Posted 16 May 2016
By Zachary Brennan
The fight over patients gaining access to investigational drugs via the compassionate use process is expected to get a lot easier in the near future, just as the US Food and Drug Administration’s (FDA) nonprofit arm, the Reagan-Udall Foundation (RUF), is working to build an online navigator to help patients and physicians understand that process better.
Compassionate use, also known as expanded access, is a process by which physicians can request that FDA allow the use of an investigational drug outside of a clinical trial for a patient with a terminal illness or no other treatment options. But the process can only be initiated if the company developing the drug and the physician treating the patient agree to move forward and make the FDA request.
Speaking at the Expanded Access Navigator Public Workshop on Monday, Richard Moscicki, M.D., deputy center director for science operations at FDA’s Center for Drug Evaluation and Research (CDER), said the agency will finalize a plan (more than a year after it was proposed) “very, very soon” that could reduce the time it takes physicians to fill out the paperwork for expanded access requests to 45 minutes, which would be a significant shift from the previous form, which in some cases took more than 100 hours to complete.
The agency also expects to release three guidance documents linked to compassionate use and expanded access soon.
As Nancy Beck, Ph.D., acting deputy director of the Reagan-Udall Foundation, explained to Focus last month, the new online navigator will help provide physicians (as they are the ones who must make the expanded access request) with a more complete picture of how to make a single patient Investigational New Drug (IND) request; the role of FDA, manufacturers and Institutional Review Boards in the process; the principles of expanded access eligibility criteria and risk-based decision-making; the challenges of translating early research findings into clinical outcomes; and perhaps most importantly, a directory of information on FDA and manufacturers’ policies, procedures and points of contact.
Jonathan Jarow, M.D., senior medical advisor to the Center Director for CDER, made clear to the workshop on Monday that the vast majority of expanded access requests are for non-emergency and emergency single IND applications, though the new navigator will only deal with non-emergency INDs as emergency INDs are requested over the phone or via email and usually acted on by FDA within hours, or at least within one day.
But the request process is currently burdensome and difficult to navigate, Michael Grimley, M.D., associate professor at the University of Cincinnati Department of Pediatrics, said, offering an example of a compassionate use navigator already in use. He and others also noted that FDA should make available data on expanded access requests, particularly in terms of health outcomes from such requests, though no specifics for the navigator were agreed to on Monday.
Alison Bateman-House, PhD, MPH, MA, a Rudin postdoctoral fellow in the Division of Medical Ethics at New York University Langone Medical Center, told Focus that she doesn’t think FDA should build “yet another stand-alone resource” that requires funding, marketing and a chance for "message confusion." She also said she believes there’s an opportunity to enhance clinicaltrials.gov, which contains listings of all of the clinical trials being run in the US, and which she said she thinks should be the first place patients should go for more information.
"Is there any reason that a navigator ought not be run by the FDA or the RUF? The
FDA budget is a perennial issue, and any money spent running the navigator
ought not be taken from the agency’s already insufficient budget," Bateman-House wrote in comments on the draft navigator. "The same
should be said for the agency’s understaffed human resources – if a new
navigator service is created, let it rely upon new hires, not be added to the
job description of already busy staff. But the main argument against having a
navigator, especially one built around a webpage, run out of the FDA or the RUF
is logistical. We do not want a webpage that has thousands of links to company
webpages that will go inactive and need to be maintained. We do not want a
webpage with lists of phone numbers that go out of service when small companies
are acquired by larger ones. We do not want a webpage that promises assistance
only to result in frustration. We already have one of these, and it is called
Right to Try
The need for such a navigator comes as 28 states since 2014 have passed “Right to Try” laws that aim to skirt FDA’s compassionate use process to help terminally ill patients or those with no treatment options gain access to potential drugs still undergoing clinical trials. But what’s unclear about these new laws is whether they are actually helping patients gain access to investigational therapies.
The Goldwater Institute, which has pushed for the passage of such legislation as a way around what they believe to be an abundance of red tape at FDA, has said in recent weeks that it’s aware of physicians and patients accessing investigational drugs because of Right to Try legislation, though none of the physicians or patients are willing to come forth.
Sen. Ron Johnson (R-WI) also introduced a bill last week that would not allow the federal government to interfere with the state laws, as well as protect companies from new liabilities and stop FDA from using data on patients taking drugs obtained under the new laws to delay or negatively impact FDA approval.
That bill made reverberations on Monday as a Goldwater representative made clear that the institute believes the federal government should not be involved in the compassionate use process and that it should only be an issue for physicians, patients and the companies developing the new drugs.
However, Richard Plotkin, vice chair of the Max Cure Foundation, explained that for many children and adults with terminal illnesses, the use of experimental drugs can reduce their quality of life in their final months and not provide any benefits.
An AIDS activist also explained during the public comment portion of the workshop that in the 1980s, when patients sought the use of new HIV and AIDS treatments, "We blamed everything on FDA, and it's not their fault, it's often the companies' fault" as no company wants to stall the development of its drug because of compassionate use.
Indeed, often times, requests for early access to a developing drug are denied because the patients don’t meet certain criteria established by the company running the trial.
The difficulty for many of these patients who have either run out of treatment options (or didn’t have any to begin with) isn’t getting FDA to sign-off on the use of the investigational drug (FDA signs off on more than 99% of the expanded access requests it receives) but in getting the companies running the clinical trials to allow new patients to gain access to the experimental treatments while trials are ongoing or even before a trial begins.
And companies, some of which are only developing one expensive therapy, have to make concessions for such new patient requests, which can potentially disrupt a trial, as has happened in the past.
Richard Klein, director of FDA’s Patient Liaison Program, noted Monday that an internal review of 10,000 expanded access INDs found only two trials that were halted because of adverse events experienced by patients who received the drugs under compassionate use requests.
However, the reverse can also be true. At least one drug, ganciclovir, which is used to treat a viral infection of the eye that blinds many AIDS patients, was approved based solely off of use of the drug on a compassionate use basis.
And one of the reasons why FDA’s so willing to sign off on almost every expanded access request that it receives is because all of the nitty-gritty work with getting a company developing an investigational drug or biologic to sign off on a patient’s compassionate use has already been finished by the time an expanded access application has been submitted to FDA, Beck told us previously.
RUF is still accepting written comments on the expanded navigator.
Mechanisms to Improve Awareness and Transparency of Expanded Access Processes and Programs; Public Workshop
DRAFT PROJECT PROPOSAL: EXPANDED ACCESS NAVIGATOR FOR INDIVIDUAL PATIENT ACCESS