WHAT USES OF DRUGS ARE INVESTIGATIONAL?
The immediate policy issues associated with the Interim Rule and its alternatives require us to consider a level of detail that is characteristic of FDA regulation but unfamiliar to many outside the drug evaluation process. Before dealing with those detailed issues, however, we address the question of what investigational means.
The critics of the Interim Rule argue that it was a violation of the basic ethical principles governing research on human subjects in its failure to require informed consent for investigational drugs. This argument is politically salient because of the history of abuse of human subjects in medical experiments, a history shared by both military and civilian agencies of the federal government and by nongovernment institutions and investigators. This history is fresh in our thinking, partly because 1997 was the 50th anniversary of the Nazi doctors' trial and the promulgation of the Nuremberg Code (JAMA, 1996, 276). Also in 1997, President Clinton publicly apologized to the survivors of the Public Health Service's Tuskegee Syphilis Study. These events had been preceded by the report of the Advisory Committee on Human Radiation Experiments (ACHRE, 1996), a 1993 Institute of Medicine report on the health effects of mustard gas and Lewisite (Pechura and Rall, 1993). This history forcefully reminds us of the need for continued vigilance regarding the ethics of human experimentation. But it should neither blind us to learning from that experience nor relieve us from the obligation to examine the particulars of the Gulf War to assess whether and how they differ from these episodes of abuse.
Did the use of investigational drugs under the Interim Rule in the Gulf War constitute research? A definitional excursion is essential to clarify the policy implications associated with the terms "investigational," "research," and medical "practice" or treatment. The Interim Rule applies to "an investigational drug or biologic," and the two waivers granted under it were for drugs FDA classified as investigational. The pertinent questions in this exercise are the following: