Name: Adcurare Rigor Record — Zoliflodacin versus ceftriaxone plus azithromycin for treatment of uncomplicated urogenital gonorrhoea: an international, randomised, controlled, open-label, phase 3, non-inferiority clinical trial
Item: Zoliflodacin versus ceftriaxone plus azithromycin for treatment of uncomplicated urogenital gonorrhoea: an international, randomised, controlled, open-label, phase 3, non-inferiority clinical trial
Rating: 100
Author: Adcurare

This phase 3 non-inferiority trial is methodologically rigorous with a well-justified scientific premise, robust study design, and clear statistical methods. Minor reporting gaps — missing body weight, unnamed IRB in main text, unspecified drug manufacturer, data availability not fully open — reduce the transparency score slightly, but none of these undermine the core findings.

Three independent reviewer evaluations were synthesised with the copyedit pass and verification components (citations, statistics, reproducibility, preregistration, claim audit). Dimensions with reviewer divergence (ethics, key resources, data availability) were resolved by weighing the specific evidence cited, not by majority vote. The statistics verification covers only 2 recomputed tests; the mathematical plausibility assessment is a high-level cross-check of reported counts, not a full audit.

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

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

Eight Dimensions8 pass

The Introduction cites global incidence estimates (82.4 million cases), WHO surveillance data on resistance, and the mechanism and phase 2 data for zoliflodacin. Prior treatment failures for solithromycin, delafloxacin, gentamicin, and fosfomycin are acknowledged. The premise rationale is logically sound: zoliflodacin has a distinct target (GyrB) and maintains activity against resistant strains, justifying phase 3 evaluation. Limitations of prior treatments (e.g., ertapenem's stewardship concerns) are discussed.

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 on the global burden of gonorrhoea, antimicrobial resistance, and the need for new treatments. The rationale for testing zoliflodacin is clearly linked to its novel mechanism and phase 2 data.

Evidence

direct quote[Introduction, paragraph 1]

“In 2020, WHO estimated that Neisseria gonorrhoeae caused 82·4 million new cases of gonorrhoea among those aged 15–49 years worldwide.”

direct quote[Introduction, paragraph 3]

“Zoliflodacin is an oral, first-in-class, spiropyrimidinetrione antibiotic with a distinct mode of bactericidal action.”

direct quote[Introduction, Research in context]

“Phase 3 studies investigating two new oral treatments, solithromycin and delafloxacin, as well as the older antibiotics, gentamicin and fosfomycin, had not shown non-inferiority to standard of care, ceftriaxone.”

PASSReviewer 2· 95% conf

The scientific premise is well-established with citations to prior research on gonorrhoea epidemiology, resistance, and previous treatment failures, with a clear rationale for the study objectives.

Evidence

direct quote[Introduction, paragraph 1]

“In 2020, WHO estimated that Neisseria gonorrhoeae caused 82·4 million new cases of gonorrhoea among those aged 15–49 years worldwide.”

direct quote[Introduction, paragraph 3]

“Zoliflodacin is an oral, first-in-class, spiropyrimidinetrione antibiotic with a distinct mode of bactericidal action.”

direct quote[Research in context, paragraph 2]

“Phase 3 studies investigating two new oral treatments, solithromycin and delafloxacin, as well as the older antibiotics, gentamicin and fosfomycin, had not shown non-inferiority to standard of care, ceftriaxone.”

PASSReviewer 3· 95% conf

The scientific premise is well-established, citing the global burden of gonorrhoea, antimicrobial resistance patterns, the mechanism of action of zoliflodacin, and prior phase 1/2 studies.

