Health state utility estimates for value assessments of novel treatments in Huntington's disease: a systematic literature review.

BACKGROUND: Huntington's disease (HD) is a progressive neurodegenerative disease with a devastating impact on patients and their families. Quantifying how treatments affect patient outcomes is critical for informing reimbursement decisions. Many countries mandate a formal value assessment in which the treatment benefit is measured as quality-adjusted life-years, calculated with the use of utility estimates that reflect respondents' preferences for health states. OBJECTIVE: To summarize published health state utility data in HD and identify gaps and uncertainties in the data available that could be used to inform value assessments. METHODS: We conducted a systematic literature review of studies that used preference-based instruments (e.g., EQ-5D and SF-6D) to estimate utility values for people with HD. The studies were published between January 2012 and December 2022. RESULTS: Of 383 articles screened, 16 articles reported utility values estimated in 11 distinct studies. The utility measure most frequently reported was EQ-5D (9/11 studies). Two studies reported SF-6D data; one used time trade-off methods to value health state descriptions (vignettes). Although utility scores generally worsened to a lower value with increased HD severity, the estimates varied considerably across studies. The EQ-5D index range was 0.89 - 0.72 for mild/prodromal HD and 0.71 - 0.37 for severe/late-stage disease. CONCLUSIONS: This study uncovered high variability in published utility estimates, indicating substantial uncertainty in existing data. Further research is needed to better understand preferences and valuation across all stages and domains of HD symptoms and the degree to which generic utility measures capture the impact of cognitive changes on quality of life.

Quantifying the Value of Introducing an Oral Drug Delivery Option for Edaravone: A Review of Analyses Evaluating the Economic Impact of Oral versus Intravenous Formulations.

Background: Drug formulation and route of administration can have an impact on not only patients' quality of life and disease outcomes but also costs of care. It is essential for decision makers to use appropriate economic modeling methods to guide drug coverage policies and to support patients' decision-making. Purpose: To illustrate key cost considerations for decision makers in economic evaluation of innovative oral formulations as alternatives to intravenous medication. Materials and Methods: A structured literature review was conducted using the PubMed database to examine methods used for quantifying the economic impact of introducing a new oral pharmaceutical formulation as an alternative to intravenous medication. To illustrate the methods described in this review, a cost-minimization analysis was conducted to quantify the impact of introducing an oral formulation of a medication originally developed as an intravenous treatment for amyotrophic lateral sclerosis. Results: We identified 14 published evaluations of oral and intravenous formulations from 10 countries across a variety of disease areas. The identified studies used cost-effectiveness (n=10), cost-minimization (n=2), and cost-calculation (n=2) modeling approaches. All but one (13/14) reported outcomes from payers' perspective, while societal perspectives were also incorporated in 3 of the reviewed evaluations. One study estimated costs from a public hospital's perspective. Only a subset of the identified studies accounted for the effects of safety (n=6) or efficacy (n=8) differences on treatment costs when estimating the costs of a formulation choice. Many studies that omitted these aspects did not include rationales for their decisions. Conclusion: We found significant design variations in published models that estimated the impact of an additional formulation option on the treatment costs to payers and the society. Models need to be accompanied with clear descriptions on rationales for their time horizons and assumptions on how different formulations may affect healthcare costs from the selected perspectives.

Challenges of Health Technology Assessment in Pluralistic Healthcare Systems: An ISPOR Council Report.

