Although there are many long-term prophylactic treatments available for hereditary angioedema, few studies have assessed patient preferences for these treatments. We aimed to assess patient preferences for long-term prophylactic treatment attributes, including treatment trade-offs and the likelihood of starting or switching to a new treatment. An online discrete-choice experiment survey instrument was developed and administered to adults in the USA with a self-reported diagnosis of hereditary angioedema. Respondents evaluated a series of choices between pairs of hypothetical long-term prophylactic hereditary angioedema treatment alternatives. A total of 250 respondents (81.6

Purpose:People's risk preferences may differ depending on the domain in which someone is taking the risk, influencing their demand for innovative medical treatment with uncertain future benefits. This study aims to examine how monetary risk preferences are associated with health risk preferences for a hypothetical lung cancer preventative treatment (one that reduces the chance of getting lung cancer) and the demand for other preventative treatments or measures. Methods:A total of 803 individuals aged 50-80 years at high risk of lung cancer completed a hypothetical investment exercise to measure monetary risk preference, as well as a discrete-choice experiment to measure health risk preference for lung cancer preventative treatment. They also answered questions about other preventative treatments or measures and screening tests they have taken. Results:On average, respondents were willing to invest $67.40 (SD= $31.20) out of $100 in the hypothetical investment exercise. Given the presented levels of benefits and side effects of hypothetical treatment, 50.2% of the participants favored lung cancer preventative treatment, 29.2% were undecided, while 20.7% disliked it. Compared to those not willing to invest any amount, those willing to invest higher amounts were less likely to fall into the no-treatment group (OR=0.171 (p<0.001) to 0.335 (p=0.049), depending on the investment amount category). Additionally, individuals who expressed greater willingness to invest were also more likely to have previously received other forms of preventative healthcare (OR=1.008, p=0.025). Conclusion:Monetary risk preference is related with risk preferences in health and can predict demand for preventative treatments or measures.

OBJECTIVE:To elicit preferences for available and emerging systemic treatments among patients with muscle-invasive bladder cancer in the United States. MATERIALS AND METHODS:Patients with self-reported muscle-invasive bladder cancer participated in an online discrete-choice experiment evaluating preferences for attributes of systemic treatments that could be administered with radical cystectomy or bladder-sparing approaches. Evidence-based attributes included timing and duration of therapy, time until cancer recurrence, overall survival at 5 years, and chance of treatment-related adverse events. Direct-elicitation questions offered choices among fixed profiles of bladder-sparing treatment and radical cystectomy with adjuvant and neoadjuvant systemic treatments. The 9-item Shared Decision Making Satisfaction Questionnaire (SDM-Q-9) captured patients' levels of satisfaction with treatment. RESULTS:Two hundred two respondents completed the survey. Most patients preferred to keep their bladder. Improvements in efficacy were most important (overall survival at 5 years, followed by the time until cancer recurrence). The average patient was tolerant of hypothetical adverse events and willing to accept increasing levels of risk for all overall survival improvements offered. Approximately 75% of respondents chose perioperative immunotherapy plus neoadjuvant chemotherapy with radical cystectomy over neoadjuvant chemotherapy alone with radical cystectomy in a fixed-choice question. On the SDM-Q-9, almost 20% of respondents disagreed with the statement "My doctor asked me which treatment option I prefer." CONCLUSION:Improving overall survival and delaying recurrence were the most important attributes to respondents, and they were willing to accept clinically relevant treatment-related adverse events for improvements in efficacy. Results may inform patient education and engagement in shared treatment decisions.

