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: Adcurare Rigor Record — 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: 100
Author: Adcurare

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

Paper source

Read full text (PMC)Journal

Embed this Rigor badge

Adcurare Rigor Review — 1.5★ (Critical), 0 critical, 6 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)”

Links back to this Rigor Record.

Adcurare Editorial

This rigor review was examined and confirmed by Adcurare Editorial · July 6, 2026

Adcurare Rigor Review

Rigor Reviewed

1.5 / 5

Critical — a demonstrable failure

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×4−2★
CitationsCitations & links (capped) ×5−1★
ClaimsOverstated claim−0.5★

Citations & links are capped at −1★ combined, however many are flagged.

Model-reported confidence: highReviewer agreement: moderateEngine: 7.6.0Source: full text

Problems surfaced5 types

Conclusions overstated beyond the evidence
Methods and results do not match
Internal contradictions in the reported numbers
Other integrity concern
References not resolvable to a published paper

This Adcurare Rigor Review uses AI 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 and transparently reported open-label RCT of early BCG Danish and OPV in low-birth-weight newborns. The study design is rigorous with adequate randomisation and power analysis. Minor gaps include an absent regulatory compliance statement, lack of an explicit reporting guideline citation, and a few copyedit issues.

All three independent reviewers (all using AI) scored the same full-text paper. There was near-unanimous agreement; the only divergence was on ethical approvals (warn vs pass) and key resources (pass vs warn), resolved by weighing evidence. Copyedit and verification components were integrated. No statistical errors were detected in the recomputed tests (2 of 2 consistent); coverage is limited.

12 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).

Recomputed 2 tests: 2 consistent, 0 inconsistent, 2 via agent-written checks.

4 integrity concerns flagged (0 high).

Reporting

Eight Dimensions8 pass

The introduction extensively cites prior work on BCG non-specific effects, the Guinea-Bissau trials, the earlier BLOW1 trials of BCG Russian in India, and strain differences. It explains the logical rationale: BCG Danish may be more effective than BCG Russian, and a trial in the same NICUs was needed. Limitations of prior work (small size, different strains, inconclusive primary endpoints) are acknowledged and addressed by the larger, same-design BLOW2 trial.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper establishes a clear scientific premise: it cites prior observational and trial evidence on BCG’s non-specific effects, acknowledges conflicting results from different BCG strains (Russian vs Danish), and rationally motivates the present trial.

Evidence

direct quote[Introduction, paragraphs 1-6]

“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.”

direct quote[Introduction, paragraph 6]

“Soon after completion of our trials of BCG Russian, and because this vaccine may be less effective than BCG Danish, we performed a trial in newborn babies weighing <2000 g (BLOW2) to test the effect of BCG Danish and OPV in the same three NICUs that had tested BCG Russian using the same trial design.”

paraphrase[Discussion, 'Interpretation of results and comparison with other studies']

“The paper notes that the trial is larger than all previous BCG-Danish trials combined (511 vs 285 deaths) and uses the same NICUs and design as the prior null BLOW1 trials, strengthening the comparison.”

PASSReviewer 2· 95% conf

The paper clearly establishes its scientific foundation by citing prior trials, acknowledging differences between BCG strains, and providing a logical rationale for testing BCG Danish.

Evidence

paraphrase[Introduction, paragraphs 2-4]

“Paraphrase: The introduction discusses the Guinea-Bissau trials of BCG Danish, the BLOW1 trials of BCG Russian, and the differences between strains.”

direct quote[Introduction, paragraph 4]

direct quote[Discussion, paragraph 2]

“Our trial differs in important ways from the four other smaller randomised trials... Firstly, we administered 0.1 mL of the vaccine rather than 0.05 mL... Secondly, our trial was larger, with 511 deaths compared with 285 deaths in the four Guinea-Bissau trials combined.”

PASSReviewer 3· 95% conf

The scientific premise is well-established with extensive citation of prior trials and a clear rationale for testing BCG Danish versus BCG Russian, including acknowledgement of limitations of prior work.

Evidence

direct quote[Introduction, paragraphs 3-5]

“In two large trials in three neonatal intensive care units (NICUs) in India (BLOW1), 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.”

direct quote[Introduction, paragraph 5]

direct quote[Introduction, paragraph 4; Methods, Trial design]

“In newborn babies with low birth weight, however, administration of BCG is often delayed ; therefore it is ethical to compare early versus delayed BCG vaccination in these babies.”

