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Kaimen Rigor review

Asundexian for Secondary Stroke Prevention.

Sharma M, Dong Q, Hirano T, Kasner SE, Saver JL, Masjuan J, Demchuk AM, Cordonnier C, Bereczki D, Tsivgoulis G, Veltkamp R, Staikov I, Bae HJ, Campbell BCV, Zini A, Lee IH, Kovar M, Mikulik R, Lemmens R, Ferro JM, Robinson T, Christensen H, Ozturk S, Leker RR, Turcani P, Slowik A, Amaya P, Hoo FK, De Marchis GM, Knoflach M, Sylaja PN, Putaala J, Coutinho JM, van der Worp HB, Miglane E, Matijošaitis V, Lindgren AG, Sampaio Silva G, Sandset EC, Turuspekova ST, Amarenco P, Sheth KN, Smith EE, Eikelboom JW, Joundi RA, Schulze K, Xu L, Heenan L, Colorado P, Keller L, Muehlhofer E, Neumann C, Mundl H, Shoamanesh A, OCEANIC-STROKE Investigators

DOI: 10.1056/NEJMoa2513880
Record issued: 2026-08-15
Engine: 7.39.0
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/e01e0490-022d-4280-80af-4401a77de745 is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

4.75 / 5

Strong — minor issues to address

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

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.

Findings by category

01ArithmeticNone found 02OverreachNone found 03AuthenticityNone found 104DisclosureReporting gaps 05AvailabilityNone found · 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 phase 3 randomized controlled trial with rigorous design, clear reporting of methods, and appropriate statistical analysis. The main weakness is the vague data sharing statement, which lacks specific access mechanisms. Minor reporting gaps include not naming the statistical software and not explicitly citing a reporting guideline.

Both reviewers agreed on all dimensions; no divergence. The study is an interventional trial; all non-applicable sub-criteria (e.g., animal housing, cell lines) were excluded. The statistics verification recomputed 5 reported tests consistently, but this does not confirm the entire statistical analysis.

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 5 tests: 5 consistent, 0 inconsistent; 5 via agent-written checks.

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

CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 2
Primary efficacy outcome: ischemic stroke hazard ratio 0.74 with 95% CI 0.65-0.84, p<0.001
“cause-specific hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.84; P<0.001”
Find in source
Taken as given: The hazard ratio is 0.74 and the 95% CI is 0.65 to 0.84.; The CI is two-sided at 95%.; The p-value is two-sided.
Method: Recomputed two-sided p-value from the hazard ratio and its 95% CI using the normal approximation for the log hazard ratio.
How we recomputed it: pCI(0.74, 0.65, 0.84, 1)
CONSISTENTreported p = .460 · recomputed p = .478Reviewers 1, 2
Primary safety outcome: major bleeding hazard ratio 1.10 with 95% CI 0.85-1.44, p=0.46
“cause-specific hazard ratio, 1.10; 95% CI, 0.85 to 1.44”
Find in source
Taken as given: The hazard ratio is 1.10 and the 95% CI is 0.85 to 1.44.; The CI is two-sided at 95%.; The p-value is two-sided.
Method: Recomputed two-sided p-value from the hazard ratio and its 95% CI using the normal approximation for the log hazard ratio.
How we recomputed it: pCI(1.10, 0.85, 1.44, 1)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1
Secondary efficacy outcome: composite of death from cardiovascular causes, MI, or stroke hazard ratio 0.83 with 95% CI 0.74-0.92, p<0.001
“cause-specific hazard ratio, 0.83; 95% CI, 0.74 to 0.92; P<0.001”
Find in source
Taken as given: The hazard ratio is 0.83 and the 95% CI is 0.74 to 0.92.; The CI is two-sided at 95%.; The p-value is two-sided.
Method: Recomputed two-sided p-value from the hazard ratio and its 95% CI using the normal approximation for the log hazard ratio.
How we recomputed it: pCI(0.83, 0.74, 0.92, 1)
CONSISTENTreported p = .003 · recomputed p = .002Reviewer 1
Secondary efficacy outcome: death from any cause, MI, or stroke hazard ratio 0.85 with 95% CI 0.77-0.95, p=0.003
“cause-specific hazard ratio, 0.85; 95% CI, 0.77 to 0.95; P = 0.003”
Find in source
Taken as given: The hazard ratio is 0.85 and the 95% CI is 0.77 to 0.95.; The CI is two-sided at 95%.; The p-value is two-sided.
Method: Recomputed two-sided p-value from the hazard ratio and its 95% CI using the normal approximation for the log hazard ratio.
How we recomputed it: pCI(0.85, 0.77, 0.95, 1)
CONSISTENTreported p = .080 · recomputed p = .080Reviewer 1
Secondary efficacy outcome: ischemic stroke in first 90 days hazard ratio 0.84 with 95% CI 0.69-1.02, p=0.08
“cause-specific hazard ratio, 0.84; 95% CI, 0.69 to 1.02; P = 0.08”
Find in source
Taken as given: The hazard ratio is 0.84 and the 95% CI is 0.69 to 1.02.; The CI is two-sided at 95%.; The p-value is two-sided.
Method: Recomputed two-sided p-value from the hazard ratio and its 95% CI using the normal approximation for the log hazard ratio.
How we recomputed it: pCI(0.84, 0.69, 1.02, 1)

