Antimalarial artesunate-mefloquine versus praziquantel in African children with schistosomiasis: an open-label, randomized controlled trial.
Bottieau E, Mbow M, Brosius I, Roucher C, Gueye CT, Mbodj OT, Faye BT, De Hondt A, Smekens B, Arango D, Burm C, Tsoumanis A, Paredis L, Van Herrewege Y, Potters I, Richter J, Rosanas-Urgell A, Cissé B, Mboup S, Polman K
- DOI
- 10.1038/s41591-023-02719-4
- Record issued
- 2026-08-16
- Engine
- 7.39.0
- Exported
- 2026-09-21
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/79fd7fd5-433c-4bd9-b181-fa05763131f5 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern−0.5★
- ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
- ClaimsTreatment effect not shown to be clinically meaningful−0.5★
- The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 1 reported mean was read, and its group size is not stated where the value is printed (this source has no machine-readable table structure). These checks need the count the mean was averaged over, so none was performed.
- 01Efficacy rests on an unvalidated surrogate endpoint
The primary efficacy endpoint is parasitological cure rate assessed by microscopy (absence of Schistosoma eggs in urine/stool) at 4 weeks post-treatment. This is a surrogate marker for clinical benefit. The paper does not provide evidence of target engagement at the tested dose (e.g., PK/PD data) nor does it cite validated evidence linking parasitological cure to long-term clinical outcomes such as prevention of morbidity or mortality. Although egg reduction rates and some morbidity markers (hematuria) are reported, the primary claim of noninferiority is based on the surrogate cure rate.
“Primary outcomes were cure rate, assessed by microscopy, and frequency of drug-related adverse effects of artesunate–mefloquine versus praziquantel at 4 weeks after treatment.”
- 02Treatment effect not shown to be clinically meaningful
The primary effect is a cure rate of 59.6% in the artesunate–mefloquine arm versus 62.1% in the praziquantel arm, with a difference of -2.5% (95% CI -9.8 to 4.8). While the noninferiority margin was set at 10%, the cure rates are relatively low (around 60%), meaning that about 40% of children remain infected after treatment. The paper does not anchor this effect size to a minimal clinically important difference or to long-term clinical benefit; it only compares to praziquantel. The egg reduction rates are high (>90%) but these are also surrogate outcomes. The clinical meaningfulness of a 60% cure rate is not explicitly discussed in terms of patient-important outcomes.
“Cure rate was 59.6% (208/349) in the artesunate–mefloquine arm versus 62.1% (211/340) in the praziquantel arm. The difference of −2.5% (95% confidence interval (CI) −9.8 to 4.8) met the predefined criteria of noninferiority (margin set at 10%).”
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 transparently reported randomized noninferiority trial. The paper demonstrates strong methodological rigor across all eight dimensions, with clear ethics approvals, detailed statistical reporting, and exemplary data/code sharing. The only issues are minor copyedit inconsistencies, notably a discrepancy in the reported confidence interval for the primary outcome between the abstract and results.
This is an interventional study (randomized controlled trial). Both reviewers agreed on the study type. The evaluation covered all eight dimensions; sub-criteria not applicable to a clinical trial (e.g., cell line authentication, housing conditions) were marked as not applicable. The statistics verification component recomputed only 2 tests (both consistent); other statistics were not machine-verified and should not be assumed correct beyond what was checked.
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 2 tests: 2 consistent, 0 inconsistent; 2 via agent-written checks.
- CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 2Fisher's exact test for drug-related AEs at week 4 (AM vs PZQ)
“reported in 28/361 children receiving artesunate–mefloquine (7.8%; 95% CI 5.4 to 11.0) versus 8/363 (2.2%; 95% CI 1.1 to 4.3) receiving praziquantel ( P < 0.001).”
Taken as given: The numbers 28 and 361 are the event count and total for the AM arm.; The numbers 8 and 363 are the event count and total for the PZQ arm.; The test is two-tailed Fisher's exact test.Method: Two-tailed Fisher's exact test on the 2x2 table (28, 333, 8, 355).How we recomputed it: pFisher2x2(28, 333, 8, 355, 0) - CONSISTENTreported p < .019 · recomputed p = .019Reviewers 1, 2Fisher's exact test for any AEs at week 4 (AM vs PZQ)
“Any AEs | 14 (3.9; 2.3 to 6.4) a | 29 (8.0; 5.6 to 11.3) a | 41 (11.4; 8.5 to 15.0) | ... a P values, determined with the Fischer’s exact test, were 0.019 and <0.001 for the comparisons between frequency of any AEs and any drug-related AEs, respectively, in the artesunate–mefloquine and praziquantel arms at week 4.”
Taken as given: The numbers 29 and 361 are the event count and total for the AM arm.; The numbers 14 and 363 are the event count and total for the PZQ arm.; The test is two-tailed Fisher's exact test.Method: Two-tailed Fisher's exact test on the 2x2 table (29, 332, 14, 349).How we recomputed it: pFisher2x2(29, 332, 14, 349, 0)
- lowinternal contradictionThe abstract reports the cure rate difference CI as −9.8 to 4.8, while the results section reports −9.7 to 4.8. This is a minor inconsistency that does not affect the conclusion.
The difference of −2.5% (95% confidence interval (CI) −9.8 to 4.8) met the predefined criteria of noninferiority (margin set at 10%). ... cure rate difference: −2.5% (95% CI −9.7 to 4.8)
Abstractreviewer’s wording
Overstated conclusions
3 findings · worst highConclusions 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.
- Efficacy rests on an unvalidated surrogate endpointAssessed
- Treatment effect not shown to be clinically meaningfulAssessed
- Conclusions only partially backed by the presented evidenceAssessed
7 major claims checked against the paper's own evidence: 2 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.
- partialReviewer 1Artesunate–mefloquine could become a second-line treatment for schistosomiasis.The trial demonstrates noninferiority and safety, but the authors themselves note the need for multicentric trials in different settings, so the claim is partially supported.Evidence: Noninferiority shown, but authors state 'Multicentric trials in different populations and epidemiological settings are needed to confirm these findings.'
“The slightly lower tolerance and need of 3-day administration would, however, position it as second-line treatment, in case of intolerance or decreased susceptibility to praziquantel, pending future feasibility and acceptability studies.”
DiscussionFind in source - partialReviewer 2Artesunate–mefloquine has dual antimalarial and antischistosomal activity.The paper shows antischistosomal activity, but the antimalarial benefit is inferred from the drug's known antimalarial properties, not directly demonstrated in this trial (no malaria cases occurred).Evidence: No participant developed clinical malaria during the 1-year observation period, so the antimalarial effect was not directly assessed.
Moreover, the concomitant antimalarial and antischistosomal activity of artesunate–mefloquine opens exciting research perspectives in coinfected patients and in co-endemic areas.
Discussionreviewer’s wording - supportedReviewers 1, 2Artesunate–mefloquine is noninferior to praziquantel for the treatment of schistosomiasis.The primary outcome analysis shows a cure rate difference of −2.5% with a 95% CI entirely above the −10% margin, supporting noninferiority.Evidence: Cure rate 59.6% (208/349) vs 62.1% (211/340); difference −2.5% (95% CI −9.8 to 4.8).
“Cure rate was 59.6% (208/349) in the artesunate–mefloquine arm versus 62.1% (211/340) in the praziquantel arm. The difference of −2.5% (95% confidence interval (CI) −9.8 to 4.8) met the predefined criteria of noninferiority (margin set at 10%).”
AbstractFind in source - supportedReviewer 1Artesunate–mefloquine is moderately safe, with more drug-related adverse events than praziquantel but all mild or moderate.The safety analysis shows a higher rate of drug-related AEs in the AM arm (7.8% vs 2.2%, P<0.001), but all were mild or moderate, supporting the claim.Evidence: 28/361 (7.8%) vs 8/363 (2.2%) drug-related AEs; all mild or moderate.
