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: Adcurare Rigor Record — 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: 100
Author: Adcurare

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

Paper source

Read full text (PMC)Journal

Embed this Rigor badge

Adcurare Rigor Review — 3.5★ (Adequate), 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.”

Links back to this Rigor Record.

Adcurare Editorial

This rigor review was examined and confirmed by Adcurare Editorial · July 7, 2026

Adcurare Rigor Review

Rigor Reviewed

3.5 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×3−1.5★

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

Problems surfaced1 type

Internal contradictions in the reported numbers

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 manuscript reports a rigorous phase 3 double-blind randomised controlled trial of a typhoid conjugate vaccine (Vi-TT) versus a control vaccine (MenA) in Malawian children with over 4 years of follow-up. The design, statistical analysis, and reporting are of high quality, with only minor gaps in the explicit mention of a reporting guideline and statistical assumption verification. The copyedit pass and integrity verification reveal a clear copy-paste error in Table 3 (identical incidence rates for Vi-TT and MenA in the third year) that must be corrected before submission.

The evaluation is based on full-text review by three independent rigor reviewers, a copyedit pass, and verification components for citations, statistics, reproducibility, preregistration, and integrity. The statistics verification covered 7 recomputations (all consistent) but does not cover all analyses (e.g., threshold-only p-values). The citation check found no retracted or missing references. One internal contradiction (Table 3) was flagged by the integrity check and copyedit, which is the most consequential finding.

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

Recomputed 7 tests: 7 consistent, 0 inconsistent, 7 via agent-written checks.

3 integrity concerns flagged (0 high).

Reporting

Eight Dimensions8 pass

The introduction thoroughly reviews the burden of typhoid fever, limitations of older vaccines (Vi-PS, Ty21a), and prior TCV trials. The 'Research in context' section and 'Added value of this study' explicitly address gaps (e.g., lack of long-term efficacy data, efficacy in children <2 years). The premise rationale is strong: prior trials showed high efficacy at 18–36 months, but durability beyond 2 years was unknown, justifying this 4-year follow-up.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The scientific premise is well-established with extensive prior work cited, a clear rationale linking the premise to the study objectives, and limitations of prior research addressed.

Evidence

direct quote[Introduction, paragraphs 2–5; 'Research in context' panel]

“Before 2017, globally available vaccines against typhoid fever included a parenteral Vi polysaccharide vaccine (Vi-PS) and the live oral Ty21a vaccine. Neither, however, are approved for use in children younger than 2 years, and both require repeated dosing for durable efficacy. 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.”

direct quote[Abstract, 'Background']

“Data on the durability of protection beyond 2 years are sparse. We present the final analysis of a randomised controlled trial in Malawi, encompassing more than 4 years of follow-up, with the aim of investigating vaccine efficacy over time and by age group.”

direct quote['Added value of this study' panel, under 'Research in context']

“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.”

PASSReviewer 2· 95% conf

The paper establishes a strong scientific premise by citing prior work on typhoid burden, limitations of older vaccines, and short-term efficacy of TCVs, and clearly links this to the need for longer-term efficacy data.

Evidence

direct quote[Introduction, paragraphs 1-3]

“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.”

direct quote[Introduction, paragraph 4]

direct quote[Introduction, 'Added value of this study']

“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.”

PASSReviewer 3· 95% conf

The paper comprehensively establishes the scientific premise by citing prior research on typhoid burden, limitations of previous vaccines, and prior TCV trials, with a clear rationale linking to the study objectives.

Evidence

direct quote[Introduction, paragraph 3]

“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.”

direct quote[Abstract, Interpretation]

“These results support current WHO recommendations in typhoid-endemic areas for mass campaigns among children aged 9 months to 15 years, followed by routine introduction in the first 2 years of life.”

direct quote[Introduction, paragraph 4]

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

Randomization used block randomisation with block sizes 6–12 and a computer-generated sequence (blockrand package). The randomization unit is the individual child. Blinding: participants, parents/guardians, and the study team (except unmasked vaccination nurses) were masked; this is adequate. A sample size calculation is referenced and summarized: 30 total cases needed for 90% power assuming 75% efficacy. Inclusion and exclusion criteria are stated. The control is an active comparator (MenA vaccine). No separate replication cohort is reported, but this is not applicable for a single pivotal phase 3 trial of this nature.

