Health state utilities associated with hyperphagia: Data for use in cost-utility models.

Objective: Rare genetic diseases of obesity typically present with hyperphagia, a pathologic desire to consume food. Cost-utility models assessing the value of treatments for these rare diseases will require health state utilities representing hyperphagia. This study estimated utilities associated with various hyperphagia severity levels. Methods: Four health state vignettes were developed using published literature and clinician input to represent various severity levels of hyperphagia. Utilities were estimated for these health states in a time trade-off elicitation study in a UK general population sample. Results: In total, 215 participants completed interviews (39.5% male; mean age 39.1 years). Mean (SD) utilities were 0.98 (0.02) for no hyperphagia, 0.91 (0.10) for mild hyperphagia, 0.70 (0.30) for moderate hyperphagia, and 0.22 (0.59) for severe hyperphagia. Mean (SD) disutilities were -0.08 (0.10) for mild, -0.28 (0.30) for moderate, and -0.77 (0.58) for severe hyperphagia. Conclusions: These data show increasing severity of hyperphagia is associated with decreased utility. Utilities associated with severe hyperphagia are similar to those of other health conditions severely impacting quality of life (QoL). These findings highlight that treatments addressing substantial QoL impacts of severe hyperphagia are needed. Utilities estimated here may be useful in cost-utility models of treatments for rare genetic diseases of obesity.

Approaches to the Assessment of Clinical Benefit of Treatments for Conditions That Have Heterogeneous Symptoms and Impacts: Potential Applications in Rare Disease.

OBJECTIVES: Evaluating the clinical benefit of interventions for conditions with heterogeneous symptom and impact presentations is challenging. The same condition can present differently across and within individuals over time. This occurs frequently in rare diseases. The purpose of this review was to identify (1) assessment approaches used in clinical trials to address heterogeneous manifestations that could be relevant in rare disease research and (2) US Food and Drug Administration (FDA)-approved labeling claims that used these approaches. METHODS: A targeted literature review was conducted examining peer-reviewed publications and FDA-approved labeling claims from January 2002 to July 2020, focusing on claims incorporating clinical outcome assessments. Approaches were then assessed for their potential application in rare diseases. RESULTS: A total of 6 assessment approaches were identified: composite or other multicomponent endpoints, multidomain responder index, most bothersome symptom (MBS), goal attainment scaling, sliding dichotomy, and adequate relief. A total of 59 FDA-approved labeling claims associated with these approaches were identified: composite or other multicomponent endpoints (n=49), MBS (n=9), and adequate relief (n=1). A total of 10 FDA-approved labeling claims, all using multicomponent endpoints, were identified for rare diseases. CONCLUSIONS: Multicomponent, MBS, and adequate relief have been included in FDA-approved labeling claims. Multicomponent endpoints, including composite endpoints, were the most frequent way to address heterogeneous manifestations of both common and rare diseases. MBS may be acceptable to regulators, whereas multidomain responder index is unlikely to be. The goal attainment scaling and adequate relief approaches may have potential utility in rare disease trials, assuming the theoretical and statistical challenges inherent in each approach are managed.

Estimating health state utilities associated with a rare disease: familial chylomicronemia syndrome (FCS).

Aims: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder with no currently approved therapies. Treatments are in development, and cost-utility analyses will be needed to examine their value. These models will require health state utilities representing FCS. Therefore, the purpose of this study was to estimate utilities for FCS and an associated episode of acute pancreatitis (AP).Methods: Because it is not feasible to gather a large enough sample of patients with this extremely rare condition to complete standardized preference-based measures, vignette-based methods were used to estimate utilities. In time trade-off interviews, general population participants in the UK and Canada valued health state vignettes drafted based on literature review, clinician input, and interviews with patients. Four health states described variations of FCS. A fifth health state, describing AP, was added to one of the other health states to evaluate its impact on utility.Results: A total of 308 participants provided utility data (208 UK; 100 Canada). Mean utilities for FCS health states ranged from 0.46 to 0.83, with higher triglycerides, more severe symptoms, and a history of AP associated with lower utility values. The disutility (i.e. utility decrease) of AP ranged from -0.17 to -0.25, with variations depending on the health state to which it was added. Utility means were similar in the UK and Canada.Conclusions: The vignette-based approach is useful for estimating utilities of a rare disease. The health state utilities derived in this study would be useful in models examining cost-effectiveness of treatments for FCS.

