BACKGROUND: The treatment landscape for hemophilia is evolving. Hence it is important to understand how people with hemophilia and their caregivers value attributes of existing and novel prophylactic treatments. A discrete-choice experiment (DCE) was used to quantify preferences for features of hemophilia treatments among adults and caregivers of children with hemophilia in the US.
METHODS: A cross-sectional, web-based DCE survey was administered to male adults (≥18 years) and caregivers of male children (≤17 years) living with hemophilia in the US. Respondents evaluated 8 pairs of hypothetical hemophilia treatment profiles defined by 6 attributes – number of annual spontaneous bleeding episodes, lifestyle benefits from improvement in function, route of administration, frequency of administration, risk of developing inhibitors or anti-drug antibodies, and risk of hospitalization due to adverse events (AEs). Attributes for the DCE were informed by a literature review and ranking exercise among adult patients, caregivers, physicians, and stakeholders. The DCE data were analyzed using a random parameters logit (RPL) model and used to calculate the maximum acceptable risk (MAR) of AEs respondents were willing to accept for specific improvements in other study attribute levels. MAR is calculated asthe point where the disutility of an increase in risk balances the utilityassociated with an improvement in a treatment attribute.
RESULTS: The fi nal sample included 151 adults (average age 40 years) and151 caregivers (average age 38 years old, 92% female). For the adultsample, avoiding a 30% risk of developing inhibitors or anti-drugantibodies had the greatest relative importance, followed by improvingthe ability to live a more active life from limited to high, reducing thenumber of spontaneous bleeding episodes each year from 6 to 0, changein mode of administration from an intravenous (IV) with vial(s) and syringeto mix to a subcutaneous (Sub-Q) injection with pre-fi lled pen, reducingfrequency of administration from once every 2-3 days to once a month,and avoiding a 5% risk of hospitalization due to AEs ( Figure 1a ). Forcaregivers, improving the ability to live a more active life from limited tohigh had the greatest relative importance, followed by avoiding a 30% riskof developing inhibitors or anti-drug antibodies, reducing the number ofspontaneous bleeding episodes each year from 6 to 0 annual bleeds,avoiding a 5% risk of hospitalization due to AEs, reducing frequency ofadministration from once every 2-3 days to once a month, and a changein mode of administration from an IV with vial(s) and syringe to mix to aSub-Q injection with vial(s) and syringe to mix ( Figure 1b ). In general,adults and caregivers preferred treatments that needed to be taken lessfrequently (e.g., once a month compared with every 2-3 days) . Adultspreferred a Sub-Q injection with a pre-fi lled pen compared with otherroutes of administration. Caregivers preferred Sub-Q options to an IV. Looking at the MAR results, caregivers were willing to accept higher risksof developing inhibitors or anti-drug antibodies than adults forimprovements in other attributes. Caregivers were willing to accept a riskof developing inhibitors or anti-drug antibodies greater than 30% for animprovement in the ability to live a more active life from limited to highand 21% for a reduction in the number of spontaneous bleeding episodeseach year from 6 to 0, compared to 26% and 17% for adults, respectively.Both groups were willing to accept similar levels of risk of hospitalizationdue to AEs for improvements in other attributes, accepting greater than5% for improvements in the ability to live a more active life from limited tomoderate or high and for a reduction in the number of spontaneousbleeding episodes each year from 6 to either 1 or 0 spontaneous bleeds.
CONCLUSION: Patients and caregivers prefer treatments that enable moreactive lifestyle with lower risk of inhibitor development. Both groupsvalued the ability to lead an active life even over reducing spontaneousbleeding, with caregivers placing the most weight on this attributesuggesting that with the changing landscape in hemophilia treatments,patients and caregivers are willing to trade off benefi ts and risks of hemophilia treatments. These fi ndings highlight the need for healthcareprofessionals and patients to share decision making based on clinicaljudgement and individual preferences.