Sub-criteria

controlsADEQUATE

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· 95% conf

The study design is rigorous: it is a double-blind, randomized controlled trial with appropriate randomization, masking, a prespecified power analysis, clear inclusion/exclusion criteria, and a control vaccine.

Evidence

direct quote[Methods, 'Randomisation and masking']

“Participants, their parents or guardians, and the study team involved in subsequent disease surveillance screening, eligibility assessment, and follow-up were masked to vaccine allocation.”

direct quote[Methods, 'Statistical analysis']

“Details of sample size and power calculations have been reported. Briefly, assuming 75% vaccine efficacy, the minimum number of total cases needed to test the null hypothesis that the vaccine has no protective efficacy (ie, vaccine efficacy ≤0), with 90% power, was 30.”

PASSReviewer 2· 95% conf

The study design is rigorous: a phase 3, double-blind, randomised controlled trial with appropriate randomisation, masking, and pre-specified analyses. Most applicable sub-criteria are adequately reported.

Evidence

direct quote[Methods, 'Randomisation and masking']

“Participants, their parents or guardians, and the study team involved in subsequent disease surveillance screening, eligibility assessment, and follow-up were masked to vaccine allocation.”

direct quote[Methods, 'Statistical analysis']

“Briefly, assuming 75% vaccine efficacy, the minimum number of total cases needed to test the null hypothesis that the vaccine has no protective efficacy (ie, vaccine efficacy ≤0), with 90% power, was 30.”

PASSReviewer 3· 95% conf

The study design is rigorously reported: it is a double-blind, randomised controlled trial with clear randomization methods, masking, pre-specified inclusion/exclusion criteria, a power analysis, and per-protocol and intention-to-treat analyses.

Evidence

direct quote[Methods, Randomisation and masking]

“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). The randomisation allocation sequence was uploaded to password-protected tablets and accessed only by a restricted number of unmasked vaccination nurses in real time, immediately before vaccination, in screened-off vaccination areas.”

direct quote[Methods, Randomisation and masking]

“Participants, their parents or guardians, and the study team involved in subsequent disease surveillance screening, eligibility assessment, and follow-up were masked to vaccine allocation. Nurses administering vaccines were unmasked.”

direct quote[Methods, Statistical analysis]

“Assuming 75% vaccine efficacy, the minimum number of total cases needed to test the null hypothesis that the vaccine has no protective efficacy (ie, vaccine efficacy ≤0), with 90% power, was 30.”

Sex is reported for both groups (Table 1: ~50% female each). Age is reported as mean, median, and age groups (<2, 2–4, ≥5 years). Ethnicity is reported as 'Black African' for all participants. Age and sex are also used in subgroup analyses. Species/strain/source and housing conditions are not applicable for a human trial. Sex_justified is not_applicable because both sexes were enrolled.

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

Biological variables appropriate for a human trial are thoroughly reported: sex, age, and demographics.

Evidence

direct quote[Table 1]

“Sex: Female: Vi-TT 7065 (50.2%), MenA 7231 (51.4%); Male: Vi-TT 7004 (49.8%), MenA 6830 (48.6%)”

direct quote[Methods and Table 1]

“Age at enrolment (years): Mean (SD) 6.1 (3.3) for Vi-TT, 6.2 (3.3) for MenA. Median (range) 6.0 (0.8–12.0) for both.”

direct quote[Table 1]

“Ethnicity: Black African: 14 069 (100.0%), 14 061 (100.0%)”

PASSReviewer 2· 95% conf

Key biological variables for a human trial are reported: sex, age, and ethnicity are provided in Table 1. Sex is reported for both groups, and since both sexes are enrolled, a justification for single-sex is not applicable.

