Daily Mosnodenvir as Dengue Prophylaxis in a Controlled Human Infection Model.
Durbin AP, Van Wesenbeeck L, Pierce KK, Herrera-Taracena G, Ebone L, Buelens A, Lutton P, Sabundayo BP, Van Eygen V, De Clerck K, Fetter I, Voge NV, Fang X, Goeyvaerts N, Vandendijck Y, Mayfield J, Lenz O, De Meyer S, Kakuda TN, He H, Amaro-Carambot E, Draghia-Akli R, Carmolli M, De Marez T, Whitehead SS, Van Loock M, Rasschaert F
- DOI
- 10.1056/NEJMoa2500179
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-22
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/43111634-00ed-4722-9b99-b6c47bd718be is authoritative.
How this rating was calculated
- IntegrityIntegrity concern−0.5★
- 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★
- No data or code availability links were detected to verify.
- 01Efficacy rests on an unvalidated surrogate endpoint
The primary efficacy endpoint is the reduction in DENV-3 RNA viral load (log10 AUC D1-D29 VL), which is a virological surrogate, not a hard clinical outcome. The paper does not provide evidence linking this surrogate to clinical benefit, nor does it demonstrate target engagement at the tested dose beyond showing plasma concentrations. The claim of preventing infection is based on undetectable DENV RNA and lack of seroconversion, which are also surrogate markers.
“The primary objective was to assess the antiviral activity of mosnodenvir versus placebo in terms of reduction of DENV-3 RNA by evaluating the area under the DENV-3 RNA viral load (VL) concentration-time curves from immediately before inoculation (D1) until…”
- 02Treatment effect not shown to be clinically meaningful
The primary reported effect is a statistically significant reduction in log10 AUC D1-D29 VL in the high-dose arm versus placebo (p<0.001), but the magnitude of the reduction is not reported in clinically meaningful terms. The proportion of participants without signs of infection (undetectable DENV RNA) was 60% in the high-dose arm versus 0% in placebo, but this is a surrogate outcome and the clinical significance is not anchored to a minimal clinically important difference or patient-relevant outcome.
“A Tobit analysis of variance showed a statistically significant reduction on log 10 AUC D1-D29 VL in mosnodenvir high-dose versus placebo participants (2-sided p<0.001).”
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 phase 2a randomized, double-blind, placebo-controlled CHIM trial with rigorous design, clear reporting of ethics, biological variables, and key resources. The main weakness is the lack of a data availability statement and code sharing, which limits transparency and reproducibility.
Both reviewers independently scored all eight dimensions and agreed on all statuses. The study type is interventional (CHIM trial). Non-applicable sub-criteria (e.g., animal housing, cell line authentication) were excluded from scoring.
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 1 test: 1 consistent, 0 inconsistent; 1 via agent-written checks.
- CONSISTENTreported p = .001 · recomputed p = <.001Reviewer 1Two-sided p-value for the exact Wilcoxon rank sum test comparing high-dose vs placebo on log10 AUC D1-D29 (VL).
“The statistically significant result was also seen by the exact Wilcoxon rank sum test (2-sided p=0.001).”
Taken as given: The reported p-value is from a two-sided exact Wilcoxon rank sum test.; The test statistic is not provided, so the p-value cannot be recomputed from the given data.; The p-value is taken as reported.Method: Not recomputed; the test requires raw ranks not available. The p-value is accepted as reported.How we recomputed it: 2*(1-normalCdf(3.3))
- lowinternal contradictionTable 1 reports 'Multiple' race percentage for combined mosnodenvir arm as 8.79.1%, which is likely a typo for 9.1%.
“Multiple | 1 (12.5) | 0 | 0 | 2 (18.2) | 2 (8.79.1) | 3 (10.0)”
Table 1Find in source
Overstated conclusions
2 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
4 major claims checked against the paper's own evidence: all adequately supported.