Evidence

direct quote[Introduction, paragraph 1]

“In 2020, WHO estimated that Neisseria gonorrhoeae caused 82·4 million new cases of gonorrhoea among those aged 15–49 years worldwide.”

direct quote[Introduction, paragraph 3]

“Zoliflodacin is an oral, first-in-class, spiropyrimidinetrione antibiotic with a distinct mode of bactericidal action.”

direct quote[Research in context, paragraph 1]

“Phase 3 studies investigating two new oral treatments, solithromycin and delafloxacin, as well as the older antibiotics, gentamicin and fosfomycin, had not shown non-inferiority to standard of care, ceftriaxone.”

Randomization used computer-generated numbers with permuted blocks and stratification. Blinding was open-label but justified, with microbiology lab and sponsor team masked. Power analysis was pre-specified and achieved. Inclusion/exclusion criteria are detailed. Missing data were handled via multiple imputation and sensitivity analyses.

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 study design is robust for a phase 3 non-inferiority trial: randomization method, stratification, power analysis, and pre-specified inclusion/exclusion criteria are clearly described. Blinding is limited (open-label) but with masked microbiology and sponsor central team, and the rationale is acknowledged.

Evidence

direct quote[Methods, Randomisation and masking]

“The randomisation sequence was obtained using computer-generated random numbers, and treatment allocation was provided to each trial site by a web-based randomisation system.”

direct quote[Methods, Statistical analysis]

“Assuming a 90% cure rate in the comparator group, a –4% treatment difference, and a prespecified non-inferiority margin of less than 12% for the upper bound of the two-sided 95% CI for the primary endpoint, the microbiological intention-to-treat (urogenital) sample size was calculated as 696 participants, with a 2:1 allocation ratio, to provide 90% power to show that zoliflodacin was non-inferior to the comparator with respect to microbiological cure rate at TOC.”

direct quote[Methods, Randomisation and masking]

“The study was open-label with treatment assignment known to participants, clinical trial site personnel, and site-facing sponsor team members. The local or regional and central microbiology analytical laboratory staff who did primary endpoint microbiological analysis and the sponsor's central study team members were masked to treatment allocation until after database lock.”

PASSReviewer 2· 95% conf

The study design is rigorous with adequate randomization, blinding of key personnel, a priori power analysis, and clear inclusion/exclusion and missing data handling.

Evidence

direct quote[Methods, Randomisation and masking]

“The randomisation sequence was obtained using computer-generated random numbers, and treatment allocation was provided to each trial site by a web-based randomisation system.”

direct quote[Methods, Randomisation and masking]

“The study was open-label with treatment assignment known to participants, clinical trial site personnel, and site-facing sponsor team members. The local or regional and central microbiology analytical laboratory staff who did primary endpoint microbiological analysis and the sponsor's central study team members were masked to treatment allocation until after database lock.”

direct quote[Methods, Statistical analysis]

“Assuming a 90% cure rate in the comparator group, a –4% treatment difference, and a prespecified non-inferiority margin of less than 12% for the upper bound of the two-sided 95% CI for the primary endpoint, the microbiological intention-to-treat (urogenital) sample size was calculated as 696 participants, with a 2:1 allocation ratio, to provide 90% power to show that zoliflodacin was non-inferior to the comparator with respect to microbiological cure rate at TOC.”

PASSReviewer 3· 90% conf

The core design elements are well-reported: randomization method, unit, power analysis, inclusion/exclusion criteria, and controls are all described adequately. Blinding is open-label but justified.

Evidence

direct quote[Methods, Randomisation and masking]

“The randomisation sequence was obtained using computer-generated random numbers, and treatment allocation was provided to each trial site by a web-based randomisation system.”

direct quote[Methods, Statistical analysis]

“Assuming a 90% cure rate in the comparator group, a –4% treatment difference, and a prespecified non-inferiority margin of less than 12% for the upper bound of the two-sided 95% CI for the primary endpoint, the microbiological intention-to-treat (urogenital) sample size was calculated as 696 participants, with a 2:1 allocation ratio, to provide 90% power to show that zoliflodacin was non-inferior to the comparator with respect to microbiological cure rate at TOC.”

direct quote[Discussion]

“Limitations of the study include the open-label study design, which was necessary due to the different formulations of study treatments and the unacceptability and operational burden of placebo injections required to mask the study.”

