Extension of efficacy range for targeted malaria-elimination interventions due to spillover effects.
Benjamin-Chung J, Li H, Nguyen A, Barratt Heitmann G, Bennett A, Ntuku H, Prach LM, Tambo M, Wu L, Drakeley C, Gosling R, Mumbengegwi D, Kleinschmidt I, Smith JL, Hubbard A, van der Laan M, Hsiang MS
- DOI
- 10.1038/s41591-024-03134-z
- Record issued
- 2026-08-16
- Engine
- 7.39.0
- Exported
- 2026-09-22
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/e4f49228-f444-42e8-b43d-1ac73411d0b1 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern−0.5★
- ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
- StatisticsPrinted percentage does not match its own count (capped)−0.25★
- CitationsUnresolved reference−0.25★
- 01Efficacy rests on an unvalidated surrogate endpoint
The primary efficacy claim is based on reductions in malaria incidence, prevalence, and seroprevalence. While incidence is a clinical outcome, prevalence and seroprevalence are surrogate markers. The paper does not provide evidence linking these surrogates to hard clinical outcomes, nor does it demonstrate target engagement at the tested dose beyond the intervention's mechanism.
“Among non-recipients within 1 km of index cases, the combined intervention reduced malaria incidence by 43% (95% confidence interval, 20–59%). In analyses among non-recipients within 3 km of interventions, the combined intervention reduced infection…”
- 02Printed percentage does not match its own count
2.2% is unattainable for n=100 (nearest: 2, 3%)
“In 2015, prevalence measured by loop-mediated isothermal amplification was 2.2%”
MethodsFind in source
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.
The paper is a rigorous re-analysis of a cluster-randomized trial, using TMLE to estimate direct and spillover effects of malaria interventions. It demonstrates strong scientific premise, design, ethics, and transparency, with minor reporting gaps in power analysis, exact p-values, and reagent catalog numbers. The main concern is a minor internal inconsistency in the reported confidence interval for the primary effect.
Both reviewers classified the study as observational, which is appropriate given the re-analysis of trial data using observational methods. The evaluation covered all eight dimensions; several sub-criteria were marked not applicable (e.g., cell line authentication, housing conditions) due to the human study context. The statistics verification covered only a subset of reported tests; the one inconsistency found (CI discrepancy) is minor and does not affect the overall assessment.
Numerical inconsistencies
2 findings · worst mediumValues 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.
- Printed percentage does not match its own countRecomputed
- Internal contradictions in the reported numbersAssessed
1 printed percentage that does not match its own count.
- PERCENT2.2% is unattainable for n=100 (nearest: 2, 3%)
“In 2015, prevalence measured by loop-mediated isothermal amplification was 2.2%”
MethodsFind in source
- lowinternal contradictionThe abstract reports a 43% reduction in incidence with 95% CI 20–59%, while the results section reports 43% with 95% CI 21–58%. This minor discrepancy may be due to rounding or different model specifications.
the combined intervention reduced malaria incidence by 43% (95% confidence interval, 20–59%) ... (incidence reduction, 43%; 95% CI, 21–58%)
Abstractreviewer’s wording
Overstated conclusions
1 finding · 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
7 major claims checked against the paper's own evidence: all adequately supported.
- supportedReviewers 1, 2The combined intervention reduced malaria incidence among non-recipients within 1 km by 43%.The paper reports a 43% reduction with a 95% CI that excludes the null, and this is supported by the analysis.Evidence: Reported in the abstract and results section with a 95% CI of 20–59%.
“Among non-recipients within 1 km of index cases, the combined intervention reduced malaria incidence by 43% (95% confidence interval, 20–59%).”
AbstractFind in source - supportedReviewers 1, 2The combined intervention reduced infection prevalence by 79% among non-recipients within 3 km.The paper reports a 79% reduction with a wide CI (6–95%), which is consistent with the analysis.Evidence: Reported in the abstract and results section.
“the combined intervention reduced infection prevalence by 79% (6–95%)”
AbstractFind in source - supportedReviewers 1, 2Accounting for spillover effects increased the cost-effectiveness of the combined intervention by 42%.The paper reports a 42% increase in cost-effectiveness, which is directly derived from the analysis.Evidence: Reported in the abstract and cost-effectiveness section.
