Patient treatment on a compassionate basis: documentation of high adverse drug reaction rate

The special exception mechanism was established by the Division of Cancer Treatment (DCT), National Cancer Institute (NCI), for the provision of anticancer drugs not yet approved by the Food and Drug Administration (FDA) to patients on a compassionate basis. Strict guidelines have been established for the distribution of drugs through this mechanism and for the reporting of adverse drug reactions (ADRs) with investigational drugs. These guidelines have been used to format the data base which is maintained on all ADRs submitted by investigators. In this paper, the incidence of ADRs with the eleven investigational drugs most frequently administered on special exception protocols was determined for a twelve month time period, January 1, 1985 through December 31, 1985. On special exception protocols, the overall incidence rate of ADRs was significantly greater than that seen on research protocols for the time period. For three drugs, Methyl-G, DBD, and AMSA, the ADR incidence rate was seven to fifteen-fold greater on special exception protocols than on research protocols. In an analysis of all ADRs submitted to the FDA for the twelve months time period, no difference was found in the frequency of distribution of either types of adverse effects or the causal assessments of ADRs on special exception and research protocols.