Cost-effectiveness of weight-management pharmacotherapies in Canada: a societal perspective.

OBJECTIVES: This study aimed to assess the cost-effectiveness of weight-management pharmacotherapies approved by Canada Health, i.e., orlistat, naltrexone 32 mg/bupropion 360 mg (NB-32), liraglutide 3.0 mg and semaglutide 2.4 mg as compared to the current standard of care (SoC). METHODS: Analyses were conducted using a cohort with a mean starting age 50 years, body mass index (BMI) 37.5 kg/m2, and 27.6% having type 2 diabetes. Using treatment-specific changes in surrogate endpoints from the STEP trials (BMI, glycemic, blood pressure, lipids), besides a network meta-analysis, the occurrence of weight-related complications, costs, and quality-adjusted life-years (QALYs) were projected over lifetime. RESULTS: From a societal perspective, at a willingness-to-pay (WTP) threshold of CAD 50 000 per QALY, semaglutide 2.4 mg was the most cost-effective treatment, at an incremental cost-utility ratio (ICUR) of CAD 31 243 and CAD 29 014 per QALY gained versus the next best alternative, i.e., orlistat, and SoC, respectively. Semaglutide 2.4 mg extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg and remained cost-effective both under a public and private payer perspective. Results were robust to sensitivity analyses varying post-treatment catch-up rates, longer treatment durations and using real-world cohort characteristics. Semaglutide 2.4 mg was the preferred intervention, with a likelihood of 70% at a WTP threshold of CAD 50 000 per QALY gained. However, when the modeled benefits of weight-loss on cancer, mortality, cardiovascular disease (CVD) or osteoarthritis surgeries were removed simultaneously, orlistat emerged as the best value for money compared with SoC, with an ICUR of CAD 35 723 per QALY gained. CONCLUSION: Semaglutide 2.4 mg was the most cost-effective treatment alternative compared with D&E or orlistat alone, and extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg. Results were sensitive to the inclusion of the combined benefits of mortality, cancer, CVD, and knee osteoarthritis.

Variation in Initiation, Engagement, and Retention on Medications for Opioid Use Disorder Based on Health Insurance Plan Design.

BACKGROUND: The association between cost-sharing and receipt of medication for opioid use disorder (MOUD) is unknown. METHODS: We constructed a cohort of 10,513 commercially insured individuals with a new diagnosis of opioid use disorder and information on insurance cost-sharing in a large national deidentified claims database. We examined 4 cost-sharing measures: (1) pharmacy deductible; (2) medical service deductible; (3) pharmacy medication copay; and (4) medical office copay. We measured MOUD (naltrexone, buprenorphine, or methadone) initiation (within 14 d of diagnosis), engagement (second receipt within 34 d of first), and 6-month retention (continuous receipt without 14-d gap). We used multivariable logistic regression to assess the association between cost-sharing and MOUD initiation, engagement, and retention. We calculated total out-of-pocket costs in the 30 days following MOUD initiation for each type of MOUD. RESULTS: Of 10,513 individuals with incident opioid use disorder, 1202 (11%) initiated MOUD, 742 (7%) engaged, and 253 (2%) were retained in MOUD at 6 months. A high ($1000+) medical deductible was associated with a lower odds of initiation compared with no deductible (odds ratio: 0.85, 95% confidence interval: 0.74-0.98). We found no significant associations between other cost-sharing measures for initiation, engagement, or retention. Median initial 30-day out-of-pocket costs ranged from $100 for methadone to $710 for extended-release naltrexone. CONCLUSIONS: Among insurance plan cost-sharing measures, only medical services deductible showed an association with decreased MOUD initiation. Policy and benefit design should consider ways to reduce cost barriers to initiation and retention in MOUD.

Cost-effectiveness of alcohol use treatments in patients with alcohol-related cirrhosis.