Sex assigned at birth (male/female percents) and gender are reported in Table 1. Age (mean, SD, range) and health status (HIV status, symptoms) are provided. Race, ethnicity, and region are also reported as demographics. Species/strain and housing conditions are not applicable for a human clinical trial. Sex justification is not applicable as both males and females 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· 92% conf

Key biological variables are well reported: sex, age, race/ethnicity, comorbidities (HIV status), and region are detailed. Sex justification is not required as both sexes are enrolled. Age and health status are given.

Evidence

direct quote[Results, paragraph 2 and Table 1]

“815 (88%) of 930 participants were assigned male at birth and 115 (12%) participants were assigned female at birth.”

direct quote[Results and Table 1]

“The mean participant age was 29·7 years (SD 9·4).”

PASSReviewer 2· 80% conf

Sex, age, and demographics are well-reported, but weight is not reported, making age_weight_health incomplete. However, the majority of applicable criteria are adequate.

Evidence

direct quote[Results, paragraph 2]

“815 (88%) of 930 participants were assigned male at birth and 115 (12%) participants were assigned female at birth.”

direct quote[Results, paragraph 2]

“The mean participant age was 29·7 years (SD 9·4).”

absence[Methods and Results]

Weight is not reported.

PASSReviewer 3· 95% conf

Demographics, sex, and age are comprehensively reported. Species/strain and housing are not applicable. Sex is reported for both groups, and as both sexes are enrolled, justification is not required.

Evidence

direct quote[Results, Table 1]

“Sex assigned at birth: Male: 544 (88%) for zoliflodacin, 271 (88%) for comparator.”

direct quote[Results, Table 1]

“Age, years: Mean (SD): 30·0 (9·6) for zoliflodacin, 29·2 (9·1) for comparator.”

direct quote[Methods, Study design and participants]

“Race and ethnicity were also self-reported.”

The Methods state: 'The study protocol and its amendments were approved by the institutional review board or ethics committee of all participating centres, and all participants provided written informed consent.' This meets the requirement for a named body. Regulatory compliance is addressed: 'designed and conducted in accordance with US Food and Drug Administration (FDA) guidance' and the protocol is publicly available. IACUC is not applicable for a human 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 approvals are fully reported: the study was approved by IRB/ethics committees of all participating centres, informed consent was obtained, and regulatory compliance with applicable guidance is stated.

Evidence

direct quote[Methods, Study design and participants]

“The study protocol and its amendments were approved by the institutional review board or ethics committee of all participating centres, and all participants provided written informed consent.”

direct quote[Methods, Study design and participants]

“This phase 3, multinational, open-label, randomised, controlled, non-inferiority trial was designed and conducted in accordance with US Food and Drug Administration (FDA) guidance and advice from research and public health bodies.”

WARNReviewer 2· 90% conf

The ethics statement is adequate but does not name the specific IRB in the main text, and the appendix is not provided. Informed consent and regulatory compliance are adequately reported.

Evidence

direct quote[Methods, Study design and participants]

“The study protocol and its amendments were approved by the institutional review board or ethics committee of all participating centres (see appendix pp 11–12 for full inclusion and exclusion criteria).”

direct quote[Methods, Study design and participants]

“all participants provided written informed consent.”

direct quote[Methods, Study design and participants]

“This phase 3, multinational, open-label, randomised, controlled, non-inferiority trial was designed and conducted in accordance with US Food and Drug Administration (FDA) guidance and advice from research and public health bodies.”

PASSReviewer 3· 95% conf

Ethics approval from institutional review boards or ethics committees is reported, informed consent was obtained, and regulatory compliance is stated. The study involves human subjects, so human-subjects ethics criteria apply.

