Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial.

Name: Kaimen Rigor review — Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial.
Item: Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial.
Rating: 59
Author: Alpha1

Mahalingam D, Shroff RT, Carneiro BA, Ji Y, Coveler AL, Cervantes A, Sahai V, Ploquin A, Hiret S, LoConte NK, Percent IJ, Lopez CD, Pernot S, Kavan P, Mulcahy M, Carr R, Giles FJ, Seifarth C, Ugolkov A, Weiskittel T, Fine G, Jaros M, Mazar AP, Bekaii-Saab TS

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Kaimen Rigor review — 3★ (Adequate), 0 critical, 4 high issues for “Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial.”

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This rigor review was examined and confirmed by Alpha1 Editorial · August 15, 2026

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Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial.

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DOI

10.1038/s41591-026-04327-4

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035b35da3615fcd85393d94bbd370c0be8e2a6880c51eb88ef7917a250db67c8

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial.

Paper source

Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial.

Read full text (PMC)

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Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 15, 2026

Kaimen Rigor review

Kaimen Rigor reviewed

3 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×3−1.5★
StatisticsStatistic did not reproduce−0.5★

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

Biggest issues

01Significance claim does not survive recomputation
highOverreachrecomputedFull detail
Recomputed HR 0.32 (95% CI 0.12–0.87), reported p=0.089
“HR 0.32; 95% CI 0.12 to 0.87; P = 0.089”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 202OverreachOverstated conclusions 103AuthenticityData authenticity concerns 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 is a well-conducted and transparently reported phase 2 randomized trial with strong scientific premise, detailed methods, and comprehensive reporting of demographics, ethics, and data availability. The main weakness is a statistical inconsistency detected in one recomputed test (HR 0.32 with reported p=0.089 vs recomputed p=0.024), which warrants caution in interpreting that specific result, and the primary endpoint revision without sample size re-estimation.

Both reviewers agreed on study type (interventional) and on all dimensions except statistical analysis, where the deterministic statistics check revealed an inconsistency not flagged by either reviewer. The statistics check covered only 7 tests; the rest are unverified. The paper is a human clinical trial, so many checklist items (e.g., cell line authentication, housing conditions) are not applicable.

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 6 tests: 5 consistent, 1 inconsistent (1 change significance at p<.05); 5 recomputed directly from the reported test statistics, 1 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.

Significance claim flips when recomputedRecomputed
Conclusions only partially backed by the presented evidenceAssessed

8 major claims checked against the paper's own evidence: 2 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.

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

Data authenticity concerns

1 finding · worst low

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.

Other integrity concernAssessed

3 integrity concerns flagged (0 high).

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 extensive prior work on GSK-3β as a therapeutic target, including preclinical models and early-phase clinical trials of elraglusib, and acknowledges both strengths and limitations (e.g., toxicity of existing regimens, failure of immunotherapy). The rationale for the study follows logically from the cited evidence, and the paper addresses limitations of prior research by noting the need for new agents and the exploratory nature of some analyses.

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 strong scientific premise by citing prior preclinical and clinical evidence for GSK-3β inhibition in pancreatic cancer and clearly links this to the study objectives.

Evidence

paraphrase[Introduction, paragraphs 2-4]

“Glycogen synthase kinase-3 beta (GSK-3β), a serine/threonine kinase, has been identified as a potential therapeutic target in human pancreatic cancer.”

“Because of the promising survival trends, this trial transitioned to a phase 2 randomized trial that also explored weekly dosing of elraglusib with GnP.”

Introduction ¶4Find in source

“Some concerns include toxicity with the FOLFIRINOX and NALIRIFOX regimens, limiting their use to patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 and 1”

Introduction ¶1Find in source

PASSReviewer 2· 90% conf

The paper establishes a strong scientific premise by citing prior preclinical and clinical evidence for GSK-3β inhibition in pancreatic cancer and clearly links this to the study objectives.

Evidence

paraphrase[Introduction, paragraphs 3-4]

“In a single-arm, phase 2 trial in 42 patients with previously untreated mPDAC, elraglusib/GnP led to a median OS of 11.9 months (95% CI 7.8 to 16.5) and 1-year survival rate of 48% (95% CI 32.1 to 62.3) in the intention-to-treat (ITT) population.”

“Because of the promising survival trends, this trial transitioned to a phase 2 randomized trial that also explored weekly dosing of elraglusib with GnP.”