BACKGROUND & AIMS: Alcohol use treatment such as medication-assisted therapies (MATs) and counseling are available and effective in promoting alcohol abstinence. We sought to explore the cost-effectiveness of different alcohol use treatments among patients with compensated alcohol-related cirrhosis (AC). METHODS: We simulated a cohort of patients with compensated AC receiving care from a hepatology clinic over their lifetimes. We estimated costs (in 2017 US$) and benefits in terms of quality-adjusted life years (QALYs) gained from healthcare and societal perspectives. Transition probabilities, costs, and health utility weights were taken from the literature. Treatment effects of FDA-approved MATs (acamprosate and naltrexone) and non-FDA approved MATs (baclofen, gabapentin, and topiramate) and counseling were based on a study of employer-insured patients with AC. We calculated incremental cost-effectiveness ratios (ICERs) and performed one-way and probabilistic sensitivity analyses to understand the impact of parameter uncertainty. RESULTS: Compared to a do-nothing scenario, MATs and counseling were found to be cost-saving from a healthcare perspective, which means that they provide more benefits with less costs than no intervention. Compared to other interventions, acamprosate and naltrexone cost the least and provide the most QALYs. If the effectiveness of MATs and counseling decreased, these interventions would still be cost-effective based on the commonly used $100,000 per QALY gained threshold. Several sensitivity and scenario analyses showed that our main findings are robust. CONCLUSIONS: Among patients with compensated AC, MATs and counseling are extremely cost-effective, and in some cases cost-saving, interventions to prevent decompensation and improve health. Health policies (e.g. payer reimbursement) should emphasize and appropriately compensate for these interventions. LAY SUMMARY: Alcohol use treatments, including physician counseling and medication-assisted therapies (MATs), improve the outcomes of patients with compensated alcohol-related cirrhosis, though use and access have remained suboptimal. In this study, we found that counseling and MATs are extremely cost-effective, and in some cases cost-saving, interventions to help patients with alcohol-related cirrhosis abstain from alcohol and improve their health. Wider use of these interventions should be encouraged.

Health and economic outcomes of treatment with extended-release naltrexone among pre-release prisoners with opioid use disorder (HOPPER): protocol for an evaluation of two randomized effectiveness trials.

BACKGROUND: Persons with an opioid use disorder (OUD) who were incarcerated face many challenges to remaining abstinent; concomitantly, opioid-overdose is the leading cause of death among this population, with the initial weeks following release proving especially fatal. Extended-release naltrexone (XR-NTX) is the most widely-accepted, evidence-based OUD pharmacotherapy in criminal justice settings, and ensures approximately 30 days of protection from opioid overdose. The high cost of XR-NTX serves as a barrier to uptake by many prison/jail systems; however, the cost of the medication should not be viewed in isolation. Prison/jail healthcare budgets are ultimately determined by policymakers, and the benefits/cost-offsets associated with effective OUD treatment will directly and indirectly affect their overall budgets, and society as a whole. METHODS: This protocol describes a study funded by the National Institute of Drug Abuse (NIDA) to: evaluate changes in healthcare utilization, health-related quality-of-life, and other resources associated with different strategies of XR-NTX delivery to persons with OUD being released from incarceration; and estimate the relative "value" of each strategy. Data from two ongoing, publicly-funded, randomized-controlled trials will be used to evaluate these questions. In Study A, (XR-NTX Before vs. After Reentry), participants are randomized to receive their first XR-NTX dose before release, or at a nearby program post-release. In Study B, (enhanced XR-NTX vs. XR-NTX), both arms receive XR-NTX prior to release; the enhanced arm receives mobile medical (place of residence) XR-NTX treatment post-release, and the XR-NTX arm receives referral to a community treatment program post-release. The economic data collection instruments required to evaluate outcomes of interest were incorporated into both studies from baseline. Moreover, because the same instruments are being used in both trials on comparable populations, we have the opportunity to not only assess differences in outcomes between study arms within each trial, but also to merge the data sets and test for differences across trials. DISCUSSION: Initiating XR-NTX for OUD prior to release from incarceration may improve patient health and well-being, while also producing downstream cost-offsets. This study offers the unique opportunity to assess the effectiveness and cost-effectiveness of multiple strategies, according to different stakeholder perspectives.

A Summary from the Institute for Clinical and Economic Review's New England Comparative Effectiveness Public Advisory Council.

