WWARN Clinical Trials Publication Library

Between 1946 to 2022 a total of 1,457 published clinical efficacy studies were identified from over 63,000 screened articles, enrolling a total of 393,625 patients.

See attachments on the right-hand side to download a WWARN publication library of the references and the key parameters of these studies. The library is updated every six months.

The highlights are detailed below:

Descriptive characteristics

- Overall 1,032 (75.9%) of studies assessed P. falciparum, 211 assessed P. vivax, 108 assessed both, and 8 assesses other Plasmodium species

- Of the 1,432 studies which recorded location, 668 (46.7%) were conducted in Africa, 594 (41.5%) in Asia, and 116 (8.1%) in South and Central America

- Of the 1,355 (93.9%) studies where age was described, 787 (65.1%) enrolled children under five years old

- 1,210 (83.0%) studies recorded information on pregnancy status, of which 67 (5.5%) recruited pregnant women

- Of the 1,357 studies with information on study design, 744 (54.8%) of studies were randomised, of which 152 (20.4%) were at least single blinded.

Temporal trends 

Figure 1. Number of publications per year by region. The number of studies published per year increased over time, with 73.6% of P. falciparum and 85.3% of P. vivax studies published after 2000. Most of this increase was due to an increasing number of studies in Africa, especially for P. falciparum.

Spatial trends 

Figure 2. Distribution of study sites. The majority of studies have been conducted in Africa (52%) or Asia (47.5%), with 93 multi-centred. The most common study locations were in Thailand, Nigeria, India and Tanzania for P. falciparum, and Thailand, India, Brazil and Indonesia for P. vivax. There has been a marked increase of P. falciparum studies in African centres since the 2010s.

Treatments 

Figure 3. Most common treatment regimens by number of treatment arms. Panel A: P. falciparum; Panel B: P. vivax. Numbers indicate the number of treatment arms that assessed the drug. The most commonly studied regimen for P. falciparum was artemether-lumefantrine, and chloroquine-primaquine was the most common combination studied for P. vivax.

For clarity, chloroquine in combination with other drugs were included with “chloroquine”, and all quinine combinations were combined with “other”.  AL = Artemether-Lumefantrine, AS+AQ = Artesunate-Amodiaquine, CQ = Chloroquine, SP = Sulfadoxine-Pyrimethamine, DHA+PPQ = Dihydroartemisinin-Piperaquine, AS+MQ = Artesunate-Mefloquine, MQ = Mefloquine, AQ = Amodiaquine, AS = Artesunate, QN = quinine, PQ = Primaquine, TQ = tafenoquine.

Figure 4. Number of treatment arms per year by drug type. Panel A: P. falciparum, Panel B: P. vivax. WHO-recommended ACTs were tested in 44.9% of P. falciparum arms and 11% of P. vivax arms. There has been a significant increase in the number of P. falciparum studies testing ACTs over time, especially in Africa.

Conclusions

• The volume of research on antimalarial therapy has increased substantially over the last 50 years, the predominant increase attributable to new studies conducted in Africa for P. falciparum, and an increase in P. vivax studies.
• Significant knowledge gaps remain: in some heavily affected countries, in non-Pf species, and in at-risk populations such as pregnant women.
• There is a relatively long delay to publication, which undermines the availability of contemporaneous evidence for policymakers.