The value of knowing: preferences for genetic testing to diagnose rare muscle diseases.

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.

Making Use of Technology to Improve Stated Preference Studies.

The interest in quantifying stated preferences for health and healthcare continues to grow, as does the technology available to support and improve health preference studies. Technological advancements in the last two decades have implications and opportunities for preference researchers designing, administering, analysing, interpreting and applying the results of stated preference surveys. In this paper, we summarise selected technologies and how these can benefit a preference study. We discuss empirical evaluations of the technology in preference research, with examples from health where possible. The technologies reviewed include serious games, virtual reality, eye tracking, innovative formats and decision aids with values clarification components. We conclude with a critical reflection on the benefits and limitations of implementing (often costly) technology alongside stated preference studies.

Preferences of healthcare providers in Switzerland for attributes of pediatric hexavalent vaccines: a discrete-choice experiment.

OBJECTIVE: To understand the preferences of healthcare providers (HCPs) in Switzerland for pediatric hexavalent vaccine attributes. METHODS: A discrete-choice experiment included a series of choices between 2 hypothetical pediatric hexavalent vaccines with varying attributes: device type (including preparation time and risk of dosage errors), proportion of infants seroprotected against Haemophilus influenzae type b (Hib) at 11-12 months (pre-booster), packaging size, years on the market, and the thermostability at room temperature. Odds ratios (ORs) and conditional relative attribute importance (CRAI) were calculated using random-parameters logit. RESULTS: HCPs (150 pediatricians and 40 nursing staff) in Switzerland were unlikely to choose a vaccine conferring 50% (OR 0.00; 95% CI 0.00-0.00) or 70% (OR 0.01; 95% CI 0.00-0.01) of infants with Hib seroprotection at 11-12 months (pre-booster) compared with a vaccine conferring 90% seroprotection. The odds of choosing a vaccine available on the market for more than 3 years were nearly 5 times the odds of choosing a vaccine available on the market for less than 1 year (OR 4.76; 95% CI 1.87-7.65). The odds of choosing a vaccine in a prefilled syringe were nearly 3 times the odds of choosing a reconstituted vaccine (OR 2.77; 95% CI 1.39-4.15), and the odds of choosing a vaccine with a smaller package size were nearly 2 times the odds of choosing a vaccine with larger package size (OR 1.89; 95% CI 1.23-2.55). HCPs were equally likely to choose vaccines that can stay at room temperature for 6 versus 3 days (OR 1.07; 95% CI 0.73-1.42). According to CRAI, the most important attribute was Hib seroprotection, followed by years on the market, device type, and packaging size. CONCLUSION: Hib seroprotection at 11-12 months was the most important hexavalent vaccine attribute to HCPs in this study.

Adult, adolescent, and caregiver preferences for attributes of topical treatments for mild-to-moderate atopic dermatitis: a discrete-choice experiment.

Purpose: Topical treatments for mild-to-moderate (MM) atopic dermatitis (AD) include emollients, corticosteroids, calcineurin inhibitors, a Janus kinase inhibitor, and a phosphodiesterase 4 inhibitor, which differ in multiple ways. This study aimed to quantify the conditional relative importance (CRI) of attributes of topical treatments for MM AD among adult and adolescent patients and caregivers of children with MM AD.Materials and methods: A discrete-choice experiment (DCE) survey was administered to US adults and adolescents with MM AD and caregivers of children with MM AD. Each choice task comprised 2 hypothetical topical treatments characterized by efficacy, adverse events, vehicle, and application frequency. Data were analyzed using a random-parameters logit model to calculate the CRI of each attribute.Results and conclusions: 300 adults, 331 adolescents, and 330 caregivers completed the DCE. Avoiding changes in skin color (CRI 29.0) and time until itch improves (26.6) were most important to adults, followed by time until clear/almost clear skin (17.8). Application frequency (3.0) did not have a statistically significant impact on adults' choices. Adolescents were less concerned about changes in skin color than adults or caregivers; caregivers were less concerned about time until clear/almost clear skin than patients. Physicians should consider age-relevant aspects of preferences in treatment discussions with patients and caregivers.

A discrete choice experiment to quantify the influence of trial features on the decision to participate in cystic fibrosis trials.

BACKGROUND: Patient-centred trial design optimises recruitment and retention, reduces trial failure rates and increases the diversity of trial cohorts. This allows safe and effective treatments to reach clinic more quickly. To achieve this, patients' views must be incorporated into trial design. METHODS: A discrete choice experiment was used to quantify preferences of pwCF for trials features; medicine type, trial location, stipend, washout, drug access on trial completion and trial design. Respondents were presented pairs of hypothetical trial scenarios with different level combinations assigned through experimental design. Respondents were asked to pick their preferred option or decline both. The cross-sectional data were explored using a Random Parameters Logit model. RESULTS: We received 207 eligible responses between Oct2020-Jan2021. The strongest influence on the decision to participate was trial location; pwCF favour participation at their usual clinical centre. Greater travel distances made respondents less willing to participate. Post-trial drug access ranked second. pwCF would rather participate in modulator trials than trials of other drugs. In general, pwCF did not favour a washout period, but were more prepared to washout non-modulators than modulators. Stipend provision was not ranked highly, but higher stipends increased intention to participate. Trial design (placebo vs open-label) had minimal influence on the decision to participate. There are complex interactions between placebos and washouts. CONCLUSIONS: We used quantitative methods to systematically elicit preferences of pwCF for clinical trials' features. We explore the relevance of our findings to trial design and delivery in the current CF trials landscape.

Adolescent and caregiver preferences for juvenile idiopathic arthritis treatment: a discrete-choice experiment.

BACKGROUND: This study aimed to elicit and quantify preferences for treatments for juvenile idiopathic arthritis (JIA). METHODS: We conducted a discrete-choice experiment among adolescents with JIA in the United States (US) (n = 197) and United Kingdom (UK) (n = 100) and caregivers of children with JIA in the US (n = 207) and UK (n = 200). In a series of questions, respondents chose between experimentally designed profiles for hypothetical JIA treatments that varied in efficacy (symptom control; time until next flare-up), side effects (stomachache, nausea, and vomiting; headaches), mode and frequency of administration, and the need for combination therapy. Using a random-parameters logit model, we estimated preference weights for these attributes, from which we derived their conditional relative importance. RESULTS: On average, respondents preferred greater symptom control; greater time until the next flare-up; less stomachache, nausea, and vomiting; and fewer headaches. However, adolescents and caregivers in the US were generally indifferent across varying modes and frequencies of administration. UK adolescents and caregivers preferred tablets, syrup, or injections to intravenous infusions. US and UK adolescents were indifferent between treatment with monotherapy or combination therapy; caregivers in the UK preferred treatment with combination therapy to monotherapy. Subgroup analysis showed preference heterogeneity across characteristics including gender, treatment experience, and symptom experience in both adolescents and caregivers. CONCLUSIONS: Improved symptom control, prolonged time to next flare-up, and avoidance of adverse events such as headache, stomachache, nausea, and vomiting are desirable characteristics of treatment regimens for adolescents with JIA and their caregivers.

Patients' willingness to accept adverse event and cost tradeoffs from oral nicotinamide for reduced risk of non-melanoma skin cancer.

BACKGROUND: Non-immunosuppressed patients with a history of multiple non-melanoma skin cancers (NMSCs) taking oral nicotinamide supplementation experienced a 23% decrease in annual NMSC risk in a randomized clinical trial. Patient preferences for risks and costs associated with nicotinamide are unknown. OBJECTIVES: To understand how patients prioritize NMSC reduction, infection risk, and cost. METHODS: A sample of adults with history of ≥2 NMSC within the past five years undergoing Mohs procedure completed a discrete-choice experiment comprising two hypothetical treatments-characterized by varying reductions in NMSC incidence, increased severe infection risk, and cost-and no treatment. The data were analyzed with random-parameters logit models. RESULTS: A total of 203 subjects (mean age 71.5 years, 65.5% males) participated. For a 23% annual reduction in NMSC incidence, a 26% [95% CI: 8%-45%] annual increase in severe infection risk and $8 [95% CI: $2-14] monthly cost was acceptable. Outcomes across analyzed subgroups (before vs. during COVID pandemic, site of interview, less vs. more prior NMSCs) were similar. CONCLUSIONS: Patients were unwilling to accept high severe infection risks to obtain the reduction in NMSC incidence observed in a nicotinamide trial, suggesting that routinely recommending nicotinamide may run counter to some patients' preferences.

