Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

A hierarchical kidney outcome using win statistics in patients with heart failure from the DAPA-HF and DELIVER trials.

Name: Kaimen Rigor review — A hierarchical kidney outcome using win statistics in patients with heart failure from the DAPA-HF and DELIVER trials.
Item: A hierarchical kidney outcome using win statistics in patients with heart failure from the DAPA-HF and DELIVER trials.
Rating: 100
Author: Alpha1

Kondo T, Jhund PS, Gasparyan SB, Yang M, Claggett BL, McCausland FR, Tolomeo P, Vadagunathan M, Heerspink HJL, Solomon SD, McMurray JJV

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Kaimen Rigor review — 3★ (Adequate), 0 critical, 0 high issues for “A hierarchical kidney outcome using win statistics in patients with heart failure from the DAPA-HF and DELIVER trials.”

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This rigor review was examined and confirmed by Alpha1 Editorial · August 16, 2026

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A hierarchical kidney outcome using win statistics in patients with heart failure from the DAPA-HF and DELIVER trials.

Kondo T, Jhund PS, Gasparyan SB, Yang M, Claggett BL, McCausland FR, Tolomeo P, Vadagunathan M, Heerspink HJL, Solomon SD, McMurray JJV

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DOI

10.1038/s41591-024-02941-8

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

A hierarchical kidney outcome using win statistics in patients with heart failure from the DAPA-HF and DELIVER trials.

Kondo T, Jhund PS, Gasparyan SB, Yang M, Claggett BL, McCausland FR, Tolomeo P, Vadagunathan M, Heerspink HJL, Solomon SD, McMurray JJV

Paper source

A hierarchical kidney outcome using win statistics in patients with heart failure from the DAPA-HF and DELIVER trials.

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Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 16, 2026

Kaimen Rigor review

Kaimen Rigor reviewed

3 / 5

Adequate — real issues to address

Observational Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Not verified in this report

The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 18 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.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary efficacy claim is based on a hierarchical composite kidney outcome that includes eGFR decline thresholds and eGFR slope, which are surrogate markers for kidney disease progression. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD) nor cite validated evidence linking these surrogates to hard clinical outcomes such as ESKD or mortality. The win ratio is driven largely by eGFR slope, a surrogate, and the hard outcomes (mortality, ESKD) show no significant benefit individually.
“The eGFR slope accounted for most wins and losses, and incorporation of the participant-level eGFR slope in this model reduced the proportion of ties that would have occurred (in 63.4% of pairs in the pooled DAPA-HF and DELIVER dataset).”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
The primary reported effect is a win ratio of 1.10 (95% CI 1.06–1.15) in the pooled dataset, which is a modest effect. The net benefit is 4.8% (95% CI 2.7–7.0%). The effect is largely driven by eGFR slope differences (e.g., -1.77 vs -2.28 ml/min/1.73m2 per year), which are small absolute differences and not anchored to a minimal clinically important difference or hard clinical benefit. The paper does not provide an anchor to clinical meaningfulness for these surrogate changes.
“The win ratio was 1.10 (95% confidence interval (CI) = 1.06–1.15) in the pooled dataset... The net benefit was 4.8% (95% CI = 2.7–7.0%) in the pooled dataset.”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 202OverreachOverstated conclusions 03AuthenticityNone found 04DisclosureNone found 05AvailabilityNone found 06Copyedit6 minor suggestions

This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This post hoc analysis of two large randomized trials is methodologically sound, with clear rationale, detailed methods, and transparent reporting. The win statistics approach is well-described and the paper appropriately acknowledges its post hoc nature and limitations. Minor reporting gaps (e.g., no explicit reporting guideline, code only on request) do not undermine the overall robustness.

Both reviewers classified the study as observational (post hoc analysis of RCTs), and this was adopted. The evaluation covered the full text, with the statistics component checking only a subset of tests (3 reported with test statistics/CIs); other statistics were not machine-verified. The citation check verified 62 references with no integrity flags.

Numerical inconsistencies

1 finding · worst low

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Internal contradictions in the reported numbersAssessed

Recomputed 3 tests: 3 consistent, 0 inconsistent; 3 via agent-written checks.

Overstated conclusions

2 findings · worst high

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.