DISCLOSURES: Funding for this summary was contributed by the Laura and John Arnold Foundation, Blue Shield of California, and California Health Care Foundation to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, AHIP Anthem, Blue Shield of California, CVS Caremark, Express Scripts, Harvard Pilgrim Health Care, Cambia Health Solutions, United Healthcare, Kaiser Permanente, Premera Blue Cross, AstraZeneca, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, National Pharmaceutical Council, Prime Therapeutics, Sanofi, Spark Therapeutics, Health Care Service Corporation, Editas, Alnylam, Regeneron, Mallinkrodt, Biogen, HealthPartners, and Novartis. Otuonye, Kumar, and Pearson are ICER employees. Banken received consulting fees from ICER for work on this report.

Extended-release vs. oral naltrexone for alcohol dependence treatment in primary care (XON).

BACKGROUND: Extended-release naltrexone (XR-NTX, Vivitrol®) and daily oral naltrexone tablets (O-NTX) are FDA-approved mu opioid receptor antagonist medications for alcohol dependence treatment. Despite the efficacy of O-NTX, non-adherence and poor treatment retention have limited its adoption into primary care. XR-NTX is a once-a-month injectable formulation that offers a potentially more effective treatment option in reducing alcohol consumption and heavy drinking episodes among persons with alcohol use disorders. METHODS: This pragmatic, open-label, randomized controlled trial examines the effectiveness of XR-NTX vs. O-NTX in producing a Good Clinical Outcome, defined as abstinence or moderate drinking (<2 drinks/day, men; <1 drink/day, women; and < 2 heavy drinking occasions/month) during the final 20 of 24 weeks of primary care-based Medical Management treatment for alcohol dependence. Secondary aims will estimate the cost effectiveness of XR-NTX vs. O-NTX, in conjunction with primary-care based Medical Management for both groups, and patient-level characteristics associated with effectiveness in both arms. Alcohol dependent persons are recruited from the community into treatment in a New York City public hospital primary care setting (Bellevue Hospital Center) for 24 weeks of either XR-NTX (n = 117) or O-NTX (n = 120). RESULTS: We describe the rationale, specific aims, design, and recruitment results to date. Alternative design considerations and secondary aims and outcomes are reported. CONCLUSIONS: XR-NTX treatment in a primary care setting is potentially more efficacious, feasible, and cost-effective than oral naltrexone when treating community-dwelling persons with alcohol use disorders. This study will estimate XR-NTX's treatment and cost effectiveness relative to oral naltrexone.

The Affordable Care Act In The Heart Of The Opioid Crisis: Evidence From West Virginia.

West Virginia is at the epicenter of a national opioid crisis, with a 2016 fatal opioid overdose rate of 43.4 per 100,000 population-more than triple the US average. We used claims data for 2014-16 to examine trends in treatment for opioid use disorder (OUD) among people enrolled in the West Virginia Medicaid expansion program under the Affordable Care Act. Expanding Medicaid could provide services to populations that may previously have had limited access to OUD treatment. We thus sought to understand trends over time in OUD diagnosis and treatment, especially with medications. About 5.5 percent of all enrollees were diagnosed with OUD per year, and the monthly prevalence of OUD diagnoses nearly tripled during this three-year period. The ratio of people filling buprenorphine to the number diagnosed with OUD was around one-third in early 2014, increasing to more than 75 percent by late 2016. Mean annual duration of filled buprenorphine increased from 161 days in 2014 to 185 days in 2016, and most people filling buprenorphine also received counseling and drug testing during the study period. The growing use of medication treatment for OUD in the West Virginia Medicaid expansion population provides an opportunity to reduce overdose deaths.

Cost-Effectiveness Analysis of Genotype-Guided Treatment Allocation in Patients with Alcohol Use Disorders Using Naltrexone or Acamprosate, Using a Modeling Approach.

