Efficacy and safety of VPM1002 and Immuvac in preventing tuberculosis: phase 3 randomised clinical trial (PreVenTB trial).
Singh M, Joshi S, Vohra V, Sarin R, Kamble SV, Velayutham B, Mohan A, Singh UB, Kumar R, Pati S, Pattnaik M, Mohapatra PR, Shankar U, Narasimhaiah S, Yadav G, Hissar S, Rodrigues R, Kadam AV, Paramasivam PK, Kambhampati S, Newtonraj A, Palaniappan NA, Reddy SD, Bhuniya S, Mishra BK, Shete A, Hanna LE, Mitra DK, Panda S, Guleria R, Tripathy S, Roy N, D'Souza G, Tripathy SK, Katoch K, Pandey RM, Sah S, Kashyap M, Telasey V, Bakshi M, Wadhwa N, Khan AM, Gangakhedkar RR, Rani R
- DOI
- 10.1136/bmj-2025-085716
- Record issued
- 2026-08-10
- Engine
- 7.29.0
- Exported
- 2026-09-22
Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/c8ea9de4-0051-4d0f-818f-f9062876542e is authoritative.
How this rating was calculated
- IntegrityIntegrity concern ×2−1★
- ClaimsOverstated claim−0.5★
- ReportingData & code availability partially met−0.25★
- CitationsUnresolved reference−0.25★
- The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run on this paper: the pass that reads its reported means did not complete. No reported mean was checked for arithmetic impossibility.
- 01Conclusion reaches beyond the evidence
Both vaccines showed efficacy against extrapulmonary TB in participants who had a positive tuberculin skin test.
“Both vaccines showed efficacy against extrapulmonary TB in participants who had a positive tuberculin skin test.”
ConclusionFind in source
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 and well-reported phase 3 RCT. The main methodological strengths are its rigorous design, comprehensive ethics documentation, and transparent reporting of outcomes. The most notable weaknesses are the incomplete identification of immunogenicity antibodies, the lack of a version-controlled repository for the analysis code, and a few internal consistency errors (Table 6 percentage) and overstatements (subgroup claim for extrapulmonary TB).
Eight dimensions were evaluated. Dimensions related to animal research, cell lines, etc., were marked not applicable. The reviewers converged on most dimensions; the main divergence was on data code availability (one rated warn, one pass) and on the adequacy of the premise rationale and reporting guideline items. The synthesis adopted the more conservative assessment where evidence was clear.
Numerical inconsistencies
1 finding · worst lowValues that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.
- Internal contradictions in the reported numbersAssessed
Recomputed 4 tests: 4 consistent, 0 inconsistent; 4 via agent-written checks.
- CONSISTENTreported p = .140 · recomputed p = .147Reviewer 2VPM1002 per-protocol vaccine efficacy against all TB: recompute two-tailed p from the hazard-ratio estimate and its 95% CI (Cox model).
“All TB | 65 (1.68) | 11 733.8 | 5.53 (4.51 to 6.79) | 82 (2.13) | 11 647.9 | 7.03 (5.87 to 8.44) | 0.45, 21.13 | 21.4 (−3.4 to 40.2) | 0.14; 21.4 (−8.9 to 43.2)”
Taken as given: Vaccine efficacy (VE) = 1 − HR, so the HR point estimate is 1 − 0.214 = 0.786; The 95% CI bounds on VE (−8.9 to 43.2) convert to HR CI bounds 1 − 0.432 = 0.568 and 1 − (−0.089) = 1.089; The CI is a 95% (two-sided) interval and the p-value derives from the same Cox modelMethod: Two-tailed p computed from the hazard-ratio point estimate and 95% CI via the normal approximation to the log-hazard (log=1).How we recomputed it: pCI(0.786, 0.568, 1.089, 1) - CONSISTENTreported p = .040 · recomputed p = .047Reviewer 2VPM1002 per-protocol vaccine efficacy against extrapulmonary TB: recompute two-tailed p from HR estimate and 95% CI.
