Abstract

.Parasite resistance to antimalarial drugs poses a serious threat to malaria control. The WorldWide Antimalarial Resistance Network (WWARN) aims to provide a collaborative platform to support the global malaria research effort. Here, we describe the “WWARN clinical trials publication library,” an open-access, up-to-date resource to streamline the synthesis of antimalarial safety and efficacy data. A series of iteratively refined database searches were conducted to identify prospective clinical trials assessing antimalarial drug efficacy with at least 28 days of follow-up. Of approximately 45,000 articles screened, 1,221 trials published between 1946 and 2018 were identified, representing 2,339 treatment arms and 323,819 patients. In trials from endemic locations, 75.7% (787/1,040) recruited patients with Plasmodium falciparum, 17.0% (177/1,040) Plasmodium vivax, 6.9% (72/1,040) both, and 0.4% (4/1,040) other Plasmodium species; 57.2% (585/1,022) of trials included under-fives and 5.3% (55/1,036) included pregnant women. In Africa, there has been a marked increase in both P. falciparum and P. vivax studies over the last two decades. The WHO-recommended artemisinin-based combination therapies alone or with a gametocidal drug were assessed in 39.5% (705/1,783) of P. falciparum treatment arms and 10.5% (45/429) of P. vivax arms, increasing to 78.0% (266/341) and 22.9% (27/118), respectively, in the last five years. The library is a comprehensive, open-access tool that can be used by the malaria community to explore the collective knowledge on antimalarial efficacy (available at https://www.wwarn.org/tools-resources/literature-reviews/wwarn-clinical-trials-publication-library). It is the first of its kind in the field of global infectious diseases, and lessons learnt in its creation can be adapted to other infectious diseases.

Highlights

  • One of the greatest challenges facing malaria control is the ability of Plasmodium species to adapt to selective drug pressure

  • Synthesizing the available evidence on antimalarial efficacy is essential to understand the drivers of resistance, ensure the optimal use of available treatment options, and facilitate timely and appropriate decision-making by policy-makers

  • 45,000 papers were screened to identify a total of 1,221 clinical trials published since 1946 (Figure 1)

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Summary

Introduction

One of the greatest challenges facing malaria control is the ability of Plasmodium species to adapt to selective drug pressure. The WorldWide Antimalarial Resistance Network (WWARN) was established in 2009, with the aim to provide innovative tools and a collaborative data platform to facilitate the optimal use of antimalarial drugs and support the global research effort toward malaria elimination. One such tool is the “WWARN clinical trials publication library,” a comprehensive, systematically constructed database of published antimalarial efficacy trials. The library is actively maintained with periodic updates and can be rapidly searched for relevant studies with pre-extracted data, expediting the process of evidence identification and synthesis.

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