Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Effect of a Reduced PCV10 Dose Schedule on Pneumococcal Carriage in Vietnam.

Name: Kaimen Rigor review — Effect of a Reduced PCV10 Dose Schedule on Pneumococcal Carriage in Vietnam.
Item: Effect of a Reduced PCV10 Dose Schedule on Pneumococcal Carriage in Vietnam.
Rating: 96
Author: Alpha1

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

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Kaimen Rigor review — 2.5★ (Weak), 0 critical, 5 high issues for “Effect of a Reduced PCV10 Dose Schedule on Pneumococcal Carriage in Vietnam.”

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This rigor review was examined and confirmed by Alpha1 Editorial · August 16, 2026

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Effect of a Reduced PCV10 Dose Schedule on Pneumococcal Carriage in Vietnam.

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DOI

10.1056/NEJMoa2400007

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Effect of a Reduced PCV10 Dose Schedule on Pneumococcal Carriage in Vietnam.

Paper source

Effect of a Reduced PCV10 Dose Schedule on Pneumococcal Carriage in Vietnam.

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Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 16, 2026

Kaimen Rigor review

Kaimen Rigor reviewed

2.5 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

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★

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

Not verified in this report

No reported statistical tests were found to recompute.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
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.”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
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”
Find in source
03Other integrity concern
mediumAuthenticityreviewer-assessedFull detail
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

Findings by category

101ArithmeticNumerical inconsistencies 202OverreachOverstated conclusions 103AuthenticityData authenticity concerns 104DisclosureReporting gaps 105AvailabilityBroken references and links 06Copyedit5 minor suggestions

This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This is a well-conducted 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 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

Overstated conclusions

2 findings · worst high

Conclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.

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.

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

Data authenticity concerns

1 finding · worst medium

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

Other integrity concernAssessed

2 integrity concerns flagged (0 high).

Reporting gaps

1 finding · worst medium

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/code availability incompleteAssessed

Eight Dimensions7 pass · 1 warn

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.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise with prior work cited and a logical rationale for the study.

Evidence

“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.”

Introduction ¶2Find in source

“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.”

Introduction ¶3Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise with prior work cited and a logical rationale for the study.

Evidence

Introduction ¶2Find in source

“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.”

Introduction ¶2Find in source

“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.”

Introduction ¶1Find in source

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.

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsINADEQUATE

outlier handlingNOT REPORTED

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The cluster-randomized design is well-described with adequate randomization, sample size calculation, and pre-specified analysis.

Evidence

paraphrase[Methods, Study Design]

“To ensure random but geographically balanced allocation of clusters that were similarly representative of rural and urban communities and that were included in the ongoing hospital-based pediatric ARI surveillance, 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 between a reduced dose arms/schedule and a three-dose arm/schedule with an assumed residual VTs carriage prevalence of 5%.”

Statistical analysisFind in source

“An open-label, non-inferiority, cluster randomized trial, was conducted across the 27 communes of Nha Trang city, south-central Vietnam.”

MethodsFind in source

PASSReviewer 2· 85% conf

The cluster-randomized design is well-described with adequate randomization, sample size calculation, and pre-specified analysis.

Evidence

“we used automated rejection sampling as previously described”

MethodsFind in source

Statistical analysisFind in source

“An open-label, non-inferiority, cluster randomized trial”

MethodsFind in source

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.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

Demographic and health characteristics of participants are reported, though sex is not broken down by arm.

Evidence

“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”

ResultsFind in source

PASSReviewer 2· 80% conf

Demographic and health characteristics of participants are reported, including sex, age, and health status.

Evidence

“about 55% were male”

ResultsFind in source

“Children were generally healthy with <2% reporting underlying medical conditions”

ResultsFind in source

“we aimed to recruit 60 children 4 to 11 months old (“infants”), and 60 children 14 to 24 months old (“toddlers”)”

MethodsFind in source

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.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approval from named bodies and informed consent are clearly documented.

Evidence

“Ethical approval for the study was obtained from the Ministry of Health, Vietnam (4875/QD-BYT), and Nagasaki University (15120149).”