AimsTo quantify patient preferences for attributes of novel treatments for triple-class-exposed (TCE) relapsed and/or refractory multiple myeloma (RRMM).MethodsUsing a discrete-choice experiment, we elicited preferences for 7 attributes: objective response rate (ORR), overall survival (OS), all-grade cytokine release syndrome risk, all-grade immune effector cell-associated neurotoxicity syndrome risk, serious infection risk (grade 3+), treatment administration, and initial hospitalization requirements.ResultsOS was the most important attribute (conditional relative importance [CRI] 32.0% for a 24-month increase), followed by serious infection risk (CRI 17.3% for avoiding a 60% risk), initial hospitalization requirements (CRI 15.0% for avoiding 14 days of initial hospitalization), and ORR (CRI 13.7% for a 38% increase). Based on differences between relative preference weights, fewer initial hospitalization days when starting treatment and off-the-shelf (vs. chimeric antigen receptor T [CAR T] cell-like) options were significantly preferred.ConclusionsTherapy decisions for patients with TCE RRMM should consider tradeoffs between efficacy, safety, and attributes related to treatment process and initial monitoring.

Patient and caregiver treatment preferences should be incorporated into the drug development process. We updated a 2018 survey to reflect current knowledge about gene therapy for Duchenne muscular dystrophy (DMD) and obtained new data in the U.S., U.K., and other countries. At data collection in 2023, there were no approved gene therapies for DMD. Using the threshold technique, we assessed the maximum acceptable risk of death (MAR) from non-curative gene therapy with time-limited benefit at different stages of DMD progression. Among 263 participants, mean MAR ranged from 2.4 % (treatment in newborns) to 5.4 % (last year able to lift hands to mouth); risk tolerance increased with advancing disease stages. Significant proportions (22.4 %-32.8 %) were willing to accept MAR >10 %. Reasons for higher MAR included the progressive and severe disease, limited treatment alternatives, and participant-reported expected therapy benefits. Those who demonstrated less risk tolerance described uncertainty, maintaining quality of life, optimism regarding future therapies, and the currently uncertain duration of benefit. There were no significant differences in MAR between caregivers and adults with DMD and between respondents in the U.S. and U.K except in the newborn period, though our small sample size is a limitation. MARs remained relatively stable from 2018 to 2023.

Novel therapies, including disease-modifying and cell replacement therapies, may preserve or replace beta cells in people with type 1 diabetes. This study sought to understand how people living with type 1 diabetes or caring for someone with type 1 diabetes perceive the benefits and risks of novel therapies. Semistructured qualitative interviews were conducted with 26 participants in the United States: four adolescents and 12 adults with type 1 diabetes, and 10 caregivers of children with type 1 diabetes. A description of the benefits and risks of disease-modifying and cell replacement therapies, developed with a steering committee of patients and clinicians, was presented during interviews to facilitate discussion among people living with type 1 diabetes and caregivers. A qualitative directed content analysis was conducted. Participants reported that type 1 diabetes and insulin therapy regimens impacted many life areas, with some participants reporting diabetes burnout. Most participants expressed that they would have considered trying disease-modifying therapies, most frequently citing perceived benefits such as reduced insulin reliance and an extended post-diagnosis “honeymoon period” providing time to prepare for life with diabetes. Cancer risk was the most frequently reported risk of concern for disease-modifying therapies. All participants expressed willingness to consider cell replacement therapies, with insulin independence and restored pancreatic function perceived to offer greater normalcy and freedom from the constant demands of diabetes. Participants reported concerns about the use of immunosuppressants and the risks and drawbacks of the cell replacement surgical procedure. Despite concerns about the risks and drawbacks of novel therapies, most participants reported that they would consider trying disease-modifying and cell replacement therapies. There is no substitute for consulting people living with or caring for someone with type 1 diabetes when considering new therapies with novel risks and benefits.

Integrating patient preferences into the design of randomized clinical trials (RCTs) may help accelerate innovation for alternative kidney replacement therapy by appropriately selecting a trial's significance level and sample size, and have a meaningful impact on people suffering from kidney failure. While a conventional one-sided significance level threshold of 2.5 % is often used to assess the safety of a proposed device, we show in this study that it is not necessarily consistent with the risk-preferences of patients with dialysis-dependent kidney disease. We apply a Bayesian decision analysis (BDA) framework to results from a patient preference survey and estimate the optimal significance level and sample size required in an RCT to assess the safety of a hypothetical dialysis device. Based on survey responses from 599 patients with dialysis-dependent kidney failure, we found that the optimal significance level threshold differs significantly from the classical 2.5 % threshold used in two-sided hypothesis tests across various patient subgroups. On average, patients tended to require a significance level of 1.2 % for the risk of bleeding and a significance level <0.1 % for the risk of serious infection, suggesting that the survey respondents were not willing to bear either type of additional risk presented by the hypothetical device in exchange for the possible benefits described in the survey. However, there was heterogeneity among the patient subgroups of dialysis modality, age, gender, ethnicity, and time on dialysis. Overall, our study shows that the BDA framework is a robust, systematic, transparent, and reproducible method for incorporating patient preference information into the design and regulatory review process of clinical trials for novel therapeutics.