Evidence

direct quote[Table 1]

“Sex: Female 7065 (50.2%) in Vi-TT, 7231 (51.4%) in MenA; Male 7004 (49.8%) in Vi-TT, 6830 (48.6%) in MenA.”

direct quote[Table 1]

“Age at enrolment (years): Mean (SD) 6.1 (3.3) for Vi-TT, 6.2 (3.3) for MenA; Median (range) 6.0 (0.8–12.0) for both.”

direct quote[Table 1]

“Ethnicity: Black African 14 069 (100.0%) for Vi-TT, 14 061 (100.0%) for MenA.”

PASSReviewer 3· 90% conf

Biological variables are well-reported: sex, age, health status, and demographics are provided. Species/strain/source is not applicable as this is a human study, and housing conditions are not applicable.

Evidence

direct quote[Table 1]

“Female: 7065 (50·2%) Vi-TT, 7231 (51·4%) MenA”

direct quote[Table 1]

“Age at enrolment (years): Mean (SD): 6·1 (3·3) Vi-TT, 6·2 (3·3) MenA”

direct quote[Table 1]

“Black African: 14 069 (100·0%) Vi-TT, 14 061 (100·0%) MenA”

Local ethics approval from the Malawi National Health and Sciences Research Committee, international ethics approval from the University of Liverpool Ethics Review Board and the University of Maryland Baltimore Institutional Review Board are all named. Written informed consent from parent/guardian and assent from children ≥8 years are described. The study states compliance with Good Clinical Practice guidelines.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approvals are fully documented: named local and international ethics committees approved the study, informed consent was obtained, and regulatory compliance is stated.

Evidence

direct quote[Methods, 'Study design']

“Local ethics approval was obtained from the Malawi National Health and Sciences Research Committee, and international ethics approval from the University of Liverpool Ethics Review Board and the University of Maryland Baltimore Institutional Review Board.”

direct quote[Methods, 'Participants']

“Written informed consent was obtained from the parent or guardian of all children before any study procedures, and written assent was also required for all children aged 8 years and older.”

direct quote[Methods, 'Study design']

“This study was conducted under Good Clinical Practice guidelines, with internal and external monitoring for quality.”

PASSReviewer 2· 95% conf

Ethical approvals are adequately reported: named ethics committees approved the study, informed consent was obtained, and regulatory compliance is stated.

Evidence

direct quote[Methods, 'Study design']

direct quote[Methods, 'Participants']

“Written informed consent was obtained from the parent or guardian of all children before any study procedures, and written assent was also required for all children aged 8 years and older.”

direct quote[Methods, 'Study design']

“This study was conducted under Good Clinical Practice guidelines, with internal and external monitoring for quality.”

PASSReviewer 3· 95% conf

Ethical approvals are reported: local and international ethics committees are named, written informed consent (and assent for older children) is described, and regulatory compliance (Good Clinical Practice) is stated.

Evidence

direct quote[Methods, Study design]

direct quote[Methods, Participants]

“Written informed consent was obtained from the parent or guardian of all children before any study procedures, and written assent was also required for all children aged 8 years and older.”

direct quote[Methods, Study design]

“This study was conducted under Good Clinical Practice guidelines, with internal and external monitoring for quality.”

The two vaccines are identified: Vi-TT (Bharat Biotech International, Hyderabad, India) and MenA (Serum Institute of India, Pune, India). The statistical software is identified (Stata/SE version 17). REDCap database is mentioned. No antibodies, cell lines, mycoplasma testing, or organisms are applicable. No custom analysis code is mentioned as deposited, but software is standard.

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

Key resources are adequately identified: vaccines are named with manufacturer and formulation; statistical and data-collection software are identified with versions.

Evidence

direct quote[Methods, 'Randomisation and masking']

“Vi-TT (Bharat Biotech International, Hyderabad, India) or a meningococcal capsular group A conjugate control vaccine (MenA, Serum Institute of India, Pune, India).”

direct quote[Methods, 'Statistical analysis']

“All analyses were performed using Stata/SE version 17.”

direct quote[Methods, 'Statistical analysis']

“All trial data were collected directly on tablets by study staff and uploaded to a REDCap database.”

PASSReviewer 2· 95% conf

Key resources are adequately identified: the investigational products (Vi-TT and MenA) are named with manufacturer and source, and statistical software is identified with version.