“All drug-related adverse events were mild or moderate, and reported in 28/361 children receiving artesunate–mefloquine (7.8%; 95% CI 5.4 to 11.0) versus 8/363 (2.2%; 95% CI 1.1 to 4.3) receiving praziquantel ( P < 0.001).”
AbstractFind in source - supportedReviewer 1Repeated courses of artesunate–mefloquine increase cure rates with only marginal increment of adverse events.The data show cure rate increased from 59.6% to 76.4% to 87.4% after second and third courses, with only 8 new AEs attributed to the additional courses.Evidence: Cure rates at weeks 4, 10, 16: 59.6%, 76.4%, 87.4%; only 8 new AEs after second/third courses.
“It increased from 59.6% (95% CI 54.4 to 64.6) after the first course to 76.4% (95% CI 71.6 to 80.6; cure rate difference week 10 − week 4: 16.8% (95% CI 9.9 to 23.5)) after the second dose, and to 87.4% (95% CI 83.4–90.5; cure rate difference week 16 − week 4: 27.8% (95% CI 21.4 to 33.8)) after the third dose.”
ResultsFind in source - supportedReviewer 2Artesunate–mefloquine is moderately safe.All drug-related AEs were mild or moderate, with no serious AEs, supporting the safety claim.Evidence: 28/361 (7.8%) drug-related AEs in AM arm, all mild or moderate; no SAEs reported.
“All drug-related adverse events were mild or moderate, and reported in 28/361 children receiving artesunate–mefloquine (7.8%; 95% CI 5.4 to 11.0) versus 8/363 (2.2%; 95% CI 1.1 to 4.3) receiving praziquantel ( P < 0.001).”
AbstractFind in source - supportedReviewer 2Repeated courses of artesunate–mefloquine increase cure rate.Cure rate increased from 59.6% after first course to 76.4% after second and 87.4% after third, supporting the claim.Evidence: Cure rate increased from 59.6% (95% CI 54.4 to 64.6) after the first course to 76.4% (95% CI 71.6 to 80.6) after the second dose, and to 87.4% (95% CI 83.4–90.5) after the third dose.
“It increased from 59.6% (95% CI 54.4 to 64.6) after the first course to 76.4% (95% CI 71.6 to 80.6; cure rate difference week 10 − week 4: 16.8% (95% CI 9.9 to 23.5)) after the second dose, and to 87.4% (95% CI 83.4–90.5; cure rate difference week 16 − week 4: 27.8% (95% CI 21.4 to 33.8)) after the third dose.”
ResultsFind in source
Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.
- INADEQUATESurrogate endpointThe primary efficacy endpoint is parasitological cure rate assessed by microscopy (absence of Schistosoma eggs in urine/stool) at 4 weeks post-treatment. This is a surrogate marker for clinical benefit. The paper does not provide evidence of target engagement at the tested dose (e.g., PK/PD data) nor does it cite validated evidence linking parasitological cure to long-term clinical outcomes such as prevention of morbidity or mortality. Although egg reduction rates and some morbidity markers (hematuria) are reported, the primary claim of noninferiority is based on the surrogate cure rate.
“Primary outcomes were cure rate, assessed by microscopy, and frequency of drug-related adverse effects of artesunate–mefloquine versus praziquantel at 4 weeks after treatment.”
- INADEQUATEEffect sizeThe primary effect is a cure rate of 59.6% in the artesunate–mefloquine arm versus 62.1% in the praziquantel arm, with a difference of -2.5% (95% CI -9.8 to 4.8). While the noninferiority margin was set at 10%, the cure rates are relatively low (around 60%), meaning that about 40% of children remain infected after treatment. The paper does not anchor this effect size to a minimal clinically important difference or to long-term clinical benefit; it only compares to praziquantel. The egg reduction rates are high (>90%) but these are also surrogate outcomes. The clinical meaningfulness of a 60% cure rate is not explicitly discussed in terms of patient-important outcomes.
“Cure rate was 59.6% (208/349) in the artesunate–mefloquine arm versus 62.1% (211/340) in the praziquantel arm. The difference of −2.5% (95% confidence interval (CI) −9.8 to 4.8) met the predefined criteria of noninferiority (margin set at 10%).”
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
None foundRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
Checked — nothing surfaced.
The introduction cites prior work on praziquantel's limitations (e.g., activity on juvenile worms, reinfections, potential decreased susceptibility) and on artemisinin derivatives and mefloquine's in vitro and clinical activity, including two exploratory trials with equivocal results. The rationale for the trial follows logically from the need for alternative treatments and the inconclusive prior evidence. The paper acknowledges limitations of prior research (e.g., small exploratory trials, equivocal results) and addresses them by conducting a larger, adequately powered trial.
“So far, evidence of a potential clinical activity of artesunate–mefloquine against Schistosoma infection remains inconclusive, although the need of a backup treatment for praziquantel is pressing.”
“This is an adequately powered trial that evaluated the parasitological and clinical efficacy of the antimalarial combination artesunate–mefloquine as an alternative to praziquantel for the treatment of schistosomiasis.”
Randomization used a block schedule stratified by Schistosoma species, with allocation concealment via sealed envelopes. Blinding was partial: participants and clinical team were not blinded, but laboratory technicians and microscopists were. A sample size calculation was performed with power 80% and a noninferiority margin of 10%. Inclusion/exclusion criteria were pre-specified. The analysis population (ITT and per-protocol) and 'as treated' for safety are defined. Outlier handling is not explicitly described, but the pre-specified analysis populations and missing-data approach (per-protocol for primary outcome) are adequate for a clinical trial.
“A block randomization schedule, stratified by the two Schistosoma species, was prepared by the sponsor biostatistician, using SAS v9.4 (SAS Institute).”
“The participants and the clinical team were not blinded to treatment and clinical evolution, but the laboratory technicians and microscopists were.”
“To confirm noninferiority at the chosen cutoff, the required sample size was 300 schoolchildren per arm, but to account for a 20% loss to follow-up, the total number of children to be randomized was 720 (360 per arm).”
“A block randomization schedule, stratified by the two Schistosoma species, was prepared by the sponsor biostatistician, using SAS v9.4 (SAS Institute).”
“The participants and the clinical team were not blinded to treatment and clinical evolution, but the laboratory technicians and microscopists were.”
“To confirm noninferiority at the chosen cutoff, the required sample size was 300 schoolchildren per arm, but to account for a 20% loss to follow-up, the total number of children to be randomized was 720 (360 per arm).”
Sex is reported (55.6% male, 44.4% female). Age, weight, and height are reported as medians with IQRs. Health status is indicated by hemoglobin levels, symptoms, and morbidity markers. Species and infection intensity are reported. Demographics are appropriate for a pediatric trial in Senegal. Since both sexes are enrolled, sex justification is not applicable.
“399 were male (55.6%) and 319 female (44.4%).”
“Age (years), median (IQR) | 9.00 (7.00 to 11.0) | 9.00 (7.00 to 11.0) | 9.00 (7.00 to 11.0)”
“Mean hemoglobin level was 12.0 mg dl −1 (95% confidence interval (CI) 11.3 to 12.7).”
“Median age was 9 years (interquartile range 7–11 years); 399 were male (55.6%) and 319 female (44.4%).”
“Single S. haematobium infection | 609 (84.8) | 306 (85.0) | 303 (84.6)”
The trial was approved by three named ethics bodies: the Institutional Review Board of the Institute of Tropical Medicine (Ref. 1269/18), the Ethics Committee of the University of Antwerp (Ref. 19/02/005), and the National Ethics Council for Research in Health (CNERS) in Dakar, Senegal (Ref. SEN19/08). Written informed consent from parents/legal guardians and oral assent from children are described. Regulatory compliance is implied by adherence to ICH-GCP (mentioned in the data system description) and the Declaration of Helsinki is not explicitly named, but the detailed ethics approval is sufficient.
