TERN-501 monotherapy and combination therapy with TERN-101 in metabolic dysfunction-associated steatohepatitis: the randomized phase 2a DUET trial.
Noureddin M, Alkhouri N, Lawitz EJ, Kowdley KV, Loomba R, Lee L, Jones C, Schlegel A, Marmon T, Anderson K, Li Y, Quirk E, Harrison SA
- DOI
- 10.1038/s41591-025-03722-7
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-21
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/7221bd13-2ef2-48a2-ace4-6397bc10ae63 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern ×3−1.5★
- ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
- ClaimsTreatment effect not shown to be clinically meaningful−0.5★
- ReportingData & code availability partially met−0.25★
- 01Efficacy rests on an unvalidated surrogate endpoint
The primary endpoint is MRI-PDFF, a surrogate for liver fat content, not a hard clinical outcome. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD showing receptor occupancy) nor cite validated evidence linking MRI-PDFF reduction to clinical outcomes such as mortality or cirrhosis. Although the discussion mentions associations with histologic response, this is not a validated surrogate for clinical benefit.
“The primary endpoint was relative change from baseline at week 12 in liver fat content with TERN-501 monotherapy versus placebo, using magnetic resonance imaging proton density fat fraction (MRI-PDFF).”
- 02Treatment effect not shown to be clinically meaningful
The reported effect is a reduction in liver fat content (MRI-PDFF) of up to 44.8% relative to baseline, but this is a surrogate biomarker change. The paper does not anchor this to a minimal clinically important difference or demonstrate that it translates to improved clinical outcomes. The effect size is presented as statistically significant but lacks clinical meaningfulness.
“Least squares mean (s.e.) changes from baseline at week 12 in MRI-PDFF with TERN-501 were: −15.4% (5.2%) with 1 mg, −27.5% (5.7%) with 3 mg (P = 0.0036) and −44.8% (5.9%) with 6 mg (P < 0.0001), versus −4.0% (5.4%) with placebo.”
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 2a randomized controlled trial with rigorous design, clear ethical approvals, and appropriate statistical methods. The main weakness is the vague data availability statement and lack of code sharing, which limits reproducibility. Minor internal inconsistencies and copyedit issues (e.g., drug name typo, p-value discrepancy) should be corrected.
Both reviewers agreed on study type (interventional) and on all dimension statuses except a minor divergence on reporting guideline (Reviewer 2 flagged it as inadequate, Reviewer 1 as adequate). The statistics verification recomputed only 2 tests (both consistent); other reported statistics were not machine-verified. The citation check found no retracted or unresolved references. The integrity check flagged three low-severity internal inconsistencies (see action items).
Numerical inconsistencies
1 finding · worst lowValues 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 2 tests: 2 consistent, 0 inconsistent; 2 via agent-written checks.
- CONSISTENTreported p = .004 · recomputed p = .003Reviewer 2Primary endpoint: LS mean difference in MRI-PDFF for TERN-501 3 mg vs placebo
“The LS mean differences were statistically significant compared to placebo for the TERN-501 3-mg ( P = 0.0036) and 6-mg ( P < 0.0001) treatment groups”
Taken as given: The reported p-value is from a two-sided test.; The test statistic is approximately t-distributed with df around 100 (not directly reported).; The p-value corresponds to the comparison of TERN-501 3 mg vs placebo.Method: Approximated using a t-distribution with df=100; exact df not reported, so this is an approximation.How we recomputed it: pT(3.0, 100) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2Secondary endpoint: cT1 change for TERN-501 6 mg vs placebo
“cT1 relaxation time—a marker of fibroinflammation in the liver—decreased significantly from baseline in the TERN-501 6-mg monotherapy group at week 12 (LS mean (s.e.) change: −72.0 (16.1) ms) versus placebo (3.6 (14.9) ms; P = 0.0008)”
Taken as given: The reported p-value is from a two-sided test.; The test statistic is approximately t-distributed with df around 100.; The p-value corresponds to the comparison of TERN-501 6 mg vs placebo.Method: Approximated using a t-distribution with df=100; exact df not reported, so this is an approximation.How we recomputed it: pT(3.5, 100)
- lowinternal contradictionThe abstract states '162 patients were randomized' but the Methods state 'Of the 140 patients to be randomized' in the context of the PK/PD substudy planning, which may be a typo or inconsistency.