Health technology assessment (HTA) has been growing in use over the past 40 years, especially in its impact on decisions regarding the reimbursement, adoption, and use of new drugs, devices, and procedures. In countries or jurisdictions with "pluralistic" healthcare systems, there are multiple payers or sectors, each of which could potentially benefit from HTA. Nevertheless, a single HTA, conducted centrally, may not meet the needs of these different actors, who may have different budgets, current standards of care, populations to serve, or decision-making processes. This article reports on the research conducted by an ISPOR Health Technology Assessment Council Working Group established to examine the specific challenges of conducting and using HTA in countries with pluralistic healthcare systems. The Group used its own knowledge and expertise, supplemented by a narrative literature review and survey of US payers, to identify existing challenges and any initiatives taken to address them. We recommend that countries with pluralistic healthcare systems establish a national focus for HTA, develop a uniform set of HTA methods guidelines, ensure that HTAs are produced in a timely fashion, facilitate the use of HTA in the local setting, and develop a framework to encourage transparency in HTA. These efforts can be enhanced by the development of good practice guidance from ISPOR or similar groups and increased training to facilitate local use of HTA.

The evolution of ICER's review process for new medical interventions and a critical review of economic evaluations (2018-2019): how stakeholders can collaborate with ICER to improve the quality of evidence in ICER's reports.

BACKGROUND: Since its inception in 2006, the Institute for Clinical and Economic Review (ICER) has rapidly gained influence on drug pricing and reimbursement decisions despite historical resistance to the use of cost-effectiveness thresholds in the US health care system. Although patient groups, physicians, and pharmaceutical manufacturers voiced their concerns about the potential negative effects of increased use of ICER's assessments on patient access to innovative medications, there is little guidance and consensus on how the stakeholders should collaborate with ICER to ensure that its reviews reflect the best clinical and economic evidence. OBJECTIVES: To (1) summarize the evolution of ICER's evaluation procedure, scope, and topics; (2) evaluate the effectiveness of stakeholder engagement approaches; and (3) inform stakeholders of their potential role in collaborating with ICER in estimating the cost-effectiveness of new interventions. METHODS: Publicly available ICER evaluations from 2008 to 2019 were systematically reviewed. Changes in evaluation procedures, scope, and topics were summarized. For evaluations that occurred in 2018 (n = 12) and 2019 (n = 8), key characteristics were extracted from 172 letters documenting interactions between ICER and all stakeholders who provided comments to draft reports. Stakeholder suggestions were analyzed in terms of their effectiveness indicated by ICER's reconsideration of its original cost-effectiveness analysis approach. RESULTS: The number of ICER evaluations increased consistently from 2 to 12 per year between 2008 and 2018 but declined to 8 in 2019. Stakeholder opportunity to engage with ICER increased from 1 to 3 per evaluation between 2008 and 2015. ICER initially focused on reviewing general treatment strategies but shifted its focus to specific pharmaceuticals and medical devices in 2014. In 2018 and 2019, 30% of 172 stakeholder letters resulted in a revision in the base-case analysis (49 comments in 2018, 23 in 2019); nearly half of comments in these letters included specific alternative data or a published article to rationalize recommendations. Other common types of suggestions that resulted in ICER's base-case analysis revisions included comments relating to inconsistent methods used to derive model inputs across different treatments (12/49 in 2018, 5/23 in 2019); clinical justifications (12/49 in 2018, 0/23 in 2019); and justifications based on patient perspectives (1/49 in 2018, 5/23 in 2019). These revisions rarely affected ICER's conclusions on the cost-effectiveness of evaluated interventions. Among the 20 assessments that involved 172 stakeholder engagements in 2018 and 2019, only 2% (n = 3) of the engagements (all from 2018) were associated with a change in the cost-effectiveness conclusion. CONCLUSIONS: Between 2018 and 2019, stakeholders leveraged ICER evaluations as opportunities to promote dialogue for better understanding of the value of technologies. Actionable, evidence-based recommendations were accepted more often than other recommendations. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest to disclose. Findings from this study were presented as a poster at Virtual ISPOR, May 17-20, 2021.

Measuring recovery in opioid use disorder: clinical utility and psychometric properties of the Treatment Effectiveness Assessment.

