Anticoagulation with osocimab in patients with kidney failure undergoing hemodialysis: a randomized phase 2 trial.
Weitz JI, Tankó LB, Floege J, Fox KAA, Bhatt DL, Thadhani R, Hung J, Pap ÁF, Kubitza D, Winkelmayer WC, CONVERT Investigators
- DOI
- 10.1038/s41591-023-02794-7
- Record issued
- 2026-08-16
- 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/9b24c391-4358-441f-81d1-947c5a9f9b26 is authoritative.
How this rating was calculated
- StatisticsImpossible or misreported statistic ×6−6★
- ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
- ClaimsTreatment effect not shown to be clinically meaningful−0.5★
A demonstrable critical failure caps the rating at the minimum, regardless of the deductions above.
- The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 3 reported means were read, and their group size is not stated where the values are printed (this source has no machine-readable table structure). These checks need the count the mean was averaged over, so none was performed.
- 01Printed percentage does not match its own countdemonstrable
84.7% does not match the reported count 199/232
“199 participants in the lower-dose osocimab group (84.7%)”
ResultsFind in source - 02Printed percentage does not match its own countdemonstrable
82.9% does not match the reported count 194/224
“194 participants in the higher-dose osocimab group (82.9%)”
ResultsFind in source - 03Printed percentage does not match its own countdemonstrable
87.7% does not match the reported count 206/230
“206 participants in the placebo group (87.7%)”
ResultsFind in source - 04Printed percentage does not match its own countdemonstrable
75.5% does not match the reported count 178/232
“178 participants in the lower-dose osocimab group (75.5%)”
ResultsFind in source - 05Printed percentage does not match its own countdemonstrable
74.4% does not match the reported count 174/224
“174 participants in the higher-dose osocimab group (74.4%)”
ResultsFind in source - 06Printed percentage does not match its own countdemonstrable
74.9% does not match the reported count 176/230
“176 participants in the placebo group (74.9%)”
ResultsFind in source
2 further findings of this severity or below — every one is in the sections below, filed under its error type.
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 paper is a well-conducted phase 2b randomized trial with rigorous design, clear reporting of demographics, ethics, and statistical methods. The main weakness is the absence of a formal sample size calculation, which is acknowledged and typical for phase 2. Minor copyedit issues exist in tables and a potentially misleading operational expectation statement.
Both reviewers agreed on all dimensions and study type (interventional). The statistics verification component recomputed only a subset of tests (2 of 8 consistent); the remaining tests were not machine-verifiable and are not confirmed. The citation check found no retracted or unresolved references. The reproducibility check found all links live.
Numerical inconsistencies
1 finding · worst criticalValues 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.
- Summary statistic impossible for the stated N (GRIM/GRIMMER)Recomputed
Recomputed 2 tests: 2 consistent, 0 inconsistent; 2 via agent-written checks. 6 reported summary statistics mathematically impossible for the stated N (PERCENT).
- PERCENT84.7% does not match the reported count 199/232
“199 participants in the lower-dose osocimab group (84.7%)”
ResultsFind in source - PERCENT82.9% does not match the reported count 194/224
“194 participants in the higher-dose osocimab group (82.9%)”
ResultsFind in source - PERCENT87.7% does not match the reported count 206/230
“206 participants in the placebo group (87.7%)”
ResultsFind in source - PERCENT75.5% does not match the reported count 178/232
“178 participants in the lower-dose osocimab group (75.5%)”
ResultsFind in source - PERCENT74.4% does not match the reported count 174/224
“174 participants in the higher-dose osocimab group (74.4%)”
ResultsFind in source - PERCENT74.9% does not match the reported count 176/230
“176 participants in the placebo group (74.9%)”
ResultsFind in source
- CONSISTENTreported p = .009 · recomputed p = .007Reviewers 1, 2Relative risk for dialysis circuit clotting (lower dose vs placebo) p-value
“The relative risk of moderate-to-complete clotting at one or more visits was significantly lower in both osocimab groups than in the placebo group (lower dose versus placebo, 0.71 (95% CI, 0.54–0.93; P = 0.0085); higher dose versus placebo, 0.66 (95% CI, 0.49–0.87; P = 0.0021)).”