Introduction ¶4Find in source

paraphrase[Introduction, paragraph 4]

“Paraphrase: The paper states that the promising survival trends from the single-arm trial led to the design of a randomized trial, implying the need for a controlled comparison.”

Randomization was stratified by center with block size three, and the unit is the patient. The open-label design is explicitly acknowledged and justified in the discussion. A sample size calculation is reported with assumptions (1-year survival 55% vs 35%, 80% power, alpha 0.05). Inclusion/exclusion criteria are detailed. The mITT population is defined as the primary analysis set, addressing missing data. Blinding is not applicable due to open-label design, which is stated. Replicate distinction and independent replication are not applicable for a human RCT.

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 rigorous for a phase 2 trial: randomization method and unit are described, the open-label design is stated with rationale, a power analysis is provided, and inclusion/exclusion criteria are pre-specified.

Evidence

“Randomization for all stages of the study was stratified according to study center with a block size of three.”

MethodsFind in source

“Initial limitations of this study were its open-label design and regional treatment access”

Discussion ¶1Find in source

“The calculation assumptions included achieving a 1-year survival rate of 55% with elraglusib/GnP and 35% with GnP (20% difference between the arms) with 80% power using a chi-squared test for equal proportions at a two-sided significance level of 0.05.”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The study design is rigorous for a phase 2 trial: randomization is described with stratification, the primary analysis population is defined, and a power calculation is provided, though the primary endpoint was revised after study initiation.

Evidence

“Randomization for all stages of the study was stratified according to study center with a block size of three.”

MethodsFind in source

Statistical analysisFind in source

“Following regulatory feedback after study initiation, the primary efficacy analysis was revised to a comparison of survival curves using a log-rank test; the sample size was not reestimated.”

Statistical analysisFind in source

The paper reports sex (male 52.4%), age (median 66 years), ethnicity (White 83.2%), and other demographics in Table 1. Since both sexes are enrolled, sex_justified is not applicable. Age, weight, and health status (ECOG PS) are reported. Species/strain and housing conditions are not applicable for a human trial.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Demographic and baseline characteristics are comprehensively reported, including age, sex, ethnicity, and disease status.

Evidence

“The key characteristics of treated patients were a median age of 66 years (range 42–86 years), male sex in 52.4% of patients and White ethnicity in 83.2% of patients”

ResultsFind in source

paraphrase[Table 1]

“ECOG PS, n (%) | 0 | 64 (41.3) | 31 (39.7)”

PASSReviewer 2· 90% conf

Demographic and baseline characteristics are comprehensively reported for the human trial population, including age, sex, ethnicity, and disease status.

Evidence

“Female | 75 (48.4) | 35 (44.9)”

Table 1Find in source

“Median (range) | 65.0 (42.0 to 86.0) | 68.0 (42.0 to 85.0)”

Table 1Find in source

paraphrase[Table 1]

“ECOG PS, n (%) | 0 | 64 (41.3) | 31 (39.7)”

The paper states that local institutional review boards or independent ethics committees approved the protocol, and all patients signed informed consent. Regulatory compliance with Good Clinical Practice and the Declaration of Helsinki is stated. The approval statement names the type of body (IRB/ethics committee) but does not provide a protocol number; however, this is adequate for a clinical trial report.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

Ethics approval and informed consent are adequately reported, with a named ethics body and compliance statement.

Evidence

“Local institutional review boards or the independent ethics committees of the participating centers approved the study protocol.”

EthicsFind in source

“All enrolled patients signed the informed consent form.”

EthicsFind in source

“The study was performed in compliance with Good Clinical Practice and the Declaration of Helsinki (v2013).”

EthicsFind in source

PASSReviewer 2· 90% conf

Ethics approval and informed consent are adequately reported, with a named ethics body and compliance with the Declaration of Helsinki.

Evidence

“Local institutional review boards or the independent ethics committees of the participating centers approved the study protocol.”

EthicsFind in source

“All enrolled patients signed the informed consent form.”

EthicsFind in source

“The study was performed in compliance with Good Clinical Practice and the Declaration of Helsinki (v2013).”

