The microRNA inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: a randomized phase 2 trial.
Bauersachs J, Solomon SD, Anker SD, Antorrena-Miranda I, de Boer RA, Filippatos G, Friede T, Hauke W, Ponikowski P, Vardeny O, Altschul R, Gamborg M, Vinther K, Thum T
- DOI
- 10.1038/s41591-026-04408-4
- 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/b3b353bf-bbf5-4ed8-9c1a-472b40ea24a8 is authoritative.
How this rating was calculated
- StatisticsImpossible or misreported statistic ×3−3★
- IntegrityIntegrity concern ×3−1.5★
- StatisticsPrinted percentage does not match its own count (capped) ×13−0.25★
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: 12 reported means were read, and their group size is not stated where the values are printed. These checks need the count the mean was averaged over, so none was performed.
- 01Printed percentage does not match its own countdemonstrable
4% is unattainable for n=4 (nearest: 0, 25%)
“Class III/IV | 4 (4)”
Table 1Find in source - 02Printed percentage does not match its own countdemonstrable
7% is unattainable for n=7 (nearest: 0, 14%)
“Class III | 7 (7)”
Table 1Find in source - 03Printed percentage does not match its own countdemonstrable
4% is unattainable for n=4 (nearest: 0, 25%)
“Class III | 4 (4)”
Table 1Find in source - 04Printed percentage does not match its own count
12% is unattainable for n=11 (nearest: 9, 18%)
“Female | 11 (12)”
Table 1Find in source - 05Printed percentage does not match its own count
16% is unattainable for n=15 (nearest: 13, 20%)
“Female | 15 (16)”
Table 1Find in source - 06Printed percentage does not match its own count
10% is unattainable for n=9 (nearest: 0, 11%)
“Female | 9 (10)”
Table 1Find in source
11 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-designed and transparently reported phase 2 randomized controlled trial. Both reviewers found all eight rigor dimensions adequate, with strong methodology, ethical compliance, and proportional conclusions. Minor reporting gaps (e.g., race/ethnicity, exact p-values in abstract) and a few internal consistency issues in the safety population description are noted but do not undermine the overall rigor.
Both reviewers classified the study as interventional, which was adopted. The evaluation covered all eight dimensions; several sub-criteria were not applicable (e.g., animal housing, cell line authentication) for this human trial. The statistics verification component checked only a subset of tests (those with test statistics/df or effect estimates with CIs); 16 of 19 recomputations were inconsistent, but this is likely due to rounding or unverifiable threshold-only p-values, and no decision errors were found. The integrity component flagged a retrospective registration concern and minor internal contradictions in the safety population description.
Numerical inconsistencies
3 findings · 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
- Printed percentage does not match its own countRecomputed
- Internal contradictions in the reported numbersAssessed
Recomputed 1 test: 1 consistent, 0 inconsistent; 1 via agent-written checks. 3 reported summary statistics mathematically impossible for the stated N (PERCENT). 13 printed percentages that do not match their own count.
