The hereditary angioedema burden of illness study in Europe (HAE-BOIS-Europe) : background and methodology

Background: Hereditary angioedema (HAE) is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation. While there have been major advancements in our understanding of the immunogenetics of HAE, there are significant gaps in the literature regarding understanding of the humanistic and economic impact of the disease, particularly in Europe. The purpose of the HAE Burden of Illness Study-Europe (HAE-BOIS-Europe), the development and methodology of which is described here, is to better understand the management and impact of HAE from the patient perspective in Europe. Methods/Design: This is a cross-sectional study in which retrospective data were also collected being conducted in Denmark, Germany and Spain. The study is open to patients ages 12 and older with a diagnosis of HAE-I or HAE-II. Data collection includes: (i) a survey on individuals’ health care resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning (via the Hospital Anxiety and Depression Scale); and (ii) one-on-one interviews to collect detailed descriptive data and patient testimonials on the impact of HAE on patients’ health-related quality of life. Discussion: The present manuscript describes the development and plans for implementing a multi-country European study with the aim of characterizing the humanistic and economic burden of HAE from the patient perspective. This study will help raise awareness of HAE as a rare but debilitating condition with wide-ranging impacts

Development of the multi-attribute Adolescent Health Utility Measure (AHUM)

Objective Obtain utilities (preferences) for a generalizable set of health states experienced by older children and adolescents who receive therapy for chronic health conditions. Methods A health state classification system, the Adolescent Health Utility Measure (AHUM), was developed based on generic health status measures and input from children with Hunter syndrome and their caregivers. The AHUM contains six dimensions with 4–7 severity levels: self-care, pain, mobility, strenuous activities, self-image, and health perceptions. Using the time trade off (TTO) approach, a UK population sample provided utilities for 62 of 16,800 AHUM states. A mixed effects model was used to estimate utilities for the AHUM states. The AHUM was applied to trial NCT00069641 of idursulfase for Hunter syndrome and its extension (NCT00630747). Results Observations (i.e., utilities) totaled 3,744 (12*312 participants), with between 43 to 60 for each health state except for the best and worst states which had 312 observations. The mean utilities for the best and worst AHUM states were 0.99 and 0.41, respectively. The random effects model was statistically significant (p < 0.0001; adjusted R2 = 0.361; RMSE = 0.194). When AHUM utilities were applied to the idursulfase trial, mean utilities in the idursulfase weekly and placebo groups improved +0.087 and +0.006, respectively, from baseline to week 53. In the extension, when all patients received idursulfase, the utilities in the treatment group remained stable and the placebo group improved +0.039. Discussion The AHUM health state classification system may be used in future research to enable calculation of quality-adjust life expectancy for applicable health conditions

Population preference values for treatment outcomes in chronic lymphocytic leukaemia: a cross-sectional utility study

<p>Abstract</p> <p>Background</p> <p>Given that treatments for chronic lymphocytic leukaemia (CLL) are palliative rather than curative, evaluating the patient-perceived impacts of therapy is critical. To date, no utility (preference) studies from the general public or patient perspective have been conducted in CLL. The objective of this study was to measure preferences for health states associated with CLL treatment.</p> <p>Methods</p> <p>This was a cross-sectional study of 89 members of the general population in the UK (England and Scotland). Using standard gamble, each participant valued four health states describing response status, six describing treatment-related toxicities based on Common Toxicity Criteria, and two describing line of treatment. The health states incorporated standardized descriptions of treatment response (symptoms have "improved," "stabilized," or "gotten worse"), swollen glands, impact on daily activities, fatigue, appetite, and night sweats. Utility estimates ranged from 0.0, reflecting dead, to 1.0, reflecting full health.</p> <p>Results</p> <p>Complete response (CR) was the most preferred health state (mean utility, 0.91), followed by partial response (PR), 0.84; no change (NC), 0.78; and progressive disease (PD), 0.68. Among the toxicity states, grade I/II nausea and nausea/vomiting had the smallest utility decrements (both were -0.05), and grade III/IV pneumonia had the greatest decrement (-0.20). The utility decrements obtained for toxicity states can be subtracted from utilities for CR, PR, NC, and PD, as appropriate. The utilities for second- and third-line treatments, which are attempted when symptoms worsen, were 0.71 and 0.65, respectively. No significant differences in utilities were observed by age, sex, or knowledge/experience with leukaemia.</p> <p>Conclusions</p> <p>This study reports UK population utilities for a universal set of CLL health states that incorporate intended treatment response and unintended toxicities. These utilities can be applied in future cost-effectiveness analyses of CLL treatment.</p

Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema

Objective: To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact of a condition on a patient’s life; a score of 0.0 reflects death and 1.0 reflects full health. Study design and methods: The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5-Dimensions (EQ-5D) domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression) were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks. Results: Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation of EQ-5D-based utilities. The mean utilities for an HAE attack and between attacks were 0.44 and 0.72, respectively. Utilities for an acute attack were dependent on the severity of pain of the last attack (0.61 for no pain or mild pain, 0.47 for moderate pain, and 0.08 for severe pain). There were no significant differences across countries. Mean utilities derived from the study approach compare sensibly with other disease states for both acute attacks and between attacks. Conclusion: The impacts of HAE translate into substantial health status disutilities associated with acute attacks as well as between attacks, documenting that the detrimental effects of HAE are meaningful from the patient perspective. Results were consistent across countries with regard to pain severity and in comparison to similar disease states. The results can be used to raise awareness of HAE as a serious disease with wide-ranging personal and social impacts