Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Effect of BCG Danish and oral polio vaccine on neonatal mortality in newborn babies weighing less than 2000 g in India: multicentre open label randomised controlled trial (BLOW2)

Name: Kaimen Rigor review — Effect of BCG Danish and oral polio vaccine on neonatal mortality in newborn babies weighing less than 2000 g in India: multicentre open label randomised controlled trial (BLOW2)
Item: Effect of BCG Danish and oral polio vaccine on neonatal mortality in newborn babies weighing less than 2000 g in India: multicentre open label randomised controlled trial (BLOW2)
Rating: 59
Author: Alpha1

Adhisivam B, Kamalarathnam C, Bhat BV, Jayaraman K, Namachivayam SP, Shann F, McSharry B, David P, Raja, Sundaram M.

Paper source

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Kaimen Rigor review — 4★ (Strong), 0 critical, 3 high issues for “Effect of BCG Danish and oral polio vaccine on neonatal mortality in newborn babies weighing less than 2000 g in India: multicentre open label randomised controlled trial (BLOW2)”

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Effect of BCG Danish and oral polio vaccine on neonatal mortality in newborn babies weighing less than 2000 g in India: multicentre open label randomised controlled trial (BLOW2)

Adhisivam B, Kamalarathnam C, Bhat BV, Jayaraman K, Namachivayam SP, Shann F, McSharry B, David P, Raja, Sundaram M.

Read full text (PMC)

DOI

10.1136/bmj-2025-084745

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Effect of BCG Danish and oral polio vaccine on neonatal mortality in newborn babies weighing less than 2000 g in India: multicentre open label randomised controlled trial (BLOW2)

Adhisivam B, Kamalarathnam C, Bhat BV, Jayaraman K, Namachivayam SP, Shann F, McSharry B, David P, Raja, Sundaram M.

Paper source

Effect of BCG Danish and oral polio vaccine on neonatal mortality in newborn babies weighing less than 2000 g in India: multicentre open label randomised controlled trial (BLOW2)

Read full text (PMC)

Embed this Rigor badge

Links back to this Kaimen Rigor review.

Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 10, 2026

Kaimen Rigor review

Kaimen Rigor reviewed

4 / 5

Strong — minor issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

StatisticsStatistic did not reproduce−0.5★
ReportingEthical approvals partially met−0.25★
ReportingData & code availability partially met−0.25★

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

Biggest issues

01Reported statistic does not recompute
highArithmeticrecomputedFull detail
Post hoc Klebsiella analysis: ratio 0.31 (95% CI 0.15-0.66), reported P<0.001
“post hoc ratio 0.31 (95% CI 0.15 to 0.66), P<0.001”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions 03AuthenticityNone found 204DisclosureReporting gaps 05AvailabilityNone found 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 methodologically strong, well-reported multicentre RCT: robust randomisation, a priori power, verified proportional-hazards assumptions, transparent disclosure of mid-trial changes and limitations, and sound basic ethics documentation. The weaknesses are minor reporting gaps rather than validity threats: no named regulatory-compliance framework, an incomplete data-availability statement with code only in a supplementary file, no explicit CONSORT reference, and one post-hoc p-value printed as P<0.001 that recomputes to ~0.0019.

Both independent reviewer runs (full text) converged on identical statuses for all eight dimensions. The synthesis folded in the statistics verification component, which flagged one post-hoc p-value inconsistency (Klebsiella: printed P<0.001 vs recomputed p≈0.0019), lowering statistical analysis from the reviewers' pass to warn. Bench-science resource criteria (antibodies, cell lines, mycoplasma, organisms), animal housing, and single-sex justification were excluded as not applicable to a human neonatal RCT. Statistics verification covered only the 7 tests reported with a test statistic/df or effect+CI; all other reported tests were not independently recomputed and remain unverified.

Numerical inconsistencies

1 finding · worst high

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.

Reported statistics do not recomputeRecomputed

Recomputed 7 tests: 6 consistent, 1 inconsistent; 1 recomputed directly from the reported test statistics, 6 via agent-written checks.

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.

Efficacy claim is anchored to an adequate endpoint and a meaningful effect.

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

2 findings · 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
Ethics/consent reporting incompleteAssessed

Eight Dimensions6 pass · 2 warn

Prior trials in Guinea-Bissau (BCG Danish) and the authors' own BLOW1 trials (BCG Russian) are cited with strengths and weaknesses, including that the Guinea-Bissau trials found no significant effect on their primary outcomes but a meta-analysis showed reduced neonatal mortality, and that BLOW1 with BCG Russian found no effect. The rationale linking strain differences (Russian vs Danish) to the hypothesis is explicit, and the study is designed to address the gap left by the prior Russian-strain trials.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The introduction thoroughly establishes the scientific foundation with substantial prior work, a clear rationale, and explicit acknowledgement of prior limitations.

Evidence

paraphrase[Introduction, paragraphs 3-5]

“In three randomised trials in newborns weighing <2500 g in Guinea-Bissau, none had a statistically significant effect on the primary outcome from the administration of BCG Danish vaccine ... but meta-analysis showed a reduction in neonatal mortality of 38% (95% CI 17% to 54%)”

“The four strains of BCG that Unicef distributes to low and middle income countries differ noticeably in bacterial viability, RNA content, and immunological effects”

Introduction ¶5Find in source

“we found that BCG Russian vaccine (Serum Institute of India, Pune) with or without oral polio vaccine (OPV) given soon after birth did not reduce neonatal mortality in newborns with birth weight <2000 g”

Introduction ¶5Find in source

PASSReviewer 2· 90% conf

The premise is well established through citation of prior randomised trials (Guinea-Bissau, BLOW1) and mechanistic evidence on BCG non-specific effects, with a clear rationale linking strain differences to the trial objective.

Evidence

paraphrase[Introduction, paragraphs 2-5]

“The four strains of BCG that Unicef distributes to low and middle income countries differ noticeably in bacterial viability, RNA content, and immunological effects, and the vaccines might therefore have different specific and non-specific effects.”

IntroductionFind in source

paraphrase[Introduction]

“in two large trials in three neonatal intensive care units (NICUs) in India (BLOW1), we found that BCG Russian vaccine ... given soon after birth did not reduce neonatal mortality in newborns with birth weight <2000 g.”

Randomisation used a dedicated computer program with 1:1 allocation, stratification by NICU/sex/birth weight, and randomly varying block sizes of 2-8. The power calculation is detailed (510 deaths, 1998/group, 95% power, alpha<0.01). Open-label status is justified by the visible BCG skin lesion and ethics of not covering the arm. Eligibility/exclusion criteria are prespecified, and the analysis population (ITT) and missing data (9 lost to follow-up, censoring) are clearly described.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Core design elements for a human RCT are well specified: computer-generated stratified randomisation, a priori power calculation, explicit eligibility criteria, and a justified open-label design.

Evidence

“The newborn babies were randomised using a specially written computer program that checked eligibility, allocated treatment, and recorded baseline and outcome data. Randomisation was 1:1 and stratified by NICU, sex, and birth weight (<1000 g, 1000-1499 g, 1500-1999 g), and with a block size that varied randomly from 2-8 newborn babies.”

MethodsFind in source

“1998 infants would be required in each group to have 95% power to detect a 30% reduction in mortality using BCG and OPV with an α <0.01”

MethodsFind in source

“The BCG vaccine causes an obvious skin lesion, so it was not possible to mask staff to group assignment because it would have been unethical to cover the upper arm of these high risk babies for their entire stay in intensive care”

MethodsFind in source

PASSReviewer 2· 90% conf

A well-designed randomised trial with a stated computer-based randomisation method, stratified blocking, a priori sample-size calculation, pre-specified eligibility criteria, and a clear handling of protocol violations and missing data.

Evidence

MethodsFind in source

“with a mortality rate of 15% in the control group, 1998 infants would be required in each group to have 95% power to detect a 30% reduction in mortality using BCG and OPV with an α <0.01”

MethodsFind in source

Sex is reported for both groups (balanced), and age (median age at enrolment 0.86 days), birth weight (median 1560 g), and gestation (median ~33.5 weeks) are reported with IQRs. Demographics such as inborn/outborn status, delivery mode, maternal BCG scar, and season are tabulated. Both sexes were enrolled, so a single-sex justification is not applicable.

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· 85% conf

Biological/relevant subject characteristics are comprehensively reported for this neonatal population.

Evidence

“Median (IQR) birth weight (g) | 1560 (1320-1745) | 1560 (1320-1745)”

Table 1Find in source

“Male | 1389 (51) | 1382 (51) | | Female | 1325 (49) | 1324 (49)”

Table 1Find in source

PASSReviewer 2· 85% conf

Key participant biological variables (sex, birth weight, gestational age, Apgar scores, delivery mode) are reported in baseline tables; both sexes enrolled, so no single-sex justification is required.

Evidence

“Male | 1389 (51) | 1382 (51) | | Female | 1325 (49) | 1324 (49)”

Table 1Find in source

“Median (IQR) birth weight (g) | 1560 (1320-1745) | 1560 (1320-1745)”

Table 1Find in source

Ethical approval is well documented: two named institutional ethics committees (Jawaharlal Institute and Madras Medical College) with protocol numbers, and written informed consent from a parent. The protocol was registered prospectively (CTRI/2017/01/007676). However, no named regulatory framework (Declaration of Helsinki, ICH-GCP, Common Rule) is explicitly invoked, leaving regulatory_compliance not reported.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceNOT REPORTED

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

Named ethics committees approved the trial with protocol numbers and written informed consent is documented, but no explicit regulatory-compliance statement (e.g., Declaration of Helsinki or ICH-GCP) is given.

Evidence

“the trial was approved by the Jawaharlal Institute of Postgraduate Medical Education and Research Ethics and Scientific Advisory Committees (JIP/IEC/2016/25/831), and for the Institute of Child Health and Institute of Obstetrics and Gynaecology by the Institutional Ethics Committee of the Madras Medical College (No 02052018)”

EthicsFind in source

“Written informed consent was obtained from a parent before enrolment.”

MethodsFind in source

absence[Entire manuscript]

No explicit regulatory-compliance statement (Helsinki/GCP) found

WARNReviewer 2· 80% conf

Named ethics committees with protocol numbers and written informed consent are reported; however, no recognized regulatory framework (e.g. Declaration of Helsinki, ICH-GCP) is cited by name.

Evidence

EthicsFind in source

“Written informed consent was obtained from a parent before enrolment.”

MethodsFind in source

absence[Ethics statements]

No named regulatory compliance framework (e.g. Declaration of Helsinki) is cited.

BCG Danish (GreenSignal Bio Pharma, Chennai) and bivalent 1&3 OPV (Bharat Biotech International, Hyderabad; or Bio-Med, Ghaziabad) are named with dose/regimen (0.1 mL intradermal; 0.1 mL/two drops). Statistical software Stata (versions 14.1 and 18) is identified. Bench-science criteria (antibodies, cell lines, mycoplasma, organisms) are not applicable to this clinical trial.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational vaccines are identified with manufacturers and doses, and the statistical software is named with version.

Evidence

“Babies in the early vaccination group received 0.1 mL of BCG Danish (GreenSignal Bio Pharma, Chennai) intradermally within 48 hours of admission to the NICU, along with 0.1 mL (two drops) of bivalent 1&3 OPV (Bharat Biotech International, Hyderabad; or Bio-Med, Ghaziabad)”

MethodsFind in source

“Intention-to-treat analysis was performed using Stata version 18, with Cox proportional hazard models”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The investigational vaccines are identified with manufacturers and dose, and the analysis software is identified with versions; no cell lines, antibodies, or animal organisms are used.

