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Kaimen Rigor review

Low-Dose Yellow Fever Vaccine in Adults in Africa.

Kimathi D, Juan-Giner A, Bob NS, Orindi B, Namulwana ML, Diatta A, Cheruiyot S, Fall G, Dia M, Hamaluba MM, Nyehangane D, Karanja HK, Gitonga JN, Mugo D, Omuoyo DO, Hussein M, Oloo E, Kamau N, Wafula J, Bendera J, Silvester N, Mwavita J, Joshua M, Mwendwa J, Agababyona C, Ngetsa C, Aisha N, Moki F, Buluku T, Munene M, Mwanga-Amumpaire J, Lutwama J, Kayiwa J, Kamaara E, Barrett AD, Kaleebu P, Bejon P, Sall AA, Grais RF, Warimwe GM, NIFTY Investigators

DOI: 10.1056/NEJMoa2407293
Record issued: 2026-08-10
Engine: 7.29.0
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/d56bbc05-b45b-4db4-9585-aa95260c74a7 is authoritative.

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−0.5★
ReportingKey resources not met−0.5★
ReportingData & code availability not met−0.5★
ReportingBiological variables partially met−0.25★
ReportingEthical approvals partially met−0.25★

Model-reported confidence: moderateReviewer agreement: moderateEngine: 7.29.0Source: full text

Not verified in this report

No reported statistical tests were found to recompute.

Biggest issues

01Key resources not identified
highDisclosurereviewer-assessedFull detail
The investigational product (vaccine) is identified by manufacturer and substrain, but dose preparation details are only referenced in the supplementary appendix, and statistical software is not named.
“the Institut Pasteur de Dakar 17D-204 yellow fever vaccine at a standard dose (13,803 IU) or at a fractional dose of 1000 IU, 500 IU, or 250 IU.”
AbstractFind in source
02Data and code not shared
highDisclosurereviewer-assessedFull detail
The data availability statement is vague and does not provide a concrete access route. No code or data repository is mentioned.

Findings by category

101ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions · partly checked 03AuthenticityNone found 404DisclosureReporting gaps 05AvailabilityNone found 06Copyedit10 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 methodologically rigorous, well-registered, double-blind randomized noninferiority trial with a sound scientific premise, a priori powering, CI-based estimation, and internally consistent tabulated results. Its main weaknesses are documentation gaps — no explicit informed-consent statement, a vague data-sharing reference without a concrete access route, unnamed statistical software/test, and unreported weight and race/ethnicity — plus minor copyedit issues; none of these undermine the core conclusions.

Three independent reviewer runs of the same model were reconciled; they diverged on biological variables (2 warn vs 1 pass), key resources (1 pass / 1 warn / 1 fail), and statistical analysis (2 pass vs 1 warn), and these splits are reflected in the evidence and confidence. The statistics verification component recomputed 0 tests (coverage limited to tests with a statistic+df or effect+CI), so reported statistics were not machine-verified; the citation check found no retracted or not-found references; the copyedit pass flagged 10 minor issues.

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

lowinternal contradiction
The 500-IU group's proportion of participants with an adverse event is reported as 63% in the Results text but 62% in Table 3; 75/120 = 62.5%, so both are legitimate roundings and this is not an arithmetic error.
“75 (63%) of the participants in the 500-IU group reported 163 adverse events”
Table 3Find in source

Overstated conclusions

1 finding · worst low

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.