EthicsFind in source

Elraglusib is identified as a GSK-3β inhibitor with dose (9.3 mg/kg) and schedule. Gemcitabine and nab-paclitaxel are identified with doses. The manufacturer/source of elraglusib is implied (Actuate Therapeutics) but not explicitly stated in the methods; however, the drug is well-defined. Statistical software (SAS v9.4) is identified. Antibodies, cell lines, and mycoplasma testing are not applicable as this is a clinical trial without wet-lab assays.

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· 80% conf

The investigational product (elraglusib) and comparator (gemcitabine/nab-paclitaxel) are identified with dosing details, and the statistical software is named.

Evidence

“During the study, intravenous elraglusib 9.3 mg kg −1 was administered on day 1 for the once-weekly schedule or days 1 and 4 for the twice-weekly schedule.”

MethodsFind in source

“All statistical analyses were performed using SAS v.9.4”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The investigational product (elraglusib) and comparator chemotherapy are identified with dosing details, and the statistical software is named.

Evidence

“During the study, intravenous elraglusib 9.3 mg kg −1 was administered on day 1 for the once-weekly schedule or days 1 and 4 for the twice-weekly schedule.”

MethodsFind in source

“GnP treatment consisted of intravenous nab-paclitaxel 125 mg m − 2 followed by intravenous gemcitabine 1,000 mg m 2 on days 1, 8 and 15 in a 28-day cycle.”

MethodsFind in source

“All statistical analyses were performed using SAS v.9.4”

Statistical analysisFind in source

Tests are named (log-rank, Cox proportional hazards, Cochran–Mantel–Haenszel). Exact p-values are reported (e.g., P = 0.01). Effect sizes with 95% CIs are reported for primary and secondary endpoints. Statistical software is identified. Data presentation includes Kaplan-Meier curves and forest plots, appropriate for a trial. Assumptions are handled by design (Cox model, log-rank). Mathematical plausibility is not applicable for large-N continuous outcomes.

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· 80% conf

Statistical methods are well described, with named tests, exact p-values, effect sizes with CIs, and software identified. The analysis is appropriate for a clinical trial.

Evidence

“Statistical tests: log-rank tests for time-to-event variables; Cox proportional hazards model for HRs; and Cochran–Mantel–Haenszel general association tests for responder variables.”

Table 2Find in source

“HR 0.62; 95% CI 0.46 to 0.84; P = 0.01”

ResultsFind in source

“median OS of 10.1 months (95% CI 7.7 to 12.5) with elraglusib/GnP versus 7.2 months (95% CI 5.7 to 9.0) with GnP (HR 0.62; 95% CI 0.46 to 0.84; P = 0.01”

ResultsFind in source

PASSReviewer 2· 80% conf

Statistical methods are appropriate and well-described, with exact p-values and effect sizes with confidence intervals reported; however, the primary endpoint revision and some subgroup analyses warrant caution.

Evidence

“Statistical tests: log-rank tests for time-to-event variables; Cox proportional hazards model for HRs; and Cochran–Mantel–Haenszel general association tests for responder variables.”

Table 2Find in source

“HR 0.62; 95% CI 0.46 to 0.84; P = 0.01”

ResultsFind in source

“HR 0.62 (0.46 to 0.84)”

Table 2Find in source

The data availability statement describes a managed-access process through ClinicalStudyDataRequest and a contact email, with a response timeframe. This is reported_and_adequate for identifiable patient data. Repository deposit and accession numbers are not applicable for patient-level data. Code sharing is not applicable as no bespoke code is mentioned.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

A data availability statement is present with a concrete access mechanism via ClinicalStudyDataRequest, which is adequate for patient-level data.

Evidence

“Trial data availability is according to the criteria and process described at www.clinicalstudydatarequest.com”

Data availabilityFind in source

PASSReviewer 2· 90% conf

A data availability statement is provided with a concrete access mechanism via a data-sharing platform, which is adequate for patient-level clinical trial data.

Evidence

paraphrase[Data availability]

“Trial data availability is according to the criteria and process described at www.clinicalstudydatarequest.com . The data described in this publication will be made available for any qualified request.”

The trial is registered (NCT03678883). Methods are detailed enough for replication. Limitations are explicitly discussed (open-label, early mortality, exploratory analyses). Conclusions are proportional, acknowledging the phase 2 nature and exploratory findings. Funding and competing interests are disclosed. A reporting guideline is not explicitly mentioned, but the paper follows CONSORT-like structure with a flow diagram.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The manuscript is transparent: trial registration is provided, methods are detailed, limitations are discussed, and conclusions are proportional.

