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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.

Background: Patients with moderate-to-severe atopic dermatitis (AD) experience skin lesions and intense itch that substantially affect quality of life. Patients have choices among systemic AD treatments that offer varied benefit-risk profiles., Objective: Measure patients' willingness to trade off the risks and benefits of systemic treatments among individuals with a physician-confirmed diagnosis of moderate-to-severe AD., Methods: Patients participated in a discrete choice experiment online survey with a series of choices between hypothetical AD treatments defined by six attributes reflecting benefits and risks of treatments (itch reduction, time until noticeable itch reduction, chance of clear or almost clear skin, risk of serious infection, risk of developing acne, and need for prescription topical steroids). Data were analyzed with a random parameters logit model to quantify preferences and the relative importance of attributes for treatment alternatives., Results: Respondents ( n  = 200) placed the highest relative importance on itch reduction, speed of itch reduction, and skin clearance, and were generally willing to accept clinically relevant levels of risk of serious infection and acne in exchange for treatment benefits., Conclusions: Patients with moderate-to-severe AD were willing to trade clinically relevant treatment risks for greater or more rapid itch reduction and skin clearance offered by systemic therapies.

Importance: Interception therapy requires individuals to undergo treatment to prevent a future medical event, but little is known about preferences of individuals at high risk for lung cancer and whether they would be interested in this type of treatment., Objective: To explore preferences of individuals at high risk for lung cancer for potential interception therapies to reduce this risk., Design, Setting, and Participants: This survey study used a discrete-choice experiment and included hypothetical lung cancer interception treatments with 4 attributes: reduction in lung cancer risk over 3 years, injection site reaction severity, nonfatal serious infection, and death from serious infection. Respondents were assigned to a baseline lung cancer risk of 6%, 10%, or 16% over 3 years. The discrete-choice experiment was administered online (July 13 to September 6, 2022) to US respondents eligible for lung cancer screening according to US Preventive Services Task Force guidelines. Participants included adults aged 50 to 80 years with at least a 20 pack-year smoking history. Statistical analysis was performed from September to December 2022., Main Outcomes and Measures: Attribute-level preference weights were estimated, and conditional relative attribute importance, maximum acceptable risks, and minimum acceptable benefits were calculated. Characteristics of respondents who always selected no treatment were also explored., Results: Of the 803 survey respondents, 495 (61.6%) were female, 138 (17.2%) were African American or Black, 55 (6.8%) were Alaska Native, American Indian, or Native American, 44 (5.5%) were Asian or Native Hawaiian or Other Pacific Islander, 104 (13.0%) were Hispanic, Latin American, or Latinx, and 462 (57.5%) were White, Middle Eastern or North African, or a race or ethnicity not listed; and mean (SD) age was 63.0 (7.5) years. Most respondents were willing to accept interception therapy and viewed reduction in lung cancer risk as the most important attribute. Respondents would accept a greater than or equal to a 12.0 percentage point increase in risk of nonfatal serious infection if lung cancer risk was reduced by at least 20.0 percentage points; and a greater than or equal to 1.2 percentage point increase in risk of fatal serious infection if lung cancer risk was reduced by at least 30.0 percentage points. Respondents would require at least a 15.4 (95% CI, 10.6-20.2) percentage point decrease in lung cancer risk to accept a 12.0 percentage point increase in risk of nonfatal serious infection; and at least a 23.1 (95% CI, 16.4-29.8) percentage point decrease in lung cancer risk to accept a 1.2 percentage point increase in risk of death from serious infection. Respondents who were unwilling to accept interception therapy in any question (129 [16.1%]) were more likely to be older and to currently smoke with no prior cessation attempt, and less likely to have been vaccinated against COVID-19 or examined for skin cancer., Conclusions and Relevance: In this survey study of individuals at high risk of lung cancer, most respondents were willing to consider interception therapy. These results suggest the importance of benefit-risk assessments for future lung cancer interception treatments.

Background: Several adjunctive medications are available to reduce OFF time between levodopa/carbidopa (LD/CD) doses for people with Parkinson's disease (PD)., Objective: To explore how individuals with PD balance benefits and burdens when considering adjunctive medications., Methods: US adults (30-83 years) with self-reported PD, currently treated with LD/CD, who experienced OFF episodes were recruited through the Fox Insight study to complete a discrete-choice experiment survey. Respondents selected among experimentally designed profiles for hypothetical adjunctive PD treatments that varied in efficacy (additional ON time), potential adverse effects (troublesome dyskinesia, risk of diarrhea, risk of change in bodily fluid color), and dosing frequency or the option "No additional medicine". Data were analyzed with random-parameters logit models., Results: Respondents (N=480) would require ≥60 additional minutes of daily ON time to accept either a 40% risk of change in bodily fluid color or 10 additional minutes with troublesome dyskinesia daily. Respondents would require 40 additional minutes of daily ON time to accept a 10% risk of diarrhea and 22 additional minutes of daily ON time to switch from 1 additional pill each day to 1 pill with each LD/CD dose. On average, respondents preferred adjunctive PD medication over no additional medication. Results predicted that 59.1% of respondents would select a hypothetical treatment profile similar to opicapone, followed by no additional medication (27.5%) and a hypothetical treatment profile similar to entacapone (13.4%)., Limitations: The data collected were based on responses to hypothetical choice profiles in the survey questions. The attributes and levels selected for this study were intended to reflect the characteristics of opicapone and entacapone; attributes associated with other adjunctive therapies were not evaluated., Conclusion: Patients with PD expressed interest in adjunctive treatment to increase ON time and would accept reduced ON time to avoid adverse effects., Competing Interests: Michael Serbin, Charles Yonan, and Olga Klepitskaya are employees of Neurocrine Biosciences. Carol Mansfield is an employee of RTI Health Solutions, and Colton Leach was an employee of RTI Health Solutions when this research was conducted. Connie Marras is on the steering committee for the Fox Insight study. Margaret Sheehan and Anne Donnelly have nothing to disclose for this work., (© 2023 Serbin et al.)