Health state utilities associated with treatment options for acute myeloid leukemia (AML).

Aims: Acute myeloid leukemia (AML) treatment typically involves remission induction chemotherapy followed by consolidation chemotherapy. New treatments for AML have recently been introduced, including a chemotherapy formulation called CPX-351, which is administered via less time-intensive IV infusion than the standard "7 + 3" continuous infusion regimen of cytarabine plus an anthracycline. The purpose of this study was to estimate utilities that could be used in economic modeling of AML treatment. Materials and methods: In time trade-off interviews, participants from the UK general population valued 12 health states drafted based on literature and clinician interviews. To identify disutility associated with chemotherapy, two types of induction and four types of consolidation were added to an otherwise identical health state describing AML. The decrease in utility when adding these chemotherapy regimens represents the disutility of each regimen. Five additional health states were valued to estimate utilities associated with other AML treatments. Results: Two hundred participants completed interviews. Mean (SD) utilities were 0.55 (0.31) for pre-treatment AML and 0.66 (0.29) for AML in temporary remission. Adding any chemotherapy significantly decreased utility (p < 0.0001). Induction had a mean disutility of -0.11 with CPX-351 and -0.15 with 7 + 3. Mean disutility for consolidation ranged from -0.03 with outpatient CPX-351 to -0.11 with inpatient 5 + 2. Utilities are also reported for other AML treatments (e.g. transplant, low-intensity chemotherapy). Limitations: One limitation is that the differences in adverse event profiles between the treatment regimens were based on clinician opinion. Future use of CPX-351 in clinical trials or clinical settings will provide additional information on its adverse event profile. Conclusions: While all chemotherapy regimens were associated with disutility, regimens with shorter hospitalization and less time-intensive infusion were generally perceived as preferable. These utilities may be useful in cost-utility models comparing the value of AML treatments.

The identification and assessment of late-life ADHD in memory clinics.

OBJECTIVE: Little data exist about ADHD in late life. While evaluating patients' memory problems, the memory clinic staff has periodically identified ADHD in previously undiagnosed older adults. The authors conducted a survey to assess the extent to which other memory clinics view ADHD as a relevant clinical issue. METHOD: The authors developed and sent a questionnaire to memory clinics in the United States to determine the extent to which they identified patients with ADHD and the extent to which they took it into consideration. RESULTS: Approximately one half of the memory clinics that responded reported seeing ADHD patients, either identifying previously diagnosed cases and/or newly diagnosing ADHD themselves. One fifth of clinics reported screening regularly for ADHD, and few clinics described accessing collateral informants to establish the diagnosis. CONCLUSION: This article suggests that U.S. memory clinics may not adequately identify and address ADHD in the context of late-life cognitive disorders.

The association of individual and facility characteristics with psychiatric hospitalization among nursing home residents.

OBJECTIVE: To examine resident and facility characteristics associated with psychiatric hospitalizations (PH) for Medicaid enrolled nursing home (NH) residents. METHODS: Participants were all Medicaid enrolled NH residents (n = 32,604) from all Medicaid certified nursing homes in Florida (n = 584) with complete data. We used individual demographic and diagnostic characteristics, as well as facility characteristics, to explore risk of psychiatric hospitalization in this dataset. RESULTS: Using generalized estimating equations, we found that younger age, male gender, poor physical health, serious mental illness, dementia, and drug use disorder were associated with risk of psychiatric hospitalization. Most notably, residents under 65 were more than three times more likely to undergo psychiatric hospitalization and dementia was associated with a three-fold increase in the risk of psychiatric hospitalization. Predictors of PH differed somewhat for younger and older residents. Among facility characteristics, greater facility size, low proportion of those paying via Medicare and high proportion of residents with serious mental illness were associated with increased risk of psychiatric hospitalization, whereas, low proportion of residents paying via Medicaid, high proportion of residents paying via Medicare, and low proportion of resident with serious mental illness were associated with reduced risk. CONCLUSIONS: Both resident and facility characteristics impact risk for psychiatric hospitalization. Attention to identified predictors may reduce risk and improve outcomes for nursing home residents.