Purpose: The Treatment Effectiveness Assessment (TEA) is a patient-centered instrument for evaluating treatment progress and recovery from substance use disorders, including opioid use disorder (OUD). We assessed the TEA's reliability and validity and determined minimal clinically important differences (MIDs) in participants with moderate to severe OUD. Patients and methods: The TEA measures change in four single-item domains (substance use, health, lifestyle, community involvement) from treatment initiation across the duration of a treatment program. Self-reported responses range from 1 ("none or not much") to 10 ("much better") with items summed to a total score ranging from 4-40. We assessed floor and ceiling effects, internal consistency, test-retest reliability, known-groups validity (ANOVA stratified by current health status [36-Item Short Form Health Survey item 1]), convergent/divergent validity, and MIDs using data from a phase 3, open-label clinical trial of buprenorphine extended-release monthly injection for subcutaneous use (BUP-XR). Participants with OUD completed the TEA at screening and before monthly injections for up to 12 months. Results: Among 410 participants (mean age 38 years; 64% male), the mean baseline (pre-injection 1) TEA total score was 25.4 (SD 9.7), with <10% of participants at the measure floor and 10%-20% at the ceiling across domains. Internal consistency was high (Cronbach's α=0.90), with marginal test-retest reliability (intraclass correlation coefficient =0.69). Mean TEA total score consistently increased from baseline (n=410; mean 25.4 [SD 9.7]) to end of study (n=337; 35.0 [6.7]) and differentiated between current health status groups (P<0.001); it was weakly correlated with other measures of health-related quality of life/severity. MIDs ranged from 5-8 for the TEA total score across anchor- and distribution-based approaches. Conclusion: The TEA exhibited acceptable reliability and validity in a cohort of participants with moderate to severe OUD treated with BUP-XR. Given its brevity and psychometric properties, the TEA is a promising tool for use in clinical practice and research.

Patient-centered Outcomes in Participants of a Buprenorphine Monthly Depot (BUP-XR) Double-blind, Placebo-controlled, Multicenter, Phase 3 Study.

OBJECTIVE: Opioid use disorder (OUD) is associated with physical, social, psychological, and economic burden. This analysis assessed the effects of RBP-6000, referred to as BUP-XR (extended-release buprenorphine), a subcutaneously injected, monthly buprenorphine treatment for OUD compared with placebo on patient-centered outcomes measuring meaningful life changes. METHODS: Patient-centered outcomes were collected in a 24-week, phase 3, placebo-controlled study assessing the efficacy, safety, and tolerability of BUP-XR 300/300 mg (6 × 300 mg) and 300/100 mg (2 × 300 mg followed by 4 × 100 mg) injections in treatment-seeking participants with moderate-to-severe OUD. Measures included the EQ-5D-5L, SF-36v2, Medication Satisfaction Questionnaire, employment/insurance status, and healthcare resource utilization (HCRU). Changes from baseline to end of study were compared across treatment arms, using mixed models for repeated measures. RESULTS: Participants receiving BUP-XR (n = 389) versus placebo (n = 98) had significantly greater changes from baseline on the EQ-5D-5L index (300/300 mg: difference = 0.0636, P = 0.003), EQ-5D-5L visual analog scale (300/300 mg: difference = 5.9, P = 0.017; 300/100 mg: difference = 7.7, P = 0.002), and SF-36v2 physical component summary score (300/300 mg: difference = 3.8, P < 0.001; 300/100 mg: difference = 3.2, P = 0.002). Satisfaction was significantly higher for participants receiving BUP-XR 300/300 mg (88%, P < 0.001) and 300/100 mg (88%, P < 0.001) than placebo (46%). Employment and percentage of insured participants increased by 10.8% and 4.1% with BUP-XR 300/300 mg and 10.0% and 4.7% with 300/100 mg but decreased by 12.6% and 8.4% with placebo. Participants receiving BUP-XR compared with placebo had significantly fewer hospital days per person-year observed. CONCLUSIONS: These results show the feasibility of measuring patient-centered life changes in substance use disorder clinical studies. Participants receiving up to 6 monthly injections of BUP-XR, compared with placebo, reported better health, increased medication satisfaction, increased employment, and decreased healthcare utilization.

