Expanded access program (EAP) to investigational drugs

Reviewer: Maria Luisa Veronese, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 6, 2004

Presenter: L. Talarico
Presenter's Affiliation: Food and Drug Administration, Rockville, MD
Type of Session: Scientific


Unapproved drugs which have shown evidence of clinical activity during the conduct of registration trials can be made available to treat patients with serious or immediately life-threatening diseases ineligible for clinical trials and without available alternative therapy according to Title 21 part 312.34 of the Code of Federal Regulations.  Expanded access programs (EAPs) can provide drugs to individual patients under "Single Patient Investigational New Drug (IND)"  applications and to larger number under "Treatment IND" applications.   The criteria for drug use under "Treatment IND" include a life threatening disease, no other treatments available, preliminary evidence of efficacy, ongoing or completed definitive clinical trials, marketing approval has been pursued, and absence of interference with the registration process.  EAPs are voluntarily initiated by the drug sponsor and FDA and IRB approvals and safety monitoring are required.  This analysis was conducted to determine whether EAPs can provide additional insites on the efficacy and safety of the agents in clinical development.

Materials and Methods

  • This analysis reviewed 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)


  • The number of patients in each EAP ranged from 168 to 24,261, with a total of > 40,000 patients
  • No unanticipated serious adverse events were reported
  • Reporting of efficacy was limited and assessed only by the investigators
  • Treatment outcomes were assessed as consistent with those of registration trials
  • Additional information obtained from the EAPs include: 1. Efficacy of imatinib in Ph+ ALL; 2. tolerability  of oxaliplatin in heavily pretreated patients and elderly; 3. the correlation between efficacy and baseline characteristics for gemcitabine; 4. the incidence of interstitial lung disease during gefitinib treatment and its tolerability in sicker and elderly patients; 5. the use of pemetrexed as second line therapy 

    Author's Conclusions

  • Information on activity of new drugs in clinical development cause demand from patients seeking new therapeutic options
  • Large EAPs include patients with common tumors
  • Well designed EAPs can provide important safety information from larger, more diverse populations and are effective mechanisms to provide investigational drugs to patients
  • Efforts should be made to design EAPs to provide additional clinical information (subpopulation analyses of outcome, dose ranging, drug combinations)

    Clinical/Scientific Implications

    EAPs are drug sponsor initiated clinical trials conducted to provide investigational drugs to patients not eligible for current clinical trials and seeking new tharapeutic treatments.  This study was conducted to investigate whether  EAPs can provide additional information to the clinical drug development process.  EAPs are often very large studies involving heterogeneous populations. EAPs have provided additional safety information for several drugs.  Clinical outcomes of EAPs are consistent with those of registration trials.  EAPs represent important studies within the clinical development process.  EAPs should be designed in a way that can provide safety and efficacy information.  Formal post-marketing studies may be irrilevant if the drugs are effective.

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