Conclusions only partially backed by the presented evidenceAssessed

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

partialReviewers 1, 3
The findings support the WHO recommendation to use one fifth of a standard dose in epidemics when the standard dose is 500 IU or higher.
The trial data support the dose range, but the leap to the operational WHO-policy recommendation rests on extrapolation beyond the trial's direct comparisons.
Evidence: Noninferiority of 500 IU and 1000 IU at day 28; the 500-IU dose is roughly one 27th of the 13,803 IU standard, so 'one fifth' of a 500 IU-minimum standard is within the noninferior range shown.
“The findings from our trial provide support to the WHO recommendation that one fifth of a standard dose of vaccine be considered for use in epidemics, provided that the standard dose in the vaccine used is 500 IU or higher.”
Discussion ¶2Find in source
supportedReviewers 1, 2, 3
A yellow fever vaccination dose as low as 500 IU was noninferior to the standard dose of 13,803 IU for producing seroconversion within 28 days.
The data show that the 500-IU dose had a difference in seroconversion of 0.01 percentage points (95% CI -5.0 to 5.1) in ITT and -1.8 (95% CI -6.7 to 3.2) in PP, both with lower bounds above -10.
Evidence: Table 2 and Figure 2 show the differences and CIs.
“A yellow fever vaccination dose as low as 500 IU was noninferior to the standard dose of 13,803 IU for producing seroconversion within 28 days.”
AbstractFind in source
supportedReviewers 1, 3
The 250-IU dose did not meet the noninferiority criteria in the per-protocol analysis at 28 days.
The per-protocol analysis shows a difference of -6.7 percentage points (95% CI -11.7 to 1.6), with the lower bound below -10.
Evidence: Table 2 and Figure 2B.
“Therefore, the 250-IU dose did not meet the noninferiority criteria in the per-protocol analysis at 28 days.”
ResultsFind in source
supportedReviewers 1, 2
Postvaccination viremia was infrequent.
Only 12 of 480 participants (2.5%) had detectable viremia, which is low.
Evidence: Results, immunogenicity paragraph
“Of the total trial population, 12 participants (2.5%; 95% CI, 1.3 to 4.3) were positive for yellow fever vaccine viremia between days 2 and 10”
ResultsFind in source
supportedReviewer 1
The incidence of adverse events was similar in the four groups.
The percentages of participants with adverse events were 55%, 62%, 57%, and 54% across groups, showing no major differences.
Evidence: Table 3.
“The incidence of adverse events was similar in the four groups.”
ResultsFind in source
supportedReviewer 2
The 250-IU dose met the noninferiority criterion in the intention-to-treat analyses but did not meet the noninferiority criterion in per-protocol analyses.
The intention-to-treat analysis for 250 IU shows a difference of -4.4 percentage points (95% CI -9.4 to 0.7), with lower bound -9.4 > -10, meeting noninferiority. The per-protocol analysis shows -6.7 percentage points (95% CI -11.7 to -1.6), with lower bound -11.7 < -10, not meeting noninferiority.
Evidence: Table 2, Figure 2, Results text.
The 250-IU dose met the noninferiority criterion in the intention-to-treat analyses... but did not meet the noninferiority criterion in per-protocol analyses.
Discussionreviewer’s wording
supportedReviewers 2, 3
Lower doses led to considerably lower neutralization titers and lower levels of seroconversion at day 10, even though these differences were erased by the peak antibody responses seen at day 28.
Table 2 shows that at day 10, seroconversion rates were 50% for 250 IU, 61% for 500 IU, 61% for 1000 IU, vs 85% for standard dose. GMTs were also lower. By day 28, seroconversion rates were similar (94-98%).
Evidence: Table 2: Day 10 and Day 28 seroconversion rates and GMTs.
“Our trial showed that lower doses led to considerably lower neutralization titers and lower levels of seroconversion at day 10, even though these differences were erased by the peak antibody responses seen at day 28.”
Table 2Find in source

Data authenticity concerns

None found

An adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.

Checked — nothing surfaced.

Reporting gaps

4 findings · worst high

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.

Data and code not sharedAssessed
Key resources not identifiedAssessed
Biological variables underreported (sex, age, strain)Assessed
Ethics/consent reporting incompleteAssessed

Eight Dimensions4 pass · 2 warn · 2 fail

The paper cites prior trials on fractional dosing, WHO recommendations, and a Brazilian dose-finding study. It acknowledges that previous data were not formally analyzed for noninferiority and may not be generalizable to adults in Africa or other vaccine substrains. The rationale for the trial is clearly linked to the need for dose-sparing strategies during outbreaks.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The scientific premise is well-established, with prior work cited and limitations addressed.

