The Hepatitis C Cascade of Care: Identifying Priorities to Improve Clinical Outcomes

Background: As highly effective hepatitis C virus (HCV) therapies emerge, data are needed to inform the development of interventions to improve HCV treatment rates. We used simulation modeling to estimate the impact of loss to follow-up on HCV treatment outcomes and to identify intervention strategies likely to provide good value for the resources invested in them. Methods: We used a Monte Carlo state-transition model to simulate a hypothetical cohort of chronically HCV-infected individuals recently screened positive for serum HCV antibody. We simulated four hypothetical intervention strategies (linkage to care; treatment initiation; integrated case management; peer navigator) to improve HCV treatment rates, varying efficacies and costs, and identified strategies that would most likely result in the best value for the resources required for implementation. Main measures Sustained virologic responses (SVRs), life expectancy, quality-adjusted life expectancy (QALE), costs from health system and program implementation perspectives, and incremental cost-effectiveness ratios (ICERs). Results: We estimate that imperfect follow-up reduces the real-world effectiveness of HCV therapies by approximately 75%. In the base case, a modestly effective hypothetical peer navigator program maximized the number of SVRs and QALE, with an ICER compared to the next best intervention of $48,700/quality-adjusted life year. Hypothetical interventions that simultaneously addressed multiple points along the cascade provided better outcomes and more value for money than less costly interventions targeting single steps. The 5-year program cost of the hypothetical peer navigator intervention was$14.5 million per 10,000 newly diagnosed individuals. Conclusions: We estimate that imperfect follow-up during the HCV cascade of care greatly reduces the real-world effectiveness of HCV therapy. Our mathematical model shows that modestly effective interventions to improve follow-up would likely be cost-effective. Priority should be given to developing and evaluating interventions addressing multiple points along the cascade rather than options focusing solely on single points

Cost Effectiveness and Cost Containment in the Era of Interferon-Free Therapies to Treat Hepatitis C Virus Genotype 1

Abstract Background. Interferon-free regimens to treat hepatitis C virus (HCV) genotype 1 are effective but costly. At this time, payers in the United States use strategies to control costs including (1) limiting treatment to those with advanced disease and (2) negotiating price discounts in exchange for exclusivity. Methods. We used Monte Carlo simulation to investigate budgetary impact and cost effectiveness of these treatment policies and to identify strategies that balance access with cost control. Outcomes included nondiscounted 5-year payer cost per 10000 HCV-infected patients and incremental cost-effectiveness ratios. Results. We found that the budgetary impact of HCV treatment is high, with 5-year undiscounted costs of $1.0 billion to 2.3 billion per 10000 HCV-infected patients depending on regimen choices. Among noncirrhotic patients, using the least costly interferon-free regimen leads to the lowest payer costs with negligible difference in clinical outcomes, even when the lower cost regimen is less convenient and/or effective. Among cirrhotic patients, more effective but costly regimens remain cost effective. Controlling costs by restricting treatment to those with fibrosis stage 2 or greater disease was cost ineffective for any patient type compared with treating all patients. Conclusions. Treatment strategies using interferon-free therapies to treat all HCV-infected persons are cost effective, but short-term cost is high. Among noncirrhotic patients, using the least costly interferon-free regimen, even if it is not single tablet or once daily, is the cost-control strategy that results in best outcomes. Restricting treatment to patients with more advanced disease often results in worse outcomes than treating all patients, and it is not preferred

Harmonizing healthcare and other resource measures for evaluating economic costs in substance use disorder research

Background Standardization and harmonization of healthcare resource utilization data can improve evaluations of the economic impact of treating people with substance use disorder (SUD), including reductions in use of expensive hospital and emergency department (ED) services, and can ensure consistency with current cost-effectiveness and cost-benefit analysis guidelines. Methods We examined self-reported healthcare and other resource utilization data collected at baseline from three National Institute on Drug Abuse (NIDA)-funded Seek, Test, Treat, and Retain intervention studies of individuals living with/at risk for HIV with SUD. Costs were calculated by multiplying mean healthcare resource utilization measures by monetary conversion factors reflecting cost per unit of care. We normalized baseline recall timeframes to past 30 days and evaluated for missing data. Results We identified measures that are feasible and appropriate for estimating healthcare sector costs including ED visits, inpatient hospital and residential facility stays, and outpatient encounters. We also identified two self-reported measures to inform societal costs (days experiencing SUD problems, participant spending on substances). Missingness was 8% or less for all study measures and was lower for single questions measuring utilization in a recall period. Conclusions We recommend including measures representing units of service with specific recall periods (e.g., 6 months vs. lifetime), and collecting healthcare resource utilization data using single-question measures to reduce missingness