Evidence

direct quote[Methods, Study design and participants]

“The study protocol and its amendments were approved by the institutional review board or ethics committee of all participating centres (), and all participants provided written informed consent.”

direct quote[Methods, Study design and participants]

“all participants provided written informed consent.”

direct quote[Methods, Study design and participants]

“This phase 3, multinational, open-label, randomised, controlled, non-inferiority trial was designed and conducted in accordance with US Food and Drug Administration (FDA) guidance and advice from research and public health bodies.”

The drugs are identified: zoliflodacin 3 g oral suspension, ceftriaxone 500 mg intramuscular, azithromycin 1 g oral. The manufacturer (Innoviva Specialty Therapeutics for zoliflodacin) is implied by author affiliations but not explicitly stated for the product itself; however, for a trial of this nature, the naming of the drug with dose and formulation is standard. SAS version 9.4 is identified as the statistical software. Reagents like antibodies are not used. The trial is a human drug trial, so the investigational product is the key resource.

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· 85% conf

Key resources are adequately identified: the investigational drugs (zoliflodacin, ceftriaxone, azithromycin) are named with doses and regimens; software (SAS 9.4) is identified with version; the central microbiology laboratory (JMI Laboratories) is named. Antibodies and cell lines are not applicable.

Evidence

direct quote[Methods, Procedures]

“a single oral dose of zoliflodacin 3 g (granules as oral suspension) or the comparator, a single intramuscular 500 mg dose of ceftriaxone plus a single oral 1 g dose of azithromycin”

direct quote[Methods, Statistical analysis]

“Statistical analyses were done by Plus-Project (Knutsford, UK) using SAS version 9.4.”

WARNReviewer 2· 85% conf

The investigational product is identified by dose and regimen but not by manufacturer, and software is adequately identified. The lack of manufacturer for the drugs is a minor gap.

Evidence

direct quote[Methods, Procedures]

“either a single oral dose of zoliflodacin 3 g (granules as oral suspension) or the comparator, a single intramuscular 500 mg dose of ceftriaxone plus a single oral 1 g dose of azithromycin”

direct quote[Methods, Statistical analysis]

“Statistical analyses were done by Plus-Project (Knutsford, UK) using SAS version 9.4.”

PASSReviewer 3· 90% conf

The investigational products (zoliflodacin, ceftriaxone, azithromycin) are named with formulation and dose. Software tools (SAS version 9.4) are identified. Other resources like antibodies and cell lines are not applicable to this clinical trial.

Evidence

direct quote[Methods, Procedures]

“a single oral dose of zoliflodacin 3 g (granules as oral suspension) or the comparator, a single intramuscular 500 mg dose of ceftriaxone plus a single oral 1 g dose of azithromycin”

direct quote[Methods, Statistical analysis]

“Statistical analyses were done by Plus-Project (Knutsford, UK) using SAS version 9.4.”

The primary analysis uses the Clopper-Pearson method for CIs and Newcombe score for the difference, which are appropriate for binomial data. Exact p-values are not the focus in a non-inferiority trial; the CI is the primary inference, and 95% CIs are provided. Effect sizes (differences with 95% CIs) are reported for all primary and secondary analyses. Statistical software (SAS 9.4) is identified. Data presentation in tables and figures (forest plot) follows clinical trial standards; per-group Ns and CIs are shown. Assumptions for logistic regression (multiple imputation) are handled by the model. Mathematical plausibility: the numbers in Table 2 (460/506 = 90.9%) and (229/238 = 96.2%) are arithmetically consistent; the reported CIs are plausible. No internal contradictions are apparent in the reported counts.

Sub-criteria

tests namedADEQUATE

exact p valuesINADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Statistical methods are rigorous and well-described: tests are named (Clopper-Pearson, Newcombe score, logistic regression, multiple imputation), exact p-values and confidence intervals are reported, effect sizes (differences) with CIs are provided, software is identified, and data presentation includes individual Ns, CIs, and forest plots. Mathematical plausibility checks reveal no obvious errors.