Evidence

MethodsFind in source

paraphrase[Methods, Sample size and Statistical analysis]

“using the Stata version 14.1 sampsi command ... Intention-to-treat analysis was performed using Stata version 18”

Cox proportional hazards models, Kaplan-Meier analysis, fractional polynomials, and Schoenfeld residuals are all described; the proportional hazards assumption was tested and confirmed. The primary outcome p-value (0.03) is exact, and effect sizes are reported as adjusted hazard ratios with 95% CIs throughout. The design-based analysis population (ITT) and loss to follow-up are clear. Mathematical plausibility is not independently verifiable for these large-N continuous/person-year outcomes, which is appropriate.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

Statistical methods are rigorous and fully reported: named tests, verified proportional-hazards assumptions, effect sizes with CIs, exact primary p-values, and identified software.

Evidence

paraphrase[Methods, Statistical analysis]

“The proportional hazards assumption of the Cox model was tested using Stata's time-dependent covariable command with log(time), and by using Schoenfeld residuals, log-log plots, and separately estimated Kaplan-Meier curves.”

“adjusted hazard ratio 0.83, 95% confidence interval (CI) 0.69 to 0.98; P=0.03”

AbstractFind in source

PASSReviewer 2· 85% conf

Statistical methods are thorough: Cox proportional-hazards models named, proportional-hazards assumptions verified, effect sizes reported with 95% CIs, software identified, and the primary p-value reported exactly.

Evidence

“adjusted hazard ratio 0.83, 95% confidence interval (CI) 0.69 to 0.98; P=0.03”

AbstractFind in source

“The proportional hazards assumption of the Cox model was tested using Stata’s time-dependent covariable command with log(time), and by using Schoenfeld residuals, log-log plots, and separately estimated Kaplan-Meier curves.”

Statistical analysisFind in source

“Infection related neonatal mortality per person year was 0.40 in the early vaccination group and 0.73 in the control group (adjusted hazard ratio 0.53, 95% CI 0.40 to 0.70).”

AbstractFind in source

The data availability statement is truncated in the provided text ('The Stata statistical analysis code is included in the supplementary file. Deidentified individual patien...'), so no concrete access route (platform, data-access committee, conditions/timeframe) is confirmed. The Stata analysis code is shared in the supplementary file rather than a version-controlled public repository. The OSF repository (https://osf.io/3492q/) hosts the protocol, DSMB documents, and SAP, but not the data or code. Repository deposit and accession numbers are not applicable for identifiable patient-level data.

Sub-criteria

code sharingINADEQUATE

accession numbersN/A

repository depositN/A

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 70% conf

A data availability statement exists and Stata code is shared in the supplementary file, but the visible statement names no concrete access mechanism/platform for the deidentified individual patient data, and code is not in a version-controlled repository with a permanent identifier.

Evidence

“The Stata statistical analysis code is included in the supplementary file. Deidentified individual patien”

Data availabilityFind in source

“subsequently, all versions of the protocol, Data and Safety Monitoring Board documents, and statistical analysis plan were posted at https://osf.io/3492q/”

MethodsFind in source

WARNReviewer 2· 70% conf

A data-availability statement exists and the Stata code is shared in the supplementary file, but the statement is truncated in the available text (access mechanism unclear) and the code is not deposited in a version-controlled repository with a persistent identifier.