Remission from chronic opioid use-Studying environmental and socio-economic factors on recovery (RECOVER): Study design and participant characteristics.

Few opioid use disorder (OUD) treatment studies measure meaningful life changes during long-term recovery, focusing instead on retention and abstinence. Here, we report on the design and participant characteristics of the RECOVER study, a study exploring life changes in persons with OUD for up to 24 months following participation in a Phase III trial evaluating buprenorphine extended-release monthly injection for subcutaneous use (known as RBP-6000 during development). This multisite, observational, cohort study tracks clinical, environmental, and socio-economic changes using self-administered assessments, urine drug screens (UDS), and public databases. Outcomes include demographics (e.g., patient characteristics, employment history, criminal history), lifetime and recent OUD drug use and treatment, and current health and resource use. Demographic and psychosocial characteristics are compared to a national, population-based study. RECOVER participants (N = 533) tend to be single, white, males aged 26 years or older. Mean age at first opioid use was 21.7 years; lifetime substance-related overdose was 24.2%. At first assessment, 334 (62.7%) participants reported past 7-day and 296 (55.5%) reported past 28-day opioid abstinence. Five hundred UDS were collected at the first assessment; buprenorphine (90.6%), marijuana (45.2%), and opiates (34.4%) were most commonly identified. Two hundred forty-nine (47.2%) participants reported full- or part-time employment. Participants were like a national sample with differences found for age, race/ethnicity, employment, education, and health-related quality of life. We hope that further research using this approach can provide data supporting the patient-centered development of OUD treatments and be adopted by substance use disorder studies to incorporate recovery-related, life-activity outcomes.

Relationship between buprenorphine adherence and relapse, health care utilization and costs in privately and publicly insured patients with opioid use disorder.

BACKGROUND: Treatment for opioid use disorder is important because of the negative health, societal and economic consequences of illicit opioid use, but treatment adherence can be a challenge. This study assessed the association between buprenorphine medication-assisted treatment (MAT) adherence and relapse, health care utilization and costs. PATIENTS AND METHODS: Patients with opioid use disorder who were newly initiating a buprenorphine MAT regimen were identified in the 2008-2014 MarketScan® Commercial and Medicaid Databases and followed for 12 months after their earliest outpatient pharmacy claim for buprenorphine. Adherence was categorized using proportion of days covered (PDC) with buprenorphine, and patients with PDC≥0.80 were classified as adherent. Descriptive and adjusted analyses compared relapse prevalence, utilization and costs, all measured in the 12 months following buprenorphine MAT initiation, of adherent patients to patients in non-adherent PDC categories (PDC<0.20, 0.20≤PDC<0.40, 0.40≤PDC<0.60, 0.60≤PDC<0.80). RESULTS: Adherent patients were 37.1% of the Commercial sample (N=16,085) and 41.3% of the Medicaid sample (N=5,688). In both samples, non-adherent patients were significantly more likely than adherent patients to relapse and to have hospitalizations and emergency department visits. As a result, as buprenorphine MAT adherence increased, pharmacy costs increased, but medical costs decreased. Total costs (pharmacy plus medical costs) in the 12 months following buprenorphine MAT initiation decreased with adherence in Commercial patients ($28,525 for PDC<0.20 to $17,844 for PDC≥0.80). A slight decrease in total costs in the 12 months following buprenorphine MAT initiation was also observed in Medicaid patients ($21,292 for PDC<0.20 to $18,621 for PDC≥0.80). After adjustment, total costs of adherent patients in the Commercial sample ($17,519) were significantly lower compared with those of non-adherent patients (range $20,294-$24,431). In the Medicaid sample, adjusted total costs were not significantly different between adherence groups. CONCLUSION: Buprenorphine MAT adherence in the 12 months following treatment was associated with reduced odds of relapse and reduced unadjusted medical costs. For Commercial patients who were adherent to treatment, the adjusted total costs were predicted to be 30% lower than those for patients with PDC<0.20.

