Symptoms, impacts, and suitability of the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT™) questionnaire in patients with sarcoidosis-associated pulmonary hypertension (SAPH): a qualitative interview study.

BACKGROUND: Sarcoidosis-associated pulmonary hypertension (SAPH) is a prevalent and serious complication of sarcoidosis. No SAPH-specific self-report instruments for assessing SAPH symptoms and their impact on patients are available to date. This study sought to determine whether the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT™) questionnaire is suitable for use in patients with SAPH. METHODS: Patients diagnosed with SAPH participated in qualitative one-on-one telephone interviews to better understand SAPH symptoms and their impacts on patients' lives and to determine the appropriateness of the PAH-SYMPACT™ for use in patients with SAPH. The interviews comprised concept elicitation, completion of the PAH-SYMPACT™, and cognitive debriefing. Interview transcripts were analyzed by content analysis. RESULTS: Eleven patients with SAPH were interviewed between August 2019 and June 2020. In the concept elicitation, all 11 participants endorsed shortness of breath and nine participants (82%) rated it as their "most bothersome or severe" symptom. Impacts endorsed by all 11 participants were difficulty walking uphill or up stairs and difficulty in performing daily activities. Cognitive debriefing indicated that the PAH-SYMPACT™ items were relevant and understandable to most participants and reflected their experiences of SAPH. Participants indicated that no key symptoms or impacts of SAPH were missing. They also reported that the PAH-SYMPACT™ instructions and response options were clear, and that it would be feasible to complete the 11 symptom items and one oxygen use item as part of their daily schedule. CONCLUSIONS: This study suggests the PAH-SYMPACT™ is suitable for assessing symptoms and their impact in patients with SAPH. However, larger longitudinal studies are needed to confirm that it is fit for use in this patient population and that it can be used to reliably detect temporal changes in patients' symptom status. Trial registration Not applicable.

Elicitation of health state utilities associated with the mode of administration of drugs acting on the prostacyclin pathway in pulmonary arterial hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare, incurable disease associated with decreased life expectancy and a marked impact on quality of life (QoL). There are three classes of drugs available for treatment: endothelin receptor antagonists (ERA), drugs acting on nitric oxide pathway (riociguat and phosphodiesterase type 5 inhibitors [PDE5i]), and drugs acting on prostacyclin pathway. The latter have widely different modes of administration - continuous intravenous infusion, continuous subcutaneous infusion, inhaled, and oral - each associated with variable treatment burden, and implications for health economic assessment. This study aimed to establish utility values associated with different modes of administration of drugs acting on the prostacyclin pathway for use in economic evaluations of PAH treatments. METHODS: A UK general public sample completed the EQ-5D-5L and valued four health states in time trade-off interviews. The health states drafted from literature and interviews with PAH experts (n=3) contained identical descriptions of PAH and ERA/PDE5i treatment, but differed in description of administration including oral (tablets), inhaled (nebulizer), continuous subcutaneous infusion, and continuous intravenous infusion. RESULTS: A total of 150 participants (63% female; mean age 37 years) completed interviews. Utilities are presented as values between 0 and 1, with 0 representing the state of being dead and 1 representing being in full health. The mean (SD) utility for oral health state was 0.85 (0.16), while all other health states were significantly lower at 0.74 (0.27) for inhaled (p=0.001), 0.59 (0.31) for subcutaneous (p<0.001) and 0.54 (0.32) for intravenous (p<0.001), indicating that there are disutilities (negative differences) associated with non-oral health states. Disutilities were -0.11 for inhaled, -0.26 for subcutaneous, and -0.31 for intravenous administration. CONCLUSION: The results demonstrate quantifiable QoL differences between modes of administration of drugs acting on the prostacyclin pathway. QoL burden should be considered for economic evaluation of drugs for PAH treatment.

Health state utilities associated with attributes of weekly injection devices for treatment of type 2 diabetes.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are often recommended as part of combination therapy for type 2 diabetes when oral medication does not result in sufficient glycemic control. Several GLP-1 receptor agonists are available as weekly injections. These medications vary in their injection delivery systems, and these differences could impact quality of life and treatment preference. The purpose of this study was to estimate utilities associated with attributes of injection delivery systems for weekly GLP-1 therapies. METHODS: Participants with type 2 diabetes in the UK valued health states in time trade-off interviews. The health states (drafted based on literature, device instructions for use, and clinician interviews) had identical descriptions of type 2 diabetes, but differed in description of the treatment process. One health state described oral treatment, while six others described oral treatment plus a weekly injection. The injection health states varied in three aspects of the treatment administration process: requirements for reconstituting the medication (i.e., mixing the medication prior to the injection), waiting during medication preparation, and needle handling. Every participant valued all seven health states. RESULTS: A total of 209 participants completed interviews (57.4% male; mean age = 60.4y). The mean utility of the oral treatment health state was 0.89. All injection health states had significantly (p < 0.01) lower utilities ranging from 0.86 to 0.88. Differences among health state utilities suggest that each administration requirement had a small but measureable disutility: -0.004 (reconstitution), -0.004 (needle handling), -0.010 (reconstitution, needle handling), and -0.020 (reconstitution, waiting, needle handling). CONCLUSIONS: Findings suggest it is feasible to use the TTO method to quantify preferences among injection treatment processes. It may be useful to incorporate these utility differences into cost-utility models comparing weekly injectable treatments for patients with type 2 diabetes.