Randomisation was computer-generated with varying block sizes and stratification by NICU, sex, and birth weight. The open-label design is justified by the visible BCG skin lesion. The sample size was based on mortality events with 95% power to detect a 30% reduction. Inclusion/exclusion criteria are clearly listed. The primary analysis is ITT, with a per-protocol sensitivity analysis. The control group was not censored for early vaccination as recommended by the DSMB, addressing potential bias.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The design is a well-planned open-label RCT with stratified randomisation, a pre-specified power analysis, clear inclusion/exclusion criteria, and appropriate handling of controls and censoring. Blinding was not possible (open-label) but was justified.

Evidence

direct quote[Methods, 'Sample size, randomisation, and masking']

“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.”

direct quote[Methods, 'Sample size, randomisation, and masking']

“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; the caregivers who assessed whether the baby died or survived were not blinded.”

direct quote[Methods, 'Sample size, randomisation, and masking']

“we estimated that a total of 510 deaths would be required: 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”

PASSReviewer 2· 95% conf

The study design is rigorous: randomisation method, stratification, power analysis, inclusion/exclusion criteria, and analysis population are all well-described.

Evidence

direct quote[Methods, Sample size, randomisation, and masking]

“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.”

direct quote[Methods, Sample size, randomisation, and masking]

“using the Stata version 14.1 sampsi command, we estimated that a total of 510 deaths would be required: 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”

direct quote[Methods, Sample size, randomisation, and masking]

WARNReviewer 3· 88% conf

Overall, the design is reasonably rigorous for a clinical trial, but the lack of blinding is a significant limitation, and the addition of a secondary outcome mid-trial without multiplicity adjustment weakens some inferences.

Evidence

direct quote[Methods, Sample size, randomisation, and masking]

“We estimated that a total of 510 deaths would be required: 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”

direct quote[Methods, Outcomes]

“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”

Sex is reported in Table 1 (51% male, 49% female in both groups). Age (gestational age, enrolment age) and birth weight are reported. Health status is implicit: all babies are in NICUs, weighing <2000 g, with various conditions; baseline characteristics include Apgar scores, delivery mode, etc. Species/strain/source and housing conditions are n/a (human study). Demographics relevant to the population (Indian NICUs, maternal BCG scar, inborn/outborn, season) are reported.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Key biological variables (sex, birth weight, gestational age, and several other baseline characteristics) are reported in a comprehensive table. Since the study is human and both sexes are enrolled, sex justification is not applicable. Demographics for the Indian population are adequately described.

Evidence

direct quote[Results, Table 1]

“Male | 1389 (51) | 1382 (51)”

direct quote[Results, Table 1]

“Median (IQR) gestational age (weeks) | 33.4 (31.7-35.4) | 33.6 (31.7-35.4)”

direct quote[Results, Table 1]

“Maternal BCG scar | 1601 (59) | 1658 (61)”

PASSReviewer 2· 95% conf

Sex, age, birth weight, gestation, and other baseline characteristics are well-reported in Table 1.

Evidence

direct quote[Table 1]

“Male: 1389 (51%) [early], 1382 (51%) [control]; Female: 1325 (49%), 1324 (49%)”

direct quote[Table 1]

“Median (IQR) age at enrolment (days): 0.86 (0.54-1.46) [early], 0.86 (0.56-1.38) [control]; Median (IQR) birth weight (g): 1560 (1320-1745) [both]”

paraphrase[Table 1]

“Paraphrase: The table also reports the proportion born in the study hospital, maternal BCG scar, vaginal delivery, twin/triplet, and season.”

PASSReviewer 3· 95% conf

Biological variables are well-reported for a human clinical trial, including sex, age, birth weight, gestational age, and relevant clinical characteristics.

Evidence

direct quote[Table 1]

“Male 1389 (51) | 1382 (51)”

direct quote[Table 1]

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

direct quote[Table 1]

“Born in study hospital 2460 (91) | 2454 (91)”

The paper reports approval by the Jawaharlal Institute of Postgraduate Medical Education and Research Ethics and Scientific Advisory Committees (protocol JIP/IEC/2016/25/831) and the Institutional Ethics Committee of the Madras Medical College (No 02052018). Written informed consent from a parent was obtained. The trial is registered (CTRI/2017/01/007676) and the paper states compliance with ethical standards. Regulatory compliance is implicit in the trial registration and ethics approval; the paper does not explicitly name the Declaration of Helsinki but the ethics framework is covered by the trial registration and standard Indian ethics processes, which are adequate for a non-US/EU trial.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 98% conf

Ethical approval is clearly stated with named committees and protocol numbers, informed consent was obtained, and regulatory compliance is addressed by the trial registration and ethical standards.

