Those affected by sickle cell disease willing to accept gene therapy risks
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Key takeaways:
- Adults with sickle cell disease expect higher efficacy from gene therapy in exchange for mortality risk.
- Caregivers and parents of patients with sickle cell disease had a higher risk tolerance for gene therapy.
Individuals with severe sickle cell disease showed willingness to accept the risks associated with emerging gene therapy treatments, according to survey results published in Blood Advances.
Although most respondents with sickle cell disease showed interest in these novel gene therapies, those with milder disease also saw other treatments as feasible, the study reported.
“We knew that there were several technologies and sponsors looking to use gene therapy to treat different conditions, and sickle cell disease is one of them,” lead author Juan Marcos Gonzalez Sepulveda, PhD, associate professor in population health sciences, associate professor in medicine and member of the Duke Clinical Research Institute, told Healio. “Given the novelty of the trade-offs that patients were asked to take on with these technologies, we thought it was important for FDA to get direct input from patients and caregivers as a way to inform their own decision-making if and when these products are submitted to FDA for review.”
Weighing risks and benefits
In the FDA funded study, Gonzalez Sepulveda and colleagues developed and administered a discrete-choice experiment survey. In this survey, respondents chose their preferred treatment alternatives in a series of controlled pairs of hypothetical gene therapies as well as a “no gene therapy” option. The study defined gene therapy alternatives based on their likelihood of eliminating sickle cell disease symptoms and increasing life expectancy, as well as their treatment-related mortality risk and possible increases in lifetime cancer risk.
Study respondents made choices based on the current severity of their sickle cell disease and in the context of anticipated worsening disease.
Researchers recruited 174 adult respondents with sickle cell disease and 109 parents of pediatric patients with sickle cell disease from three clinical sites. One patient organization, Cayenne Wellness, also helped with enrollment.
The study found that both adult and parent respondents had a general interested in pursuing gene therapies, but adult respondents expected higher levels of efficacy than parent respondents, particularly in terms of symptom elimination, as a condition of choosing gene therapies that posed mortality risks of 10% or higher.
When researchers presented adult patients and parents of pediatric patients with less severe sickle cell disease symptoms with hypothetical scenarios that involved higher disease severity, the respondents expressed an increased risk tolerance, and the minimum acceptable level of efficacy for gene therapies with mortality risks declined by more than 50%.
“We noted that adult patients were less risk tolerant than caregivers, and patients and caregivers of patients with milder symptoms were also less risk tolerant,” Gonzalez Sepulveda told Healio. “If you’re not experiencing severe symptoms, you’re potentially more likely to wait for this kind of technology, given the potential risks.”
Eliciting priorities to inform decision-making
Gonzalez Sepulveda found caregivers and parents to be more risk tolerant when considering gene therapies for their children, most likely to ensure the best chance of cure and symptom relief. A feeling of not “being in control” may be a factor in caregiver/parent decision-making, he added.
“I liken it to driving a car — an adult patient knows they’re holding the steering wheel, and they understand that if anything happens, they are in control and can correct the situation,” Gonzalez Sepulveda said. “In the context of gene therapy, we seem to have found that parents, because of that lack of control, are more willing to try things that could reduce the burden on the patient.”
In an unexpected result, survey respondents did not appear to be greatly concerned with potential lifetime cancer risk associated with novel gene therapies, according to Gonzalez Sepulveda.
“We were limited, of course, by the amount of information we had on that kind of risk — we had to present that more qualitatively in terms of what could happen if they opted for treatment,” he said. “Even so, we were surprised to see that it was not really a big factor in their decision-making.”
Gonzalez Sepulveda said he hopes the results of this study will have value in the decision-making process for patients, parents of patients, clinicians and regulatory agencies.
“We hope it provides some information that FDA can use in the future as they’re reviewing these technologies, so that the patient and caregiver perspective is incorporated formally into the decision-making process,” he said. “Beyond that, we hope this triggers some interest in the use of methods like this that look at eliciting priorities or preferences from patients to inform clinical decision-making, not just regulatory decision-making.”
For more information:
Juan Marcos Gonzalez Sepulveda, PhD, can be reached at Population Health Sciences, Duke University, 200 Morris St., Durham, NC 27701; email: jm.gonzalez@duke.edu.
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