“Accounting for spillover effects increased the cost-effectiveness of the combined intervention by 42%.”
AbstractFind in source - supportedReviewer 1Targeting hotspots with combined chemoprevention and vector-control interventions can indirectly benefit non-recipients up to 3 km away.The paper provides evidence of spillover effects on prevalence up to 3 km, supporting this claim.Evidence: Prevalence analyses show spillover effects up to 3 km.
“Targeting hotspots with combined chemoprevention and vector-control interventions can indirectly benefit non-recipients up to 3 km away.”
AbstractFind in source - supportedReviewer 1There was no or weak evidence of direct effects of the interventions.The paper reports no evidence of direct effects on incidence and weak evidence on prevalence, consistent with the claim.Evidence: Direct effects analyses show confidence intervals including the null.
“There was no or weak evidence of direct effects, but the sample size of intervention recipients was small, limiting statistical power.”
AbstractFind in source - supportedReviewer 2Spillover effects were stronger in lower-transmission settings.Subgroup analysis shows stronger effects when baseline incidence was below median, as reported.Evidence: Reported in results: 'the combined intervention reduced incidence by 68% (95% CI, 35–84%) when baseline incidence was below the median'.
“the combined intervention reduced incidence by 68% (95% CI, 35–84%) when baseline incidence was below the median”
ResultsFind in source - supportedReviewer 2Spillover effects were present for men but not women for chemoprevention.The paper reports this subgroup finding, though it may be underpowered.Evidence: Reported in results: 'Spillover effects of the chemoprevention intervention were present for men but not women.'
“Spillover effects of the chemoprevention intervention were present for men but not women.”
ResultsFind in source
Premise concern: surrogate not validated for clinical benefit.
- INADEQUATESurrogate endpointThe primary efficacy claim is based on reductions in malaria incidence, prevalence, and seroprevalence. While incidence is a clinical outcome, prevalence and seroprevalence are surrogate markers. The paper does not provide evidence linking these surrogates to hard clinical outcomes, nor does it demonstrate target engagement at the tested dose beyond the intervention's mechanism.
“Among non-recipients within 1 km of index cases, the combined intervention reduced malaria incidence by 43% (95% confidence interval, 20–59%). In analyses among non-recipients within 3 km of interventions, the combined intervention reduced infection prevalence by 79% (6–95%) and seroprevalence, which captures recent infections and has higher statistical power, by 34% (20–45%).”
- ADEQUATEEffect sizeThe reported effect sizes are substantial (e.g., 43% reduction in incidence, 79% reduction in prevalence) and are presented with confidence intervals that exclude the null for key outcomes. The paper also discusses cost-effectiveness improvements, indicating clinical and economic meaningfulness.
“Among non-recipients within 1 km of index cases, the combined intervention reduced malaria incidence by 43% (95% confidence interval, 20–59%). In analyses among non-recipients within 3 km of interventions, the combined intervention reduced infection prevalence by 79% (6–95%) and seroprevalence, which captures recent infections and has higher statistical power, by 34% (20–45%).”
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 studies on spillover effects of various interventions and identifies a gap: no studies have estimated spillover effects of malaria interventions designed for low-transmission settings approaching elimination. The rationale for the study follows logically from this gap, and the authors acknowledge limitations of prior work, such as non-randomized designs and residual confounding.
“Furthermore, to our knowledge, no studies have estimated spillover effects of malaria interventions designed for low-transmission settings approaching elimination.”
“To shed light on whether focal interventions reduce transmission to nearby uninfected or asymptomatic individuals who did not receive interventions, we re-analyzed this cluster-randomized trial to separately estimate direct effects among intervention recipients and spillover effects among nearby non-recipients.”
“Furthermore, to our knowledge, no studies have estimated spillover effects of malaria interventions designed for low-transmission settings approaching elimination.”
The original trial used restricted randomization with 100,000 generated assignments, and the analysis plan was pre-specified and available online. Blinding of laboratory and primary statistical analyses is stated. Inclusion/exclusion criteria for clusters are described. However, a formal power analysis is not reported, and the analysis is observational in nature, so randomization and blinding are not directly applicable to the re-analysis.
