Priorities when deciding on participation in early-phase gene therapy trials for Duchenne muscular dystrophy: a best–worst scaling experiment in caregivers and adult patients

Ryan S. Paquin, Ryan Fischer, Carol Mansfield, Brennan Mange, Katherine Beaverson, Annie Ganot, Amy Strong Martin, Carl Morris, Colin Rensch, Valeria Ricotti, Leo J. Russo, Alesia Sadosky, Edward C. Smith and Holly L.; Orphanet Journal of Rare Diseases 2019 14:102 doi:10.1186/s13023-019-1069-6

Several gene therapy trials for Duchenne muscular dystrophy initiated in 2018. Trial decision making is complicated by non-curative, time-limited benefits; the progressive, fatal course; and high unmet needs. Here, caregivers and patients prioritize factors influencing decision making regarding participation in early-phase gene therapy trials.

Objects used to construct choice sets for the best-worst choice experiment

Object	Description
Chance of improved muscle function	Data are positive about the chance of maintaining, and maybe improving, muscle function.
Chance of improved heart function	Data are positive about the chance of maintaining, and maybe improving, heart function.
Chance of improved lung function	Data are positive about the chance of maintaining, and maybe improving, lung function.
Benefit lasts about 10 years	Data suggest that gene therapy will last for 10 years. It may be shorter or longer, but no one knows. It is currently not possible to give a second dose of gene therapy. It may be possible in the future, but no one knows.
Chance of being in placebo group	The trial uses a placebo group, where some participants are randomly assigned to a group that gets an inactive (fake) treatment. People who get placebo during the trial would be eligible for gene therapy in the future.
Lowest dose may be too low for benefit	One of the trial’s goals is to test the right dose of gene therapy. If participants get a dose that is too low to work, they will not get another chance to use gene therapy.
Two muscle biopsies required	Being in the trial requires 2 muscle biopsies (one from the arm and one from the leg) to test for dystrophin production.
Not eligible for future trials	People who get gene therapy will most likely not be eligible for other clinical trials for the rest of their lives. It may someday be possible, but no one knows.
Limits later use of gene therapies or CRISPR	People who get gene therapy may not be able to use some newer types of gene therapy or gene editing (like CRISPR) for the rest of their lives. It may someday be possible, but no one knows.
Chance of long hospitalization	Data suggest a low risk of needing a long hospitalization of 4 weeks or more to recover from serious side effects.
Chance of death (low risk)	Data suggest a very low risk of death soon after using gene therapy. That risk should be even lower than we showed you in the first survey task.