Quantifying Benefit-Risk Preferences Of Adult Patient With Hemophilia A For Prophylactic Treatment

Background and ObjectiveHemophilia is a serious chronic disease that requires high compliance with treatment.China has the second largest number of hemophilia patients in the world,with type A accounting for approximately 80%-85%.At present,hemophilia cannot be cured.Clinical studies have shown that prophylactic treatment is an effective way to control bleeding.The transition from childhood to adulthood causes hemophilia patients to be less compliant with prophylactic treatment,which has a detrimental effect on both health and quality of life.Evidence-based medicine is greatly reliant on patient preference.Understanding the preferences and willingness of hemophilia patients for prophylactic treatment are contribute to improve the compliance.Discrete Choice Experiment is commonly used to measure patient preferences for health care services and can help physicians develop personalized treatment plans based on patient preferences.This study aimed to quantitatively explore the benefit-risk assessment of adult hemophilia A patients without inhibitors for prophylaxis by discrete choice experimental methods,calculating the relative importance of each attribute,the maximum acceptable risk,and the preference heterogeneity.To provide a reference for government decision-making,clinical treatment protocol development,and drug company innovation.Data source and methodsIn this study,purposive sampling and snowball methods were used to collect 113 patients with hemophilia A without inhibitors from 7 provinces/municipalities,including Shandong,Hebei,Henan,Beijing,Jiangsu,Hubei and Chongqing.Discrete choice experiment was used to elicit preference.The first step was to identify attributes and levels.We reviewed the literature on measuring treatment preferences of hemophilia patients using discrete choice experiments and best-worst scaling multi-profile case.Four attributes were identified after qualitative interviews and focus group,including annual bleeding rate,the development of inhibitors,dosing frequency and dosing administration.The second step was questionnaire design.A D-optimal design was used and produced 18 choice sets in SAS 9.4.In order to minimize the cognitive burden,18 choice sets were split into two blocks,and each version contains 9 choice sets.The 3rd choice set was repeated as the 10th choice set to test the consistency of respondents’ responses.And ach choice set added one opt-out option.The third step was data analysis.Sociodemographic information and discrete choice experiment data were calculated in STATA 15.1.Patient socio-demographic information was analyzed using descriptive statistics,with chi-square and t-tests.Conditional logit model was sed to the sensitivity analysis to determine the analysis data.Finally,an appropriate data analysis model was selected to analysis preferences and calculate the relative importance of attributes,maximum acceptable risk and preference heterogeneity.ResultsA total of 140 patients participated in the survey and 113 patients were eligible and completed the questionnaire.The mean time was 14.7 minutes.The majority of patients were male(n=100,98.0%),and more than half of patients(n=61,59.8%)had a family history of hemophilia..Mixed logit model showed that four attributes were statistically significant(P<0.05).Adult patients with hemophilia A showed a negative preference for the risk of inhibitors,they prefer prophylaxis that controls the annual number of bleeds to zero,with a 0%risk of inhibitor development,administered subcutaneously and weekly.Comparing the relative importance of the four attributes,the annual number of bleeds was the most important attribute,followed by the risk of inhibitor development and the frequency of administration was slightly higher than the dosing administration.Subgroup analysis showed that there were preference differences among patients with different sociodemographic characteristics.Patients with education of junior high school or below paid more attention to the annual bleeding frequency and drug administration mode.Patients living in the county and below showed a stronger preference for drug administration.The appetite for risk was most pronounced in patients treated on demand.-MAR results showed that if the annual bleeding was reduced from 12 to 0,the maximum acceptable risk of inhibitors was 4.6%.If the dosing administration was reduced from three times a week to once a week,the maximum acceptable risk of inhibitor was 2.0%.When the dosing mode was upgraded from intravenous infusion to subcutaneous,the maximum acceptable risk of inhibitors was 1.7%.Conclusions and SuggestionsOverall,the annual bleeding frequency and the development of inhibitors were patients value most when selecting prophylactic treatment.The dosing frequency has a certain impact on patients’ preferences.The dosing administration was the attribute that patients value least when selecting prophylactic treatment.Education,place of residence and current treatment modality can influence patient preferences.Patients were willing to accept greater inhibitor risk for health benefits.However,there were differences in the maximum acceptable risk that patients can withstand for different health benefits.Proposing the following recommendations,(1)Government must take into account the patient preference results on a macro level,incorporating them into health management decisions such as drug review and approval,drug supervision,and medical insurance.(2)Medical and health service providers must bolster communication with patients,comprehend their needs for prevention and treatment,prioritize patient welfare,and offer differentiated medical services based on patient preferences.(3)Pharmaceutical companies must incorporate patient.Initiating development and upgrading,take the lead.(4)Researchers must devise a research protocol that is as realistic as feasible in order to gauge patient inclinations.