Health State Utilities Associated with Glucose Monitoring Devices.

BACKGROUND: Glucose monitoring is important for patients with diabetes treated with insulin. Conventional glucose monitoring requires a blood sample, typically obtained by pricking the finger. A new sensor-based system called "flash glucose monitoring" monitors glucose levels with a sensor worn on the arm, without requiring blood samples. OBJECTIVES: To estimate the utility difference between these two glucose monitoring approaches for use in cost-utility models. METHODS: In time trade-off interviews, general population participants in the United Kingdom (London and Edinburgh) valued health states that were drafted and refined on the basis of literature, clinician input, and a pilot study. The health states had identical descriptions of diabetes and insulin treatment, differing only in glucose monitoring approach. RESULTS: A total of 209 participants completed the interviews (51.7% women; mean age = 42.1 years). Mean utilities were 0.851 ± 0.140 for conventional monitoring and 0.882 ± 0.121 for flash monitoring (significant difference between the mean utilities; t = 8.3; P < 0.0001). Of the 209 participants, 78 (37.3%) had a higher utility for flash monitoring, 2 (1.0%) had a higher utility for conventional monitoring, and 129 (61.7%) had the same utility for both health states. CONCLUSIONS: The flash glucose monitoring system was associated with a significantly greater utility than the conventional monitoring system. This difference may be useful in cost-utility models comparing the value of glucose monitoring devices for patients with diabetes. This study adds to the literature on treatment process utilities, suggesting that time trade-off methods may be used to quantify preferences among medical devices.

Risks associated with antiretroviral treatment for human immunodeficiency virus (HIV): qualitative analysis of social media data and health state utility valuation.

PURPOSE: Despite benefits of antiretroviral therapies (ART), people with HIV infection have increased risk of cardiovascular disease, kidney disease, and low bone mineral density. Some ARTs increase risk of these events. The purpose of this study was to examine patients' perspectives of these risks and estimate health state utilities associated with these risks for use in cost-utility models. METHODS: Qualitative thematic analysis was conducted to examine messages posted to the POZ/AIDSmeds Internet community forums, focusing on bone, kidney, and cardiovascular side effects and risks of HIV/AIDS medications. Then, health state vignettes were drafted based on this qualitative analysis, literature review, and clinician interviews. The health states (representing HIV, plus treatment-related risks) were valued in time trade-off interviews with general population participants in the UK. RESULTS: Qualitative analysis of the Internet forums documented patient concerns about ART risks, as well as treatment decisions made because of these risks. A total of 208 participants completed utility interviews (51.4% female; mean age 44.6 years). The mean utility of the HIV health state (virologically suppressed, treated with ART) was 0.86. Adding a description of risk resulted in statistically significant disutility (i.e., utility decreases): renal risk (disutility = -0.02), bone risk (-0.03), and myocardial infarction risk (-0.05). CONCLUSIONS: Patient concerns and treatment decisions were documented via qualitative analysis of Internet forum discussions, and the impact of these concerns was quantified in terms of health state utilities. The resulting disutilities may be useful for differentiating among ARTs in economic modeling of treatment for patients with HIV.

Evaluating the Measurement Properties of the Self-Assessment of Treatment Version II, Follow-Up Version, in Patients with Painful Diabetic Peripheral Neuropathy.

Background. The Self-Assessment of Treatment version II (SAT II) measures treatment-related improvements in pain and impacts and impressions of treatment in neuropathic pain patients. The measure has baseline and follow-up versions. This study assesses the measurement properties of the SAT II. Methods. Data from 369 painful diabetic peripheral neuropathy (PDPN) patients from a phase III trial assessing capsaicin 8% patch (Qutenza®) efficacy and safety were used in these analyses. Reliability, convergent validity, known-groups validity, and responsiveness (using the Brief Pain Inventory-Diabetic Neuropathy [BPI-DN] and Patient Global Impression of Change [PGIC]) analyses were conducted, and minimally important differences (MID) were estimated. Results. Exploratory factor analysis supported a one-factor solution for the six impact items. The SAT II has good internal consistency (Cronbach's alpha: 0.96) and test-retest reliability (intraclass correlation coefficients: 0.62-0.88). Assessment of convergent validity showed moderate to strong correlations with change in other study endpoints. Scores varied significantly by level of pain intensity and sleep interference (p < 0.05) defined by the BPI-DN. Responsiveness was shown based on the PGIC. MID estimates ranged from 1.2 to 2.4 (pain improvement) and 1.0 to 2.0 (impact scores). Conclusions. The SAT II is a reliable and valid measure for assessing treatment improvement in PDPN patients.