Evidence

direct quote[Methods, 'Randomisation and masking']

“Children were randomly assigned (1:1) to receive a single dose of either Vi-TT (Bharat Biotech International, Hyderabad, India) or a meningococcal capsular group A conjugate control vaccine (MenA, Serum Institute of India, Pune, India).”

direct quote[Methods, 'Statistical analysis']

“All analyses were performed using Stata/SE version 17.”

PASSReviewer 3· 95% conf

Key resources are adequately identified: the investigational vaccines (Vi-TT and MenA) are named with manufacturer and location; statistical software (Stata/SE version 17) is identified. Other sub-criteria (antibodies, cell lines, mycoplasma, organisms) are not applicable as this is a human clinical trial with no wet-lab bench components.

Evidence

direct quote[Methods, Randomisation and masking]

“Vi-TT (Bharat Biotech International, Hyderabad, India)”

direct quote[Methods, Randomisation and masking]

“MenA (Serum Institute of India, Pune, India)”

direct quote[Methods, Statistical analysis]

“All analyses were performed using Stata/SE version 17.”

The primary analysis uses incidence rate ratio and vaccine efficacy calculation, with 95% CIs. Subgroup analyses use the Mantel-Haenszel method. Kaplan-Meier method with log-rank and Wilcoxon-Breslow-Gehan tests is used. Exact p-values are provided (e.g., p=0.77, p<0.0001, p=0.85, p=0.44, p=0.65). Effect sizes (vaccine efficacy) and 95% CIs are the main reporting format. Software is Stata/SE v17. The data presentation includes individual person-time contributions; per-group Ns are in tables. No arithmetic errors are apparent. Assumptions_verified is not explicitly tested for normality/equal variance, but the analysis uses standard large-sample methods (incidence rate ratios, Mantel-Haenszel) where those assumptions are less critical; this is adequate for a trial of this scale.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Statistical analysis is rigorous: tests are named, exact p-values are reported (e.g., p=0.77 for trend, p<0.0001 for Kaplan-Meier), effect sizes with 95% CIs are given, software is identified, and data presentation includes person-years incidence, NNT, and Kaplan-Meier curves. Mathematical plausibility is not applicable for continuous outcomes with large N.

Evidence

direct quote[Methods, 'Statistical analysis']

“The vaccine efficacy was calculated as (1 – incidence rate ratio) × 100%, where the incidence rate ratio was defined as the ratio of the incidence rate in the Vi-TT group to that in the MenA group.”

direct quote[Results and Table 3 footnotes]

“The trend in efficacy by yearly increments, analysed using a random effects meta-regression taking into account the precision for each annual estimate, suggests there was a 1.3% decline in vaccine efficacy each year (slope –0.013, 95% CI –0.098 to 0.072, p=0.77).”

direct quote[Abstract and Table 2]

“efficacy of Vi-TT was 78.3% (95% CI 66.3–86.1)”

PASSReviewer 2· 95% conf

Statistical analysis is rigorous: tests are named, exact p-values are reported, effect sizes with confidence intervals are provided, software is identified, and data presentation is clear. Assumptions are not explicitly verified but are standard for the methods used.

Evidence

direct quote[Results, paragraph 5]

“The overall vaccine efficacy was similar among the three age groups (70.6% for children younger than 2 years, 79.6% for children aged 2–4 years, and 79.3% for children aged 5–12 years; p=0.85).”

direct quote[Table 2]

“Protective efficacy of Vi-TT (95% CI): 78.3% (66.3–86.1) for intention-to-treat population.”

direct quote[Methods, 'Statistical analysis']

“All analyses were performed using Stata/SE version 17.”

PASSReviewer 3· 90% conf

Statistical analysis is rigorous: tests are named (e.g., log-rank, Mantel-Haenszel, weighted linear regression), exact p-values are reported, effect sizes with 95% CIs are provided, software is identified, and data presentation includes per-group n, incidence rates, and Kaplan-Meier curves. Assumption verification is not explicitly detailed, which is acceptable for a large trial using standard methods.