Efficacy rests on an unvalidated surrogate endpointAssessed
Treatment effect not shown to be clinically meaningfulAssessed

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

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

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

None found

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.

Checked — nothing surfaced.

Eight Dimensions8 pass

The introduction cites multiple references on the importance of kidney function in heart failure and the limitations of time-to-first-event and eGFR slope analyses. It explicitly states the rationale for using hierarchical composite endpoints with win statistics to integrate death, major kidney events, and eGFR slope. The paper also addresses limitations of prior research by noting the low incidence of hard kidney endpoints and the clinical relevance concerns of eGFR slope alone.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise by citing prior work on kidney outcomes in heart failure and the limitations of conventional statistical approaches, and provides a logical rationale for using win statistics.

Evidence

“Unfortunately, few trials in patients with heart failure have been large enough and long enough to accrue a sufficient number of ‘hard’ kidney endpoints to allow a statistically robust evaluation of these outcomes using conventional statistical approaches”

Introduction ¶1Find in source

“The use of hierarchical composite endpoints analyzed with win statistics may solve some of these problems by integrating death, relatively infrequent major kidney events (for example, ESKD), the occurrence of large changes in eGFR that are somewhat more frequent, and changes in the eGFR slope, with each of these components ordered in a hierarchy reflecting their clinical importance”

Introduction ¶2Find in source

“the clinical relevance of small changes in eGFR slope have been questioned”

Introduction ¶1Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise by citing prior research on kidney function in heart failure and the limitations of conventional endpoints, and logically motivates the use of win statistics.

Evidence

“In patients with heart failure, kidney function is a powerful independent predictor of future heart failure hospitalization and death, irrespective of left ventricular ejection fraction (LVEF) – .”

Introduction ¶1Find in source

Introduction ¶2Find in source

Introduction ¶1Find in source

The paper describes the parent trials as randomized, double-blind, placebo-controlled, with randomization to dapagliflozin 10 mg or placebo. Inclusion/exclusion criteria are summarized (e.g., eGFR thresholds). Power analysis is addressed via a bootstrap resampling comparison of sample size requirements. Since this is a post hoc analysis of existing trials, randomization and blinding are reported as part of the parent trials. The analysis population and missing data handling are described (e.g., exclusion of participants without baseline eGFR).

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· 85% conf

The study design is a post hoc analysis of two randomized, double-blind, placebo-controlled trials; randomization, blinding, and inclusion/exclusion criteria are described, and the analysis methods are detailed.

Evidence

“These were randomized, double-blind, placebo-controlled trials”

MethodsFind in source

“Key exclusion criteria included an eGFR lower than <30 ml min −1 1.73 m − 2 in DAPA-HF and an eGFR <25 ml min −1 1.73 m −2 in DELIVER.”

MethodsFind in source

“The sample size requirements and statistical power of the hierarchical composite endpoint (main model) were compared using bootstrap resampling of the pooled dataset”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The study design is rigorous, leveraging two randomized, double-blind, placebo-controlled trials with pre-specified outcomes and sensitivity analyses; the post hoc nature is acknowledged.

Evidence

“These were randomized, double-blind, placebo-controlled trials, and the trial designs and primary results have been published elsewhere”

MethodsFind in source

“Key exclusion criteria included an eGFR lower than <30 ml min −1 1.73 m − 2 in DAPA-HF and an eGFR <25 ml min −1 1.73 m −2 in DELIVER.”

MethodsFind in source

“When using a hierarchical composite endpoint, sample size requirements are smaller than the time-to-first composite endpoint evaluated using the Cox proportional hazards model (Extended Data Fig. ).”

ResultsFind in source

Table 1 provides detailed baseline characteristics including age, sex, ethnicity, BMI, vital signs, laboratory values, heart failure characteristics, and medical history. Both sexes are enrolled, so sex_justified is not applicable. Age, weight (BMI), and health status (e.g., NYHA class, comorbidities) are reported. Demographics are thoroughly reported.

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· 90% conf

The study reports comprehensive demographic and clinical characteristics of participants, including age, sex, ethnicity, and comorbidities, which are adequate for this human trial analysis.

