but many people regarded the ddI trial as the prototype of the new "parallel track system." (On May 21, 1990, the Department of Health and Human Services published a proposed policy statement, "Expanded Availability of Investigational New Drugs Through a Parallel Track Mechanism for People with AIDS and HIV-related Disease," in the Federal Register.)

The controversy continues today. Opponents of the parallel track worry that it will disrupt efforts to assess the safety and efficacy of drug candidates through conventional clinical trials. They question the value of information gathered through the parallel track system and express concern about exposing large numbers of people to relatively unknown agents. Advocates of parallel track acknowledge that increasing access to investigational drugs without definitive evidence of either safety or efficacy carries serious potential risks, but they believe that many desperately ill patients are willing to assume such risks. After all, they say, investigational drugs are the only hope for thousands of AIDS patients who either cannot tolerate or fail to respond to zidovudine. (commonly known as AZT), the only anti-HIV drug licensed in the United States.

One fact often ignored by both sides is that access to investigational drugs for therapeutic purposes is not new in this country. In fact, it is as old as the history of drug regulation itself. Two features that make the current situation somewhat different from the past are (1) the desire to establish a written policy and (2) the large number of people who could receive a single investigational drug in a short period of time. A brief review of earlier approaches to expanded access and a summary of the drug approval process prior to the start of the AIDS epidemic help place the debate over the parallel track mechanism in perspective.

EARLY DEVELOPMENT OF EXPANDED ACCESS

Modern drug regulation in the United States began in 1938 with enactment of the Federal Food, Drug, and Cosmetic Act, prompted by the elixir sulfanilamide tragedy of November 1937 (more than 100 people died when a drug containing the poisonous solvent diethylene glycol was marketed without animal tests). The new act contained one brief section, labeled 505(i), in which Congress authorized the FDA to issue rules governing investigational use of drug candidates. The FDA regulations that resulted from this authorization contained four requirements: (1) an experimental drug had to be labeled "for investigational use only"; (2) the drug could be delivered only to



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