Study Highlights How the FDA is Improving Expanded Access

When physicians believe that a patient with cancer may benefit from an agent that has not yet been approved by the U.S. Food and Drug Administration (FDA), yet a clinical trial either is unavailable or would exclude that patient from enrollment, they can submit a single-patient Investigational New Drug (IND) application to the FDA. If this request is granted, the patient, under “expanded access” or “compassionate use,” can proceed to receive the investigational agent.

An analysis of individual IND applications received and granted by the FDA’s Office of Hematology and Oncology Products (OHOP), presented at the ASCO Annual Meeting by Steven J. Lemery, MD, MHS, the OHOP’s lead medical officer, debunks some of the myths about expanded access physicians may have – including that the FDA rarely grants these requests, there are long delays in the process, and/or that the necessary paperwork is confusing and time-consuming.

“Due to the life-threatening nature of many cancers, many expanded access requests are submitted to the FDA’s OHOP,” the study authors explained. “An evaluation of these requests was undertaken to increase the transparency related to [single-patient IND applications] and foster awareness of the process.”

Dr. Lemery and authors extracted data for all single-patient and emergency-use IND applications submitted to the FDA between January 2012 and December 2014, including information about the dates the IND was received and allowed to proceed, drug names, underlying malignancy of patients, and whether the IND was placed on hold.

During the study timeframe, the FDA received a total of 1,332 individual IND submissions, including 525 emergency applications. Nearly all of the IND applications (99.8%; n=1,330) were included in the analysis.

These individual IND applications covered approximately 157 unique drugs, the researchers found, noting that 59 percent of the requested drugs were subsequently approved by the FDA.

The most frequent drug requests were for:

  • Chronic myeloid leukemia (CML; 28%)
  • Breast cancer (12%)
  • Acute lymphocytic leukemia (9%)
  • Acute myeloid leukemia (not acute promyelocytic leukemia; 6%)
  • Ovarian cancer (6%)
  • Sarcoma (5%)

The majority of CML requests were for ponatinib, the authors explained, because, at the time of the analysis, ponatinib was still under restricted access and only available through an IND request.

The FDA received requests from all but one state, and most requests came from patients treated at a major university-related hospital (67%). Six percent were from dedicated children’s hospitals and 0.7 percent were from Veterans Affairs hospitals.

The median review time for the 1,309 INDs with documented receipt and “proceed” dates was one day, and the mean review time for all requests was 2.2 days (3.1 days for single-patient requests and 0.4 days for emergency requests). Notably, 75 percent of INDs were reviewed within three days.

All but 30 of the single-patient IND requests were granted within 14 days of receipt; of the requests that took longer to grant decisions, 22 had major issues with documentation, the authors noted.

“OHOP’s review time and approval of nearly all cancer-related, single-patient expanded access requests is consistent with FDA goals to facilitate expanded access,” the authors concluded. “OHOP is continuing to work to improve this process and increase transparency to facilitate access for more patients.”

As part of these efforts, on June 2, 2016, the FDA finalized its plan to streamline the process physicians use to request expanded access to INDs and biologics for their patients. “Access to investigational treatments requires the active cooperation of the FDA, industry, and health-care professionals to be successful,” FDA Commissioner Robert Califf, MD, said in a statement released by the agency. “But we know that navigating that process can be challenging and time-consuming, and we are committed to reducing the procedural burdens on physicians and patients whenever possible.”

The first part of this plan is the “Individual Patient Expanded Access Investigational New Drug Application – Form FDA 3926.” According to the FDA, the form is much shorter than the previous version used for individual patient expanded access requests and is designed specifically for these requests.


Lemery SJ, Mailankody S, Kazandjian D, et al. Food and Drug Administration analysis of 1332 single patient and emergency use expanded access (compassionate use) requests for patients with cancer over a duration of three years (2012-2014). Abstract #6523. Presented at the 2016 American Society of Clinical Oncology Annual Meeting, June 4, 2016; Chicago, IL.