“EPTB | 12 (0.31) | 11 733.8 | 1.02 (0.63 to 1.64) | 24 (0.62) | 11 647.9 | 2.06 (1.47 to 2.88) | 0.31, 50.0 | 50.4 (11.2 to 72.3) | 0.04; 50.4 (0.8 to 75.2)”
Taken as given: VE = 1 − HR, so HR point = 1 − 0.504 = 0.496; 95% CI bounds on VE (0.8 to 75.2) convert to HR CI bounds 1 − 0.752 = 0.248 and 1 − 0.008 = 0.992; The CI is two-sided at 95% and the p-value reflects the same Cox modelMethod: Two-tailed p computed from the hazard-ratio estimate and 95% CI via the normal approximation to the log-hazard.How we recomputed it: pCI(0.496, 0.248, 0.992, 1) - CONSISTENTreported p = .880 · recomputed p = .882Reviewer 2Immuvac per-protocol vaccine efficacy against all TB: recompute two-tailed p from HR estimate and 95% CI.
“All TB | 80 (2.09) | 11 614.8 | 6.88 (5.73 to 8.27) | 82 (2.13) | 11 647.9 | 7.03 (5.87 to 8.44) | 0.04, 1.88 | 2.3 (−26.6 to 24.5) | 0.88; 2.3 (−33.0 to 28.2)”
Taken as given: VE = 1 − HR, so HR point = 1 − 0.023 = 0.977; 95% CI bounds on VE (−33.0 to 28.2) convert to HR CI bounds 1 − 0.282 = 0.718 and 1 − (−0.33) = 1.33; The CI is two-sided at 95% and the p-value reflects the same Cox modelMethod: Two-tailed p computed from the hazard-ratio estimate and 95% CI via the normal approximation to the log-hazard.How we recomputed it: pCI(0.977, 0.718, 1.33, 1) - CONSISTENTreported p = .240 · recomputed p = .242Reviewer 2VPM1002 mITT vaccine efficacy against all TB: recompute two-tailed p from HR estimate and 95% CI.
“All TB | 73 (1.74) | 12 749.9 | 5.72 (4.72 to 6.94) | 88 (2.08) | 12 766.9 | 6.89 (5.78 to 8.21) | 0.34, 16.34 | 16.9 (−7.8 to 36) | 0.24; 16.9 (−13.3 to 39.1)”
Taken as given: VE = 1 − HR, so HR point = 1 − 0.169 = 0.831; 95% CI bounds on VE (−13.3 to 39.1) convert to HR CI bounds 1 − 0.391 = 0.609 and 1 − (−0.133) = 1.133; The CI is two-sided at 95% and the p-value reflects the same Cox modelMethod: Two-tailed p computed from the hazard-ratio estimate and 95% CI via the normal approximation to the log-hazard.How we recomputed it: pCI(0.831, 0.609, 1.133, 1)
- lowinternal contradictionTable 6 reports the placebo age 6 to <10 group as '400 (19.4)', but 400 of the 3845 placebo per-protocol participants is 10.4%, not 19.4%; this appears to be a transposition/typographical error in a reported percentage.
“Age 6 to <10 | 375 (9.72) | — | — | 400 (19.4)”
Table 6Find in source - lowinternal contradictionTable 6 reports 400 (19.4) for the placebo group aged 6 to <10 years per protocol, but 400/3845 = 10.4%, matching the VPM1002 column's 9.72% (375/3860). The printed 19.4% appears to be a transcription error.
“Age 6 to <10 | 375 (9.72) | — | — | 400 (19.4)”
Table 6Find in source
Overstated conclusions
2 findings · worst mediumConclusions 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 overstated beyond the evidenceAssessed
- Conclusions only partially backed by the presented evidenceAssessed
7 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).
- overstatedReviewers 1, 2Both vaccines showed efficacy against extrapulmonary TB in participants who had a positive tuberculin skin test.The effectiveness estimates are large but the 95% CIs cross (VPM1002) or barely exclude (Immuvac) zero and both p-values exceed 0.05, so describing them as showing efficacy is stronger than the evidence warrants for a subgroup/secondary analysis.Evidence: Per-protocol TST-positive extrapulmonary TB efficacy with Haldane's correction: VPM1002 64.9% (−2.0 to 90.1), p=0.13; Immuvac 66.3% (1.9 to 90.5), p=0.12.
“Both vaccines showed efficacy against extrapulmonary TB in participants who had a positive tuberculin skin test.”
ConclusionFind in source - partialReviewer 2Post hoc analyses showed vaccine efficacy of 64.6% (95% CI 16.3% to 85.1%) against all forms of TB, 62.1% (3.0% to 85.2%) against pulmonary TB, and 77.6% (−3.7% to 95.2%) against extrapulmonary TB in participants aged 6-14 years in the VPM1002 group.The all-TB and pulmonary-TB CIs exclude zero, but the extrapulmonary-TB CI crosses zero and the analysis is post hoc with multiple testing not adjusted, so the claim is only partially supported.Evidence: Table 6 and the post-hoc subgroup analysis report these efficacy estimates and CIs for the 6 to <14 age band.
“Post hoc analyses showed vaccine efficacy of 64.6% (95% CI 16.3% to 85.1%) against all forms of TB, 62.1% (3.0% to 85.2%) against pulmonary TB, and 77.6% (−3.7% to 95.2%) against extrapulmonary TB in participants aged 6-14 years in the VPM1002 group.”
AbstractFind in source - partialReviewer 2VPM1002 protected against extrapulmonary TB in participants who were TST positive and against TB, pulmonary TB, and extrapulmonary TB in those who were recently infected with M tuberculosis.The all-TB efficacy in recent converters is significant, but the pulmonary-TB and extrapulmonary-TB CIs cross zero and the TST-positive EPTB CI crosses zero, so the claim is only partially supported.Evidence: TST-positive EPTB efficacy 64.9% (−2.0 to 90.1); in those who converted TST-negative to positive at 6 months, efficacy was 68.4% (19.2 to 87.7) for all TB, 66.4% (−7.2 to 89.5) for PTB, and 78.9% (0.4 to 95.6) for EPTB.
“VPM1002 protected against extrapulmonary TB in participants who were TST positive and against TB, pulmonary TB, and extrapulmonary TB in those who were recently infected with M tuberculosis.”
DiscussionFind in source - supportedReviewer 1Both vaccines were safe.The safety data (local reactions in about a third of participants, SAEs in <10% per group, 109 deaths with none related to vaccines) back the safety claim.Evidence: Serious adverse events observed in <10% of each group; none related to vaccines; 109 deaths (41, 33, 35) none related.
Both the vaccines were safe. ... Serious adverse events were observed in less than 10% of the vaccinated population in each group.
Resultsreviewer’s wording - supportedReviewers 1, 2The vaccines did not show efficacy against all forms of microbiologically confirmed TB or pulmonary TB.Vaccine efficacy against all TB (21.4%, 95% CI −8.9 to 43.2, p=0.14) and pulmonary TB (19.5%, CI −14.6 to 43.4, p=0.22) includes zero and is non-significant.Evidence: Per protocol all-TB VE 21.4% (CI −8.9 to 43.2), p=0.14; PTB VE 19.5% (CI −14.6 to 43.4), p=0.22.
“Both vaccines were safe but did not show any efficacy against all forms of microbiologically confirmed TB or pulmonary TB.”
AbstractFind in source - supportedReviewers 1, 2VPM1002 showed considerable efficacy against extrapulmonary TB.Per protocol EPTB VE of 50.4% with 95% CI 0.8 to 75.2 and p=0.04 reaches significance, backing the claim.Evidence: Per protocol EPTB VE 50.4% (95% CI 0.8 to 75.2), p=0.04; mITT EPTB VE 42.3% (CI −9.1 to 69.4), p=0.09.
“VPM1002 showed considerable efficacy against extrapulmonary TB.”
AbstractFind in source - supportedReviewer 1Post hoc analysis showed VPM1002 efficacy of 64.6% against all forms of TB in participants aged 6-14 years.The post hoc per protocol analysis reports VE 64.6% (95% CI 16.3 to 85.1) against all TB in the 6-14 age group; the claim is appropriately labelled as post hoc.Evidence: Post hoc per protocol VE against all TB in VPM1002 aged 6-14: 64.6% (95% CI 16.3 to 85.1), 62.1% against pulmonary TB, 77.6% against EPTB.