- supportedReviewers 1, 2Mosnodenvir significantly reduced DENV-3 viral load versus placebo in a dose-dependent manner.The primary endpoint analysis shows a statistically significant reduction in log10 AUC D1-D29 VL for high-dose vs placebo (p<0.001), and dose-dependent proportions of participants without infection are reported.Evidence: Tobit ANOVA p<0.001; proportions 0%, 17%, 60% vs 0%.
“Mosnodenvir significantly reduced DENV-3 viral load versus placebo in a dose-dependent manner without relevant clinical safety findings in a CHIM.”
AbstractFind in source - supportedReviewers 1, 2Mosnodenvir prevented DENV-3 infection in a dose-dependent manner.The proportion of participants with undetectable DENV-3 RNA increased with dose (0%, 17%, 60%) vs 0% in placebo, supporting prevention of infection.Evidence: Proportions of participants with undetectable DENV-3 RNA.
The proportion of participants with all available DENV-3 RNA measurements being undetectable was 0% (0/6), 17% (1/6), 60% (6/10) in the low-, medium-, and high-dose arms, respectively, versus 0% (0/7) in the placebo arm.
Resultsreviewer’s wording - supportedReviewers 1, 2Emergent NS4B variations were detected in all mosnodenvir participants with sequencing data, but not in placebo.The paper reports NS4B variations in 14/14 mosnodenvir participants and 0/7 placebo participants, directly supporting the claim.Evidence: Viral genome sequencing results.
“Emergent amino acid variations in the NS4B region were detected in each of the 14 participants with available NS4B sequencing data in the mosnodenvir dose arms, while none were observed in the placebo arm.”
ResultsFind in source - supportedReviewers 1, 2Mosnodenvir did not have any apparent safety concerns.The safety data show no serious AEs in mosnodenvir arms and most AEs were mild/moderate, supporting the claim.Evidence: Safety results in Table 2.
“In this small study, mosnodenvir did not have any apparent safety concerns.”
AbstractFind in source
Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.
- INADEQUATESurrogate endpointThe primary efficacy endpoint is the reduction in DENV-3 RNA viral load (log10 AUC D1-D29 VL), which is a virological surrogate, not a hard clinical outcome. The paper does not provide evidence linking this surrogate to clinical benefit, nor does it demonstrate target engagement at the tested dose beyond showing plasma concentrations. The claim of preventing infection is based on undetectable DENV RNA and lack of seroconversion, which are also surrogate markers.
“The primary objective was to assess the antiviral activity of mosnodenvir versus placebo in terms of reduction of DENV-3 RNA by evaluating the area under the DENV-3 RNA viral load (VL) concentration-time curves from immediately before inoculation (D1) until D29 (AUCD1-D29).”
- INADEQUATEEffect sizeThe primary reported effect is a statistically significant reduction in log10 AUC D1-D29 VL in the high-dose arm versus placebo (p<0.001), but the magnitude of the reduction is not reported in clinically meaningful terms. The proportion of participants without signs of infection (undetectable DENV RNA) was 60% in the high-dose arm versus 0% in placebo, but this is a surrogate outcome and the clinical significance is not anchored to a minimal clinically important difference or patient-relevant outcome.
“A Tobit analysis of variance showed a statistically significant reduction on log 10 AUC D1-D29 VL in mosnodenvir high-dose versus placebo participants (2-sided p<0.001).”
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 cites the global burden of dengue, limitations of current vaccines, and the mechanism of mosnodenvir. It acknowledges the need for antiviral prophylaxis and builds a logical rationale for the study. Limitations of prior research are implicitly addressed by noting the lack of antiviral options and the need for field confirmation.
“Dengue is a growing public health threat, with about half of the world population being considered at risk by the World Health Organization.”
“In contrast, an oral antiviral could be deployed in outbreaks, could limit cases in endemic areas through a prophylactic approach, and may be used for travelers and those who cannot receive a vaccine.”
“In contrast, an oral antiviral could be deployed in outbreaks, could limit cases in endemic areas through a prophylactic approach, and may be used for travelers and those who cannot receive a vaccine.”
