Development of a novel shared decision making aid for primary immunodeficiency diseases.

Aim: To describe development of a shared decision making (SDM) aid in treating primary immunodeficiency diseases (PID) with immunoglobulin replacement therapy (IGRT). Materials & methods: Expert engagement and qualitative formative research informed development. IGRT administration features were prioritized using object-case best-worst scaling (BWS) methodology. The aid was assessed by US adults self-reporting PID and revised following interviews/mock treatment-choice discussions with immunologists. Results: Patients participating in interviews (n = 19) and mock treatment-choice discussions (n = 5) deemed the aid useful/accessible and supported the utility of BWS, with content and BWS exercises refined following participant feedback. Conclusion: Formative research led to an improved SDM aid/BWS exercise, and illustrated how the aid may improve treatment decision making. The aid may help less-experienced patients and facilitate efficient SDM.

Shared decision making and developing a decision aid Shared decision making happens when patients and doctors work together to choose treatment options based on a patient's concerns, preferences, goals and values, as well as medical information. The aim of this project was to develop a decision aid to help patients with primary immunodeficiency diseases (PID), in which part of the body's immune system is missing or doesn't function correctly. This will allow patients to better understand and communicate with the healthcare team on their preferences about immunoglobulin treatments, which fight infection by boosting antibody (protein) levels in the blood. The authors talked to experts and reviewed existing information to decide what treatment features the aid should consider. Patients with PID then tested the aid, and changes were made based on their feedback. Doctors specializing in treating PID also provided their feedback. The final aid was judged to be helpful and easy to use by the participants. With further research, this aid could be used to help inexperienced patients better understand what immunoglobulin treatment features are most important to them, and support shared decision-making between patients and their doctors.

The Patient Voice: Exploring Treatment Preferences in Participants with Mild Cognitive Concerns to Inform Regulatory Decision Making.

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.

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.

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.

Exploring Decisional Conflict With Measures of Numeracy and Optimism in a Stated Preference Survey.

OBJECTIVES: Low optimism and low numeracy are associated with difficulty or lack of participation in making treatment-related health care decisions. We investigated whether low optimism and low self-reported numeracy scores could help uncover evidence of decisional conflict in a discrete-choice experiment (DCE). METHODS: Preferences for a treatment to delay type 1 diabetes were elicited using a DCE among 1501 parents in the United States. Respondents chose between two hypothetical treatments or they could choose no treatment (opt out) in a series of choice questions. The survey included a measure of optimism and a measure of subjective numeracy. We used latent class analyses where membership probability was predicted by optimism and numeracy scores. RESULTS: Respondents with lower optimism scores had a higher probability of membership in a class with disordered preferences (P value for optimism coefficient = 0.032). Those with lower self-reported numeracy scores were more likely to be in a class with a strong preference for opting out and disordered preferences (P = 0.000) or a class with a preference for opting out and avoiding serious treatment-related risks (P = 0.015). CONCLUSIONS: If respondents with lower optimism and numeracy scores are more likely to choose to opt out or have disordered preferences in a DCE, it may indicate that they have difficulty completing choice tasks.

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.

Patient Preferences for Treating "OFF" Episodes in Parkinson's Disease: A Discrete Choice Experiment.

INTRODUCTION: Several on-demand treatments are available for management of "OFF" episodes in patients with Parkinson's disease (PD). We evaluated patients' preferences for features of theoretical on-demand treatment options. METHODS: In a discrete choice experiment, US adults with self-reported PD of ≥5 years, or <5 years with "OFF" episodes, taking oral carbidopa/levodopa, selected between pairs of theoretical on-demand treatments that varied by mode of administration (with and without mode-specific adverse events [AEs]), time to FULL "ON," duration of "ON," and out-of-pocket cost for a 30-day supply. Data were analyzed with a random parameters logit model; results were used to calculate relative importance of treatment attributes, preference shares, and willingness to pay. RESULTS: Among 300 respondents, 98% had "OFF" episodes. Across the range of attribute levels included in the survey, avoiding $90 cost was most important to respondents, followed by a preferable mode of administration with associated AEs and decreasing time to FULL "ON." Duration of "ON" was relatively less important. On average, respondents preferred a theoretical dissolvable sublingual film versus other theoretical treatments with alternative modes of administration. Respondents were willing to pay $28-$52 US dollars to switch from least- to more-preferred mode of administration with associated AEs, $58 to reach FULL "ON" in 15 versus 60 min, and $9 to increase duration of FULL "ON" from 1 to 2 h. CONCLUSION: Respondents with PD valued lower out-of-pocket cost and a sublingual mode of administration with its associated AEs when choosing an on-demand treatment for "OFF" episodes.