Objectives: To adapt a patient-reported outcome (PRO) measure, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), into efficacy attributes for a discrete choice experiment (DCE) survey designed to quantify the relative importance of endpoints commonly used in knee osteoarthritis (KOA) trials., Methods: The adaptation comprised four steps: (1) selecting domains of interest; (2) determining presentation and framing of selected attributes; (3) determining attribute levels; and (4) developing choice tasks. This process involved input from multiple stakeholders, including regulators, health preference researchers, and patients. Pretesting was conducted to evaluate if patients comprehended the adapted survey attributes and could make trade-offs among them., Results: The WOMAC pain and function domains were selected for adaption to two efficacy attributes. Two versions of the discrete choice experiment (DCE) instrument were created to compare efficacy using (1) total domain scores and (2) item scores for "walking on a flat surface." Both attributes were presented as improvement from baseline scores by levels of 0%, 30%, 50%, and 100%. Twenty-six participants were interviewed in a pretest of the instrument (average age 60 years; 58% female; 62% had KOA for ≥ 5 years). The participants found both versions of attributes meaningful and relevant for treatment decision-making. They demonstrated willingness and ability to tradeoff improvements in pain and function separately, though many perceived them as inter-related., Conclusions: This study adds to the growing literature regarding adapting PRO measures for patient preference studies. Such adaptation is important for designing a preference study that can incorporate a clinical trial's outcomes with PRO endpoints., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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., Competing Interests: CM is an employee of RTI Health Solutions and receives funding from commercial and federal entities to conduct studies on healthcare, outside the submitted work. JC was an employee of RTI Health Solutions at the time of the study conduct. RPJ is an employee of Sanofi and may hold shares and/or stock options in the company. LN and DJ were full-time employees of Sanofi when this study was conducted. The authors report no other conflicts of interest in this work., (© 2023 Mansfield et al.)

Treatments for unresectable hepatocellular carcinoma (HCC) have varying benefit-risk profiles. We elicited 200 US patients' preferences for attributes associated with various first-line systemic treatments for unresectable HCC in a discrete-choice experiment (DCE) survey. Respondents answered nine DCE questions, each offering a choice between two hypothetical treatment profiles defined by six attributes with varying levels: overall survival (OS), months of maintained daily function, severity of palmar-plantar syndrome, severity of hypertension, risk of digestive-tract bleeding, and mode and frequency of administration. A random-parameters logit model was used to analyze the preference data. Patients regarded an additional 10 months of maintaining daily function without decline to be as important or more important than 10 additional months of OS, on average. Respondents valued avoiding moderate-to-severe palmar-plantar syndrome and hypertension more than extended OS. A respondent would require >10 additional months of OS (the greatest increase presented in the study) on average to offset the increased burden of adverse events. Patients with unresectable HCC prioritize avoiding adverse events that would severely impact their quality of life over mode and frequency of administration or digestive-tract bleeding risk. For some patients with unresectable HCC, maintaining daily functioning is as important or more important than the survival benefit of a treatment.

Background: We aimed to quantify patients' benefit-risk preferences for attributes associated with human epidermal growth factor receptor 2 (HER2)-targeted breast cancer treatments and estimate minimum acceptable benefits (MABs), denominated in additional months of progression-free survival (PFS), for given treatment-related adverse events (AEs)., Methods: We conducted an online discrete-choice experiment (DCE) among patients with self-reported advanced/metastatic breast cancer in the United States, United Kingdom, and Japan (N = 302). In a series of nine DCE questions, respondents chose between two hypothetical treatment profiles created by an experimental design. Profiles were defined by six attributes with varying levels: PFS, nausea/vomiting, diarrhea, liver function problems, risk of heart failure, and risk of serious lung damage and infections. Data were analyzed using an error component random-parameters logit model., Results: Among the attributes, patients placed the most importance on a change in PFS from 5 to 26 months; change from no diarrhea to severe diarrhea was the least important. Avoiding a 15% risk of heart failure had the largest MAB (5.8 additional months of PFS), followed by avoiding a 15% risk of serious lung damage and infections (4.6 months), possible severe liver function problems (4.2 months), severe nausea/vomiting (3.7 months), and severe diarrhea (2.3 months) compared with having none of the AEs. The relative importance of 21 additional months of PFS (increasing from 5 to 26 months) increased for women with HER2-negative disease and those with children., Conclusions: Patients valued PFS gain higher than the potential risk of AEs when deciding between hypothetical breast cancer treatments., (© 2022. The Author(s).)

