Patient preferences and priorities for haemophilia gene therapy in the US: A discrete choice experiment

Abstract

Introduction Gene therapy has shown promise in clinical trials for patients with haemophilia, but patient preference studies have focused on factor replacement treatments. Aim We conducted a discrete choice experiment (DCE) to investigate the relative importance and differential preferences patients provide for gene therapy attributes. Methods We surveyed male adults with haemophilia in the United States recruited from patient panels including the National Hemophilia Foundation Community Voices in Research platform using an online survey over 4 months in 2020/21. Participants indicated preferences for gene therapy attributes including dosing frequency/durability, effect on annual bleeding, uncertainty related to side effects, impact on daily activities, impact on mental health, and post‐treatment requirements. The relative importance of each attribute was analysed overall and for subgroups based on haemophilia type and severity. Results A total of 183 males with haemophilia A (n = 120) or B (n = 63) were included. Half (47%) had severe haemophilia; most (75%) were White. Overall, participants gave effect on bleeding rate the greatest relative importance (31%), followed by dose frequency/durability (26%), uncertainty regarding safety issues (17%), and impact on daily activities (11%). Dose frequency/durability had the greatest importance for those with haemophilia B (35%). Conclusion People with haemophilia prioritised reduced bleeding and treatment burden; the former was more important in haemophilia A and the latter in haemophilia B, followed by safety and impact on daily life in this DCE of gene therapy attributes. These findings and differences can inform clinical and health policy decisions to improve health equity for people with haemophilia.

Gene therapy preferences and informed decision‐making: Results from a National Hemophilia Foundation Community Voices in research survey

“…In studies including attribute ranking, 30,31,33 discrete choice experiments, 32 and trade-offs, 34 the top attributes for decisionmaking include annual bleeding rate, factor level expression, the uncertainty of long-term effects, impact on daily life, chance to stop prophylaxis, dose frequency and durability, impact on ability to participate in physical activity, frequency of monitoring, uncertainty regarding short-term or long-term significant safety issues and duration of follow-up on side effects. A key theme in those studies and the current survey is the unpredictability of the duration of therapeutic response and variability in factor expression.…”

Discrete choice experiments: An overview of experience to date in haemophilia

“…Of the 120 full-text articles assessed for eligibility, 108 were deemed ineligible due to not being a DCE (n=89), not being a full-journal article (n=18) or not having a pharmacological focus (n=1). This led to 12 full text articles being included, with a date range from 2005-2021 [16,[27][28][29][30][31][32][33][34][35][36][37] . The results are summarised in Table 2.…”

“…The review also identified 3 literature reviews [39][40][41] assessing patient preferences in haemophilia, all of which were not full journal articles. There have been two published studies exploring haemophilia patient preferences in relation to gene therapy: one DCE [37] and one utilising a threshold technique [42] . Surveyed audiences included physicians, patients, pharmacists, healthcare professionals and caregivers (either alone or in combination).…”

“…As shown in Table 1, a number of gene therapies are being developed for both haemophilia A and B. Two published studies to date have explored haemophilia patient preferences in relation to gene therapy: one DCE [37] and one utilising a threshold technique [42] . Whilst DCEs have been explored extensively in this paper, the threshold technique is a method that determines the maximal change in one attribute respondents are willing to accept to achieve a given change in another attribute [43] .…”

Gene Therapy and Hemophilia: Where Do We Go from Here?

“…Uncertainty regarding potential short- and long-term safety issues and impact on daily life were weighed at 17% and 11%, respectively. 71 A qualitative study in Belgium with 20 hemophilia participants demonstrated a positive attitude towards gene therapy with 40% of patients “very willing” (N=8) or 35% “willing” (N=7) to receive gene therapy. Annual bleeding rate, factor level, uncertainty of long-term risk, impact on daily life and probability to stop prophylaxis were found to be the important factors to discuss.…”