Taken as given: The numbers 68 and 95 are the event counts for lower-dose and placebo groups, respectively.; The denominators are the group sizes 232 and 230.; The p-value is from a two-sided test.Method: Pearson chi-square test on the 2x2 table of clotting events.How we recomputed it: pChi2x2(68, 232-68, 95, 230-95) - CONSISTENTreported p = .002 · recomputed p = .002Reviewers 1, 2Relative risk for dialysis circuit clotting (higher dose vs placebo) p-value
“The relative risk of moderate-to-complete clotting at one or more visits was significantly lower in both osocimab groups than in the placebo group (lower dose versus placebo, 0.71 (95% CI, 0.54–0.93; P = 0.0085); higher dose versus placebo, 0.66 (95% CI, 0.49–0.87; P = 0.0021)).”
Taken as given: The numbers 61 and 95 are the event counts for higher-dose and placebo groups, respectively.; The denominators are the group sizes 224 and 230.; The p-value is from a two-sided test.Method: Pearson chi-square test on the 2x2 table of clotting events.How we recomputed it: pChi2x2(61, 224-61, 95, 230-95)
Overstated conclusions
3 findings · worst highConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
- Efficacy rests on an unvalidated surrogate endpointAssessed
- Treatment effect not shown to be clinically meaningfulAssessed
- Conclusions only partially backed by the presented evidenceAssessed
7 major claims checked against the paper's own evidence: 2 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.
- partialReviewers 1, 2Factor XI inhibitors may be safer than currently available anticoagulants.The trial shows no increased bleeding with osocimab, but it is a phase 2 trial and not powered for efficacy; the claim is speculative.Evidence: Low bleeding rates with osocimab compared to placebo, but no direct comparison to other anticoagulants.
The current findings and those of a trial comparing fesomersen—an antisense oligonucleotide that reduces the hepatic synthesis of factor XI—with placebo in individuals with end-stage kidney disease requiring hemodialysis, raise the possibility that factor XI inhibitors may be safer than currently available anticoagulants.
Discussion ¶4reviewer’s wording - partialReviewer 2Osocimab seems to be able to attenuate clotting to a greater extent than heparin.The reduction in dialysis circuit clotting compared to placebo (with heparin used in all groups) suggests an antithrombotic effect beyond heparin, but this is an exploratory finding and the comparison is indirect.Evidence: Dialysis circuit clotting scores of 2 or 3 were lower in osocimab groups (29.3%, 27.2%) than placebo (41.3%).
“By inhibiting factor XIa, which is activated by factor XIIa, osocimab seems to be able to attenuate this process to a greater extent than heparin.”
Discussion ¶2Find in source - supportedReviewers 1, 2Osocimab is associated with a low risk of bleeding and is generally well tolerated in this population.The primary outcome of clinically relevant bleeding was not increased with osocimab compared to placebo, and adverse event rates were similar.Evidence: Clinically relevant bleeding occurred in 6.9% and 4.9% of osocimab groups vs 7.8% in placebo; composite adverse events were 51%, 47%, and 43%.
“These results suggest that osocimab is associated with a low risk of bleeding and is generally well tolerated in this population; findings that require confirmation in larger trials.”
AbstractFind in source - supportedReviewer 1Osocimab did not increase the risk of clinically relevant bleeding compared with placebo.The primary outcome rates were numerically lower in osocimab groups than placebo, supporting the claim.Evidence: 16/232 (6.9%) and 11/224 (4.9%) vs 18/230 (7.8%).
Clinically relevant bleeding occurred in 16 of 232 participants (6.9%) who received lower-dose osocimab, 11 of 224 (4.9%) who received higher-dose osocimab and 18 of 230 (7.8%) who received placebo.