Evidence

“Previous data from Brazil (substrain 17DD) had indicated that immunogenicity is reduced at doses below 587 IU.”

Introduction ¶2Find in source

“However, these data were not formally analyzed for noninferiority and may not be generalizable to adults in Africa or vaccines from other substrains.”

Introduction ¶2Find in source

paraphrase[Background, paragraph 1-2]

“The paper argues that vaccine supply is limited and that fractional doses could be a dose-sparing strategy, leading to the trial of noninferiority of fractional doses.”

PASSReviewer 2· 95% conf

The paper clearly establishes the scientific premise by citing prior research on fractional yellow fever vaccine doses, acknowledging limitations of prior work, and providing a logical rationale for the study.

Evidence

paraphrase[Introduction, paragraph 1-2]

“However, because the potency of doses can vary substantially according to manufacturer and batch, the generalizability of these data may be limited. ... This trial involved young men with a mean age of 19.4 years, and hence further data are needed.”

paraphrase[Introduction, paragraph 3]

“We conducted the Noninferiority Fractional-Doses Trial for Yellow Fever Vaccine (NIFTY) to assess the immunogenicity of fractional doses (1000 IU, 500 IU, or 250 IU) of the 17D-204 yellow fever vaccine ... for noninferiority to the standard vaccine dose (13,803 IU).”

paraphrase[Methods, Discussion]

“The trial includes adults in Africa, both sexes, and HIV-positive participants, and uses a noninferiority design, addressing the limitation of the Brazilian trial which was limited to young men and lacked formal noninferiority analysis.”

PASSReviewer 3· 90% conf

The rationale is well established: vaccine supply is limited, the minimum dose for seroconversion is unknown, and prior evidence has important gaps. The hypothesis follows directly from cited evidence.

Evidence

“However, because the potency of doses can vary substantially according to manufacturer and batch, the generalizability of these data may be limited.”

Introduction ¶2Find in source

“We conducted the Noninferiority Fractional-Doses Trial for Yellow Fever Vaccine (NIFTY) to assess the immunogenicity of fractional doses (1000 IU, 500 IU, or 250 IU) of the 17D-204 yellow fever vaccine manufactured by the Institut Pasteur de Dakar in Dakar, Senegal, for noninferiority to the standard vaccine dose (13,803 IU).”

IntroductionFind in source

Randomization was performed by an independent firm using a computerized system with fixed blocks. The trial is described as double-blind. A power analysis is provided with 90% power at a one-sided alpha of 0.025. Inclusion/exclusion criteria are clearly defined. The analysis populations (ITT and per-protocol) are specified, and missing data are handled by random distribution.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The study design is rigorous, with adequate randomization, blinding, power analysis, and inclusion/exclusion criteria.

Evidence

“Randomization was performed in fixed blocks prepared in advance by an independent firm (DiagnoSearch LifeSciences) with the use of a computerized randomization system, with equal allocation to each of the four dose groups.”

MethodsFind in source

paraphrase[Methods, Trial Design and Participants]

“This double-blind, randomized, noninferiority trial was conducted...”

“Assuming a 95% incidence of seroconversion, we estimated that 120 participants per dose group would provide the trial with 90% power to determine noninferiority at a margin of −10 percentage points and at a one-sided alpha level of 0.025.”

MethodsFind in source

PASSReviewer 2· 95% conf

The study design is rigorous with clear randomization, predefined populations, and sample size calculation, though blinding details are not fully described.

Evidence

MethodsFind in source

“This double-blind, randomized, noninferiority trial was conducted at the Kenya Medical Research Institute−Wellcome Trust Research Programme Clinical Trials Facility in Kilifi County, Kenya, and the Epicenter Mbarara Research Centre in Mbarara City, Uganda.”

