Expanded access (also known as compassionate use or "pre-approval access") refers to the use of an investigational new drug (IND) outside of a clinical trial by patients with serious or life-threatening conditions who do not meet the enrollment criteria for the clinical trial in progress. In the US, the FDA may also allow expanded access in other situations, for example, where drugs have been withdrawn from the market, or are subject to a REMS. (Outside the US, such access is allowed through Named patient programs.) Expanded access may be available, in accordance with United States Food and Drug Administration (FDA) regulations, when it appears the drug does not pose a greater risk than the disease itself, no alternative therapy is available, use will not interfere with the conduct of clinical trials, and the drug developer agrees to provide access to the drug. The FDA refers to such a program as an expanded access program (EAP). EAPs can be leveraged in a wide range of therapeutic areas including HIV/AIDS and other infectious diseases, cancer, rare diseases, and cardiovascular diseases, to name a few.
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There are several types of EAPs allowed in the United States. Treatment protocols and treatment INDs provide large numbers of patients access to investigational drugs. A single-patient IND is a request from a physician to the FDA that an individual patient be allowed access to an investigational drug on an emergency or compassionate use basis. When the FDA receives a significant number of requests (~10 to 100) for individual patient expanded access to an investigational drug for the same use, they may ask the trial sponsor to consolidate these requests, creating an intermediate-size group. “Compassionate use” is a more colloquial term that is not generally used by the FDA.
Physicians can apply for use of an investigational drug using FDA Form 3926, an application form created by the agency in June 2016. The FDA estimates that it takes 45 minutes to complete this form. According to FDA statistics, the FDA approves more than 99% of all expanded access requests that it receives. Emergency approval is usually granted immediately, over the phone. For non-emergency requests, the FDA reports that its median approval time is 4 days.
FDA regulations
Since 1987, the FDA has had rules in place that have enabled patients, under specific circumstances, to access drugs or biologics that are still in development for treatment purposes. These expanded access program rules were amended in 2009 by the FDA to ensure “broad and equitable access to investigational drugs for treatment.”
The regulations include the following:
The regulations also include general criteria for granting expanded access:
Despite the updated regulations, debate remains over key elements of expanded access:
A number of challenges can exist when patients seek access to investigational drugs:
State law
As of September 2016, 32 states have passed right-to-try laws that permit manufacturers to provide experimental medicines to terminally ill patients without US FDA authorization. Legal, medical, and bioethics scholars, including Jonathan Darrow and Arthur Caplan, have argued that these state laws have little practical significance because patients can already obtain pre-approval access through the FDA's expanded access program, and because the FDA is generally not the limiting factor in obtaining pre-approval access.
Outside the United States
Outside the U.S., programs that enable access to drugs in the pre-approval and pre-launch phase are referred to by a variety of names including “named patient programs,” “named patient supply” and “temporary authorization for use.” In the EU, named patient programs also allow patients to access drugs in the time period between centralized European Medicines Agency (EMA) approval and launch in their home countries which can range from one year to eighteen months.
Ethical guidelines
Weighing risks to the patient against the potential benefits is one of the specified FDA regulations, as it is also the case in medical practice in general. In questions concerning expanded access this is particularly difficult, however, because treatments by new drugs (or unapproved dosages of known drugs) bear unknown risks. How should then a doctor decide (to treat or not) if he or she cannot know the success probability of the treatment for a given patient? For a single decision to make, this question is not meaningful. The situation is different if the doctor has several requests of different patients and therefore a possibiity of sequential learning of the effect of the treatment. If the first treatments were all unsuccessful the conscientious doctor may try to convince the other patients not to take the treatment, but as soon as a treatment is successful then it can be seen as an encouragement to go on. Note that if the physician were a prophet in the sense of being able to recognize the last successful treatment in the series then he or she would stop and would have with this last success all successes in the series and would spare the others from useless pain. Since the physician is no prophet, an ethically valuable strategy is to maximize the probability to stop with a last successful treatment. The solution to this optimization problem is provided by the odds algorithm where the odds are sequentially updated with each new observation.