Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial.
Malhotra A, Grunstein R, Azarbarzin A, Sands S, Somers VK, Aronne LJ, Jastreboff AM, Lou J, Chakladar S, Dunn JP, Bunck MC, Bednarik J
- DOI
- 10.1038/s41591-025-04071-1
- 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/0f045850-9dc4-43d1-9b69-d4c28acf5f82 is authoritative.
How this rating was calculated
- StatisticsImpossible or misreported statistic ×3−3★
- IntegrityIntegrity concern−0.5★
- ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
- ClaimsTreatment effect not shown to be clinically meaningful−0.5★
- StatisticsPrinted percentage does not match its own count (capped) ×7−0.25★
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: 36 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
70.6% does not match the reported count 84/120
“84 (70.6)”
Table 1 - 02Printed percentage does not match its own countdemonstrable
65.8% does not match the reported count 75/115
“75 (65.8)”
Table 1 - 03Printed percentage does not match its own countdemonstrable
68.2% does not match the reported count 159/235
“159 (68.2)”
Table 1 - 04Efficacy rests on an unvalidated surrogate endpoint
The primary efficacy claim is based on changes in cardiometabolic risk markers (e.g., hsCRP, lipids, HOMA-IR, blood pressure) which are surrogate biomarkers, not hard clinical outcomes. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD) nor cite validated evidence linking these surrogates to clinical outcomes in this context. The mediation analysis is exploratory and does not establish clinical benefit.
“The improvements in cardiometabolic risk measures were both statistically significant and clinically meaningful and, therefore, tirzepatide treatment may lead to improvement in overall cardiometabolic risk in patients with OSA and obesity.”
- 05Treatment effect not shown to be clinically meaningful
The reported effect sizes are relative changes in biomarkers (e.g., hsCRP -28.9% to -45.1%, HOMA-IR -48.0% to -54.5%) without anchoring to established minimal clinically important differences or demonstrating restoration to normal levels. The paper claims clinical meaningfulness but does not provide a quantitative anchor to clinical benefit.
“The improvements in cardiometabolic risk measures were both statistically significant and clinically meaningful”
- 06Printed percentage does not match its own count
36.1% does not match the reported count 43/120
“43 (36.1)”
Table 1
6 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.
This is a well-conducted secondary analysis of two phase 3 randomized trials, with strong reporting of design, ethics, biological variables, and data availability. The main weaknesses are minor reporting gaps: exact p-values are often given as thresholds, the randomization method and power analysis for secondary outcomes are not detailed, and a few copyedit issues exist.
Both reviewers classified the study as interventional, which is appropriate given the randomized controlled trial design. The evaluation covered the full text, with verification components for citations, statistics, reproducibility, and preregistration. Non-applicable sub-criteria (e.g., animal housing, cell lines) were excluded. The statistics verification could only recompute a subset of tests; most p-values were threshold-only and not machine-verifiable, so no claim of statistical correctness is made.
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 3 tests: 3 consistent, 0 inconsistent; 3 via agent-written checks. 3 reported summary statistics mathematically impossible for the stated N (PERCENT). 7 printed percentages that do not match their own count.