Evidence

“ClinicalTrials.gov registration: NCT03678883”

AbstractFind in source

“Initial limitations of this study were its open-label design and regional treatment access”

Discussion ¶1Find in source

“This work was supported by Actuate Therapeutics.”

Competing interestsFind in source

PASSReviewer 2· 85% conf

The manuscript is transparent: methods are detailed, the trial is registered, limitations are discussed, and funding/COI are disclosed.

Evidence

“ClinicalTrials.gov registration: NCT03678883”

AbstractFind in source

“Initial limitations of this study were its open-label design and regional treatment access as several patients withdrew from the study once randomized to the control arm to pursue alternative treatment options closer to home.”

Discussion ¶10Find in source

“This work was supported by Actuate Therapeutics.”

Competing interestsFind in source

Registered (3 IDs: ClinicalTrials.gov). No reporting guideline cited.

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 54 references by DOI: 3 verified — 51 no DOI (shown, not verified).

4 of 5 data/code links checked; 4 live; 1 not probed.

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, other.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is largely robust, but the statistical inconsistency in one reported p-value (HR 0.32, reported p=0.089 vs recomputed p=0.024) is a validity concern that warrants an erratum or independent re-analysis. An informed reader should weigh this alongside the primary endpoint revision without sample size re-estimation when interpreting the results.

1.
HIGHstatistics
Investigate and correct the inconsistent p-value for the HR 0.32 (95% CI 0.12–0.87) result: the reported p=0.089 does not match the recomputed p=0.024; verify the source data and issue a correction if needed.
A demonstrable inconsistency between the reported p-value and the recomputed value is a validity threat that could mislead readers about the significance of that finding.
2.
HIGHstatistics
In the Methods (Statistical analysis), explicitly discuss the impact of revising the primary endpoint from 1-year survival to log-rank test without re-estimating sample size, and state the potential reduction in power.
The primary endpoint revision without sample size re-estimation is a major methodological concern that affects the interpretation of the primary p-value.
3.
HIGHreporting
Add an explicit reference to the CONSORT checklist in the Methods or Reporting Summary, and include a completed CONSORT flow diagram in the main text.
Explicit adherence to a reporting guideline strengthens transparency and is expected for randomized trials.
4.
HIGHreporting
Reconcile the HR discrepancy between the Results (HR 0.62) and the Discussion (HR 0.63) for the same OS comparison, and ensure consistent reporting throughout.
Internal inconsistency in a key effect size undermines reader confidence and may indicate a rounding or transcription error.
5.
MEDIUMethics
In the Methods (Ethics approval and consent), provide the specific IRB/ethics committee names and protocol approval numbers for each participating center.
Full auditability of ethics approvals is expected for clinical trials and facilitates verification.
6.
MEDIUMreporting
In the Methods (Statistical analysis), describe how the proportional hazards assumption was checked for the Cox model, or state that it was assumed.
Verifying model assumptions is part of sound statistical reporting and helps readers assess the validity of the HR estimates.
7.
MEDIUMreporting
In the Results (Patient disposition), clarify whether the twice-weekly elraglusib arm is excluded from all efficacy analyses or only from the primary analysis.
The current wording is ambiguous about the inclusion of the twice-weekly arm, which could confuse readers about the analysis population.
8.
MEDIUMreporting
In the Discussion, explicitly state that the exploratory biomarker analyses are hypothesis-generating and were not adjusted for multiple comparisons.
Clarifying the exploratory nature of these analyses prevents overinterpretation of potentially spurious findings.
9.
MEDIUMdata code
In the Data Availability section, provide a direct hyperlink to the ClinicalStudyDataRequest portal and specify the expected timeline for data availability.
A direct link and timeline improve the usability of the data access statement for qualified researchers.
10.
MEDIUMreporting
In the Results, report the number of patients who withdrew after randomization and were lost to follow-up, to clarify the mITT vs ITT difference.
Detailed disposition data enhance transparency and allow readers to assess potential attrition bias.
11.
LOWcopyedit
Standardize the use of 'P' vs 'p' for p-values throughout the manuscript (Abstract uses uppercase, tables use lowercase).
Consistent notation is a basic copyedit requirement that improves professionalism.
12.
LOWcopyedit
Rephrase the Abstract sentence with double parentheses to avoid punctuation clutter.
Minor punctuation issues detract from readability.
13.
LOWreporting
In the Methods (Statistical analysis), add a citation for the rationale for using the log-rank test to account for censored survival times.
Citing a standard reference for the log-rank test strengthens the methodological justification.
14.
LOWreporting
In the Methods (Procedures), specify the manufacturer/source of elraglusib and the chemotherapy agents.
Identifying the source of investigational products is part of complete resource reporting.
15.
LOWreporting
In the Abstract, add confidence intervals for the 1-year survival rates to be consistent with the main text.
Consistency between abstract and main text improves clarity and completeness.