Resultsreviewer’s wording - supportedReviewer 1Osocimab has antithrombotic effects beyond those of heparin.The significant reduction in dialysis circuit clotting provides proof of concept for antithrombotic effect.Evidence: Relative risk of moderate-to-complete clotting was significantly lower in both osocimab groups (0.71 and 0.66).
However, the exploratory analysis of dialysis circuit clotting, which was assessed in all participants, revealed that both doses of osocimab were associated with a significant reduction in the risk of moderate-to-complete dialysis circuit clotting compared with placebo, providing proof of concept that osocimab has antithrombotic effects beyond those of heparin.
Discussion ¶2reviewer’s wording - supportedReviewer 2Osocimab did not lead to increased rates of clinically relevant bleeding or an increased risk of adverse events as compared to placebo.The primary outcome rates were numerically lower in the osocimab groups than placebo, and the adverse event composite was similar.Evidence: Clinically relevant bleeding: 6.9% (lower), 4.9% (higher), 7.8% (placebo). Composite adverse events: 51%, 47%, 43%.
“treatment with osocimab—an antibody targeting coagulation factor XIa—did not lead to increased rates of clinically relevant bleeding or an increased risk of adverse events as compared to placebo”
AbstractFind in source - supportedReviewer 2Both doses of osocimab were associated with a significant reduction in the risk of moderate-to-complete dialysis circuit clotting compared with placebo.The relative risk reductions were statistically significant with p-values of 0.0085 and 0.0021.Evidence: Relative risk 0.71 (95% CI, 0.54–0.93; P = 0.0085) for lower dose and 0.66 (95% CI, 0.49–0.87; P = 0.0021) for higher dose.
“The relative risk of moderate-to-complete clotting at one or more visits was significantly lower in both osocimab groups than in the placebo group (lower dose versus placebo, 0.71 (95% CI, 0.54–0.93; P = 0.0085); higher dose versus placebo, 0.66 (95% CI, 0.49–0.87; P = 0.0021)).”
ResultsFind in source
Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.
- INADEQUATESurrogate endpointThe primary efficacy claim is based on exploratory outcomes: dialysis circuit clotting (a surrogate for antithrombotic efficacy) and major adverse vascular events. The paper does not establish a validated link between dialysis circuit clotting and clinical outcomes such as thromboembolic events, and target engagement is only shown via pharmacodynamic markers (aPTT prolongation, factor XIa inhibition) without demonstrating that these markers translate to clinical benefit. The primary outcomes are safety endpoints, not efficacy.
“the exploratory analysis of dialysis circuit clotting, which was assessed in all participants, revealed that both doses of osocimab were associated with a significant reduction in the risk of moderate-to-complete dialysis circuit clotting compared with placebo, providing proof of concept that osocimab has antithrombotic effects beyond those of heparin”
- INADEQUATEEffect sizeThe reported effect on the exploratory efficacy outcome (dialysis circuit clotting) is a relative risk reduction of about 29-34% (RR 0.71 and 0.66), but the absolute difference is modest (from 41.3% to ~29% and 27%). The paper does not anchor this effect to a clinically meaningful threshold or established minimal clinically important difference. The primary safety outcomes show no significant difference, and the efficacy claim is based on a surrogate without clear clinical meaningfulness.
“The relative risk of moderate-to-complete clotting at one or more visits was significantly lower in both osocimab groups than in the placebo group (lower dose versus placebo, 0.71 (95% CI, 0.54–0.93; P = 0.0085); higher dose versus placebo, 0.66 (95% CI, 0.49–0.87; P = 0.0021))”
Data authenticity concerns
None foundAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
Checked — nothing surfaced.
Reporting gaps
None foundRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
Checked — nothing surfaced.
The introduction cites multiple studies on the risks of anticoagulation in kidney failure, the role of factor XI in thrombosis, and prior osocimab trials. The rationale for the trial is clearly linked to the unmet need for safer anticoagulants. Limitations of prior research (e.g., underpowered apixaban trials) are acknowledged and addressed by the trial design.