- PERCENT36.1% does not match the reported count 43/120
“43 (36.1)”
Table 1 - PERCENT35.2% does not match the reported count 82/234
“82 (35.2)”
Table 1 - PERCENT29.4% does not match the reported count 35/120
“35 (29.4)”
Table 1 - PERCENT32.5% does not match the reported count 37/115
“37 (32.5)”
Table 1 - PERCENT30.9% does not match the reported count 72/235
“72 (30.9)”
Table 1 - PERCENT61.3% does not match the reported count 73/120
“73 (61.3)”
Table 1 - PERCENT63.1% does not match the reported count 147/234
“147 (63.1)”
Table 1 - PERCENT70.6% does not match the reported count 84/120
“84 (70.6)”
Table 1 - PERCENT65.8% does not match the reported count 75/115
“75 (65.8)”
Table 1 - PERCENT68.2% does not match the reported count 159/235
“159 (68.2)”
Table 1
- CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 2Check p-value for SBP ETD in study 1 from CI
“−7.9 mmHg; 95% confidence interval (CI) −11.0 to −4.9; P < 0.001”
Taken as given: The CI is a 95% confidence interval for the difference in means.; The estimate is the difference in means.; The test is two-sided.Method: Compute p-value from estimate and 95% CI using normal approximation.How we recomputed it: pCI(-7.9, -11.0, -4.9, 0) - CONSISTENTreported p < .007 · recomputed p = .006Reviewers 1, 2Check p-value for SBP ETD in study 2 from CI
“−4.3 mmHg; 95% CI −7.3 to −1.2; P = 0.007”
Taken as given: The CI is a 95% confidence interval for the difference in means.; The estimate is the difference in means.; The test is two-sided.Method: Compute p-value from estimate and 95% CI using normal approximation.How we recomputed it: pCI(-4.3, -7.3, -1.2, 0) - CONSISTENTreported p < .005 · recomputed p = .004Reviewers 1, 2Check p-value for DBP ETD in study 1 from CI
“−3.2 mmHg; 95% CI −5.4 to −1.0; P = 0.005”
Taken as given: The CI is a 95% confidence interval for the difference in means.; The estimate is the difference in means.; The test is two-sided.Method: Compute p-value from estimate and 95% CI using normal approximation.How we recomputed it: pCI(-3.2, -5.4, -1.0, 0)
- lowinternal contradictionThe abstract states 'significant reduction of a number of cardiometabolic risk measures' but the results show some non-significant findings (e.g., DBP in study 2). This is not a contradiction but a nuance.
“demonstrated a significant reduction of a number of cardiometabolic risk measures”
AbstractFind in source
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
4 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, 2Treating both sleep-disordered breathing and obesity is likely required to optimize the treatment effect on cardiometabolic benefits.The mediation analysis shows independent effects of OSA metrics on some outcomes, but not on blood pressure, so the claim is partially supported.Evidence: Mediation analysis shows significant independent mediation by OSA metrics for hsCRP, HOMA-IR, and triglycerides, but not for SBP or DBP.
“Based on the mediation analysis, treating both sleep-disordered breathing and obesity is likely required to optimize the treatment effect on cardiometabolic benefits for patients with moderate-to-severe OSA and obesity.”
AbstractFind in source - supportedReviewers 1, 2Tirzepatide treatment was associated with greater alleviation of cardiometabolic risk factors than placebo.The presented results show significant ETDs for most cardiometabolic measures in both studies, supporting the claim.Evidence: Table 2 shows significant ETDs for SBP, hsCRP, HDL-C, non-HDL-C, triglycerides, VLDL-C, fasting insulin, and HOMA-IR in both studies, with some exceptions like DBP in study 2.
“tirzepatide treatment was associated with greater alleviation of cardiometabolic risk factors than placebo.”
AbstractFind in source - supportedReviewers 1, 2Independent mediation effect of changes in OSA metrics was observed on hsCRP, HOMA-IR and triglycerides.The mediation analysis results show significant mediation by AHI and SASHB for these outcomes, as stated in the Results.Evidence: Results section states that the tirzepatide-associated change in hsCRP, triglycerides, and HOMA-IR was significantly mediated by changes in OSA metrics AHI and SASHB.
“Independent mediation effect of changes in OSA metrics was observed on high-sensitivity C-reactive protein, homeostatic model assessment for insulin resistance and triglycerides.”
AbstractFind in source - supportedReviewers 1, 2The combination of changes in weight and OSA metrics, as well as weight alone, had a significant mediation effect on systolic blood pressure.The mediation analysis results show significant mediation by combined weight and OSA metrics and by weight alone for SBP.Evidence: Results section states that the tirzepatide effect on SBP was significantly mediated by combined effect of changes in body weight, AHI and SASHB, and by change in body weight alone.
“The combination of changes in weight and OSA metrics, as well as weight alone, had a significant mediation effect on systolic blood pressure”
AbstractFind 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 changes in cardiometabolic risk markers (e.g., hsCRP, lipids, HOMA-IR, blood pressure) which are surrogate biomarkers, not hard clinical outcomes. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD) nor cite validated evidence linking these surrogates to clinical outcomes in this context. The mediation analysis is exploratory and does not establish clinical benefit.