A systematic review to identify and collate factors influencing patient journeys through clinical trials.

Patient-centred trial design and delivery; improves recruitment and retention; increases participant satisfaction; encourages participation by a more representative cohort; and allows researchers to better meet participants' needs. Research in this area mostly focusses on narrow facets of trial participation. We aimed to systematically identify the breadth of patient-centred factors influencing participation and engagement in trials, and collate them into a framework. Through this we hoped to assist researchers to identify factors that could improve patient-centred trial design and delivery. Robust qualitative and mixed methods systematic reviews are becoming increasingly common in health research. The protocol for this review was prospectively registered on PROSPERO, CRD42020184886. We used the SPIDER (Sample, Phenomenon of Interest, Design, Evaluation, Research Type) framework as a standardised systematic search strategy tool. 3 databases were searched as well as references checking, and thematic synthesis was conducted. Screening agreement was performed and code and theme checking were conducted by 2 independent researchers. Data were drawn from 285 peer-reviewed articles. 300 discrete factors were identified, and sorted into 13 themes and subthemes. The full catalogue of factors is included in the Supplementary Material. A summary framework is included in the body of the article. This paper focusses on outlining common ground that themes share, highlighting critical features, and exploring interesting points from the data. Through this, we hope researchers from multiple specialities may be better able to meet patients' needs, protect patients' psychosocial wellbeing, and optimise trial recruitment and retention, with direct positive impact on research time and cost efficiency.

Risk thresholds for patients to switch between daily tablets and biweekly infusions in second-line treatment for advanced hepatocellular carcinoma: a patient preference study.

BACKGROUND: Historically, high hepatocellular carcinoma (HCC)-related mortality has been, in part, due to lack of effective therapies; however, several systemic therapies have been recently approved for HCC treatment, including regorafenib and ramucirumab. These two treatments utilize different routes of administration (four daily tablets and biweekly intravenous infusions, respectively) and have different risks of adverse events (AEs). However, we lack data on patient preferences in balancing the route of administration and risk of AEs in patients with HCC. We aimed to determine patient preferences and trade-offs for second-line treatment in patients with HCC.  METHODS: Patients with advanced or metastatic HCC were recruited through their physicians for this study. Patient preferences were assessed by using a modified threshold technique (TT) design in which respondents were asked two direct-elicitation questions before (assuming same safety and efficacy and only varying mode of administration) and after (incorporating the safety profiles of ramucirumab and regorafenib) the TT series on seven risks of clinically relevant AEs. RESULTS: In total, of the 157 patients recruited by their physicians, 150 were eligible and consented to participate. In the first elicitation question (assuming risk and efficacy were equivalent), 61.3% of patients preferred daily tablets. However, 76.7% of patients preferred the biweekly infusion when the safety profiles of the two available second-line therapies were included. The TT analysis confirmed that preferences for oral administration were not strong enough to balance out the risk of AEs that differentiate the two therapies. DISCUSSION: We found that when patients were asked to choose between a daily, oral medication and a biweekly IV medication for HCC, they were more likely to choose a daily, oral medication if efficacy and safety profiles were the same. However, when risks of AEs representing the safety profiles of two currently available second-line treatments were introduced in a second direct-elicitation question, respondents often selected an IV administration with a safety profile similar to ramucirumab, rather than oral tablets with a safety profile similar to regorafenib. Our findings indicate that the risk profile of a second-line treatment for HCC may be more important than the mode of administration to patients.

Travelers' preferences for tick-borne encephalitis vaccination.

