Using Patient Preferences in Health Technology Assessment: Evaluating Quality-Adjusted Survival Equivalents (QASE) for the Quantification of Non-health Benefits.

Interest in using patient preference (PP) data alongside traditional economic models in health technology assessment (HTA) is growing, including using PP data to quantify non-health benefits. However, this is limited by a lack of standardised methods. In this article, we describe a method for using discrete choice experiment (DCE) data to estimate the value of non-health benefits in terms of quality-adjusted survival equivalence (QASE), which is consistent with the concept of value prevalent among HTA agencies. We describe how PP data can be used to estimate QASE, assess the ability to test the face-validity of QASE estimates of changes in mode of administration calculated from five published DCE oncology studies and review the methodological and normative considerations associated with using QASE to support HTA. We conclude that QASE may have some methodological advantages over alternative methods, but this requires DCEs to estimate second-order effects between length and quality of life. In addition, empirical work has yet to be undertaken to substantiate this advantage and demonstrate the validity of QASE. Further work is also required to align QASE with normative objectives of HTA agencies. Estimating QASE would also have implications for the conduct of DCEs, including standardising and defining more clear attribute definitions.

Patients' Preferences for Systemic Lupus Erythematosus Treatments-A Discrete Choice Experiment.

BACKGROUND: Symptoms of systemic lupus erythematosus (SLE) vary between patients, but those of increased disease activity typically include musculoskeletal and mucocutaneous manifestations such as joint pain, swelling, and rashes. Several treatment options are available to patients with SLE with variable efficacy. Many treatments, especially corticosteroids, cause unwanted side effects, although little is currently known about patients' preferences for treatments of SLE. OBJECTIVE: We aimed to identify which attributes of SLE treatment are valued by patients and to quantify their relative importance. METHODS: Adult participants with moderate-to-severe SLE were asked to make a series of choices between two hypothetical treatments in an online discrete choice experiment (DCE). A latent class model (LCL) was estimated to analyze choice data. Relative attribute importance (RAI) was calculated to determine the importance of each attribute to participants. RESULTS: A total of 342 participants from the USA completed the survey. A three-class LCL model was found to have the best fit. Class 1 (non-attenders) had non-significant preferences across all attributes. To achieve a better fit, a constrained LCL (cLCL) model was run with the two remaining classes. The most important attributes for participants in class 2 (benefit-seekers) were joint pain (RAI = 32.0%), non-joint pain (RAI = 21.8%), fatigue (RAI = 20.1%), and skin rashes and itching (RAI = 19.1%). The most important attributes for participants in class 3 (risk-avoiders) were risk of non-severe side effects from corticosteroids (RAI = 28.4%), risk of severe side effects from corticosteroids (RAI = 21.4%), and the risk of infections (RAI = 19.2%). Risk-avoiders were more likely to have been diagnosed with SLE for a longer period (>1 year) and were more likely to have experience with oral corticosteroids. CONCLUSIONS: SLE patients fall into two groups with distinct preferences: benefit-seekers, who prioritize reducing the impact of disease symptoms, and risk-avoiders, who prioritize avoiding treatment risks. The implication of this finding will depend on the reasons for these differences, which warrant further research. Our study suggests that these differences arise due to the impact of disease and treatment experience on preferences. If so, well-informed patients may not be willing to tolerate the risks associated with oral corticosteroids in exchange for their benefits.

Patient Preferences for Treatment of Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Bladder Cancer: A Cross-country Choice Experiment.

Background: Patients with non-muscle-invasive bladder cancer (NMIBC) that is unresponsive to bacillus Calmette-Guérin (BCG) immunotherapy face a difficult choice. Immediate radical cystectomy (RC) is effective but might represent overtreatment. Continuing bladder preservation with medical therapy is an alternative, but it risks progression to muscle-invasive bladder cancer (MIBC) and a reduction in survival. Objective: To understand the trade-offs patients are willing to make in selecting treatments for BCG-unresponsive NMIBC. Design setting and participants: Adults with NMIBC from the UK, France, Germany, and Canada who reported current receipt of BCG, disease unresponsive to BCG, or receipt of RC in the previous 12 mo after failure of BCG were recruited to participate in an online choice experiment. Patients were asked to make repeated choices between two hypothetical medical treatments and the option to undergo immediate RC. The medical treatments required trade-offs between the time to RC, the mode and frequency of administration, the risk of experiencing serious side effects, and the risk of disease progression. Outcome measurements and statistical analysis: Error component logit models were used to calculate relative attribute importance (RAI) scores as the maximum percentage contribution to a preference and acceptable benefit-risk trade-offs. Results and limitations: Most of the 107 participants (average age 63 yr) never selected RC (89%) as their preferred option in the choice experiment. Preferences were most affected by time to RC (RAI 55%), followed by risk of progressing to MIBC (RAI 25%), medication administration (RAI 12%), and the risk of serious side effects (RAI 8%). To increase the time to RC from 1 yr to 6 yr, patients accepted a 43.8% increase in the risk of progression and a 66.1% increase in the risk of serious side effects. Conclusions: Patients with BCG-treated NMIBC valued bladder-sparing treatments and were willing to make substantial benefit-risk trade-offs to delay RC. Patient summary: Adults with bladder cancer not invading the bladder muscle completed an online experiment in which they chose between hypothetical medications and bladder removal. The results show that patients would be willing to accept different risks associated with medications to delay bladder removal. Patients considered disease progression the most important risk of medicinal treatment.

Current Health State Affected Patient Preferences More Than Disease Status: A Discrete Choice Experiment in Multiple Myeloma.

OBJECTIVES: To examine how disease status and current health state influence treatment preferences of patients with multiple myeloma (MM). METHODS: Participants with MM from France, Germany, and the United Kingdom completed a web-based survey that included a discrete choice experiment (DCE) and EQ-5D assessment. The DCE elicited preferences for 8 attributes: increased life expectancy, increased time to relapse, pain, fatigue, risk of infection, administration (route and duration), frequency of administration, and monitoring. Multinomial logit models were used to analyze DCE preference data and to calculate life expectancy trade-offs. RESULTS: Three hundred participants with MM (newly diagnosed, transplant eligible, n = 108; newly diagnosed, transplant ineligible, n = 105; relapsed-refractory, n = 87) completed the survey. The most valued attributes were pain, fatigue, and increased life expectancy. Participants would want an additional 2.7 years of life expectancy (95% confidence interval [CI] 2.4-3.1 years) to tolerate extreme pain and an additional 2.0 years of life expectancy (95% CI 1.6-2.3 years) to tolerate constant fatigue. Participants in a better health state (third EQ-5D score quartile [0.897]) required less additional life expectancy than participants with a worse health state (first EQ-5D score quartile [0.662]) to tolerate extreme pain (2.3 years [95% CI 1.9-2.6 years] vs 3.0 years [95% CI 2.6-3.4 years]; P = .007). There was little difference in treatment preferences between newly diagnosed and relapsed-refractory patients for pain, fatigue, and increased life expectancy. CONCLUSIONS: Current health state influenced treatment preferences of patients with MM more than disease status and should be considered when making treatment decisions.

Patient and Physician Preferences for Regimen Attributes for the Treatment of HIV in the United States and Canada.

A long-acting injectable (LAI) antiretroviral therapy (ART) regimen is now available as a treatment option for virologically suppressed adults with HIV-1. This study assessed preference for a LAI regimen using an online survey of virally suppressed people living with HIV (PLWH) and physicians treating HIV in the US and Canada. Preference was elicited in a discrete choice experiment (DCE) with three choice options (switch to a LAI regimen, switch to another daily oral ART regimen, or stay on their current daily oral ART regimen) and four treatment attributes. A total of 553 PLWH and 450 physicians completed the survey. From the DCE results, 59% of PLWH were predicted to prefer a LAI over an alternative oral ART or staying on their current oral treatment, and 55-66% of physicians were predicted to recommend LAI for PLWH, depending on the treatment challenge scenario presented. PLWH indicated LAI would remove daily reminders of HIV (75%) and reduce feelings of being stigmatized (68%). A majority of PLWH and physicians preferred a LAI over oral ART to overcome treatment challenges such as daily pill burden and adherence. These benefits of LAI ART along with preferences of PLWH and physicians can help to inform ART choice.

A Systematic and Critical Review of Discrete Choice Experiments in Asthma and Chronic Obstructive Pulmonary Disease.

BACKGROUND: Regulators have called for greater emphasis on the role of the patient voice to inform medical product development and decision making, and expert guidelines and reports for asthma and chronic obstructive pulmonary disease (COPD) both explicitly recommend the consideration of patient preferences in the management of these diseases. Discrete choice experiments (DCEs) are commonly used to quantify stakeholders' treatment preferences and estimate the trade-offs they are willing to make between outcomes such as treatment benefits and risks. OBJECTIVE: The aim of this systematic literature review is to provide an up-to-date and critical review of DCEs published in asthma and COPD; specifically, we aim to evaluate the subject of preference studies conducted in asthma and COPD, what attributes have been included, stakeholders' preferences, and the consistency in reporting of instrument development, testing and reporting of results. METHODS: A systematic review of published DCEs on asthma and COPD treatments was conducted using Embase, Medline and the Cochrane Database of Systematic Reviews. Studies were included if they included a DCE conducted in a relevant population (e.g. patients with asthma or COPD or their caregivers, asthma or COPD-treating clinicians, or the general population), and reported quantitative outcomes on participants' preferences. Study characteristics were summarised descriptively, and descriptive analyses of attribute categories, consistency in reporting on key criteria, and stakeholder preferences were undertaken. RESULTS: A total of 33 eligible studies were identified, including 28 unique DCEs. The majority (n = 20; 71%) of studies were conducted in a patient sample. Studies focused on inhaler treatments, and included attributes in five key categories: symptoms and treatment benefits (n = 23; 82%), treatment convenience (n = 19; 68%), treatment cost (n = 17; 61%), treatment risks (n = 13; 46%), and other (n = 10; 36%). Symptoms and treatment benefits were the attributes most frequently ranked as important to patients (n = 26, 72%), followed by treatment risks (n = 7, 39%). Several studies (n = 9, 32%) did not qualitatively pre-test their DCE, and a majority did not report the uncertainty in estimated outcomes (n = 18; 64%). CONCLUSIONS: DCEs in asthma and COPD have focused on treatment benefits and convenience, with less evidence generated on participants' risk tolerance. Quality criteria and reporting standards are needed to promote study quality and ensure consistency in reporting between studies.

A Systematic Review of Discrete Choice Experiments in Oncology Treatments.

BACKGROUND: As the number and type of cancer treatments available rises and patients live with the consequences of their disease and treatments for longer, understanding preferences for cancer care can help inform decisions about optimal treatment development, access, and care provision. Discrete choice experiments (DCEs) are commonly used as a tool to elicit stakeholder preferences; however, their implementation in oncology may be challenging if burdensome trade-offs (e.g. length of life versus quality of life) are involved and/or target populations are small. OBJECTIVES: The aim of this review was to characterise DCEs relating to cancer treatments that were conducted between 1990 and March 2020. DATA SOURCES: EMBASE, MEDLINE, and the Cochrane Database of Systematic Reviews were searched for relevant studies. STUDY ELIGIBILITY CRITERIA: Studies were included if they implemented a DCE and reported outcomes of interest (i.e. quantitative outputs on participants' preferences for cancer treatments), but were excluded if they were not focused on pharmacological, radiological or surgical treatments (e.g. cancer screening or counselling services), were non-English, or were a secondary analysis of an included study. ANALYSIS METHODS: Analysis followed a narrative synthesis, and quantitative data were summarised using descriptive statistics, including rankings of attribute importance. RESULT: Seventy-nine studies were included in the review. The number of published DCEs relating to oncology grew over the review period. Studies were conducted in a range of indications (n = 19), most commonly breast (n =10, 13%) and prostate (n = 9, 11%) cancer, and most studies elicited preferences of patients (n = 59, 75%). Across reviewed studies, survival attributes were commonly ranked as most important, with overall survival (OS) and progression-free survival (PFS) ranked most important in 58% and 28% of models, respectively. Preferences varied between stakeholder groups, with patients and clinicians placing greater importance on survival outcomes, and general population samples valuing health-related quality of life (HRQoL). Despite the emphasis of guidelines on the importance of using qualitative research to inform attribute selection and DCE designs, reporting on instrument development was mixed. LIMITATIONS: No formal assessment of bias was conducted, with the scope of the paper instead providing a descriptive characterisation. The review only included DCEs relating to cancer treatments, and no insight is provided into other health technologies such as cancer screening. Only DCEs were included. CONCLUSIONS AND IMPLICATIONS: Although there was variation in attribute importance between responder types, survival attributes were consistently ranked as important by both patients and clinicians. Observed challenges included the risk of attribute dominance for survival outcomes, limited sample sizes in some indications, and a lack of reporting about instrument development processes. PROTOCOL REGISTRATION: PROSPERO 2020 CRD42020184232.