Evaluating preferences for profiles of GLP-1 receptor agonists among injection-naïve type 2 diabetes patients in the UK.

OBJECTIVE: To use a discrete choice experiment (DCE) to evaluate preferences for the actual treatment features and overall profiles of two injectable glucagon-like peptide-1 receptor agonists (dulaglutide and liraglutide) among patients with type 2 diabetes mellitus (T2DM) in the UK. METHODS: In-person interviews were conducted in the UK to administer a DCE to patients with self-reported T2DM, naïve to treatment with injectable medications. The DCE examined six attributes of T2DM treatment each described by two levels: "dosing frequency," "hemoglobin A1c change," "weight change," "type of delivery system," "frequency of nausea," and "frequency of hypoglycemia." Part-worth utilities were estimated using random effects logit models and were used to calculate relative importance (RI) values for each attribute. A chi-square test was used to determine differences in preferences for dulaglutide versus liraglutide profiles. RESULTS: A total of 243 participants [mean age: 60.5 (standard deviation 10.9) years; 76.1% male; mean body mass index: 29.8 (standard deviation 5.4) kg/m(2)] completed the study. RI values for the attributes in rank order were: "dosing frequency" (41.6%), "type of delivery system" (35.5%), "frequency of nausea" (10.4%), "weight change" (5.9%), "hemoglobin A1c change" (3.6%), and "frequency of hypoglycemia" (3.0%). Significantly more participants preferred the dulaglutide profile (83.1%) compared with the liraglutide profile (16.9%; P<0.0001). CONCLUSION: This study elicited patients' preferences for attributes and levels representing the actual characteristics of two specific glucagon-like peptide-1 medications. In this context, dosing frequency and type of delivery system were most important, accounting for over 75% of the RI. While previous studies have identified efficacy as highly important in T2DM medication decisions, this study suggests that when differences in efficacy between medications are small, other treatment features (eg, dosing frequency and delivery system) are of much greater importance to patients.

Health state utilities associated with major clinical events in the context of secondary hyperparathyroidism and chronic kidney disease requiring dialysis.

BACKGROUND: Patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT) who require dialysis are at increased risk for cardiovascular events and bone fractures. To assist in economic evaluations, this study aimed to estimate the disutility of these events beyond the impact of CKD and SHPT. METHODS: A basic one-year health state was developed describing CKD and SHPT requiring dialysis. Further health states added acute events (cardiovascular events, fractures, and surgical procedures) or chronic post-event effects. Acute health states described a year including an event, and chronic health states described a year subsequent to an event. General population participants in Canada completed time trade-off interviews from which utilities were derived. Pairwise comparisons were made between the basic state and event, and between comparable health states. RESULTS: A total of 199 participants (54.8% female; mean age = 46.3 years) completed interviews. Each health state had ≥130 valuations. The mean (SD) utility of the basic health state was 0.60 (0.34). For acute events, mean utility differences versus the basic state were: myocardial infarction, -0.06; unstable angina, -0.05; peripheral vascular disease (PVD) with amputation, -0.33; PVD without amputation, -0.11; heart failure, -0.14; stroke, -0.30; hip fracture, -0.14; arm fracture, -0.04; parathyroidectomy, +0.02; kidney transplant, +0.06. Disutilities for chronic health states were: stable angina, -0.09; stroke, -0.27; PVD with amputation, -0.30; PVD without amputation, -0.12; heart failure, -0.14. CONCLUSIONS: Cardiovascular events and fractures were associated with lower utility scores, suggesting a perceived decrease in quality of life beyond the impact of CKD and SHPT.

Acute and chronic impact of cardiovascular events on health state utilities.

BACKGROUND: Cost-utility models are frequently used to compare treatments intended to prevent or delay the onset of cardiovascular events. Most published utilities represent post-event health states without incorporating the disutility of the event or reporting the time between the event and utility assessment. Therefore, this study estimated health state utilities representing cardiovascular conditions while distinguishing between acute impact including the cardiovascular event and the chronic post-event impact. METHODS: Health states were drafted and refined based on literature review, clinician interviews, and a pilot study. Three cardiovascular conditions were described: stroke, acute coronary syndrome (ACS), and heart failure. One-year acute health states represented the event and its immediate impact, and post-event health states represented chronic impact. UK general population respondents valued the health states in time trade-off tasks with time horizons of one year for acute states and ten years for chronic states. RESULTS: A total of 200 participants completed interviews (55% female; mean age = 46.6 y). Among acute health states, stroke had the lowest utility (0.33), followed by heart failure (0.60) and ACS (0.67). Utility scores for chronic health states followed the same pattern: stroke (0.52), heart failure (0.57), and ACS (0.82). For stroke and ACS, acute utilities were significantly lower than chronic post-event utilities (difference = 0.20 and 0.15, respectively; both p < 0.0001). CONCLUSIONS: Results add to previously published utilities for cardiovascular events by distinguishing between chronic post-event health states and acute health states that include the event and its immediate impact. Findings suggest that acute versus chronic impact should be considered when selecting scores for use in cost-utility models. Thus, the current utilities provide a unique option that may be used to represent the acute and chronic impact of cardiovascular conditions in economic models comparing treatments that may delay or prevent the onset of cardiovascular events.

Health state utilities associated with attributes of treatments for hepatitis C.

BACKGROUND: Cost-utility analyses are frequently conducted to compare treatments for hepatitis C, which are often associated with complex regimens and serious adverse events. Thus, the purpose of this study was to estimate the utility associated with treatment administration and adverse events of hepatitis C treatments. DESIGN: Health states were drafted based on literature review and clinician interviews. General population participants in the UK valued the health states in time trade-off (TTO) interviews with 10- and 1-year time horizons. The 14 health states described hepatitis C with variations in treatment regimen and adverse events. RESULTS: A total of 182 participants completed interviews (50% female; mean age = 39.3 years). Utilities for health states describing treatment regimens without injections ranged from 0.80 (1 tablet) to 0.79 (7 tablets). Utilities for health states describing oral plus injectable regimens were 0.77 (7 tablets), 0.75 (12 tablets), and 0.71 (18 tablets). Addition of a weekly injection had a disutility of -0.02. A requirement to take medication with fatty food had a disutility of -0.04. Adverse events were associated with substantial disutilities: mild anemia, -0.12; severe anemia, -0.32; flu-like symptoms, -0.21; mild rash, -0.13; severe rash, -0.48; depression, -0.47. One-year TTO scores were similar to these 10-year values. CONCLUSIONS: Adverse events and greater treatment regimen complexity were associated with lower utility scores, suggesting a perceived decrease in quality of life beyond the impact of hepatitis C. The resulting utilities may be used in models estimating and comparing the value of treatments for hepatitis C.

Health state utilities associated with adult attention-deficit/hyperactivity disorder.

OBJECTIVES: With growing awareness of the importance of adult attention-deficit/hyperactivity disorder (ADHD) treatment, cost-effectiveness analyses, including utilities, are needed to compare the value of treatment options. Although utilities have been reported for childhood ADHD, little is known about utilities representing adult ADHD. Therefore, the purpose of this study was to estimate utilities associated with adult ADHD. METHODS: Health-state descriptions of adult ADHD were drafted based on literature review, interviews with four clinicians, and clinical trial data. Health states were revised based on a pilot study with 26 participants. Final health states were rated in time trade-off interviews with general population respondents in London and Edinburgh, UK. RESULTS: A total of 158 participants completed interviews (mean age =47.0 years; 49.4% female; Edinburgh =80 participants). Mean (standard deviation [SD]) utilities were 0.82 (0.17), 0.68 (0.28), and 0.67 (0.28) for health states describing treatment responders (health state A), nonresponders (health state B), and untreated patients (health state C), respectively. Most participants rated health state A as preferable to B (n=92; 58.2%) and C (n=97; 61.4%). The majority rated B and C as equal (n=125; 79.1%). Paired Student's t-tests found that A had a significantly greater mean utility than B (t=10.0; P<0.0001) and C (t=10.2; P<0.0001). CONCLUSION: The current study provides utilities that may be used in cost-utility models of treatment for adult ADHD. Results reflected clear differences between health states representing treatment responders and nonresponders/untreated patients. Current utilities were comparable to those previously reported for childhood ADHD.

A systematic literature review of cardiovascular event utilities.

Cardiovascular disease (CVD) results in half of the non-communicable disease-related deaths worldwide. Rising treatment costs have increased the need for cost-utility models designed to compare the value of new and existing therapies. Cost-utility models require utilities, values representing the strength of preferences for various health states. This systematic literature review aimed to identify and evaluate utilities reported for stroke, myocardial infarction (MI) and angina. In total, 83 unique studies were identified that reported utilities for these events. Approximately two-thirds reported utility values for stroke, and most used the EuroQoL five dimension to derive utilities. Utility values were lower in patients who experienced cardiovascular (CV) events than in patients who did not. The utility estimates for each condition varied greatly, likely due to differences in assessment methodologies and patient populations. This variability must be considered when choosing values for cost-utility models. Comparisons among reported utilities are further complicated by inconsistent CV event definitions.