Full text (74,187 chars)Analyzed: Aug 15, 2026

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Read alongside

Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial.

Read full text (PMC)

DOI

10.1038/s41591-026-04327-4

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Record fingerprint

035b35da3615fcd85393d94bbd370c0be8e2a6880c51eb88ef7917a250db67c8

Verify via API

Issued Aug 15, 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

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×3−1.5★
StatisticsStatistic did not reproduce−0.5★

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

Biggest issues

01Significance claim does not survive recomputation
highOverreachrecomputedFull detail
Recomputed HR 0.32 (95% CI 0.12–0.87), reported p=0.089
“HR 0.32; 95% CI 0.12 to 0.87; P = 0.089”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 202OverreachOverstated conclusions 103AuthenticityData authenticity concerns 04DisclosureNone found 05AvailabilityNone found 06Copyedit6 minor suggestions

Numerical inconsistencies

1 finding · worst low

Internal contradictions in the reported numbersAssessed

Recomputed 6 tests: 5 consistent, 1 inconsistent (1 change significance at p<.05); 5 recomputed directly from the reported test statistics, 1 via agent-written checks.

Overstated conclusions

2 findings · worst high

Significance claim flips when recomputedRecomputed
Conclusions only partially backed by the presented evidenceAssessed

8 major claims checked against the paper's own evidence: 2 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.

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

Data authenticity concerns

1 finding · worst low

Other integrity concernAssessed

3 integrity concerns flagged (0 high).

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

The paper establishes a strong scientific premise by citing prior preclinical and clinical evidence for GSK-3β inhibition in pancreatic cancer and clearly links this to the study objectives.

Evidence

paraphrase[Introduction, paragraphs 2-4]

“Glycogen synthase kinase-3 beta (GSK-3β), a serine/threonine kinase, has been identified as a potential therapeutic target in human pancreatic cancer.”

“Because of the promising survival trends, this trial transitioned to a phase 2 randomized trial that also explored weekly dosing of elraglusib with GnP.”

Introduction ¶4Find in source

“Some concerns include toxicity with the FOLFIRINOX and NALIRIFOX regimens, limiting their use to patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 and 1”

Introduction ¶1Find in source

PASSReviewer 2· 90% conf

The paper establishes a strong scientific premise by citing prior preclinical and clinical evidence for GSK-3β inhibition in pancreatic cancer and clearly links this to the study objectives.

Evidence

paraphrase[Introduction, paragraphs 3-4]

“Because of the promising survival trends, this trial transitioned to a phase 2 randomized trial that also explored weekly dosing of elraglusib with GnP.”

Introduction ¶4Find in source

paraphrase[Introduction, paragraph 4]

“Paraphrase: The paper states that the promising survival trends from the single-arm trial led to the design of a randomized trial, implying the need for a controlled comparison.”

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

“Randomization for all stages of the study was stratified according to study center with a block size of three.”

MethodsFind in source

“Initial limitations of this study were its open-label design and regional treatment access”

Discussion ¶1Find in source

Statistical analysisFind in source

PASSReviewer 2· 85% conf

Evidence

“Randomization for all stages of the study was stratified according to study center with a block size of three.”

MethodsFind in source

Statistical analysisFind in source

“Following regulatory feedback after study initiation, the primary efficacy analysis was revised to a comparison of survival curves using a log-rank test; the sample size was not reestimated.”

Statistical analysisFind 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

Demographic and baseline characteristics are comprehensively reported, including age, sex, ethnicity, and disease status.

Evidence

“The key characteristics of treated patients were a median age of 66 years (range 42–86 years), male sex in 52.4% of patients and White ethnicity in 83.2% of patients”

ResultsFind in source

paraphrase[Table 1]

“ECOG PS, n (%) | 0 | 64 (41.3) | 31 (39.7)”

PASSReviewer 2· 90% conf

Demographic and baseline characteristics are comprehensively reported for the human trial population, including age, sex, ethnicity, and disease status.

