Clinical research in the context of rapidly emerging public health threats

A key lesson from a series of recent outbreaks of emerging pathogens of global public health importance including SARS-CoV, highly pathogenic avian influenza A (H5N1) virus, Nipah virus and the 2009 H1N1 virus pandemic was that mounting clinical research in response to a rapidly emerging infectious disease is extremely challenging and often delayed. During these events, important pathogenesis and clinical management data came mostly from sites that were already undertaking related clinical studies including those on inter-pandemic influenza (e.g., SEAICRN, Institute Pasteur Networks, Chinese University of Hong Kong, and University of Hong Kong) or from established national or regional research networks such as the Canadian and Australia/New Zealand Critical Care Trials Group. However there was very little cross-border coordination, unlike that which now exists in epidemiology and to an extent in virology and genomics. The clinical research response was cumbersome and slow despite years of global preparations for a potentially devastating influenza pandemic of avian origin or the next SARS-like outbreak. Although observational registries were mobilized, initiatives to launch randomized controlled trials or more sophisticated biologic studies generally missed the initial waves of the 2009 H1N1 pandemic and in many cases failed to enrol sufficient numbers of patients across the entire clinical spectrum of disease into studies, even during subsequent waves. During the 2009 H1N1 virus pandemic the efforts to prepare for a respiratory disease outbreak allowed a reasonably rapid and coordinated response on epidemiologic and diagnostic aspects of disease but failed in the timely conduct of clinical research aimed at improving patient management or understanding pathogenesis. The failure to have coordinated, comparable data on clinical management and pathogenesis of 2009 H1N1 virus infection meant that we missed the opportunity to improve patient outcomes. Indeed this has been a problem in almost all epidemics over the last decade (Nipah, SARS, H5N1, and in outbreaks of VHF) with very little research aimed at improving clinical management or understanding pathogenesis. This has demonstrated that unless something is done now to change the barriers faced in 2009, the next influenza (or other) outbreak will result in a similar missed opportunity to save lives. Furthermore, no integrated analyses exist of combined microbiological/virological, immunological, clinical, epidemiological, and genetic data for comprehensive assessment of host-emerging pathogen interactions that can inform prevention and control activities, and guide clinical management. There is an urgent need to establish a sustainable consortium of clinical research groups with broad geographic coverage (including low resource settings), cross-border coordination, commitment to open access, and capacity to conduct complementary high-quality, hospital-based pathogenesis and clinical management studies and the flexibility to respond immediately to rapidly emergent threats. We need a new paradigm for clinical research in the context of rapidly emerging public health threats and one appropriate to the sorts of challenges we will face in the 21st Century.