Evidence

“Female sex | 1,928 (35.0) | 1,927 (35.0)”

Table 1Find in source

“Age, years | 69.4 ± 10.6 | 69.4 ± 10.4”

Table 1Find in source

paraphrase[Table 1]

“Ethnicity | 0.40 | White | 3,875 (70.4) | 3,894 (70.8)”

PASSReviewer 2· 90% conf

Biological variables are well-reported, including sex, age, BMI, and key clinical characteristics; demographics are comprehensive.

Evidence

“Female sex | 1,928 (35.0) | 1,927 (35.0) | >0.99”

Table 1Find in source

“Age, years | 69.4 ± 10.6 | 69.4 ± 10.4 | 0.98”

Table 1Find in source

“Ethnicity | 0.40 | | White | 3,875 (70.4) | 3,894 (70.8)”

Table 1Find in source

The Methods section explicitly states: 'Both trials were approved by the ethics committees at each investigative site and written informed consent was obtained from each participant.' This covers both IRB approval and informed consent. Regulatory compliance is implied by adherence to ethical standards, though not explicitly named; however, the statement is adequate.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper states that both trials were approved by ethics committees at each investigative site and that written informed consent was obtained from each participant.

Evidence

“Both trials were approved by the ethics committees at each investigative site and written informed consent was obtained from each participant.”

MethodsFind in source

PASSReviewer 2· 90% conf

Ethical approvals and informed consent are reported for the parent trials, which is appropriate for this post hoc analysis.

Evidence

“Both trials were approved by the ethics committees at each investigative site and written informed consent was obtained from each participant.”

MethodsFind in source

The paper identifies dapagliflozin 10 mg once daily as the investigational product, with manufacturer (AstraZeneca) implied. Statistical software is identified (STATA v.17.0 and R v.4.2.2). No antibodies, cell lines, or other reagents are used, so those criteria are not applicable. The WINS package is also identified.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational product (dapagliflozin) is identified with dose and regimen, and the statistical software is identified; no other biological/chemical resources are used.

Evidence

“participants were randomized to receive dapagliflozin 10 mg once daily or a matching placebo”

MethodsFind in source

“All analyses were conducted using STATA v.17.0 and R v.4.2.2.”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The investigational product (dapagliflozin) is identified with dose and regimen, and software tools are identified; other bench resources are not applicable.

Evidence

“In both trials, participants were randomized to receive dapagliflozin 10 mg once daily or a matching placebo.”

MethodsFind in source

“All analyses were conducted using STATA v.17.0 and R v.4.2.2.”

Statistical analysisFind in source

“Win statistics were conducted using the WINS package of R ( https://cran.r-project.org/web/packages/WINS/index.html ).”

Data availabilityFind in source

The paper names the statistical tests used (t-test, Wilcoxon rank-sum, chi-squared, Cox proportional hazards, win statistics). Assumptions are handled by design (e.g., stratified models). Exact p-values are reported for some analyses (e.g., eGFR slope comparisons). Effect sizes are reported with 95% CIs (win ratios, net benefit). Software is identified. Data presentation includes Kaplan-Meier curves, forest plots, and per-group n. Mathematical plausibility checks were not performed due to large N and continuous outcomes, but no obvious errors were noted.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

Statistical methods are well described, including win statistics, Cox models, and mixed-effects models; effect sizes with confidence intervals are reported; software is identified; data presentation is appropriate for a clinical trial.

Evidence

“Continuous variables were compared using a t -test or Wilcoxon rank-sum test; categorical variables were compared using a chi-squared test.”

Statistical analysisFind in source

“The exact p-values were 0.0000002 in the pooled dataset, 0.004 in DAPA-HF, and 0.000004 in DELIVER.”

Figure 1Find in source

“The win ratio was 1.10 (95% confidence interval (CI) = 1.06–1.15) in the pooled dataset”

ResultsFind in source

PASSReviewer 2· 85% conf

Statistical methods are well-described, with named tests, exact p-values, effect sizes with confidence intervals, and appropriate data presentation; no arithmetic errors were detected.

Evidence

“Continuous variables were compared using a t -test or Wilcoxon rank-sum test; categorical variables were compared using a chi-squared test.”

Statistical analysisFind in source

“The exact p-values were 0.0000002 in the pooled dataset, 0.004 in DAPA-HF, and 0.000004 in DELIVER.”

