Clinical Research During a Public Health Emergency: A Systematic Review of Severe Pandemic Influenza Management

Objective: Rigorous evaluation of clinical interventions in the setting of a public health emergency is necessary to identify best practices, to develop clinical management guidelines, and to inform resource allocation. The 2009 influenza A (H1N1) pandemic necessitated care of critically ill patients around the world. To inform the World Health Organization Public Health Research Agenda for Influenza, we conducted a systematic review to identify clinical interventions other than antiviral therapies that would benefit severely ill 2009 H1N1 influenza patients (adults and children) in both high- and low-resource settings. Data Sources: PubMed, EMBASE, Cochrane Central Register of Clinical Trials, and Cochrane Database of Systematic Reviews; hand search of abstracts from six professional society annual conferences and bibliographies of clinical review articles; and personal communication with leaders in the field. Study Selection: English language; human studies; citations added to databases from January 1, 2009 (Cochrane databases) or March 15, 2009 (PubMed and EMBASE) through January 31, 2012; randomized controlled trials, prospective cohort studies, or systematic reviews/meta-analyses of non-antiviral clinical interventions in hospitalized 2009 influenza A (H1N1) patients. Data Extraction: The search identified 2,452 articles. Thirty-six potentially relevant articles were read. Seven articles met criteria. All were observational studies. Data Synthesis: One study found benefit of convalescent plasma infusion, three studies found no benefit of corticosteroids, and three studies had mixed results on the benefit of extracorporeal lung support. No study was applicable to health care delivery in low-resource settings. Conclusions: There is a paucity of high quality clinical research to inform clinical care of severe H1N1 influenza, and we found no beneficial interventions appropriate for low-resource settings. This may be due to the logistical difficulties of conducting clinical research in response to a public health emergency. Our investigation underscores the need for the development of outbreak-ready research capacity in both high- and low-resource settings. (Crit Care Med 2013; 41: 1345-1352)