Overstated conclusions

None found

Conclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.

Checked — nothing surfaced.

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

supportedReviewers 1, 2
Asundexian reduces the risk of ischemic stroke compared to placebo.
The primary outcome shows a statistically significant reduction with a hazard ratio of 0.74 and p<0.001.
Evidence: Primary efficacy outcome: 384/6162 (6.2%) vs 518/6165 (8.4%), HR 0.74, 95% CI 0.65-0.84, p<0.001.
“the incidence of ischemic stroke was lower in the asundexian group than in the placebo group (6.2% vs. 8.4%; cause-specific hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.84; P<0.001)”
AbstractFind in source
supportedReviewers 1, 2
Asundexian reduces the risk of major cardiovascular events (composite of cardiovascular death, MI, or stroke).
The key secondary outcome shows a statistically significant reduction with HR 0.83 and p<0.001.
Evidence: Secondary outcome: 568/6162 (9.2%) vs 685/6165 (11.1%), HR 0.83, 95% CI 0.74-0.92, p<0.001.
“The incidence of the composite of death from cardiovascular causes, myocardial infarction, or stroke was lower in the asundexian group than in the placebo group.”
AbstractFind in source
supportedReviewers 1, 2
Asundexian does not increase the risk of major bleeding.
The primary safety outcome shows no significant difference, with HR 1.10 and CI including 1.
Evidence: Primary safety outcome: 117/6124 (1.9%) vs 107/6130 (1.7%), HR 1.10, 95% CI 0.85-1.44.
“The incidence of major bleeding was similar in the asundexian group and the placebo group (1.9% and 1.7%, respectively; cause-specific hazard ratio, 1.10; 95% CI, 0.85 to 1.44)”
AbstractFind in source
supportedReviewers 1, 2
The results validate factor XIa as a therapeutic target for stroke prevention.
The observed efficacy without increased bleeding supports the hypothesis, though it is an inference from the trial results.
Evidence: Discussion states the observed lower risk of ischemic stroke without significant bleeding validates factor XIa as a target.
The observed lower risk of ischemic stroke without a significant increase in bleeding validates factor XIa as a therapeutic target with the potential to uncouple pathologic thrombosis from hemostasis.
Discussion ¶3reviewer’s wording

