Patients’ and caregivers’ maximum acceptable risk of death for non‐curative gene therapy to treat Duchenne muscular dystrophy

Abstract

Abstract Background Gene therapy offers an etiologically targeted treatment for genetic disorders. Little is known about the acceptance of mortality risk among patients with progressive, fatal conditions. We assessed patients’ and caregivers’ maximum acceptable risk (MAR) of mortality for gene therapy when used to treat Duchenne muscular dystrophy (DMD). Methods The threshold technique was used to assess tolerance for mortality risks using a hypothetical vignette. Gene therapy was described as non‐curative and resulting in a slowing of progression and with a 10‐year benefit duration. MAR was analyzed using interval regression for gene therapy initiated “now”; in the last year of walking well; in the last year of being able to bring arms to mouth; and in newborns (for caregivers only). Results Two hundred eighty‐five caregivers and 35 patients reported the greatest MAR for gene therapy initiated in last year of being able to lift arms (mean MAR 6.3%), followed by last year of walking well (mean MAR 4.4%), when used “now” (mean MAR 3.5%), and when used in the newborn period (mean MAR 2.1%, caregivers only). About 35% would accept ≥200/2000 risk in the last year of being able to lift arms. Non‐ambulatory status predicted accepting 1.8 additional points in MAR “now” compared with ambulatory status (p = 0.010). Respondent type (caregiver or patient) did not predict MAR. Conclusion In this first quantitative study to assess MAR associated with first‐generation DMD gene therapy, we find relatively high tolerance for mortality risk in response to a non‐curative treatment scenario. Risk tolerance increased with disease progression. Patients and caregivers did not have significantly different MAR. These results have implications for protocol development and shared decision making.

Keywords

• Duchenne muscular dystrophy
• gene therapy
• patient‐reported outcomes
• risk