Patient Perceptions Regarding Multiple Myeloma and Its Treatment: Qualitative Evidence from Interviews with Patients in the United Kingdom, France, and Germany.

BACKGROUND: The current standard of care for multiple myeloma requires several regimens of treatment, with patients experiencing high symptom burden and side effects, which negatively impact health-related quality of life (HRQoL). Thus, it is crucial to understand patient perceptions of multiple myeloma and how patients value different treatment options. OBJECTIVE: The purpose of this study was to conduct an exploratory investigation into concepts that could form attributes that influence treatment choices for patients with multiple myeloma and to identify trade-offs that patients are willing to make between treatment attributes. METHODS: In total, 30 patients with newly diagnosed or relapsed/refractory multiple myeloma from the UK, France, and Germany participated in semistructured interviews talking about their disease experience and symptoms, treatment benefits, treatment burden, perceived side effects, and benefit/risk trade-offs in treatment. The interview audio recordings were transcribed and analyzed using content analysis to identify treatment and disease aspects relevant to patients. RESULTS: Symptoms of fatigue and bone pain and treatment side effects of peripheral neuropathy, diarrhea, and constipation were cited by patients as the most disruptive to their HRQoL. Treatment duration was reported most frequently as a major treatment burden, and patients emphasized the importance of increased life expectancy as a treatment benefit. All patients showed good understanding of benefit/risk trade-offs in treatment, and some patients expressed a preference for more convenient modes of treatment administration. CONCLUSIONS: Qualitative interviews identified key aspects of multiple myeloma treatment that are most important to patients. These findings will inform a wider patient-preferences study, which could improve treatment choice and HRQoL for patients with multiple myeloma.

How to integrate evidence from patient preference studies into health technology assessment: a critical review and recommendations.

Health technology assessment (HTA) agencies vary in their use of quantitative patient preference data (PP) and the extent to which they have formalized this use in their guidelines. Based on the authors' knowledge of the literature, we identified six different PP "use cases" that integrate PP into HTA in five different ways: through endpoint selection, clinical benefit rating, predicting uptake, input into economic evaluation, and a means to weight all HTA criteria. Five types of insight are distinguished across the use cases: understanding what matters to patients, predicting patient choices, estimating the utility generated by treatment benefits, estimating the willingness to pay for treatment benefits, and informing distributional considerations. Summarizing the literature on these use cases, we recommend circumstances in which PP can add value to HTA and the further research and guidance that is required to support the integration of PP in HTA. Where HTA places more emphasis on clinical outcomes, novel endpoints are available; or where there are already many treatment options, PP can add value by helping decision makers to understand what matters to patients. Where uptake is uncertain, PP can be used to estimate uptake probability. Where indication-specific utility functions are required or where existing utility measures fail to capture the value of treatments, PP can be used to generate or supplement existing utility estimates. Where patients are paying out of pocket, PP can be used to estimate willingness to pay.