Effect of a Reduced PCV10 Dose Schedule on Pneumococcal Carriage in Vietnam.
Yoshida LM, Toizumi M, Nguyen HAT, Quilty BJ, Lien LT, Hoang LH, Iwasaki C, Takegata M, Kitamura N, Nation ML, Hinds J, van Zandvoort K, Ortika BD, Dunne EM, Satzke C, Do HT, Mulholland K, Flasche S, Dang DA
- DOI
- 10.1056/NEJMoa2400007
- Record issued
- 2026-08-16
- Engine
- 7.39.0
- Exported
- 2026-09-20
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/a50a09d0-668a-4907-97f4-f4cac4977912 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern ×2−1★
- 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★
- CitationsUnresolved reference−0.25★
- No reported statistical tests were found to recompute.
- 01Efficacy rests on an unvalidated surrogate endpoint
The primary endpoint is pneumococcal vaccine-type (VT) carriage prevalence, a surrogate for pneumococcal disease. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD data) and does not cite validated evidence linking carriage reduction to clinical outcomes in this context.
“Nasopharyngeal carriage is a pre-requisite for disease and reduction of carriage is an indicator of reduction of risk for disease as well as an indirect measure of herd immunity.”
- 02Treatment effect not shown to be clinically meaningful
The primary effect is a reduction in VT carriage prevalence from 11.7% to 1.8% in the 1p+1 arm, but the clinical meaningfulness is not anchored to a minimal clinically important difference or a validated clinical outcome. The non-inferiority margin is based on an assumption of 80% retention of protective effect, but the absolute effect size is not explicitly linked to clinical benefit.
“Overall VT carriage in infants in 2016 before PCV10 introduction in intervention arms was 160/1363 (11.7%) and in 2020 reduced to 6/333 (1.8%), 5/340 (1.5%), and 4/313 (1.3%) in 1p+1, 2p+1, and 3p+0 arms respectively”
- 03Other integrity concern
Trial NCT02961231 was first submitted to ClinicalTrials.gov on 2016-11-01, after the registered study start date of 2016-10-01. Retrospective registration means the protocol and outcomes were not on the public record before the study ran, which is what prospective registration exists to establish.
NCT02961231
reviewer’s wording
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 cluster-randomized non-inferiority trial with clear scientific premise, adequate design, and transparent reporting. The main weakness is the vague data availability statement, which lacks a concrete access mechanism. Minor reporting gaps include missing statistical software identification, lack of explicit reporting guideline adherence, and retrospective trial registration.
Both reviewers agreed on study type (interventional) and on all dimension statuses; no divergence required reconciliation. The statistics component checked 0 tests (none recomputable from reported statistics), so statistical correctness is not verified beyond the reported methods. The citation check found 1 reference not found in registry, which is a potential fabrication signal.
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
- lowinternal contradictionThe abstract reports VT carriage in infants in 2016 as 160/1363 (11.7%), but the results section reports 160/307 (52.1%) of carriers and 160/1363 (11.7%) prevalence. The denominator 1363 is used for prevalence, while 307 is the number of carriers. This is consistent but could be confusing.
“Overall VT carriage in infants in 2016 before PCV10 introduction in intervention arms was 160/1363 (11.7%)”
AbstractFind 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, 2The 1p+1 reduced dosing schedule of PCV10 was not inferior to alternative vaccine dosing schedules in protection against VT carriage in infants and toddlers.The primary endpoint analysis shows non-inferiority with 95% CIs below the 5% margin for both infants and toddlers.Evidence: Non-inferiority results in October 2020: 1p+1 vs 2p+1 difference 0.3% (95% CI -1.6, 2.2) in infants and 0.0% (-2.9, 2.8) in toddlers; vs 3p+0 difference 0.5% (-1.4, 2.4) in infants and 2.0% (-0.5, 4.4) in toddlers.
“The 1p+1 reduced dosing schedule of PCV10 was not inferior to alternative vaccine dosing schedules in protection against VT carriage in infants and toddlers.”
ConclusionFind in source - supportedReviewers 1, 2The 0p+1 schedule was also non-inferior to three-dose schedules in infants and toddlers.The results show non-inferiority for 0p+1 against both 2p+1 and 3p+0 in both age groups, with CIs below the margin.Evidence: 0p+1 vs 2p+1 in infants: 2.3% (-0.1, 4.8); in toddlers: -1.3% (-3.9, 1.3). Similar for 3p+0.