Overall, 162 patients were randomized to: ... Of the 140 patients to be randomized, approximately 42 patients (about six per group) were planned to take part in an intensive PK and PD collection
Abstractreviewer’s wording - lowinternal contradictionIn Figure 3b, the p-value for TERN-501 1 mg is reported as P = 0.9645, but in the text it is P = 0.09645, which is inconsistent.
“≥80-ms reduction in cT1 ( b , TERN-501 1 mg, P = 0.9645; TERN-501 3 mg, P = 0.09645; TERN-501 6 mg, P = 0.0449)”
Figure 3BFind in source - lowinternal contradictionThe Methods state the study was conducted at 35 centers, but the Results say 27 sites enrolled patients.
“conducted at 35 centers (with 27 enrolling patients) across the United States”
MethodsFind 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
5 major claims checked against the paper's own evidence: 2 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.
- partialReviewers 1, 2TERN-501 has the potential to avoid adverse drug interactions with commonly coprescribed medication classes in MASH.The PK data show low-to-moderate variability and no effect of concomitant therapies, but this is not a formal drug-drug interaction study.Evidence: PK profile predictable; exposures consistent with healthy participants; no relevant effects of concomitant therapies.
“TERN-501 may have the potential to avoid adverse drug interactions with commonly coprescribed medication classes in MASH.”
DiscussionFind in source - partialReviewer 2The addition of TERN-501 to a patient's existing treatment regimen may not result in overlapping gastrointestinal AE profiles.GI AEs were low and not dose-dependent, but the study was not designed to assess interactions with GLP-1 analogs, so the claim is preliminary.Evidence: GI AEs in TERN-501 monotherapy groups occurred at low rates similar to placebo; 17 patients were on GLP-1 analogs.
“Our data suggest that the addition of TERN-501 to a patient’s existing treatment regimen may not result in overlapping gastrointestinal AE profiles”
DiscussionFind in source - supportedReviewers 1, 2TERN-501 treatment resulted in dose-dependent, significant reductions from baseline in MRI-PDFF compared to placebo in patients with MASH.The primary endpoint was met with significant reductions for 3mg and 6mg doses, and the data support a dose-dependent effect.Evidence: LS mean changes: -15.4%, -27.5%, -44.8% for 1,3,6 mg vs -4.0% placebo; p=0.0036 and p<0.0001 for 3 and 6 mg.
“TERN-501 treatment resulted in dose-dependent, significant reductions from baseline in MRI-PDFF compared to placebo in patients with MASH.”
AbstractFind in source - supportedReviewers 1, 2TERN-501 monotherapy demonstrated a favorable tolerability profile with no safety signals identified.Safety data show similar AE rates to placebo and no dose-dependent safety findings.Evidence: AE incidence similar across groups; no Grade 4/5 AEs; no treatment-related serious AEs.
“TERN-501 monotherapy demonstrated a favorable tolerability profile in a MASH population, with no safety signals identified and no dose-dependent safety findings.”
DiscussionFind in source - supportedReviewer 1The addition of TERN-101 to TERN-501 resulted in broadly comparable changes from baseline in MRI-PDFF and cT1 compared to monotherapy.Combination groups showed significant reductions, but not clearly superior to monotherapy; the claim of 'comparable' is supported.Evidence: Combination LS mean changes: -20.8% and -47.7% for 3mg and 6mg combos; cT1 reductions significant.
“The addition of TERN-101 10 mg to TERN-501 3 mg or 6 mg resulted in broadly comparable changes from baseline in MRI-PDFF and cT1 relaxation time compared to TERN-501 monotherapy at the same dose.”
DiscussionFind in source
Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.
- INADEQUATESurrogate endpointThe primary endpoint is MRI-PDFF, a surrogate for liver fat content, not a hard clinical outcome. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD showing receptor occupancy) nor cite validated evidence linking MRI-PDFF reduction to clinical outcomes such as mortality or cirrhosis. Although the discussion mentions associations with histologic response, this is not a validated surrogate for clinical benefit.
“The primary endpoint was relative change from baseline at week 12 in liver fat content with TERN-501 monotherapy versus placebo, using magnetic resonance imaging proton density fat fraction (MRI-PDFF).”
- INADEQUATEEffect sizeThe reported effect is a reduction in liver fat content (MRI-PDFF) of up to 44.8% relative to baseline, but this is a surrogate biomarker change. The paper does not anchor this to a minimal clinically important difference or demonstrate that it translates to improved clinical outcomes. The effect size is presented as statistically significant but lacks clinical meaningfulness.
“Least squares mean (s.e.) changes from baseline at week 12 in MRI-PDFF with TERN-501 were: −15.4% (5.2%) with 1 mg, −27.5% (5.7%) with 3 mg (P = 0.0036) and −44.8% (5.9%) with 6 mg (P < 0.0001), versus −4.0% (5.4%) with placebo.”
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
1 finding · worst mediumRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Data/code availability incompleteAssessed
The introduction thoroughly reviews the pathophysiology of MASH, the role of THRβ agonism, and prior clinical data on resmetirom and TERN-501, establishing a strong rationale. Limitations of prior research are implicitly addressed by noting the need for additional THRβ agonists with favorable safety and PK profiles, and the rationale for combination therapy is clearly articulated.
“Thyroid hormone receptor-β (THRβ) agonism is a validated mechanism for treating metabolic dysfunction-associated steatohepatitis (MASH).”
“there remains a need for additional THRβ agonist treatment options with favorable safety and drug–drug interaction profiles, and reduced pharmacokinetic (PK) variability.”
“there remains a need for additional THRβ agonist treatment options with favorable safety and drug–drug interaction profiles, and reduced pharmacokinetic (PK) variability.”
Randomization used an interactive web response system with a 1:1:1:1:1:1:1 ratio. Blinding of patients, investigators, and study personnel is stated. A power analysis is provided for the primary endpoint. Inclusion/exclusion criteria are detailed. The analysis populations (efficacy, safety, PK/PD) are defined. Outlier handling is addressed through the pre-specified analysis population and missing data approach (no imputation for primary analysis).
“An interactive web response system was used to randomize patients in a 1:1:1:1:1:1:1 ratio to TERN-501 1 mg, TERN-501 3 mg, TERN-501 6 mg, TERN-101 10 mg, TERN-501 3 mg plus TERN-101 10 mg, TERN-501 6 mg plus TERN-101 10 mg or matching placebo.”
“Patients, investigators and study personnel were masked to treatment assignment during the study.”
“Based on an assumed pooled SD of 22% with a two-sided alpha of 0.05, a mean relative reduction difference in MRI-PDFF at week 12 of 23% between TERN-501 monotherapy and placebo would provide approximately 90% power”
“An interactive web response system was used to randomize patients in a 1:1:1:1:1:1:1 ratio to TERN-501 1 mg, TERN-501 3 mg, TERN-501 6 mg, TERN-101 10 mg, TERN-501 3 mg plus TERN-101 10 mg, TERN-501 6 mg plus TERN-101 10 mg or matching placebo.”
“Patients, investigators and study personnel were masked to treatment assignment during the study.”
“Based on an assumed pooled SD of 22% with a two-sided alpha of 0.05, a mean relative reduction difference in MRI-PDFF at week 12 of 23% between TERN-501 monotherapy and placebo would provide approximately 90% power”
Sex is reported for all patients (54.9% female), and age, BMI, and health status (including T2D, hypertension, dyslipidemia) are detailed in Table 1. Since both sexes are enrolled, sex_justified is not applicable. Demographics include race and ethnicity. Species/strain and housing conditions are not applicable for a human trial.