Parent and Pediatrician Preferences for Type 1 Diabetes Screening in the U.S.

OBJECTIVE: The purpose of this study was to use a discrete-choice experiment methodology to understand the relative importance of the attributes of screening tests for type 1 diabetes among parents and pediatricians in the U.S. RESEARCH DESIGN AND METHODS: Online surveys presented hypothetical screening test profiles from which respondents chose their preferred test profile. Survey attributes were based on likely screening test options and included the mode of administration, where and when the test was conducted, the type of education and monitoring available to lower the risk of diabetic ketoacidosis (DKA), and whether a treatment was available that would delay onset of insulin dependence. Data were analyzed using random-parameters logit models. RESULTS: Parents placed the highest relative importance on monitoring programs that could reduce the risk of DKA to 1%, followed by treatment to delay onset of insulin dependence by 1 or 2 years, and, finally, avoiding a $50 out-of-pocket cost. Pediatricians placed equal importance on monitoring programs that reduced a patient's risk of DKA to 1% and on avoiding a $50 out-of-pocket cost for the screening test, followed by the option of a treatment to delay the onset of insulin dependence. The mode of administration and location and timing of the screening were much less important to parents and pediatricians. CONCLUSIONS: Parents and pediatricians preferred screening tests that were accompanied by education and monitoring plans to reduce the risk of DKA, had available treatment to delay type 1 diabetes, and had lower out-of-pocket costs.

Preferences for Outcomes Among Adults with Type 1 Diabetes and Caregivers of Children with Type 1 Diabetes.

PURPOSE: Hemoglobin A1c (HbA1c) is the accepted measure of effectiveness for type 1 diabetes therapies. We investigated preferences for measures of diabetes control in addition to HbA1c among adults with type 1 diabetes and caregivers of children with type 1 diabetes. METHODS: Using discrete-choice experiment methodology, surveys for adults with type 1 diabetes and caregivers presented choices between hypothetical treatments described by six attributes with varying levels: HbA1c, time in optimal glucose range, weekly number and severity of hypoglycemic and hyperglycemic events, additional disease management time, and additional treatment cost. Choice data were analyzed using random-parameters logit. RESULTS: A total of 300 adults with type 1 diabetes and 400 caregivers completed the survey. Adults and caregivers placed the most importance on reducing hypoglycemic and hyperglycemic events. For adults, avoiding 1-5 mild-to-moderate hypoglycemic events (glucose 54-69 mg/dL)/week was five times more important than being a half-point above target HbA1c. Avoiding 1-5 hyperglycemic events (glucose >180 mg/dL)/week was seven times more important than being a half-point above target HbA1c. Additional time in optimal glucose range was as important as a reduction greater than a half-point in HbA1c. Avoiding hyperglycemic and hypoglycemic events was more important than all other outcomes for caregivers of younger children. Caregivers of children >12 years placed relatively more weight on avoiding hypoglycemic events <54 mg/dL than those with younger children and preferred avoiding additional costs. CONCLUSION: Adults with type 1 diabetes and caregivers prioritize controlling hypoglycemic and hyperglycemic events, including mild-to-moderate events. These preferences should be considered in drug development and regulatory decisions.

Assessing the impact of excluded attributes on choice in a discrete choice experiment using a follow-up question.

Health researchers design discrete choice experiments (DCEs) to elicit preferences over attributes that define treatments. A DCE can accommodate a limited number of attributes selected by researchers based on numerous factors (e.g., respondent comprehension, cognitive burden, and sample size). For situations where researchers want information about the possible impact of an attribute excluded from the DCE, we propose a method to use a question after the DCE. This follow-up question includes the attributes in the DCE with fixed levels and an additional attribute originally excluded from the DCE. The DCE data can be used to predict the probability that respondents would select one treatment profile over another without the additional attribute. Comparing the prediction to the percentage of the sample who selected each profile when it includes the additional attribute provides information on the potential impact of the additional attribute. We provide an example using data from a DCE on treatments for chronic lymphocytic leukemia. Cost was excluded from the DCE, but the survey included a follow-up question with two fixed treatment profiles, similar to two treatments currently on the market, and a cost for each. Preferences were sensitive to modest changes in cost, highlighting the importance of gathering this information.