“The study statistician randomly generated 100,000 assignments meeting restriction criteria.”
“It was not practical to blind study participants or field staff to intervention assignment, but laboratory analyses and primary statistical analyses were blinded.”
“Enumeration areas were eligible for inclusion in the trial if they (1) were located in the catchment areas of 11 health facilities, (2) had complete incidence data from 2012–13 and (3) had at least one incident case during the trial”
“The study statistician randomly generated 100,000 assignments meeting restriction criteria.”
“It was not practical to blind study participants or field staff to intervention assignment, but laboratory analyses and primary statistical analyses were blinded.”
“Enumeration areas were eligible for inclusion in the trial if they (1) were located in the catchment areas of 11 health facilities, (2) had complete incidence data from 2012–13 and (3) had at least one incident case during the trial”
The paper reports sex and age distributions in the study population, and discusses demographic factors such as nationality and occupation. Health status is implied through malaria incidence and prevalence measures. Species (Plasmodium falciparum) is identified, and the study setting is described in detail. Housing conditions are not directly reported, but the study is human-based, so species/strain and housing are not applicable.
“Spillover effects of the chemoprevention intervention were present for men but not women.”
“A parent or guardian was required to provide written informed consent for children younger than 18 years receiving rfMDA or RACD, and written assent for receiving these interventions was also obtained from children aged 12–17 years.”
“Sixty percent of index cases in the study were in men”
“A parent or guardian was required to provide written informed consent for children younger than 18 years receiving rfMDA or RACD”
“12% of men were of Zambian nationality, as opposed to 7% of women”
The paper states that the trial protocol was approved by the Namibia Ministry of Health and Social Services and the IRBs at UCSF and LSHTM, and the analysis protocol was approved by Stanford IRB. Informed consent is described for the original trial, including written consent from participants and heads of households, and assent for children. Regulatory compliance is implied through adherence to ethical standards.
“The trial protocol was approved by the Namibia Ministry of Health and Social Services (17/3/3) and the Institutional Review Boards at the University of California San Francisco (15–17422) and London School of Hygiene & Tropical Medicine (10411). The protocol for this analysis was approved by the Stanford University Institutional Review Board (60708).”
“In the original trial, written informed consent was obtained from individual participants for rfMDA or RACD, and from heads of households (≥18 years of age) for RAVC.”
“The trial protocol was approved by the Namibia Ministry of Health and Social Services (17/3/3) and the Institutional Review Boards at the University of California San Francisco (15–17422) and London School of Hygiene & Tropical Medicine (10411).”
“In the original trial, written informed consent was obtained from individual participants for rfMDA or RACD, and from heads of households (≥18 years of age) for RAVC.”
“The protocol for this analysis was approved by the Stanford University Institutional Review Board (60708).”
The paper identifies the drugs (artemether–lumefantrine, primaquine) with manufacturers, the insecticide (pirimiphos-methyl) with product name, and statistical software (R packages). Antibodies, cell lines, and mycoplasma testing are not applicable. Reagents like dried blood spots and Luminex assays are described but not with catalog numbers.
“In the RACD arms, individuals were eligible to receive rapid diagnostic tests, and individuals who tested positive were eligible for treatment with artemether–lumefantrine and single-dose primaquine (Coartem, Novartis Pharmaceuticals, or Komefan 140, Mylan Laboratories).”
“We used TMLE with individual-level data with the same learners included in incidence analyses (tmle3 R package version 0.2.0).”
“artemether–lumefantrine and single-dose primaquine (Coartem, Novartis Pharmaceuticals, or Komefan 140, Mylan Laboratories)”
“IRS with pirimiphos-methyl (Actellic 300CS, Syngenta)”
“tmle3 R package version 0.2.0”
The paper uses hierarchical TMLE, a doubly-robust method, and reports effect sizes with 95% confidence intervals. It names the software and describes covariate adjustment. Exact p-values are not reported for the main effects, but the paper reports confidence intervals, which is acceptable for estimation-based reporting. The mathematical plausibility of the reported numbers appears sound, though not all can be independently verified.
“Among non-recipients within 1 km of index cases, the combined intervention reduced malaria incidence by 43% (95% confidence interval, 20–59%).”
“We used TMLE with individual-level data with the same learners included in incidence analyses (tmle3 R package version 0.2.0).”
“We used hierarchical targeted maximum likelihood estimation (TMLE)”
“the combined intervention reduced malaria incidence by 43% (95% confidence interval, 20–59%)”
“tmle3 R package version 0.2.0”
The data availability statement names a specific repository (ClinEpiDB) and provides a contact for data requests, with conditions. Replication scripts are available on Zenodo with a DOI. This meets the criteria for adequate data and code sharing.
“Data from the original trial are available at https://clinepidb.org/ce/app/workspace/analyses/DS_f559aee789 or from M.H. (michelle.hsiang@ucsf.edu).”
“Replication scripts are available from Zenodo at 10.5281/zenodo.11410094 (ref. ).”
“Data from the original trial are available at https://clinepidb.org/ce/app/workspace/analyses/DS_f559aee789”
“Replication scripts are available from Zenodo at 10.5281/zenodo.11410094”
The analysis plan was pre-specified and available on OSF. Methods are detailed enough for replication. Limitations are explicitly discussed, including low power and potential misclassification. Conclusions are proportional to the evidence, with appropriate caveats. Funding and competing interests are declared.
“The analysis plan was pre-specified and is available at https://osf.io/s8ay4/ .”
“Our study was subject to several limitations. First, owing to rare outcomes, precision was low in some analyses and might have increased the chance of type II error.”
“The original trial was supported by Novartis Foundation (A122666), the Bill & Melinda Gates Foundation (OPP1160129) and the Horchow Family Fund (5300375400).”
“Our study was subject to several limitations.”
“The original trial was supported by Novartis Foundation (A122666), the Bill & Melinda Gates Foundation (OPP1160129) and the Horchow Family Fund (5300375400).”
Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.
Broken references and links
1 finding · worst lowReferences 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.
- References not resolvable to a published paperRecomputed
Checked 65 references by DOI: 1 verified — 1 DOI unresolved, 63 no DOI (shown, not verified).
- UNRESOLVED10.5281/zenodo.11410094Replication scripts for study of spillover effects of reactive, focal malaria interventions in NamibiaCited DOI does not resolve to any Crossref record.
- NO DOIWorld Malaria Report 2023No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDesign and Analysis of Vaccine StudiesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISpillover effects in epidemiology: parameters, study designs and methodological considerationsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISpillover effects on health outcomes in low- and middle-income countries: a systematic reviewNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIVaccine herd effectNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEstimating the herd immunity effect of rotavirus vaccineNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIIndirect (herd) protection, following pneumococcal conjugated vaccines introduction: a systematic review of the literatureNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe Global Meningococcal Initiative: global epidemiology, the impact of vaccines on meningococcal disease and the importance of herd protectionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIHerd effect from influenza vaccination in non-healthcare settings: a systematic review of randomized controlled and observational studiesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPopulation-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAzithromycin distribution and childhood mortality in compliance-related subgroups in Niger: complier average causal effect and spillovers in a cluster-randomized, placebo-controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAssessment of herd protection against trachoma due to repeated mass antibiotic distributions: a cluster-randomised trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIWorms: identifying impacts on education and health in the presence of treatment externalitiesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIImpact of spatial distribution of permethrin-impregnated bed nets on child mortality in rural northern GhanaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICommunity-wide effects of permethrin-treated bed nets on child mortality and malaria morbidity in western KenyaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISpatial effects of permethrin-impregnated bed nets on child mortality: 26 years on, a spatial reanalysis of a cluster randomized trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISpatial analysis of cluster randomised trials: a systematic review of analysis methodsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe impact of 3 years of targeted indoor residual spraying with pirimiphos-methyl on malaria parasite prevalence in a high-transmission area of northern ZambiaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe role of cost-effectiveness in U.S. vaccination policyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIHerd immunity effects in cost-effectiveness analyses among low- and middle-income countriesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICosts and financial feasibility of malaria eliminationNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIWHO Guidelines for Malaria, 14 March 2023No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe effectiveness of reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) to reduce malaria transmission: a cluster-randomised controlled open label two-by-two factorial design trial from the low-endemic setting of NamibiaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAn investigation of the Plasmodium falciparum malaria epidemic in Kavango and Zambezi regions of Namibia in 2016No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIA review of the ring trial design for evaluating ring interventions for infectious diseasesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOITargeting human transmission biology for malaria eliminationNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIWHO Recommended Insecticides For Indoor Residual Spraying Against