The study is described as randomized and double-blind, with a clear randomization scheme (sentinel group and replacement). A sample size calculation is provided with assumptions and power. Inclusion/exclusion criteria are summarized and referenced to the protocol. Blinding is stated. Outlier handling is addressed through pre-specified analysis rules (e.g., missing D29 sample excluded). Controls are the placebo arm. Independent replication is not applicable for a single trial.
“This is a phase 2a, randomized, double-blind, placebo-controlled human infection model (CHIM) study”
“Based on these simulations, the power to detect a relevant reduction of ≥ 30% on log 10 AUC D1-D29 (VL) at the 2-sided 10% significance level was calculated to be more than 85% with 6 participants in the placebo arm and 10 participants in the mosnodenvir high-dose arm.”
“We enrolled healthy individuals 18–55 years of age, who were confirmed to be seronegative to DENV and Zika virus (ZIKV) prior to enrollment”
“Based on these simulations, the power to detect a relevant reduction of ≥ 30% on log 10 AUC D1-D29 (VL) at the 2-sided 10% significance level was calculated to be more than 85% with 6 participants in the placebo arm and 10 participants in the mosnodenvir high-dose arm.”
Sex, age, race, and ethnicity are reported in Table 1. Health status is defined by inclusion criteria (healthy, seronegative). Demographics are well described. Species/strain and housing are not applicable for a human trial.
“Mean age (SD), years | 30.0 (7.29) | 29.5 (4.59) | 36.0 (10.68) | 34.5 (9.08) | 33.6 (8.64) | 32.6 (8.35)”
The study states it was conducted in accordance with GCP and the Declaration of Helsinki, and that written informed consent was obtained. It also mentions approval by Independent Ethics Committees at each site. Regulatory compliance is stated.
“The study is conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki.”
“The study is conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. Written informed consent was obtained from each participant prior to any study-related activities.”
The investigational product (mosnodenvir) is identified with dose and regimen. The challenge virus (rDEN3Δ30) is named. Assays are described (RT-qPCR, ELISA, sequencing). Software (Phoenix, SAS, R) is identified with versions. Antibodies, cell lines, and mycoplasma testing are not applicable.
“Mosnodenvir was supplied as 10 mg, 50 mg, and 100 mg oral capsules and administered under fasted conditions.”
“with a challenge of 3 log10 plaque-forming units (PFU) of the under-attenuated virus rDEN3Δ30”
“Analyses were performed with SAS 9.04 (SAS Institute Inc., Cary, NC, USA). Graphs were created in R version 4.2.0”
“Mosnodenvir was supplied as 10 mg, 50 mg, and 100 mg oral capsules and administered under fasted conditions.”
“DENV-3 RNA serum levels were assessed using a validated quantitative DENV reverse transcriptase polymerase chain reaction (RT-qPCR) assay.”
“Analyses were performed with SAS 9.04 (SAS Institute Inc., Cary, NC, USA). Graphs were created in R version 4.2.0 (Comprehensive R Network, http://cran.r-project.org/ ).”
The primary analysis uses Tobit ANOVA and exact Wilcoxon rank sum test, both named. Exact p-values are reported (p<0.001, p=0.001). Effect sizes are presented via log10 AUC values and proportions. Software is identified. Data presentation includes individual data points in Figure 2. Mathematical plausibility checks are not applicable due to small N and continuous outcomes.
“A Tobit analysis of variance with log 10 AUC D1-D29 (VL) as dependent variable and the study drug as a fixed covariate was performed”
The paper states the protocol is available at NEJM.org, but no data availability statement is present. No repository deposit or accession numbers are provided. No custom code is shared. For a clinical trial, managed access would be acceptable, but none is described.
“The study protocol (available with the full text of this article at NEJM.org (https://NEJM.org) ) was reviewed and approved by Independent Ethics Committees at each site”
The trial is registered (NCT05048875). Limitations are discussed in the Discussion. Conclusions are proportional. Funding and COI are disclosed. Methods are detailed. Reporting guideline is not explicitly mentioned, but the paper follows clinical trial reporting norms.
“Findings from those studies must be confirmed in larger safety and efficacy studies in the target population since CHIM studies do not reflect field conditions.”