BACKGROUND: This study aimed to quantify preferences and risk tolerance for a tick-borne encephalitis (TBE) vaccination. RESEARCH DESIGN AND METHODS: A stated-preference survey instrument was administered to international travelers living in the United States to elicit preferences for a no-cost TBE vaccine when planning an international trip, conditional upon four different qualitative levels of endemic TBE risk. RESULTS: The likelihood of choosing the vaccine increased with a destination's level of endemic risk. Most respondents (94%) would choose to receive the vaccine at the highest risk level presented in the survey (i.e. when multiple TBE cases among humans are reported year after year); 6% of the sample would choose not to receive the vaccine at any risk level. Respondents who engage in outdoor activities were twice as likely as the average respondent to choose vaccination rather than opting out of vaccination, and were one-third more likely than the average respondent to choose to receive the vaccine at the lowest risk level. CONCLUSIONS: Respondents were highly interested in a TBE vaccine, assuming no cost, and most were willing to be vaccinated at all qualitative TBE risk levels. Respondents who participated in outdoor activities were more likely than the average respondent to choose the vaccine.

Considerations Around Coding the Membership Probability Function in a Latent Class Analysis: Renewed Insights.

This technical note discusses how dummy and effects coding of categorical respondent characteristics in a class membership probability function should be interpreted by researchers employing a latent class analysis to explore preference heterogeneity in a discrete-choice experiment. Previous work highlighted issues arising from such coding when interpreting an alternative specific constant that represents an opt-out alternative or current situation in a discrete-choice experiment and did not fully address how this coding impacts the interpretation of parameters resulting from the membership probability function in a latent class analysis. Although latent class membership probability could be predicted separately for each respondent or subgroup of respondents, conclusions are often drawn directly from the model estimation using the full sample, which requires correctly interpreting the estimated parameters. In these cases, the misinterpretation that may arise if the problem is ignored could impact the policy conclusions and recommendations drawn based on the discrete-choice experiment results. This note provides an example comparing dummy and effects coding used to model respondent characteristics in the membership probability function in a discrete-choice experiment aimed to explore preferences for the treatment of chronic pain in the USA.

Accounting for Preference Heterogeneity in Discrete-Choice Experiments: An ISPOR Special Interest Group Report.

OBJECTIVES: Discrete choice experiments (DCEs) are increasingly used to elicit preferences for health and healthcare. Although many applications assume preferences are homogenous, there is a growing portfolio of methods to understand both explained (because of observed factors) and unexplained (latent) heterogeneity. Nevertheless, the selection of analytical methods can be challenging and little guidance is available. This study aimed to determine the state of practice in accounting for preference heterogeneity in the analysis of health-related DCEs, including the views and experiences of health preference researchers and an overview of the tools that are commonly used to elicit preferences. METHODS: An online survey was developed and distributed among health preference researchers and nonhealth method experts, and a systematic review of the DCE literature in health was undertaken to explore the analytical methods used and summarize trends. RESULTS: Most respondents (n = 59 of 70, 84%) agreed that accounting for preference heterogeneity provides a richer understanding of the data. Nevertheless, there was disagreement on how to account for heterogeneity; most (n = 60, 85%) stated that more guidance was needed. Notably, the majority (n = 41, 58%) raised concern about the increasing complexity of analytical methods. Of the 342 studies included in the review, half (n = 175, 51%) used a mixed logit with continuous distributions for the parameters, and a third (n = 110, 32%) used a latent class model. CONCLUSIONS: Although there is agreement about the importance of accounting for preference heterogeneity, there are noticeable disagreements and concerns about best practices, resulting in a clear need for further analytical guidance.

Implementation of personalised medicine policies in mental healthcare: results from a stated preference study in the UK.