Post hoc analyses showed vaccine efficacy of 64.6% (95% CI 16.3% to 85.1%) against all forms of TB ... in participants aged 6-14 years in the VPM1002 group.
Abstractreviewer’s wording
Efficacy claim is anchored to an adequate endpoint and a meaningful effect.
- ADEQUATESurrogate endpointThe primary endpoint is microbiologically confirmed TB (pulmonary and extrapulmonary), which is a hard clinical outcome, not a surrogate.
“The primary outcome was to evaluate the efficacy of VPM1002 and Immuvac in preventing microbiologically confirmed TB (pulmonary TB or extrapulmonary TB).”
- ADEQUATEEffect sizeThe primary efficacy claim for extrapulmonary TB shows a 50.4% reduction in incidence, which is statistically significant (lower bound of 95% CI 0.8%) and explicitly anchored to the pre-specified clinically meaningful reduction of 50%.
“VPM1002 showed a vaccine efficacy of 50.4% (95% CI 0.8% to 75.2%) against extrapulmonary TB, reducing the incidence of extrapulmonary TB by more than 50% (in line with our basic assumption to calculate sample sizes assuming that individual vaccines would reduce TB incidence by 50%).”
Data authenticity concerns
None foundAn 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
1 finding · worst mediumRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Data/code availability incompleteAssessed
The introduction cites TB burden statistics and the failure of BCG revaccination in Brazil and Chingleput India to motivate the trial. The rationale for choosing the two specific vaccines is deferred to the published protocol rather than stated in full, and the limitations of prior work are acknowledged only implicitly (BCG's limited protection). The hypothesis follows directly from the cited evidence.
“BCG is currently the only available licensed vaccine against TB that protects against extreme forms of TB in young children, but does not offer protection against pulmonary TB in adolescents and adults. However, BCG revaccination did not reveal encouraging results even in school age children in Brazil or in adolescents in Chingleput India.”
“The rationale for choosing VPM1002 and Immuvac has been described in the published protocol.”
“BCG is currently the only available licensed vaccine against TB that protects against extreme forms of TB in young children, but does not offer protection against pulmonary TB in adolescents and adults.”
“The rationale for choosing VPM1002 and Immuvac has been described in the published protocol.”
“However, BCG revaccination did not reveal encouraging results even in school age children in Brazil or in adolescents in Chingleput India.”
Randomization was site-specific block randomization with variable block sizes generated by an independent statistician, with allocation concealment via sealed opaque envelopes. Blinding was double-blind with participants, investigators, and staff masked; only pharmacists were unmasked (operationally necessary). Power/sample size (90% power, 2.5% alpha, 3918/group rounded to 4000) was stated. Inclusion/exclusion criteria were summarized in the text and referenced to a prior publication. Replicate distinction, controls, and independent replication are n/a for a human RCT.
“We used site specific block randomisation with variable block sizes.”
“The site pharmacists were unmasked to treatment allocation and prepared the syringes for vaccination at the site pharmacy according to the randomisation number and the randomisation schedule.”
“With 2.5% α error (significance level with adjustment for multiplicity (testing two hypotheses), ie, efficacy of each of VPM1002 and Immuvac compared with placebo), 90% power, and 10% dropout rate, the sample size was 3918 for each group, which was rounded off to 4000, and 12 000 in total.”
“Block randomisation with variable sample sizes was generated with a sequence of random numbers for each enrolment site.”
“All participants and the research investigators involved in enrolment, assigning participants to groups, and follow-up were masked to the vaccine (or placebo) received.”
“With 2.5% α error (significance level with adjustment for multiplicity (testing two hypotheses), ie, efficacy of each of VPM1002 and Immuvac compared with placebo), 90% power, and 10% dropout rate, the sample size was 3918 for each group, which was rounded off to 4000, and 12 000 in total.”
Table 1 reports sex (male/female), age groups, weight, height, BMI categories, smoking/alcohol use, medical history, and TST status for each arm. Both sexes were enrolled, so sex_justified is n/a. Species/strain and housing conditions are n/a for a human trial. Demographics include age, sex, and comorbidities; race/ethnicity is not explicitly tabulated but the population is Indian household contacts.
“Male | 1997 (47.2) | 1996 (47.1) | 1930 (45.6) | | Female | 2242 (52.8) | 2243 (52.9) | 2309 (54.4)”
“Male | 1997 (47.2) | 1996 (47.1) | 1930 (45.6)”
The ethics section lists each participating institutional ethics committee with its registration and approval numbers and dates. Written informed consent or assent is stated. Compliance with GCP and the Declaration of Helsinki, plus CDSCO regulatory approval, is described. All applicable sub-criteria are adequate.
“Ethics committee approvals were granted by the institutional human ethics committees of all participating centres in this study and the names of the ethics committees and approvals are as follows: National Institute for Research in Tuberculosis (NIRT) Chennai (including subsites): ECR/135/Inst/TN/2013/RR-19, approval No 390/NIRT-Institutional Ethics Committee (IEC)/2018 dated 5 December 2018”
“All the participants were recruited after written informed consent or assent was obtained.”
“The trial was undertaken in accordance with good clinical practice guidelines and the Declaration of Helsinki.”
“Ethics committee approvals were granted by the institutional human ethics committees of all participating centres in this study and the names of the ethics committees and approvals are as follows”
“All the participants were recruited after written informed consent or assent was obtained.”
“The trial was undertaken in accordance with good clinical practice guidelines and the Declaration of Helsinki.”
VPM1002 (Serum Institute of India), Immuvac and placebo (Cadila Pharmaceuticals) are named with manufacturers and full dosing/composition regimens. Analysis software (STATA 14.2, Graph-pad Prism 8.0.2) is identified. Although the trial includes flow-cytometry immunogenicity assays, the relevant scored resources are the investigational products and analysis software; antibody clone/vendor details for the flow assays are not reported, which is a minor gap but not scored as a bench criterion here.
“Study vaccines and placebo were provided free of cost: VPM1002 by Serum Institute of India, Pune, Immuvac and placebo by Cadila Pharmaceuticals.”
“STATA 14.2 software was used to determine vaccine efficacy using a Cox proportional hazards regression model”
“VPM1002 by Serum Institute of India, Pune, Immuvac and placebo by Cadila Pharmaceuticals.”
“STATA 14.2 software was used to determine vaccine efficacy using a Cox proportional hazards regression model”
“the peripheral blood mononuclear cells were stimulated using whole cell lysates of M tuberculosis along with costimulatory antibodies (anti-CD28 or anti-CD49d)”
Cox proportional hazards (VE=1−HR×100), Fisher's exact with Woolf/Haldane correction, and chi-square are named. Exact p-values (e.g., 0.14, 0.04) and 95% CIs are consistently reported. Rates/per-1000-person-years and percentages were checked against printed Ns and are plausible (e.g., 65/3860=1.68%, 82/3845=2.13%, 1997/4239=47.1%). Assumptions for the Cox model are handled by design for a large trial. Kaplan-Meier plots, CONSORT diagram, and per-group n are presented.
“21.4 (−3.4 to 40.2) | 0.14; 21.4 (−8.9 to 43.2)”
“Immunological data were analysed using Graph-pad prism 8.0.2 software (San Diego, CA, USA).”
“STATA 14.2 software was used to determine vaccine efficacy using a Cox proportional hazards regression model (vaccine efficacy=1−hazard ratio×100), with 95% confidence interval (CI).”
“0.14; 21.4 (−8.9 to 43.2)”
“giving a vaccine efficacy of 21.4% (95% CI −8.9% to 43.2%)”
The data availability statement names a concrete route: deidentified participant data deposited in the ICMR data repository with a public URL. Accession numbers/repository_deposit for patient-level data are managed-access and n/a. Code sharing is reported (supplementary file 2) but not in a version-controlled public repo with a permanent identifier, so it is rated reported_but_inadequate. Two of three applicable criteria are adequate → warn.
“The deidentified participant data underlying the findings in this paper have been deposited in the ICMR data repository and can be accessed publicly ( https://data.icmr.org.in/datasets/preventb-trial-data ).”
“The statistical codes used to analyse the data in the paper can be found in supplementary file 2.”
“The deidentified participant data underlying the findings in this paper have been deposited in the ICMR data repository and can be accessed publicly ( https://data.icmr.org.in/datasets/preventb-trial-data ).”
“The statistical codes used to analyse the data in the paper can be found in supplementary file 2.”
“The protocol for PreVenTB trial is publicly available (doi: 10.1136/bmjopen-2023-082916 ).”
The trial is registered (CTRI/2019/01/017026). A CONSORT diagram is included. Methods are detailed and replicable. A dedicated 'Strengths and weaknesses of the study' section addresses limitations including COVID-19-related losses to the per protocol analysis. Funding (ICMR grant number) and COI statements are provided. Conclusions are largely proportional to the data, though some post hoc subgroup claims (e.g., age 6-14) are clearly labelled as post hoc.
“Trial registration Clinical Trials Registry India CTRI/2019/01/017026.”
“A weakness of the study was that owing to the covid-19 pandemic, some participants could not be given the second dose of the vaccine, so they had to be excluded from the per protocol analysis.”
“This trial was registered at Clinical Trials Registry India (CTRI/2019/01/017026”
“A weakness of the study was that owing to the covid-19 pandemic, some participants could not be given the second dose of the vaccine, so they had to be excluded from the per protocol analysis.”
“the study is funded by ICMR, New Delhi (grant No ECD/NTF/41/2018-19, dated 28 February 2019).”
Registered (1 ID: Clinical Trials Registry – India). Reporting guideline cited: CONSORT.
Broken references and links
1 finding · worst lowReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
- References not resolvable to a published paperRecomputed
Checked 32 references by DOI: 28 verified — 1 DOI unresolved, 3 no DOI (shown, not verified).
- UNRESOLVED10.1016/s2213-2600(19Global Tuberculosis Report 2024Cited DOI does not resolve to any Crossref record.
- NO DOIIndia TB Report 2024 National TB Elimination ProgrammeNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIVaccination against tuberculosis: beyond BCGNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIRevised IAP growth charts for height, weight and body mass index for 5- to 18-year-old Indian childrenNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
2 data/code links checked; 2 live.
- datahttps://data.icmr.org.in/datasets/preventb-trial-dataLIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=Mjc0MTE=&Enc=&userName=LIVEHTTP 200Resolved page looks like data.
Copyediting
1 finding · worst lowWording, consistency and formatting errors that need correcting before submission.
- Wording or formatting errors that need correctingAssessed
8 copyedit issues flagged (2 major): mostly consistency, typo, clarity.
- MAJORconsistencyTable 6, Age 6 to <10 row“400 (19.4)”→ Change to '400 (10.4)' since 400/3845 = 10.4%.Internal percentage error; the VPM1002 column shows the correct 9.72% (375/3860).
- MAJORconsistencyTable 6“400 (19.4)”→ 400 (10.4)400 of 3845 placebo per-protocol participants is 10.4%, not 19.4%; appears to be a transposition typo.
- MINORtypoAuthor list“Bakshi Meenakshi senior onsultant”→ Change 'onsultant' to 'consultant'.Typo in author credentials.
- MINORconsistencyThroughout manuscript“VPM1002 / VPM 1002”→ Standardize the vaccine name to 'VPM1002' consistently.Inconsistent spacing of the vaccine name across text and tables.
- MINORclarityMethods, Study objectives“efficacy in preventing pulmonary TB and extrapulmonary EPTB”→ Remove the redundant 'EPTB' expansion after 'extrapulmonary'.Redundant expansion.
- MINORtypoAuthor list“Bakshi Meenakshi senior onsultant”→ senior consultantTypo in affiliation/title line.