Objective: We aimed to assess the feasibility of developing a discrete-choice experiment survey to elicit preferences for a treatment to delay cognitive decline among people with a clinical syndrome consistent with early Alzheimer's disease, including the development of self-reported screening criteria to recruit the sample., Methods: Using input from qualitative interviews, we developed a discrete-choice experiment survey containing a multifaceted beneficial treatment attribute related to slowing cognitive decline for respondents with self-reported cognitive concerns. In two rounds of in-person pretest interviews, we tested and revised the survey text and discrete-choice experiment questions, including examples, language, and levels associated with the Alzheimer's Disease Assessment Scale-Cognitive Subscale, along with a set of de novo self-reported questions for identifying respondents who had neither too mild nor too advanced cognitive decline. Self-reported memory and thinking problems were compared with symptoms from studies of patients with early Alzheimer's disease (e.g., mild cognitive impairment, mild Alzheimer's disease) to determine whether those studies' recruited patients were similar to our anticipated target population. Round 1 pretest interviews resulted in significant simplifications in the survey instrument, revisions to the inclusion and exclusion criteria, and revisions to the screening process. In round 2 of the pretest interviews, the ability of participants to provide consistent responses to the self-reported screening questions was further assessed. In addition, to evaluate participants' ability to understand and independently complete the discrete-choice experiment survey, two interviewers independently evaluated each participant's ability to make trade-offs in the discrete-choice experiment questions and to understand the content of the survey., Results: Round 1 (15 pretest interviews) identified challenges with the survey instrument related to the complexity of the choice questions. The screening process did not screen out seven respondents with more advanced cognitive decline, as determined qualitatively by the interviewers and by these participants' inability to complete the survey. The survey instrument and screening criteria were revised, and an initial online screener was added to the screening process before round 2 pretests. In round 2 pretests, 12 participants reported cognitive problems similar to the target population for the survey but were judged able to understand and independently complete the discrete-choice experiment survey., Conclusions: We developed self-reported screening criteria that identified a sample of individuals with memory and thinking concerns who were similar to individuals with clinical symptoms of early Alzheimer's disease and who were able to independently complete a simplified discrete-choice experiment survey. Quantitative patient preference studies provide important information on patients' willingness to trade off treatment benefits/risks. Adapting the technique for patients with cognitive decline requires careful testing and adjustments to survey instruments. This work suggests it is the severity of cognitive impairment, rather than its presence, that determines the ability to complete a simplified discrete-choice experiment survey., (© 2022. Eli Lilly.)