Alcohol use disorders (AUD) are a major contributor to the global burden of disease, and have huge societal impact. Some studies show that AUD patients carrying the G-allele of the OPRM1 variant c.118A>G respond better to naltrexone, resulting in reduced relapse rates compared to carriers of the AA genotype. Genotype-guided treatment allocation of these patients carrying a G-allele to naltrexone could potentially improve the treatment outcome. However, cost-effectiveness of this strategy should be investigated before considering clinical implementation. We, therefore, evaluated costs and Quality-Adjusted Life-Years (QALYs), using a modelling approach, from an European perspective, of genotype-guided treatment allocation (G-allele carriers receiving naltrexone; AA homozygotes acamprosate or naltrexone) compared to standard care (random treatment allocation to acamprosate or naltrexone), by using a Markov model. Genotype-guided treatment allocation resulted in incremental costs of EUR 66 (95% CI -28 to 149) and incremental effects of 0.005 QALYs (95% CI 0.000-0.011) per patient (incremental cost-effectiveness ratio of EUR 13,350 per QALY). Sensitivity analyses showed that the risk ratio to relapse after treatment allocation had the largest impact on the cost-effectiveness. Depending on the willingness to pay for a gain of one QALY, probabilities that the intervention is cost-effective varies between 6 and 79%. In conclusion, pharmacogenetic treatment allocation of AUD patients to naltrexone, based on OPRM1 genotype, can be a cost-effective strategy, and could have potential individual and societal benefits. However, more evidence on the impact of genotype-guided treatment allocation on relapse is needed to substantiate these conclusions, as there is contradictory evidence about the effectiveness of OPRM1 genotyping.

A health economic model to assess the cost-effectiveness of OPTIFAST for the treatment of obesity in the United States.

OBJECTIVES: Obesity is associated with high direct medical costs and indirect costs resulting from productivity loss. The high prevalence of obesity generates a justified need to identify cost-effective weight loss approaches from a payer's perspective. Within the variety of weight management techniques, OPTIFAST is a clinically recognized and scientifically proven total meal replacement Low Calorie Diet that provides meaningful results in terms of weight loss and reduction in comorbidities. The objective of this study is assess potential cost-savings of the OPTIFAST program in the US, as compared to "no intervention" and pharmacotherapy. METHODS: An event-driven decision analytic model was used to estimate payer's cost-savings from reimbursement of the 1-year OPTIFAST program over 3 years in the US. The analysis was performed for the broad population of obese persons (BMI >30 kg/m2) undergoing the OPTIFAST program vs liraglutide 3 mg, naltrexone/bupropion and vs "no intervention". The model included the risk of complications related to increased BMI. Data sources included published literature, clinical trials, official US price/tariff lists, and national population statistics. The primary perspective was that of a US payer; costs were provided in 2016 US dollars. RESULTS: OPTIFAST leads over a period of 3 years to cost-savings of USD 9,285 per class I and II obese patient (BMI 30-39.9 kg/m2) as compared to liraglutide and USD 685 as compared to naltrexone/bupropion. In the same time perspective, the OPTIFAST program leads to a reduction of cost of obesity complications of USD 1,951 as compared to "no intervention", with the incremental cost-effectiveness ratio of USD 6,475 per QALY. Scenario analyses also show substantial cost-savings in patients with class III obesity (BMI ≥ 40.0 kg/m2) and patients with obesity (BMI = 30-39.9 kg/m2) and type 2 diabetes vs all three previous comparators and bariatric surgery. CONCLUSIONS: Reimbursing OPTIFAST leads to meaningful cost-savings for US payers as compared with "no intervention" and liraglutide and naltrexone/bupropion in obese patients. Similar results can be expected in matching healthcare settings of other countries. Moreover, OPTIFAST has additional clinical and economic advantages through very low complication and adverse events rates.

Healthcare utilization and costs associated with treatment for opioid dependence.

