Posted 04 February 2015
By Alexander Gaffney, RAC
In response to repeated criticism that terminally ill patients find it too difficult to obtain access to experimental and potentially life-saving drugs, the US Food and Drug Administration (FDA) has announced changes to its "compassionate use" process in the hopes of making it easier for physicians to request access to medical products on behalf of their patients.
FDA's "compassionate use" process—formally known as its Expanded Access Program—is meant to allow terminally ill patients who are otherwise ineligible to obtain an experimental therapy through a clinical trial to access that drug.
Only patients with serious or immediately life-threatening diseases with no comparable or satisfactory therapeutic alternatives are eligible to receive a product through FDA's expanded access program. Even then, the company that produces the drug they wish to access must agree to provide the drug to the patient and obtain FDA approval under one of several types of clinical trial applications, known as investigational new drug applications (INDs).
Expanded access works, in general, in one of two ways: Either a company with an experimental product creates a new clinical trial for a patient through the use of an IND, or it amends an existing clinical trial to add new types of participants through the use of a "protocol amendment."
Once a company determines which approach it wants to take, it then needs to decide on how many patients it is willing to accommodate. There are four general types of expanded access INDs and protocols:
- Single Patient (Emergency Access): Used to grant access to a single patient who does not have time to obtain written permission from FDA
- Single Patient (Regular Access): Used to allow a single patient access to a trial
- Intermediate Size: Used for intermediate-sized patient populations
- Treatment: Used for large patient populations (i.e. widespread use).
Those four types are found within both INDs and protocols, resulting in the following matrix:
|Expanded Access IND||Expanded Access Protocol|
|Single Patient Emergency IND||Single Patient Emergency Protocol|
|Single Patient IND||Single Patient Protocol|
|Intermediate Size IND||Intermediate Size Protocol|
|Treatment IND||Treatment Protocol|
More information can be found at 21 CFR 312 Subpart I.
While FDA cannot compel a company to give a patient an experimental drug, it is required to sign off on all requests to obtain experimental treatments through a clinical trial to ensure the patient understands the probable risks of the trial, and that the trial is more likely to help than harm the patient.
For a thorough explanation of FDA's expanded access/compassionate use programs, please see our comprehensive explainer article here.
Expanded Access Success
FDA approves the overwhelming majority of expanded access requests it receives, according to program data reviewed by Regulatory Focus.
In 2014, for example, FDA rejected just nine requests for expanded access (7 single patient and 2 intermediate patient INDs). From 2010 through 2014, it rejected just 33 requests out of 5,995 received. In plain terms, that means FDA accepts 99.5% of all compassionate use requests it receives.
Expanded Access Criticism
But even as FDA has touted the success of its expanded access program, it has also come under fire.
Critics contend the process of filling out an expanded access request is long and difficult, which they say causes many patients to never even have the option to obtain an experimental therapy. Those critics, which include the libertarian-leaning Goldwater Institute, have launched a nationwide campaign to pass so-called "Right to Try" bills to make it easier for patients to obtain experimental drugs.
Read more about the Right to Try movement and states taking action here.
New FDA Approach
Now FDA is unveiling revisions to its process, which it contends will make the filing of expanded access requests even easier.
On 4 February 2015, FDA released a new draft guidance document, Individual Patient Expanded Access Applications: Form 3926. The document explains that FDA is moving toward a new, "streamlined alternative" for submitting individual patient expanded access applications.
Under the old system, FDA required that a "cover sheet" be included with any IND submission, known as Form 1571. However, that form was originally intended to be used by companies involved in drug development—not physicians, who submit the vast majority of expanded access requests. FDA said it was "concerned" that some physicians might not understand how to fill out that cover sheet "and associated documents because it is not tailored to requests for individual patient expanded access."
Under FDA's new proposed system, the agency said it will create a new form, Form FDA 3926, which physicians will use instead to enroll patients into expanded access trials.
The new form is relatively straightforward, and asks for the patient's initials, clinical information about the patient, treatment information about the investigational drug and its planned use, and a letter of authorization (LOA) from the drug company allowing the physician to use its product on the patient.
The form should also contain information about the physician, and a certification by the physician that they will not begin treatment for 30 days (the time it takes FDA to review IND submissions, per statute) unless emergency use procedures are followed.
Peter Laurie, FDA's associate commissioner for public health strategy and analysis, said the changes would greatly simplify the compassionate use process. The form "called for 26 separate types of information and seven attachments," he noted. The new form calls for a small fraction of that.
"The new draft form, when finalized, will require only eight elements of information and a single attachment. We estimate that physicians will be able to complete the finalized version of the form in just 45 minutes, as compared to the 100 hours listed on the previous form."
Compassionate Use by Telephone
FDA said it will continue to permit physicians to request expanded access for patients in an "emergency situation" over the phone or by "other rapid means of communication."
"Authorization of the emergency use may be given by an FDA official over the telephone, provided the physician explains how the expanded access use will meet [federal requirements for expanded access use] and agrees to submit an expanded access submission within 15 working days of FDA"s initial authorization of the expanded access use," FDA wrote.
FDA has also unveiled a new website meant to make it easier for physicians to find information, it said.
The changes announced by FDA would affect a significant number of patients each year. For example, in 2014, FDA processed 1,758 single patient INDs and emergency INDs—97% of all expanded access requests.