TGen News

PHOENIX, AZ (July 30, 2024) – Following years of informal discussions with researchers and regulators, TGen distinguished professor and director of the Quantitative Medicine & Systems Biology Division Nicholas Schork, Ph.D., is proposing a meeting with the Food and Drug Administration to determine how to move forward with aggregated “n-of-1” clinical trials, which analyze combined data from single-patient studies.

The proposal is for a FDA Critical Path Innovation Meeting (CPIM) where researchers like Schork can share information on an emerging treatment pathway and ask for advice from FDA officials on how aggregated patient-focused trials can be used and recognized by the FDA.

Learning how to combine data from these single-patient studies will speed up drug development and point the way toward more personalized treatments that could be tailored to a patient's unique biology, behavior and environment, according to Schork and TGen colleagues Sunil Sharma, M.D., F.A.C.P., M.B.A., TGen Physician-in-Chief and TGen distinguished professor, Daniel Von Hoff, M.D., F.A.C.P.  

N-of-1 studies are often used in rare diseases, such as those treated at TGen’s Center for Rare Childhood Disorders, where “you’re kind of forced into designing studies to test interventions in individuals given that so few people have the disorder,” Schork explains.

But TGen is also a leader in clinical trials for treatments that are personalized but used across large groups of patients, such as CAR T-cell therapy for cancers. These therapies use T cells that target proteins specific to a person’s tumor. No two people have the same tumor proteins, so essentially each treatment is an unofficial n-of-1 study.

So are CAR T-cells, as a class of therapy, more effective than chemotherapy to treat a specific cancer? One way to answer this, Schork says, is to find a way to aggregate the results of all these n-of-1 treatments.

Schork, who has personally worked on several n-of-1 trials, says he has “come to the realization that if we’re going to live in a precision medicine era, then we have to come up with study designs and ways of vetting drugs and health interventions that focus on individual patients’ treatment responses.”

Aggregated n-of-1 trials will help researchers vet specific interventions, while exploring variations in treatment responses, he notes. They will also help scientists learn more about the biological processes behind certain responses and discover biomarkers that might guide whether a patient receives one drug over another.

“And because we are collecting more data [on each patient] and more monitoring is involved, we might be able to find things that could benefit the patients in real time, while we’re actually studying them,” Schork notes.

Schork says there are three key areas that need to be addressed for aggregated n-of-1 studies to become widely conducted and accepted.

“The first is infrastructure,” he explains. “You need more exam rooms, more phlebotomists to draw blood, more people to write the IRB protocols, and more people to collect all the relevant data. Not all health systems have been interested yet in putting together infrastructure for this but now they are coming to realize this is a very advanced and sophisticated form of patient care.”

“We also need people with interventions who are willing to pursue these sorts of studies, and the appropriate gadgetry to carry them out,” he continues, noting that clinical grade equipment will be needed to continuously monitor patients during these interventions.

N-of-1 studies also need more buy-in from the scientific community, says Schork. “It’s not that people are rejecting the idea they’ve just never been exposed it. We therefore need more education and exposure to the concepts, which are very intuitive.”

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About TGen, part of City of Hope
Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based nonprofit organization dedicated to conducting groundbreaking research with life-changing results. TGen is part of City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases. This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. TGen is focused on helping patients with neurological disorders, cancer, diabetes and infectious diseases through cutting-edge translational research (the process of rapidly moving research toward patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and complex rare diseases in adults and children. Working with collaborators in the scientific and medical communities worldwide, TGen makes a substantial contribution to help patients through efficiency and effectiveness of the translational process. Follow TGen on Facebook, LinkedIn and Twitter @TGen.