Parents of Patients Value Small Quality-of-life Benefits Not Targeted in Most Trials

Parents of children with Sanfilippo syndrome place high value on therapies that provide even modest benefits to a narrower set of symptoms than most clinical trials address, according to a recent study.

Understanding the impacts felt by caregivers and their treatment priorities can help determine the outcomes measured in clinical trials and the symptoms to target in future drug development.

The study, “Parent Experiences of Sanfilippo Syndrome Impact and Unmet Treatment Needs: A Qualitative Assessment,” was published in Neurology and Therapy and is the first publication of the international Caregiver Preference Study, led by the Cure Sanfilippo Foundation.

“The Sanfilippo Caregiver Preference Study provides critical information and perspectives that further informs key stakeholders, allowing the incorporation of patient voice into the decision making regarding the drug approval process and access,” Cara O’Neill, MD, the foundation’s chief science officer, said in a press release.

With no approved treatment yet in hand, Sanfilippo syndrome places a substantial burden on family life, resulting in high levels of anxiety, depression, distress, and post-traumatic stress disorder among caregivers.

For this and other reasons, the U.S. Food and Drug Administration, along with other regulatory authorities, have prioritized integrating patient and caregiver perspectives into drug development and regulatory decision-making processes.

In the current study, 25 parents acting as primary caregivers of patients with Sanfilippo syndrome participated in a series of focus groups.

Their children, ranging from 4 to 36 years of age, were diagnosed with Sanfilippo syndrome subtype A (17 children), B (6), or C (2). Five children had participated in a prior or ongoing clinical trial of either an enzyme replacement therapy or a gene therapy.

Participants’ largely sorted impactful symptoms into those affecting cognitive, behavioral, and psychological characteristics and those affecting physical health.

Parents listed symptoms related to communicating with others, problematic behaviors, mobility, and pain as the most impactful overall. From their perspective, these represented the greatest unmet needs.

In contrast to the goals of many clinical trials, which tend to focus on treating broad cognitive measures, parents responded that treating any of these symptoms would reduce the burden they felt and improve quality of life for them and their children.

Participants advocated for clinical trials whose primary outcomes focused less on overall cognition and more on multisystem outcomes, including mobility improvement and pain management, or treatments that maintain quality of life by slowing the disorder’s progression.

Finally, parents pressed for trials to broaden their inclusion criteria to allow children in more advanced stages of Sanfilippo syndrome to participate.

The study’s investigators interpreted these results as showing a high risk tolerance for what future therapy studies should attempt.

“Participants advocated for clinical trials that shift focus from primary cognitive outcomes to other multisystem endpoints, and perceptions of non-curative therapies revealed a preference for treatment options that stop or slow the disorder progression to maintain the child’s current function to ensure quality of life; thus parents express high risk tolerance and a desire for broader inclusion criteria for trials,” the researchers wrote.

“These data provide insight into parents’ treatment priorities and impact of various disease manifestations,” they concluded, adding that they “can be used to guide the selection of outcome measures in clinical trials, symptom targets for future therapeutic development, and regulatory decision-making.”