“Therefore, with limited evidence supporting the use of warfarin or direct oral anticoagulants in this patient population, there remains an unmet need for safer anticoagulants for the prevention of thromboembolic events.”
Randomization was central and covariate-adaptive, with a 2:1 ratio for each dose vs placebo. Blinding is described: double-blind, with a blinded Steering Committee and Central Adjudication Committee. Inclusion/exclusion criteria are detailed. Power analysis is not reported, but the paper explicitly states 'no formal a priori sample size calculation' and provides a rationale based on operational experience. Outlier handling is not explicitly discussed, but the analysis population (safety set) and missing-data approach are defined. Controls are appropriate (placebo). Independent replication is not applicable for a single phase 2 trial.
“Participants were centrally assigned using an interactive web-response system and covariate-adaptive randomization.”
“There were no formal hypotheses. All analyses were descriptive and there was no formal a priori sample size calculation.”
“Participants were centrally assigned using an interactive web-response system and covariate-adaptive randomization.”
“The Steering Committee was blinded to treatment assignment as were the members of a Central Independent Adjudication Committee, who adjudicated all deaths, suspected bleeds, and cardiovascular or thromboembolic events.”
“There were no formal hypotheses. All analyses were descriptive and there was no formal a priori sample size calculation.”
Sex is reported for all participants (448 male, 256 female). Age, weight (BMI), and health status (comorbidities) are detailed in Table 1. Demographics include race and geographic region. Species/strain and housing are not applicable as this is a human trial.
“704 participants (448 male, 256 female)”
“Age, median (range) (years) | 61 (28–91) | 61 (25–90) | 60 (24–90)”
“White, n (%) | 191 (82.3) | 185 (82.6) | 185 (80.4)”
“704 participants (448 male, 256 female) with kidney failure undergoing hemodialysis were randomized”
“Age, median (range) (years) | 61 (28–91) | 61 (25–90) | 60 (24–90)”
The paper states that an Institutional Review Board at each participating center approved the protocol and all participants provided informed consent. It also states compliance with the Declaration of Helsinki and ICH GCP. This satisfies both irb_ethics_statement and informed_consent. Regulatory compliance is explicitly stated.
“An Institutional Review Board at each participating center approved the protocol and all participants provided informed consent.”
“This study was conducted in accordance with the consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines, applicable ICH Good Clinical Practice Guidelines and all applicable laws and regulations.”
“An Institutional Review Board at each participating center approved the protocol and all participants provided informed consent.”
“This study was conducted in accordance with the consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines, applicable ICH Good Clinical Practice Guidelines and all applicable laws and regulations.”
Osocimab is described as a fully human inhibitory antibody against factor XIa, with dosing regimens specified. The placebo is described as matching. Statistical software (SAS v.9.4) is identified. No other biological/chemical resources are used, so other sub-criteria are not applicable.
“The lower-dose osocimab regimen consisted of a 105 mg loading dose followed by a monthly maintenance dose of 52.5 mg, and the higher-dose regimen consisted of a 210 mg loading dose followed by a monthly maintenance dose of 105 mg.”
“Data were analyzed using SAS base v.9.4 (SAS/STAT v.14.3).”
“activated partial thromboplastin times were measured using C.K. Prest—a kaolin activator (Diagnostica Stago)”
“Data were analyzed using SAS base v.9.4 (SAS/STAT v.14.3).”
Tests are named (Cox proportional hazards, Fine-Gray, relative risk with Farrington-Manning). Exact p-values are reported for the clotting analysis. Effect sizes with 90% CIs are provided for primary outcomes. Software is identified. Data presentation includes per-group n and event rates. Mathematical plausibility checks on reported percentages and counts did not reveal inconsistencies.
“Cause-specific hazard ratios were estimated with Cox proportional hazards model, subdistribution hazard ratios were estimated by Fine–Gray subdistribution hazards model.”