Monetary conversion factors for economic evaluations of substance use disorders

Estimating the economic consequences of substance use disorders (SUDs) is important for evaluating existing programs and new interventions. Policy makers in particular must weigh program effectiveness with scalability and sustainability considerations in deciding which programs to fund with limited resources. This study provides a comprehensive list of monetary conversion factors for a broad range of consequences, services, and outcomes, which can be used in economic evaluations of SUD interventions (primarily in the United States), including common co-occurring conditions such as HCV and HIV. Economic measures were selected from standardized clinical assessment instruments that are used in randomized clinical trials and other research studies (e.g., quasi-experimental community-based projects) to evaluate the impact of SUD interventions. National datasets were also reviewed for additional SUD-related consequences, services, and outcomes. Monetary conversion factors were identified through a comprehensive literature review of published articles as well as targeted searches of other sources such as government reports. Eight service/consequence/outcome domains were identified containing more than sixty monetizable measures of medical and behavioral health services, laboratory services, SUD treatment, social services, productivity outcomes, disability outcomes, criminal activity and criminal justice services, and infectious diseases consequences. Unit-specific monetary conversion factors are reported, along with upper and lower bound estimates, whenever possible. Having an updated and standardized source of monetary conversion factors will facilitate and improve future economic evaluations of interventions targeting SUDs and other risky behaviors. This exercise should be repeated periodically as new sources of data become available to maintain the timeliness, comprehensiveness, and quality of these estimates. •Comprehensive source of Monetary Conversion Factors for estimating the economic consequences of Substance Use Disorders•Features eight service/consequence domains and more than sixty unique measures•Valuable tool for clinicians, researchers, and policy makers seeking to conduct economic evaluation

Economic Evaluations of Pharmacologic Treatment for Opioid Use Disorder: A Systematic Literature Review

The crisis of opioid use puts a strain on resources in the United States and worldwide. There are 3 US Food and Drug Administration–approved medications for treatment of opioid use disorder: methadone, buprenorphine, and injectable extended-release naltrexone (XR-NTX). The comparative effectiveness and cost vary considerably among these 3 medications. Economic evaluations provide evidence that help stakeholders efficiently allocate scarce resources. Our objective was to summarize recent health economic evidence of pharmacologic treatment of opioid use disorder interventions. We searched PubMed for peer-reviewed studies in English from August 2015 through December 2019 as an update to a 2015 review. We used the Drummond checklist to evaluate and categorize economic evaluation study quality. We summarized results by economic evaluation methodology and pharmacologic treatment modality. We identified 105 articles as potentially relevant and included 21 (4 cost-offset studies and 17 cost-effectiveness/cost-benefit studies). We found strengthened evidence on buprenorphine and methadone, indicating that these treatments are economically advantageous compared with no pharmacotherapy, but found limited evidence on XR-NTX. Only half of the cost-effectiveness studies used a generic preference-based measure of effectiveness, limiting broad comparison across diseases/disorders. The disease/disorder-specific cost-effectiveness measures vary widely, suggesting a lack of consensus on the value of substance use disorder treatment. We found studies that provide new evidence supporting the cost-effectiveness of buprenorphine compared with no pharmacotherapy. We found a lack of evidence supporting superior economic value for buprenorphine versus methadone, suggesting that both are attractive alternatives. Further economic research is needed on XR-NTX, as well as other emerging pharmacotherapies, treatment modalities, and dosage forms. •There is new evidence on buprenorphine and strengthened evidence on methadone, indicating that both are economically advantageous treatments for opioid use disorder compared with no pharmacotherapy.•Approximately half of the recent cost-effectiveness studies used a generic preference-based measure of effectiveness (ie, quality-adjusted life-years or disability-adjusted life-years), limiting broad comparison across diseases/disorders because quality-adjusted life-years or disability-adjusted life-years are the only health economic effectiveness measures with commonly accepted value thresholds. There is wide variation in disease/disorder-specific measures, thereby limiting comparisons within the substance use disorder literature.•More economic evidence is needed on injectable naltrexone and novel treatment-delivery modalities

Implementation of a nationwide health economic consultation service to assist substance use researchers: Lessons learned

Background: Health economic evaluation findings assist stakeholders in improving the quality, availability, scalability, and sustainability of evidence-based services, and in maximizing the efficiency of service delivery. The Center for Health Economics of Treatment Interventions for Substance Use Disorders, HCV, and HIV (CHERISH) is a NIDA-funded multi-institutional center of excellence whose mission is to develop and disseminate health-economic research on healthcare utilization, health outcomes, and health-related behaviors that informs substance use disorder treatment policy, and HCV and HIV care of people who use substances. Methods: We designed a consultation service that is free to researchers whose work aligns with CHERISH's mission. The service includes up to six hours of consulting time. After prospective consultees submit their request online, they receive a screening call from the consultation service director, who connects them with a consultant with relevant expertise. Consultees and consultants complete web-based evaluations following the consultation; consultees also complete a six-month follow-up. We report on the status of the service from its inception in July 2015 through June 2017. Results: We have received 28 consultation requests (54% Early Stage Investigators, 57% MD or equivalent, 28% PhD, 61% women) on projects typically related to planning a study or grant application (93%); 71% were HIV/AIDS-related. Leading topics included cost-effectiveness (43%), statistical-analysis/econometrics (36%), cost (32%), cost-benefit (21%), and quality-of-life (18%). All consultees were satisfied with their overall experience, and felt that consultation expectations and objectives were clearly defined and the consultant's expertise was matched appropriately with their needs. Results were similar for consultants, who spent a median of 3 hours on consultations. Conclusions: There is a need for health-economic methodological guidance among substance use, HCV, and HIV researchers. Lessons learned pertain to the feasibility of service provision, the need to implement systems to measure and improve service value, and strategies for service promotion

Cost of pharmacotherapy for opioid use disorders following inpatient detoxification

To estimate the costs of providing extended-release injectable naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX) following inpatient detoxification using data derived from a multisite randomized controlled trial at 8 US community-based treatment programs. Cost data were collected for 3 intervention phases: program start-up, inpatient detoxification, and up to 24 weeks of medication induction and management visits (post detoxification). Cost analyses were from the healthcare sector perspective (2015 US$); patient costs are also reported. We conducted site visits, administered a cost survey to treatment programs, and analyzed study data on medication and services utilization. Nationally representative sources were used to estimate unit costs. Uncertainty was evaluated in sensitivity analyses. Mean start-up costs were$1071 per program for XR-NTX and $828 per program for BUP-NX. Mean costs per participant were$5416 for XR-NTX (57% detoxification, 37% medication, 3% provider, 3% patient) and $4148 for BUP-NX (64$2979 to $8963 for XR-NTX and from$2521 to $6486 for BUP-NX. For treatment providers, offering XR-NTX and/or BUP-NX as part of existing detoxification treatment modalities generates modest costs in addition to the costs of detoxification, which vary substantially among the 8 sites. From the patient's perspective, the costs associated with medication management visits may be a barrier for some individuals considering these treatments

Closing the gaps in opioid use disorder research, policy and practice: conference proceedings