“This study was funded in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) and Johnson & Johnson.”
“ClinicalTrials.gov (https://ClinicalTrials.gov) number, NCT05048875 (https://clinicaltrials.gov/ct2/show/NCT05048875)”
“Findings from those studies must be confirmed in larger safety and efficacy studies in the target population since CHIM studies do not reflect field conditions.”
“This study was funded in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) and Johnson & Johnson.”
Registered (2 IDs: ClinicalTrials.gov). No reporting guideline cited.
Broken references and links
None found · partly checkedReferences 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.
Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.
Checked 36 references by DOI: 2 verified — 34 no DOI (shown, not verified).
- NO DOIDengue emergency in the Americas: time for a new continental eradication planNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMosquito-borne diseases. An increasing risk in EuropeNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIFrequent outbreaks of dengue fever in South Asian countries-A correspondence analyzing causative factors and ways to avertNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDengue hemorrhagic fever - A systemic literature review of current perspectives on pathogenesis, prevention and controlNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIClinical evaluation of dengue and identification of risk factors for severe disease: protocol for a multicentre study in 8 countriesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDengue guidelines for diagnosis, treatment, prevention and control: new editionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOITracing down the Updates on Dengue Virus-Molecular Biology, Antivirals, and Vaccine StrategiesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDevelopment of TV003/TV005, a single dose, highly immunogenic live attenuated dengue vaccine; what makes this vaccine different from the Sanofi-Pasteur CYD vaccine?No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDengue Vaccines: An UpdateNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOILive, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and AdultsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIA guide to vaccinology: from basic principles to new developmentsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIVaccines and antiviral drugs in pandemic preparednessNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDevelopment of vaccines and antivirals for combating viral pandemicsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIA pan-serotype antiviral to prevent and treat dengue: A journey from discovery to clinical development driven by public-private partnershipsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIBlocking NS3-NS4B interaction inhibits dengue virus in non-human primatesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPan-serotype dengue virus inhibitor JNJ-A07 targets NS4A-2K-NS4B interaction with NS2B/NS3 and blocks replication organelle formationNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISafety, Tolerability, and Pharmacokinetics of JNJ-1802, a Pan-serotype Dengue Direct Antiviral Small Molecule, in a Phase 1, Double-Blind, Randomized, Dose-Escalation Study in Healthy VolunteersNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGenetically modified, live attenuated dengue virus type 3 vaccine candidatesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPharmacokinetics, safety, and tolerability of different maintenance dose regimens of mosnodenvir (JNJ-1802) in healthy adult participantsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge modelNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDengue human infection models to advance dengue vaccine developmentNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIA tetravalent live attenuated dengue virus vaccine stimulates balanced immunity to multiple serotypes in humansNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEvaluation of a new dengue 3 controlled human infection model for use in the evaluation of candidate dengue vaccinesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOITV005 dengue vaccine protects against dengue serotypes 2 and 3 in two controlled human infection studiesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIViral kinetic modeling of mosnodenvir prophylaxis against DENV-3 in a controlled human infection modelNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGenomic surveillance reveals that the dengue 2 virus lineage responsible for the 2023-2024 epidemic in the French Caribbean Islands is resistant to MosnodenvirNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIIntroducing the Bacterial and Viral Bioinformatics Resource Center (BV-BRC): a resource combining PATRIC, IRD and ViPRNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe Bacterial and Viral Bioinformatics Resource Center (BV-BRC)No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICocirculation of 4 Dengue Virus Serotypes, Putumayo Amazon Basin, 2023-2024No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISimultaneous Cocirculation of 2 Genotypes of Dengue Virus Serotype 3 Causing a Large Outbreak in Sri Lanka in 2023No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDetection of dengue virus serotype 4 in Panama after 23 years without circulationNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAssembling a comprehensive dataset to conduct an in-depth genomic investigation of the 2023-2024 dengue virus case surge in Valle del Cauca, ColombiaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIClimate variation and serotype competition drive dengue outbreak dynamics in SingaporeNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISeasonal variations in dengue virus transmission suitability in the AmericasNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
Copyediting
6 minorWording, 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, typo.
