• the number of pivotal and supportive efficacy trials conducted on which the approval was based, including the number of comparator arms in those trials;

  • whether the efficacy trials were controlled and, if so, whether the drug was compared against an active comparator or a placebo;

  • whether efficacy trials were blinded;

  • whether the efficacy trials were classified as Phase I, II, III, or IV by the FDA medical officer;

  • whether the efficacy trials were multicenter or single-center studies;

  • the average time of exposure during the efficacy trials;

  • whether the end points of the efficacy trials were surrogate (hematologic markers, interval response rate, etc.) or final (i.e., mortality, disease cure, etc.);

  • the number of patients enrolled in efficacy trials;

  • the existence of a data safety monitoring board or independent review committee organized by the manufacturer to assist in evaluation of the efficacy trials;

  • the total number of human trials conducted by the manufacturer;

  • the total number of human subjects in whom the drug was tested;

  • whether the FDA identified methodological concerns about the clinical development trials;

  • whether published data were used to support the application;

  • whether the FDA convened an Advisory Committee to evaluate the drug prior to approval and, if so, whether the vote was unanimous; and

  • whether the FDA imposed postmarketing commitments on the manufacturer, and the nature of those requirements (i.e., additional trials, a patient registry, a Risk Evaluation and Mitigation Strategy [REMS]).


All Approved Drugs

From 1983 through 2009, the FDA approved 347 total drugs with orphan designations. However, a single drug can be approved for multiple orphan indications. For example, while somatropin (human growth hormone) accounted for 16 approvals overall, these approvals involved 9 brand-name drugs (some with multiple orphan approvals); the criteria used in this study—drugs having the same active ingredients and manufacturers—identified 6 “separate” products for further study (see Table B-1). Novartis’ imatinib (Gleevec) was approved for the treatment of chronic myelogenous leukemia (2001), gastrointestinal stromal tumors (2002), eosinophilic leukemia (2006), mastocytosis (2006), myeloproliferative disease

The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement