Research Article: Improving rational use of ACTs through diagnosis-dependent subsidies: Evidence from a cluster-randomized controlled trial in western Kenya

Date Published: July 17, 2018

Publisher: Public Library of Science

Author(s): Wendy Prudhomme O’Meara, Diana Menya, Jeremiah Laktabai, Alyssa Platt, Indrani Saran, Elisa Maffioli, Joseph Kipkoech, Manoj Mohanan, Elizabeth L. Turner, Lorenz von Seidlein

Abstract: BackgroundMore than half of artemisinin combination therapies (ACTs) consumed globally are dispensed in the retail sector, where diagnostic testing is uncommon, leading to overconsumption and poor targeting. In many malaria-endemic countries, ACTs sold over the counter are available at heavily subsidized prices, further contributing to their misuse. Inappropriate use of ACTs can have serious implications for the spread of drug resistance and leads to poor outcomes for nonmalaria patients treated with incorrect drugs. We evaluated the public health impact of an innovative strategy that targets ACT subsidies to confirmed malaria cases by coupling free diagnostic testing with a diagnosis-dependent ACT subsidy.Methods and findingsWe conducted a cluster-randomized controlled trial in 32 community clusters in western Kenya (population approximately 160,000). Eligible clusters had retail outlets selling ACTs and existing community health worker (CHW) programs and were randomly assigned 1:1 to control and intervention arms. In intervention areas, CHWs were available in their villages to perform malaria rapid diagnostic tests (RDTs) on demand for any individual >1 year of age experiencing a malaria-like illness. Malaria RDT-positive individuals received a voucher for a discount on a quality-assured ACT, redeemable at a participating retail medicine outlet. In control areas, CHWs offered a standard package of health education, prevention, and referral services. We conducted 4 population-based surveys—at baseline, 6 months, 12 months, and 18 months—of a random sample of households with fever in the last 4 weeks to evaluate predefined, individual-level outcomes. The primary outcome was uptake of malaria diagnostic testing at 12 months. The main secondary outcome was rational ACT use, defined as the proportion of ACTs used by test-positive individuals. Analyses followed the intention-to-treat principle using generalized estimating equations (GEEs) to account for clustering with prespecified adjustment for gender, age, education, and wealth. All descriptive statistics and regressions were weighted to account for sampling design. Between July 2015 and May 2017, 32,404 participants were tested for malaria, and 10,870 vouchers were issued. A total of 7,416 randomly selected participants with recent fever from all 32 clusters were surveyed. The majority of recent fevers were in children under 18 years (62.9%, n = 4,653). The gender of enrolled participants was balanced in children (49.8%, n = 2,318 boys versus 50.2%, n = 2,335 girls), but more adult women were enrolled than men (78.0%, n = 2,139 versus 22.0%, n = 604). At baseline, 67.6% (n = 1,362) of participants took an ACT for their illness, and 40.3% (n = 810) of all participants took an ACT purchased from a retail outlet. At 12 months, 50.5% (n = 454) in the intervention arm and 43.4% (n = 389) in the control arm had a malaria diagnostic test for their recent fever (adjusted risk difference [RD] = 9 percentage points [pp]; 95% CI 2–15 pp; p = 0.015; adjusted risk ratio [RR] = 1.20; 95% CI 1.05–1.38; p = 0.015). By 18 months, the ARR had increased to 1.25 (95% CI 1.09–1.44; p = 0.005). Rational use of ACTs in the intervention area increased from 41.7% (n = 279) at baseline to 59.6% (n = 403) and was 40% higher in the intervention arm at 18 months (ARR 1.40; 95% CI 1.19–1.64; p < 0.001). While intervention effects increased between 12 and 18 months, we were not able to estimate longer-term impact of the intervention and could not independently evaluate the effects of the free testing and the voucher on uptake of testing.ConclusionsDiagnosis-dependent ACT subsidies and community-based interventions that include the private sector can have an important impact on diagnostic testing and population-wide rational use of ACTs. Targeting of the ACT subsidy itself to those with a positive malaria diagnostic test may also improve sustainability and reduce the cost of retail-sector ACT subsidies.Trial NCT02461628

Partial Text: Each year, half of the 215 million cases of malaria—and hundreds of millions of cases of nonmalaria febrile illnesses—seek care in the informal health sector [1]. In the mid-2000s, most malaria-endemic countries changed their first-line antimalarial to an artemisinin combination therapy (ACT) due to widespread resistance to older drugs. At the time, it was recognized that most malaria cases cared for in the retail sector were being inappropriately treated due to the high cost of new ACTs [2]. In response to this, the Affordable Medicines Facility-malaria (AMFm) piloted retail-sector ACT subsidies in 7 countries that were subsequently widely adopted. As a result, the market share of ACTs dramatically increased [3, 4]. By 2017, 10 years after retail-sector subsidies were introduced, 44% of quality-assured ACTs were distributed through the retail sector [5, 6].

We estimate the public health impact of free malaria testing and conditional antimalarial subsidies implemented through a partnership between CHWs and the private retail sector. We conducted a cluster-randomized trial in 32 community units (CUs; i.e., clusters) across a population of more than 160,000 people (Fig 1). CHWs offered free, community-based malaria testing using RDTs to individuals experiencing a malaria-like illness. The conditional subsidy was in the form of a voucher issued to participants with a positive malaria test, which could be redeemed at a local drug retailer for the purchase of a quality-assured ACT at a reduced, fixed price. The voucher was intended to create an incentive for an individual with suspected malaria to seek out a test from their CHW (individual benefit) while also allowing drug subsidies to be targeted to those with confirmed malaria (community-wide benefit).

The study area included over 160,000 people (based on estimates from the 2009 census) in 32 clusters across 3 subcounties (Fig 1). A total of 292 CHWs in 16 intervention clusters were trained to perform RDTs, and 42 retail outlets serving these clusters were enrolled to redeem vouchers.

In 2016, there were an estimated 216 million cases of malaria globally, but more than 400 million courses of ACT distributed [40]. Overconsumption of ACTs on this scale has grave implications for the spread of antimalarial resistance [18, 41] and results in poor outcomes for inappropriately treated nonmalaria fevers [11]. In our study area, nearly 70% of individuals with a recent fever reported taking an ACT, two-thirds of which was sourced from the retail sector. Against this background of very high ACT consumption, we rigorously tested a sustainable and scalable community-based intervention designed to increase malaria diagnostic testing and improve ACT targeting. Our intervention was specifically designed to reach individuals purchasing drugs over the counter and to incorporate the retail sector, which delivers the majority of ACTs in Kenya [30]. A particular strength of our study is the evaluation of outcomes in a representative sample of malaria-like illnesses in the population, rather than only in those who access the intervention. As a result, we were able to estimate the impact of the intervention on malaria diagnostic testing rates and targeting of ACTs among all fevers in the population as well as on the proportion of the total ACT consumed by those with a positive test. We find that population-wide targeting and rational use of ACTs improved by 46% and 40%, respectively, relative to the control arm.



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