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The Food and Drug Administration (FDA) reviews clinical-trial data for new drugs and determines whether the benefits of these drugs outweigh the risks.1 This requirement, legislated in 1962,2 raised the bar to approval and reduced the likelihood that new drugs would be ineffective or cause major health problems. Developing such data about investigational drugs takes time for the assessment of products that ultimately prove to be safe and effective. Such a time lag can be a problem if alternative treatments for the condition are not available. The FDA therefore developed a system of expanded access to permit patients with serious conditions to receive investigational drugs before formal product approval.
The expanded-access system has become increasingly controversial. Recently, the family of Josh Hardy, a 7-year-old with a life-threatening infection, sought an experimental antiviral drug — brincidofovir — that was recommended by his doctors. After the media drew attention to his plight,3 the drug's manufacturer offered to include him in a newly created open-label study.4 The question of making untested drugs or vaccines available has also entered public debate in the context of the treatment or prevention of Ebola virus disease, which is often fatal and for which no clearly effective medications or vaccines exist. Each year, thousands of patients wanting to expand their treatment options seek access to incompletely evaluated treatments, but not all obtain them.5 We discuss the practical, legal, and ethical issues associated with expanded access and use of investigational drugs.
Regulation of Expanded Access
After Congress mandated that the FDA validate substantial evidence of safety and effectiveness for new drug products based on adequately controlled clinical trials, the average development time for a new drug predictably rose from 2.5 to 8 years.6,7 Although Congress stipulated that the FDA must act on new-drug applications within 180 days, staff shortages in that era caused the agency to often miss its deadlines in the years after this codification, a problem that has been largely addressed since then.8 To address the lengthened development cycle, the FDA permitted patients or physicians to petition to receive access to unapproved drugs.
These informal pathways were institutionalized in 1987 in the context of the growing AIDS epidemic and were substantially revised in...