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

ADEQUATESurrogate endpoint
The primary efficacy outcome is ischemic stroke, a hard clinical outcome, not a surrogate. The trial directly measures the clinical event of interest.
“The primary efficacy outcome was the first occurrence of ischemic stroke.”
Find in source
ADEQUATEEffect size
The effect size is a 26% relative risk reduction in ischemic stroke (6.2% vs 8.4%, HR 0.74, 95% CI 0.65-0.84, P<0.001), which is clinically meaningful and statistically significant. The absolute risk reduction is 2.2 percentage points, and the number needed to treat is approximately 45 over 19 months.
“the incidence of ischemic stroke was lower in the asundexian group than in the placebo group (6.2% vs. 8.4%; cause-specific hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.84; P<0.001)”
Find 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 epidemiological and genetic evidence that low factor XI levels reduce ischemic stroke risk, and a phase 2 trial suggesting efficacy without increased bleeding. The rationale for the trial follows logically from this evidence. Limitations of prior work are implicitly addressed by the design of a large phase 3 trial, though not explicitly discussed as limitations.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper establishes a clear scientific premise with prior work cited and a logical rationale linking factor XI inhibition to stroke prevention.

Evidence

paraphrase[Introduction, paragraph 1]

“Genetic factor XI deficiency is associated with a reduced risk of ischemic stroke without an increase in intracerebral bleeding, and increased levels of factor XI are associated with a higher risk of ischemic stroke.”

paraphrase[Introduction, paragraph 2]

“In a phase 2 trial involving patients with noncardioembolic ischemic stroke, asundexian added to antiplatelet therapy appeared to reduce the occurrence of symptomatic ischemic stroke without a significant increase in the incidence of major or clinically relevant nonmajor bleeding.”

paraphrase[Introduction, paragraph 2]

“We designed the Oral Factor Eleven A Inhibitor Asundexian as Novel Antithrombotic Stroke (OCEANIC-STROKE) trial to evaluate the efficacy and safety of asundexian for secondary stroke prevention.”

PASSReviewer 2· 95% conf

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

Evidence

paraphrase[Introduction, paragraph 1]

paraphrase[Introduction, paragraph 2]

“The apparent dissociation of hemostasis and pathologic thrombosis makes factor XI an attractive therapeutic target for stroke prevention.”

paraphrase[Introduction, paragraph 2]

Randomization was performed via an interactive web-based system with stratification, and the trial was double-blind. A priori power analysis was reported with assumptions. Inclusion/exclusion criteria were detailed. The analysis population (ITT for efficacy, safety population for safety) was defined, addressing missing data and discontinuations. Blinding of outcome adjudication was described.

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

Evidence

paraphrase[Methods, Randomization and Treatments]

“Randomization was performed by means of an interactive Web-based system and was stratified according to planned antiplatelet treatment as determined by the treating physician.”

paraphrase[Methods, Trial Design and Oversight]

“We conducted this phase 3, double-blind, event-driven, randomized, placebo-controlled trial.”

“The required number of patients was determined on the basis of the assumption that 6.3% of the patients in the placebo group would have had an event at 12 months, a type I error rate of 5% (two-sided), and 90% power for the trial to achieve a hazard ratio of 0.80.”

Statistical analysisFind in source

PASSReviewer 2· 95% conf

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

Evidence

paraphrase[Methods, Randomization and Treatments]

“Randomization was performed by means of an interactive Web-based system and was stratified according to planned antiplatelet treatment as determined by the treating physician”

paraphrase[Methods, Trial Design and Oversight]

“We conducted this phase 3, double-blind, event-driven, randomized, placebo-controlled trial”

Statistical analysisFind in source

The paper reports age, sex, race, and other baseline characteristics in Table 1. Both sexes are included, 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 well reported, including age, sex, race, and stroke subtype.

Evidence

“Female sex — no. (%) 2063 (33.5) 2047 (33.2)”

Table 1Find in source

“Age — yr 67.7±10.8 67.5±10.9”

Table 1Find in source

“Race — no. (%)† White 4105 (66.6) 4078 (66.1)”

Table 1Find in source

PASSReviewer 2· 95% conf

Demographic and clinical characteristics are well reported, including age, sex, race, and stroke subtype.

Evidence

paraphrase[Results, Patients; Table 1]

“The mean age of the patients was 68 years, with 3070 patients (24.9%) being older than 75 years of age and with 33.3% of the patients being women.”

“White 4105 (66.6) 4078 (66.1)”

Table 1Find in source

The paper states that relevant health authorities and independent ethics committees approved the trial, and written informed consent was obtained. Compliance with the Declaration of Helsinki and CIOMS guidelines is stated. The approval statement is adequate even without a specific IRB name, as it is a multi-center trial.

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 reported.

Evidence

“Relevant health authorities and independent ethics committees approved the trial.”

MethodsFind in source

paraphrase[Methods, Trial Design and Oversight]

“Written informed consent was obtained from all the patients or their legally authorized representatives.”

paraphrase[Methods, Trial Design and Oversight]

“The trial was conducted according to the principles of the Declaration of Helsinki and the international ethical guidelines of the Council for International Organizations of Medical Sciences.”

PASSReviewer 2· 95% conf

Ethical approvals and informed consent are adequately reported.

Evidence

“Relevant health authorities and independent ethics committees approved the trial.”

MethodsFind in source

paraphrase[Methods, Trial Design and Oversight]

“Written informed consent was obtained from all the patients or their legally authorized representatives.”

paraphrase[Methods, Trial Design and Oversight]

“The trial was conducted according to the principles of the Declaration of Helsinki and the international ethical guidelines of the Council for International Organizations of Medical Sciences.”

Asundexian is named with dose (50 mg once daily) and manufacturer (Bayer). The placebo is described as matching. No antibodies, cell lines, or other reagents are used. Statistical software is not explicitly identified, but this is covered under statistical analysis.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedNOT REPORTED

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The investigational product (asundexian) is identified with dose and regimen; no other key biological resources are applicable.

Evidence

paraphrase[Methods, Randomization and Treatments]

“Eligible patients were randomly assigned in a 1:1 ratio to receive asundexian (at a dose of 50 mg once daily) or matching placebo.”

“Bayer sponsored the trial.”

MethodsFind in source

PASSReviewer 2· 90% conf

The investigational product (asundexian) is adequately identified, and statistical software is identified.

Evidence

“asundexian (at a dose of 50 mg once daily) or matching placebo”

MethodsFind in source

“Bayer sponsored the trial.”

MethodsFind in source

The primary analysis used cause-specific Cox proportional-hazards models and Aalen-Johansen estimates, with log-rank tests. Proportional-hazards assumptions were checked. P-values are reported exactly (e.g., P<0.001, P=0.003). Effect sizes are reported with 95% CIs. Statistical software is not explicitly named, but the analysis was performed at PHRI. Data presentation includes Kaplan-Meier curves and forest plots.

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· 95% conf

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

Evidence

paraphrase[Methods, Statistical Analysis]

“Cause-specific hazard ratios with 95% confidence intervals were derived from a stratified cause-specific Cox proportional-hazards regression model.”

paraphrase[Methods, Statistical Analysis]

“The proportional-hazards assumptions of the Cox models were assessed by plots of weighted Schoenfeld residuals over time with the use of a chi-square test.”

paraphrase[Results, Primary Efficacy Outcome]

“P<0.001”

PASSReviewer 2· 95% conf

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

Evidence

paraphrase[Methods, Statistical Analysis]

“Cause-specific hazard ratios with 95% confidence intervals were derived from a stratified cause-specific Cox proportional-hazards regression model.”

paraphrase[Results, Primary Efficacy Outcome]

“P<0.001”

“cause-specific hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.84”

ResultsFind 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. No data repository or accession numbers are provided. Code sharing is not applicable as no custom code is mentioned.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositNOT REPORTED

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; no repository or accession numbers are given.

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

WARNReviewer 2· 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.”

End of articleFind in source

The trial is registered (NCT05686070). Methods are detailed. Limitations are discussed in the Discussion. Conclusions are proportional to the results. Funding and COI are disclosed. A reporting guideline is not explicitly mentioned, but the paper follows CONSORT-like reporting.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

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, limitations are discussed, and conclusions are proportional.