“Overall, mean (s.d.) age was 53.3 (11.8) years and 54.9% were female.”
“Most patients were white (85.8%) and were Hispanic or Latino (61.1%).”
“T2D, n (%) | 11 (45.8) | 8 (34.8) | 10 (43.5) | 6 (27.3) | 7 (29.2) | 13 (56.5) | 13 (56.5) | 68 (42.0)”
The study states it was conducted in accordance with ICH GCP and the Declaration of Helsinki, and that the protocol was approved by the institutional review board or independent ethics committee at each study center. All patients provided written informed consent. Regulatory compliance is explicitly stated.
“The protocol and subsequent amendments, and other relevant documents, were approved by the institutional review board or independent ethics committee at each study center”
“All patients provided written informed consent before enrollment.”
“The study was conducted in accordance with the applicable International Council for Harmonisation Good Clinical Practice guidelines and the principles of the Declaration of Helsinki”
“The protocol and subsequent amendments, and other relevant documents, were approved by the institutional review board or independent ethics committee at each study center”
“All patients provided written informed consent before enrollment.”
“The study was conducted in accordance with the applicable International Council for Harmonisation Good Clinical Practice guidelines and the principles of the Declaration of Helsinki”
TERN-501 and TERN-101 are named as investigational drugs with their mechanisms and doses. The study is a drug trial, so antibodies, cell lines, mycoplasma, and organisms are not applicable. Reagents are scored against the investigational products, which are adequately described. Software tools (SAS v.9.4, Phoenix WinNonlin v.8.3.5) are identified.
“TERN-501 monotherapy (1 mg ( n = 23), 3 mg ( n = 23) or 6 mg ( n = 22)), TERN-101 10-mg monotherapy ( n = 24)”
“Data analysis was performed using SAS v.9.4.”
“TERN-501 (THRβ agonist) as monotherapy or combined with TERN-101 (farnesoid X receptor agonist)”
“Data analysis was performed using SAS v.9.4.”
“Noncompartmental PK parameters were estimated from individual plasma concentration data using Phoenix WinNonlin v.8.3.5.”
The primary analysis uses ANCOVA with treatment group and baseline as covariates. Tests are named (ANCOVA, chi-square). Exact p-values are reported (e.g., P = 0.0036). Effect sizes are reported as LS means with s.e. and 95% CIs. Software is identified. Data presentation includes per-group n and error bars defined as s.e. or s.d. Mathematical plausibility checks were not performed due to continuous outcomes and large N, but no obvious inconsistencies were noted.
“Statistical analysis was performed using a type III sum of squares ANCOVA model with treatment group as a fixed effect and baseline value as the covariate”
“The LS mean differences were statistically significant compared to placebo for the TERN-501 3-mg ( P = 0.0036) and 6-mg ( P < 0.0001) treatment groups”
“Estimates of the LS mean difference between treatment groups and placebo are presented with the associated s.e. of the difference, 95% CI of the difference and pairwise comparisons.”
“Efficacy endpoints (cT1 and MRI-PDFF analyses) used an analysis of covariance (ANCOVA) model with relative change from baseline at week 12 as the dependent variable including treatment group as a fixed effect and baseline as the covariate”
“The LS mean differences were statistically significant compared to placebo for the TERN-501 3-mg ( P = 0.0036) and 6-mg ( P < 0.0001) treatment groups”
“Estimates of the LS mean difference between treatment groups and placebo are presented with the associated s.e. of the difference, 95% CI of the difference and pairwise comparisons.”
The data availability statement says data are not publicly available but requests will be considered on a case-by-case basis 3 years after publication, with conditions. This is reported_but_inadequate because it lacks a concrete mechanism or platform. Repository deposit and accession numbers are not applicable for patient-level data. Code availability is stated as 'Not applicable', which is acceptable if no bespoke code was used, but the statistical analysis code is not shared.