“The 0p+1 was also non-inferior to 2p+1 in infants with a 2.3% (95% CI: −0.1, 4.8%) higher VT carriage prevalence in Oct 2020.”
ResultsFind in source - supportedReviewers 1, 2No PCV-associated severe adverse effects were observed.The safety data show 49 serious adverse events within 28 days of vaccination, but an independent panel deemed none related to PCV10.Evidence: Safety section: 49 SAEs reported, 0.09% of 51,819 doses, none deemed related.
“After review by an independent panel, this panel deemed that none were thought to be related to PCV10 vaccination.”
ResultsFind in source - supportedReviewers 1, 2The 1p+1 schedule remained non-inferior to 2p+1 but not to 3p+0 when including 6A as a VT.The results explicitly state this, and the sensitivity analysis supports it.Evidence: Results: 'With the inclusion of 6A as a VT the 1p+1 schedule remained non-inferior to 2p+1 but not to 3p+0.'
“With the inclusion of 6A as a VT the 1p+1 schedule remained non-inferior to 2p+1 but not to 3p+0.”
ResultsFind in source
Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.
- INADEQUATESurrogate endpointThe primary endpoint is pneumococcal vaccine-type (VT) carriage prevalence, a surrogate for pneumococcal disease. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD data) and does not cite validated evidence linking carriage reduction to clinical outcomes in this context.
“Nasopharyngeal carriage is a pre-requisite for disease and reduction of carriage is an indicator of reduction of risk for disease as well as an indirect measure of herd immunity.”
- INADEQUATEEffect sizeThe primary effect is a reduction in VT carriage prevalence from 11.7% to 1.8% in the 1p+1 arm, but the clinical meaningfulness is not anchored to a minimal clinically important difference or a validated clinical outcome. The non-inferiority margin is based on an assumption of 80% retention of protective effect, but the absolute effect size is not explicitly linked to clinical benefit.
“Overall VT carriage in infants in 2016 before PCV10 introduction in intervention arms was 160/1363 (11.7%) and in 2020 reduced to 6/333 (1.8%), 5/340 (1.5%), and 4/313 (1.3%) in 1p+1, 2p+1, and 3p+0 arms respectively”
Data authenticity concerns
1 finding · worst mediumAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
- Other integrity concernAssessed
2 integrity concerns flagged (0 high).
- mediumotherTrial NCT02961231 was first submitted to ClinicalTrials.gov on 2016-11-01, after the registered study start date of 2016-10-01. Retrospective registration means the protocol and outcomes were not on the public record before the study ran, which is what prospective registration exists to establish.
NCT02961231
reviewer’s wording
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 prior trials in England, South Africa, India, and Vietnam showing 1p+1 schedules induce similar post-booster protection, and identifies the gap in evidence for indirect protection. The rationale linking reduced-dose schedules to cost savings and sustainability is logical. Limitations of prior work (lack of evidence on indirect protection) are explicitly addressed as the study's motivation.
“Trials in England, South Africa, India and Vietnam with either immunogenicity or carriage outcomes have demonstrated that a 1p+1 schedule indeed induces a similar protection to a 2p+1 schedule following administration of the booster dose, however, they also confirmed suspected inferiority before the booster.”
“While the similar post-booster direct protection against VT carriage is thought to sustain indirect protection in the first year of life, available evidence is lacking.”
“Trials in England, South Africa, India and Vietnam with either immunogenicity or carriage outcomes have demonstrated that a 1p+1 schedule indeed induces a similar protection to a 2p+1 schedule following administration of the booster dose”
“While the similar post-booster direct protection against VT carriage is thought to sustain indirect protection in the first year of life, available evidence is lacking.”
“However, high vaccine costs have proven a barrier for introduction in many middle income countries and raise concerns for sustainability of the PCV program in LMICs who transition out of Gavi’s support for vaccine costs.”
Randomization used automated rejection sampling for balanced allocation, and the unit (communes) is stated. The trial is open-label with no blinding, but this is typical for vaccine schedule trials and not a major flaw. Power analysis is reported with assumptions. Inclusion criteria (children eligible for routine immunization) and pre-specified primary endpoint are clear. Outlier handling is not explicitly discussed, but the analysis population is defined. Controls are the standard-dose arms. Independent replication is not applicable for a single trial.
“Sample size calculations deemed that with six clusters per intervention arm and 60 infants recruited per cluster we would have >80% power under a type I error probability of 5% to detect a at least five percentage point higher VTs carriage between a reduced dose arms/schedule and a three-dose arm/schedule with an assumed residual VTs carriage prevalence of 5%.”
