Bridging the gap: improving clinical development and the regulatory pathways for health products for neglected diseases.

backgroundThere has been tremendous progress over the last decade in the development of health products--drugs, vaccines, and diagnostics--for neglected diseases. There are now dozens of candidate products in the pipeline. PURPOSE: Our purpose is to assess challenges that will arise in later-stage clinical development of these candidate health products and propose a strategy that would help bring the costs, risks, and finances for their clinical trials into a better, more sustainable balance.

methodsWe conducted a literature review of clinical trial-related publications, interviewed individuals sponsoring and conducting interventional clinical trials for neglected diseases, and analyzed data from Clinicaltrials.gov, a clinical trials registry, on neglected disease clinical trials initiating subject recruitment between January 1, 2003 and December 31, 2009. We quantified Clinicaltrials.gov data into country-specific participation in clinical trials and aggregated them into geographic regions. We employed bioinformatics and keyword methods to classify trials by type of intervention, sponsor, study phase, and therapeutic area.

resultsTwo substantial bottlenecks threaten our capacity to bring these candidate neglected disease therapies to those in need. First, the research and regulatory capacity in many neglected disease-endemic settings is not adequate to support the clinical trials that need to occur there in order to complete the development of these products. Second, even with expected attrition in the pipeline, current levels of financing are insufficient to support the clinical development of these products under current cost assumptions. LIMITATIONS: The proportion of trials of relevant studies not registered on Clinicaltrials.gov is not known, but is thought to be smaller post-2005, after the International Committee of Medical Journal Editors initiated a policy requiring investigators to deposit information about trial design into an accepted clinical trials registry before beginning patient enrollment.

conclusionsRealizing the promise of the neglected disease product pipeline will require not only increased funding for large-scale clinical trials and capacity building, but also greater attention to how these trials and their regulatory pathways can be improved to reduce unnecessary costs, delays, and risks to trial subjects. We propose a two-prong strategy: (1) adaptation and adoption of emerging research on 'sensible guidelines' for reducing large-scale, randomized clinical trial costs to the demands of the neglected disease product pipeline and (2) regional approaches to regulation and ethical review of clinical trials for health products for neglected diseases.