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 2x2 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 study 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.

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

“…17,18 While extensions of constrained randomization to three-arm parallel cRCTs were recently pursued, 8,19 investigations on the choice of design parameters are currently limited, and the statistical tests previously considered were restricted to LMMs. 8 Motivated by a recent multi-arm cRCT, 7 we investigated the application of constrained randomization and provided a comprehensive evaluation of its statistical properties. For the design of multi-arm cRCTs, we proposed two alternative balance metrics (the maximum pairwise l2 metric and the maximum Mahalanobis distance metric) for the implementation of constrained randomization, and provided a detailed discussion of the impact of these alternative balance metrics as well as different sizes of the constrained space.…”

“…In this motivating example, forty‐eight randomly selected retail outlets in Lagos will be allocated evenly across three intervention arms as described in Woolsey et al 7 Given the highly heterogeneous nature of the retail outlets, it is important to ensure balance on several baseline cluster‐level factors of interest at the design stage. Three cluster‐level variables can be obtained from the pre‐randomization survey conducted by the study team, including daily patient volume of an outlet (continuous), which of the two geographical regions (A & B) within the city of Lagos the outlet is located in (binary), and whether the outlet has malaria rapid diagnostic tests (mRDT) in stock prior to the intervention (binary).…”

“…The Malaria Diagnostic Testing and Conditional Subsidies to Target Artemisinin-Based Combination Therapies in the Retail Sector (TESTsmART) study is an ongoing cRCT to evaluate strategies to increase appropriate treatment of malaria cases in the retail sector. 7 In response to the over-consumption of artemisinin-based combination therapies (ACTs) in malaria-endemic countries, the study aims to target subsidized ACTs to those who receive a confirmatory diagnosis in private sector retail outlets. The study was originally planned as two four-arm cRCTs among registered retail outlets (clusters) conducted separately in two distinct study sites: western Kenya and Lagos, Nigeria.…”

“…As noted in Section 3, different types of hypotheses could be of interest in multi-arm parallel cRCTs. 45 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.…”

“…There are various types of cRCT designs, including parallel‐arm and stepped wedge designs 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, 8 or it could be of interest to simultaneously examine the effects of multiple types of interventions.…”