Evidence

direct quote[Ethics statements section]

“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).”

direct quote[Methods, 'Sample size, randomisation, and masking']

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

direct quote[Abstract and Ethics statements]

“Clinical Trials Registry India CTRI/2017/01/007676”

WARNReviewer 2· 85% conf

Ethics approval and informed consent are adequately reported, but a statement of regulatory compliance (e.g., Declaration of Helsinki) is missing.

Evidence

direct quote[Ethics statements]

“Before randomisation began at each site, 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).”

direct quote[Methods, Sample size, randomisation, and masking]

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

absence[Ethics statements]

No explicit statement of compliance with an ethical framework (e.g., Declaration of Helsinki) is found.

PASSReviewer 3· 95% conf

Ethical approvals are clearly documented with named ethics committees and protocol numbers, informed consent was obtained, and regulatory compliance is stated.

Evidence

direct quote[Ethics statements]

direct quote[Methods, Sample size, randomisation, and masking]

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

This is a human RCT of drug products: BCG Danish (GreenSignal Bio Pharma, Chennai) and OPV (Bharat Biotech International, Hyderabad; or Bio-Med, Ghaziabad) are named with manufacturer and formulation. Dose and route are specified (0.1 mL intradermally for BCG, 0.1 mL OPV orally). This is adequate for the investigational products. Antibodies, cell lines, mycoplasma, and organisms are not applicable. Software tools: Stata versions 14.1 and 18 are identified. Custom code (the computer program that allocated treatment) is described but not deposited as a standalone resource; the Stata analysis code is stated to be in the supplementary file.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The investigational products (BCG Danish vaccine and OPV) are identified with manufacturer and location, and the software used (Stata, version 18) is stated. Other wet-lab resources are not applicable.

Evidence

direct quote[Methods, 'Procedures']

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

direct quote[Methods, 'Statistical analysis']

“Intention-to-treat analysis was performed using Stata version 18”

WARNReviewer 2· 80% conf

The investigational vaccines are adequately identified, but the custom randomization software is not fully identified and the analysis code is not deposited in a public repository.

Evidence

direct quote[Methods, Procedures]

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

direct quote[Methods, Sample size, randomisation, and masking]

“The newborn babies were randomised using a specially written computer program that checked eligibility, allocated treatment, and recorded baseline and outcome data.”

direct quote[Data availability statement]

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

PASSReviewer 3· 90% conf

Investigational products (BCG Danish and OPV) are identified with manufacturer and dose; statistical software is named and versioned. No bench resources are applicable.

Evidence

direct quote[Methods, Procedures]

“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).”

direct quote[Methods, Statistical analysis]

“Intention-to-treat analysis was performed using Stata version 18”

The primary analysis is a Cox proportional hazards model stratified by NICU with age as the underlying time. Tests are named (log-rank, Cox regression, Kaplan-Meier). Assumptions: proportional hazards tested via Schoenfeld residuals, log-log plots, and time-dependent covariable test. Exact p-values are reported for the primary outcome (P=0.03) and secondary outcomes (P<0.001). Effect sizes (hazard ratios) with 95% CIs are given. Software: Stata 18 and 14.1. Data presentation: Kaplan-Meier survival curves with 95% CIs, person-years denominators, per-group n, and a detailed Table 2. Mathematical plausibility is sound: numbers are consistent (e.g., the reported person-years and deaths give mortality rates matching the table). The paper acknowledges that secondary outcome CIs and p-values are not adjusted for multiplicity. The censoring strategy was adapted on DSMB advice and is clearly explained.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The statistical analysis is thorough and well-reported: tests are named, assumptions verified, exact p-values and CIs are provided, software is identified, and data presentation is adequate for a large clinical trial.

Evidence

direct quote[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.”

direct quote[Results, Table 2]

“0.83 (0.69 to 0.98) | 0.03”

direct quote[Methods, 'Statistical analysis']

“We did not adjust the 95% confidence intervals (CIs) and P values of the secondary outcomes for multiplicity.”

PASSReviewer 2· 95% conf

Statistical methods are well-described, assumptions are tested, exact p-values and effect sizes with CIs are reported, and data presentation is appropriate for a large trial.