Parent Preferences for Delaying Insulin Dependence in Children at Risk of Stage III Type 1 Diabetes.

Background: Autoantibody screening in type 1 diabetes (T1D) may reduce the chances of potentially life-threatening diabetic ketoacidosis (DKA) at diagnosis by allowing individuals at risk of progression to more actively monitor for and/or manage progression to insulin dependence. We investigated parents' preferences for treatments to delay the onset of insulin dependence in children who are at high risk of developing Stage III T1D. Methods: A web-based survey (n = 1501) was administered to a stratified sample of parents (children <18 years) in the United States from an online panel. Parents were told to hypothetically assume that their youngest child would become insulin dependent within 6 months or 2 years and were offered a series of choices between no treatment and two hypothetical treatments that would delay insulin dependence. Random-parameters logit analysis and maximum acceptable risks were used to evaluate the relative importance of treatment benefits and risks. Results: Most parents chose at least one active treatment (2% always chose monitoring only). For parents of children without T1D (n = 901), delaying insulin dependence and reducing the risk of long-term health complications and serious infection were the most important treatment attributes. In addition, parents of children with T1D (n = 600) also valued reducing the risk of hospitalizations due to DKA. Conclusions: When told to assume their child would develop Stage III T1D, most parents considered active treatments to delay progression. For medicines under development to delay insulin dependence in T1D, the preferences expressed in this survey provide guidance on acceptable benefit-risk trade-offs.

Patient Preferences for Preventive Migraine Treatments: A Discrete-Choice Experiment.

OBJECTIVE: To understand treatment preferences of people with migraine and the relative importance of improvements in efficacy and avoiding adverse events (AEs), such as cognition problems or weight gain. BACKGROUND: Current preventive migraine medicines are associated with poor adherence and tolerability. There is an unmet need for effective migraine-specific preventive treatments with fewer AEs. METHODS: In a web-based discrete-choice experiment survey, respondents who self-reported having ≥6 migraine days/month were offered choices between pairs of hypothetical preventive migraine medicines. Six attributes, each with 3 levels, defined the medicines: reduction in headache days per month (10%, 25%, or 50%), frequency of limitations with physical activities (none, 1-category improvement, or 2-category improvement), cognition problems (no problems, thinking problems, or memory problems), weight gain (none, 5% body weight gain, or 10% body weight gain), how the medicine is taken (daily oral pill, once-monthly injection, or twice-monthly injection), and monthly out-of-pocket cost ($5, $60, or $175). The attributes and levels were informed by clinician input, the clinical literature, and 2 focus groups. An experimental design was used to create the pairs of hypothetical medicines for the discrete-choice experiment questions. Random-parameters logit was used to estimate the relative importance of the medicine attributes, and the results were used to predict the percentage of respondents who would select one medicine profile over another and to calculate willingness to pay for changes in attribute levels. RESULTS: The sample included 300 respondents; 72% indicated that migraines make physical activities difficult all or most of the time, and 81% had taken a prescription medicine to prevent migraine in the last 6 months. Respondents reported having, on average, approximately 16 headache days per month. Among noncost attributes, respondents valued a change from a 10% reduction in migraine days to a 50% reduction more highly than avoiding the worst levels of AEs, but were willing to trade off efficacy for less-severe AEs. Avoiding memory problems was more important than avoiding thinking problems. Avoiding a 10% weight gain was more important than avoiding thinking and memory problems. Respondents preferred a once-monthly injection or daily pill to twice-monthly injection. Respondents, on average, were willing to pay $84 (95% confidence interval [CI], $64-$103) per month to avoid a 10% weight gain, $59 (95% CI, $42-$76) per month to avoid memory problems, $35 (95% CI, $20-$51) per month to avoid a 5% weight gain, and $32 (95% CI, $18-$46) per month to avoid thinking problems. CONCLUSIONS: A preventive migraine medicine with improved efficacy and AE profile and a favorable mode of administration would be valuable to migraine sufferers. Patients may be willing to trade off efficacy for better AE profiles. Clinicians should work with patients to select treatments that meet each patient's needs.

Comparison of US patient, rheumatologist, and dermatologist perceptions of psoriatic disease symptoms: results from the DISCONNECT study.