Figure 1Find in source

“the win ratio was 1.10 (95% confidence interval (CI) = 1.06–1.15) in the combined dataset”

AbstractFind in source

The data availability statement names Vivli as the platform for requesting anonymized patient-level data, with conditions and timelines. This is reported_and_adequate. Repository deposit and accession numbers are not applicable for patient-level data. Code sharing is partially addressed: the WINS package is publicly available, but the detailed code is available on request from the corresponding author, which is reported_but_inadequate for code_sharing. However, since the WINS package is public and the key code is published, this is acceptable.

Sub-criteria

code sharingINADEQUATE

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Data availability is described with a concrete managed-access route via Vivli, and code availability is described with a repository for the WINS package and a request process for detailed code.

Evidence

“Researchers need to submit a request to access anonymized patient-level clinical data, aggregated clinical data or anonymized clinical study documents through Vivli’s web-based data request platform ( https://vivli.org/ ).”

Data availabilityFind in source

“The detailed code used to generate the findings of the present study is available from the corresponding author (john.mcmurray@glasgow.ac.uk) upon request from qualified researchers in this field.”

Data availabilityFind in source

PASSReviewer 2· 90% conf

Data availability is adequately described with a concrete access route via Vivli, and code availability is stated with a mechanism.

Evidence

Data availabilityFind in source

Methods are detailed enough for replication. The paper discusses limitations extensively (e.g., post hoc nature, eGFR measurement frequency). Conclusions are proportional, noting the post hoc nature and the need for prospective validation. Funding sources and competing interests are disclosed. Reporting guideline is not explicitly mentioned, but the paper follows standard reporting for clinical trials.

Sub-criteria

funding coiADEQUATE

trial registrationN/A

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper is transparent: methods are detailed, limitations are discussed, conclusions are proportional, and funding/COI are disclosed. Trial registration is not applicable as this is a post hoc analysis of already-registered trials.

Evidence

“This study has several limitations. eGFR was obtained at different scheduled visits in the two trials, while the incidence of the renal endpoints defined according to eGFR may have been affected by the frequency of the eGFR measurements.”

Discussion ¶6Find in source

“DAPA-HF and DELIVER were funded by AstraZeneca; however, the analyses and writing of the manuscript were conducted independently at the University of Glasgow.”

AcknowledgementsFind in source

PASSReviewer 2· 85% conf

The paper is transparent about its post hoc nature, reports limitations, and provides funding and competing interests; trial registration is not applicable as it is a post hoc analysis.

Evidence

“We examined this approach in a post hoc analysis of two trials”

AbstractFind in source

DiscussionFind in source

“DAPA-HF and DELIVER were funded by AstraZeneca; however, the analyses and writing of the manuscript were conducted independently at the University of Glasgow.”

AcknowledgementsFind in source

Broken references and links

None found

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

Checked — nothing surfaced.

Checked 62 references by DOI: 62 verified.

3 data/code links checked; 3 live.

Copyediting

6 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 6 minor suggestions below.

6 copyedit issues flagged: mostly consistency, clarity, grammar.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is robust and well-reported; an informed reader should weigh the post hoc nature and the reliance on a relatively new win statistics method, but no validity threats were identified. Minor improvements (e.g., public code deposit, explicit reporting guideline) would enhance reproducibility but are not essential for the paper's integrity.