“Requests for data supporting the findings in this manuscript should be made to the corresponding author (M.N.: NoureddinMD@houstonresearchinstitute.com) and will be considered on a case-by-case basis 3 years after publication.”
“Code availability Not applicable.”
“Requests for data supporting the findings in this manuscript should be made to the corresponding author (M.N.: NoureddinMD@houstonresearchinstitute.com) and will be considered on a case-by-case basis 3 years after publication.”
“Code availability Not applicable.”
The trial is registered (NCT05415722). Methods are detailed enough for replication. A reporting guideline (CONSORT) is implied by the flow diagram, though not explicitly referenced. All pre-specified outcomes are reported, including negative results. Limitations are discussed. Conclusions are proportional to the evidence. Funding and COI are disclosed.
“ClinicalTrials.gov registration: NCT05415722”
“Our study had a small sample size that resulted in baseline imbalance in some treatment groups, including in presence of T2D, hypertension and statin use.”
“The study was funded by Terns Pharmaceuticals.”
“ClinicalTrials.gov registration: NCT05415722”
“Our study had a small sample size that resulted in baseline imbalance in some treatment groups, including in presence of T2D, hypertension and statin use.”
“The study was funded by Terns Pharmaceuticals.”
Registered (1 ID: ClinicalTrials.gov). Reporting guideline cited: CONSORT.
Broken references and links
None foundReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
Checked — nothing surfaced.
Checked 54 references by DOI: 42 verified — 12 no DOI (shown, not verified).
- NO DOIUpdate on clinical trials for nonalcoholic steatohepatitisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIRezdiffra (resmetirom) tablets, for oral useNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISAT066: TERN-501, a potent and selective agonist of thyroid hormone receptor beta, strongly reduces histological features and biomarkers of non-alcoholic steatohepatitis associated pathology in rodent modelsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIOS123 – Multiple doses of thyroid hormone receptor-beta agonist TERN-501 were well-tolerated and resulted in significant dose-dependent changes in serum lipids and sex hormone binding globulin in a first-in-human clinical studyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOILiver-distributed FXR agonist TERN-101 demonstrates favorable safety and efficacy profile in NASH phase 2a LIFT studyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISAT107: favorable lipid and pruritus profile of liver-distributed farnesoid X receptor agonist TERN-101 at clinically efficacious doses in nonalcoholic steatohepatitis (NASH) phase 2a LIFT studyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMASH resolution without fibrosis worsening after bariatric surgery improves long-term survivalNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISAT-208 Sex hormone binding globulin as an effective predictor of treatment response to TERN-501, a potent, highly selective thyroid hormone receptor β agonist: post-hoc analyses from a 12-week phase 2a trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIResmetirom treatment helps restore thyroid levels in patients with nonalcoholic steatohepatitis: 52-week data from the phase 3 MAESTRO-NASH trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOI760-P: TERN-501 enhances weight loss efficacy of a GLP-1R agonist in obese mice via increased fat mass loss without additional loss of lean massNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe novel thyroid hormone receptor beta agonist VK2809 significantly reduces liver fat in patients with NASH and fibrosis, results from the primary endpoint of the ongoing phase 2b VOYAGE studyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISAT-202 TERN-501, a highly selective thyroid hormone receptor β agonist, significantly improved MRI-PDFF, cT1, and liver volume in clinically relevant patient populations with presumed MASH: subgroup analyses from a 12-week phase 2a trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
2 data/code links checked; 2 live.
- datahttps://clinicaltrials.gov/study/NCT05415722LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://clinicaltrials.gov/ct2/show/NCT05415722LIVEHTTP 200Resolves, but the content could not be matched to the paper.
Copyediting
7 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 7 minor suggestions below.
7 copyedit issues flagged: mostly consistency, typo, clarity.
- MINORconsistencyAbstract“TERN-501 (3 mg ( n = 23) or 6 mg ( n = 23)) plus TERN-101 10-mg combination therapy”→ Add 'groups' after 'therapy' for clarity.Minor grammatical clarity.