“The improvements in cardiometabolic risk measures were both statistically significant and clinically meaningful and, therefore, tirzepatide treatment may lead to improvement in overall cardiometabolic risk in patients with OSA and obesity.”
- INADEQUATEEffect sizeThe reported effect sizes are relative changes in biomarkers (e.g., hsCRP -28.9% to -45.1%, HOMA-IR -48.0% to -54.5%) without anchoring to established minimal clinically important differences or demonstrating restoration to normal levels. The paper claims clinical meaningfulness but does not provide a quantitative anchor to clinical benefit.
“The improvements in cardiometabolic risk measures were both statistically significant and clinically meaningful”
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 prior work on OSA and cardiovascular risk, the limitations of PAP therapy, and the rationale for tirzepatide. It explicitly states the hypothesis and the need to assess cardiometabolic outcomes beyond the primary AHI endpoint. The limitations of prior research are acknowledged, such as the lack of consistent cardiovascular benefits from PAP and the need to understand the relative contributions of weight loss and OSA improvement.
“we sought to test the hypothesis that tirzepatide treatment in the SURMOUNT-OSA studies would yield improvement in cardiometabolic risk measures as compared to placebo.”
“we sought to test the hypothesis that tirzepatide treatment in the SURMOUNT-OSA studies would yield improvement in cardiometabolic risk measures as compared to placebo.”
The paper describes randomization (1:1 ratio), blinding (double-blind), and a prespecified statistical analysis plan. Power analysis was not reported in this secondary analysis, but the primary studies were powered. Inclusion/exclusion criteria are referenced to prior publications. The analysis population and missing data handling (multiple imputation) are described.
“Participants were randomly assigned in a 1:1 ratio to receive either tirzepatide at the maximum tolerated dose (10 or 15 mg) or placebo once weekly.”
“randomized, double-blind, placebo-controlled phase 3 studies”
“the two studies’ full design, key eligibility criteria, procedures and primary efficacy and safety results have been published previously”
“Participants were randomly assigned in a 1:1 ratio to receive either tirzepatide at the maximum tolerated dose (10 or 15 mg) or placebo once weekly.”
“For efficacy analysis, missing values were imputed using multiple imputation based on the reason of intercurrent events.”
“the two studies’ full design, key eligibility criteria, procedures and primary efficacy and safety results have been published previously”
The paper reports sex (female percentages), age, BMI, and other clinical characteristics in Table 1. Both sexes are enrolled, so sex justification is not applicable. Age, weight (BMI), and health status (e.g., hypertension, prediabetes) are reported. Demographics are adequately described.
“Female, n (%) | 36 (31.6) | 41 (34.2) | 77 (32.9) | 33 (27.5) | 32 (27.8) | 65 (27.7)”
“Age, years | 47.3±11.0 | 48.4±11.9 | 47.9±11.5 | 50.8±10.7 | 52.7±11.3 | 51.7±11.0”
“Hypertension, n (%) | 84 (73.7) | 93 (77.5) | 177 (75.6) | 91 (75.8) | 91 (79.1) | 182 (77.4)”
“Female, n (%) | 36 (31.6) | 41 (34.2) | 77 (32.9) | 33 (27.5) | 32 (27.8) | 65 (27.7)”
“Age, years | 47.3±11.0 | 48.4±11.9 | 47.9±11.5 | 50.8±10.7 | 52.7±11.3 | 51.7±11.0”
The paper states that the study was approved by ethics review boards at each site, and informed consent was obtained. It also mentions compliance with the Declaration of Helsinki and ICH GCP guidelines. The approval statement is adequate, though specific protocol numbers are not provided in this secondary analysis.
“The study was approved by ethics review boards at each site, presented in .”
“Participants or their legally authorized representatives signed a statement of informed consent that meets the requirements of 21 Code of Federal Regulations 50, local regulations, ICH guidelines, privacy and data protection requirements, where applicable, and the IRB/IEC or study center.”