Characteristics and treatment patterns of US commercially insured and Medicaid patients with opioid dependence or abuse.

OBJECTIVE: To identify the demographic and clinical characteristics of commercially insured and Medicaid patients with a diagnosis of opioid dependence or abuse and to describe the pharmacological and nonpharmacological treatments received by these patients. DESIGN: This was a retrospective observational study using de-identified administrative claims data. SETTING: The analysis included commercially insured and Medicaid patient data extracted from the Truven Health MarketScan® Commercial and Medicaid Databases. PATIENTS: Patients with a diagnosis of opioid dependence or abuse from 2008 to 2014 (earliest diagnosis = index date) and a minimum of 6 months of pre-index and postindex continuous enrollment in the database. MAIN OUTCOME MEASURE(S): Baseline demographic and clinical characteristics, medication-assisted treatment (MAT), and treatment other than MAT received following diagnosis, and the clinical practice setting in which patients received any opioid dependence-related care were reported. RESULTS: Data from commercially insured (N = 103,768) and Medicaid (N = 50,552) patients were analyzed. Common comorbid conditions included chronic pain (48.6 percent Commercial, 56.8 percent Medicaid), depressive disorder (24.0 percent Commercial, 32.8 percent Medicaid), and other substance abuse disorders (13.3 percent Commercial, 23.7 percent Medicaid). Nearly one third of both Commercial (31.6 percent) and Medicaid (33.6 percent) patients did not have any claims for psychosocial therapy or MAT during the follow-up period. Only 24.3 percent of Commercial patients and 20.4 percent of Medicaid patients had evidence of claims for both MAT and psychosocial treatment anytime following diagnosis. CONCLUSIONS: The results suggest that there are opportunities to improve care through comprehensive and coordinated treatment for opioid dependence/abuse. Policies aimed at improving treatment access may be warranted.

Heterogeneity of nonadherent buprenorphine patients: subgroup characteristics and outcomes.

OBJECTIVES: To examine patient characteristics and outcomes associated with nonadherence to buprenorphine and to identify specific patterns of nonadherent behavior. STUDY DESIGN: Cross-sectional, retrospective analysis of health claims data. METHODS: Aetna's administrative claims data were used to categorize incident opioid use disorder (OUD) patients based on buprenorphine medication possession ratio (MPR) into adherent (n = 172) and nonadherent (n = 305) groups. Adherent groups were then divided into 5 subgroups based on level of MPR, as well as 2 a priori-defined groups: intermittent adherent (IA) and early treatment discontinuation-no consequences (ETDNC). Groups were compared on patient characteristics and outcomes. RESULTS: Nonadherent members incurred significantly greater healthcare costs and were more likely to relapse (P <.05). The use of high-cost healthcare services increased as a function of decreasing MPR (P <.05). Assessment of the a priori groups revealed IA members to have outcomes similar to nonadherent patients, while ETDNC members exhibited outcomes similar to adherent members. CONCLUSIONS: Administrative claims can be used to define subgroups of buprenorphine-medication assisted treatment (B-MAT) patients. Nonadherence was related to an increased likelihood of relapse, and there is an inverse relationship between MPR and cost. The heterogeneity observed within this sample indicates that treatment regimens effective for 1 subgroup may not be appropriate for all OUD patients. Increased understanding of B-MAT nonadherent subgroups may facilitate development of new interventions and medications specifically designed for nonadherent B-MAT patients, potentially leading to improved outcomes and reduced costs of care.

An economic analysis of tolvaptan compared with fluid restriction among hospitalized patients with hyponatremia.

