Incentivizing appropriate malaria case management in the private sector: a study protocol for two linked cluster randomized controlled trials to evaluate provider- and client-focused interventions in western Kenya and Lagos, Nigeria

Abstract

Background A large proportion of artemisinin-combination therapy (ACT) anti-malarial medicines is consumed by individuals that do not have malaria. The over-consumption of ACTs is largely driven by retail sales in high malaria-endemic countries to clients who have not received a confirmatory diagnosis. This study aims to target ACT sales to clients receiving a confirmatory diagnosis using malaria rapid diagnostic tests (mRDTs) at retail outlets in Kenya and Nigeria. Methods This study comprises two linked four-arm 2 × 2 factorial cluster randomized controlled trials focused on malaria diagnostic testing and conditional ACT subsidies with the goal to evaluate provider-directed and client-directed interventions. The linked trials will be conducted at two contrasting study sites: a rural region around Webuye in western Kenya and the urban center of Lagos, Nigeria. Clusters are 41 and 48 participating retail outlets in Kenya and Nigeria, respectively. Clients seeking care at participating outlets across all arms will be given the option of paying for a mRDT—at a study-recommended price—to be conducted at the outlet. In the provider-directed intervention arm, the outlet owner receives a small monetary incentive to perform the mRDT. In the client-directed intervention arm, the client receives a free ACT if they purchase an mRDT and receive a positive test result. Finally, the fourth study arm combines both the provider- and client-directed interventions. The diagnosis and treatment choices made during each transaction will be captured using a mobile phone app. Study outcomes will be collected through exit interviews with clients, who sought care for febrile illness, at each of the enrolled retail outlets. Results The primary outcome measure is the proportion of all ACTs that are sold to malaria test-positive clients in each study arm. For all secondary outcomes, we will evaluate the degree to which the interventions affect purchasing behavior among people seeking care for a febrile illness at the retail outlet. Conclusions If our study demonstrates that malaria case management can be improved in the retail sector, it could reduce overconsumption of ACTs and enhance targeting of publicly funded treatment reimbursements, lowering the economic barrier to appropriate diagnosis and treatment for patients with malaria. Trial registration ClinicalTrials.govNCT04428307, registered June 9, 2020, and NCT04428385, registered June 9, 2020.

Constrained randomization and statistical inference for multi-arm parallel cluster randomized controlled trials

“…15,16 While extensions of constrained randomization to three-arm parallel cRCTs were recently pursued, 1,2 investigations on the choice of design parameters are currently limited, and the statistical tests previously considered were restricted to linear mixed models. 2 Motivated by a recent multi-arm cRCT, 7 we provided a detailed discussion of the implementation of constrained randomization with alternative balance metrics (the maximum pairwise 2 metric and the maximum Mahalanobis distance metric) for multi-arm cRCTs. For statistical inference under constrained randomization, we additionally developed novel permutation tests for two types of null hypotheses describing the comparative effectiveness of multiple treatments.…”

“…As noted in Section 3, different types of hypotheses could be of interest in multi-arm parallel cRCTs. 34 We specified a set of three hypotheses (see Table 2) based on model (7) where there is one control condition and two treatment conditions. We adopted a hierarchical approach and specified a global hypothesis comparing all three arms at once as the first step.…”

“…6 In this article, we focus on multi-arm parallel cRCTs, motivated by the design of TESTsmART, an ongoing trial evaluating interventions to improve antimalarial stewardship in the retail sector. 7 In a multi-arm cRCT, each distinct arm can be defined by different combinations of interventions, or different "doses" of a single type of intervention, 2 or it could be of interest to simultaneously examine the effects of multiple types of interventions.…”

Correction: Incentivizing appropriate malaria case management in the private sector: a study protocol for two linked cluster randomized controlled trials to evaluate provider- and client-focused interventions in western Kenya and Lagos, Nigeria

“…Following publication of the original article [ 1 ] the authors reported a correction to their published study protocol.…”

“…The purpose of this correction is to update the design of one of the two linked cluster randomized trials (CRTs) in our study protocol entitled “ Incentivizing appropriate malaria case management in the private sector: a study protocol for two linked cluster randomized controlled trials to evaluate provider- and client-focused interventions in western Kenya and Lagos, Nigeria” [ 1 ] and to provide justification for a lower target sample size in the other trial. This study included a CRT enrolling clusters (retail outlets) into four treatment arms in Nigeria using estimated sample sizes based on malaria prevalence and testing rates in the published literature.…”