Evidence

“Female | 75 (48.4) | 35 (44.9)”

Table 1Find in source

“Median (range) | 65.0 (42.0 to 86.0) | 68.0 (42.0 to 85.0)”

Table 1Find in source

paraphrase[Table 1]

“ECOG PS, n (%) | 0 | 64 (41.3) | 31 (39.7)”

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

Ethics approval and informed consent are adequately reported, with a named ethics body and compliance statement.

Evidence

“Local institutional review boards or the independent ethics committees of the participating centers approved the study protocol.”

EthicsFind in source

“All enrolled patients signed the informed consent form.”

EthicsFind in source

“The study was performed in compliance with Good Clinical Practice and the Declaration of Helsinki (v2013).”

EthicsFind in source

PASSReviewer 2· 90% conf

Ethics approval and informed consent are adequately reported, with a named ethics body and compliance with the Declaration of Helsinki.

Evidence

“Local institutional review boards or the independent ethics committees of the participating centers approved the study protocol.”

EthicsFind in source

“All enrolled patients signed the informed consent form.”

EthicsFind in source

“The study was performed in compliance with Good Clinical Practice and the Declaration of Helsinki (v2013).”

EthicsFind 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· 80% conf

The investigational product (elraglusib) and comparator (gemcitabine/nab-paclitaxel) are identified with dosing details, and the statistical software is named.

Evidence

“During the study, intravenous elraglusib 9.3 mg kg −1 was administered on day 1 for the once-weekly schedule or days 1 and 4 for the twice-weekly schedule.”

MethodsFind in source

“All statistical analyses were performed using SAS v.9.4”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The investigational product (elraglusib) and comparator chemotherapy are identified with dosing details, and the statistical software is named.

Evidence

“During the study, intravenous elraglusib 9.3 mg kg −1 was administered on day 1 for the once-weekly schedule or days 1 and 4 for the twice-weekly schedule.”

MethodsFind in source

“GnP treatment consisted of intravenous nab-paclitaxel 125 mg m − 2 followed by intravenous gemcitabine 1,000 mg m 2 on days 1, 8 and 15 in a 28-day cycle.”

MethodsFind in source

“All statistical analyses were performed using SAS v.9.4”

Statistical analysisFind 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· 80% conf

Statistical methods are well described, with named tests, exact p-values, effect sizes with CIs, and software identified. The analysis is appropriate for a clinical trial.

Evidence

“Statistical tests: log-rank tests for time-to-event variables; Cox proportional hazards model for HRs; and Cochran–Mantel–Haenszel general association tests for responder variables.”

Table 2Find in source

“HR 0.62; 95% CI 0.46 to 0.84; P = 0.01”

ResultsFind in source

“median OS of 10.1 months (95% CI 7.7 to 12.5) with elraglusib/GnP versus 7.2 months (95% CI 5.7 to 9.0) with GnP (HR 0.62; 95% CI 0.46 to 0.84; P = 0.01”

ResultsFind in source

PASSReviewer 2· 80% conf

Evidence

“Statistical tests: log-rank tests for time-to-event variables; Cox proportional hazards model for HRs; and Cochran–Mantel–Haenszel general association tests for responder variables.”

Table 2Find in source

“HR 0.62; 95% CI 0.46 to 0.84; P = 0.01”

ResultsFind in source

“HR 0.62 (0.46 to 0.84)”

Table 2Find in source

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

A data availability statement is present with a concrete access mechanism via ClinicalStudyDataRequest, which is adequate for patient-level data.

Evidence

“Trial data availability is according to the criteria and process described at www.clinicalstudydatarequest.com”

Data availabilityFind in source

PASSReviewer 2· 90% conf

A data availability statement is provided with a concrete access mechanism via a data-sharing platform, which is adequate for patient-level clinical trial data.

Evidence

paraphrase[Data availability]

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The manuscript is transparent: trial registration is provided, methods are detailed, limitations are discussed, and conclusions are proportional.

Evidence

“ClinicalTrials.gov registration: NCT03678883”

AbstractFind in source

“Initial limitations of this study were its open-label design and regional treatment access”

Discussion ¶1Find in source

“This work was supported by Actuate Therapeutics.”