Background: Recent innovations have the potential to disrupt the current paradigm for kidney failure treatment. The US Food and Drug Administration is committed to incorporating valid scientific evidence about how patients weigh the benefits and risks of new devices into their decision making, but to date, premarket submission of patient preference information (PPI) has been limited for kidney devices. With input from stakeholders, we developed a survey intended to yield valid PPI, capturing how patients trade off the potential benefits and risks of wearable dialysis devices and in-center hemodialysis., Methods: We conducted concept elicitation interviews with individuals receiving dialysis to inform instrument content. After instrument drafting, we conducted two rounds of pretest interviews to evaluate survey face validity, comprehensibility, and perceived relevance. We pilot tested the survey with in-center hemodialysis patients to assess comprehensibility and usability further. Throughout, we used participant input to guide survey refinements., Results: Thirty-six individuals receiving in-center or home dialysis participated in concept elicitation ( N =20) and pretest ( N =16) interviews. Participants identified reduced fatigue, lower treatment burden, and enhanced freedom as important benefits of a wearable device, and many expressed concerns about risks related to device disconnection-specifically bleeding and infection. We drafted a survey that included descriptions of the risks of serious bleeding and serious infection and an assessment of respondent willingness to wait for a safer device. Input from pretest interviewees led to various instrument modifications, including treatment descriptions, item wording, and risk-level explanations. Pilot testing of the updated survey among 24 in-center hemodialysis patients demonstrated acceptable survey comprehensibility and usability, although 50% of patients required some assistance., Conclusions: The final survey is a 54-item web-based instrument that will yield estimates of the maximal acceptable risk for the described wearable device and willingness to wait for wearable devices with lower risk., Competing Interests: K.L. Cavanaugh reports consultancy for the Kidney Health Initiative, REATA Pharmaceuticals, and Responsum Health; ownership interest in HCA Healthcare; and an advisory or leadership role for the National Kidney Foundation (KDQOI education committee), Clinical Journal of American Society of Nephrology (editorial board), American Journal of Kidney Diseases (editorial board), Kidney360 (associate editor), and Medical Decision Making (editorial board). J.E. Flythe reports consultancy for AstraZeneca and Fresenius Medical Care Medical Advisory Board; research funding from National Institutes of Health/National Heart, Lung, and Blood Institute, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, Renal Research Institute (subsidiary of Fresenius Medical Care, North America), and Robert Wood Johnson Foundation; honoraria from the American Society of Nephrology, National Kidney Foundation, and numerous universities; and an advisory or leadership role for the American Journal of Kidney Diseases (editorial board 2017–2021), Clinical Journal of American Society of Nephrology (editorial board 2017–), Hemodialysis (theme editor 2018–), KDIGO Executive Committee (2020–), Kidney Health Initiative (board of directors 2019–), Kidney Health Initiative (Patient Preferences Project chairperson 2019–), Kidney Medicine (editorial board 2019–), Kidney360 (associate editor 2019–), and Nephrology Dialysis and Transplantation (editorial board). D. Forfang reports employment by the American Society of Nephrology Kidney Health Initiative; consultancy for Ardelyx, Inc., Scientific Advisory Board, the American Society of Nephrology and Responsum, CareDX, HSAG, and University of North Carolina Kidney Center; honoraria from the American Society of Nephrology, European Association for Dialysis, HSAG ESRD Network #17, National Kidney Foundation; an advisory or leadership role for Arbor Research, HSAG ESRD Network #17 (board member), Kidney Health Initiative (Patient Advisory Committee), National Forum of ESRD Networks (board member), National Forum of ESRD Networks Kidney Patient Advisory Council (chair); National Kidney Foundation, SONG Group, and Unity Health Toronto OPPUS, UCSF Kidney Project (patient advisor); and other interests or relationships as a volunteer for the Forum of ESRD Networks as Kidney Patient Advisory Council chair and board member, a volunteer for ESRD Network #17 as Patient Advisory Committee Chair and Network board member, a volunteer for the National Kidney Foundation as a member of their Public Policy Committee, and a volunteer for the National Kidney Foundation as a Regional Leader of their Kidney Advocacy Committee, Kidney Health Initiative PFPC member. N. Gedney reports honoraria from the American Society of Nephrology, IDEAs, and the University of Washington. R.C. Harris reports consultancy for Bayer, Fibrocor, and Nicoya; ownership interest in Apple; research funding from Bayer; patents or royalties from eNOS db/db mouse; an advisory or leadership role for the Kidney Health Initiative (paid); and other interests or relationships with the Kidney Health Initiative (co-chair, board of directors). F.P. Hurst reports employment by the Food and Drug Administration/Center for Drug Evaluation and Research, and other interests or relationships with a US government employee. C. Mansfield reports the employment by RTI Health Solutions, which receives funding from for-profit pharmaceutical companies to conduct research. C.Y. Neuland reports being a member of the board of directors for the Kidney Health Initiative, representing the Food and Drug Administration/Center for Devices and Radiological Health during this time period. A. Saha reports employment by the Food and Drug Administration. C.S. Soloe reports employment by RTI International. G. Squillaci reports consultancy for The Griff Group. M.E. Tarver reports employment by the Food and Drug Administration/Center for Devices and Radiological Health. K. Treiman reports employment by RTI International. M.L. Unruh reports consultancy for Cara Therapeutics to chair of Data Monitoring Committee; a consulting agreement between Cara and the University of New Mexico; research funding from DCI; and honoraria related to lectures from the American Society of Nephrology, National Kidney Foundation, and Renal Research Institute. M. West reports employment by the American Society of Nephrology. D.M. White reports employment by Debevoise & Plimpton; consultancy for the Kidney Transplant Collaborative, the National Committee for Quality Assurance, and Responsum Health; ownership interest in Amgen, Inc.; honoraria from AstraZeneca, Hennepin Healthcare, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, New York Academy of Medicine, and PFCC partners; and other interests or relationships with the American Association of Kidney Patients, American Society of Transplantation, Kidney Health Initiative, National Kidney Foundation, National Patient Advocate Foundation, Patient Advocate Foundation, and Quality Insights. C. Wilkie reports employment by Kuhns Law Firm, PLLC; consultancy for the University of North Carolina, University of Pennsylvania, and University of Pittsburg; ownership interest in Kuhns Law Firm, PLLC; an advisory or leadership role for the Kidney Health Initiative, University of Pennsylvania with the HOPE Consortium, and University of Pittsburgh; and other interests or relationships with the Kidney Health Initiative, National Kidney Foundation, University of Pennsylvania with the HOPE Consortium, University of North Carolina at Chapel Hill, and University of Pittsburgh. D. Wood reports employment by RTI International. The remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Introduction: Despite recent advances in treatment for psoriatic arthritis (PsA), many patients experience inadequate response or intolerance to therapy, indicating that unmet treatment-related needs remain. To further characterize these unmet needs, we evaluated patients' experiences regarding the burden of PsA symptoms and disease impacts, and patients' preferences for treatment., Methods: Patients from ArthritisPower, a rheumatology research registry, completed a web-based survey. Object case best-worst scaling (BWS) was used to evaluate the relative burden of 11 PsA-related symptoms and the relative importance of improvement in nine PsA-related disease impacts. BWS data were analyzed using a random-parameters logit model. Patient demographics, preferences for mode and frequency of therapy, and preferences for methotrexate were analyzed descriptively., Results: Among the 332 participants, most were White (94%), female (80%), with mean age of 54 years (SD 11.4). In the BWS, joint pain was the most bothersome symptom, followed by other musculoskeletal pain and fatigue. The BWS for disease impacts found that improvements in the ability to perform physical activities were most important, followed by improvements in the ability to function independently, sleep quality, and the ability to perform daily activities. The most burdensome symptoms and desired disease impact improvements were similar in patients regardless of their experience with biologic disease-modifying antirheumatic drugs. The most preferred mode and frequency of treatment administration was oral, once-daily medication (preferred by 38% of respondents), and 74% prioritized therapies that significantly improved joint-related symptoms versus psoriasis-related symptoms. The majority of respondents (65%) preferred PsA treatment regimens that did not include methotrexate., Conclusions: Patients with PsA from a rheumatology registry found musculoskeletal pain symptoms to be the most bothersome and prioritized improvements to functional impacts of their disease. These findings can better inform development of new therapies and guide shared patient-provider treatment decision-making., (© 2022. The Author(s).)

Introduction/background: This study aimed to describe patient and caregiver preferences for treatments of relapsed or refractory multiple myeloma (MM)., Materials and Methods: A survey including discrete-choice experiment (DCE) and best-worst scaling (BWS) exercises was conducted among US patients with relapsed or refractory MM and their caregivers. The DCE included six attributes with varying levels including progression-free survival (PFS), toxicity, and mode and frequency of administration. In addition, the impact of treatment cost was assessed using a fixed-choice question. The BWS exercise included 18 items (modes and frequency of administration, additional treatment convenience, and toxicity items). The survey was administered online to patients recruited from the Multiple Myeloma Research Foundation CoMMpass study (NCT01454297)., Results: The final samples consisted of 94 patients and 32 caregivers. Avoiding severe nerve damage was most important to patients, followed by longer PFS. Caregivers considered PFS to be the most important attribute. We estimate that a third or more of patients were cost-sensitive, meaning their treatment preference was altered based on cost implications. Caregivers were not cost-sensitive. The three most bothersome treatment features in the BWS exercise were risk of kidney failure, lowering white blood cell counts, and weakening the immune system., Conclusion: Patients with relapsed or refractory MM and their caregivers consider many factors including efficacy, toxicity, mode/frequency of administration, and cost in their decisions regarding treatment options. The study provides a basis for future Research on patient and caregiver treatment preferences, which could be incorporated into shared decision-making with physicians., Competing Interests: Daniel Auclair reports grants from Takeda, during the conduct of the study performed at MMRF; he is now an AstraZeneca employee. Carol Mansfield and Brennan Mange are salaried employees of RTI Health Solutions which was contracted by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical International Co. to assist in the analysis and writing. Craig E Cole reports personal fees and/or grants from Oncopeptides, Sanofi, and GlaxoSmithKline, outside the submitted work. Jonathan L Kaufman reports grants and/or personal fees from Janssen, Amgen, AbbVie, Roche, Sutro, TG therapeutics, Incyte, BMS, and Tecnofarma, outside the submitted work. Jeffrey A Zonder reports personal fees and/or grants from Janssen, Takeda, Regeneron, Amgen, Intellia, Eidos, Alnylam, Oncopeptides, BMS, and Caelum, outside the submitted work. Mehul Dalal is a salaried employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical International Co. Joseph R Mikhael has received honoraria from Amgen, BMS, GSK, Karyopharm, Celgene, Janssen, Sanofi, and Takeda Pharmaceuticals. David S Siegel has received honoraria from Amgen, BMS, GSK, Celgene, Janssen, Karyopharm and Takeda Pharmaceuticals. The authors report no other conflicts of interest in this work., (© 2022 Auclair et al.)