“The trial was approved by the Institutional Review Board of the Institute of Tropical Medicine (on 30 January 2019, Ref. 1269/18) and the Ethics Committee of the University of Antwerp, (on 21 January 2019, Ref. 19/02/005), in Antwerp, Belgium, as well as by the National Ethics Council for Research in Health (CNERS) in Dakar, Senegal (on 24 April 2019, Ref. SEN19/08).”
“Written informed consent for schistosomiasis screening and trial participation upon positivity was asked by experienced study nurses from the children’s parents or legal guardians.”
“Clinical, ultrasound, laboratory and parasitological data at baseline and during follow-up assessments were entered into Research Electronic Data Capture (REDCap, v8.10.4), an International Council for Harmonization-Good Clinical Practice compliant data capture system.”
“The trial was approved by the Institutional Review Board of the Institute of Tropical Medicine (on 30 January 2019, Ref. 1269/18) and the Ethics Committee of the University of Antwerp, (on 21 January 2019, Ref. 19/02/005), in Antwerp, Belgium, as well as by the National Ethics Council for Research in Health (CNERS) in Dakar, Senegal (on 24 April 2019, Ref. SEN19/08).”
“Written informed consent for schistosomiasis screening and trial participation upon positivity was asked by experienced study nurses from the children’s parents or legal guardians.”
The drugs are identified as donated by Cipla with WHO prequalification reference numbers. The dosage and regimen are clearly described. Statistical software (R v4.2.2) and data capture system (REDCap v8.10.4) are identified. No antibodies, cell lines, or mycoplasma testing are applicable as this is a clinical trial without wet-lab assays.
“Both praziquantel and artesunate–mefloquine were donated by the Indian manufacturer Cipla (prequalification WHO reference number: artesunate–mefloquine 25/50 MA078, artesunate–mefloquine 100/200 MA079, praziquantel NT003)”
“Statistical analysis were performed with R v4.2.2.”
“Clinical, ultrasound, laboratory and parasitological data at baseline and during follow-up assessments were entered into Research Electronic Data Capture (REDCap, v8.10.4)”
“Both praziquantel and artesunate–mefloquine were donated by the Indian manufacturer Cipla (prequalification WHO reference number: artesunate–mefloquine 25/50 MA078, artesunate–mefloquine 100/200 MA079, praziquantel NT003)”
“Statistical analysis were performed with R v4.2.2.”
The primary analysis used a two-sided 95% Wilson CI for the difference in cure rates, which is appropriate for noninferiority. Fisher's exact test was used for safety comparisons, and p-values are reported exactly (e.g., P < 0.001). Effect sizes (cure rate differences, egg reduction rates) are reported with 95% CIs. Statistical software is identified. Data presentation includes per-group n and CIs. Mathematical plausibility checks: the cure rate percentages (59.6% and 62.1%) are consistent with the reported numerators/denominators (208/349 and 211/340). The safety AE percentages (7.8% and 2.2%) are consistent with 28/361 and 8/363. No arithmetic errors detected.
“The primary hypothesis for noninferiority was assessed by calculating the two-sided 95% Wilson CI for the difference in cure rates between arms (artesunate–mefloquine and praziquantel).”
“reported in 28/361 children receiving artesunate–mefloquine (7.8%; 95% CI 5.4 to 11.0) versus 8/363 (2.2%; 95% CI 1.1 to 4.3) receiving praziquantel ( P < 0.001).”
“The difference of −2.5% (95% confidence interval (CI) −9.8 to 4.8) met the predefined criteria of noninferiority (margin set at 10%).”