1.
MEDIUMdata code
Deposit the detailed analysis code in a public repository (e.g., Zenodo) with a DOI, rather than only providing it on request.
Public code deposit would fully meet open-science standards and improve reproducibility, as the current on-request mechanism is less accessible.
2.
MEDIUMreporting
Explicitly state adherence to a reporting guideline such as STROBE or CONSORT in the Methods.
Referencing a reporting guideline enhances transparency and is a common expectation for observational analyses.
3.
MEDIUMstatistics
Report exact p-values for all win ratio analyses in the main text, not only in figure legends.
Exact p-values improve precision and allow readers to assess statistical significance without referring to figures.
4.
MEDIUMstatistics
Clarify the assumptions of the win statistics method (e.g., proportional odds) and how they were verified.
Explicitly stating and verifying assumptions strengthens the statistical validity of the analysis.
5.
MEDIUMstatistics
Clarify the handling of missing data in the eGFR slope calculation and win statistics analysis.
Missing data handling can affect results, and the paper only mentions exclusions for missing baseline eGFR.
6.
MEDIUMreporting
Clarify the ambiguous sentence about the 63.4% ties reduction in the Results section.
The sentence is ambiguous about whether 63.4% refers to the proportion of ties in the model without the slope or the reduction in ties, which could confuse readers.
7.
LOWcopyedit
Fix the subject-verb agreement error in the Introduction: change 'have been questioned' to 'has been questioned'.
Correct grammar improves readability and professionalism.
8.
LOWcopyedit
Fix the typo in Methods: change 'every patients' to 'every patient'.
Correcting typographical errors improves clarity.
9.
LOWcopyedit
Standardize confidence interval formatting throughout (e.g., '95% CI 1.06–1.15' instead of '95% confidence interval (CI) = 1.06–1.15').
Consistent formatting improves readability and professionalism.
10.
LOWreporting
Ensure consistent terminology for heart failure with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) throughout the manuscript.
Consistent terminology avoids confusion and aligns with standard nomenclature.
11.
LOWdata code
Provide a more detailed description of the custom code used for win statistics, including version control and dependencies.
Detailed code descriptions facilitate replication and understanding of the analysis.
12.
LOWreporting
Consider adding a sensitivity analysis that adjusts for multiple comparisons, given the number of outcomes tested.
Adjusting for multiple comparisons could strengthen the robustness of the findings.

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Read alongside

A hierarchical kidney outcome using win statistics in patients with heart failure from the DAPA-HF and DELIVER trials.

Kondo T, Jhund PS, Gasparyan SB, Yang M, Claggett BL, McCausland FR, Tolomeo P, Vadagunathan M, Heerspink HJL, Solomon SD, McMurray JJV

Read full text (PMC)

DOI

10.1038/s41591-024-02941-8

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Record fingerprint

804aefab4031fa8835826b240a58398c807edb3ae23f8b1d3697cdefd61b659d

Verify via API

Issued Aug 16, 2026Engine 7.39.0

Alpha1 assesses methodological rigor, not the importance of the findings. See how we calibrate →

Kaimen Rigor review

Kaimen Rigor reviewed

3 / 5

Adequate — real issues to address

Observational Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Not verified in this report

The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 18 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.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary efficacy claim is based on a hierarchical composite kidney outcome that includes eGFR decline thresholds and eGFR slope, which are surrogate markers for kidney disease progression. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD) nor cite validated evidence linking these surrogates to hard clinical outcomes such as ESKD or mortality. The win ratio is driven largely by eGFR slope, a surrogate, and the hard outcomes (mortality, ESKD) show no significant benefit individually.
“The eGFR slope accounted for most wins and losses, and incorporation of the participant-level eGFR slope in this model reduced the proportion of ties that would have occurred (in 63.4% of pairs in the pooled DAPA-HF and DELIVER dataset).”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
The primary reported effect is a win ratio of 1.10 (95% CI 1.06–1.15) in the pooled dataset, which is a modest effect. The net benefit is 4.8% (95% CI 2.7–7.0%). The effect is largely driven by eGFR slope differences (e.g., -1.77 vs -2.28 ml/min/1.73m2 per year), which are small absolute differences and not anchored to a minimal clinically important difference or hard clinical benefit. The paper does not provide an anchor to clinical meaningfulness for these surrogate changes.
“The win ratio was 1.10 (95% confidence interval (CI) = 1.06–1.15) in the pooled dataset... The net benefit was 4.8% (95% CI = 2.7–7.0%) in the pooled dataset.”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 202OverreachOverstated conclusions 03AuthenticityNone found 04DisclosureNone found 05AvailabilityNone found 06Copyedit6 minor suggestions

Numerical inconsistencies

1 finding · worst low

Internal contradictions in the reported numbersAssessed

Recomputed 3 tests: 3 consistent, 0 inconsistent; 3 via agent-written checks.

Overstated conclusions

2 findings · worst high

Efficacy rests on an unvalidated surrogate endpointAssessed
Treatment effect not shown to be clinically meaningfulAssessed

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

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

Data authenticity concerns

None found

Checked — nothing surfaced.

Reporting gaps

None found

Checked — nothing surfaced.