BACKGROUND: Public support for the implementation of personalised medicine policies (PMPs) within routine care is important owing to the high financial costs involved and the potential for redirection of resources from other services. AIMS: We aimed to determine the attributes of a PMP most likely to elicit public support for implementation. We also aimed to determine whether such support differed between a depression PMP and one for cystic fibrosis. METHOD: In a discrete-choice experiment, paired vignettes illustrating both the current model of care (CMoC) and a hypothetical PMP for either depression or cystic fibrosis were presented to a representative sample of the UK public (n = 2804). Each vignette integrated varying attributes, including anticipated therapeutic benefit over CMoC, and the annual cost to the taxpayer. Respondents were invited to express their preference for either the PMP or CMoC within each pair. RESULTS: The financial cost was the most important attribute influencing public support for PMPs. Respondents favoured PMP implementation where it benefited a higher proportion of patients or was anticipated to be more effective than CMoC. A reduction in services for non-eligible patients reduced the likelihood of support for PMPs. Respondents were more willing to fund PMPs for cystic fibrosis than for depression. CONCLUSIONS: Cost is a significant factor in the public's support for PMPs, but essential caveats, such as protection for services available to PMP-ineligible patients, may also apply. Further research should explore the factors contributing to condition-specific nuances in public support for PMPs.

Quantifying patient preferences for systemic atopic dermatitis treatments using a discrete-choice experiment.

OBJECTIVES: To identify meaningful treatment attributes and quantify patient preferences for attributes of systemic atopic dermatitis (AD) treatments. MATERIALS AND METHODS: Qualitative interviews were conducted with adults with moderate-to-severe AD (N = 21) to identify AD treatment attributes that patients consider most important and inform attribute selection for an online discrete-choice experiment (DCE) survey administered to patients in the United States with moderate-to-severe AD. Participants identified probability of clear/almost clear skin at 16 weeks, time to itch relief, mode of administration, and safety risks as very important. DCE data were analyzed using a random-parameters logit model to estimate the relative importance of treatment attributes and maximum acceptable risk. RESULTS: A total of 320 respondents completed the DCE survey (74% female; mean age, 35 years). Annual risk of malignancy was the most important attribute, followed by mode of administration, probability of clear skin at 16 weeks, and time to onset of itch relief. Respondents preferred daily oral treatment over injectable treatment. Respondents were willing to accept increases in adverse event risks for improvements in efficacy and mode of administration. CONCLUSION: The findings of this study can help inform joint patient-physician decision making in managing moderate-to-severe AD.

Impact of clinical and demographic characteristics on patient preferences for psoriasis treatment features: Results from a discrete-choice experiment in a multicountry study.

OBJECTIVES: This study aimed to elicit preferences for psoriasis treatment features and to test for preference heterogeneity across groups of respondents. MATERIALS AND METHODS: A discrete-choice experiment was employed to elicit preferences of patients with plaque psoriasis in multiple countries. The survey instrument included a series of choice questions between three hypothetical treatments, each characterized by varying levels of six attributes (namely, lesion reduction, risk of impairing side effects, time to reach results, mode and frequency of administration, itching reduction, and side effects). Random parameters logit was used to model the data. Results were compared across a total of 18 subgroup sets. RESULTS: The data analysis from 1,123 respondents showed that, on average, respondents receive more utility gain from higher levels of lesion reduction and lower risks of impairing side effects than changes in other attributes included in the study. Systematic differences were detected for 13 sets; the most pronounced differences were observed based on disease severity, nail psoriasis, biologic experience, and quality-of-life scores. CONCLUSION: These many sources of preference heterogeneity identified by our analysis suggest that to improve patient satisfaction and, probably, adherence and persistence, clinicians should discuss options with patients when prescribing their treatment.

Exploring determinants of psoriasis patients' treatment choices: a discrete-choice experiment study in the United States and Germany.

BACKGROUND: Biologic psoriasis treatments are differentiated by efficacy, side effects, and other attributes. OBJECTIVE: Determine attributes of biologic psoriasis treatments that drive patients' treatment choices. METHODS: Respondents (USA: n = 300; Germany: n = 300) with moderate-to-severe psoriasis completed a discrete-choice-experiment survey, choosing between hypothetical treatments characterized by attributes with varying levels: chance of clear skin after 1 year, number of first-year treatments, first-year risks of mild-to-moderate injection site reaction (ISR) and serious infection, and years of proven efficacy/safety. RESULTS: U.S. respondents most valued clear skin (conditional relative importance, 1.88; p < .05). While other attributes were of generally equivalent importance, ISR risk outweighed serious-infection risk (1.06 vs. 0.70; p < .05). German respondents placed greatest importance on ISR risk (1.61; p < .05) and clear skin (1.49; p < .05). LIMITATIONS: Respondents evaluated hypothetical treatments and were recruited from web panels. CONCLUSIONS: Clear skin and ISR risk are stronger drivers of treatment choice than injection frequency and infection risk.

