Expanded Access Program

Through FDA’s expanded access program, licensed physicians, on behalf  of their patients with serious or immediately life-threatening ailments, who  have no other comparable medical options, and who are unable to  participate in a clinical trial, can request and possibly access  investigational drugs for treatment of the patients, if the patients meet  certain eligibility requirements. For  expanded access protocol requests sponsored by manufacturers, the  roles and responsibilities of the various entities involved in the process  typically are as follows:
The manufacturer: In addition to submitting the request for the  expanded access protocol to FDA, the manufacturer, as the sponsor  of the request, is responsible for the collection and submission of data  to FDA on any adverse events that occurred from administering the  drug to patients who received it under the expanded access protocol. Expanded Access IND Requests

An expanded access IND request aims to provide access to an  investigational drug outside of a clinical trial and under a new IND. Where the drug is at in the drug development process can affect the type  of expanded access request that may be submitted to FDA. Selected Drug Manufacturers Reported Different Experiences with Expanded Access Requests, and FDA Allowed Nearly All Requests to Proceed from Fiscal Year 2012 through 2015

		Selected Drug Manufacturers Reported Different Experiences with the Number and Types of Expanded Access Requests They Received

Each of the nine selected manufacturers from whom we obtained  information reported having experiences with the expanded access  program, but the extent of the experiences, and with what type of request,  varied. Nearly all of the expanded access requests FDA received and reviewed  (approximately 96 percent) were for single patients (including both  emergency and non-emergency requests). If FDA has not otherwise responded to an expanded access treatment  protocol request within 30 days, the request is automatically allowed to  proceed. 2. 3. FDA and Others Have Taken Steps to Improve the Expanded Access Program and Patient Access to Investigational Drugs, but Stakeholders Continue to Cite Concerns

		FDA Continues to Undertake Efforts to Improve the Expanded Access Program

According to FDA officials and stakeholders, FDA has undertaken efforts  to improve the expanded access program. Simplified Application Form, Guidance, and Website

In response to concerns raised by patients and physicians that the  process for physicians trying to request expanded access to drugs for  single patients was complex and cumbersome, FDA issued a new  simplified, alternative application form for these requests (Form FDA  3926) in June 2016, finalized its related guidance, and made changes to  its website. The stakeholders we spoke with, including representatives of drug  manufacturers and patient and physician advocacy groups, reported  concerns about these legislative changes:
Some contended that the laws would not help patients gain access to  investigational drugs because they do not compel manufacturers to  give access. FDA Reported Limited Use of Expanded Access Safety Data in its Drug Approval Process, and Some Manufacturers Have Asked for More Clarity on This Use by FDA

FDA reported using expanded access safety data, specifically adverse  events data, in a few cases in approving new drugs for marketing in the  United States and not more widely because expanded use situations  generally lack controls used in most clinical trials. Some of the manufacturers  reported that they have concerns about the possibility that FDA’s use of  adverse events data from expanded access requests would result in a  clinical hold on their drug, which would halt all testing on human subjects  and, as a result, delay the drug’s development process. Specifically, our review of FDA’s regulations and nine related documents  FDA uses to communicate with manufacturers regarding expanded  access use found little information communicating how FDA uses adverse  events data from expanded access in new drug application reviews. Only one of the documents—its expanded access treatment  use guidance that was issued in June of 2016—refers to how expanded  access data might be used by FDA in the drug approval process. Some  manufacturers also noted that the lack of clear information about how  FDA uses these data can influence their decision not to give patients  access to their drugs. This could impact FDA’s goal of facilitating  expanded access to drugs for treatment use by patients with serious or  life-threatening diseases or conditions, when appropriate. Recommendation for Executive Action

To help FDA meet its goal of facilitating expanded access to  investigational drugs by patients with serious or life-threatening diseases  or conditions, when appropriate, the Commissioner of FDA should clearly  communicate how the agency will use adverse event data from expanded  access use when reviewing drugs and biologics for approval for  marketing and sale in the United States. Food and Drug Administration’s (FDA) Individual Patient Expanded Access Application, Form FDA 3926, is to be completed and submitted to FDA by a patient’s physician requesting single-patient expanded access of an investigational drug.
Why GAO Did This Study

FDA's goal for the expanded access program is to allow patients with immediately life-threatening and serious ailments access to investigational drugs when appropriate. Stakeholders have raised concerns that FDA's process is confusing or burdensome, particularly for the entities that have roles in the process—such as physicians, manufacturers, and institutional review boards.
GAO was asked to examine the expanded access program. Among other objectives, GAO examined 1) what is known about the number, type, and time frames of expanded access requests received by FDA; 2) what actions FDA and other stakeholders have taken to improve expanded access; and 3) how FDA uses data from expanded access in the drug approval process.
GAO reviewed regulations and FDA documents and analyzed FDA data on the numbers and types of expanded access requests it received from FY2012 through 2015, the most recent at the time of the review. GAO also interviewed FDA officials and other stakeholders including nine manufacturers—selected to represent large and small companies—and patient and physician representatives.

What GAO Found

Under the Food and Drug Administration's (FDA) expanded access program, patients with serious or life threatening ailments and no other comparable medical options can obtain access to investigational drugs outside of a clinical trial. Expanded access requests must be submitted to FDA but manufacturers must also grant permission for patients to access their investigational drugs. Of the nearly 5,800 expanded access requests that were submitted to FDA from fiscal year 2012 through 2015, FDA allowed 99 percent to proceed. Almost 96 percent of these requests were for single patients (either emergency or non-emergency). FDA's review process for expanded access requests is designed such that all requests are either allowed or not allowed to proceed within 30 days of receiving each request. FDA typically responded to emergency single-patient requests within hours and other types of requests within the allotted 30 days.
FDA and other stakeholders, including a non-profit organization and a drug manufacturer, have taken steps to improve the expanded access process and patient access to drugs. For example, in response to concerns that the process to request expanded access to drugs was complex and cumbersome, FDA simplified its website, guidance, and the forms required for the most common types of requests. Efforts by other stakeholders include a project to educate and streamline the process by which institutional review boards approve treatment plans for expanded access drug use and a pilot advisory group to help a drug manufacturer manage expanded access requests. Some states have also enacted “Right-to-Try” laws to facilitate patient access to investigational drugs. These laws provide liability and licensing protections for manufacturers and providers under state law if an adverse event—such as an adverse reaction to the drug—occurs with patients who were allowed access to investigational drugs. However, some stakeholders GAO interviewed cited concerns that these laws may not help patients access drugs, in part because they do not compel a manufacturer to provide access.
Manufacturers sponsoring clinical trials must submit safety reports to FDA that include adverse events data resulting from clinical trials and any expanded access use, to be used in assessing the safety of a drug within the drug approval process. FDA reported using these data from expanded access use in a few cases during the drug approval process but not more widely, because its use does not have the same controls as clinical trials. FDA officials reported that they communicate with manufacturers on how they will use expanded access adverse events data. However, GAO's review of documents FDA uses to communicate with drug manufacturers about the expanded access program found that only one included a reference to its use of these data, and it did not include specific examples of how the data might be used. Further, some of the manufacturers told GAO the guidance was unclear. These manufacturers noted that the lack of clear information can influence their decision whether to give patients access to their drugs because of their concerns that an adverse event will result in FDA placing a clinical hold on their drug, which could delay its development. This could impact FDA's goal of facilitating expanded access to drugs for treatment use by patients with serious or life-threatening diseases or conditions, when appropriate.

What GAO Recommends

FDA should clearly communicate how it uses adverse events data from expanded access use in the drug approval process. FDA agreed with the recommendation.