Evidence

direct quote[Results, paragraph 5]

“the trend in efficacy by yearly increments...slope –0·013, 95% CI –0·098 to 0·072, p=0·77”

direct quote[Abstract, Findings]

“efficacy of Vi-TT was 78·3% (95% CI 66·3–86·1)”

direct quote[Methods, Statistical analysis]

“All analyses were performed using Stata/SE version 17.”

There is a dedicated 'Data sharing' section stating data will be available on the Vivli platform (a named managed-access platform for clinical trial data). This meets the standard for patient-level data: a concrete access route with conditions. No depositable non-identifiable data (e.g., sequencing) were generated. No bespoke code was written beyond standard statistical software, so code_sharing is not_applicable.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Data availability is concretely stated: the full dataset will be available on the Vivli platform with a searchable link. Code sharing is not applicable as standard software was used.

Evidence

direct quote['Data sharing' section]

“The full data set will be available on the Vivli platform ( https://search.vivli.org/studyDetails/fromSearch/0bb6a051-8149-4161-bb99-d95cdc700714 ).”

PASSReviewer 2· 95% conf

Data availability is adequately addressed: a data sharing statement is provided with a concrete route via the Vivli platform. Code sharing is not applicable as the analysis used standard statistical software.

Evidence

direct quote[Data sharing section]

“The full data set will be available on the Vivli platform ( https://search.vivli.org/studyDetails/fromSearch/0bb6a051-8149-4161-bb99-d95cdc700714 ).”

PASSReviewer 3· 95% conf

Data availability is well-handled: a data-sharing statement is provided with a concrete route via the Vivli platform, including a direct link/identifier. Code sharing is not applicable as the analysis used standard statistical software (Stata); no custom code is mentioned.

Evidence

direct quote[Data sharing]

“The full data set will be available on the Vivli platform ( https://search.vivli.org/studyDetails/fromSearch/0bb6a051-8149-4161-bb99-d95cdc700714 ).”

Methods are very detailed, including randomization, surveillance, and statistical analysis. Trial registration is provided with number and URL. Limitations are discussed (COVID-19 disruption, potential underestimation of incidence, loss to follow-up). Conclusions are proportional and align with what the data show. Funding (Bill & Melinda Gates Foundation) and author conflicts of interest are stated. No formal reporting guideline checklist is mentioned, but the reporting is consistent with CONSORT standards (flow diagram, registration).

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

Reporting is highly transparent: methods are detailed, the trial is registered (NCT03299426), limitations are discussed, conclusions are proportional, and funding/COI are disclosed. A specific reporting guideline (CONSORT) is not mentioned, but the trial follows standard clinical trial reporting norms with a flow diagram.

Evidence

direct quote[Abstract and Methods]

“This trial is registered at ClinicalTrials.gov (http://ClinicalTrials.gov), NCT03299426 (https://clinicaltrials.gov/ct2/show/NCT03299426).”

direct quote[Discussion, paragraph 6]

“This trial had some limitations. The number of children presenting for passive surveillance and blood culture collection decreased during the first 2 years.”

direct quote['Declaration of interests' and 'Acknowledgments']

“Funding: Bill & Melinda Gates Foundation. YL, SD, LPJ, MBL, and KMN receive funding from the TyVAC grant (grant number OPP1151153).”

PASSReviewer 2· 95% conf

Reporting is transparent: methods are detailed, the trial is registered, limitations are discussed, conclusions are proportional, and funding/COI are disclosed. A reporting guideline is not explicitly referenced but the paper follows CONSORT-like structure.

Evidence

direct quote[Abstract and Methods]

“This trial is registered at ClinicalTrials.gov (http://ClinicalTrials.gov), NCT03299426 (https://clinicaltrials.gov/ct2/show/NCT03299426).”

direct quote[Discussion, paragraph 5]

“This trial had some limitations. The number of children presenting for passive surveillance and blood culture collection decreased during the first 2 years.”

direct quote[Declaration of interests and Acknowledgments]

“Funding Bill & Melinda Gates Foundation.”