“An open-label, non-inferiority, cluster randomized trial, was conducted across the 27 communes of Nha Trang city, south-central Vietnam.”
“we used automated rejection sampling as previously described”
“Sample size calculations deemed that with six clusters per intervention arm and 60 infants recruited per cluster we would have >80% power under a type I error probability of 5% to detect a at least five percentage point higher VTs carriage”
“An open-label, non-inferiority, cluster randomized trial”
Sex is reported overall (about 55% male) but not per arm. Age groups (infants and toddlers) are defined. Health status is described (generally healthy, <2% underlying conditions). Demographics include household size and vaccination history. Species/strain and housing are not applicable as this is a human trial.
“Briefly, about 55% were male, more than 99% had received at least one dose of BCG and DTP and less than 2% had received at least one dose of PCV. Children were generally healthy with <2% reporting underlying medical conditions”
“about 55% were male”
“Children were generally healthy with <2% reporting underlying medical conditions”
“we aimed to recruit 60 children 4 to 11 months old (“infants”), and 60 children 14 to 24 months old (“toddlers”)”
The paper states ethical approval from the Ministry of Health, Vietnam (with protocol number) and Nagasaki University (with protocol number). Written informed consent was obtained from parents/guardians. Regulatory compliance is implied by adherence to approved guidelines.
“Ethical approval for the study was obtained from the Ministry of Health, Vietnam (4875/QD-BYT), and Nagasaki University (15120149).”
“Written informed consent was obtained from the parents or guardian of the study participants at vaccination and sampling”
“Ethical approval for the study was obtained from the Ministry of Health, Vietnam (4875/QD-BYT), and Nagasaki University (15120149).”
“Written informed consent was obtained from the parents or guardian of the study participants at vaccination and sampling”
“the study was conducted in accordance with the approved guidelines.”
PCV10 (Synflorix, GSK Vaccines) is named with manufacturer. Laboratory methods identify the QiaCube HT instrument and kit, and the Senti-SP microarray with vendor. However, catalog numbers for reagents and software versions are not provided. Since this is a clinical trial, the bench criteria are not applicable, and the product identification is adequate.
“PCV10 (Synflorix ® , GSK Vaccines) was used since it was the only PCV registered at the time of the study initiation in Vietnam.”
“DNA was extracted from the nasopharyngeal samples using a QiaCube HT instrument (QIAmp 96 DNA QIAcube HT Kit) and screened for S.pneumoniae lytA gene by realtime PCR at Pasteur Institute in Nha Trang.”
“PCV10 (Synflorix ® , GSK Vaccines) was used”
“DNA was extracted from the nasopharyngeal samples using a QiaCube HT instrument (QIAmp 96 DNA QIAcube HT Kit)”
The primary analysis uses Poisson regression and non-inferiority testing with 95% CIs. Tests are named. Assumptions are not explicitly verified but the methods are standard for the design. Exact p-values are not reported; instead, effect estimates with CIs are used, which is acceptable for non-inferiority trials. Software is not identified. Data presentation includes figures with CIs and per-group n. Mathematical plausibility checks are not applicable due to large N and continuous outcomes.
“We used Poisson regression with a log offset for the number of positive samples to assess the change in the risk of VT carriage”
“VT carriage prevalence was 0.3 percentage points (95% confidence interval (CI): −1.6, 2.2) higher in infants residing in the 1p+1 arm compared to those in the 2p+1 arm”
“We used Poisson regression with a log offset for the number of positive samples”
“VT carriage prevalence was 0.3 percentage points (95% confidence interval (CI): −1.6, 2.2) higher”
The statement says data will be shared on request from the corresponding author on a collaborative basis, but does not specify a platform, conditions, or timeframe. This is reported_but_inadequate. No repository deposit or accession numbers are provided, which is acceptable for patient-level data, but the vague statement does not meet the standard for managed access.
“In accordance with the Bill & Melinda Gates Foundation policy on open data access, data will be shared on request from the corresponding author on a collaborative basis.”
“data will be shared on request from the corresponding author on a collaborative basis.”
The trial is registered (NCT02961231). Methods are detailed enough for replication. Limitations are discussed (COVID-19 impact, contamination). Conclusions are proportional to the evidence. Funding and COI statements are provided. Reporting guideline (CONSORT) is not explicitly mentioned, but the paper follows standard reporting.