“This study was conducted in accordance with consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethics Guidelines, applicable ICH GCP Guidelines, International Organization for Standardization (ISO) 14155 and applicable laws and regulations.”
“The study was approved by ethics review boards at each site, presented in .”
“Participants or their legally authorized representatives signed a statement of informed consent that meets the requirements of 21 Code of Federal Regulations 50, local regulations, ICH guidelines, privacy and data protection requirements, where applicable, and the IRB/IEC or study center.”
“This study was conducted in accordance with consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethics Guidelines, applicable ICH GCP Guidelines, International Organization for Standardization (ISO) 14155 and applicable laws and regulations.”
Tirzepatide is identified as a GIP/GLP-1 receptor agonist, with dose (10 or 15 mg) and regimen (once weekly) described. The manufacturer (Eli Lilly) is implied. Statistical software (SAS 9.3, R 4.1.2) is identified. No other biological/chemical resources are used.
“tirzepatide at the maximum tolerated dose (10 or 15 mg)”
“Statistical analyses were performed using SAS version 9.3.”
“The mediation analyses were performed using the ‘CMAverse’ package version 0.1.0 in R version 4.1.2”
“tirzepatide at the maximum tolerated dose (10 or 15 mg) or placebo once weekly”
“Statistical analyses were performed using SAS version 9.3.”
The paper names the statistical tests (mixed model repeated measures, mediation analysis with bootstrap), reports effect sizes with 95% CIs, and identifies software. P-values are reported as thresholds (e.g., P < 0.001) rather than exact values, which is common in clinical trials. Data presentation includes tables with per-group n and dispersion.
“The mixed model repeated measures analysis, a restricted-maximum-likelihood-based model, was used to analyze continuous longitudinal variables.”
“−7.9 mmHg; 95% confidence interval (CI) −11.0 to −4.9; P < 0.001”
“The mixed model repeated measures analysis, a restricted-maximum-likelihood-based model, was used to analyze continuous longitudinal variables.”
“There was a significant estimated treatment difference (ETD) between tirzepatide and placebo for change in SBP from baseline at week 48 both in study 1 (−7.9 mmHg; 95% confidence interval (CI) −11.0 to −4.9; P < 0.001)”
“The mediation analyses were performed using the ‘CMAverse’ package version 0.1.0 in R version 4.1.2”
The data availability statement provides a concrete route: data are available through Vivli after proposal approval and data sharing agreement. This is adequate for individual patient data. No code was used, so code sharing is not applicable.
“Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement.”
“No novel code was used for data analysis in the current study.”
“Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the USA and European Union and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement.”
“No novel code was used for data analysis in the current study.”
The trial is registered (NCT05412004). Funding and competing interests are disclosed. Limitations are discussed in the Discussion. Conclusions are proportional to the evidence. A reporting summary is mentioned.
“The ClinicalTrials.gov (http://ClinicalTrials.gov) registration number for this study is NCT05412004”
“First, the studies did not have sufficient duration of follow-up or statistical power to examine the impact of tirzepatide on cardiometabolic outcomes such as myocardial infarction or stroke.”
“This study was funded by Eli Lilly and Company.”
“The ClinicalTrials.gov (http://ClinicalTrials.gov) registration number for this study is NCT05412004”
“This study was funded by Eli Lilly and Company.”
“First, the studies did not have sufficient duration of follow-up or statistical power to examine the impact of tirzepatide on cardiometabolic outcomes such as myocardial infarction or stroke.”
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 42 references by DOI: 40 verified — 2 no DOI (shown, not verified).
- NO DOIPractice parameters for the medical therapy of obstructive sleep apneaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEffect of CPAP therapy on serum lipids and blood pressure in patients with obstructive sleep apnea syndromeNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
2 data/code links checked; 2 live.
- datahttps://doi.org/10.1038/s41591-025-04071-1LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttp://www.vivli.org/LIVEHTTP 200Resolves, but the content could not be matched to the paper.
Copyediting
5 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 5 minor suggestions below.
5 copyedit issues flagged: mostly consistency, clarity.