Competing interestsFind in source

PASSReviewer 2· 85% conf

The manuscript is transparent: methods are detailed, the trial is registered, limitations are discussed, and funding/COI are disclosed.

Evidence

“ClinicalTrials.gov registration: NCT03678883”

AbstractFind in source

Discussion ¶10Find in source

“This work was supported by Actuate Therapeutics.”

Competing interestsFind in source

Registered (3 IDs: ClinicalTrials.gov). No reporting guideline cited.

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 54 references by DOI: 3 verified — 51 no DOI (shown, not verified).

4 of 5 data/code links checked; 4 live; 1 not probed.

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, other.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
HIGHstatistics
Investigate and correct the inconsistent p-value for the HR 0.32 (95% CI 0.12–0.87) result: the reported p=0.089 does not match the recomputed p=0.024; verify the source data and issue a correction if needed.
A demonstrable inconsistency between the reported p-value and the recomputed value is a validity threat that could mislead readers about the significance of that finding.
2.
HIGHstatistics
In the Methods (Statistical analysis), explicitly discuss the impact of revising the primary endpoint from 1-year survival to log-rank test without re-estimating sample size, and state the potential reduction in power.
The primary endpoint revision without sample size re-estimation is a major methodological concern that affects the interpretation of the primary p-value.
3.
HIGHreporting
Add an explicit reference to the CONSORT checklist in the Methods or Reporting Summary, and include a completed CONSORT flow diagram in the main text.
Explicit adherence to a reporting guideline strengthens transparency and is expected for randomized trials.
4.
HIGHreporting
Reconcile the HR discrepancy between the Results (HR 0.62) and the Discussion (HR 0.63) for the same OS comparison, and ensure consistent reporting throughout.
Internal inconsistency in a key effect size undermines reader confidence and may indicate a rounding or transcription error.
5.
MEDIUMethics
In the Methods (Ethics approval and consent), provide the specific IRB/ethics committee names and protocol approval numbers for each participating center.
Full auditability of ethics approvals is expected for clinical trials and facilitates verification.
6.
MEDIUMreporting
In the Methods (Statistical analysis), describe how the proportional hazards assumption was checked for the Cox model, or state that it was assumed.
Verifying model assumptions is part of sound statistical reporting and helps readers assess the validity of the HR estimates.
7.
MEDIUMreporting
In the Results (Patient disposition), clarify whether the twice-weekly elraglusib arm is excluded from all efficacy analyses or only from the primary analysis.
The current wording is ambiguous about the inclusion of the twice-weekly arm, which could confuse readers about the analysis population.
8.
MEDIUMreporting
In the Discussion, explicitly state that the exploratory biomarker analyses are hypothesis-generating and were not adjusted for multiple comparisons.
Clarifying the exploratory nature of these analyses prevents overinterpretation of potentially spurious findings.
9.
MEDIUMdata code
In the Data Availability section, provide a direct hyperlink to the ClinicalStudyDataRequest portal and specify the expected timeline for data availability.
A direct link and timeline improve the usability of the data access statement for qualified researchers.
10.
MEDIUMreporting
In the Results, report the number of patients who withdrew after randomization and were lost to follow-up, to clarify the mITT vs ITT difference.
Detailed disposition data enhance transparency and allow readers to assess potential attrition bias.
11.
LOWcopyedit
Standardize the use of 'P' vs 'p' for p-values throughout the manuscript (Abstract uses uppercase, tables use lowercase).
Consistent notation is a basic copyedit requirement that improves professionalism.
12.
LOWcopyedit
Rephrase the Abstract sentence with double parentheses to avoid punctuation clutter.
Minor punctuation issues detract from readability.
13.
LOWreporting
In the Methods (Statistical analysis), add a citation for the rationale for using the log-rank test to account for censored survival times.
Citing a standard reference for the log-rank test strengthens the methodological justification.
14.
LOWreporting
In the Methods (Procedures), specify the manufacturer/source of elraglusib and the chemotherapy agents.
Identifying the source of investigational products is part of complete resource reporting.
15.
LOWreporting
In the Abstract, add confidence intervals for the 1-year survival rates to be consistent with the main text.
Consistency between abstract and main text improves clarity and completeness.

Full text (74,187 chars)Analyzed: Aug 15, 2026