Patient Voice Should Guide Clinical Trial Design for Rare Disease Treatments
Patient voice is a key ingredient for both sponsors and regulators in developing new therapeutics for rare diseases, according to the FDA.
Patient listening sessions are crucial in mid- and late-stage drug development for these disorders, FDA officials said at a public meeting sponsored by the Margolis Center for Health Policy at Duke University. Their lived experiences can shape entire clinical trials, influence approval decisions and guide long-term follow-up plans.
“Input from patients is central even before the first step in the development of drugs,” said Peter Stein, director of CDER’s Office of New Drugs. “The burdens that patients experience, the benefits and problems with current treatments, what they view as the most troublesome symptoms — collecting this vital information is a key objective of patient-focused drug development.”
By listening to the experiences and concerns of patients with rare diseases as well as their caregivers and families, the FDA can get a better picture of the most troublesome symptoms; the daily physical, social and economic burdens that might affect clinical trial participation; and the risks patients are willing to accept for a treatment that could confer benefit. These are often different from the experiences of patients with more common disorders and sometimes quite surprising, Stein said.
Sponsors should seek patient input diligently, he added. “It’s critical that developers reach out to the patient community in developing endpoints for trials. We work to ensure that trials reflect what patients think is important and how the drug can effectively impact that.”
Although always open to patient input, the FDA can’t downgrade its commitment to safety and efficacy, said Nicole Verdun, director of CBER’s Office of Blood Research and Review. “But in the rare disease space, these standards may vary from those expected in other areas of drug development. In rare diseases, where there’s just not a lot of treatment options, patients tell us that they are willing to accept more risk to potentially get a benefit.”
How patients experience the burden of their disease affects clinical trial design in important ways, said Teresa Buracchio, director of CDER’s Office of Neuroscience. For example, an external control group might replace a placebo group to allow more patients treatment access, and if a placebo group is used, there’s an effort to minimize trial duration and the number of patients.
“Decentralized trials also make it much easier for patients to participate and expand the geographic outreach to patients who wouldn’t otherwise be able to participate,” Buracchio said. They also allow people with limited financial resources to participate without the need for travel expenses or time away from work. And for patients with mobility issues, decentralized trials may be the only feasible option.
“The burden of the assessments that are proposed and the feasibility of the assessments are really critical endpoints,” she said. “Sponsors must have that input on whether patients are able and willing to participate with the number of clinical visits that are prescribed and the types of assessments that are done.”