EthicsFind in source

“Written informed consent was obtained from the parents or guardian of the study participants at vaccination and sampling”

EthicsFind in source

PASSReviewer 2· 95% conf

Ethical approval from named bodies and informed consent are clearly reported.

Evidence

“Ethical approval for the study was obtained from the Ministry of Health, Vietnam (4875/QD-BYT), and Nagasaki University (15120149).”

EthicsFind in source

“Written informed consent was obtained from the parents or guardian of the study participants at vaccination and sampling”

EthicsFind in source

“the study was conducted in accordance with the approved guidelines.”

EthicsFind in source

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.

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational product (PCV10) and key laboratory reagents are identified, though some details are incomplete.

Evidence

“PCV10 (Synflorix ® , GSK Vaccines) was used since it was the only PCV registered at the time of the study initiation in Vietnam.”

MethodsFind in source

“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.”

MethodsFind in source

PASSReviewer 2· 85% conf

The investigational product (PCV10) is identified with manufacturer, and laboratory methods are described with specific kits and software.

Evidence

“PCV10 (Synflorix ® , GSK Vaccines) was used”

MethodsFind in source

“DNA was extracted from the nasopharyngeal samples using a QiaCube HT instrument (QIAmp 96 DNA QIAcube HT Kit)”

MethodsFind in source

paraphrase[Methods, Outcome]

“serotype determination by microarray (Senti-SP v1.5, BUGS Bioscience, London, UK; https://bugsbio.org)”

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.

Sub-criteria

tests namedADEQUATE

exact p valuesN/A

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedNOT REPORTED

assumptions verifiedINADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

Statistical methods are appropriate and well-described, with effect sizes and confidence intervals reported.

Evidence

“We used Poisson regression with a log offset for the number of positive samples to assess the change in the risk of VT carriage”

Statistical analysisFind in source

“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”

ResultsFind in source

PASSReviewer 2· 80% conf

Statistical methods are appropriate and well-described, with effect sizes and confidence intervals reported; p-values are not the primary focus.

Evidence

“We used Poisson regression with a log offset for the number of positive samples”

Statistical analysisFind in source

“VT carriage prevalence was 0.3 percentage points (95% confidence interval (CI): −1.6, 2.2) higher”

ResultsFind in source

absence[Methods, Statistical Analyses]

Statistical software not identified.

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.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 90% conf

A data availability statement exists but is vague, lacking a concrete access mechanism.

Evidence

“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 availabilityFind in source

WARNReviewer 2· 90% conf

A data availability statement exists but is vague, lacking a concrete access mechanism or timeframe.

Evidence

“data will be shared on request from the corresponding author on a collaborative basis.”

Data availabilityFind in source

absence[Data Sharing]

No repository deposit mentioned.

absence[Data Sharing]

No code sharing mentioned.

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.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The manuscript is transparent with trial registration, funding, and limitations discussed.

Evidence

“ClinicalTrials.gov (http://ClinicalTrials.gov) number, NCT02961231”

AbstractFind in source

“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.”

LimitationsFind in source

PASSReviewer 2· 85% conf

The paper is transparent with trial registration, funding, and conflict of interest statements, and limitations are discussed.

Evidence

paraphrase[Abstract]

“ClinicalTrials.gov number, NCT02961231”

“supported by the Bill and Melinda Gates Foundation (OPP1139859)”

FundingFind in source

“Due to COVID-19, non-pharmaceutical interventions were introduced in the study site between April and July 2020.”

LimitationsFind in source

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

Broken references and links

1 finding · worst low

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.

References not resolvable to a published paperRecomputed

Checked 27 references by DOI: 0 verified — 1 DOI unresolved, 26 no DOI (shown, not verified).

1 of 2 data/code links checked; 1 live; 1 not probed.

Copyediting

5 minor

Wording, 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.