- PERCENT12% is unattainable for n=11 (nearest: 9, 18%)
“Female | 11 (12)”
Table 1Find in source - PERCENT16% is unattainable for n=15 (nearest: 13, 20%)
“Female | 15 (16)”
Table 1Find in source - PERCENT10% is unattainable for n=9 (nearest: 0, 11%)
“Female | 9 (10)”
Table 1Find in source - PERCENT17% is unattainable for n=16 (nearest: 13, 19%)
“NSTEMI | 16 (17)”
Table 1Find in source - PERCENT16% is unattainable for n=15 (nearest: 13, 20%)
“NSTEMI | 15 (16)”
Table 1Find in source - PERCENT14% is unattainable for n=13 (nearest: 8, 15%)
“≥1 | 13 (14)”
Table 1Find in source - PERCENT20% is unattainable for n=18 (nearest: 17, 22%)
“≥1 | 18 (20)”
Table 1Find in source - PERCENT19% is unattainable for n=18 (nearest: 17, 22%)
“Class II | 18 (19)”
Table 1Find in source - PERCENT16% is unattainable for n=15 (nearest: 13, 20%)
“Class II | 15 (16)”
Table 1Find in source - PERCENT4% is unattainable for n=4 (nearest: 0, 25%)
“Class III/IV | 4 (4)”
Table 1Find in source - PERCENT2% is unattainable for n=2 (nearest: 0, 50%)
“Class III/IV | 2 (2)”
Table 1Find in source - PERCENT3% is unattainable for n=3 (nearest: 0, 33%)
“Class III/IV | 3 (3)”
Table 1Find in source - PERCENT7% is unattainable for n=7 (nearest: 0, 14%)
“Class III | 7 (7)”
Table 1Find in source - PERCENT3% is unattainable for n=3 (nearest: 0, 33%)
“Class III | 3 (3)”
Table 1Find in source - PERCENT4% is unattainable for n=4 (nearest: 0, 25%)
“Class III | 4 (4)”
Table 1Find in source - PERCENT29% is unattainable for n=26 (nearest: 27, 31%)
“Non-anterior | 26 (29)”
Table 1Find in source
- CONSISTENTreported p = .370 · recomputed p = .544Reviewers 1, 2Primary endpoint LSM difference for 5 mg/kg vs placebo
“The resulting placebo-adjusted least squares mean (LSM) differences were −1.11% (s.e.m. 3.37; F-test P = 0.37) for 5 mg kg−1”
Taken as given: The F-test has 1 numerator degree of freedom (two groups comparison).; The denominator degrees of freedom is approximately 276 (mITT N minus parameters).; The reported p-value is two-sided.Method: Recomputed p-value from F-statistic using F distribution with df1=1, df2=276.How we recomputed it: pF(0.37, 1, 276) - UNCOMPUTABLEreported p = .260 · recomputed p = .611Reviewer 1Primary endpoint LSM difference for 10 mg/kg vs placebo
“and −2.14% (s.e.m. 3.27; F-test P = 0.26) for 10 mg kg−1”
Taken as given: The F-test has 1 numerator degree of freedom.; The denominator degrees of freedom is approximately 276.; The reported p-value is two-sided.Method: Recomputed p-value from F-statistic using F distribution with df1=1, df2=276.How we recomputed it: pF(0.26, 1, 276) - UNCOMPUTABLEreported p = .227 · recomputed p = .821Reviewer 2Secondary endpoint LVEF LSM difference for pooled CDR132L vs placebo
“LSM difference, CDR132L versus placebo (95% CI; one-sided P value) | 0.87 (−1.41, 3.15; P = 0.227)”
Taken as given: The p-value is one-sided as stated.; The test statistic is a t-statistic with 278 degrees of freedom (approximate, based on mITT N=280 minus parameters).Method: Recomputed the one-sided p-value from the t-statistic using the t distribution with 278 degrees of freedom.How we recomputed it: pT(0.227, 278)
- lowinternal contradictionThe safety population is described as identical to mITT, but one patient randomized to 10 mg/kg received placebo and is counted in the placebo arm for safety, making the safety population N=280 but with different group assignments than mITT.
This population was identical to the mITT population. However, one patient randomized to receive CDR132L 10 mg kg−1 erroneously received placebo and so was included in the placebo arm of the safety population, despite being in the CDR132L 10 mg kg−1 arm of the mITT population.
Resultsreviewer’s wording - lowinternal contradictionThe safety population is described as identical to the mITT population, but one patient was moved from the 10 mg/kg arm to the placebo arm in the safety population, making the group sizes differ (94, 95, 91 vs 94, 96, 90).
This population was identical to the mITT population. However, one patient randomized to receive CDR132L 10 mg kg−1 erroneously received placebo and so was included in the placebo arm of the safety population, despite being in the CDR132L 10 mg kg−1 arm of the mITT population.
Resultsreviewer’s wording
Overstated conclusions
1 finding · worst lowConclusions 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
8 major claims checked against the paper's own evidence: 1 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.
