Kafy 2017.

Methods	Study design: cRCT with 2 intervention arms Unit of allocation: clusters (villages) Number of units: 26 villages randomized into 2 arms equally. Each cluster consisting of ≥ 500 households Outcome assessment/surveillance type: 60 children randomly selected from each village to participate in the study Active case detection for malaria episodes was done on the cohort of children aged 0.5–10 years weekly during the peak of the malaria season (September to November) and fortnightly during the remainder of the year, for a total of 30 annual visits. during 12 periods of 6 consecutive days at 6‐weekly intervals. Malaria was confirmed by RDT (SD BIOLINE‐Malaria Ag P.f/P.v.; Standard Diagnostics, Inc.), or microscopy, or both. Prevalence of infection was measured once each year, during September to October. Cohort of children were tested for P falciparum infection using RDTs (SD BIOLINE‐Malaria Ag P.f/P.v.; Standard Diagnostics, Inc.) irrespective of symptoms. Length of follow‐up: 1 June 2012 to 31 May 2015 Adjustment for clustering: yes
Participants	Number of participants: total population in study area in 2011 was 139,566. Over the 3‐year study period, 7529 children were recruited who were followed up cumulatively for 17,284 person‐years. Population characteristics: a baseline household census estimated that the area comprised approximately 119,000 households in 197 villages with 600,000 inhabitants who were predominantly dependent on rain‐fed agriculture. Mean age of cohort children were similar across all study arms (about 5–6 years old) Withdrawal and loss to follow‐up: not reported
Interventions	Comparison: IRS + ITN versus ITN alone IRS: Active ingredient, dosage, and formulation: deltamethrin 25 mg/m² in 2012 (formulation not reported, Chema Industries), bendiocarb 200 mg/m² in 2013 and 2014 (Ficam 80%, wettable powder, Bayer) Frequency of spraying: IRS was conducted in August and late December of each year Coverage: 99% in 2012, 82% in 2013, and 83% in 2014 Buffer size between clusters: minimum 3 km between the edges of adjoining clusters ITN: Active ingredient and dosage: deltamethrin 55 mg (PermaNet 2.0) Coverage: an annual intervention assessment survey showed that household net ownership was 99.6% in 2012, 82.1% in 2013, and 98.6% in 2014. Compliance: defined as the proportion of affirmative responses to the question "Did this child sleep under an LLIN last night?" In 2012, this was 79% in both arms. In 2013, it was 74% in the LLIN‐only arm and 75% in the LLIN + IRS arm. In 2014, it was 82% in both study arms. Control: ITN only as above Cointerventions: none reported
Outcomes	Incidence of malaria in children aged 0.5–10 years Prevalence of malaria infection in children aged 0.5–10 years Deltamethrin susceptibility using WHO discriminating dose tests Prevalence of pyrethroid‐resistant 1014F kdr allele Cost and cost‐effectiveness
Location profile	Study location: Galabat, south‐eastern Sudan, located around 80 km from Gedarif town and borders Ethiopia Malaria endemicity: highly seasonal EIR: not reported Population proximity/density: not reported Plasmodium spp:P falciparum accounts for 95% of the malaria burden
Vector profile	Primary (and secondary) vector species:An arabiensis Vector behaviour (nature, stability, adult habitat, peak biting times, exophilic/endophilic, exophagic/endophagic, anthropophilic/zoophilic): not reported Phenotypic resistance profile: mean percentage mortality in the LLIN arm (65.0%, 95% CI 44.6% to 85.3%) was not significantly different from that of the LLIN + IRS arm (60%, 95% CI 38.2% to 82.2%) during 2012 (t = 0.425; degrees of freedom 9; P = 0.68). Genotypic resistance profile:Vgsc‐1014F allelic frequency was around 60% in mosquitoes sampled from both study arms in 2012 Method of mosquito collection:Anopheles larvae and pupae were collected annually during the rainy season. Adults were collected using pyrethrum spray catches. 24 An arabiensis females per cluster were selected at random for Vgsc‐1014F genotyping to estimate a cluster‐specific resistance marker frequency.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Clusters were randomly allocated using a restricted randomization computerized procedure. Balance criteria were prevalence of P falciparum infection, ITN use, kdr frequency in An arabiensis and cluster population size. Out of 200,000 random allocations, 8000 yielded balance between study arms on these criteria, from which 1 sequence was randomly selected.
Allocation concealment (selection bias)	Low risk	The 26 clusters in Gedarif, Sudan were randomized to receive LLIN + IRS or LLINs alone, using restricted randomization to ensure balance between study arms. Balance criteria were: prevalence of P falciparum infection and ITN use as determined in a baseline survey, kdr frequency in An arabiensis from a survey of mosquito collections carried out in each cluster, and cluster population size. Out of 200,000 random allocations of the 26 clusters, 8000 yielded balance between study arms on these criteria. Of these, 1 allocation was randomly chosen, after verifying that the imposed restriction did not introduce undue dependence between clusters.
Blinding of participants and personnel (performance bias) Incidence of malaria	Low risk	Participants and personnel were not blinded to intervention. Low risk of bias for both incidence and prevalence. RDTs and microscopy were used to confirm malaria infection.
Blinding of participants and personnel (performance bias) Prevalence of malaria	Low risk	Participants and personnel were not blinded to intervention. Low risk of bias for both incidence and prevalence. RDTs and microscopy were used to confirm malaria infection.
Blinding of outcome assessment (detection bias) Incidence of malaria	Low risk	Participants and personnel were not blinded to intervention. Low risk of bias for both incidence and prevalence. RDTs and microscopy were used to confirm malaria infection.
Blinding of outcome assessment (detection bias) Prevalence of malaria	Low risk	Participants and personnel were not blinded to intervention. Low risk of bias for both incidence and prevalence. RDTs and microscopy were used to confirm malaria infection.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No report of withdrawals.
Selective reporting (reporting bias)	Low risk	All children‐days were analyzed. The study protocol reports 1 each outcome as stated in the clinical trials register (note: retrospectively registered)
Recruitment bias	Low risk	Cohort of children were randomly selected
Baseline imbalance	Low risk	Although baseline information was not available, key effect modifiers such as age and LLIN usage were measured during the study and there were no significant differences.
Loss of clusters	Low risk	No clusters were lost.
Incorrect analysis	Low risk	Adjustment for clustering was done.
Comparability with RCTs randomizing participants	Low risk	Because the intervention is expected to have community level impact as well as individual impact, cRCTs are the most appropriate study design to capture this.
Other bias	Low risk	No other biases.