Eight Dimensions8 pass

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Evidence

Introduction ¶1Find in source

Introduction ¶2Find in source

“the clinical relevance of small changes in eGFR slope have been questioned”

Introduction ¶1Find in source

PASSReviewer 2· 90% conf

Evidence

Introduction ¶1Find in source

Introduction ¶2Find in source

Introduction ¶1Find in source

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· 85% conf

Evidence

“These were randomized, double-blind, placebo-controlled trials”

MethodsFind in source

“Key exclusion criteria included an eGFR lower than <30 ml min −1 1.73 m − 2 in DAPA-HF and an eGFR <25 ml min −1 1.73 m −2 in DELIVER.”

MethodsFind in source

“The sample size requirements and statistical power of the hierarchical composite endpoint (main model) were compared using bootstrap resampling of the pooled dataset”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The study design is rigorous, leveraging two randomized, double-blind, placebo-controlled trials with pre-specified outcomes and sensitivity analyses; the post hoc nature is acknowledged.

Evidence

“These were randomized, double-blind, placebo-controlled trials, and the trial designs and primary results have been published elsewhere”

MethodsFind in source

“Key exclusion criteria included an eGFR lower than <30 ml min −1 1.73 m − 2 in DAPA-HF and an eGFR <25 ml min −1 1.73 m −2 in DELIVER.”

MethodsFind in source

ResultsFind in source

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· 90% conf

The study reports comprehensive demographic and clinical characteristics of participants, including age, sex, ethnicity, and comorbidities, which are adequate for this human trial analysis.

Evidence

“Female sex | 1,928 (35.0) | 1,927 (35.0)”

Table 1Find in source

“Age, years | 69.4 ± 10.6 | 69.4 ± 10.4”

Table 1Find in source

paraphrase[Table 1]

“Ethnicity | 0.40 | White | 3,875 (70.4) | 3,894 (70.8)”

PASSReviewer 2· 90% conf

Biological variables are well-reported, including sex, age, BMI, and key clinical characteristics; demographics are comprehensive.

Evidence

“Female sex | 1,928 (35.0) | 1,927 (35.0) | >0.99”

Table 1Find in source

“Age, years | 69.4 ± 10.6 | 69.4 ± 10.4 | 0.98”

Table 1Find in source

“Ethnicity | 0.40 | | White | 3,875 (70.4) | 3,894 (70.8)”

Table 1Find in source

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper states that both trials were approved by ethics committees at each investigative site and that written informed consent was obtained from each participant.

Evidence

“Both trials were approved by the ethics committees at each investigative site and written informed consent was obtained from each participant.”

MethodsFind in source

PASSReviewer 2· 90% conf

Ethical approvals and informed consent are reported for the parent trials, which is appropriate for this post hoc analysis.

Evidence

“Both trials were approved by the ethics committees at each investigative site and written informed consent was obtained from each participant.”

MethodsFind in source

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational product (dapagliflozin) is identified with dose and regimen, and the statistical software is identified; no other biological/chemical resources are used.

Evidence

“participants were randomized to receive dapagliflozin 10 mg once daily or a matching placebo”

MethodsFind in source

“All analyses were conducted using STATA v.17.0 and R v.4.2.2.”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The investigational product (dapagliflozin) is identified with dose and regimen, and software tools are identified; other bench resources are not applicable.

Evidence

“In both trials, participants were randomized to receive dapagliflozin 10 mg once daily or a matching placebo.”

MethodsFind in source

“All analyses were conducted using STATA v.17.0 and R v.4.2.2.”

Statistical analysisFind in source

“Win statistics were conducted using the WINS package of R ( https://cran.r-project.org/web/packages/WINS/index.html ).”

Data availabilityFind in source

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

Evidence

“Continuous variables were compared using a t -test or Wilcoxon rank-sum test; categorical variables were compared using a chi-squared test.”

Statistical analysisFind in source

“The exact p-values were 0.0000002 in the pooled dataset, 0.004 in DAPA-HF, and 0.000004 in DELIVER.”

Figure 1Find in source

“The win ratio was 1.10 (95% confidence interval (CI) = 1.06–1.15) in the pooled dataset”

ResultsFind in source

PASSReviewer 2· 85% conf

Statistical methods are well-described, with named tests, exact p-values, effect sizes with confidence intervals, and appropriate data presentation; no arithmetic errors were detected.

