Box 2 Research in context and added value of the study

Evidence before this study: This is the first review to address the question of the representativeness of the patients enrolled in malaria treatment trials with respect to the population of patients seen in clinical practice, covering the last two decades. No relevant previous study conducted on this subject could be identified after searching MEDLINE and the Cochrane Library

Added-value of this study: The findings of this study provide evidence of knowledge gaps on the generalizability of current malaria clinical efficacy trials to the general population. The study identifies and quantifies systematic exclusions based on parasite counts (especially high parasitaemia) and parasite species (in particular mixed infections); these patients will be treated in practice but are under-researched in clinical trials. There was also significant under-reporting of the reason for exclusions of malaria-positive patients in trials

Implications of all the available evidence: These results point to three main needs: conducting pragmatic (effectiveness) trials to capture the full range of cases treated in real-life; filling the knowledge gap on the treatment of mixed infections; and providing accurate reporting of exclusions. The CONSORT statement offers a valuable framework for improving the transparency of clinical trials, including adequate reporting of the eligibility criteria and of patient attrition. Papers should report details on the reasons for excluding subjects against pre-established eligibility criteria, for which trial screening logs could be an important source of information. Recording and sharing this information would allow better profiling of the patients seen in routine practice and a better understanding of the representativeness of the body of evidence from clinical trials