Evidence

direct quote[Methods, Statistical analysis]

“the proportion of participants with microbiological cure at TOC was calculated for the microbiological intention-to-treat (urogenital) population, and 95% CIs were calculated using the Clopper–Pearson method. The point estimate for the treatment difference (comparator minus zoliflodacin) and the two-sided 95% CI were calculated using the Newcombe score method.”

direct quote[Results]

“460 (90·9%, 95% CI 88·1–93·3) of 506 participants for zoliflodacin and 229 (96·2%, 92·9–98·3) of 238 participants for comparator.”

PASSReviewer 2· 90% conf

Statistical methods are well-described, with appropriate tests, effect sizes, and confidence intervals. Software is identified. Exact p-values are not reported for all comparisons, but the primary analysis is based on CIs.

Evidence

direct quote[Methods, Statistical analysis]

“The proportion of participants with microbiological cure at TOC was calculated for the microbiological intention-to-treat (urogenital) population, and 95% CIs were calculated using the Clopper–Pearson method. The point estimate for the treatment difference (comparator minus zoliflodacin) and the two-sided 95% CI were calculated using the Newcombe score method.”

paraphrase[Results, Table 2 and Table 3]

“Table 2 and Table 3 present proportions with 95% CIs and differences with 95% CIs for urogenital, pharyngeal, and rectal sites.”

PASSReviewer 3· 85% conf

Statistical tests are named, exact p-values are not the primary focus (non-inferiority uses CIs), effect sizes/CI are central, software is identified, and data presentation includes CIs and per-group n. Mathematical plausibility checks confirm no obvious errors.

Evidence

direct quote[Methods, Statistical analysis]

“95% CIs were calculated using the Clopper–Pearson method. The point estimate for the treatment difference (comparator minus zoliflodacin) and the two-sided 95% CI were calculated using the Newcombe score method.”

direct quote[Results, Table 2]

“Difference (95% CI): 5.3% (1.4 to 8.6)”

paraphrase[Results, paragraph 4]

“The primary analysis does not report a p-value for non-inferiority, only CIs.”

The data availability statement is concrete, specifying a data-sharing email, conditions, and a 6-month timeframe after regulatory approval. This meets the criteria for adequate managed access.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 88% conf

Data availability is addressed transparently: a data-sharing statement provides a concrete route (email to GARDP) with conditions and timeframe. The protocol and SAP are publicly accessible via ClinicalTrials.gov. Code sharing is not applicable as no custom code is expected to be shared.

Evidence

direct quote[Data sharing section]

“The data underlying the results of this study and related study documents (eg, study protocol, statistical analysis plan, and informed consent form) can be made available upon request. Requests from researchers should be sent to GARDP at datasharing@gardp.org for consideration. If granted, relevant individual participant data will be anonymised and securely transferred. Participant-level data will be made available within 6 months of first regulatory approval.”

direct quote[Methods, Study design and participants]

“The protocol (https://cdn.clinicaltrials.gov/large-docs/27/NCT03959527/Prot_000.pdf) and statistical analysis (https://cdn.clinicaltrials.gov/large-docs/27/NCT03959527/SAP_001.pdf) plan can be accessed online.”

PASSReviewer 2· 95% conf

A detailed data availability statement is provided, with a contact email and timeframe. No repository deposit or code sharing is required for this patient-level data.

Evidence

direct quote[Data sharing section]

“The data underlying the results of this study and related study documents (eg, study protocol, statistical analysis plan, and informed consent form) can be made available upon request. Requests from researchers should be sent to GARDP at datasharing@gardp.org for consideration. If granted, relevant individual participant data will be anonymised and securely transferred. Participant-level data will be made available within 6 months of first regulatory approval.”

WARNReviewer 3· 85% conf

A data availability statement is present but is inadequate as it only offers data 'upon request' with a generic mechanism, and does not mention a repository. No custom code was shared.

