In rare disease research, patient-centered clinical trial design is key

Since the introduction of the 21st Century Cures Act nearly five years ago, policymakers, regulators, advocates, and researchers have been working together to enhance the way experimental medicines are developed and assessed by placing a greater emphasis on patient-centered approaches.

Of its many provisions, the law built on the U.S. Food and Drug Administration’s ongoing work to incorporate the perspectives of patients into the clinical development and regulatory decision-making process. This is particularly important in the area of rare diseases given the immense burden these conditions place on patients and their families. In such instances, putting patients’ needs and perspectives at the forefront can be a constructive way to assess certain treatments by augmenting standard measurements of safety and effectiveness.

“Including patient and caregiver input into the clinical trial design at the very beginning brings extremely important perspectives to bear on the outcomes we should be studying,” said Dr. Bobby Gaspar, chief executive officer of Orchard Therapeutics, a company developing gene therapies for severe diseases. “Ultimately, if the trial does not objectively measure what is important for patients and their families, then it is not serving its purpose.”

An advocate for change

Cara O’Neill is the mother of a little girl with Sanfilippo syndrome, and a founder of the Cure Sanfilippo Foundation, a patient organization focused on helping find and fund research for new treatments for this rare, progressive genetic disease that afflicted her daughter along with approximately one in every 70,000 newborns. Sanfilippo syndrome has a particularly significant effect on the brain, with developmental delays starting between ages 2 and 6, ultimately leading to early death.

Her organization “has enjoyed wonderful working partnerships with many industry groups in the field,’’ O’Neill says. “When engaged early and often, patient advocacy groups can bring otherwise difficult-to-access insights about the ‘lived disease’ experience to the table.’’

They have partnered with companies and organizations to complete research into Sanfilippo syndrome caregiver treatment preferences and the burden of disease, leading to published “guideposts for developing multiple new clinical trial protocols’’ that will support the potential use of measurable and meaningful clinical endpoints, she says.¹

The research revealed multiple areas of need that impact child and family quality of life, including cognitive-behavioral challenges in communication, relationships, anxiety and child safety, as well as physical health symptoms including sleep, pain and mobility.

Patient advocacy groups serve to help researchers find study participants while also helping families to learn about research being undertaken. “In rare diseases like Sanfilippo syndrome where there are no approved therapies, foundations like ours work to ensure that families are informed about clinical trial options,’’ O’Neill says. “Because we are so focused on the disease of interest, we can provide up-to-date information on what is an ever-evolving clinical trial landscape and connect patients to trial sites and expert clinicians very quickly.’’

Additionally, where payers may question the upfront costs of newly approved therapies, patient-centered outcomes can be critically important to demonstrate the value of such treatments today and in the future.

Industry and patient organizations now are working with regulatory authorities in the U.S. and around the world to provide data that supports approval for treatments. The U.S. Food and Drug Administration and the European Medicines Agency encourage such patient engagement and in 2016 launched a forum for the two agencies to share best practices on involving patients in development, evaluation and other activities related to authorization of new medicines.²

“By incorporating a patient-centered approach to treatment targets and outcome measurements,’’ says O’Neill, “there is hope that we will be more likely to demonstrate any potential treatment effect on symptoms that are meaningful to patients’ quality of life.”

For more information, visit www.orchard-tx.com.

References
¹ Porter, K.A., O’Neill, C., Drake, E. et al. Parent Experiences of Sanfilippo Syndrome Impact and Unmet Treatment Needs: A Qualitative Assessment. Neurol Ther 10, 197–212 (2021). https://doi.org/10.1007/s40120-020-00226-z
² https://www.ema.europa.eu/en/news/ema-fda-reinforce-collaboration-patient-engagement