Drug Development Papers in PLoS Medicine: How We Try to Spot a Winner

T his month's PLoS Medicine publishes a paper describing the results of a very early drug discovery study. The nature of early drug development is to identify many promising compounds, only a small number of which eventually make it into routine treatment. Consequently, there are many more papers reporting promising leads in early drug development than ones that report effi cacy in large clinical trials. Because of this natural attrition, medical journals (including this one) are often reluctant to publish intriguing results from the early stages of drug discovery. However, PLoS Medicine occasionally does publish such reports, and the manuscript by Dominique Mazier and colleagues [1] in this issue is an example. What made us and our advisers select this paper above the many similar ones we receive? As editors, we ask several general questions about any submitted manuscript: how important is the research question (both globally and in relation to the journal's audience); what is the likelihood of the conclusions holding up over time (and when is it worth publishing preliminary results that would be important if confi rmed but where confi rmation is uncertain); and, for a highly selective general medical journal, do the results represent a substantial advance—be it in understanding pathogenesis, suggesting treatment options, or having implications for public health. More specifi cally, for drug development papers, questions we consider include: how substantial is the disease burden that the drug would treat; are any treatments currently available (or do the available treatments have serious limitations); has a novel or interesting mechanism been developed; (or was a novel system used in the development of the drug); and fi nally, is there a realistic path to clinical development? Malaria is clearly a topic of great relevance to PLoS Medicine's mission (of publishing papers on the diseases causing a high global burden of disease), and to our authors and readers. A substantial number of papers submitted to us concern malaria, and the 44 articles of all types on malaria that we have published have been cumulatively downloaded more than 100,000 times. The World Health Organization estimates that malaria is responsible for more than 1 million deaths per year, most of them young children living in Africa (see http:⁄⁄www.who.int/mediacentre/ factsheets/fs094/en/). A recent PLoS Medicine paper by Mathers and Loncar [2] reported that malaria was the 12th leading cause of death worldwide in 2002. We also know there are substantial limitations …