Expanded Access Program Improving, But Sponsor Concerns Linger
Executive Summary
Many stakeholders interviewed by the GAO find the US FDA's updated guidance on treatment of adverse event data gathered under expanded access to be helpful, but some continue to be concerned that the data will be used to negatively impact development programs.
Several drug makers believe the US Food and Drug Administration has made improvements to the expanded access program, but concerns persist that the agency may use adverse event data from the program against their products, according to a report from the Government Accountability Office.
Seven of the 10 different manufacturers interviewed by the GAO believe that the FDA's updated October 2017 guidance on how the agency views adverse events that occur under expanded access is an improvement. The report, required by the FDA Reauthorization Act of 2017, examines efforts taken by the FDA and drug companies to facilitate individual access to investigational drugs.
In the updated guidance, the FDA aims to quell industry fears that adverse events occurring during expanded access will negatively impact ongoing development programs. The guidance states that the FDA is not aware of any instances where such adverse event information prevented a drug from being approved, and that there have only been a few clinical holds resulting from adverse events observed during expanded access treatment. (Also see " Expanded Access: US FDA Told To Increase Regulatory Clarity, Early Interactions With Sponsors" - Pink Sheet, 8 Nov, 2018.)
Of the seven sponsors who felt the guidance is an improvement, officials from one of the companies said that the document contributed to their company's decision to allow patients access to investigational drugs, the report states.
Among the other sponsors, two did not view the changes as improvements and one was not sufficiently familiar with the policy. The GAO did not characterize the sponsors contacted, other than that they varied in size and number of products.
The GAO interviewed 24 stakeholders in total for the report, which was released on 9 September. Other organizations represented included three trade associations representing manufacturers, three patient advocacy organizations and two physician organizations.
The broader group of stakeholders was complimentary of the FDA's simplified institutional review board (IRB) requirements, under which physicians only need approval from one IRB member – either the chair or another "appropriate" member – at their facility to treat a patient under expanded access. (Also see " Expanded Access: US FDA Told To Increase Regulatory Clarity, Early Interactions With Sponsors" - Pink Sheet, 8 Nov, 2018.)
Of the 24 stakeholders interviewed, 20 were familiar with the simplified IRB requirements, the report states, and 18 of them said the updates were helpful for physicians and patients.
But concerns about expanded access persist among some sponsors, according to the report. And there might be little FDA can do to alleviate their worries.
Both of the drugs firms that said the guidance is not an improvement noted expressed reservations that the FDA will use adverse event data from expanded access programs to negatively impact a development program, the GAO says.
"An official from one of the two manufacturers commented that these concerns remained despite FDA’s statement in the guidance that it is difficult for FDA to link expanded access use to a particular adverse event," according to the report.
Two of the other drugmakers which did view the guidance as an improvement expressed similar concerns about adverse event data arising from expanded access programs.
What's more, the GAO says that "officials from four of the 10 drug manufacturers we interviewed, including two who viewed the updated guidance as an improvement, said they believed that manufacturers’ concerns about this issue may never be fully resolved even with additional FDA guidance."
The GAO notes that a caveat of the report is that the selection of stakeholders it interviewed is not generalizable.
Mostly Positive Views On Project Facilitate
Stakeholders offered a generally positive assessment about the FDA's Project Facilitate pilot program. The recently launched is designed to help physicians navigate the expanded access pathway for oncology products. (Also see "US FDA Expanded Access Pilot Launching Soon With Staffing Questions Unanswered" - Pink Sheet, 20 May, 2019.)
The GAO spoke to 12 of the stakeholders about the pilot, nine of which "generally had positive views of the agency’s planned activities."
Officials from one drug company, however, offered a mixed review. The officials said the pilot could help reduce the burden on oncologists seeking to use the expanded access program, according to the report. But they also felt there is the potential for FDA "to intentionally or unintentionally pressure companies to make their investigational drugs available to patients, should FDA have increased involvement with drug manufacturers as part of the pilot program."
Right To Try Regulations On The Way
The GAO report also notes that the FDA is planning to issue propose regulations in September 2019 to implement the right-to-try (RTT) law, specifically related to the provision requiring companies to submit an annual summary to the FDA regarding the use of their investigational products under the RTT pathway. (Also see "Right To Try Conversation Should Be Redirected Toward Reimbursement Of Unapproved Drugs, Experts Say" - Pink Sheet, 29 Jan, 2019.)
"The regulations will include a due date for manufacturers to submit the annual summaries as well as information on what they are to contain, according to FDA," the report states.
The GAO asked the 24 stakeholders about whether they were familiar with the FDA's webpage outlining the eligibility criteria for RTT. Of the 14 who were familiar with it, eight stated that "it communicated useful and balanced information for physicians and patients," while the other six did not find it helpful for physicians or patients.
Two stakeholders, one being a manufacturer, commented that the webpage could be misleading by giving the impression that the RTT law compels companies to supply investigational products under the pathway, which it does not do. The FDA subsequently updated the webpage to explicitly clarify that sponsors are not obligated to provide such products.
Sponsor Efforts
Sponsors, for their part, have also made efforts to expand access to investigational treatments.
One drugmaker interviewed by the GAO, for instance, said they broadened their clinical trial eligibility, and another said it is taking steps to do so. The latter company noted that their efforts are, in part, a response to a 2018 FDA public workshop on broadening eligibility criteria.
"These two manufacturers told us they were taking these steps in part because both believe it will facilitate the drug approval process," the report says.
But several companies also cited challenges to broadening clinical trial eligibility, such as the extra time and resources it takes in determining whether to remove exclusion criteria.