MethodsFind in source

PASSReviewer 3· 90% conf

A well-designed randomized, double-blind, noninferiority trial with a stated randomization method, a priori power calculation, and defined analysis populations.

Evidence

MethodsFind in source

“we estimated that 120 participants per dose group would provide the trial with 90% power to determine noninferiority at a margin of −10 percentage points and at a one-sided alpha level of 0.025.”

MethodsFind in source

“This double-blind, randomized, noninferiority trial was conducted at the Kenya Medical Research Institute−Wellcome Trust Research Programme Clinical Trials Facility in Kilifi County, Kenya”

AbstractFind in source

The paper reports sex (62% women) and age (mean 39.7 years) in Table 1, and health status (HIV, previous medical illness) is partially reported. However, weight is not reported, and race/ethnicity is not mentioned. For a human trial, these are expected but not critical for vaccine response. The absence of weight and race/ethnicity constitutes incomplete reporting of biological variables.

Sub-criteria

demographicsINADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthINADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

Sex and age are reported, but weight and race/ethnicity are not reported for human participants.

Evidence

paraphrase[Table 1]

“Female — 78 (65), 68 (57), 71 (59), 79 (66)”

paraphrase[Table 1 and Results]

“Mean age is reported as 39.7±11.5 years, but weight is not mentioned anywhere in the paper.”

absence[Entire paper]

Race/ethnicity is not reported.

WARNReviewer 2· 65% conf

Sex and age are reported, but weight and race/ethnicity are not, leading to a warning.

Evidence

paraphrase[Table 1]

“Age — yr | 40.2±11.0 | 38.5±11.7 | 40.4±11.6 | 39.8±11.9 | Sex — no. (%) | Female | 78 (65) | 68 (57) | 71 (59) | 79 (66) | Male | 42 (35) | 52 (43) | 49 (41) | 41 (34)”

absence[Table 1, Methods]

Weight is not reported.

absence[Table 1, Methods]

Race/ethnicity is not reported.

PASSReviewer 3· 85% conf

Key participant characteristics (age, sex, HIV status, comorbidities) are reported; both sexes are enrolled so a single-sex justification is not required.

Evidence

“The mean (±SD) age at enrollment was 39.7±11.5 years, the majority of the participants (296 [62%]) were women, and 38 (8%) were HIV-positive at baseline.”

ResultsFind in source

paraphrase[Table 1]

“Table 1 reports per-group age, sex, temperature, yellow-fever seropositivity, previous flavivirus infection, previous medical illness, HIV status, and CD4 count for all 480 participants.”

The paper lists four ethics committees that approved the trial protocol. However, there is no explicit statement that informed consent was obtained from participants. The paper mentions community meetings but not individual consent. Regulatory compliance with the Declaration of Helsinki or other frameworks is not explicitly stated, though regulatory approvals are mentioned.

Sub-criteria

iacuc statementN/A

informed consentNOT REPORTED

irb ethics statementADEQUATE

regulatory complianceINADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

Ethics approval is documented, but informed consent is not explicitly stated in the main text.

Evidence

“The trial protocol was reviewed and approved by the Oxford Tropical Research Ethics Committee, the Kenya Medical Research Institute Scientific and Ethics Review Unit, Mbarara University of Science and Technology Research Ethics Committee, and the Uganda National Council of Sciences and Technology.”

MethodsFind in source

absence[Methods, Trial Design and Participants]

Informed consent is not mentioned.

“Regulatory approval was obtained from the Kenya Pharmacy and Poisons Board and the Uganda National Drug Authority.”

MethodsFind in source

WARNReviewer 2· 90% conf

Ethics approval from named committees is documented, but an explicit statement of informed consent is missing, and regulatory compliance with a recognized framework is not stated.

Evidence

MethodsFind in source

absence[Methods, Trial Oversight, Procedures]

Informed consent is not mentioned.

paraphrase[Methods, Trial Oversight]

“Regulatory approval from Kenya Pharmacy and Poisons Board and Uganda National Drug Authority is mentioned, but adherence to the Declaration of Helsinki or other framework is not stated.”

WARNReviewer 3· 70% conf

Named ethics committees and regulatory bodies approved the trial, but informed consent is not explicitly described anywhere in the manuscript text.

Evidence

MethodsFind in source

“Regulatory approval was obtained from the Kenya Pharmacy and Poisons Board and the Uganda National Drug Authority.”

MethodsFind in source

absence[Methods, Trial Design and Participants]

Informed consent is not explicitly stated.

The vaccine is identified as 'Institut Pasteur de Dakar 17D-204 yellow fever vaccine' with doses specified. However, the method for preparing the fractional doses is only referenced to the supplementary appendix. No lot number or formulation details are given in the main text. The statistical software used for analysis is not mentioned. These omissions result in a fail as no applicable sub-criterion is fully adequate.

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedNOT REPORTED

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

The vaccine is adequately identified, but statistical software is not reported.

Evidence

“The participants were randomly assigned to receive vaccination with yellow fever vaccine at a full standard dose (13,803 IU) or at a fractionated dose of 1000 IU, 500 IU, or 250 IU.”

MethodsFind in source

absence[Methods, Statistical Analysis]

Statistical software is not reported.

FAILReviewer 2· 60% conf

The investigational product (vaccine) is identified by manufacturer and substrain, but dose preparation details are only referenced in the supplementary appendix, and statistical software is not named.

Evidence

“the Institut Pasteur de Dakar 17D-204 yellow fever vaccine at a standard dose (13,803 IU) or at a fractional dose of 1000 IU, 500 IU, or 250 IU.”

AbstractFind in source

paraphrase[Methods, Trial Design and Participants]

“The various dose levels were prepared according to the manufacturer’s instructions (see the in the , available with the full text of this article at NEJM.org).”

absence[Methods, Statistical Analysis]

Statistical software is not identified.

PASSReviewer 3· 80% conf

The investigational product (the vaccine) is identified by manufacturer, substrain, and dose; the bench-resource criteria are not applicable to this trial.

Evidence

paraphrase[Abstract / Methods]

“we assigned adults ... to receive vaccination with the Institut Pasteur de Dakar 17D-204 yellow fever vaccine at a standard dose (13,803 IU) or at a fractional dose of 1000 IU, 500 IU, or 250 IU.”

The paper reports differences in seroconversion rates with 95% confidence intervals, which is standard for noninferiority trials. The power analysis and alpha level are stated. Assumptions are handled by design (large sample, binary outcome). Exact p-values are not reported because the primary analysis uses confidence intervals, which is acceptable. Statistical software is not identified, which is a minor gap. Data presentation includes per-group n and confidence intervals.

Sub-criteria

tests namedINADEQUATE

exact p valuesN/A

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedNOT REPORTED

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 80% conf

The analysis is appropriate for a noninferiority trial, with effect sizes and confidence intervals reported. The specific test is not named, but the approach is clear.

Evidence

“Noninferiority was shown if the lower boundary of the 95% confidence interval of the difference in the incidence of seroconversion was greater than −10 percentage points.”

Statistical analysisFind in source

absence[Methods, Statistical Analysis]

Statistical software is not named.

paraphrase[Table 2]

“Incidence of Seroconversion (95% CI) — 108/115, 94 (88 to 97)”

WARNReviewer 2· 80% conf

Effect sizes with confidence intervals are reported, and data presentation is adequate, but the specific statistical test is not named, assumptions are not verified, and software is not identified.

Evidence

“Noninferiority was shown if the lower boundary of the 95% confidence interval of the difference in the incidence of seroconversion was greater than −10 percentage points.”

Statistical analysisFind in source

“The difference in the incidence of seroconversion between the 1000-IU dose and the standard dose was 0.01 percentage points (95% CI, −5.0 to 5.1) in the intention-to-treat population”

Table 2Find in source

absence[Methods, Statistical Analysis]

Statistical software is not identified.