“ClinicalTrials.gov (http://ClinicalTrials.gov) number, NCT02961231”
“Due to COVID-19, non-pharmaceutical interventions were introduced in the study site between April and July 2020. As a result, pneumococcal carriage prevalence reduced by about 30% and decreased our power to detect a 5% absolute difference and detect potential inferiority.”
“supported by the Bill and Melinda Gates Foundation (OPP1139859)”
“Due to COVID-19, non-pharmaceutical interventions were introduced in the study site between April and July 2020.”
Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.
Broken references and links
1 finding · worst lowReferences 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.
- References not resolvable to a published paperRecomputed
Checked 27 references by DOI: 0 verified — 1 DOI unresolved, 26 no DOI (shown, not verified).
- UNRESOLVED10.1016/s2214-109x(18Pneumococcal vaccination: guidance for HCWs on the changes to the infant scheduleCited DOI does not resolve to any Crossref record.
- NO DOIBurden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGlobal, regional, and national estimates of pneumonia morbidity and mortality in children younger than 5 years between 2000 and 2015: a systematic analysisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIIndirect effects of childhood pneumococcal conjugate vaccination on invasive pneumococcal disease: a systematic review and meta-analysisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEffects of vaccination on invasive pneumococcal disease in South AfricaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPneumococcal carriage and antibiotic resistance in young children before 13-valent conjugate vaccineNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISerotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sitesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEffect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort studyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPneumococcal vaccines WHO position paper—2012No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe potential for reducing the number of pneumococcal conjugate vaccine doses while sustaining herd immunity in high-income countriesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPneumococcal conjugate vaccine 13 delivered as one primary and one booster dose (1 +1) compared with two primary doses and a booster (2 + 1) in UK infants: a multicentre, parallel group randomised controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIImmunogenicity of a single dose compared with a two-dose primary series followed by a booster dose of ten-valent or 13-valent pneumococcal conjugate vaccine in South African children: an open-label, randomised, non-inferiority trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEffect of reduced two-dose (1 + 1) schedule of 10 and 13-valent pneumococcal conjugate vaccines (SynflorixTM and Prevenar13TM)) on nasopharyngeal carriage and serotype-specific immune response in the first two years of life: Results from an open-labelled randomized controlled trial in Indian childrenNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIImmunogenicity of alternative ten-valent pneumococcal conjugate vaccine schedules in infants in Ho Chi Minh City, Vietnam: results from a single-blind, parallel-group, open-label, randomised, controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAssociation of pneumococcal carriage in infants with the risk of carriage among their contacts in Nha Trang, Vietnam: A nested cross-sectional surveyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIStreptococcus pneumoniae : Transmission, Colonization and InvasionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIImpact of pneumococcal conjugate vaccines on nasopharyngeal carriage and invasive disease among unvaccinated people: Review of evidence on indirect effectsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEvaluation of the effect of reduced-dose pneumococcal conjugate vaccine schedules on vaccine serotype carriage in children and their caretakers in a naïve population in Vietnam: Protocol for a cluster randomized non-inferiority trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIStandard method for detecting upper respiratory carriage of Streptococcus pneumoniae : updated recommendations from the World Health Organization Pneumococcal Carriage Working GroupNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICarriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis , and Staphylococcus aureus in Indonesian children: A cross-sectional studyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEvaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA genes for detection of pneumococcal DNANo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIChallenges in the Design and Interpretation of Noninferiority TrialsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEffect of reduced two-dose (1 + 1) schedule of 10 and 13-valent pneumococcal conjugate vaccines (Synflorix ™ and Prevenar13 ™ ) on nasopharyngeal carriage and serotype-specific immune response in the first two years of life: Results from an open-labelled randomized controlled trial in Indian childrenNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEffect of different schedules of ten-valent pneumococcal conjugate vaccine on pneumococcal carriage in Vietnamese infants: results from a randomised controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEfficacy against pneumococcal carriage and the immunogenicity of reduced-dose (0+1 and 1+1) PCV10 and PCV13 schedules in Ho Chi Minh City, Viet Nam: a parallel, single-blind, randomised controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIImmunogenicity and reactogenicity of ten-valent versus 13-valent pneumococcal conjugate vaccines among infants in Ho Chi Minh City, Vietnam: a randomised controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPneumococcal conjugate vaccine use during humanitarian crisesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
1 of 2 data/code links checked; 1 live; 1 not probed.
- datahttps://clinicaltrials.gov/ct2/show/NCT02961231LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://www.nejm.org/doi/full/10.1056/NEJMoa2400007UNVERIFIEDHTTP 403Liveness indeterminate — content not checked.