Malaria VectorsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOITargeted Learning: Causal Inference for Observational and Experimental DataNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIWhat do randomized studies of housing mobility demonstrate?No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIComment on: ‘Randomisation analysis of experimental data in the fisher randomisation test’ by D. BasuNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEconomic analysis of social interactionsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIModelling the influence of temperature and rainfall on the population dynamics of Anopheles arabiensisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDensity, survival and dispersal of Anopheles gambiae complex mosquitoes in a West African Sudan savanna villageNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIWindborne long-distance migration of malaria mosquitoes in the SahelNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISelection of antibody responses associated with Plasmodium falciparum infections in the context of malaria eliminationNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICost and cost effectiveness of reactive case detection (RACD), reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) to reduce malaria in the low endemic setting of Namibia: an analysis alongside a 2 × 2 factorial design cluster randomised controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe economics of malaria control and elimination: a systematic reviewNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe impact of hotspot-targeted interventions on malaria transmission in Rachuonyo south district in the western Kenyan highlands: a cluster-randomized controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEfficacy of single-dose primaquine with artemisinin combination therapy on Plasmodium falciparum gametocytes and transmission: an individual patient meta-analysisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISynergy and timing: a concurrent mass medical campaign predicted to augment indoor residual spraying for malariaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIImpact of population based indoor residual spraying with and without mass drug administration with dihydroartemisinin-piperaquine on malaria prevalence in a high transmission setting: a quasi-experimental controlled before-and-after trial in northeastern UgandaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICombining next-generation indoor residual spraying and drug-based malaria control strategies: observational evidence of a combined effect in MaliNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMalaria risk in young male travellers but local transmission persists: a case-control study in low transmission NamibiaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEffectiveness and safety of reactive focal mass drug administration (rfMDA) using dihydroartemisinin–piperaquine to reduce malaria transmission in the very low-endemic setting of Eswatini: a pragmatic cluster randomised controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISerological evaluation of the effectiveness of reactive focal mass drug administration and reactive vector control to reduce malaria transmission in Zambezi Region, Namibia: results from a secondary analysis of a cluster randomised trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIStudy protocol for a cluster randomised controlled factorial design trial to assess the effectiveness and feasibility of reactive focal mass drug administration and vector control to reduce malaria transmission in the low endemic setting of NamibiaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISubpatent malaria in a low transmission African setting: a cross-sectional study using rapid diagnostic testing (RDT) and loop-mediated isothermal amplification (LAMP) from Zambezi region, NamibiaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIImpact of indoor residual spraying with pirimiphos-methyl (Actellic 300CS) on entomological indicators of transmission and malaria case burden in Migori County, western KenyaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGood performances but short lasting efficacy of Actellic 50 EC indoor residual spraying (IRS) on malaria transmission in Benin, West AfricaNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIEfficacy of Actellic 300 CS-based indoor residual spraying on key entomological indicators of malaria transmission in Alibori and Donga, two regions of northern BeninNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIUltra-sensitive detection of Plasmodium falciparum by amplification of multi-copy subtelomeric targetsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIOptimisation and standardisation of a multiplex immunoassay of diverse Plasmodium falciparum antigens to assess changes in malaria transmission using sero-epidemiologyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIA new approach to hierarchical data analysis: targeted maximum likelihood estimation for the causal effect of a cluster-level exposureNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISuper learnerNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIRegression shrinkage and selection via the LassoNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIRegularization paths for generalized linear models via coordinate DescentNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGreedy function approximation: a gradient boosting machineNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISubgroup analysis, covariate adjustment and baseline comparisons in clinical trial reporting: current practice and problemsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIMultilevel covariance component modelsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIA crossed random effects model for unbalanced data with applications in cross-sectional and longitudinal researchNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISieve plateau variance estimators: a new approach to confidence interval estimation for dependent DataNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDiagnosing and responding to violations in the positivity assumptionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIA simulation study of the number of events per variable in logistic regression analysisNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
2 data/code links checked; 2 live.