Exploring patient preference heterogeneity for pharmacological treatments for chronic pain: A latent class analysis.

BACKGROUND: Several pharmaceutical treatments for chronic pain caused by osteoarthritis (OA) and chronic low back pain (CLBP) are available or currently under development, each associated with different adverse events (AEs) and efficacy profiles. It is therefore important to understand what trade-offs patients are willing to make when choosing between treatments. METHODS: A discrete-choice experiment (DCE) was conducted with 437 adults with chronic pain caused by OA and/or CLBP. Respondents were presented with a series of scenarios and asked to choose between pairs of hypothetical treatments, each defined by six attributes: level of symptom control; risks of heart attack, rapidly progressive osteoarthritis and dependency; frequency and mode of administration and cost. Attributes were based on known profiles of oral nonsteroidal anti-inflammatory drugs, opioids and injected nerve growth factor inhibitors, the last of which were under clinical development at the time of the study. Data were analysed using a latent class (LC) model to explore preference heterogeneity. RESULTS: Overall, respondents considered improving symptom control and reducing risk of physical dependency to be the most important attributes. The LC analysis identified four participant classes: an 'efficacy-focused' class (33.7%), a 'cost-averse' class (29.4%), a 'physical-dependence-averse' class (19.6%) and a 'needle-averse' class (17.3%). Subgroup membership was incompletely predicted by participant age and their responses to comprehension questions. CONCLUSIONS: Preference heterogeneity across respondents indicates a need for a personalized approach to offering treatment options. Symptom improvement, cost, physical dependence and route of administration might be important to different patients. SIGNIFICANCE: Multiple treatment options that differ substantially in terms of efficacy and adverse events are available for the management of chronic pain. With a growing emphasis on a patient-centred care model that incorporates patients' priorities and values into treatment decisions, there is a need to understand how individuals with chronic musculoskeletal pain balance the benefits and risks of treatment and how treatment priorities vary among individuals. This study was designed to identify patient preferences for different characteristics of treatments for the management of chronic pain and to investigate how preferences differ among respondents.

A General Public Study on Preferences and Welfare Impacts of Antimicrobial Resistance in the United Kingdom.

BACKGROUND: Antibiotics have led to considerable increases in life expectancy. However, over time, antimicrobial resistance has accelerated and is now a significant global public health concern. Understanding societal preferences for the use of antibiotics as well as eliciting the willingness to pay for future research is crucial. OBJECTIVE: To investigate preferences for different strategies to optimize antibiotic use and to understand the willingness to pay for future research in antimicrobial resistance and antimicrobial drug development. METHODS: A discrete-choice experiment was administered to a sample of the UK general population. Respondents were asked to make nine choices, each offering three options-two hypothetical "doctor and antibiotics" and one "no doctor-no antibiotics"-defined by five attributes: treatment, days needed to recover, risk of bacterial infection that needs antibiotics, risk of common side effects, and risk of antimicrobial resistance by 2050. Data were analyzed using random parameters logit models. A double-bounded contingent valuation was also included in the survey to explore the willingness to pay for policies to contain antimicrobial resistance. RESULTS: Among the 2579 respondents who completed the survey, 1151 always selected "no doctor-no antibiotics" and 57 never varied their choices; therefore, 1371 responses were used in the analysis. Risk of antimicrobial resistance by 2050 was the most important attribute and the "treatment" was the least important attribute, although this was sensitive to a higher risk of bacterial infection. The aggregate annual willingness to pay for containing antimicrobial resistance was approximately £8.35 billion (~£5-£10 billion). CONCLUSIONS: The antimicrobial resistance risk is relevant and important to the general public. The high willingness to pay suggests that large investments in policies or interventions to combat antimicrobial resistance are justified.