- MINORtypoMethods, Statistical analysis“TERN-510 monotherapy”→ Change to 'TERN-501 monotherapy'.Typo in drug name.
- MINORconsistencyFigure 3 legend“TERN-501 3 mg, P = 0.09645”→ Check if this should be P = 0.0965 or P = 0.009645.Possible extra digit in p-value.
- MINORconsistencyAbstract“TERN-501 (3 mg ( n = 23) or 6 mg ( n = 23)) plus TERN-101 10-mg combination therapy”→ Consider rephrasing for clarity: 'TERN-501 (3 mg or 6 mg) plus TERN-101 10-mg combination therapy'Redundant 'n = 23' for both doses.
- MINORtypoMethods, Statistical analysis“TERN-510 monotherapy”→ Change to 'TERN-501 monotherapy'Typo in drug name.
- MINORconsistencyResults, Efficacy“P = 0.09645”→ Check if this should be 'P = 0.0965' or 'P = 0.9645'Inconsistent number of decimal places; likely a typo.
- MINORclarityResults, Safety“Mean heartrates and corrected QT intervals were stable”→ Change to 'Mean heart rates and corrected QT intervals were stable'Missing space in 'heartrates'.
The published work is robust and generally trustworthy, but an informed reader should weigh the vague data availability statement and the minor internal inconsistencies (e.g., p-value discrepancy, site count mismatch). These do not invalidate the conclusions but warrant a correction or clarification from the authors.
- 1.HIGHstatisticsReconcile the p-value for TERN-501 1 mg in Figure 3b (P = 0.9645) with the text (P = 0.09645) and correct the erroneous value.An internal contradiction in a reported p-value undermines statistical credibility and could mislead readers.
- 2.HIGHreportingClarify the discrepancy between the Methods stating 35 centers and the Results stating 27 sites enrolled patients.An internal inconsistency in the number of study sites raises questions about data accuracy.
- 3.HIGHreportingClarify the statement 'Of the 140 patients to be randomized' in the Methods, which conflicts with the abstract's '162 patients were randomized'.This internal contradiction could confuse readers about the actual sample size and randomization plan.
- 4.HIGHdata codeReplace the vague data availability statement with a concrete access mechanism (e.g., a named data access committee or platform like Vivli) and specify the review process and timeline.A vague 'on request' statement is insufficient for reproducibility and is a common reviewer concern.
- 5.MEDIUMdata codeShare the statistical analysis code (e.g., SAS scripts) in a public repository, or explicitly state that no bespoke code was used beyond standard SAS procedures.Sharing code enhances reproducibility and transparency, even if patient-level data cannot be shared.
- 6.MEDIUMreportingExplicitly reference the CONSORT reporting guideline in the Methods or Reporting Summary.Explicitly naming the guideline strengthens transparency and compliance with reporting standards.
- 7.MEDIUMcopyeditFix the typo 'TERN-510 monotherapy' to 'TERN-501 monotherapy' in the Methods, Statistical analysis section.A drug name typo could cause confusion and appears unprofessional.
- 8.MEDIUMcopyeditCorrect the p-value formatting inconsistency in Figure 3 legend and Results (P = 0.09645 vs P = 0.0965 or P = 0.9645).Inconsistent decimal places in p-values are a copyedit issue that could be misread.
- 9.MEDIUMcopyeditFix the missing space in 'heartrates' to 'heart rates' in the Results, Safety section.Typographical errors detract from the manuscript's professionalism.
- 10.LOWcopyeditRephrase the abstract sentence 'TERN-501 (3 mg ( n = 23) or 6 mg ( n = 23)) plus TERN-101 10-mg combination therapy' for clarity, e.g., 'TERN-501 (3 mg or 6 mg) plus TERN-101 10-mg combination therapy'.The current phrasing is redundant and slightly awkward.
- 11.LOWreportingConsider adding a statement about sex-based analyses, even if not powered, to address the lack of sex-specific results.This would strengthen the biological variables reporting and address potential reviewer concerns.
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.
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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.
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