Background: Long-acting pre-exposure prophylaxis (LA-PrEP) formulated as implants and injections are promising prevention method strategies offering simplicity, discretion, and long dose duration. Men are important end users of LA-PrEP, and early assessment of their preferences could enhance downstream male engagement in HIV prevention., Methods: A discrete-choice experiment survey was conducted with 406 men, aged 18-24, in Cape Town, South Africa, to assess preferences for 5 LA-PrEP attributes with 2-4 pictorially-depicted levels: delivery form, duration, insertion location, soreness, and delivery facility. Latent class analysis was used to explore heterogeneity of preferences and estimate preference shares., Results: The median age was 21 (interquartile range 19-22), and 47% were men who have sex with men. Duration was the most important product attribute. Latent class analysis identified 3 classes: "duration-dominant decision makers" (46%) were the largest class, defined by significant preference for a longer duration product. "Comprehensive decision makers" (36%) had preferences shaped equally by multiple attributes and preferred implants. "Injection-dominant decision makers" (18%) had strong preference for injections (vs. implant) and were significantly more likely to be men who have sex with men. When estimating shares for a 2-month injection in the buttocks with mild soreness (HPTN regimen) vs. a 6-month implant (to arm) with moderate soreness (current target), 95% of "injection-dominant decision makers" would choose injections, whereas 79% and 63% of "duration-dominant decision makers" and "comprehensive decision makers" would choose implant., Conclusions: Young South African men indicated acceptability for LA-PrEP. Preferences were shaped mainly by duration, suggesting a sizeable market for implants, and underscoring the importance of product choice. Further research into men's acceptability of LA PrEP strategies to achieve engagement in these HIV prevention tools constitutes a priority., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Women with a BRCA1 or BRCA2 mutation have high lifetime risks of developing breast and ovarian cancer. The decision to embark on risk reduction strategies is a difficult and personal one. We surveyed an international group of women with BRCA mutations and measured choices and sequence of breast cancer risk reduction strategies., Methods: Women with a BRCA1/2 mutation and no previous cancer diagnosis were recruited from the US, Canada, the UK, Australia, and from a national advocacy group. Using an online survey, we asked about cancer-risk reduction preferences including for one of two hypothetical medicines, randomly assigned, and women's recommendations for a hypothetical woman (Susan, either a 25- or 36-year-old). Sunburst diagrams were generated to illustrate hierarchy of choices., Results: Among 598 respondents, mean age was 40.9 years (range 25-55 years). Timing of the survey was 4.8 years (mean) after learning their positive test result and 33% had risk-reducing bilateral salpingo-oophorectomy (RRBSO) and bilateral mastectomy (RRBM), while 19% had RRBSO only and 16% had RRBM only. Although 30% said they would take a hypothetical medicine, 6% reported taking a medicine resembling tamoxifen. Respondents were 1.5 times more likely to select a hypothetical medicine for risk reduction when Susan was 25 than when Susan was 36. Women assigned to 36-year-old Susan were more likely to choose a medicine if they had a family member diagnosed with breast cancer and personal experience taking tamoxifen., Conclusions: Women revealed a willingness to undergo surgeries to achieve largest reduction in breast cancer risk, although this would not be recommended for a younger woman in her 20s. The goal of achieving the highest degree of cancer risk reduction is the primary driver for women with BRCA1 or BRCA2 mutations in selecting an intervention and a sequence of interventions, regardless of whether it is non-surgical or surgical., Competing Interests: Competing interestsThis study was conducted by RTI Health Solutions under the direction of and funding by Amgen Inc., Thousand Oaks, California. CM is a current and JP is a former employee of RTI Health Solutions that were contracted by Amgen Inc. for the conduct of this study. AL was employed by Amgen at the time of the study and discloses salary and stock ownership. AL discloses current salary and stock ownership with AbbVie Inc. (North Chicago, Illinois) as of April 2019. GL has received research funding support from Amgen and has served on an Amgen Advisory Board. No other conflicts of interest are declared for remaining authors., (© The Author(s) 2020.)

Introduction: Existing biomedical HIV prevention options, though highly effective, present substantial adherence challenges. End-user input on early-stage design of new HIV prevention approaches is critical to yielding products that achieve high uptake and adherence. The iPrevent Study examined youths' preferences for key attributes of long-acting Pre-Exposure Prophylaxis (PrEP), with a focus on characteristics pertinent to product delivery alongside key modifiable product attributes., Methods: A discrete choice experiment was conducted with female and male youth aged 18 to 24 in two high-density communities in Cape Town, South Africa during the period July 2017 to January 2019. Sexually active, PrEP-naïve youth were recruited using population-based sampling; targeted sampling was used to enrol men who have sex with men (MSM). In a series of nine questions, participants were asked to choose between two hypothetical products composed of five attributes (form, dosing frequency, access, pain, insertion site). We used a random-parameters logit model to estimate preference weights and trade-offs among product alternatives. We examined differences across three subgroups: females, men who have sex with only women (MSW) and MSM., Results: A total of 807 participants (401 female) were enrolled with a median age of 21 years. Males included 190 MSM. Most youth had tested for HIV (95%) and reported being HIV-negative (91%). Across all groups, duration of effectiveness was the most important attribute, with strong preference for less frequent dosing. Injections were favoured over implants, though these preferences were strongest for females and MSM. Females preferred a product offered at a health clinic and disliked pharmacy access; all groups preferred the arm as the insertion site. Youth were willing to trade their preferred product form for longer duration., Conclusions: Youth indicated strong preferences for longer duration products. Each attribute nonetheless influenced preferences, offering insight into trade-offs that inform long-acting PrEP development., (© 2020 RTI International-non funded through US NIH grant award. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS society.)