PASSReviewer 3· 80% conf

The primary analysis is reported by estimation with 95% CIs (field norm), and all tabulated proportions and counts are internally consistent. Statistical software is not identified.

Evidence

“Noninferiority was shown if the lower boundary of the 95% confidence interval of the difference in the incidence of seroconversion was greater than −10 percentage points.”

Statistical analysisFind in source

paraphrase[Results, Immunogenicity]

“The difference in the incidence of seroconversion between the factional doses and the standard dose at 28 days was −4.4 percentage points (95% CI, −9.4 to 0.7) with the 250-IU dose, and 0.01 percentage points (95% CI, −5.0 to 5.1) with both the 500-IU and 1000-IU doses in the intention-to-treat analysis.”

paraphrase[Table 3]

“Adverse-event counts sum correctly: 122+163+136+125 = 546; severity totals 415+128+3 = 546; relatedness 111+70+365 = 546; participants with AEs 66+75+68+65 = 274.”

The paper states 'A data sharing statement provided by the authors is available with the full text of this article at NEJM.org' but does not specify the content of that statement. Without knowing the details, this is insufficient. The trial registration number is provided, but that is not a data repository. No code sharing is mentioned. For a clinical trial, a concrete data access mechanism (e.g., managed access platform) is expected.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementINADEQUATE

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 90% conf

The data availability statement is vague and does not provide a concrete access route. No code or data repository is mentioned.

Evidence

paraphrase[End of Discussion, before References]

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

absence[Entire paper]

No repository or code is mentioned.

FAILReviewer 2· 50% conf

A data sharing statement is referenced but not provided in the text, and no repository deposit or code sharing is mentioned.

Evidence

paraphrase[End of manuscript]

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

absence[Entire paper]

No repository deposit is mentioned.

absence[Entire paper]

No code sharing is mentioned.

WARNReviewer 3· 60% conf

A data sharing statement is referenced as available at NEJM.org, but its concrete access route is not stated in the text; repository deposit, accession numbers, and code sharing are not applicable.

Evidence

paraphrase[End of article (Funding/Acknowledgments)]

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

The trial is registered at ClinicalTrials.gov (NCT04059471). Methods are sufficiently detailed for replication. All pre-specified outcomes are reported, including negative findings for the 250-IU dose in per-protocol analysis. Limitations are explicitly discussed (statistical power, generalizability, long-term follow-up). Conclusions are proportional to the evidence. Funding and conflicts of interest are disclosed. The only missing element is reference to a reporting guideline (e.g., CONSORT), which is minor.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The trial is registered, methods are detailed, limitations are discussed, and conclusions are proportional. A reporting guideline is not referenced.

Evidence

“NIFTY ClinicalTrials.gov number, NCT04059471”

AbstractFind in source

“Our trial has limitations, including with regard to statistical power.”

Discussion ¶5Find in source

absence[Methods]

No reporting guideline is mentioned.

PASSReviewer 2· 90% conf

The manuscript is well-structured with detailed methods, registration, and discussion of limitations, though a reporting guideline is not referenced and the COI statement is only available as a disclosure form.

Evidence

“NIFTY ClinicalTrials.gov number, NCT04059471”

AbstractFind in source

paraphrase[Discussion]

“Our trial has limitations, including with regard to statistical power. ... we cannot exclude lower margins of noninferiority that may be relevant in some circumstances.”

“Supported by grants from the European and Developing Countries Clinical Trials Partnership (EDCTP- RIA2016V-1633) and the Wellcome Trust (203077_Z_16_Z).”

End of manuscriptFind in source

PASSReviewer 3· 85% conf

Methods, trial registration, outcome reporting, limitations, and funding/COI are all reported; the only gap is that no reporting guideline (e.g., CONSORT) is explicitly referenced.

Evidence

“NIFTY ClinicalTrials.gov number, NCT04059471”

AbstractFind in source

paraphrase[End of article]

“Supported by grants from the European and Developing Countries Clinical Trials Partnership (EDCTP-RIA2016V-1633) and the Wellcome Trust (203077_Z_16_Z).”