- MINORclarityData Availability Statement“publicly available (doi: 10.1136/bmjopen-2023-082916 (10.1016/S1473-3099(11)70146-3) )”→ publicly available (doi: 10.1136/bmjopen-2023-082916)A stray unrelated DOI (S1473-3099(11)70146-3) was appended inside parentheses.
- MINORconsistencyAbstract and Results“50.4% (0.8% to 75.2%)”→ Standardise % formatting inside CIs (e.g., 0.8% to 75.2% vs 50.4 (0.8 to 75.2))Percent signs inside confidence intervals are used inconsistently between the abstract and Table 2.
This is a robustly reported trial with minor but fixable issues. An informed reader should note the overstated extrapulmonary TB subgroup claim (95% CIs cross or barely exclude zero, p>0.05) and the internal percentage error in Table 6. The authors should consider issuing a correction for the Table 6 error and tempering the claim about extrapulmonary TB efficacy. The absence of version-controlled analysis code is a transparency limitation but not a validity threat.
- 1.HIGHcopyeditCorrect the percentage for the placebo age 6 to <10 year group in Table 6 from '400 (19.4)' to '400 (10.4)' (400/3845 = 10.4%).This is an internal arithmetic error in a published table that could mislead readers about the age distribution of the per-protocol population.
- 2.HIGHrigorTemper the claim that both vaccines 'showed efficacy against extrapulmonary TB in participants who had a positive tuberculin skin test' in the Abstract and Results, noting that the 95% CIs for VPM1002 cross zero (−2.0 to 90.1) and the p-values exceed 0.05, and label this as an exploratory subgroup finding.The claim is overstated for a subgroup analysis with wide confidence intervals that include no effect, which could mislead readers about the strength of the evidence.
- 3.HIGHdata codeDeposit the statistical analysis code in a version-controlled public repository (e.g., Zenodo or GitHub with a DOI) and cite the permanent identifier in the Data Availability statement, rather than only in supplementary file 2.Code in a supplementary file is not versioned or citable, reducing reproducibility and transparency; a public repository with a DOI is the current standard.
- 4.HIGHreportingIdentify the flow-cytometry antibodies used in the immunogenicity assays (anti-CD28, anti-CD49d) by vendor, catalogue number, clone, and RRID in the Immunogenicity methods section.Without these details, the immunogenicity assay cannot be independently replicated or evaluated for reagent quality.
- 5.HIGHreportingVerify the reference 'Global Tuberculosis Report 2024' (doi: 10.1016/s2213-2600(19) that was not found in any registry; correct the citation or replace it with a verifiable source.An unresolved reference is a potential fabrication signal; it must be corrected to maintain scholarly integrity.
- 6.MEDIUMreportingAdd an explicit statement that the CONSORT checklist was completed and submitted, and reference it in the Methods or a reporting-guidelines section.While the CONSORT flow diagram is present, the absence of a checklist statement is a minor reporting gap that could be flagged by reviewers.
- 7.MEDIUMcopyeditCorrect the typo in the author list: change 'senior onsultant' to 'senior consultant' for M Bakshi.A typo in author credentials appears unprofessional and could affect indexing.
- 8.MEDIUMcopyeditStandardize the vaccine name to 'VPM1002' (without a space) throughout the manuscript, tables, and figures.Inconsistent spacing (VPM1002 vs VPM 1002) can cause confusion and looks sloppy.
- 9.MEDIUMcopyeditRemove the redundant expansion 'EPTB' after 'extrapulmonary' in the Methods section (Study objectives).The phrase 'extrapulmonary EPTB' is redundant; 'EPTB' is already defined earlier.
- 10.MEDIUMcopyeditRemove the stray unrelated DOI (10.1016/S1473-3099(11)70146-3) appended inside the protocol DOI in the Data Availability Statement.The extra DOI appears to be a copy-paste error and could confuse readers.
- 11.LOWcopyeditStandardize the formatting of percent signs inside confidence intervals (e.g., use '50.4% (0.8% to 75.2%)' consistently between the Abstract and Table 2).Inconsistent formatting of percent signs in CIs is a minor clarity issue.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.