MEDIUMcopyedit
Fix the BMI unit string in Table 1 from 'm kg − 2' to 'kg/m²'.
The copyedit pass flagged this as a likely conversion artifact that renders the unit unreadable.
6.
MEDIUMcopyedit
Fix the left atrial volume unit string in Table 1 from 'ml m − 2' to 'ml/m²'.
The copyedit pass flagged the same unit-formatting artifact as the BMI row.
7.
LOWdata code
Deposit non-identifiable aggregate data (baseline characteristics, event rates) in a public repository such as Dryad or Zenodo to complement the controlled-access statement.
Reviewer 1 suggested this as a low-cost way to broaden access beyond the on-site SERIANT mechanism for readers who only need aggregate results.

Full text (60,557 chars)Analyzed: Aug 10, 2026

RigorReviewer 1

RigorReviewer 2

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

ReproducibilityLink verification (liveness + content)· no model (rule-based)

PreregistrationDeterministic check· no model (rule-based)

The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”

How stars are deducted

Reporting — 8 dimensionseach dimension that fully fails−½★
each dimension partially met−¼★
Statistics · Integrity · Claimseach serious problem−1★
each medium problem−½★
Citationseach retracted or unverifiable reference−¼★
Copyeditonly when the manuscript needs a full edit−½★

The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.

The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.

The eight reporting dimensions

Scientific PremisePrior work, rationale, and how it addresses gaps.

Study Design & RigorRandomization, blinding, power, controls, replication.

Biological VariablesSex, age, species/strain, housing, demographics.

Ethical ApprovalsIRB/IACUC approval, informed consent, regulatory compliance.

Key ResourcesAntibodies, cell lines, organisms, software — identified with persistent IDs.

Statistical ReportingNamed tests, exact p-values, effect sizes, plausible summary stats.

Data & Code AvailabilityAvailability statements, repositories, accession numbers, shared code.

Reporting TransparencyMethods, registration, guidelines, outcomes, limitations, funding/COI.

Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.

This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.

Anticoagulation to prevent ischemic stroke and neurocognitive impairment in atrial fibrillation: the BRAIN-AF randomized clinical trial.

DOI

10.1038/s41591-025-04101-y

Record issued

2026-08-10

Engine

7.29.0

Exported

2026-09-20