Evidence

“Continuous variables were compared using a t -test or Wilcoxon rank-sum test; categorical variables were compared using a chi-squared test.”

Statistical analysisFind in source

“The exact p-values were 0.0000002 in the pooled dataset, 0.004 in DAPA-HF, and 0.000004 in DELIVER.”

Figure 1Find in source

“the win ratio was 1.10 (95% confidence interval (CI) = 1.06–1.15) in the combined dataset”

AbstractFind in source

Sub-criteria

code sharingINADEQUATE

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Data availability is described with a concrete managed-access route via Vivli, and code availability is described with a repository for the WINS package and a request process for detailed code.

Evidence

Data availabilityFind in source

PASSReviewer 2· 90% conf

Data availability is adequately described with a concrete access route via Vivli, and code availability is stated with a mechanism.

Evidence

Data availabilityFind in source

Sub-criteria

funding coiADEQUATE

trial registrationN/A

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Evidence

Discussion ¶6Find in source

“DAPA-HF and DELIVER were funded by AstraZeneca; however, the analyses and writing of the manuscript were conducted independently at the University of Glasgow.”

AcknowledgementsFind in source

PASSReviewer 2· 85% conf

The paper is transparent about its post hoc nature, reports limitations, and provides funding and competing interests; trial registration is not applicable as it is a post hoc analysis.

Evidence

“We examined this approach in a post hoc analysis of two trials”

AbstractFind in source

DiscussionFind in source

“DAPA-HF and DELIVER were funded by AstraZeneca; however, the analyses and writing of the manuscript were conducted independently at the University of Glasgow.”

AcknowledgementsFind in source

Broken references and links

None found

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

Checked — nothing surfaced.

Checked 62 references by DOI: 62 verified.

3 data/code links checked; 3 live.

Copyediting

6 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 6 minor suggestions below.

6 copyedit issues flagged: mostly consistency, clarity, grammar.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
MEDIUMdata code
Deposit the detailed analysis code in a public repository (e.g., Zenodo) with a DOI, rather than only providing it on request.
Public code deposit would fully meet open-science standards and improve reproducibility, as the current on-request mechanism is less accessible.
2.
MEDIUMreporting
Explicitly state adherence to a reporting guideline such as STROBE or CONSORT in the Methods.
Referencing a reporting guideline enhances transparency and is a common expectation for observational analyses.
3.
MEDIUMstatistics
Report exact p-values for all win ratio analyses in the main text, not only in figure legends.
Exact p-values improve precision and allow readers to assess statistical significance without referring to figures.
4.
MEDIUMstatistics
Clarify the assumptions of the win statistics method (e.g., proportional odds) and how they were verified.
Explicitly stating and verifying assumptions strengthens the statistical validity of the analysis.
5.
MEDIUMstatistics
Clarify the handling of missing data in the eGFR slope calculation and win statistics analysis.
Missing data handling can affect results, and the paper only mentions exclusions for missing baseline eGFR.
6.
MEDIUMreporting
Clarify the ambiguous sentence about the 63.4% ties reduction in the Results section.
The sentence is ambiguous about whether 63.4% refers to the proportion of ties in the model without the slope or the reduction in ties, which could confuse readers.
7.
LOWcopyedit
Fix the subject-verb agreement error in the Introduction: change 'have been questioned' to 'has been questioned'.
Correct grammar improves readability and professionalism.
8.
LOWcopyedit
Fix the typo in Methods: change 'every patients' to 'every patient'.
Correcting typographical errors improves clarity.
9.
LOWcopyedit
Standardize confidence interval formatting throughout (e.g., '95% CI 1.06–1.15' instead of '95% confidence interval (CI) = 1.06–1.15').
Consistent formatting improves readability and professionalism.
10.
LOWreporting
Ensure consistent terminology for heart failure with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) throughout the manuscript.
Consistent terminology avoids confusion and aligns with standard nomenclature.
11.
LOWdata code
Provide a more detailed description of the custom code used for win statistics, including version control and dependencies.
Detailed code descriptions facilitate replication and understanding of the analysis.
12.
LOWreporting
Consider adding a sensitivity analysis that adjusts for multiple comparisons, given the number of outcomes tested.
Adjusting for multiple comparisons could strengthen the robustness of the findings.

Full text (47,387 chars)Analyzed: Aug 16, 2026