Dispelling the Myths and Misconceptions Around Expanded Access

Richard Klein recently left the FDA after more than 40 years. He spent much of that time working on policies and regulations surrounding expanded access, also referred to as compassionate use or pre-approval access.

There are a lot of myths and misunderstandings about expanded access circulating these days, and a good deal of confusion related to the so-called "Right to Try" movement.

Expanded access, or the treatment use of promising investigational medical products outside of clinical trials, has been going on for more than 4 decades under the FDA. Expanded access rules were officially codified in FDA regulations in 1987, and refined and clarified in a new subsection of regulations in 2009. The FDA allows more than 99% of the requests for treatment use of investigational products it receives to proceed.

Many physicians and patients are unaware that expanded access is available. Patients with serious or life-threatening illnesses who have exhausted, or are intolerant of, approved therapeutic options might be eligible for expanded access if they don’t qualify to participate in clinical trials.

There are many resources available to physicians and patients looking to make use of expanded access. The FDA has developed a comprehensive expanded access web site to provide information to the public, and created guidance to help explain and facilitate access to unapproved products for treatment use. The Reagan Udall Foundation Expanded Access Navigator strives to help physicians and patients understand the application process further, and identify existing access programs. The Kids v Cancer Compassionate Use Navigator provides a similar service related to childhood cancers.

A common misconception is that the process of applying for expanded access is burdensome for the physician, which may discourage many from considering it. The myth, touted by the Goldwater Institute in support of Right to Try laws, is that it takes a physician 100 hours to complete the request form. For perspective, that is a full 2.5 40-hour work weeks of solid paperwork time for physicians who typically have about 15 to 20 minutes to spend on each patient. Does that seem plausible when FDA receives about 1,200 of these applications a year?

In fact, for individual patient access, a streamlined form takes about 45 minutes to complete. The physician fills out a short patient medical history, provides rationale for why the treatment is likely to benefit the patient and describes the proposed treatment plan. The physician's CV establishes their qualification to administer the treatment, and use must be certified by an institutional review board, which ensures adequate informed consent.

On average, the FDA turns around applications for expanded access in about 4 or 5 days. When there is no time to submit a written request, there are special emergency use procedures. Through a 24/7 emergency phone number, the FDA generally rules on such requests within hours so that a company can ship the product to the physician or hospital.

Some have suggested that expanded access is avoided by physicians because the reporting requirements are too burdensome. The FDA is quite cognizant that treating physicians are not researchers, and efforts were made when formulating the expanded access regulations to minimize the reporting burden.

For individual patient expanded access, the regulations in § 312.310(c)(2) specify that, at the conclusion of treatment, the sponsor must provide the FDA a written summary of the results of the expanded access use, including serious and unexpected adverse reactions. These are reported only if there is evidence to suggest a causal relationship between the drug and the adverse event.

Adverse reaction and summary reports can be submitted using the same form used to apply for the expanded access use. For individual patient Investigational New Drug applications (INDs), this can be the FDA Form 3926 or the Form 1571. The FDA will also, however, accept a written summary citing the appropriate IND number, submitted to the review division from which the IND was obtained.

Drug developers and manufacturers must be willing to provide their investigational product outside of the clinical trial before the FDA can process a request.

The fact is, the FDA is much more flexible and amenable to working with physicians than most people realize. Physicians treating patients who can’t participate in clinical trials and have exhausted existing therapeutic options can contact the FDA to discuss the possibility of treating them with a promising investigational product.

Patients have long had the "right to try" potentially-beneficial investigational drugs when they have no other options. The agency takes expanded access seriously and works with physicians and industry to facilitate appropriate efforts to provide treatment. It is incumbent upon physicians to consult with patients, drug manufacturers, and the FDA to explore the option of treating their patients with drugs that are still in development.