Rigor Reviewed

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Mass azithromycin distribution and antibiotic resistance in the gut and nasopharynx: a cluster-randomized trial.

Name: Adcurare Rigor Record — Mass azithromycin distribution and antibiotic resistance in the gut and nasopharynx: a cluster-randomized trial.
Item: Mass azithromycin distribution and antibiotic resistance in the gut and nasopharynx: a cluster-randomized trial.
Rating: 100
Author: Adcurare

Doan T, Yan D, Arzika AM, Abdou A, Maliki R, Aichatou B, Bello IM, Beidi D, Galo N, Harouna N, Karamba AM, Mahamadou S, Abarchi M, Ibrahim A, Zhong L, Chen C, Liu Y, Yu D, Abraham T, Cheng AS, Peterson B, Oldenburg CE, Porco TC, Arnold BF, Hinterwirth A, Lebas E, O'Brien KS, Lietman TM

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Adcurare Rigor Review — 4.75★ (Strong), 0 critical, 3 high issues for “Mass azithromycin distribution and antibiotic resistance in the gut and nasopharynx: a cluster-randomized trial.”

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Adcurare Editorial

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

Adcurare Rigor Review

Rigor Reviewed

4.75 / 5

Strong — minor issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

LinksDead data/code link−0.25★

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

Problems surfaced1 type

Dead data/code links

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.

The paper is methodologically rigorous: a well-designed cluster-randomized trial with clear randomization, blinding, power analysis, and appropriate statistical methods. Minor reporting gaps exist in code sharing, reagent catalog numbers, and outlier handling, but none threaten the validity of the findings.

Evaluated full text. Three independent reviewers scored all dimensions; their assessments converged strongly. The statistics verification component checked 6 tests, all consistent. No retracted or missing references were found. The copyedit pass flagged 9 minor issues (typos, clarity).

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

Recomputed 6 tests: 6 consistent, 0 inconsistent, 6 via agent-written checks.

Reporting

Eight Dimensions8 pass

The Introduction cites prior MORDOR and AVENIR trials on azithromycin MDA and mortality, as well as WHO guidelines. The rationale follows logically: repeated azithromycin MDA reduces mortality but risks AMR selection, and the study aims to quantify that risk across different age-targeting strategies. The Discussion explicitly addresses how limitations of prior studies (e.g., lack of placebo arm, spillover) are being addressed in ongoing work.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper clearly establishes its scientific foundation by citing prior work on azithromycin MDA and childhood mortality, provides a logical rationale for the study, and addresses limitations of prior research.

Evidence

direct quote[Introduction, paragraph 1]

“Mass drug distribution (MDA) of broad-spectrum antibiotics to preschool children prevents mortality of those under 5 years old in some regions in sub-Saharan Africa... Currently, Niger, Nigeria, Burkina Faso and Mali are implementing large-scale programs distributing azithromycin every 6 months to all children aged 1–59 months.”

direct quote[Introduction, paragraph 2]

“A fundamental challenge for local stakeholders and policymakers has been how to best balance the mortality benefits of azithromycin MDA with the risk of AMR selection.”

direct quote[Discussion, paragraph 6]

“That study, however, lacked a placebo arm for all 5 years, and AMR spillover among communities may have been a confounder and cannot be ruled out. The ongoing AVENIR II was designed to address the effect of spillover.”

PASSReviewer 2· 95% conf

The premise is well-established with citations to prior trials on azithromycin MDA and childhood mortality, and the rationale for studying AMR is clearly linked to public health needs.

Evidence

direct quote[Main, paragraph 1]

“Mass drug distribution (MDA) of broad-spectrum antibiotics to preschool children prevents mortality of those under 5 years old in some regions in sub-Saharan Africa – .”

direct quote[Main, paragraph 2]

“A fundamental challenge for local stakeholders and policymakers has been how to best balance the mortality benefits of azithromycin MDA with the risk of AMR selection , .”

direct quote[Main, paragraph 2]

“Before this study, the World Health Organization’s (WHO) conditional guidelines in 2020 were to target children aged 1–11 months to reduce the risk of antimicrobial resistance (AMR) selection . Given the challenging ethical issues involved, several additional trials were conducted after this time to provide extra data to help weigh the risks versus benefits before programs began on a larger scale, even though the guidelines were already available.”

PASSReviewer 3· 90% conf

The paper clearly establishes its scientific foundation by citing prior work on azithromycin MDA and childhood mortality, provides a logical rationale for the AMR study, and acknowledges limitations of prior research.

Evidence

direct quote[Main, paragraph 1]

“Mass drug distribution (MDA) of broad-spectrum antibiotics to preschool children prevents mortality of those under 5 years old in some regions in sub-Saharan Africa – . Currently, Niger, Nigeria, Burkina Faso and Mali are implementing large-scale programs distributing azithromycin every 6 months to all children aged 1–59 months.”

direct quote[Main, paragraph 2]

“A fundamental challenge for local stakeholders and policymakers has been how to best balance the mortality benefits of azithromycin MDA with the risk of AMR selection.”

paraphrase[Main, paragraph 2]

“The study was conducted to provide extra data to help weigh risks versus benefits before large-scale programs began.”