Copyediting
5 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 5 minor suggestions below.
5 copyedit issues flagged: mostly consistency, grammar, typo.
- MINORtypoAuthor affiliations“Murdoch Children’s Research Institute, Infection and Immunity, Melbourne, ACT, Australia”→ Melbourne is in VIC, not ACT. Correct to 'VIC'.Geographical error in affiliation.
- MINORconsistencyAbstract“1p+1”→ Ensure consistent use of '1p+1' vs '1+1' throughout.Minor inconsistency in schedule notation.
- MINORgrammarMethods, Statistical Analyses“a at least five percentage point higher”→ Change to 'an at least five percentage point higher' or 'a difference of at least five percentage points'.Article error.
- MINORconsistencyAbstract“1p+1, 0p+1, 2p+1, 3p+0”→ Ensure consistent use of hyphens and spacing (e.g., '1p+1' vs '1p+1').Minor formatting inconsistency.
- MINORgrammarMethods, Statistical Analyses“to detect a at least five percentage point higher VTs carriage”→ Change to 'to detect at least a five percentage point higher VT carriage'.Article and plural error.
The published work is robust in design and reporting, but readers should weigh the vague data availability statement and the retrospective registration as transparency limitations. The unresolved reference and the minor copyedit issues do not undermine the core findings but warrant correction or clarification.
- 1.HIGHdata codeIn the Data Sharing section, specify a concrete access mechanism (e.g., a repository or data access committee) with conditions and a timeframe for data sharing.The current statement is vague and does not meet the standard for managed access, which is a transparency gap.
- 2.HIGHreportingIn the Methods or Acknowledgements, state adherence to the CONSORT extension for cluster randomized trials.Explicitly naming the reporting guideline improves transparency and reproducibility.
- 3.HIGHstatisticsIn the Methods, Statistical Analyses section, identify the statistical software and version used.Software identification is a standard reporting requirement and aids reproducibility.
- 4.HIGHreportingIn the Methods, Ethical Approval section, clarify the timeline of trial registration relative to study start, or add a note about retrospective registration.The integrity check found the trial was registered after the study start date; transparency about this is important for readers.
- 5.HIGHotherVerify the reference 'Pneumococcal vaccination: guidance for HCWs on the changes to the infant schedule' (DOI 10.1016/s2214-109x(18) — not found in registry) and correct or replace it.A reference that cannot be found in any registry may be fabricated and must be verified.
- 6.MEDIUMreportingIn the Methods, Statistical Analyses section, add a statement on assumptions verification for the Poisson regression model (e.g., overdispersion check).Assumption checks are part of sound statistical reporting.
- 7.MEDIUMreportingIn the Methods, Study Design section, clarify the inclusion/exclusion criteria for participants, specifying any pre-specified criteria.Clear inclusion/exclusion criteria are essential for reproducibility.
- 8.MEDIUMreportingIn the Methods, Statistical Analyses section, describe how outliers or missing data were handled, or state that none were excluded.Outlier handling is a reporting gap that reviewers may question.
- 9.MEDIUMreportingIn the Limitations section, add a note on the absence of blinding and its potential impact.Open-label design is typical but should be acknowledged as a potential source of bias.
- 10.MEDIUMdata codeDeposit de-identified aggregate data in a public repository (e.g., Zenodo) with a DOI, and provide accession numbers if applicable.A concrete data deposit would strengthen the data availability statement.
- 11.MEDIUMdata codeShare custom analysis code in a public repository (e.g., GitHub) with a permanent identifier, and describe the analysis pipeline in the Methods.Code sharing enhances reproducibility.
- 12.LOWcopyeditIn the Author affiliations, correct 'Melbourne, ACT, Australia' to 'Melbourne, VIC, Australia'.Geographical error in affiliation.
- 13.LOWcopyeditIn the Abstract and throughout, ensure consistent use of '1p+1' vs '1+1' and consistent hyphenation/spacing for schedule notations.Minor consistency issue in schedule notation.
- 14.LOWcopyeditIn the Methods, Statistical Analyses, fix the grammar: 'a at least five percentage point higher' to 'an at least five percentage point higher' or 'a difference of at least five percentage points'.Article error.
- 15.LOWcopyeditIn the Methods, Statistical Analyses, fix the grammar: 'to detect a at least five percentage point higher VTs carriage' to 'to detect at least a five percentage point higher VT carriage'.Article and plural error.
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.