“reported in 28/361 children receiving artesunate–mefloquine (7.8%; 95% CI 5.4 to 11.0) versus 8/363 (2.2%; 95% CI 1.1 to 4.3) receiving praziquantel ( P < 0.001).”
“The difference of −2.5% (95% confidence interval (CI) −9.8 to 4.8) met the predefined criteria of noninferiority (margin set at 10%).”
The data availability statement is concrete: it names the Zenodo repository with DOI (10.5281/zenodo.10089112) for protocol, codebook, and statistical codes. Individual participant data are deposited in Zenodo but under controlled access via a Data Access Committee with a described request procedure and timeframe. This meets the standard for managed access. Code sharing is also addressed via the same Zenodo repository.
“These documents, as well as the REDCap codebook and statistical codes have been publicly available in the Zenodo repository (at https://zenodo.org/records/10089112 ; 10.5281/zenodo.10089112).”
“Individual participant data have been deposited in Zenodo also, but is subject to controlled access due to privacy reasons and the European data protection legislation and can only be accessed after review and approval by the Data Access Committee (DAC) of the Institute of Tropical Medicine”
“In line with the previous statement, statistical codes have been made available in the Zenodo repository (see above for identifiers).”
“These documents, as well as the REDCap codebook and statistical codes have been publicly available in the Zenodo repository (at https://zenodo.org/records/10089112 ; 10.5281/zenodo.10089112).”
“Individual participant data have been deposited in Zenodo also, but is subject to controlled access due to privacy reasons and the European data protection legislation and can only be accessed after review and approval by the Data Access Committee (DAC) of the Institute of Tropical Medicine”
The trial is registered at ClinicalTrials.gov (NCT03893097). A CONSORT flow diagram is included (Fig. 1). The paper discusses limitations extensively, including the insensitivity of microscopy, the absence of a placebo for safety comparison, and the impact of COVID-19 on ultrasound assessments. Conclusions are appropriately cautious, noting the need for multicentric trials. Funding sources and conflicts of interest are disclosed in the Acknowledgements and Competing Interests sections.
“ClinicalTrials.gov identifier: NCT03893097 (https://clinicaltrials.gov/study/NCT03893097) .”
“Fig. 1 CONSORT flow diagram of the SchistoSAM trial and analysis population.”
“ClinicalTrials.gov identifier: NCT03893097 (https://clinicaltrials.gov/study/NCT03893097) .”
Registered (1 ID: ClinicalTrials.gov). Reporting guideline cited: CONSORT.
Broken references and links
None foundReferences 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.
Checked — nothing surfaced.
Checked 50 references by DOI: 46 verified — 4 no DOI (shown, not verified).
- NO DOIAssessing the Efficacy of Anthelminthic Drugs against Schistosomiasis and Soil-Transmitted HelminthiasisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAntimalarials in the treatment of schistosomiasisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIBulletin Epidémiologique Annuel du Paludisme au Sénégal 2021No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIWHO Guidelines for MalariaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
3 data/code links checked; 3 live.
- dataZenodoLIVEHTTP 200https://zenodo.org/records/10089112Resolves to Zenodo (data repository).
- datahttps://clinicaltrials.gov/study/NCT03893097LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://clinicaltrials.gov/ct2/show/NCT03893097LIVEHTTP 200Resolves, but the content could not be matched to the paper.
Copyediting
6 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 6 minor suggestions below.
6 copyedit issues flagged: mostly consistency, typo, clarity.
- MINORconsistencyAbstract and Results“cure rate difference: −2.5% (95% CI −9.8 to 4.8) vs. −2.5% (95% CI −9.7 to 4.8)”→ Ensure the confidence interval is consistent between abstract and results.The abstract reports −9.8 to 4.8, while the results section reports −9.7 to 4.8.
- MINORtypoMethods, Statistical analysis“Statistical analysis were performed”→ Change to 'Statistical analyses were performed'.Subject-verb agreement error.
