Treatment Preference Among Patients with Hemophilia A: A Discrete Choice Experiment with - PowerPoint Presentation

1. Treatment Preference Among Patients with Hemophilia A: A Discrete Choice Experiment with Time Trade-Off (DCT-TTO)Lizheng Shi, PhD, MsPharmRegents Professor and Interim ChairDepartment of Health policy and ManagementSchool of Public Health and Tropical MedicineFunded by BioMarin Pharmaceutical, which provided input into study design.

2. BackgroundHemophilia A is an inherited bleeding disorder The blood does not clot properly characterized by factor VIII (FVIII) deficiency. This can lead to spontaneous bleeding as well as bleeding following injuries or surgery.

3. Treatment for HAAim to reduce bleeding, other morbidities, and improve quality of life. Treatments vary with little evidence on which characteristics, or ‘attributes’, matter most to patients. Keziah Cook, Shaun P. Forbes, Kelly Adamski, Janice J. Ma, Anita Chawla &Louis P. Garrison Jr. (2020): Assessing the potential cost-effectiveness of a gene therapy for thetreatment of hemophilia A, Journal of Medical Economics, DOI: 10.1080/13696998.2020.1721508TreatmentsAdministration characteristicsFVIII replacementintravenous (IV) weeklyEmicizumabsubcutaneous (SQ) treatment monthlyValoctocogene roxaparvovecSingle intravenous infusion with hypothesized 5-10 year durability

4. Decision-making context: Mid-late lifecycle decision making and gene therapy uncertaintiesKnowledge gaps:Current value measures do not capture patient preferences on uncertainties (e.g., LONG durability?) in gene therapyHTA agencies prefer generic preference-based measuresShort-term benefits & risksLong-term benefits & risksClinical trialsPost-marketingPayers: Pricing and reimbursementRegulators: Marketing authorizationMarket accessvan Overbeeke et al. Drug Discovery Today. 2020HTA

5. Treatment-Process UtilitiesTreatment process can have an impact on quality of life and health state utilitiesRoute of administration (ROA)Dose frequencyDose flexibilityInjection device characteristicsSmall differences in treatment-process utility can influence the cost-effectiveness and subsequent decision-making

6. Treatment attributes in HA“a longer injection interval implied +0.038 (0.03; 0.45)”Carlsson et al. 2017, Haemophilia. 2017;23:894–903.

7. DCE vs. VignetteDCE-TTODCE: Preference is indicated by choosing one option from alternative scenarios or health states The most important characteristics or ‘attributes’ are identified and broken down into relevant levels. TTO: Method elicits health utilities for health states by letting a patient be indifferent between the longer period of impaired health and the shorter period of full health. DCE-TTO: Utility valuations for preference-based survey (e.g., EQ-5D)Can be understood and quantified through a discrete choice experiment with TTO for treatment-process attributeCan represent a large number of hypothetical treatmentsVignette-TTO A vignette describes the impact of a medical condition that is valued in a preference elicitation task to obtain a utility estimateRare disease Treatment process utilitiesAcute and temporary health stateHealth states that change over timeVignette approach can isolate the utility impact of a specific treatment process attribute by holding all aspects of a health state constant except for this attribute. Process utilities estimated with vignettes have been included in CUAs conducted for HTA submissions, and had favorable HTA impressions of cost-effectiveness.Matza et al. 2021 VIH 24(6): 812-821

8. MethodsHA patients (aged ≥18y) were recruited from the Louisiana Center for Bleeding and Clotting Disorders at Tulane University and through national patient advocacy organization for hemophilia to participate in a web or in-clinic survey. The DCE-TTO survey was developed based on the core outcome set for hemophilia gene therapy (coreHEM), including method and frequency of administration, mental health, chronic pain, and annual bleeding rate. Patients completed a DCE-TTO instrument with 24 randomly generated hypothetical choice sets to choose their preferred treatment. Treatment characteristics were analyzed with TTO of 10, 15 and 20 years using conditional logistic models. Socio-demographic data and clinical characteristics, were obtained from medical records or self-reports.

9. Treatment characteristics (coreHEM)LevelsTreatmentFrequency and mode of treatmentOne-time IV infusion, works for 5yrs, followed by regular hemophilia treatmentOne-time IV infusion, works for 10yrs, followed by regular hemophilia treatment2-3 times IV infusion per week1-2 times SQ injection per monthMental HealthMental health statusAlways concerned your hemophiliaOccasionally concerned about your hemophilia No concern about your hemophilia Chronic PainPain from a persistent causeYesNoBleedingNumber of bleeds per yearNone1-4 times5 or moreLife DurationRemaining Years of Life10 years15 years20 years

10.  DCE Choice Set without TTO Attribute (Which scenario would you pick?) AttributeTreatment ATreatment BTreatment2-3 IV Infusions Per WeekOne-time IV infusion, works for 5yrs, followed by regular hemophilia treatmentMental HealthAlways Concerned Never ConcernedChronic PainYesNoBleedingNone1-4 timesWhich Treatment Do You Think Is BetterChoice set randomly generated by computer, based on iterations from the attribute and levels defined previously.Each patient will be asked to select a preferred scenario among 24 choice sets.Data will be used to estimate the utility impact of bleeding frequency, treatment modality, and impact of daily activity.

11. 119 HA patients completed the survey (mean age 37y, range 18-70y; 50% with moderate hemophilia A).56% reported their current treatment was moderately burdensome; 40% treated once every 4 weeks. Average EQ-5D-5L VAS for participants was 75.3; EQ-5D-5L utility score was 0.68All coreHEM outcomes were statistically significant attributes

12.  DCE Choice Set with TTO Attribute (Which scenario would you pick?) AttributeTreatment ATreatment BTreatment2-3 IV Infusions Per WeekOne-time IV infusion, works for 5yrs, followed by regular hemophilia treatmentMental HealthAlways Concerned Never ConcernedChronic PainYesNoBleedingNone1-4 timesLife duration10 years15 yearsWhich Treatment Do You Think Is Better

13. DCE-TTO Annualized Utility Decrement for Gene Therapy10yr Durability (multiple IV weekly infusions)0.0465yr Durability (multiple IV weekly infusions)0.04410yr Durability (multiple SQ monthly injections)0.0375yr Durability (multiple SQ monthly injections) 0.030

14. ConclusionA one-time IV treatment can improve the health utility over repeated prophylactic administration.Durability of the one-time IV treatment impacts the incremental utility improvement; patients with hemophilia are willing to trade life years to reduce treatment burden. Patients with hemophilia indicated that all coreHEM outcomes are important for treatment choices, but those with the most importantce are treatment characteristics and bleeding.Future work will be further benchmarked with other approaches (e.g., EQ-5D, Vignette)

15. Thank You!

16. Polling questionIs traditional preference-based utility measures feasible for measuring the utility values associated with treatment-process attributes? (Yes/No)Is a DCE-TTO method more efficient to elicit utility values for treatment-process attributes, than vignette-TTO method? (Yes/No)