Aim: Patient preferences for the features of targeted chronic lymphocytic leukemia (CLL) therapies may differ. Materials & methods: A discrete-choice experiment (DCE) survey was administered to 229 respondents recruited through the CLL Society. Results: Respondents placed most importance on increasing the chance of progression-free survival (PFS) at 2 years from 70 to 90% and confirming results with measurable residual disease (MRD) testing instead of routine testing. Respondents also preferred daily oral administration over intravenous infusion every 4 weeks, fixed-duration treatments over treat-to-progression treatments and treatments with lower side effect risks. Reducing risk of tumor lysis syndrome was least important relative to changes in other attributes. Conclusion: The combination of improving PFS combined with confirming results using MRD testing was more important than changes in all other study attributes included in the DCE. Results from this study can help inform shared decision-making when selecting therapies for CLL. Plain language summary: Several targeted treatments are available for people with chronic lymphocytic leukemia (CLL). These treatments target specific proteins present in CLL cancer cells. They differ in how long they keep cancer from progressing, how the results are measured and the side effects they cause. Some targeted CLL treatments are taken as a daily pill, and others are given by intravenous infusion. Some targeted treatments are given for a fixed amount of time, and others are given until CLL progresses. We surveyed 229 US patients with CLL to understand what features they most value in a targeted CLL treatment. Survey participants were recruited through the CLL Society, a nonprofit organization devoted to education, support, advocacy and research for the CLL community. Survey results indicated that participants placed the most importance on increasing the chance that the cancer would not progress after 2 years from 70 to 90% and confirming results with measurable residual disease testing (which can detect minute levels of leukemia cells) instead of routine testing. Participants also preferred taking a pill every day over receiving an intravenous infusion every 4 weeks and preferred treatments given for a fixed amount of time over treatments given until CLL progresses. Participants preferred treatments with lower chances of tumor lysis syndrome (a potentially organ-damaging condition that may result following treatment), irregular heartbeat and fatigue. It is important for doctors to understand the treatment features that matter to people living with CLL so that they can work with patients individually to choose the right treatment. TWEETABLE ABSTRACT Patients with CLL prioritize the chance of progression-free survival at 2 years and confirming results with measurable residual disease when considering the attributes of targeted CLL therapies.

Background Genetic testing can offer early diagnosis and subsequent treatment of rare neuromuscular diseases. Options for these tests could be improved by understanding the preferences of patients for the features of different genetic tests, especially features that increase information available to patients.Methods We developed an online discrete-choice experiment using key attributes of currently available tests for Pompe disease with six test attributes: number of rare muscle diseases tested for with corresponding probability of diagnosis, treatment availability, time from testing to results, inclusion of secondary findings, necessity of a muscle biopsy, and average time until final diagnosis if the first test is negative. Respondents were presented a choice between two tests with different costs, with respondents randomly assigned to one of two costs. Data were analyzed using random-parameters logit.Results A total of 600 online respondents, aged 18 to 50 years, were recruited from the U.S. general population and included in the final analysis. Tests that targeted more diseases, required less time from testing to results, included information about unrelated health risks, and were linked to shorter time to the final diagnosis were preferred and associated with diseases with available treatment. Men placed relatively more importance than women on tests for diseases with available treatments. Most of the respondents would be more willing to get a genetic test that might return unrelated health information, with women exhibiting a statistically significant preference. While respondents were sensitive to cost, 30% of the sample assigned to the highest cost was willing to pay $500 for a test that could offer a diagnosis almost 2 years earlier.Conclusion The results highlight the value people place on the information genetic tests can provide about their health, including faster diagnosis of rare, unexplained muscle weakness, but also the value of tests for multiple diseases, diseases without treatments, and incidental findings. An earlier time to diagnosis can provide faster access to treatment and an end to the diagnostic journey, which patients highly prefer.

