Expanded access program (EAP) to investigational drugs

Abstract

6001 Background: Title 21 part 312.34 of the Code of Federal Regulations provides for use of unapproved drugs to treat patients with serious or immediately life-threatening diseases ineligible for clinical trials and without available alternative therapy. EAPs can provide drugs to individual patients under “single patient Investigational New Drug (IND)” and to larger numbers under “treatment IND”. EAPs are implemented while sponsors are actively pursuing marketing approval. Reasonable evidence of clinical usefulness for the indication and sufficient safety information from ongoing or completed trials are required. EAPs are voluntarily initiated by the drug sponsor. FDA and IRB approvals and safety monitoring are required. Methods: Review of data reported from EAPs for the following drugs (indications): imatinib (chronic myelogenous leukemia), trastuzumab (breast cancer), temozolomide (malignant gliomas), oxaliplatin (colorectal cancer), gemcitabine (pancreatic cancer), gefitinib (non-small cell lung cancer). Results: The number of patients in each EAP ranged from 168 to 24,261, total 42,828, median 5182 (169, 11965). No new safety concerns were raised in the EAPs. For example, the incidence of interstitial lung disease in patients receiving gefitinib was about 2% in the Japanese post-marketing experience and 0.3% in about 24.000 patients in the U.S. EAP. Efficacy outcomes were consistent with registration trials. Selected EAPs provided additional information, such as tolerability of gefitinib in elderly, identification of factors predictive of response to oxaliplatin-based treatment. Conclusions: Disseminated information on new drugs in clinical development encourages patients without available treatments to seek new therapeutic options. Patients with common tumors comprise large EAP populations. EAPs are effective mechanisms to provide investigational drugs to patients and obtain additional safety information from larger, more heterogeneous populations. While providing investigational drugs to all patients who may benefit, EAPs could be designed to provide additional clinical information such as subpopulation analyses of outcome, dose ranging, drug combinations. No significant financial relationships to disclose.