- partialReviewers 1, 2Prespecified exploratory analyses suggested potential benefits in patients with advanced remodeling.The subgroup analyses show numerical trends but no significant interactions, so the claim is partially supported but appropriately labeled exploratory.Evidence: Subgroup analyses in Fig. 4 show larger LVESVI reductions in high-risk subgroups, but no significant treatment-by-subgroup interactions.
“Prespecified exploratory analyses suggested potential benefits of CDR132L treatment in patients with advanced adverse remodeling at baseline, supporting further evaluation of CDR132L, including in chronic heart failure conditions.”
AbstractFind in source - supportedReviewers 1, 2CDR132L was well tolerated with no safety signals.The safety data presented support this claim, with similar adverse event rates across groups and no organ-specific toxicity.Evidence: Safety results in Extended Data Table 3 show comparable TEAE rates and no dose-dependent serious adverse events.
“CDR132L was well tolerated, with no hepatic, renal, hematologic or cardiac toxicity signals.”
AbstractFind in source - supportedReviewer 1The primary endpoint was not met; no significant difference in LVESVI change between CDR132L and placebo.The primary analysis shows non-significant p-values for both doses, supporting the claim.Evidence: LSM differences of -1.11% (P=0.37) and -2.14% (P=0.26) for 5 and 10 mg/kg, respectively.
The primary endpoint—the percentage change in LV end-systolic volume index at 6 months—improved in all groups but did not differ significantly between the CDR132L groups (5 mg kg−1 and 10 mg kg−1) and the placebo group.
Abstractreviewer’s wording - supportedReviewer 1Secondary endpoints were not significantly different between CDR132L and placebo.All secondary endpoints show non-significant p-values, supporting the claim.Evidence: Table 2 shows non-significant p-values for LVEF, NT-proBNP, GLS, and KCCQ.
“Secondary endpoints, including LV ejection fraction, global longitudinal strain and N-terminal pro B-type natriuretic peptide, were also not significantly different between the CDR132L and placebo groups.”
AbstractFind in source - supportedReviewer 1CDR132L achieved dose-dependent target engagement as measured by plasma miR-132.The pharmacodynamic data show dose-dependent reductions in plasma miR-132, supporting the claim.Evidence: Figure 2 shows dose-dependent decreases in plasma miR-132.
Plasma miR-132 decreased in a dose-dependent manner after administration of CDR132L, with the greatest reductions observed in the 10 mg kg−1 group.
Resultsreviewer’s wording - supportedReviewer 2The primary endpoint was not met.The primary endpoint analysis showed no significant difference between CDR132L and placebo, as reported.Evidence: LSM differences were −1.11% (P=0.37) and −2.14% (P=0.26) for the two doses.
The primary endpoint—the percentage change in LV end-systolic volume index at 6 months—improved in all groups but did not differ significantly between the CDR132L groups (5 mg kg−1 and 10 mg kg−1) and the placebo group.
Abstractreviewer’s wording - supportedReviewer 2Secondary endpoints were not significantly different.All secondary endpoints showed no statistically significant differences, as reported in Table 2.Evidence: Table 2 shows p-values >0.05 for all secondary endpoints.
“Secondary endpoints, including LV ejection fraction, global longitudinal strain and N-terminal pro B-type natriuretic peptide, were also not significantly different between the CDR132L and placebo groups.”
AbstractFind in source - supportedReviewer 2CDR132L achieved dose-dependent target engagement.Plasma miR-132 levels decreased dose-dependently, supporting target engagement, though the paper notes this may not reflect cardiac tissue levels.Evidence: Figure 2 shows dose-dependent reductions in plasma miR-132.
Plasma miR-132 decreased in a dose-dependent manner after administration of CDR132L, with the greatest reductions observed in the 10 mg kg−1 group.
Resultsreviewer’s wording
Data authenticity concerns
1 finding · worst mediumAn 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.
- Other integrity concernAssessed
3 integrity concerns flagged (0 high).
- mediumotherTrial NCT04045405 was first submitted to ClinicalTrials.gov on 2019-07-23, after the registered study start date of 2019-06-21. Retrospective registration means the protocol and outcomes were not on the public record before the study ran, which is what prospective registration exists to establish.
NCT04045405
reviewer’s wording
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 prior research on miR-132's role in cardiac remodeling and preclinical studies of CDR132L, acknowledging both strengths and limitations. The rationale linking miR-132 inhibition to potential therapeutic benefit is logically presented, and the study builds on a phase 1b trial. Limitations of prior work, such as the need for human data, are implicitly addressed by the phase 2 design.
“Current pharmacological approaches predominantly target neurohormonal activation and hemodynamic load, but few interventions directly modulate the molecular and structural maladaptations of the myocardium.”
Randomization was centralized using a computer-generated schedule stratified by age and infarction location. Blinding was double-blind with a blinded core laboratory. A priori sample size calculation with power estimates is provided. Inclusion/exclusion criteria are detailed, and the mITT population is prespecified as primary. Missing data handling (LOCF, MMRM) is described. The trial is registered (NCT05350969).
“Patients were randomized centrally using a computer-generated schedule stratified by age group (<60 years, ≥60 years) and location of infarction (anterior, non-anterior).”
“Investigators, patients, core laboratory personnel and the sponsor remained blinded until all patients had completed month 6.”
“Patients were randomized centrally using a computer-generated schedule stratified by age group (<60 years, ≥60 years) and location of infarction (anterior, non-anterior).”
“Investigators, patients, core laboratory personnel and the sponsor remained blinded until all patients had completed month 6.”
Sex at birth is reported (13% women), age is reported, and extensive baseline clinical characteristics are provided in Table 1. Since both sexes are enrolled, sex justification is not applicable. Demographics include age, sex, and clinical measures; race/ethnicity is not reported but is not required for this trial.
“In the mITT population, the median age was 61.0 years (range, 35–80), and 13% were women based on sex at birth; gender data were not collected.”
“Median age a , years (min, max) | 61.0 (35, 80) | 62.0 (37, 79) | 62.0 (36, 79) | 61.0 (35, 80)”
“In the mITT population, the median age was 61.0 years (range, 35–80), and 13% were women based on sex at birth; gender data were not collected.”
“Median age a , years (min, max) | 61.0 (35, 80) | 62.0 (37, 79) | 62.0 (36, 79) | 61.0 (35, 80)”
The paper states that the protocol was approved by an independent ethics committee or IRB at each site, and that all patients provided written informed consent. It also cites compliance with ICH GCP and the Declaration of Helsinki. The trial is registered.
“The study protocol, all study protocol amendments, written study participant information, informed consent form, Investigator’s Brochure and any other relevant documents were reviewed and approved by an independent ethics committee or institutional review board at each study site.”
“All patients provided written informed consent.”
“This study was conducted in accordance with the study protocol and all approved amendments; the International Council for Harmonisation (ICH) Guideline for Good Clinical Practice E6(R2); the ethical principles of the Declaration of Helsinki;”
“The study protocol, all study protocol amendments, written study participant information, informed consent form, Investigator’s Brochure and any other relevant documents were reviewed and approved by an independent ethics committee or institutional review board at each study site.”
“All patients provided written informed consent.”
“This study was conducted in accordance with the study protocol and all approved amendments; the International Council for Harmonisation (ICH) Guideline for Good Clinical Practice E6(R2); the ethical principles of the Declaration of Helsinki; the Council for International Organizations of Medical Sciences, International Ethical Guidelines; all applicable local laws and regulations; and ICH requirements for archiving and retention of essential documents.”
CDR132L is identified as a synthetic LNA-based antisense oligonucleotide, and the miRNA assay kit is specified (CardiorHealth miR-132 Plasma PCR Kit). The drug is named with manufacturer (Cardior Pharmaceuticals) and dose regimen. Software (SAS 9.4) is identified. No antibodies or cell lines are used.
“CDR132L is a synthetic, locked nucleic acid (LNA)-based antisense oligonucleotide specifically designed and optimized to inhibit miR-132.”
“Plasma miR-132 levels were quantified at Biotype GmbH using the CardiorHealth miR-132 Plasma PCR Kit (Cardior Pharmaceuticals GmbH) in accordance with the manufacturer’s instructions.”
“All analyses performed used SAS version 9.4 software.”
“CDR132L is a synthetic, locked nucleic acid (LNA)-based antisense oligonucleotide specifically designed and optimized to inhibit miR-132.”
“Plasma miR-132 levels were quantified at Biotype GmbH using the CardiorHealth miR-132 Plasma PCR Kit (Cardior Pharmaceuticals GmbH) in accordance with the manufacturer’s instructions.”
“All analyses performed used SAS version 9.4 software.”
The primary analysis uses ANCOVA with a one-sided test at alpha 0.025. Tests are named, and effect sizes with 95% CIs are reported. P-values are reported as exact values (e.g., P = 0.37). Software is identified. Data presentation includes per-group n and dispersion. Mathematical plausibility checks were not performed due to continuous outcomes and large N.
“The primary analysis used an analysis of covariance (ANCOVA) model that included treatment as a fixed effect and baseline LVESVI as a covariate.”
“LSM difference, CDR132L versus placebo (95% CI; one-sided P value) | 0.87 (−1.41, 3.15; P = 0.227)”
“The primary analysis used an analysis of covariance (ANCOVA) model that included treatment as a fixed effect and baseline LVESVI as a covariate.”
“LSM difference, CDR132L versus placebo (95% CI; one-sided P value) | 0.87 (−1.41, 3.15; P = 0.227)”
The data availability statement provides a concrete mechanism for requesting access via Novo Nordisk's trial data platform, with conditions and timeframe. Since the data are patient-level and identifiable, repository deposit and accession numbers are not applicable. No custom code was used beyond standard SAS, so code sharing is not applicable.
“Researchers can request access to clinical trial data by submitting a research proposal for review and approval by Novo Nordisk and an internal independent review panel.”
“Requests are considered after the research is concluded or completed and the main results have been published.”
“Researchers can request access to clinical trial data by submitting a research proposal for review and approval by Novo Nordisk and an internal independent review panel. Requests are considered after the research is concluded or completed and the main results have been published.”
The trial is registered (NCT05350969). Methods are detailed enough for replication. All outcomes are reported, including negative results. Limitations are thoroughly discussed. Conclusions are appropriately cautious, emphasizing the exploratory nature of subgroup findings. Funding and COI statements are provided.
“ClinicalTrials.gov: NCT05350969”
“Several additional factors may have influenced the ability to detect a significant treatment effect in the overall study population.”
“The subgroup findings are exploratory and hypothesis generating only.”
“ClinicalTrials.gov: NCT05350969”
“Several additional factors may have influenced the ability to detect a significant treatment effect in the overall study population.”
“The subgroup findings are exploratory and hypothesis generating only.”
Registered (4 IDs: ClinicalTrials.gov). Reporting guideline cited: CONSORT.
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 12 references by DOI: 12 verified.
Every extracted reference resolved against Crossref/OpenAlex with no retraction flags.
1 data/code link checked; 1 live.
- datahttps://www.novonordisk-trials.com/LIVEHTTP 200Resolves, but the content could not be matched to the paper.
Copyediting
2 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 2 minor suggestions below.
2 copyedit issues flagged: mostly consistency, clarity.
- MINORconsistencyAbstract“As presented at the 2026 ESC Heart Failure Congress, in a phase 2 randomized trial...”→ Consider moving this sentence to the end of the abstract or removing it, as it is not a standard abstract element.The sentence about the congress presentation is unusual in an abstract.
- MINORclarityResults, Trial population“The intention-to-treat (ITT) population comprised all randomized patients (n = 294).”→ Clarify that the ITT population is the same as the randomized population, as this is standard.The definition is clear but could be more concise.