Randomization method is described (response-adaptive, biostatistician-generated sequence in R) and the unit (community/grap). Blinding is comprehensive: all study personnel, participants, laboratory, and field workers masked; treatment concealment via identical packaging. Power analysis is reported for both nasopharyngeal and rectal swab primary endpoints with assumptions based on prior data. Inclusion/exclusion criteria are clearly prespecified at community and individual levels. Controls: both a placebo arm and an active comparator (infant-azithromycin) are used. No independent replication cohort is reported (common for a single large trial; this is the primary analysis). Outlier handling is not explicitly described but the pre-specified analysis approach (Wilcoxon) is non-parametric and robust. Replicate distinction (biological vs technical) is not explicitly defined but pooling at the village level is the unit of analysis, and the sample size accounts for community-level effects.

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingNOT REPORTED

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionNOT REPORTED

independent replicationNOT REPORTED

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study design is rigorous: cluster-randomized, double-blind, placebo-controlled, with a priori power analysis, clear eligibility criteria, and appropriate controls. Masking and randomization are well described.

Evidence

direct quote[Methods, Randomization and masking]

“The AVENIR trial used response-adaptive randomization at the community level. ... The randomization sequence was generated by a biostatistician who was aware of the group assignments, using the R software.”

direct quote[Methods, Sample size]

“For load of genetic resistance determinants in nasopharyngeal swabs, we estimated that 50 communities per group would provide 80% power to detect an approximately 2-fold difference in any pairwise comparison, assuming an alpha of 0.05 and a s.d. of the log base 2 read count of 1.88.”

direct quote[Methods, Randomization and masking]

“Aside from the UCSF biostatistician and data analyst responsible for the randomization, all other study personnel, participants, laboratory personnel and all field workers responsible for administering and sample collection were masked to treatment allocation.”

PASSReviewer 2· 92% conf

The design is rigorous: a double-blind, cluster-randomized, placebo-controlled trial with a response-adaptive randomization, clear masking, and adequate sample size justification.

Evidence

direct quote[Methods, Randomization and masking]

“The randomization sequence was generated by a biostatistician who was aware of the group assignments, using the R software... The randomization unit was the grappe (community).”

direct quote[Methods, Randomization and masking]

direct quote[Methods, Sample size]

PASSReviewer 3· 85% conf

The study design is rigorous with clear randomization, blinding, power analysis, and inclusion/exclusion criteria, though outlier handling is not explicitly reported.

Evidence

direct quote[Methods, Randomization and masking]

“The AVENIR trial used response-adaptive randomization at the community level. The randomization sequence was generated by a biostatistician who was aware of the group assignments, using the R software (R Foundation for Statistical Computing).”

direct quote[Methods, Randomization and masking]

“All other study personnel, participants, laboratory personnel and all field workers responsible for administering and sample collection were masked to treatment allocation.”

direct quote[Methods, Sample size]

Table 1 provides complete demographics for both rectal and nasopharyngeal samples, including sex (%), age (median, IQR), and age categories (1–11 months vs 12–59 months). Sex is reported but not justified as a biological variable; the statistical analysis does not disaggregate by sex because the trial is cluster-randomized at the community level and analysis targets community effects. Demographics are adequate.

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

Age and sex of participants are reported in detail. The study is human (children), so species/strain and housing conditions are not applicable.

Evidence

direct quote[Table 1]

“Sex (%) ... Male: 735 (49.8%) ... Female: 740 (50.2%) ... Age, months ... Median (IQR) 36 (22, 48)”

direct quote[Methods, Statistical methods]

“As the trial was conducted at the community level and all analyses targeted community effects, both sexes were included in all analyses. Data were not reported disaggregated by sex.”

PASSReviewer 2· 95% conf

Subject demographics (age, sex) are well-reported in a detailed table; no animal work is involved so species/strain/housing are not applicable.

Evidence

direct quote[Table 1]

“Sex (%): Male 735 (49.8%), Female 740 (50.2%)”

direct quote[Table 1]

“Age, months Median (IQR): 36 (22, 48)”

WARNReviewer 3· 70% conf

Sex and age are reported, but health status and additional demographic details (race/ethnicity, comorbidities) are not, making reporting incomplete for a human study.

Evidence

direct quote[Table 1]

“Sex (%), Male, Female; Age, months, Median (IQR)”

absence[Methods, Trial participants]

Health status is not reported.

absence[Table 1]

Demographics lack race/ethnicity and comorbidities.

The ethics section names the University of California, San Francisco Committee for Human Research and the Comité National Éthique pour la Recherche en Santé in Niger as approving bodies. Informed consent is described: verbal consent from community leaders and written informed consent from guardians, documented electronically. Regulatory compliance is stated: "conducted according to Good Clinical Practice guidelines and adhered to the principles of the Declaration of Helsinki." No IACUC statement is needed (human study).

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper reports ethics approval from both UCSF and the Nigerien national ethics committee, describes informed consent procedures, and states compliance with Good Clinical Practice and the Declaration of Helsinki.

Evidence