“Our trial has limitations, including with regard to statistical power.”

DiscussionFind in source

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

ClinicalTrials.gov

NCT04059471

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 18 references by DOI: 16 verified — 2 no DOI (shown, not verified).

NO DOI
Yellow fever vaccine: WHO position on the use of fractional doses — June 2017
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A simple micro-culture method for the study of group B arboviruses
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

2 data/code links checked; 1 live.

datahttps://clinicaltrials.gov/study/NCT04059471LIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttps://www.nejm.org/UNVERIFIEDHTTP 403
Liveness indeterminate — content not checked.

Copyediting

10 minor

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

No major wording or formatting errors. 10 minor suggestions below.

10 copyedit issues flagged: mostly typo, consistency, clarity.

MINORtypoResults, paragraph 2
“factional doses”
→ fractional doses
Typo: 'factional' should be 'fractional'.
MINORtypoMethods, Statistical Analysis
“postran-domization”
→ post-randomization
Unnecessary hyphen and misspelling: 'postran-domization' should be 'post-randomization'.
MINORconsistencyTable 2 footnote
“The widths of the confidence intervals were not adjusted for multiplicity and may not be used in place of hypothesis testing except for the day-28 and safety outcomes.”
→ The widths of the confidence intervals were not adjusted for multiplicity and may not be used in place of hypothesis testing, except for the day-28 and safety outcomes.
Add a comma for clarity.
MINORtypoMethods, Trial Design and Participants
“see the in the , available with the full text”
→ see the Supplementary Appendix, available with the full text
Incomplete sentence placeholder.
MINORconsistencyFunding section
“EDCTP- RIA2016V-1633”
→ EDCTP-RIA2016V-1633
Extra space in grant number.
MINORclarityMethods, Trial Oversight
“The funders had no role in the trial design, data collection and analysis, preparation of the manuscript, or decision to submit the manuscript for publication.”
→ No change needed, but consider adding a period after the sentence.
Sentence is clear.
MINORtypoResults, Immunogenicity
“factional doses”
→ fractional doses
Misspelling of 'fractional'.
MINORclarityMethods, Trial Procedures
“see the in the , available with the full text”
→ Repair the broken cross-reference to the supplementary appendix (e.g., 'see the Supplementary Appendix, available with the full text').
The sentence contains a garbled XREF artifact: 'see the in the , available'.
MINORconsistencyResults vs. Table 3
“75 (63%) of the participants in the 500-IU group”
→ Align the rounding with Table 3 (75 (62)) or state 62.5%.
75/120 = 62.5%; the text rounds up to 63% while Table 3 rounds to 62%.
MINORotherEnd of article
“up.”
→ Remove the stray fragment.
A dangling 'up.' fragment appears before the figures section.

Kaimen Rigor Action ItemsFinal pass before journal submission

As a post-publication audit, the published trial is robust: its design, analysis, and conclusions hold up, and an informed reader should treat the reported results as credible. The main things a reader should weigh are the documentation gaps — the absence of an explicit informed-consent statement, the data-sharing statement that only points to NEJM.org without stating access conditions, and the unnamed statistical software/test — which are reporting deficiencies that would warrant a correction/clarification note rather than a retraction-level concern. The minor 500-IU rounding inconsistency (63% text vs 62% Table 3) is benign.