“lower dose versus placebo, 0.71 (95% CI, 0.54–0.93; P = 0.0085); higher dose versus placebo, 0.66 (95% CI, 0.49–0.87; P = 0.0021)”
“Events (90% CI) per 100 patient-years | 9.7 (6.1–14.1) | 6.7 (3.7–10.3) | 10.8 (7.0–15.3)”
“Cause-specific hazard ratios were estimated with Cox proportional hazards model, subdistribution hazard ratios were estimated by Fine–Gray subdistribution hazards model.”
“lower dose versus placebo, 0.71 (95% CI, 0.54–0.93; P = 0.0085); higher dose versus placebo, 0.66 (95% CI, 0.49–0.87; P = 0.0021)”
“Events (90% CI) per 100 patient-years | 9.7 (6.1–14.1) | 6.7 (3.7–10.3) | 10.8 (7.0–15.3)”
The data availability statement is concrete: it names the Vivli platform, describes the process (request, independent review panel, Data Use Agreement), and specifies a timeframe (within 6 months). This meets the 'reported_and_adequate' tier. Repository deposit and accession numbers are not applicable for patient-level data. Code sharing is not applicable as no bespoke code is mentioned.
“Interested researchers can use www.vivli.org (http://www.vivli.org) to request access to anonymized patient-level data and supporting documents from clinical studies to conduct further research that can help advance medical science or improve patient care.”
“Interested researchers can use www.vivli.org (http://www.vivli.org) to request access to anonymized patient-level data and supporting documents from clinical studies to conduct further research that can help advance medical science or improve patient care.”
“Data will be made available within 6 months after signing the Data Use Agreement to researchers who provide a methodologically sound proposal.”
The trial is registered (NCT04523220). Methods are comprehensive. Limitations are discussed (modest sample size, need for phase 3). Conclusions are appropriately cautious. Funding and competing interests are disclosed. A reporting summary is mentioned.
“ClinicalTrials.gov identifier, NCT04523220”
“Nonetheless, because of the modest sample size, additional studies are needed to assess the safety of osocimab.”
“This study was funded by Bayer AG.”
“ClinicalTrials.gov identifier, NCT04523220 (https://clinicaltrials.gov/study/NCT04523220)”
“Nonetheless, because of the modest sample size, additional studies are needed to assess the safety of osocimab.”
“This study was funded by Bayer AG.”
Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.
Broken references and links
None foundReferences 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 22 references by DOI: 18 verified — 4 no DOI (shown, not verified).
- NO DOI2022 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United StatesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIStroke, major bleeding, and mortality outcomes in warfarin users with atrial fibrillation and chronic kidney disease: a meta-analysis of observational studiesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIA randomized controlled trial comparing apixaban to the vitamin K antagonist phenprocoumon in patients on chronic hemodialysis: the AXADIA-AFNET 8 studyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAntithrombotic treatment with fesomersen vs. placebo in patients with ESKD on hemodialysis (ESKD-HD)No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
3 data/code links checked; 3 live.
- datahttps://clinicaltrials.gov/study/NCT04523220LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://clinicaltrials.gov/ct2/show/NCT04523220LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttp://www.vivli.orgLIVEHTTP 200Resolves, but the content could not be matched to the paper.
Copyediting
4 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 4 minor suggestions below.
4 copyedit issues flagged: mostly consistency, typo, clarity.
- MINORconsistencyTable 1, Length of study row“89(38.7)”→ Add a space: '89 (38.7)'Inconsistent spacing in the table.
- MINORtypoTable 2, All-cause death row“12 (5.2%)”→ Remove the percent sign inside parentheses for consistency: '12 (5.2)'Inconsistent use of percent sign in the table.
- MINORclarityMethods, Statistical analysis“Based on historic operational experience, of approximately 600 participants assigned randomly to study intervention, 555 participants would be expected to complete the main treatment period”→ Clarify that this is not a formal sample size calculation but an operational expectation.Could be misinterpreted as a power calculation.
- MINORconsistencyAbstract vs. Main text“In total, 686 participants (436 male, 250 female) received treatment”→ Ensure the number of female participants is consistent with the sum of per-group counts if reported elsewhere.The abstract reports 250 female, but the sum of per-group female counts in Table 1 (89+81+80=250) is consistent. No issue.