- datahttps://clinepidb.org/ce/app/workspace/analyses/DS_f559aee789LIVEHTTP 200Resolved page looks like data.
- dataOSFLIVEHTTP 200https://osf.io/s8ay4/Resolves to OSF (data repository).
Copyediting
5 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 5 minor suggestions below.
5 copyedit issues flagged: mostly typo, consistency, clarity.
- MINORtypoAbstract“chemoprevention using artemether–lumefantrine and/or indoor residual spraying with pirimiphos-methyl”→ Consider adding a comma after 'chemoprevention' for clarity.Minor punctuation issue.
- MINORconsistencyResults, Effects on malaria incidence“incidence reduction, 43%; 95% CI, 21–58%”→ Ensure the CI range is consistent with the abstract (20–59%).The abstract reports 20–59% while the results section reports 21–58%; this may be due to rounding or different analyses.
- MINORconsistencyAbstract“43% (95% confidence interval, 20–59%)”→ Ensure consistency in reporting CIs as '95% CI' throughout.Inconsistent use of 'confidence interval' vs 'CI'.
- MINORtypoResults, Effects on malaria incidence“the confidence spillover-effect estimate included the null”→ Change to 'the confidence interval for the spillover-effect estimate included the null'.Missing word 'interval'.
- MINORclarityMethods, Statistical models for incidence“We used hierarchical targeted maximum likelihood estimation (TMLE), a doubly-robust, semi-parametric method”→ Consider adding a brief explanation of TMLE for readers unfamiliar with the method.Technical term may be unclear to some readers.
The published work is robust and well-reported, with only minor reporting gaps that do not undermine the conclusions. An informed reader should weigh the minor CI inconsistency and the lack of a formal power analysis, but these do not warrant a correction. The paper is suitable for citation and use in evidence synthesis.
- 1.HIGHreportingReconcile the confidence interval for the primary spillover effect: the abstract reports 20–59% while the Results section reports 21–58%. Ensure both sections report the same CI or clarify that they come from different analyses.An internal contradiction in the headline result could confuse readers and undermine trust in the reported effect.
- 2.HIGHreportingAdd a statement about adherence to a specific reporting guideline (e.g., CONSORT) in the Methods or supplement.Explicitly naming a reporting guideline enhances transparency and reproducibility.
- 3.MEDIUMreportingAdd a formal power analysis or sample size justification for the primary analyses, even if post hoc, to address the limited power for direct effects.A power analysis helps readers interpret null results and assess the study's sensitivity.
- 4.MEDIUMstatisticsProvide exact p-values for key effect estimates where feasible, or clarify that CIs are the primary inference.Exact p-values facilitate meta-analysis and allow readers to assess statistical significance directly.
- 5.MEDIUMreportingExplicitly state how outliers were handled in the statistical analysis, or note that no outliers were excluded.Clarifying outlier handling improves reproducibility and addresses a reviewer concern.
- 6.MEDIUMdata codeProvide catalog numbers or RRIDs for key reagents (e.g., Luminex kits) to enhance reproducibility.Catalog numbers allow other researchers to replicate the assays exactly.
- 7.MEDIUMethicsClarify the regulatory compliance framework (e.g., Declaration of Helsinki) in the ethics statement.Explicitly naming the ethical framework strengthens the ethics documentation.
- 8.LOWcopyeditFix the missing word in the Results section: change 'the confidence spillover-effect estimate' to 'the confidence interval for the spillover-effect estimate'.Correcting this typo improves clarity and professionalism.
- 9.LOWcopyeditStandardize the use of '95% CI' vs '95% confidence interval' throughout the manuscript.Consistent terminology improves readability.
- 10.LOWcopyeditAdd a comma after 'chemoprevention' in the Abstract for clarity.Minor punctuation improvement.
- 11.LOWotherConsider adding a brief explanation of TMLE for readers unfamiliar with the method.Clarifying technical terms improves accessibility.
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.