1.
HIGHethics
Add a correction/clarification note (Methods, Trial Design and Participants or Trial Oversight) explicitly stating that written informed consent was obtained from all participants and describing the consent process.
All three reviewers flagged that no informed-consent statement appears in the text, which is a required reporting element for a human trial.
2.
HIGHdata code
Publish the actual data sharing statement content in the article, specifying the concrete access route (e.g., managed-access platform, data-access committee, request conditions and timeframe) rather than only referencing a statement at NEJM.org.
The current statement is a placeholder that does not tell readers how to obtain the data, which is the dimension's single failing criterion.
3.
HIGHstatistics
Add a correction note naming the statistical software and version (e.g., Stata, R, SAS) used for the noninferiority analyses in the Statistical Analysis section.
All three reviewers noted the software is not identified, and this is a reproducibility-relevant detail for a clinical trial.
4.
MEDIUMstatistics
Name the specific noninferiority test used for the CI-based comparison (e.g., score or Wald-type test for the difference in proportions) in the Statistical Analysis section.
Reviewer 2 specifically requested the test be named; while the CI-based approach is adequate, naming the test improves reproducibility.
5.
MEDIUMrigor
Report body weight (or body mass index) in Table 1 baseline characteristics, or state that it was not collected and why, and add a justification for the absence of race/ethnicity data.
Two reviewers flagged the missing weight and race/ethnicity as an incomplete reporting of biological variables.
6.
MEDIUMreporting
Reference the CONSORT reporting guideline in the Methods and state that the manuscript conforms to it, ideally with the checklist as supplementary material.
All three reviewers noted the absence of a reporting-guideline reference, a minor but expected element for a published RCT.
7.
LOWreporting
Add an explicit statement of adherence to the Declaration of Helsinki or another recognized ethical framework in the Trial Oversight section.
Reviewer 2 noted regulatory approvals are stated but framework adherence is not explicitly declared.
8.
LOWreporting
State the conflict-of-interest declaration in the text (e.g., 'The authors declare no competing interests') rather than only referencing disclosure forms.
Reviewer 2 noted the COI text is only available via disclosure forms, not in the article itself.
9.
LOWcopyedit
Fix the typo 'factional' → 'fractional' in Results, paragraph 2 and Results, Immunogenicity.
Misspelling of the key term 'fractional' appears twice in the copyedit pass.
10.
LOWcopyedit
Repair the broken cross-reference 'see the in the , available with the full text of this article at NEJM.org' → 'see the Supplementary Appendix, available with the full text...' in Methods, Trial Design and Participants and Trial Procedures.
The garbled XREF artifact leaves incomplete sentences that obscure where dose-preparation details are located.
11.
LOWcopyedit
Fix the extra space in the grant number 'EDCTP- RIA2016V-1633' → 'EDCTP-RIA2016V-1633' in the Funding section.
Inconsistent grant-number formatting in the funding acknowledgment.
12.
LOWcopyedit
Reconcile the 500-IU adverse-event proportion rounding (Results text '75 (63%)' vs Table 3 '75 (62)'; 75/120 = 62.5%) so the two agree, and fix the residual 'postran-domization' typo and the dangling 'up.' fragment.
The integrity check flagged the rounding as a low-severity internal inconsistency, and the copyedit pass flagged the typo and stray fragment.

Full text (31,313 chars)Analyzed: Aug 10, 2026

RigorReviewer 1

RigorReviewer 2

RigorReviewer 3

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

ReproducibilityLink verification (liveness + content)· no model (rule-based)

PreregistrationDeterministic check· no model (rule-based)

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.”

How stars are deducted

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.

The eight reporting dimensions

Scientific PremisePrior work, rationale, and how it addresses gaps.

Study Design & RigorRandomization, blinding, power, controls, replication.

Biological VariablesSex, age, species/strain, housing, demographics.

Ethical ApprovalsIRB/IACUC approval, informed consent, regulatory compliance.

Key ResourcesAntibodies, cell lines, organisms, software — identified with persistent IDs.

Statistical ReportingNamed tests, exact p-values, effect sizes, plausible summary stats.

Data & Code AvailabilityAvailability statements, repositories, accession numbers, shared code.

Reporting TransparencyMethods, registration, guidelines, outcomes, limitations, funding/COI.

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.

Low-Dose Yellow Fever Vaccine in Adults in Africa.

DOI

10.1056/NEJMoa2407293

Record issued

2026-08-10

Engine

7.29.0

Exported

2026-09-21