Relative importance of clinical outcomes and safety risks of antiseizure medication monotherapy for patients and physicians: Discrete choice experiment eliciting preferences in real-world study "VOTE".

OBJECTIVE: This study was undertaken to elicit patients' preferences for attributes characterizing antiseizure medication (ASM) monotherapy options before treatment consultation, and to explore the trade-offs patients consider between treatment efficacy and risks of side effects. Further objectives were to explore how treatment consultation may affect patient preferences, to elicit physicians' preferences in selecting treatment, and to compare patient and physician preferences for treatment. METHODS: This prospective, observational study (EP0076; VOTE) included adults with focal seizures requiring a change in their ASM monotherapy. Patients completed a discrete choice experiment (DCE) survey before and after treatment consultation. Physicians completed a similar survey after the consultation. The DCE comprised 12 choices between two hypothetical treatments defined by seven attributes. The conditional relative importance of each attribute was calculated. RESULTS: Three hundred ten patients (mean [SD] age = 46.8 [18.3] years, 52.3% female) were enrolled from eight European countries, of whom 305 completed the survey before consultation and 273 completed the survey before and after consultation. Overall, this preference study in patients who intended to receive a new ASM monotherapy suggests that patient preferences were ordered as expected, with better outcomes being preferred to worse outcomes; patients preferred a higher chance of seizure freedom, lower risk of developing clinical depression, and fewer severe adverse events; avoiding moderate-to-severe "trouble thinking clearly" was more important than avoiding any other side effect. There were qualitative differences in what patients and physicians considered to be the most important aspects of treatment for patients; compared with patients, physicians had a qualitatively stronger preference for greater chance of seizure freedom and avoiding personality changes. Patients' preference weights were qualitatively similar before and after treatment consultation. SIGNIFICANCE: For patients, seizure freedom and avoiding trouble thinking clearly were the most important treatment attributes. Physicians and patients may differ in the emphasis they place on specific attributes.

CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma: physician preferences trading off benefits, risks and time to infusion.

Aims: We evaluated physicians' willingness to trade-off benefits, risks and time to infusion for CAR T-cell therapy for relapsed or refractory diffuse large B-cell lymphoma. Materials & methods: In a discrete-choice experiment survey, 150 US oncologists/hematologists chose between two hypothetical CAR T-cell treatments defined by six attributes. Results: Decreasing time to infusion from 113 to 16 days yielded the greatest change in preference weight (1.91). Physicians were willing to accept a >20% increase in risk of severe cytokine release syndrome and 15% increase in risk of severe neurological events in exchange for an increase in the probability of overall survival at 24 months from 40 to 55%. Conclusion: Physicians value reducing time to infusion and will accept incremental increases in serious adverse event risks to gain survival improvements.

Lay abstract CAR-T therapy is a treatment option for patients with diffuse large B-cell lymphoma that has not responded to at least two other kinds of treatments. CAR-T therapies are manufactured from a patient's white blood cells, modified to attack lymphoma cells. A CAR-T therapy takes time to manufacture after these cells are collected. CAR-T therapies can result in the reduction or disappearance of lymphoma tumors and can increase the chances of survival, but also cause serious side effects for a few patients. One of these is cytokine release syndrome (CRS), in which high levels of inflammation throughout the body may cause fever, heart problems or difficulty breathing. Another is the development of temporary but serious neurological problems such as confusion, seizures and memory problems. To understand how important physicians consider certain features of CAR-T therapies to be when deciding whether to recommend them, we asked physicians to choose between two treatment options resembling CAR-T therapies in a series of questions, with the CAR-T features varying in each question. Their answers indicated whether disappearance of tumors, a patient's chances of survival after 1 and 2 years of treatment, manufacturing time, or the risk of CRS or neurological problems was the most important factor. Physicians most wanted to reduce manufacturing time from 113 to 16 days, but also were willing to accept a >20% increase in risk of severe CRS and a 15% increase in risk of severe neurological events to increase a patient's chance of survival from 40 to 55% at 2 years.