Abstract: We included four trials (two cluster-randomised trials reported in three articles and two non-randomised cluster trials). Three trials assessed retail sector ACT subsidies combined with supportive interventions (retail outlet provider training, community awareness and mass media campaigns). One trial assessed vouchers provided to households to purchase subsidised ACTs. Price subsidies ranged from 80% to 95%. One trial enrolled children under five years of age; the other three trials studied people of all age groups. The studies were done in rural districts in East Africa (Kenya, Uganda and Tanzania). In this East Africa setting, these ACT subsidy programmes increased the percentage of children under five years of age receiving ACTs on the day, or following day, of fever onset by 25 percentage points (95% confidence interval (CI) 14.1 to 35.9 percentage points; 1 study, high certainty evidence). This suggests that in practice, among febrile children under five years of age with an ACT usage rate of 5% without a subsidy, subsidy programmes would increase usage by between 19% and 41% over a one year period. The ACT subsidy programmes increased the percentage of retail outlets stocking ACTs for children under five years of age by 31.9 percentage points (95% CI 26.3 to 37.5 percentage points; 1 study, high certainty evidence). Effects on ACT stocking for patients of any age is unknown because the certainty of evidence was very low. The ACT subsidy programmes decreased the median cost of ACTs for children under five years of age by US$ 0.84 (median cost per ACT course without subsidy: US$ 1.08 versus with subsidy: US$ 0.24; 1 study, high certainty evidence). The ACT subsidy programmes increased the market share of ACTs for children under five years of age by between 23.6 and 63.0 percentage points (1 study, high certainty evidence). The ACT subsidy programmes decreased the use of older antimalarial drugs (such as amodiaquine and sulphadoxine-pyrimethamine) among children under five years of age by 10.4 percentage points (95% CI 3.9 to 16.9 percentage points; 1 study, high certainty evidence). None of the three studies of ACT subsidies reported the number of patients treated who had confirmed malaria. Vouchers increased the likelihood that an illness is treated with an ACT by 16 to 23 percentage points; however, vouchers were associated with a high rate of over-treatment of malaria (only 56% of patients taking ACTs from the drug shop tested positive for malaria under the 92% subsidy; 1 study, high certainty evidence). Programmes that include substantive subsidies for private sector retailers combined with training of providers and social marketing improved use and availability of ACTs for children under five years of age with suspected malaria in research studies from three countries in East Africa. These programmes also reduced prices of ACTs, improved market share of ACTs and reduced the use of older antimalarial drugs among febrile children under five years of age. The research evaluates drug delivery but does not assess whether the patients had confirmed (parasite-diagnosed) malaria. None of the included studies assessed patient outcomes; it is therefore not known whether the effects seen in the studies would translate to an impact on health.

Plain-language summary: We included four studies. One study looked at the effect of subsidising ACT drugs for children under five years of age and three studies looked at subsidising ACT drugs for people of all ages. All studies were from rural districts in East Africa (Kenya, Uganda and Tanzania). ACT price subsidies were accompanied with activities (such as staff training at shops and pharmacies, community awareness and mass media campaigns) to promote appropriate use of antimalarial drugs in all except one study. In all four studies, the effect of subsidising the drugs was compared to not subsidising the drugs. Price subsidies ranged from 80% to 95% of the actual price; vouchers to households were used in one study. The findings from these studies indicate that ACT subsidy programmes: (i) lead to a substantial increase in the number of children under five years of age who used ACTs when they had a fever (high certainty evidence); (ii) lead to a substantial increase in the number of shops that stocked ACTs for children under five years of age (high certainty evidence); we could not draw any conclusion on the effect on the number of shops that stocked ACTs for patients of any age because the quality of evidence was very low; (iii) lead to a substantial decrease in the price of ACTs for children under five years of age (high certainty evidence); (iv) lead to a substantial increase in the market share of ACTs for children under five years of age (high certainty evidence); and (v) lead to a decrease in the use of older, less effective antimalarials among children under five years of age (high certainty evidence). None of the studies measured whether the subsidy programmes led to any harmful effects (such as the inappropriate use of ACTs, in other words people who receive ACTs but do not actually have malaria). The review findings also showed that subsidising ACT prices using vouchers lead to an increase in the likelihood that an illness was treated with an ACT among people seeking treatment for fever or suspected malaria. However, vouchers also lead to an increase in inappropriate use of ACTs (high certainty evidence).