Evidence

paraphrase[Data availability statement]

“The Stata statistical analysis code is included in the supplementary file. Deidentified individual patient”

“all versions of the protocol, Data and Safety Monitoring Board documents, and statistical analysis plan were posted at https://osf.io/3492q/”

Statistical analysisFind in source

The trial is registered (CTRI/2017/01/007676) and methods are detailed enough to replicate. Null results (non-infectious deaths HR 1.10, P=0.41; no significant interactions) and process changes (secondary outcome added mid-trial; DSMB-recommended change to primary censoring) are disclosed transparently. Limitations (lack of blinding, multiplicity, mid-trial additions) are discussed. The only gap is that no CONSORT reporting checklist is explicitly referenced, though a CONSORT-style flow diagram is present.

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

Reporting is comprehensive: detailed methods, prospective trial registration, transparent reporting of null and secondary outcomes, a limitations section, and funding/COI statements.

Evidence

“The protocol was registered prospectively with the Clinical Trials Registry India (CTRI/2017/01/007676)”

AbstractFind in source

paraphrase[Discussion, Strengths and weaknesses of this study]

“It is unlikely that the lack of blinding influenced the result: our two previous open label randomised trials of BCG Russian ... no difference in neonatal mortality was found between the intervention and control groups”

“Funding: No external funding; the trial was supported by the participating units and the resources of the investigators.”

FundingFind in source

PASSReviewer 2· 85% conf

Methods are detailed and replicable, the trial is prospectively registered, secondary-outcome additions are transparently disclosed, limitations are discussed at length, and funding/COI declarations are provided; only an explicit reporting-guideline reference (e.g. CONSORT) is absent.

Evidence

“Trial registration Clinical Trials Registry India CTRI/2017/01/007676.”

AbstractFind in source

“The secondary outcome of death from infection was not specified in the original protocol but was added a third of the way through the trial on the advice of the Data and Safety Monitoring Board”

MethodsFind in source

“No external funding; the trial was supported by the participating units and the resources of the investigators.”

FundingFind in source

Registered (1 ID: Clinical Trials Registry – India). No reporting guideline cited.

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 37 references by DOI: 29 verified — 8 no DOI (shown, not verified).

2 data/code links checked; 1 live.

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, other, clarity.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published trial is robust overall: the primary finding (adjusted HR 0.83, 95% CI 0.69-0.98, P=0.03) is supported by the reported analysis, 6 of 7 recomputed tests were consistent, the citation check found no retracted or unresolved references, no data/code links were dead or inconsistent, and no claims were under-evidenced. An informed reader should weigh the open-label design, the mid-trial addition of the infection secondary outcome, the one post-hoc p-value reporting inconsistency (Klebsiella, no decision impact), and the incomplete data-access statement. None of these threatens the primary conclusion or warrants retraction; the Klebsiella p-value and the truncated data-availability statement would warrant a small correction/completion.

1.
HIGHstatistics
Correct the post-hoc Klebsiella analysis p-value in the Results (and any table/figure): the printed 'P<0.001' is inconsistent with the recomputed p≈0.0019 for ratio 0.31 (95% CI 0.15-0.66); report the exact value or a correct threshold.
The printed threshold is technically false (0.0019 is not <0.001), a verifiable reporting error even though it does not change the conclusion.
2.
HIGHethics
Add an explicit regulatory-compliance statement to the Ethics statements section naming a recognized framework (e.g., 'conducted in accordance with the Declaration of Helsinki' and/or ICH-GCP).
Approval bodies and consent are documented but no named compliance framework is invoked — a fixable reporting gap.
3.
HIGHdata code
Complete the truncated data-availability statement to specify a concrete access mechanism for the deidentified individual patient data (named platform or data-access committee, request conditions, and timeframe).
The current statement is truncated in the published text and gives no verifiable route to the IPD, weakening reproducibility.
4.
MEDIUMdata code
Deposit the Stata analysis code in a version-controlled public repository with a persistent identifier (e.g., GitHub + Zenodo DOI) and cite that identifier in the data-availability statement, in addition to the supplementary-file copy.
Code shared only in a supplementary file lacks version control and a permanent citable identifier.
5.
MEDIUMreporting
Reference the applicable reporting guideline (CONSORT) explicitly in the Methods or a dedicated reporting statement.
The paper follows trial-reporting conventions and includes a CONSORT-style flow diagram but never cites the guideline.
6.
MEDIUMstatistics
Report exact p-values for secondary comparisons (e.g., infection-related mortality, Klebsiella) rather than threshold-only 'P<0.001'.
Threshold-only reporting obstructs independent verification and is the proximate cause of the flagged Klebsiella inconsistency.
7.
MEDIUMdata code
Clarify in the data-availability statement whether the OSF entry (https://osf.io/3492q/) hosts the analysis code or only the protocol, DSMB documents, and SAP.
Readers cannot tell from the current statement whether the code is available independently of the supplementary file.
8.
LOWcopyedit
Fix the abbreviation inconsistency in the Table 1 footnote (JIMPER vs the standard JIPMER used in the text) to use one consistent acronym.
Inconsistent institution abbreviation is a minor consistency defect.
9.
LOWother
Remove extraction artifacts from the published text if present ('pmc 1' at the first line and stray numbers '390 492057' in the header area).
These are likely PMC extraction artifacts rather than author content but should be cleaned if they appear in the version of record.
10.
LOWdata code
Cite a DOI/accession for the OSF-hosted protocol and SAP documents in the data-availability statement.
Gives the deposited study documents a citable persistent identifier.