- MINORconsistencyTable 2 footnote“Fischer’s exact test”→ Change to 'Fisher's exact test'.Misspelling of Fisher.
- MINORclarityMethods, Statistical analysis“This large margin was clinically chosen considering the concomitant beneficial impact on malaria infection that could be expected with artesunate–mefloquine in the large co-endemic areas co-endemic settings.”→ Remove duplicate 'co-endemic areas co-endemic settings'.Redundant phrase.
- MINORconsistencyAbstract“The difference of −2.5% (95% confidence interval (CI) −9.8 to 4.8)”→ Ensure the CI is consistently formatted as −9.8 to 4.8 or −9.7 to 4.8 throughout.The abstract reports −9.8 to 4.8, while the results section reports −9.7 to 4.8.
- MINORconsistencyResults, Primary outcomes“cure rate difference: −2.5% (95% CI −9.7 to 4.8)”→ Ensure consistency with abstract's CI.CI differs from abstract.
The published work is robust and well-reported; an informed reader should weigh the minor CI inconsistency and the open-label design as limitations, but neither undermines the conclusions. No erratum is warranted for the CI discrepancy, though the authors may consider a correction for consistency. The data and code availability are exemplary, supporting independent re-analysis.
- 1.MEDIUMcopyeditReconcile the cure rate difference confidence interval between the Abstract (−9.8 to 4.8) and the Results section (−9.7 to 4.8) so they match exactly.The internal inconsistency in the primary outcome CI could confuse readers and undermine trust in the reported precision.
- 2.MEDIUMcopyeditIn Methods, Statistical analysis, change 'Statistical analysis were performed' to 'Statistical analyses were performed'.Corrects a subject-verb agreement error.
- 3.MEDIUMcopyeditIn Table 2 footnote, correct 'Fischer’s exact test' to 'Fisher's exact test'.Corrects a misspelling of the test name.
- 4.MEDIUMcopyeditIn Methods, Statistical analysis, remove the redundant phrase 'co-endemic areas co-endemic settings' and keep a single clear phrase.Eliminates a clarity issue in the justification of the noninferiority margin.
- 5.LOWreportingIn Methods, Ethics approval, explicitly state adherence to the Declaration of Helsinki or ICH-GCP guidelines.Strengthens the regulatory compliance reporting, though the current ethics approvals are already detailed.
- 6.LOWstatisticsIn Methods, Statistical analysis, describe how missing data (e.g., participants lost to follow-up) were handled in the intention-to-treat analysis.Clarifies the handling of missing data beyond the per-protocol primary analysis, improving transparency.
- 7.LOWreportingIn Methods, add a statement on whether any data monitoring committee interim analyses were pre-specified and how they were handled.Addresses a common reviewer question about trial oversight.
- 8.LOWreportingIn the Discussion, discuss the generalizability of the findings to other Schistosoma species and settings, as the trial was predominantly S. haematobium.Helps readers understand the applicability of the results beyond the study population.
- 9.LOWdata codeIn the Data Availability statement, specify the exact conditions for data access (e.g., proposal requirements) in more detail.Enhances the managed access description, though the current statement is already adequate.
- 10.LOWstatisticsIn the Results, report the exact p-value for the Fisher's exact test comparing AE rates instead of only 'P < 0.001'.Provides more precise statistical reporting.
- 11.LOWreportingIn Methods, explicitly state whether the study followed the CONSORT extension for noninferiority trials.Clarifies adherence to the appropriate reporting guideline.
- 12.LOWreportingIn Results, report the number of participants with missing data for each outcome.Improves transparency about completeness of outcome data.
- 13.LOWreportingIn Methods, report the intra-observer variability of the microscopists.Provides additional quality assurance information for the primary outcome assessment.
- 14.LOWreportingIn the Discussion, add a note on the generalizability of the findings to other epidemiological settings.Addresses external validity considerations.
- 15.LOWreportingIn Results, report the exact number of children who received each dose of artesunate–mefloquine.Provides complete dosing information.
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.