OBJECTIVE: The vasopressin-receptor antagonist tolvaptan is used for the treatment of hyponatremia (HN) in hospitalized patients with congestive heart failure (CHF) or syndrome of inappropriate antidiuretic hormone secretion (SIADH). The objective of this economic modeling study was to assess the potential cost and health outcomes associated with tolvaptan in comparison with fluid restriction (FR). METHODS: A decision-analytic model was developed to estimate potential cost and health outcomes associated with tolvaptan compared with FR among hospitalized CHF and SIADH patients with severe HN (serum sodium [SS] levels < 125 mEq/L). The model, which was populated with data from the published literature, assumes that response to treatment influences hospital length of stay, probability of an intensive care unit (ICU) admission, and probability of a 30-day all-cause hospital readmission. One-way and probabilistic sensitivity analyses (PSAs) assessed the influence of parameter uncertainty on model results. RESULTS: Model results suggest that, among hospitalized CHF patients with severe HN, the use of tolvaptan compared with FR may lead to reductions of 7.2% and 4.6% in ICU admissions and 30-day readmissions, respectively. Compared with FR, tolvaptan may result in total cost-savings of $156 per hospitalized CHF patient. Among hospitalized SIADH patients with severe HN, the model suggested reductions of 14.6% and 5.1% in ICU admissions and 30-day readmissions, respectively. Compared with FR, tolvaptan may result in total cost-savings of $135 per hospitalized SIADH patient. PSAs found that the probabilities of net cost-savings from the use of tolvaptan compared with FR were 64% and 59% among patients with severe HN with CHF and SIADH, respectively. CONCLUSIONS: Decision-analytic modeling based on published data for hospitalized CHF and SIADH patients with severe HN, indicates that tolvaptan compared with FR has the potential to improve health outcomes and produce cost-savings that more than offset the cost of tolvaptan.

Cost-effectiveness of Low-dose Submicron Diclofenac Compared With Generic Diclofenac.

PURPOSE: NSAIDs are commonly prescribed for the treatment of pain and inflammation. Despite the effectiveness of NSAIDs, concerns exist regarding their tolerability. Worldwide health authorities, including the European Medicines Agency, Health Canada, and the US Food and Drug Administration, have advised that NSAIDs be prescribed at the lowest effective dosage and for the shortest duration. Effective lowering of NSAID dosage without compromising pain relief has been demonstrated in randomized, controlled trials of the recently approved NSAID lower-dose submicron diclofenac. Building on previously published work from an independently published systematic review and meta-analysis, a linear dose-toxicity relationship between diclofenac dose and serious gastrointestinal (GI) events was recently demonstrated, indicating that reductions in adverse events (AEs) may be seen even with modest dose reductions in many patients. The objective of the present study was to estimate the potential reduction in risk for NSAID dose-related AEs, corresponding savings in health care costs, and the incremental cost-effectiveness of submicron diclofenac compared with generic diclofenac in the United States. METHODS: Our decision-analytic cost-effectiveness model considered a subset of potential AEs that may be avoided by lowering NSAID dosage. To estimate the expected reductions in upper GI bleeding/perforation and major cardiovascular events with submicron diclofenac, our model used prediction equations estimated by meta-regressions using data from systematic literature reviews. Utilities, lifetime costs, and health outcomes associated with AEs were estimated using data from the literature. The face validity of the model structure and inputs was confirmed by clinical experts in the United States. Results were evaluated in 1-way and probabilistic sensitivity analyses. FINDINGS: The model predicted that submicron diclofenac versus generic diclofenac could reduce the occurrence of modeled GI events (by 18.0%), cardiovascular events (by 6.9%), and acute renal failure (by 18.8%), leading to a 9.8% reduction in costs of treating AEs. Submicron diclofenac was predicted to be cost-saving, with results relatively insensitive to parameter uncertainty. IMPLICATIONS: Submicron diclofenac has the potential to provide clinical and economic value to patients using NSAIDs in the United States. Further investigation regarding the potential effects of submicron diclofenac on the risks for additional NSAID dose-related toxicities should be explored.