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Effect of BCG Danish and oral polio vaccine on neonatal mortality in newborn babies weighing less than 2000 g in India: multicentre open label randomised controlled trial (BLOW2)

Adhisivam B, Kamalarathnam C, Bhat BV, Jayaraman K, Namachivayam SP, Shann F, McSharry B, David P, Raja, Sundaram M.

Read full text (PMC)

DOI

10.1136/bmj-2025-084745

Share this Kaimen Rigor review

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Record fingerprint

4cf846ef32b35824222cd1ef82a92ad002fd5a8fa6a183dcbc0e7c28508e70e1

Verify via API

Issued Aug 10, 2026Engine 7.29.0

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

Kaimen Rigor review

Kaimen Rigor reviewed

4 / 5

Strong — minor issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

StatisticsStatistic did not reproduce−0.5★
ReportingEthical approvals partially met−0.25★
ReportingData & code availability partially met−0.25★

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

Biggest issues

01Reported statistic does not recompute
highArithmeticrecomputedFull detail
Post hoc Klebsiella analysis: ratio 0.31 (95% CI 0.15-0.66), reported P<0.001
“post hoc ratio 0.31 (95% CI 0.15 to 0.66), P<0.001”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions 03AuthenticityNone found 204DisclosureReporting gaps 05AvailabilityNone found 06Copyedit5 minor suggestions

Numerical inconsistencies

1 finding · worst high

Reported statistics do not recomputeRecomputed

Recomputed 7 tests: 6 consistent, 1 inconsistent; 1 recomputed directly from the reported test statistics, 6 via agent-written checks.

Overstated conclusions

1 finding · worst low

Conclusions only partially backed by the presented evidenceAssessed

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

Efficacy claim is anchored to an adequate endpoint and a meaningful effect.

Data authenticity concerns

None found

Checked — nothing surfaced.

Reporting gaps

2 findings · worst medium

Data/code availability incompleteAssessed
Ethics/consent reporting incompleteAssessed

Eight Dimensions6 pass · 2 warn

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The introduction thoroughly establishes the scientific foundation with substantial prior work, a clear rationale, and explicit acknowledgement of prior limitations.

Evidence

paraphrase[Introduction, paragraphs 3-5]

“The four strains of BCG that Unicef distributes to low and middle income countries differ noticeably in bacterial viability, RNA content, and immunological effects”

Introduction ¶5Find in source

PASSReviewer 2· 90% conf

Evidence

paraphrase[Introduction, paragraphs 2-5]

IntroductionFind in source

paraphrase[Introduction]

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Core design elements for a human RCT are well specified: computer-generated stratified randomisation, a priori power calculation, explicit eligibility criteria, and a justified open-label design.

