Tuesday, March 1, 2016

Conducting Clinical Trials in Outbreak Settings: Points to Consider

In the summer of 1981, the U.S. Centers for Disease Control and Prevention reported cases of a rare respiratory infection, Pneumocystis pneumonia and an unusual cancer, Kaposi’s sarcoma, in young, previously healthy homosexual men in Los Angeles, New York, and San Francisco. The underlying reason for these infections, immune compromise due to infection of immune competent cells by the human immunodeficiency virus (HIV), would not be understood for three more years with the discovery of HIV, and the global impact of the virus would take many more years to elucidate. Still, even in the earliest days of the HIV/AIDS pandemic, the near-inevitable mortality associated with the disease was clear. Affected individuals and their caregivers were desperate to find effective treatments, and many tried unproven interventions that would sometimes cause more harm than good. Biomedical researchers experienced intense pressure to offer access to experimental therapies in the face of near certain death.

Most investigators felt that interventions for HIV/AIDS should be tested according to sound scientific principles, using the “gold standard” of double-blinded, randomized, placebo-controlled trials to determine the safety and efficacy of candidate therapies. Prioritization for testing of drugs was based on a careful analysis of available preclinical data. This approach yielded a solid basis for the testing and ultimate proof of efficacy of the first approved antiretroviral drug, zidovudine (AZT), and other agents to treat HIV and its complications in the early years of the HIV/AIDS pandemic. However, some stakeholders felt that strict adherence to scientific practices was unnecessary and insisted upon immediate access to any therapy with a remote chance of making a difference. Eventually, through extensive dialogue and engagement of scientists, regulatory agencies and the affected communities, a compromise was reached whereby first priority was given to rigorous evaluation of the most promising treatments with immediate expanded access to those treatments upon demonstration of efficacy. The HIV/AIDS experience provides a paradigm for conducting clinical trials in other emerging epidemics, such as the Ebola outbreak of 2014-2015 in West Africa...

Core Ethical and Scientific Principles for Trial Conduct in Outbreak Settings*
Ethical conduct to avoid exploitation – including respect for volunteers, local community
engagement and carefully informed consent
Partnership with affected country investigators and officials – including identification of
interested local investigators, bolstering of trial infrastructure as needed and shared best practices
regarding regulatory oversight
Scientific validity – including plausibility of benefit from candidate countermeasures and sound
trial design
Independent review and scientific oversight – careful oversight by an independent and skilled
Data and Safety Monitoring Board
Transparency – prompt sharing of data with practitioners and affected communities
*Adapted in part from Reference 1

Full article at:  http://goo.gl/QxILEc

By:  H. Clifford Lane, MD, Hilary D. Marston, MD, MPH, and Anthony S. Fauci, MD
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Corresponding author: H. Clifford Lane,  vog.hin.diain@enalc, Mailing address: MSC 1460, 10 Center Drive, Bethesda, MD 20892

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