Patient and parent preferences for efficacy, inhibitor risk, safety, and infusion frequency associated with prophylactic factor VIII treatment

Abstract

Background: As new options become available for Factor VIII prophylaxis treatment, research is needed to understand a patient’s willingness to accept tradeoffs among treatment attributes such as effectiveness, inhibitor risk, safety, and infusion frequency.<br><br>Objective: To quantify patient and parent preferences for prophylactic Factor VIII treatments and compare the relative importance of treatment attributes. <br><br>Methods: Adult patients and parents of children with severe hemophilia A in the United States were recruited and completed a web-enabled, discrete-choice experiment survey. The survey presented a series of 10 choice questions, each including a pair of hypothetical prophylactic Factor VIII treatment profiles. Each profile was defined by average number of bleeds per year, risk of developing an inhibitor, infusion frequency, and track record of product safety. The majority of levels for each attribute were identified based on the literature or clinical trial results. Choice questions were based on a predetermined experimental design with known statistical properties. Preference weights for attribute levels were estimated using randomparameters logit. The survey was tested to help inform attribute selection and ensure respondent comprehension in 10 face-to-face interviews. All respondents provided online informed consent and the study complied with the Declaration of Helsinki, receiving ethics board approval. <br><br>Results: The final sample included 76 adult patients and 86 parents. Mean age for adult patients was 32 years and the mean age for children was 8 years. 47% of adult patients and 41% of parents reported prophylactically infusing 3 times a week. Statistical tests indicated that the two samples could not be pooled due to different preferences (p<0.01). For parents, the most important attribute was average number of bleeds per year and was assigned a mean relative importance score of 10.0. The remaining attributes in descending order of importance were track record of product safety (8.1), risk of developing an inhibitor (8.0), and infusion frequency (6.0). For adult patients, risk of developing an inhibitor was the most important attribute (10.0). The remaining attributes in descending order of importance were average number of bleeds per year (7.3), infusion frequency (6.3), and track record of product safety (4.5). Both patients and parents significantly (p<0.05) preferred 0 to 1 bleeds per year over 5 bleeds per year and a track record of 4 to 10 years of product safety over a product new to market. There were significant (p<0.05) differences between a 0%, 1% and 2% risk of inhibitor development as there were between infusions 3 times per week and infusions 2 times per week. Parents and adult patients revealed that achieving zero bleeds per year (relative to 5 bleeds) was 2.4 and 1.7 times more important than being able to infuse 2 times per week over 3 times per week, respectively. <br><br>Conclusion: While these results suggest that adult patients and parents of children with severe hemophilia A have different preferences, both were not willing to trade off having several bleeds per year to infuse less frequently. Healthcare providers are encouraged to take these preferences into account when prescribing Factor VIII prophylaxis.