Daily insulin administration can be burdensome for people with type 2 diabetes (PwT2D) and can impact treatment adherence. This study investigated preferences for once-weekly, long-acting basal insulin for treatment of PwT2D. An online discrete-choice experiment was administered to PwT2D in the USA. Qualitative interviews informed the selection of six attributes: reduction in A1c level after 6 months, amount of time spent in optimal blood sugar range each day, number of serious low blood sugar events, number of nighttime low blood sugar events, change in weight because of the insulin over 6 months, and frequency of administration. Each participant completed eight questions offering a choice between two long-acting insulins; questions varied according to an experimental design. A fixed treatment choice question asked about preferences for daily versus weekly insulin, holding other treatment features constant. Data were analyzed using random-parameters logit models, and heterogeneity was explored through subgroup analyses. Four hundred sixty-six PwT2D completed the survey (mean age, 57; mean A1c, 7.5

This study quantified patient preferences for generalized myasthenia gravis (gMG) treatment features.

Introduction & Objective: Once-weekly insulin has the potential to increase willingness to initiate and adhere to insulin therapies in people with type 2 diabetes requiring basal-only insulin therapy. However, the role of once-weekly insulin in people already treated with basal-bolus multiple daily injection regimens, such as people with type 1 diabetes (PwT1D), is less understood. This study aimed to quantify the preferences of PwT1D for novel long-acting insulins. Methods: A discrete choice experiment survey was administered to PwT1D in the United States. The survey included 8 questions offering a choice between experimentally designed pairs of hypothetical, long-acting insulins that varied by 6 attributes: reduction in A1c level after 6 months, daily time in range (TIR), number of serious low blood sugar events, number of nighttime low blood sugar events, weight change over 6 months, and administration frequency. A fixed choice question directly elicited preferences for flexible weekly over daily insulin, holding all other attributes equal. Data were analyzed with random-parameter logits. Results: The survey was completed by 200 PwT1D (mean: age = 41 years; A1c = 7.6%; 57% female). They were on a basal (100%), mealtime bolus (98%), or intermediate or premixed insulin (2%). Across attributes, respondents ranked achieving the longest TIR as the most important change, followed by equal importance on the largest change in the number of serious low blood sugar events per month, avoiding a 10 pound weight change, the largest change in the number of nighttime low blood sugar events per month, and weekly over daily basal administration. The largest reduction in HbA1c was the least important attribute in respondents’ decisions. In the fixed-choice question, 73% of people preferred flexible weekly over daily dosing for basal insulin. Conclusion: The most important attributes were changes in TIR and number of serious hypoglycemic events. PwT1D preferred weekly over daily basal insulin when all other attributes were equal. Disclosure D. Schapiro: Employee; Eli Lilly and Company. M. Perez-Nieves: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C.M. Vass: Other Relationship; Eli Lilly and Company. Consultant; National Institute for Health and Care Excellence (NICE). J. Poon: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. F. Gelsey: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. A. Pierce: None. C. Mansfield: None.