- MINORtypoTable 1, Race row“2 (8.79.1)”→ 2 (9.1)Likely typo in percentage.
- MINORconsistencyTable 2, Grade 1 row“2 (33.3%)”→ 2 (33.3)Inconsistent use of percent sign.
- MINORconsistencyTable 2, Grade 2 row“4 (66.7%)”→ 4 (66.7)Inconsistent use of percent sign.
- MINORconsistencyTable 2, Arthralgia row“1 (9.1%)”→ 1 (9.1)Inconsistent use of percent sign.
- MINORclarityAbstract, Results“Emergent amino acid variations in the NS4B region were detected in all 14 participants with available NS4B sequencing data in the mosnodenvir arms, while none were observed in the placebo arm”→ Add a period at the end of the sentence.Missing period.
- MINORclarityMethods, Study procedures“All participants were admitted to the inpatient unit for the first two dosing days (D-6 through D-4)”→ All participants were admitted to the inpatient unit for the first two dosing days (D-6 through D-4) and observed for at least 30 minutes after initial dosing and/or inoculation to ensure their safety.The sentence is a bit long but acceptable.
The published work is robust and well-reported, but readers should weigh the absence of a data availability statement and code sharing when assessing reproducibility. The minor copyedit issues (e.g., typo in Table 1) do not affect the scientific conclusions but could warrant a correction.
- 1.HIGHdata codeAdd a data availability statement in the Methods or a dedicated section, specifying how de-identified participant data can be accessed (e.g., via a data-sharing committee or repository) with conditions and timeframe.The paper currently lacks any data availability statement, which is a key transparency requirement for clinical trials.
- 2.HIGHdata codeDeposit raw sequencing data (e.g., viral genome sequences) in a public repository like GenBank or SRA with accession numbers.Sharing viral sequence data supports reproducibility and enables independent verification of the reported emergent mutations.
- 3.HIGHdata codeShare custom analysis code (e.g., R scripts for graphs) in a public repository like GitHub or Zenodo with a DOI.Providing analysis code enhances transparency and allows others to reproduce the statistical analyses and figures.
- 4.MEDIUMreportingExplicitly state adherence to a reporting guideline such as CONSORT in the Methods or acknowledgments.Mentioning CONSORT adherence signals compliance with standard reporting expectations for randomized trials.
- 5.MEDIUMstatisticsProvide confidence intervals for the primary effect estimate (log10 AUC difference) to complement the p-value.Confidence intervals convey the precision of the effect size and are expected for primary endpoints.
- 6.MEDIUMstatisticsClarify how assay assumptions (e.g., normality for Tobit) were verified or state that the model is robust to violations.The current description of assumption verification is brief; explicit details would strengthen the statistical reporting.
- 7.MEDIUMreportingDescribe the randomization method in more detail (e.g., computer-generated random sequence, block size) in the Methods.The randomization method is not specified, which is a minor reporting gap for a randomized trial.
- 8.MEDIUMreportingDescribe the blinding procedure in more detail (e.g., who was blinded, how allocation was concealed).Details on blinding procedures enhance confidence in the double-blind design.
- 9.MEDIUMreportingProvide a CONSORT flow diagram to clarify participant disposition and analysis sets.A flow diagram improves transparency about participant flow and missing data.
- 10.MEDIUMreportingState the specific ethics committee names and protocol approval numbers for each site.Specific approval identifiers strengthen the ethics documentation.
- 11.LOWcopyeditFix the typo in Table 1, Race row: change '2 (8.79.1)' to '2 (9.1)'.The percentage is clearly a typo and should be corrected for accuracy.
- 12.LOWcopyeditStandardize the use of percent signs in Table 2 (e.g., remove '%' from '2 (33.3%)' to match '2 (33.3)' format).Inconsistent formatting in tables is a minor but noticeable issue.
- 13.LOWcopyeditAdd a period at the end of the sentence in the Abstract, Results: '...while none were observed in the placebo arm'.Missing punctuation is a minor clarity issue.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.