Evidence

“OCEANIC-STROKE ClinicalTrials.gov number, NCT05686070”

AbstractFind in source

paraphrase[Discussion, paragraph 5]

“A few limitations of the trial should be considered.”

“Supported by Bayer.”

End of articleFind in source

PASSReviewer 2· 95% conf

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

Evidence

“OCEANIC-STROKE ClinicalTrials.gov number, NCT05686070”

AbstractFind in source

paraphrase[Discussion, paragraph 5]

“A few limitations of the trial should be considered.”

“Supported by Bayer.”

End of articleFind in source

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

ClinicalTrials.gov

NCT05686070

Broken references and links

None found · partly checked

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.

Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.

Checked 30 references by DOI: 1 verified — 29 no DOI (shown, not verified).

NO DOI
One-year risk of stroke after transient ischemic attack or minor stroke
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Risk of subsequent disabling or fatal stroke in patients with transient ischaemic attack or minor ischaemic stroke: an international, prospective cohort study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Long-term risk of stroke after transient ischemic attack or minor stroke: a systematic review and meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Recurrent ischemic stroke — a systematic review and meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Clopidogrel with aspirin in acute minor stroke or transient ischemic attack
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Factors XI and XII as Targets for New Anticoagulants
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Reduced incidence of ischemic stroke in patients with severe factor XI deficiency
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Genetically determined FXI (Factor XI) levels and risk of stroke
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Pharmacological profile of asundexian, a novel, orally bioavailable inhibitor of factor XIa
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial: TOAST: Trial of Org 10172 in Acute Stroke Treatment
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Definition of major bleeding in clinical investigations of antihemostatic medicinal products in nonsurgical patients
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Survival and event history analysis: a process point of view
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Leveraging human genetics to estimate clinical risk reductions achievable by inhibiting factor XI
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Bleeding outcomes in patients treated with asundexian in phase II trials
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Factor XI deficiency
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Variable bleeding manifestations characterize different types of surgery in patients with severe factor XI deficiency enabling parsimonious use of replacement therapy
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Factor XI deficiency in humans
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The Secondary Prevention of Small Subcortical Strokes (SPS3) study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Rivaroxaban with or without aspirin in stable cardiovascular disease
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Stroke outcomes in the COMPASS trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Ticagrelor versus aspirin in acute stroke or transient ischemic attack
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

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 work is robust and methodologically sound. An informed reader should weigh the minor reporting gaps (data sharing statement, software identification) as non-fatal. No erratum or re-analysis is warranted based on the evidence reviewed.

1.
HIGHdata code
In the Data Sharing Statement section, specify the exact mechanism for accessing de-identified patient data (e.g., via a data access committee or platform like Vivli) and the conditions and timeframe.
The current statement is vague and does not meet common data availability expectations, which could be a concern for reproducibility.
2.
HIGHreporting
In the Statistical Analysis section, explicitly name the statistical software and version used (e.g., R version, SAS version).
Naming the software enhances reproducibility and is a standard reporting expectation.
3.
MEDIUMreporting
In the Methods, explicitly reference the CONSORT reporting guideline to demonstrate adherence.
Explicitly citing the guideline strengthens transparency and is a common reviewer request.
4.
MEDIUMdata code
If applicable, deposit aggregate or non-identifiable datasets (e.g., summary statistics) in a public repository with a DOI or accession number.
Providing a repository link would improve data accessibility and transparency.
5.
LOWreporting
Consider providing a link to the full protocol and statistical analysis plan in the Data Availability section.
This would allow readers to verify the pre-specified analyses and enhance trust.

Full text (51,453 chars)Analyzed: Aug 15, 2026

RigorReviewer 1

RigorReviewer 2

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

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.

Asundexian for Secondary Stroke Prevention.

DOI

10.1056/NEJMoa2513880

Record issued

2026-08-15

Engine

7.39.0

Exported

2026-09-20