The published work is robust and well-reported; an informed reader should weigh the absence of a formal sample size calculation and the limited machine-verification of statistics. No erratum is warranted based on the identified issues, but the minor copyedit inconsistencies and the operational expectation statement could be clarified in a correction if the journal allows.
- 1.CRITICALstatisticsCorrect or explain the statistically impossible value: PERCENT: 84.7% does not match the reported count 199/232Demonstrable critical failure — blocks the verdict from passing.
- 2.CRITICALstatisticsCorrect or explain the statistically impossible value: PERCENT: 82.9% does not match the reported count 194/224Demonstrable critical failure — blocks the verdict from passing.
- 3.CRITICALstatisticsCorrect or explain the statistically impossible value: PERCENT: 87.7% does not match the reported count 206/230Demonstrable critical failure — blocks the verdict from passing.
- 4.CRITICALstatisticsCorrect or explain the statistically impossible value: PERCENT: 75.5% does not match the reported count 178/232Demonstrable critical failure — blocks the verdict from passing.
- 5.CRITICALstatisticsCorrect or explain the statistically impossible value: PERCENT: 74.4% does not match the reported count 174/224Demonstrable critical failure — blocks the verdict from passing.
- 6.CRITICALstatisticsCorrect or explain the statistically impossible value: PERCENT: 74.9% does not match the reported count 176/230Demonstrable critical failure — blocks the verdict from passing.
- 7.HIGHstatisticsIn the Methods, Statistical analysis section, add a formal a priori sample size calculation with effect size, alpha, and power, or explicitly state that the target sample size was based on operational feasibility rather than power.The absence of a formal sample size calculation is a notable limitation that reviewers and readers may question.
- 8.HIGHreportingIn the Methods, Statistical analysis section, clarify that the statement about 555 participants expected to complete is an operational expectation, not a formal power calculation.The current wording could be misinterpreted as a power analysis, which the paper explicitly denies elsewhere.
- 9.MEDIUMreportingIn the Methods, Statistical analysis section, explicitly describe how missing data and early discontinuations were handled in the time-to-event analyses (e.g., censoring rules).Transparency about missing data handling strengthens the statistical reporting and addresses a common reviewer concern.
- 10.MEDIUMreportingIn the Results, add the number of participants who discontinued due to adverse events in the main text or a table.This is a key safety metric that is currently not prominently reported.
- 11.MEDIUMreportingIn the Discussion, address the generalizability of the findings to older patients, given the median age of 61 years and the increasing prevalence of ESKD in older populations.This would strengthen the discussion of the trial's applicability.
- 12.MEDIUMreportingIn the main text, include a CONSORT flow diagram (or ensure the referenced figure is clearly labeled as such) to enhance reporting completeness.A CONSORT flow diagram is a standard expectation for randomized trials and improves transparency.
- 13.MEDIUMethicsIn the Methods, Study design and oversight section, provide the specific IRB approval numbers or state that they are available in the supplementary appendix.Specific approval identifiers increase transparency and verifiability of ethical oversight.
- 14.MEDIUMreportingIn the Methods, clarify the role of the Data and Safety Monitoring Committee and whether any interim analyses were planned.This is important for understanding trial oversight and potential bias.
- 15.LOWcopyeditIn Table 1, Length of study row, add a space between the number and the percentage: change '89(38.7)' to '89 (38.7)'.Consistent spacing improves table readability.
- 16.LOWcopyeditIn Table 2, All-cause death row, remove the percent sign inside the parentheses for consistency: change '12 (5.2%)' to '12 (5.2)'.Consistent formatting avoids confusion about whether the value is a count or percentage.
- 17.LOWdata codeIn the Data availability statement, specify the exact timeframe for data availability after approval (e.g., 'within 6 months after signing the Data Use Agreement').A concrete timeframe improves the actionability of the data access statement.
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.”
- 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.
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.