- MINORconsistencyAbstract“The ClinicalTrials.gov (http://ClinicalTrials.gov) registration number for this study is NCT05412004 (https://clinicaltrials.gov/ct2/show/NCT05412004) .”→ Remove extra space before period.Minor formatting issue.
- MINORclarityMethods, Statistical analysis“The mediation analyses were performed using the ‘CMAverse’ package version 0.1.0 in R version 4.1.2 ().”→ Add a citation or reference for the CMAverse package.Missing reference.
- MINORconsistencyTable 1“OSA severity, n (%) | No apnea | 0 (0.0) | 1 (0.8) | 1 (0.4) | – | – | –”→ Use '0' instead of '–' for consistency.Minor formatting inconsistency.
- MINORclarityMethods, Statistical analysis“The mediation analyses were performed using the ‘CMAverse’ package version 0.1.0 in R version 4.1.2 ().”→ Add citation for CMAverse package.Missing citation.
- MINORconsistencyTable 1 footnote“n , number of randomized patients with at least one dose of study drug;”→ Clarify that n is the number randomized, not treated.Potential ambiguity.
The published work is robust and well-reported. An informed reader should weigh the minor reporting gaps (threshold p-values, lack of randomization method detail) and the fact that the secondary analyses were exploratory and not powered for cardiometabolic outcomes. No erratum or correction appears warranted based on the integrity checks; the copyedit issues are cosmetic.
- 1.CRITICALstatisticsCorrect or explain the statistically impossible value: PERCENT: 70.6% does not match the reported count 84/120Demonstrable critical failure — blocks the verdict from passing.
- 2.CRITICALstatisticsCorrect or explain the statistically impossible value: PERCENT: 65.8% does not match the reported count 75/115Demonstrable critical failure — blocks the verdict from passing.
- 3.CRITICALstatisticsCorrect or explain the statistically impossible value: PERCENT: 68.2% does not match the reported count 159/235Demonstrable critical failure — blocks the verdict from passing.
- 4.MEDIUMstatisticsIn the Results and Tables, replace threshold p-values (e.g., 'P < 0.001') with exact p-values where available to improve statistical transparency.Exact p-values allow readers to assess the strength of evidence more precisely and are a common reviewer request.
- 5.MEDIUMreportingIn the Methods, add a statement clarifying that the secondary analyses were exploratory and not powered for these endpoints, and reference the primary trial's power analysis.This prevents misinterpretation of non-significant secondary outcomes and clarifies the study's inferential scope.
- 6.MEDIUMreportingIn the Methods, provide more detail on the randomization method (e.g., random number generator, block size) or explicitly state that it is described in the primary publications.Adequate description of randomization is a key element of trial reporting and supports reproducibility.
- 7.MEDIUMreportingIn the Methods, describe the handling of outliers or extreme values, or state that no outliers were excluded.Transparency about outlier handling is important for the validity of the statistical analysis.
- 8.MEDIUMreportingIn the Discussion, explicitly mention the limitations of the mediation analysis, such as the assumption of no unmeasured confounding.Mediation analyses rely on strong assumptions that should be acknowledged to avoid overinterpretation.
- 9.MEDIUMdata codeConsider depositing the analysis code (even if standard) in a public repository to facilitate replication, or clarify why it is not shared.Sharing code enhances reproducibility and is increasingly expected by journals and readers.
- 10.MEDIUMreportingAdd a CONSORT-style flow diagram for the pooled analysis population to clarify participant disposition.A flow diagram improves transparency about participant flow and missing data.
- 11.LOWcopyeditIn the Abstract, remove the extra space before the period in the ClinicalTrials.gov registration sentence.Minor formatting issue that should be corrected for professional presentation.
- 12.LOWcopyeditIn the Methods, add a citation for the CMAverse package used in the mediation analyses.Citing software packages is good practice and aids reproducibility.
- 13.LOWcopyeditIn Table 1, use '0' instead of '–' for the 'No apnea' row in study 2 columns for consistency.Consistent formatting improves readability and avoids ambiguity.
- 14.LOWcopyeditIn the Table 1 footnote, clarify that 'n' is the number of randomized patients who received at least one dose, not just randomized.Clarifying the definition of 'n' prevents misinterpretation of the analysis population.
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.