Kaimen Rigor Action ItemsFinal pass before journal submission

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 code
In 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.
HIGHreporting
In the Methods or Acknowledgements, state adherence to the CONSORT extension for cluster randomized trials.
Explicitly naming the reporting guideline improves transparency and reproducibility.
3.
HIGHstatistics
In the Methods, Statistical Analyses section, identify the statistical software and version used.
Software identification is a standard reporting requirement and aids reproducibility.
4.
HIGHreporting
In 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.
HIGHother
Verify 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.
MEDIUMreporting
In 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.
MEDIUMreporting
In 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.
MEDIUMreporting
In 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.
MEDIUMreporting
In 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 code
Deposit 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 code
Share 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.
LOWcopyedit
In the Author affiliations, correct 'Melbourne, ACT, Australia' to 'Melbourne, VIC, Australia'.
Geographical error in affiliation.
13.
LOWcopyedit
In 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.
LOWcopyedit
In 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.
LOWcopyedit
In 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.

Full text (25,887 chars)Analyzed: Aug 16, 2026

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Effect of a Reduced PCV10 Dose Schedule on Pneumococcal Carriage in Vietnam.

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DOI

10.1056/NEJMoa2400007

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3d0a0bc4aaf07edfe4f93552d0b840f3e68028a56fb04b34dd93a30babde1eb6

Verify via API

Issued Aug 16, 2026Engine 7.39.0

Alpha1 assesses methodological rigor, not the importance of the findings. See how we calibrate →

Kaimen Rigor review

Kaimen Rigor reviewed

2.5 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

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★

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

Not verified in this report

No reported statistical tests were found to recompute.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
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.”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
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”
Find in source
03Other integrity concern
mediumAuthenticityreviewer-assessedFull detail
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

Findings by category

Numerical inconsistencies

1 finding · worst low

Internal contradictions in the reported numbersAssessed

Overstated conclusions

2 findings · worst high

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.

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

Data authenticity concerns

1 finding · worst medium

Other integrity concernAssessed

2 integrity concerns flagged (0 high).

Reporting gaps

1 finding · worst medium

Data/code availability incompleteAssessed

Eight Dimensions7 pass · 1 warn

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise with prior work cited and a logical rationale for the study.

Evidence

Introduction ¶2Find in source

“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.”

Introduction ¶3Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise with prior work cited and a logical rationale for the study.

Evidence

Introduction ¶2Find in source

“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.”

Introduction ¶2Find in source

Introduction ¶1Find in source

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsINADEQUATE

outlier handlingNOT REPORTED

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The cluster-randomized design is well-described with adequate randomization, sample size calculation, and pre-specified analysis.

Evidence

paraphrase[Methods, Study Design]

Statistical analysisFind in source

“An open-label, non-inferiority, cluster randomized trial, was conducted across the 27 communes of Nha Trang city, south-central Vietnam.”

MethodsFind in source

PASSReviewer 2· 85% conf

The cluster-randomized design is well-described with adequate randomization, sample size calculation, and pre-specified analysis.

Evidence

“we used automated rejection sampling as previously described”

MethodsFind in source

Statistical analysisFind in source

“An open-label, non-inferiority, cluster randomized trial”

MethodsFind in source

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

Demographic and health characteristics of participants are reported, though sex is not broken down by arm.

Evidence

ResultsFind in source

PASSReviewer 2· 80% conf

Demographic and health characteristics of participants are reported, including sex, age, and health status.

Evidence

“about 55% were male”

ResultsFind in source

“Children were generally healthy with <2% reporting underlying medical conditions”

ResultsFind in source

“we aimed to recruit 60 children 4 to 11 months old (“infants”), and 60 children 14 to 24 months old (“toddlers”)”

MethodsFind in source

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approval from named bodies and informed consent are clearly documented.

Evidence

“Ethical approval for the study was obtained from the Ministry of Health, Vietnam (4875/QD-BYT), and Nagasaki University (15120149).”

EthicsFind in source

“Written informed consent was obtained from the parents or guardian of the study participants at vaccination and sampling”

EthicsFind in source

PASSReviewer 2· 95% conf

Ethical approval from named bodies and informed consent are clearly reported.

Evidence

“Ethical approval for the study was obtained from the Ministry of Health, Vietnam (4875/QD-BYT), and Nagasaki University (15120149).”

EthicsFind in source

“Written informed consent was obtained from the parents or guardian of the study participants at vaccination and sampling”

EthicsFind in source

“the study was conducted in accordance with the approved guidelines.”