Introduction & Objective: For people with type 2 diabetes (PwT2D), daily insulin regimens can be burdensome, difficult to adhere to, and a key barrier to initiating insulin therapy. Despite developments in once-weekly basal insulins, little is known about PwT2D preferences for administration frequency or its importance relative to other insulin features. Methods: An online discrete choice experiment survey was administered to adults with T2D in the United States. Each respondent completed 8 questions offering a choice between experimentally designed pairs of hypothetical, long-acting insulins that varied by 6 attributes: reduction in A1c level after 6 months, daily time in range, number of serious low blood sugar events, number of nighttime low blood sugar events, weight change over 6 months, and administration frequency. A fixed choice question directly elicited preferences for flexible weekly over daily insulin, holding all other attributes equal. Data were analyzed with random-parameter logits. Results: A total of 466 people (mean: age = 57; A1c = 7.5%; 59% female) completed the survey. They were on a basal/bolus (33.3%), basal-only (34.3%), or insulin-naïve (32.4%) regimen. Relative to other attributes, people placed most importance on avoiding a 10-pound weight change, followed by the largest changes in the number of serious and nighttime low blood sugar events and achieving the longest time in range. There was significant heterogeneity in preference: insulin-naïve respondents strongly preferred weekly administration, whether on the same day each week or a flexible weekly schedule, over daily (p < 0.05). In the fixed-choice question, most (67.6%) preferred flexible weekly over daily dosing. Conclusion: Overall, the most important attributes were weight change due to insulin and number of serious hypoglycemic events. PwT2D preferred weekly over daily basal insulin when all other treatment attributes were equal. The dosing flexibility could be crucial for the insulin naïve. Disclosure F. Gelsey: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. M. Perez-Nieves: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C.M. Vass: Other Relationship; Eli Lilly and Company. Consultant; National Institute for Health and Care Excellence (NICE). J. Poon: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. D. Schapiro: Employee; Eli Lilly and Company. A. Pierce: None. C. Mansfield: None.

INTRODUCTION:An evolving haemophilia treatment landscape provides new possibilities for previously unattainable lifestyles.AIM:We sought to understand how people with haemophilia (PwH) and their caregivers value the potential benefits of novel prophylactic treatments. We conducted a discrete-choice experiment (DCE) to quantify preferences for features of haemophilia treatments among adults and caregivers of children with haemophilia. A best-worst scaling (BWS) exercise measured the perceived burden of treatment administration features.METHODS:A cross-sectional, web-based survey was administered to male adults (≥18 years) and caregivers of male children (≤17 years) living with haemophilia in the United States. Respondents evaluated eight pairs of hypothetical haemophilia treatment profiles defined by six attributes in the DCE and 15 features in the BWS.RESULTS:In the DCE, both adults with haemophilia (n = 151) and caregivers (n = 151) prioritised avoiding the risk of developing inhibitor/ anti-drug antibodies and treatments that allowed for a more active life. They placed a lower priority on reducing the number of spontaneous bleeding episodes, route and frequency of administration, and avoiding the risk of hospitalisation due to adverse events. The BWS documented the burdensomeness of IV infusions and medications that require mixing and refrigeration.CONCLUSION:PwH and caregivers prefer treatments that enable a more active lifestyle with a lower risk of inhibitor development. Both groups valued the ability to lead an active life over reducing spontaneous bleeding, with caregivers placing the most weight on this attribute. As new treatments expand possibilities, healthcare professionals and PwH should continue to share decision-making, incorporating clinical judgment and individual preferences.