Evidence

direct quote[Methods, Statistical analysis]

direct quote[Results, Table 2]

“Adjusted hazard ratio 0.83 (95% CI 0.69 to 0.98; P=0.03)”

direct quote[Table 2]

“Mortality rate (deaths/total person years): 1.29 (238/184); 1.50 (273/182)”

PASSReviewer 3· 88% conf

Statistical methods are appropriate and well-described, including survival analysis with Cox regression and verification of proportional hazards. Exact p-values and confidence intervals are reported. However, the use of a secondary outcome added mid-trial without multiplicity adjustment is a limitation.

Evidence

direct quote[Methods, Statistical analysis]

direct quote[Results, Table 2]

“0.83 (0.69 to 0.98); P=0.03”

direct quote[Results, Table 2 footnote]

“† Secondary outcome not adjusted for multiplicity.”

A data availability statement is present, naming a concrete repository (Synapse) with a DOI (doi.org/10.7303/syn68349250) and access conditions (registration required, which is appropriate for patient-level data). This is adequate for a clinical trial where open download may not be appropriate. The Stata analysis code is stated to be in the supplementary file. The paper does not provide sequencing accession numbers or clinical trial data-access committee details beyond the Synapse repository, but the Synapse deposit serves as both the data repository and access mechanism. The code sharing is adequate (supplementary file), though a public repository like GitHub with versioning would be ideal.

Sub-criteria

code sharingADEQUATE

accession numbersN/A

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Data and code availability are well-addressed: deidentified individual patient data are deposited in a repository with a DOI, and the Stata analysis code is included as supplementary material.

Evidence

direct quote[Data availability statement]

“Deidentified individual patient data are stored at https://doi.org/10.7303/syn68349250 and are fully accessible after registration with synapse.org.”

direct quote[Data availability statement]

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

PASSReviewer 2· 90% conf

Data are deposited in a repository with a DOI, and a data availability statement is present. Analysis code is in the supplementary file but not in a public repository, which is a minor shortfall.

Evidence

direct quote[Data availability statement]

“Deidentified individual patient data are stored at https://doi.org/10.7303/syn68349250 and are fully accessible after registration with synapse.org.”

direct quote[Data availability statement]

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

direct quote[Methods, Statistical analysis]

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

PASSReviewer 3· 85% conf

Data and code availability are reported with a concrete route: deidentified patient data are in a public repository (Synapse) with a DOI, and analysis code is in the supplementary file.

Evidence

direct quote[Data availability statement]

“Deidentified individual patient data are stored at https://doi.org/10.7303/syn68349250 and are fully accessible after registration with synapse.org.”

direct quote[Data availability statement]

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

Methods completeness is high: procedures, dosing, timing, and analysis plans are fully described. Trial registration is present (CTRI/2017/01/007676). A formal reporting guideline (CONSORT) is not explicitly named, but the paper follows its structure and includes a flow diagram. All outcomes are reported, including the added secondary outcome (infection-related mortality) with a transparent explanation that it was not in the original protocol but was added on DSMB advice. Limitations are discussed extensively: open-label design, potential for OPV contribution, manufacturing concerns, and censoring issues are all addressed. Conclusions are proportional: the authors do not claim causation beyond the trial's findings, and they appropriately discuss generalizability and policy implications. Funding (none external) and competing interests (none declared) are stated.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The manuscript is transparently reported: methods are detailed, the trial is registered, all outcomes' analyses are described even if not pre-specified (noted transparently), limitations are discussed, conclusions are proportional, and funding/COI statements are provided.

Evidence

direct quote[Abstract and Ethics statements]

“Clinical Trials Registry India CTRI/2017/01/007676”

direct quote[Methods, 'Outcomes']

“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”

direct quote[Funding and Competing interests sections, after Discussion]

“No external funding; the trial was supported by the participating units and the resources of the investigators. ... no financial relationships ... and no other relationships or activities that could appear to have influenced the submitted work.”

PASSReviewer 2· 95% conf

The manuscript is transparent: methods are detailed, trial is registered, all outcomes are reported, limitations are discussed, conclusions are proportional, and funding/COI are stated.

Evidence

direct quote[Abstract, Methods]

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

direct quote[Discussion, Strengths and weaknesses of this study]

“As skin lesions due to BCG are obvious, a double blind trial could not be performed... It is unlikely that the lack of blinding influenced the result”

absence[Methods]

No explicit reference to a reporting guideline such as CONSORT.

PASSReviewer 3· 90% conf

The manuscript is transparently reported: pre-registered, with detailed methods, discussion of limitations, and conclusions proportional to evidence. Funding and COI are stated.

Evidence

direct quote[Abstract, Trial registration]

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

direct quote[Discussion, Strengths and weaknesses of this study]

“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”

direct quote[Discussion, Implications for policy and future research]

“Our findings provide additional evidence that different strains of BCG might have different non-specific effects, and that BCG Danish might have stronger non-specific effects than BCG Russian.”

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

Checked 37 references: 32 verified — 5 unresolved.

Reproducibility

2 data/code links checked; 2 live.

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

Adcurare Rigor Action ItemsFinal pass before journal submission

The manuscript is ready to submit after addressing a small set of pre-submission actions. The most critical items are adding a regulatory compliance statement (Declaration of Helsinki), explicitly naming the CONSORT reporting guideline, investigating the striking asphyxia ratio in Table 4, and verifying five references not found in the registry. The paper is otherwise robust.

1.
HIGHrigor
Verify the five references flagged as 'not_found_in_registry': (1) The State of the World’s Children 2021, (2) BCG Market Update October 2024, (3) BCG vaccine WHO position paper, (4) BCG vaccination reaction in low birth weight infants, (5) Bacillus Calmette-Guérin (BCG) Vaccine Supply & Demand Update – December 2014. Provide correct citations or confirm their existence.
These references could not be located in any registry, which may indicate fabrication or incorrect citation details; reviewers will flag unresolved references.
2.
HIGHethics
Add an explicit statement of regulatory compliance in the Ethics statements section (e.g., 'The trial was conducted in accordance with the Declaration of Helsinki').
The current ethics section lacks an explicit compliance statement; this is a standard requirement for clinical trials and was flagged as a reporting gap.
3.
HIGHreporting
Explicitly state adherence to the CONSORT 2010 reporting guideline in the Methods section and include a completed CONSORT checklist as a supplementary file.
The paper follows a clinical trial reporting structure but does not name the guideline; explicitly citing it improves transparency and is expected by journals.
4.
HIGHrigor
Investigate the asphyxia row in Table 4: the BG to control ratio of 9.97 is based on 10 vs 1 deaths, which is unusually high and potentially erroneous. Verify the count, recalculate the ratio, and add a footnote if correct or correct the number.
This suspicious ratio may be a typographical error or a genuine signal; it requires clarification before submission.
5.
HIGHrigor
Temper the claim in the abstract and introduction that 'BCG Danish may be more effective than BCG Russian' by adding a caveat that this is a cross-trial comparison with the earlier BLOW1 trial and not a head-to-head comparison.
The claim audit rated this claim as overstated; the evidence does not support direct comparative efficacy without a direct randomised comparison.
6.
HIGHdata code
Deposit the Stata analysis code in a version-controlled public repository (e.g., Zenodo, GitHub) with a persistent DOI, and update the Data availability statement to include the new URL.
The current supplementary file is shared but not versioned; a public repository improves reproducibility and is increasingly expected.
7.
MEDIUMreporting
Add a brief note in the Methods or Statistical analysis section about the handling of outliers in the primary analysis (e.g., whether any observations were excluded beyond pre-specified criteria and with justification).
The study design checklist flagged outlier handling as not reported; this is a minor but missing element of analytical transparency.
8.
MEDIUMcopyedit
Fix the typo 'JIMPER' to 'JIPMER' in Table 1.
The institution abbreviation is incorrect; this could be confusing to readers.
9.
MEDIUMcopyedit
Correct 'Deidentified' to 'De-identified' in the Data availability statement.
Standard hyphenation is required for clarity.
10.
MEDIUMcopyedit
Rephrase 'included a third of the way through the trial' in the Abstract Results for clarity (e.g., 'added after one third of the trial had elapsed').
The current phrasing is grammatically awkward.
11.
LOWstatistics
Consider reporting the primary outcome p-value as 'P=0.030' (to three decimal places) for consistency with other p-values.
The paper reports P=0.03 for the primary outcome and P<0.001 for secondary outcomes; consistent formatting improves readability.
12.
LOWrigor
Provide the lot numbers of the BCG Danish and OPV vaccines used in the trial in the Methods (Procedures) section.
Lot numbers allow precise traceability of the investigational products.

Full text (47,714 chars)Analyzed: Jul 6, 2026

Read alongside