Evidence

direct quote[Data sharing]

“The data underlying the results of this study and related study documents (eg, study protocol, statistical analysis plan, and informed consent form) can be made available upon request. Requests from researchers should be sent to GARDP at datasharing@gardp.org for consideration.”

absence[Data sharing]

Code availability is not mentioned.

Methods completeness is high: procedures, dosing, specimen collection, and laboratory methods are described. Trial registration numbers are given (ClinicalTrials.gov NCT03959527, EudraCT 2019-000990-22). No reporting guideline checklist (CONSORT) is explicitly submitted, but the reporting follows CONSORT standards. All outcomes — primary and secondary (pharyngeal, rectal, clinical cure, safety) — are reported, including negative/null results (non-significant subgroup differences). Limitations of the open-label design, challenges with enrolling women/adolescents, and generalizability are discussed. Conclusions are proportional: 'suggest a potential role for zoliflodacin as an effective oral treatment option' — not overclaimed. Funding sources and COI declarations are extensive.

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· 94% conf

Reporting is comprehensive: methods are detailed enough for replication, the trial is registered (NCT03959527), all pre-specified outcomes are reported including pharyngeal and rectal sites, limitations are discussed, conclusions are proportional, and funding/COI statements are provided.

Evidence

direct quote[Methods, Study design and participants]

“The trial is registered with ClinicalTrials.gov (http://ClinicalTrials.gov), NCT03959527 (https://clinicaltrials.gov/ct2/show/NCT03959527), and EudraCT, 2019-000990-22.”

direct quote[Discussion, paragraph 5]

“Limitations of the study include the open-label study design, which was necessary due to the different formulations of study treatments and the unacceptability and operational burden of placebo injections required to mask the study.”

direct quote[End of main text (Funding and Declaration of interests)]

“Funding German Federal Ministry of Research, Technology and Space, UK Department of Health and Social Care as part of the Global Antimicrobial Resistance Innovation Fund, Japan Ministry of Health, Labour and Welfare, Netherlands Ministry of Health, Welfare and Sport and Directorate-General for International Cooperation, Switzerland Federal Office of Public Health, and the Canton of Geneva, Switzerland.”

PASSReviewer 2· 90% conf

Reporting is comprehensive with a detailed methods section, trial registration, discussion of limitations, proportional conclusions, and funding/COI statements. The CONSORT reporting guideline is not explicitly referenced, but the paper follows its structure.

Evidence

direct quote[Methods, Study design and participants]

“The trial is registered with ClinicalTrials.gov (http://ClinicalTrials.gov), NCT03959527 (https://clinicaltrials.gov/ct2/show/NCT03959527), and EudraCT, 2019-000990-22.”

direct quote[Discussion, paragraph 5]

“Limitations of the study include the open-label study design, which was necessary due to the different formulations of study treatments and the unacceptability and operational burden of placebo injections required to mask the study.”

paraphrase[Funding and Declaration of interests sections]

“Funding sources are listed in the Funding section, and a detailed declaration of interests is provided in the Declaration of interests section.”

PASSReviewer 3· 90% conf

Methods are complete, the trial is registered (NCT03959527, EudraCT 2019-000990-22), limitations are discussed, conclusions are proportional, and funding and COI statements are provided. A protocol is referenced. No reporting guideline checklist (CONSORT) is mentioned, though the trial appears to follow CONSORT implicitly.

Evidence

direct quote[Methods, Study design and participants]

“The trial is registered with ClinicalTrials.gov (http://ClinicalTrials.gov) , NCT03959527 ... and EudraCT, 2019-000990-22.”

direct quote[Discussion]

“Limitations of the study include the open-label study design, which was necessary due to the different formulations of study treatments... the numbers of individuals from these groups were still low.”

direct quote[Funding and Declaration of interests]

“Funding: German Federal Ministry of Research, Technology and Space... Declaration of interests: The institutions or affiliated institutions of LAB, TAB, SEC ... received funding from GARDP for the trial.”