PASSReviewer 3· 95% conf

Reporting transparency is high: methods are detailed, the trial is registered (NCT03299426), limitations are discussed, conclusions are proportional, and funding/COI are declared. A reporting guideline (e.g., CONSORT) is not explicitly mentioned, but the paper follows clinical trial reporting standards.

Evidence

direct quote[Abstract, Methods]

“This trial is registered at ClinicalTrials.gov (http://ClinicalTrials.gov), NCT03299426 (https://clinicaltrials.gov/ct2/show/NCT03299426).”

direct quote[Discussion, paragraph 4]

“The COVID-19 pandemic further disrupted surveillance activities, with an initial suspension of study activities for nearly 5 months, followed by resumption of surveillance.”

direct quote[Methods, Role of the funding source]

“The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.”

3 copyedit issues flagged: mostly typo, clarity.

Checked 29 references: 26 verified — 3 not checked.

Reproducibility

2 data/code links checked; 2 live.

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

Adcurare Rigor Action ItemsFinal pass before journal submission

The manuscript is essentially ready for submission after correcting one critical data error in Table 3 (identical Vi-TT and MenA incidence rates in Year 3) and adding a CONSORT reporting guideline statement. No major methodological or integrity concerns remain; the paper is of very high quality.

1.
HIGHrigor
Correct the copy-paste error in Table 3, 'Discrete time: Third year', where the incidence rate for Vi-TT (93.1 per 100,000 person-years) is identical to that of MenA, which is inconsistent with the case counts (3 vs 13) and the reported vaccine efficacy for that period. Replace with the correct Vi-TT incidence rate (likely much lower).
This is an internal contradiction that, if published, would be called out by readers and reviewers as a data error or fabrication signal.
2.
HIGHreporting
In the Methods (under Statistical analysis), add a sentence briefly stating that key model assumptions (e.g., proportional hazards for the log-rank test, Poisson assumptions for incidence rates) were checked and were met or are robust given the large sample size.
All three reviewers flagged the absence of explicit assumption verification as a minor gap; this addition will preempt reviewer questions about statistical appropriateness.
3.
HIGHreporting
In the Methods, add a sentence stating that the trial is reported in accordance with the CONSORT 2010 statement, and optionally provide the completed CONSORT checklist as a supplementary file.
Explicitly naming the reporting guideline is a standard expectation for clinical trials and improves transparency; it was flagged by all reviewers as a minor omission.
4.
MEDIUMreporting
In the Methods (Statistical analysis), briefly describe how protocol deviations or outliers were handled in the analysis (e.g., whether any children were excluded from the per-protocol set beyond the standard vaccination and follow-up criteria).
One reviewer noted that outlier handling was not explicitly discussed; adding a brief sentence clarifies the analysis approach.
5.
LOWdata code
Once the data are deposited, replace the Vivli URL with a more permanent identifier (e.g., DOI) to ensure a stable link.
The current URL may change; a DOI provides a persistent link.
6.
LOWreporting
Consider providing the Stata analysis code (e.g., a .do file) as a supplementary item to facilitate reproducibility.
Though the analysis uses standard software, making the code available allows independent verification and is increasingly expected by journals.

Full text (48,231 chars)Analyzed: Jul 7, 2026

Read alongside

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

Read full text (PMC)

Journal

DOI

10.1016/S0140-6736(23)02031-7

Share this Rigor Review

Post on X Share on LinkedIn Share via Email

Embed this Rigor badge

<a href="https://adcurare.com/verify/ce653ac7-61f8-4824-bb88-aa254db456e1" target="_blank" rel="noopener">
  <img src="https://adcurare.com/verify/ce653ac7-61f8-4824-bb88-aa254db456e1/badge" alt="Adcurare Rigor Review — 3.5★ (Adequate), 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.”" width="440" height="104" style="max-width:100%;height:auto" />
</a>

Every embed links back to this Rigor Record.

Record fingerprint

ac09c1d3a1c604f0b66d48bc0afc17530244e4dd9ddb121b37097d443ea203be

Verify via API

Issued Jul 7, 2026Engine 7.6.0

Adcurare assesses methodological rigor, not the importance of the findings. See how we evaluate →