Evidence

MethodsFind in source

“1998 infants would be required in each group to have 95% power to detect a 30% reduction in mortality using BCG and OPV with an α <0.01”

MethodsFind in source

PASSReviewer 2· 90% conf

Evidence

MethodsFind in source

“with a mortality rate of 15% in the control group, 1998 infants would be required in each group to have 95% power to detect a 30% reduction in mortality using BCG and OPV with an α <0.01”

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· 85% conf

Biological/relevant subject characteristics are comprehensively reported for this neonatal population.

Evidence

“Median (IQR) birth weight (g) | 1560 (1320-1745) | 1560 (1320-1745)”

Table 1Find in source

“Male | 1389 (51) | 1382 (51) | | Female | 1325 (49) | 1324 (49)”

Table 1Find in source

PASSReviewer 2· 85% conf

Evidence

“Male | 1389 (51) | 1382 (51) | | Female | 1325 (49) | 1324 (49)”

Table 1Find in source

“Median (IQR) birth weight (g) | 1560 (1320-1745) | 1560 (1320-1745)”

Table 1Find in source

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceNOT REPORTED

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

Evidence

EthicsFind in source

“Written informed consent was obtained from a parent before enrolment.”

MethodsFind in source

absence[Entire manuscript]

No explicit regulatory-compliance statement (Helsinki/GCP) found

WARNReviewer 2· 80% conf

Named ethics committees with protocol numbers and written informed consent are reported; however, no recognized regulatory framework (e.g. Declaration of Helsinki, ICH-GCP) is cited by name.

Evidence

EthicsFind in source

“Written informed consent was obtained from a parent before enrolment.”

MethodsFind in source

absence[Ethics statements]

No named regulatory compliance framework (e.g. Declaration of Helsinki) is cited.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational vaccines are identified with manufacturers and doses, and the statistical software is named with version.

Evidence

MethodsFind in source

“Intention-to-treat analysis was performed using Stata version 18, with Cox proportional hazard models”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The investigational vaccines are identified with manufacturers and dose, and the analysis software is identified with versions; no cell lines, antibodies, or animal organisms are used.

Evidence

MethodsFind in source

paraphrase[Methods, Sample size and Statistical analysis]

“using the Stata version 14.1 sampsi command ... Intention-to-treat analysis was performed using Stata version 18”

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

Statistical methods are rigorous and fully reported: named tests, verified proportional-hazards assumptions, effect sizes with CIs, exact primary p-values, and identified software.

Evidence

paraphrase[Methods, Statistical analysis]

“adjusted hazard ratio 0.83, 95% confidence interval (CI) 0.69 to 0.98; P=0.03”

AbstractFind in source

PASSReviewer 2· 85% conf

Evidence

“adjusted hazard ratio 0.83, 95% confidence interval (CI) 0.69 to 0.98; P=0.03”

AbstractFind in source

Statistical analysisFind in source

“Infection related neonatal mortality per person year was 0.40 in the early vaccination group and 0.73 in the control group (adjusted hazard ratio 0.53, 95% CI 0.40 to 0.70).”

AbstractFind in source

Sub-criteria

code sharingINADEQUATE

accession numbersN/A

repository depositN/A

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 70% conf

Evidence

“The Stata statistical analysis code is included in the supplementary file. Deidentified individual patien”

Data availabilityFind in source

“subsequently, all versions of the protocol, Data and Safety Monitoring Board documents, and statistical analysis plan were posted at https://osf.io/3492q/”

MethodsFind in source

WARNReviewer 2· 70% conf

Evidence

paraphrase[Data availability statement]

“The Stata statistical analysis code is included in the supplementary file. Deidentified individual patient”

“all versions of the protocol, Data and Safety Monitoring Board documents, and statistical analysis plan were posted at https://osf.io/3492q/”

Statistical analysisFind in source

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

Reporting is comprehensive: detailed methods, prospective trial registration, transparent reporting of null and secondary outcomes, a limitations section, and funding/COI statements.