The published work is robust and well-reported; an informed reader should weigh the minor internal consistency issues in the safety population description and the retrospective registration of the phase 1b trial (NCT04045405) as caveats. No erratum is clearly warranted, but the authors should consider clarifying the safety population discrepancy and providing exact p-values for primary endpoints in the abstract for completeness.
- 1.CRITICALstatisticsCorrect or explain the statistically impossible value: PERCENT: 4% is unattainable for n=4 (nearest: 0, 25%)Demonstrable critical failure — blocks the verdict from passing.
- 2.CRITICALstatisticsCorrect or explain the statistically impossible value: PERCENT: 7% is unattainable for n=7 (nearest: 0, 14%)Demonstrable critical failure — blocks the verdict from passing.
- 3.HIGHreportingClarify the safety population description in the Methods/Results: state explicitly that one patient randomized to 10 mg/kg received placebo and is counted in the placebo arm for safety, making the safety population group sizes differ from mITT (94, 95, 91 vs 94, 96, 90).The current text says the safety population is identical to mITT, which contradicts the reported group assignments and could confuse readers.
- 4.HIGHreportingAdd a note in the Discussion or Methods acknowledging that the phase 1b trial (NCT04045405) was registered retrospectively (first submitted 2019-07-23 after study start 2019-06-21), and discuss any implications for the current trial's interpretation.Retrospective registration of the prior trial is a transparency concern that informed readers should weigh.
- 5.MEDIUMreportingReport exact p-values for the primary endpoint in the Abstract, not just in the Results section.The abstract currently omits exact p-values, which are important for readers assessing the primary outcome.
- 6.MEDIUMreportingAdd a statement in the Methods about whether the trial was reported according to CONSORT guidelines, and include a completed CONSORT checklist as supplementary material.Explicit adherence to CONSORT improves transparency and reproducibility.
- 7.MEDIUMreportingReport the number of patients screened and reasons for exclusion at each stage in the CONSORT diagram more explicitly.The current text mentions 427 screened but does not detail exclusion reasons, which is a standard CONSORT requirement.
- 8.MEDIUMstatisticsProvide results of the sensitivity analysis using multiple imputation for the primary endpoint, as mentioned in the Methods.Reporting the results of prespecified sensitivity analyses strengthens the statistical robustness assessment.
- 9.MEDIUMreportingReport exact p-values for subgroup analyses in the text or tables, as forest plots may not provide exact values.Exact p-values allow readers to assess the strength of subgroup findings.
- 10.MEDIUMreportingAdd a statement about the availability of the statistical analysis plan in a public repository (e.g., ClinicalTrials.gov or a preprint server).Public availability of the SAP enhances transparency and reproducibility.
- 11.MEDIUMreportingDiscuss the potential impact of open-label pharmacy staff on blinding, and whether any unblinding risks were mitigated.The pharmacy staff were not blinded, which is a potential source of bias that should be addressed.
- 12.LOWreportingReport race/ethnicity in baseline demographics to enhance generalizability.Race/ethnicity is not currently reported, which limits assessment of generalizability.
- 13.LOWreportingProvide more detail on the randomization schedule generation (e.g., block size) in the Methods.Details on block size and generation method improve reproducibility of the randomization process.
- 14.LOWreportingReport the intraclass correlation coefficient for core lab echocardiography readings to assess reproducibility.ICC values would help readers assess the reliability of the primary endpoint measurements.
- 15.LOWdata codeProvide more details on the data request review process, such as a template or timeline for approval.More transparency on data access procedures would facilitate data sharing.
- 16.LOWcopyeditMove the sentence about the ESC Heart Failure Congress presentation from the Abstract to the end or remove it, as it is not a standard abstract element.The congress presentation sentence is unusual in an abstract and may distract from the scientific content.
- 17.LOWcopyeditClarify in the Results that the ITT population is the same as the randomized population (n=294) for conciseness.The current definition is clear but could be more concise and standard.
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.