When individuals with rare diseases or terminal illnesses do not meet the requirements for inclusion in a clinical trial that otherwise seems to offer hope for their condition, understanding the differences between the “expanded access” and “right-to-try” pathways to experimental medications may become a priority for both patients and their doctors.
Comprehending the differences is also important for those conducting the trials, says Preethi Sriram, DHSc, MSN, BSN, a clinical research professional in Raleigh, N.C. who wrote recently for Clinical Researcher about repurposed drugs, expanded access/compassionate use programs, and other opportunities for persons with hard-to-treat conditions to consider when enrollment in a standard clinical trial is not an option.
“If an individual does not meet the criteria for a clinical trial, or does not meet the timeline to enroll, or if there is no available trial for their specific condition, there would seem to be no options left for treatment except for the traditional standard of care, which may be insufficient, especially for those with rare diseases,” Sriram says.
However, the U.S. Food and Drug Administration (FDA) notes that expanded access, sometimes referred to interchangeably with the term “compassionate use,” is a possible route for those with rare diseases and/or life-threatening conditions to gain access to investigational medical products, especially when there is no analogous alternative therapy available. One condition of such access, Sriram notes, is that such treatment outside a clinical trial’s normal protocol must not interfere with a product’s normal development or marketing approval.
Still, there’s no guarantee a request for expanded access will be granted, so patients may need to have a Plan B. “While the process of expanded access/compassionate use requires FDA approval, the Right to Try Act bypasses this process and allows for an individual patient or healthcare provider to go directly to a company to request access to its experimental treatment,” Sriram says. Although not without its own complications, the law permits that manufacturers of an investigational product may provide it through a cooperating physician to eligible participants without the risk of liability.
“In order to gain access, the individual must meet requirements similar to the conditions of expanded access, which include having a life-threatening condition, having exhausted all other treatment options, being unable to participate in a trial involving the product, and giving written consent to the healthcare provider for the usage of the investigational product,” Sriram explains.
While it is noted under the Right to Try Act that use of the investigational product is exempt from any requirements of FDA review or approval, it does require the sponsors and manufacturers of the drug to report to the agency the number of doses supplied, individuals who were treated, indications for which the drug was utilized, and any potential serious adverse effects. Sriram notes that the FDA, in turn, is expected to make this information available to the public.
“In both strategies, the sponsor or manufacturer can refuse access to the drug out of concern over potential negative results,” Sriram warns. She notes though that, from a review of literature, the FDA is not aware of any instances in which adverse events information from expanded access has ever prevented the agency from approving a drug, and that reviewers of the data understand the context within which expanded access is performed and recognize it as being outside the phases of a controlled clinical trial setting. Regarding the costs to patients, she adds, “treatment costs for drugs used in these situations can be very high and insurance companies will not cover them, even when they’ve been approved for use.”
From her literature review on the topic, Sriram also says it seems that drug companies in general are more comfortable with the expanded access/compassionate use pathway versus the right-to-try one. “Who actually gets the drug then in these situations seems to be arbitrary, and this should be an area of further study,” she recommends.
Edited by Gary Cramer