Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.

Name: Kaimen Rigor review — Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.
Item: Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.
Rating: 59
Author: Alpha1

Patel PD, Liang Y, Meiring JE, Chasweka N, Patel P, Misiri T, Mwakiseghile F, Wachepa R, Banda HC, Shumba F, Kawalazira G, Dube Q, Nampota-Nkomba N, Nyirenda OM, Girmay T, Datta S, Jamka LP, Tracy JK, Laurens MB, Heyderman RS, Neuzil KM, Gordon MA, TyVAC team

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Kaimen Rigor review — 4★ (Strong), 0 critical, 3 high issues for “Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.”

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Alpha1 Editorial

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

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Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.

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DOI

10.1016/S0140-6736(23)02031-7

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Issued Aug 10, 2026Engine 7.29.0

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.

Paper source

Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.

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

IntegrityIntegrity concern−0.5★
ReportingStatistical analysis not met−0.5★

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

Biggest issues

01Statistical reporting inadequate
highDisclosurereviewer-assessedFull detail
Statistical methods and reporting are generally strong (tests named, exact p-values, CIs, software), but Table 3 contains a demonstrable arithmetic inconsistency in the third-year Vi-TT incidence rate.
“Third year | | Vi-TT | 14 043 | 14 031 | 3 | 93·1 (54·1–160·3) | 77·0% (16·4–95·8)”
Table 3Find in source
02Internal contradictions in the reported numbers
mediumArithmeticreviewer-assessedFull detail
Table 3's third-year Vi-TT incidence rate (93·1 per 100 000 person-years) is inconsistent with its own numerator and denominator (3 cases / 14 031 person-years = 21·4 per 100 000) and duplicates the MenA row's rate and CI.
“Third year | | Vi-TT | 14 043 | 14 031 | 3 | 93·1 (54·1–160·3) | 77·0% (16·4–95·8) | | MenA | 13 976 | 13 963 | 13 | 93·1 (54·1–160·3) | Ref |”
Table 3Find in source

Findings by category

101ArithmeticNumerical inconsistencies 02OverreachNone found 03AuthenticityNone found 104DisclosureReporting gaps 05AvailabilityNone found 106CopyeditCopyediting

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-designed and generally well-reported Phase 3 clinical trial with a strong scientific premise and robust ethical approvals. However, a critical arithmetic inconsistency in a key results table and the absence of reported baseline weight for a pediatric cohort slightly diminish its rigor. The lack of explicit reference to a reporting guideline also represents a minor reporting gap.

This review synthesized two independent rigor evaluations and a copyedit report. The reviewers largely agreed, with the main divergences concerning the completeness of biological variable reporting and the severity of the reporting guideline omission. The statistical analysis dimension's 'fail' status is driven by a clear arithmetic error identified by Reviewer 2, the integrity component, and the copyedit pass.

Numerical inconsistencies

1 finding · worst medium

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Internal contradictions in the reported numbersAssessed

Recomputed 1 test: 1 consistent, 0 inconsistent; 1 via agent-written checks.

Overstated conclusions

None found

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.

Checked — nothing surfaced.

6 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

1 finding · worst high

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.

Statistical reporting inadequateAssessed

Eight Dimensions7 pass · 1 fail

The introduction and 'Research in context' sections cite extensive prior work, including Cochrane reviews and earlier efficacy trials, and explicitly note the gap in long-term durability data. The rationale for the study is logically derived from the cited evidence, and the paper discusses how the limitations of prior studies (e.g., short follow-up, lack of data in children under 2 years) are addressed in this trial.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper thoroughly establishes the scientific premise by citing prior research, clearly articulating the rationale for the study, and addressing limitations of previous work.

Evidence

“A Cochrane systematic review estimated that the efficacy of Vi-PS fell from 69% (95% CI 63–74) after 1 year to 55% (95% CI 30–70) after 3 years.”

Introduction ¶3Find in source

“We present the final efficacy results of single-dose Vi-TT over an extended median follow-up time of 4·3 years, and by age group, including children younger than 2 years of age.”

Introduction ¶6Find in source

“Data on the durability of protection beyond 2 years are sparse.”

Introduction ¶5Find in source

PASSReviewer 2· 90% conf

The paper establishes a strong scientific premise with extensive prior literature, identifies the durability gap, and frames the study to address it.

Evidence

“Data on the durability of protection beyond 2 years are sparse.”

IntroductionFind in source

“This is the first randomised, controlled, double-blind trial to evaluate the longer-term efficacy of single-dose TCV in a typhoid fever-endemic setting from 9 months of age.”

Research in context, Added valueFind in source

“A Cochrane systematic review estimated that the efficacy of Vi-PS fell from 69% (95% CI 63–74) after 1 year to 55% (95% CI 30–70) after 3 years.”

IntroductionFind in source

Randomization uses block randomization with block sizes 6-12, generated by an unmasked statistician using the blockrand package in R. The unit of randomization is individual children. Blinding is double-blind, with participants, parents, and study team masked; only nurses administering vaccines were unmasked, which is acceptable. A power analysis was performed assuming 75% efficacy, 90% power, and a minimum of 30 cases. Inclusion/exclusion criteria are specified. The analysis populations (ITT and per-protocol) are defined, and handling of missing data is addressed through censoring in survival analysis.

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· 95% conf

The study design is rigorous for a human RCT, with clear randomization, blinding, sample size calculation, and pre-specified analysis populations.

Evidence

“Block randomisation was used with block sizes of 6–12. The randomisation allocation sequence was generated by an unmasked statistician using the blockrand package (version 1.3) in R (version 3.4.1).”

Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.

Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.

Numerical inconsistencies

Overstated conclusions

Data authenticity concerns

Reporting gaps

Broken references and links

Copyediting

Numerical inconsistencies

Overstated conclusions

Data authenticity concerns

Reporting gaps

Broken references and links

Copyediting