Evidence

“The protocol was registered prospectively with the Clinical Trials Registry India (CTRI/2017/01/007676)”

AbstractFind in source

paraphrase[Discussion, Strengths and weaknesses of this study]

“Funding: No external funding; the trial was supported by the participating units and the resources of the investigators.”

FundingFind in source

PASSReviewer 2· 85% conf

Evidence

“Trial registration Clinical Trials Registry India CTRI/2017/01/007676.”

AbstractFind in source

“The secondary outcome of death from infection was not specified in the original protocol but was added a third of the way through the trial on the advice of the Data and Safety Monitoring Board”

MethodsFind in source

“No external funding; the trial was supported by the participating units and the resources of the investigators.”

FundingFind in source

Registered (1 ID: Clinical Trials Registry – India). No reporting guideline cited.

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 37 references by DOI: 29 verified — 8 no DOI (shown, not verified).

2 data/code links checked; 1 live.

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, other, clarity.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
HIGHstatistics
Correct the post-hoc Klebsiella analysis p-value in the Results (and any table/figure): the printed 'P<0.001' is inconsistent with the recomputed p≈0.0019 for ratio 0.31 (95% CI 0.15-0.66); report the exact value or a correct threshold.
The printed threshold is technically false (0.0019 is not <0.001), a verifiable reporting error even though it does not change the conclusion.
2.
HIGHethics
Add an explicit regulatory-compliance statement to the Ethics statements section naming a recognized framework (e.g., 'conducted in accordance with the Declaration of Helsinki' and/or ICH-GCP).
Approval bodies and consent are documented but no named compliance framework is invoked — a fixable reporting gap.
3.
HIGHdata code
Complete the truncated data-availability statement to specify a concrete access mechanism for the deidentified individual patient data (named platform or data-access committee, request conditions, and timeframe).
The current statement is truncated in the published text and gives no verifiable route to the IPD, weakening reproducibility.
4.
MEDIUMdata code
Deposit the Stata analysis code in a version-controlled public repository with a persistent identifier (e.g., GitHub + Zenodo DOI) and cite that identifier in the data-availability statement, in addition to the supplementary-file copy.
Code shared only in a supplementary file lacks version control and a permanent citable identifier.
5.
MEDIUMreporting
Reference the applicable reporting guideline (CONSORT) explicitly in the Methods or a dedicated reporting statement.
The paper follows trial-reporting conventions and includes a CONSORT-style flow diagram but never cites the guideline.
6.
MEDIUMstatistics
Report exact p-values for secondary comparisons (e.g., infection-related mortality, Klebsiella) rather than threshold-only 'P<0.001'.
Threshold-only reporting obstructs independent verification and is the proximate cause of the flagged Klebsiella inconsistency.
7.
MEDIUMdata code
Clarify in the data-availability statement whether the OSF entry (https://osf.io/3492q/) hosts the analysis code or only the protocol, DSMB documents, and SAP.
Readers cannot tell from the current statement whether the code is available independently of the supplementary file.
8.
LOWcopyedit
Fix the abbreviation inconsistency in the Table 1 footnote (JIMPER vs the standard JIPMER used in the text) to use one consistent acronym.
Inconsistent institution abbreviation is a minor consistency defect.
9.
LOWother
Remove extraction artifacts from the published text if present ('pmc 1' at the first line and stray numbers '390 492057' in the header area).
These are likely PMC extraction artifacts rather than author content but should be cleaned if they appear in the version of record.
10.
LOWdata code
Cite a DOI/accession for the OSF-hosted protocol and SAP documents in the data-availability statement.
Gives the deposited study documents a citable persistent identifier.

Full text (47,064 chars)Analyzed: Aug 10, 2026