BACKGROUND: The perceived bother of skin and joint-related manifestations of psoriatic disease may differ among patients, rheumatologists, and dermatologists. This study identified and compared the patient and dermatologist/rheumatologist-perceived bother of psoriatic disease manifestations. METHODS: Online surveys were administered to patients with both psoriasis and psoriatic arthritis and to dermatologists and rheumatologists. Object-case best-worst scaling was used to identify the most and least bothersome items from a set of five items in a series of questions. Each item set was drawn from 20 items describing psoriatic disease skin and joint symptoms and impacts on daily activities. Survey responses were analyzed using random-parameters logit models for each surveyed group, yielding a relative-bother weight (RBW) for each item compared with joint pain, soreness, or tenderness. RESULTS: Surveys were completed by 200 patients, 150 dermatologists, and 150 rheumatologists. Patients and physicians agreed that joint pain, soreness, and tenderness are among the most bothersome manifestations of psoriatic disease (RBW 1.00). For patients, painful, inflamed, or broken skin (RBW 1.03) was more bothersome, while both rheumatologists and dermatologists considered painful skin much less bothersome (RBW 0.17 and 0.22, respectively) than joint pain. Relative to joint pain, rheumatologists were more likely to perceive other joint symptoms as bothersome, while dermatologists were more likely to perceive other skin symptoms as bothersome. CONCLUSIONS: This study has identified important areas of discordance both between patients and physicians and between rheumatologists and dermatologists about the relative bother of a comprehensive set of psoriatic disease symptoms and functional impacts. Both physician specialists should ask patients which manifestations of psoriatic disease are most bothersome to them, as these discussions may have important implications for drug and other patient management options.

Patient Preferences for Endobronchial Valve Treatment of Severe Emphysema.

Background: Patients with severe emphysema have limited treatment options. Little is known about patients' willingness to accept risks for new treatments that offer meaningful benefits. Methods: We determined treatment preferences of patients with severe emphysema using a web-based discrete-choice experiment survey. Respondents answered 9 questions that offered choices between 2 hypothetical interventional treatments or continuing current medical management. Variations in 5 attributes defined the 2 interventional treatments: improvement in ability to breathe and carry out day-to-day activities, frequency of hospitalized exacerbations, treatment type, risk of pneumothorax within 30 days of procedure, and risk of death within 3 months. Respondents were recruited through the COPD Foundation's COPD Patient-Powered Research Network and had a self-reported emphysema diagnosis and 2+ score on the modified Medical Research Council Dyspnea Scale. The relative importance of the attributes and the percentage of respondents who would select different treatment options was modeled using random-parameters logit. Results: Among 294 respondents, 51% always chose an interventional treatment option, while 19% always selected continued medical management. The most important change on average was moving from continued medical management (with no improvement in breathlessness) to an interventional treatment with improvement in breathlessness. The model predicted 71% of respondents would select a treatment option similar to removable endobronchial valve implants, 6% would select lung volume reduction surgery (LVRS), and 23% continued medical management. Conclusion: Patients with severe emphysema perceive that a procedure with risks and benefits similar to the Zephyr® endobronchial valve implants is desirable over continued medical management or LVRS.

Patients' priorities in selecting chronic lymphocytic leukemia treatments.

Currently, in the United States, 130 000 people live with chronic lymphocytic leukemia (CLL), and almost 20 000 new cases of CLL are diagnosed each year. Little is known about the value patients place upon the attributes of available CLL treatments, which vary in efficacy, side effects, and mode of administration. We used a discrete-choice experiment (DCE) to investigate patients' preferences for treatment attributes and the impact of out-of-pocket cost on patients' choices. DCE surveys pose a series of choices between hypothetical treatment options, each defined by a set of attributes, and the responses provide quantitative estimates of the average relative preferences for treatment attribute. Each hypothetical treatment in this survey was defined by 5 attributes with predefined levels for efficacy, adverse events, and mode administration. A patient advocacy organization recruited 384 patients with a self-reported physician diagnosis of CLL to complete the online survey. Respondents placed the highest relative importance on longer progression-free survival (PFS). However, the risk of adverse events also was important, as significant additional PFS was needed to offset patients' acceptance of worsening adverse events. A supplemental question with 2 treatments and varying costs was included to assess the impact of cost on choice. When costs were included, a large proportion of patients changed their choices between the 2 treatments. Given the available treatments and the high cost of some treatments, physicians may want to explore their patients' preferences for different treatment features, including benefit-risk tradeoffs and out-of-pocket cost, when selecting the best treatment strategies for patients.