e23309 Background: BCMA-directed T-cell–engaging therapies have been introduced into clinical practice for the treatment of TCE RRMM. While efficacious, such treatments are associated with safety considerations such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and serious infections. These treatments also vary in reported efficacy, administration processes, and hospitalization requirements. The aim of this study is to quantify patient preferences and tradeoffs regarding these attributes. Methods: A discrete choice experiment (DCE) was designed to elicit preference weights corresponding to seven attributes related to efficacy (objective response rate [ORR], overall survival [OS]), safety (all-grade CRS, all-grade ICANS, serious infections) and treatment procedures (treatment administration, hospitalization requirements). Attribute levels were based on plausible ranges of potential values. Patients in the United States (US) with a physician-confirmed diagnosis of TCE RRMM were recruited. Pre-test interviews with patients were conducted and the final survey deployed online in 2023. A random-parameters logit model was used to estimate preference weights. Conditional relative importance (CRI) was calculated to rank the relative importance of each attribute. The minimum acceptable benefit (MAB) and maximum acceptable risk (MAR) were calculated to estimate the tradeoffs between efficacy and safety attributes. Results: The sample included 200 respondents (mean [standard deviation] age: 61 [6.4] years; 43% female; 46% White; 10% African American). A total of 197 participants reported having responded to prior treatment, of whom 195 had relapsed or become refractory. In the DCE, a 24-month increase in OS was found to be the most important attribute, with a CRI of 32.0%. Next most important were avoiding a 60% risk of serious infection (CRI 17.3%), avoiding 14-day hospitalization requirements (CRI 15.0%), and a 38% increase in ORR (CRI 13.7%). A treatment that could be started immediately and administered weekly or up to every 4 weeks was preferred over a CAR T-like procedure with a waiting period. Fewer initial hospitalization days was significantly preferred over more hospitalization days. The MABs for OS when the risk of serious infection was increased from 20% to 60%, CRS from 40% to 95%, and ICANS from 3% to 20% were 24.2, 17.1, and 18.0 months, respectively. When OS was increased from 12 to 36 months, the estimated MARs for serious infections, CRS, and ICANS were > 60%, > 95%, and > 20%, respectively. Conclusions: This study highlights US patient preferences regarding treatment attributes for TCE RRMM. Treatment benefits and risks and the mutual tradeoffs considered by patients should be evaluated when developing and selecting therapeutic approaches.

Background: Duchenne muscular dystrophy (DMD) is a progressive, life-limiting, neuromuscular disorder. Clinicians play an important role in informing families about therapy options, including approved gene therapies and clinical trials of unapproved therapies. Objective: This study aimed to understand the perspectives of clinicians about gene therapy for DMD, which has not previously been studied. Methods: We conducted interviews with specialist clinicians treating patients with DMD in the United States (n = 8) and United Kingdom (n = 8). Interviews were completed in 2022, before any approved gene therapies, to gain insight into barriers and facilitators to implementing gene therapy and educational needs of clinicians. Results: Most respondents expressed cautious optimism about gene therapy. Responses varied regarding potential benefits with most expecting delayed progression and duration of benefit (1 year to lifelong). Concern about anticipated risks also varied; types of anticipated risks included immunological reactions, liver toxicity, and cardiac or renal dysfunction. Clinicians generally, but not uniformly, understood that gene therapy for DMD would not be curative. Most reported needing demonstrable clinical benefit to justify treatment-related risks. Conclusions: Our data demonstrate variability in knowledge and attitudes about gene therapy among clinicians who follow patients with DMD. As our knowledge base about DMD gene therapy grows, clinician education is vital to ensuring that accurate information is communicated to patients and families.

Purpose:Acid sphingomyelinase deficiency (ASMD) is a rare, progressive, and potentially fatal disease affecting major organs; its symptoms present heterogeneously. Data on the most bothersome symptoms for patients with ASMD types B or A/B and their caregivers or parents are limited. We conducted a survey to quantify the relative impact of potential ASMD symptoms and risks for patients and parents/caregivers.Patients and Methods:Twenty respondents, recruited via National Niemann-Pick Disease Foundation (United States) and Niemann-Pick United Kingdom, took a preference survey: 11 patients who had a self-reported diagnosis of ASMD types B or A/B and 9 parents who had a child with ASMD types B or A/B. Using object-case best-worst scaling, we explored the most and least bothersome among a set of 15 ASMD symptoms/risks selected based on clinical input and qualitative research with patients and caregivers. In 15 experimentally designed questions containing five items each, respondents ranked the symptoms/risks, irrespective of their experiences with them. Data were analyzed using a conditional multinomial logit model.Results:Patients reported constant abdominal pain, severe pain in bones and joints, and severe fatigue to be the most bothersome potential symptoms or risks, followed by a chance of bleeding in the spleen. The next most bothersome potential symptom was constant shortness of breath. Easy bruising and noticeable abdominal enlargement were among the least bothersome symptoms. The most bothersome symptom for parents was bleeding in the spleen.Conclusion:Patients and parents had similar perceptions of the most bothersome potential symptoms/risks. Despite the small sample size typical of rare disease studies, understanding patient preferences is important for such diseases and can inform shared decision-making.