5 copyedit issues flagged: mostly consistency, typo.

Checked 34 references: 27 verified — 7 unresolved.

3 data/code links checked; 3 live.

Adcurare Rigor Action ItemsFinal pass before journal submission

The published paper is methodologically sound and the findings are supported by the reported data. An informed reader should weigh three minor transparency gaps: no named IRB in the main text, no stated drug manufacturer, and a data-sharing statement that requires email request rather than providing open access. These gaps do not warrant a correction or erratum but could be addressed in a data note or correspondence to the journal. No retraction-level concerns emerge.

1.
HIGHethics
Add the name of the specific IRB or ethics committee (and approval number/identifier) to the Methods, Study design and participants section, rather than just referencing the appendix.
The main text currently states approval was obtained but omits the name of any reviewing body, which is required for adequate reporting per the IRB/ethics statement criterion.
2.
HIGHdata code
Replace the current 'available upon request' data-sharing statement with a managed-access platform (e.g., Vivli, YODA) or a public repository with a DOI, and specify the conditions and expected timeline in the Data sharing section.
Bare 'email for data' statements are increasingly considered insufficient by journals and reviewers; a named platform or repository with a clear access process strengthens transparency and reproducibility.
3.
HIGHdata code
Add a 'Code availability' statement confirming whether the SAS analysis scripts can be shared, and if so, deposit them in a public repository (e.g., GitHub, Zenodo) with a DOI.
No code-sharing mention was found; providing analysis code (even for standard statistical procedures) allows independent verification and is considered best practice.
4.
HIGHreporting
Explicitly reference the CONSORT 2010 checklist in the Methods section and submit it as supplementary material.
The paper follows CONSORT structure implicitly but does not cite the guideline; explicit referencing is standard for randomised trials and improves reporting transparency.
5.
MEDIUMrigor
Report body weight (mean, SD, range) for each treatment group in Table 1 (Demographics).
Body weight is a relevant variable for a fixed-dose antibiotic trial and was flagged missing by one reviewer; its inclusion would satisfy the age/weight/health criterion.
6.
MEDIUMrigor
State the manufacturer/supplier of the investigational products (zoliflodacin, ceftriaxone, azithromycin) in the Methods, Procedures section.
Identifying the source of key reagents is a standard rigor criterion; currently the manufacturer is only implied via author affiliations.
7.
MEDIUMstatistics
Report exact p-values for secondary and subgroup analyses where feasible, alongside the confidence intervals.
Although non-inferiority trials focus on CIs, p-values for secondary comparisons aid readers' interpretation; the current reporting is limited to one logistic regression p-value.
8.
MEDIUMreporting
Clarify the discrepancy between the 12% non-inferiority margin and the observed 8.6% upper bound of the CI in the Discussion, to emphasise robustness.
The paper already touches on this but could state more explicitly that the upper bound was substantially below the pre-specified margin, strengthening the non-inferiority conclusion.
9.
LOWcopyedit
Correct the typo in Methods, Statistical analysis: 'N gonorrheae' should be 'N gonorrhoeae'.
Species name was misspelled; copyedit flagged this as a minor error.
10.
LOWcopyedit
Correct the typo 'heath-care seeking' to 'health-care seeking' in Discussion, paragraph 5.
Typo flagged by copyedit pass.
11.
LOWcopyedit
Replace 'elucidated' with 'quantified' or 'determined' in Discussion, paragraph 5 for clarity.
Word choice suggestion from copyedit; 'elucidated' is grammatically correct but less precise for quantifying an impact.
12.
LOWcopyedit
Standardise terminology: use either 'patients' or 'participants' consistently throughout the Results section (currently switches in the same sentence).
Consistency in participant terminology is a copyedit convention; flagged by the copyedit pass.