Abstract Drug overdose deaths involving opioids have surged in recent years and the economic cost of the opioid epidemic is estimated to be over $500 billion annually. In the midst of calls for declaring a national emergency, health policy decision makers are considering the best ways to allocate resources to curb the epidemic. On June 9, 2017, 116 invited health researchers, clinicians, policymakers, health system leaders, and other stakeholders met at the University of Pennsylvania to discuss approaches to address the gaps in evidence-based substance use disorder policy and practice, with an emphasis on the opioid epidemic. The conference was sponsored by the Center for Health Economics of Treatment Interventions for Substance Use Disorder, HCV, and HIV (CHERISH), a NIDA-funded National Center of Excellence, and hosted by the Leonard Davis Institute of Health Economics of the University of Pennsylvania. The conference aims were to: (1) foster new relationships between researchers and policymakers through a collaborative work process and (2) generate evidence-based policy recommendations to address the opioid epidemic. The conference concluded with an interactive work session during which attendees self-identified as researchers or policymakers and were divided equally among 13 tables. These groups met to develop and present policy recommendations based on an opioid use disorder case study. Thirteen policy recommendations emerged across four themes: (1) quality of treatment, (2) continuity of care, (3) opioid prescribing and pain management, and (4) consumer engagement. This conference serves as a proposed model to develop equitable, working relationships among researchers, clinicians, and policymakers

Cost-Effectiveness of Buprenorphine-Naloxone Versus Extended-Release Naltrexone to Prevent Opioid Relapse

Not enough evidence exists to compare buprenorphine-naloxone with extended-release naltrexone for treating opioid use disorder. To evaluate the cost-effectiveness of buprenorphine-naloxone versus extended-release naltrexone. Cost-effectiveness analysis alongside a previously reported randomized clinical trial of 570 adults in 8 U.S. inpatient or residential treatment programs. Study instruments. Adults with opioid use disorder. 24-week intervention with an additional 12 weeks of observation. Health care sector and societal. Buprenorphine-naloxone and extended-release naltrexone. Incremental costs combined with incremental quality-adjusted life-years (QALYs) and incremental time abstinent from opioids. Use of the health care sector perspective and a willingness-to-pay threshold of $100 000 per QALY showed buprenorphine-naloxone to be preferable to extended-release naltrexone in 97% of bootstrap replications at 24 weeks and in 85% at 36 weeks. Similar results were obtained with incremental time abstinent from opioids as an outcome and with use of the societal perspective. The base-case results were sensitive to the cost of the 2 treatments and the success of randomized treatment initiation. Relatively short follow-up for a chronic condition, substantial missing data, no information on patient out-of-pocket and social service costs. Buprenorphine-naloxone is preferred to extended-release naltrexone as first-line treatment when both options are clinically appropriate and patients require detoxification before initiating extended-release naltrexone. National Institute on Drug Abuse, National Institutes of Health

Health-related quality of life and opioid use disorder pharmacotherapy: A secondary analysis of a clinical trial

To examine the health-related quality-of-life (HRQoL) of persons with opioid use disorder (OUD) seeking treatment in an inpatient detoxification or short-term residential setting; continuing treatment as outpatients. We conducted a secondary analysis of data from a clinical trial (N = 508) where participants were randomized to extended-release naltrexone or buprenorphine-naloxone for the prevention of opioid relapse. We used a generalized structural equation regression mixture model to identify associations of HRQoL (EQ-5D) trajectories, including latent characteristics, over the 24-week trial and 36-week follow-up period, among participants who reported HRQoL beyond baseline. This novel framework accounted for baseline and time-varying characteristics, while simultaneously identifying latent classes. We identified two subpopulations: HRQoL "pharmacotherapy responsive" (82.3 %) and HRQoL "characteristic sensitive" (17.7 %). The pharmacotherapy responsive subpopulation was characterized by a shortterm HRQoL improvement and then stable HRQoL over time, and by a positive association between HRQoL and receiving pharmacotherapy in the past 30 days. The characteristic sensitive subpopulation was characterized by an initial improvement in HRQoL with a gradual decline over time, and no significant HRQoL response to pharmacotherapy. HRQoL changes over time in this subpopulation were more influenced by baseline demographic, socioeconomic, and psychosocial characteristics. Our findings suggest that while HRQoL may be improved and sustained through targeted efforts to promote use of pharmacotherapy for many persons with OUD, an identifiable subpopulation may require additional services that address socioeconomic and psychosocial issues to achieve HRQoL benefits. Our analysis provides insight for improving individualized care for persons with opioid use disorder seeking treatment