As new female-initiated HIV prevention products enter development, it is crucial to incorporate women's preferences to ensure products will be desired, accepted, and used. A discrete-choice experiment was designed to assess the relative importance of six attributes to stated choice of a vaginally delivered HIV prevention product. Sexually active women in South Africa and Zimbabwe aged 18-30 were recruited from two samples: product-experienced women from a randomized trial of four vaginal placebo forms and product-naïve community members. In a tablet-administered survey, 395 women chose between two hypothetical products over eight choice sets. Efficacy was the most important, but there were identifiable preferences among other attributes. Women preferred a product that also prevented pregnancy and caused some wetness (p < 0.001). They disliked a daily-use product (p = 0.002) and insertion by finger (p = 0.002). Although efficacy drove preference, wetness, pregnancy prevention, and dosing regimen were influential to stated choice of a product, and women were willing to trade some level of efficacy to have other more desired attributes.

Purpose: Several gene therapy trials for Duchenne muscular dystrophy initiated in 2018. Trial decision making is complicated by non-curative, time-limited benefits; the progressive, fatal course; and high unmet needs. Here, caregivers and patients prioritize factors influencing decision making regarding participation in early-phase gene therapy trials., Methods: We conducted a best-worst scaling experiment among U.S. caregivers and adults with Duchenne (N = 274). Participants completed 11 choice sets, choosing features they cared about most and least when deciding whether to participate in a hypothetical gene therapy trial. We analyzed the data using sequential conditional logistic regression., Results: Participants prioritized improved muscle function in trial decision making. Concerns about participation limiting later use of gene transfer and editing were also important, as were improved lung and heart function. Low risk of death fell near the middle. Participants cared least about muscle biopsies and potential for randomization to placebo. Adults with Duchenne and caregivers of non-ambulatory children significantly prioritized improved lung function compared to caregivers of ambulatory children., Conclusion: Our data demonstrate prioritization of anticipated benefits and opportunity costs relative to potential harms and procedures in gene therapy trial decision making. Such data inform protocol development, education and advocacy efforts, and informed consent.

Background: Screening rates for colorectal cancer are below the Healthy People 2020 goal. There are several colorectal cancer screening tests that differ in terms of accuracy, recommended frequency, and administration. In this article, we compare how a set of personal characteristics correlates with preferences for colorectal cancer screening test attributes, past colorectal cancer screening behavior, and future colorectal cancer screening intentions., Methods: We conducted a discrete-choice experiment survey to assess relative preferences for attributes of colorectal cancer screening tests among adults aged 50-75 years in USA. We used a latent class logit model to identify classes of preferences and calculated willingness to pay for changes in test attributes. A set of personal characteristics were included in the latent class analysis and analyses of self-reported past screening behavior and self-assessed likelihood of future colorectal cancer screening., Results: Latent class analysis identified three types of respondents. Class 1 valued test accuracy, class 2 valued removing polyps and avoiding discomfort, and class 3 valued cost. Having had a prior colonoscopy and a higher income were predictors of the likelihood of future screening and membership in classes 1 and 2. Health insurance and a self-reported higher risk of developing colorectal cancer were associated with prior screening and higher future screening intentions, but not class membership., Conclusion: We identified distinct classes of preferences focusing on different test features and personal characteristics associated with reported behavior and intentions. Healthcare providers should engage in a careful assessment of patient preferences when recommending colorectal cancer test options to encourage colorectal cancer screening uptake.

Introduction: Understanding patient preferences for attributes of type 2 diabetes mellitus (T2DM) medications may help explain how the attributes differentially affect patient perceptions and behaviors. In this survey, we quantified the relative preferences among patients in Germany and Spain in separate analyses., Methods: A stated-preference, discrete-choice experiment (DCE) survey was designed to elicit preferences for T2DM treatment attributes among patients with self-reported T2DM and who reported being prescribed T2DM medication for > 2 years. Patients recruited from an online national consumer panel completed an online survey. The survey presented choices between eight pairs of hypothetical T2DM treatments defined by seven attributes: chance of reaching target hemoglobin A1c (HbA1c) level; reduced risk of serious heart attack or stroke; frequency of hypoglycemia; risk of gastrointestinal (GI) problems; weight change; mode of administration (oral or injectable); dosing frequency. Data were analyzed using random-parameters logit. Minimum acceptable benefit (MAB) was defined as the minimum increase in the probability of reaching target HbA1c for which respondents would accept less desirable levels of other attributes., Results: In Germany and Spain, 474 and 401 respondents completed the survey, respectively. DCE analysis showed that risk of GI problems was most important to German respondents. MAB analysis found that respondents would require a 56 percentage point increase in the probability of reaching their HbA1c target to offset a change from 0% to 30% risk of GI problems. For Spanish respondents, mode of administration was the most important attribute. These respondents would require a 59 percentage point increase in the probability of reaching their HbA1c target to offset moving from oral to injectable medications., Conclusions: Respondents in Germany and Spain were willing to trade efficacy for improvements in side effects and mode of administration. Given the variety of T2DM medications currently available, the results suggest that careful discussion about patient preferences could help improve patient satisfaction with T2DM treatment.

Purpose: Unaffected women who carry BRCA1 or BRCA2 mutations face difficult choices about reducing their breast cancer risk. Understanding their treatment preferences could help us improve patient counseling and inform drug trials. The objective was to explore preferences for various risk-reducing options among women with germline BRCA1/2 mutations using a discrete-choice experiment survey and to compare expressed preferences with actual behaviors., Methods: A discrete-choice experiment survey was designed wherein women choose between hypothetical treatments to reduce breast cancer risk. The hypothetical treatments were characterized by the extent of breast cancer risk reduction, treatment duration, impact on fertility, hormone levels, risk of uterine cancer, and ease and mode of administration. Data were analyzed using a random-parameters logit model. Women were also asked to express their preference between surgical and chemoprevention options and to report on their actual risk-reduction actions. Women aged 25-55 years with germline BRCA1/2 mutations who were unaffected with breast or ovarian cancer were recruited through research registries at five clinics and a patient advocacy group., Results: Between January 2015 and March 2016, 622 women completed the survey. Breast cancer risk reduction was the most important consideration expressed, followed by maintaining fertility. Among the subset of women who wished to have children in future, the ability to maintain fertility was the most important factor, followed by the extent of risk reduction. Many more women said they would take a chemoprevention drug than had actually taken chemoprevention., Conclusions: Women with BRCA1/2 mutations indicated strong preferences for breast cancer risk reduction and maintaining fertility. The expressed desire to have a safe chemoprevention drug available to them was not met by current chemoprevention options.

Purpose: This chapter reports estimates of consumers' preferences for plans to improve food safety., Design/methodology/approach: The plans are distinguished based on whether they address the ex ante risk of food borne illness or the ex post effects of the illness. They are also distinguished based on whether they focus on a public good--reducing risk of illness for all consumers or allowing individual households to reduce their private risks of contracting a food borne pathogen., Findings: Based on a National Survey conducted in 2007 using the Knowledge Network internet panel, our findings indicate consumers favor ex ante risk reductions and are willing to pay approximately $250 annually to reduce the risk of food borne illness. Moreover, they prefer private to public approaches and would not support efforts to reduce the severity of cases of illness over risk reductions., Originality/value: This study is the first research that allows a comparison of survey respondents' choices between public and private mechanisms for ex ante risk reductions.

Pathological events are well characterized in amyotrophic lateral sclerosis (ALS) mouse models, but review of the literature fails to identify a specific initiating event that precipitates disease pathology. There is now growing consensus in the field that axon and synapses are first cellular sites of degeneration, but controversy exists over whether axon and synapse loss is initiated autonomously at those sites or by pathology in the cell body, in nonneuronal cells or even in nonmotoneurons (MNs). Previous studies have identified pathological events in the mutant superoxide dismutase 1 (SOD1) models involving spinal cord, peripheral axons, neuromuscular junctions (NMJs), or muscle; however, few studies have systematically examined pathogenesis at multiple sites in the same study. We have performed ultrastructural examination of both central and peripheral components of the neuromuscular system in the SOD1(G93A) mouse model of ALS. Twenty percent of MNs undergo degeneration by P60, but NMJ innervation in fast fatigable muscles is reduced by 40% by P30. Gait alterations and muscle weakness were also found at P30. There was no change in axonal transport prior to initial NMJ denervation. Mitochondrial morphological changes are observed at P7 and become more prominent with disease progression. At P30 there was a significant decrease in excitatory axo-dendritic and axo-somatic synapses with an increase in C-type axo-somatic synapses. Our study examined early pathology in both peripheral and central neuromuscular system. The muscle denervation is associated with functional motor deficits and begins during the first postnatal month in SOD1(G93A) mice. Physiological dysfunction and pathology in the mitochondria of synapses and MN soma and dendrites occur, and disease onset in these animals begins more than 2 months earlier than originally thought. This information may be valuable for designing preclinical trials that are more likely to impact disease onset and progression.

Charcot first described amyotrophic lateral sclerosis (ALS) in 1869; however, its causes remain largely unknown and effective, long-term treatment strategies are not available. The first mouse model of ALS was developed after the identification of mutations in the superoxide dismutase 1 (SOD1) gene in 1993, and accordingly most of our knowledge of the etiology and pathogenesis of the disease comes from studies carried out using this animal model. Although numerous preclinical trials have been conducted in the mutant SOD1 mouse models, the results have been disappointing because they did not positively translate to clinical trials. One explanation may be that current understanding of when and where pathogenesis begins is insufficient to accurately guide preclinical trials. Further characterization of these early events may provide insight into disease onset, help in the discovery of presymptomatic diagnostic disease markers, and identify novel therapeutic targets. Here, we describe the rationale, approach, and methods for our extensive analysis of early changes that included an ultrastructural examination of central and peripheral components of the neuromuscular system in the SOD1(G93A) mouse and correlated these alterations with early muscle denervation, motor dysfunction, and motoneuron death. We also provide a discussion of published work to review what is known regarding early pathology in the SOD1 mouse model of ALS. The significance of this work is that we have examined early pathology simultaneously in both the spinal cord and peripheral neuromuscular system, and the results are presented in the companion paper (Part II, Results and Discussion). Our results provide evidence as to why a thorough characterization of animal models throughout the life span is critical for a strong foundation to design preclinical trials that may produce meaningful results.