EthicsFind in source

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational product (PCV10) and key laboratory reagents are identified, though some details are incomplete.

Evidence

“PCV10 (Synflorix ® , GSK Vaccines) was used since it was the only PCV registered at the time of the study initiation in Vietnam.”

MethodsFind in source

PASSReviewer 2· 85% conf

The investigational product (PCV10) is identified with manufacturer, and laboratory methods are described with specific kits and software.

Evidence

“PCV10 (Synflorix ® , GSK Vaccines) was used”

MethodsFind in source

“DNA was extracted from the nasopharyngeal samples using a QiaCube HT instrument (QIAmp 96 DNA QIAcube HT Kit)”

MethodsFind in source

paraphrase[Methods, Outcome]

“serotype determination by microarray (Senti-SP v1.5, BUGS Bioscience, London, UK; https://bugsbio.org)”

Sub-criteria

tests namedADEQUATE

exact p valuesN/A

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedNOT REPORTED

assumptions verifiedINADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

Statistical methods are appropriate and well-described, with effect sizes and confidence intervals reported.

Evidence

“We used Poisson regression with a log offset for the number of positive samples to assess the change in the risk of VT carriage”

Statistical analysisFind in source

“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”

ResultsFind in source

PASSReviewer 2· 80% conf

Statistical methods are appropriate and well-described, with effect sizes and confidence intervals reported; p-values are not the primary focus.

Evidence

“We used Poisson regression with a log offset for the number of positive samples”

Statistical analysisFind in source

“VT carriage prevalence was 0.3 percentage points (95% confidence interval (CI): −1.6, 2.2) higher”

ResultsFind in source

absence[Methods, Statistical Analyses]

Statistical software not identified.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 90% conf

A data availability statement exists but is vague, lacking a concrete access mechanism.

Evidence

“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 availabilityFind in source

WARNReviewer 2· 90% conf

A data availability statement exists but is vague, lacking a concrete access mechanism or timeframe.

Evidence

“data will be shared on request from the corresponding author on a collaborative basis.”

Data availabilityFind in source

absence[Data Sharing]

No repository deposit mentioned.

absence[Data Sharing]

No code sharing mentioned.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The manuscript is transparent with trial registration, funding, and limitations discussed.

Evidence

“ClinicalTrials.gov (http://ClinicalTrials.gov) number, NCT02961231”

AbstractFind in source

LimitationsFind in source

PASSReviewer 2· 85% conf

The paper is transparent with trial registration, funding, and conflict of interest statements, and limitations are discussed.

Evidence

paraphrase[Abstract]

“ClinicalTrials.gov number, NCT02961231”

“supported by the Bill and Melinda Gates Foundation (OPP1139859)”

FundingFind in source

“Due to COVID-19, non-pharmaceutical interventions were introduced in the study site between April and July 2020.”

LimitationsFind in source

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

Broken references and links

1 finding · worst low

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.

References not resolvable to a published paperRecomputed

Checked 27 references by DOI: 0 verified — 1 DOI unresolved, 26 no DOI (shown, not verified).

1 of 2 data/code links checked; 1 live; 1 not probed.

Copyediting

5 minor

Wording, 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.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
HIGHdata code
In 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.
HIGHreporting
In the Methods or Acknowledgements, state adherence to the CONSORT extension for cluster randomized trials.
Explicitly naming the reporting guideline improves transparency and reproducibility.
3.
HIGHstatistics
In the Methods, Statistical Analyses section, identify the statistical software and version used.
Software identification is a standard reporting requirement and aids reproducibility.
4.
HIGHreporting
In 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.
HIGHother
Verify 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.
MEDIUMreporting
In 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.
MEDIUMreporting
In 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.
MEDIUMreporting
In 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.
MEDIUMreporting
In 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 code
Deposit 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 code
Share 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.
LOWcopyedit
In the Author affiliations, correct 'Melbourne, ACT, Australia' to 'Melbourne, VIC, Australia'.
Geographical error in affiliation.
13.
LOWcopyedit
In 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.
LOWcopyedit
In 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.
LOWcopyedit
In 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.

Full text (25,887 chars)Analyzed: Aug 16, 2026