OBJECTIVE: Opioid use disorder (OUD) can be managed with medication assisted therapy (MAT) (methadone [MET], buprenorphine [BUP], or extended-release naltrexone [XR-NTX]) or counseling alone (non-pharmacological therapy [NPT]). The objective of this study was to evaluate healthcare resource utilization and costs associated with XR-NTX compared with alternative treatments for opioid dependence. METHODS: Adults with a diagnosis of opioid dependence who initiated treatment with XR-NTX, BUP, MET, or NPT between January 1, 2011 and December 31, 2014 were identified in the Truven Health MarketScan Commercial administrative claims database. Healthcare resource utilization, costs (inpatient [IP], emergency department [ED], outpatient [OP], and pharmacy) and adherence were evaluated for each cohort during 12-month baseline and follow-up periods. RESULTS: A total of 29,235 patients were included in the analysis; 1,041, 20,566, 745, and 6,883 received XR-NTX, BUP, MET, and NPT, respectively. Patients in the XR-NTX cohort were significantly younger and had more comorbidities compared with the other cohorts. Patients in the XR-NTX group had the largest percentage decrease in IP and ED utilization and costs from baseline to follow-up. OP and pharmacy costs increased significantly from baseline to follow-up for all cohorts. Overall, there was no significant change in total healthcare costs for the XR-NTX group, whereas the costs increased significantly for other groups (BUP = +43%, MET = +47.7%, NPT = +38.8%). CONCLUSIONS: Healthcare resource utilization and costs increased from baseline to follow-up in BUP, MET, and NPT patients, whereas patients receiving XR-NTX experienced no such increase. This analysis suggests there may be economic value in the use of XR-NTX for OUD.

State-Targeted Funding and Technical Assistance to Increase Access to Medication Treatment for Opioid Use Disorder.

OBJECTIVE: As the United States grapples with an opioid epidemic, expanding access to effective treatment for opioid use disorder is a major public health priority. Identifying effective policy tools that can be used to expand access to care is critically important. This article examines the relationship between state-targeted funding and technical assistance and adoption of three medications for treating opioid use disorder: oral naltrexone, injectable naltrexone, and buprenorphine. METHODS: This study draws from the 2013-2014 wave of the National Drug Abuse Treatment System Survey, a nationally representative, longitudinal study of substance use disorder treatment programs. The sample includes data from 695 treatment programs (85.5% response rate) and representatives from single-state agencies in 49 states and Washington, D.C. (98% response rate). Logistic regression was used to examine the relationships of single-state agency targeted funding and technical assistance to availability of opioid use disorder medications among treatment programs. RESULTS: State-targeted funding was associated with increased program-level adoption of oral naltrexone (adjusted odds ratio [AOR]=3.14, 95% confidence interval [CI]=1.49-6.60, p=.004) and buprenorphine (AOR=2.47, 95% CI=1.31-4.67, p=.006). Buprenorphine adoption was also correlated with state technical assistance to support medication provision (AOR=1.18, 95% CI=1.00-1.39, p=.049). CONCLUSIONS: State-targeted funding for medications may be a viable policy lever for increasing access to opioid use disorder medications. Given the historically low rates of opioid use disorder medication adoption in treatment programs, single-state agency targeted funding is a potentially important tool to reduce mortality and morbidity associated with opioid disorders and misuse.

Cost-effectiveness of extended release naltrexone to prevent relapse among criminal justice-involved individuals with a history of opioid use disorder.

BACKGROUND AND AIMS: Criminal justice-involved individuals are highly susceptible to opioid relapse and overdose-related deaths. In a recent randomized trial, we demonstrated the effectiveness of extended-release naltrexone (XR-NTX; Vivitrol® ) in preventing opioid relapse among criminal justice-involved US adults with a history of opioid use disorder. The cost of XR-NTX may be a significant barrier to adoption. Thus, it is important to account for improved quality of life and downstream cost-offsets. Our aims were to (1) estimate the incremental cost per quality-adjusted life-year (QALY) gained for XR-NTX versus treatment as usual (TAU) and evaluate it relative to generally accepted value thresholds; and (2) estimate the incremental cost per additional year of opioid abstinence. DESIGN: Economic evaluation of the aforementioned trial from the taxpayer perspective. Participants were randomized to 25 weeks of XR-NTX injections or TAU; follow-up occurred at 52 and 78 weeks. SETTING: Five study sites in the US Northeast corridor. PARTICIPANTS: A total of 308 participants were randomized to XR-NTX (n = 153) or TAU (n = 155). MEASUREMENTS: Incremental costs relative to incremental economic and clinical effectiveness measures, QALYs and abstinent years, respectively. FINDINGS: The 25-week cost per QALY and abstinent-year figures were $162 150 and $46 329, respectively. The 78-week figures were $76 400/QALY and $16 371/abstinent year. At 25 weeks, we can be 10% certain that XR-NTX is cost-effective at a value threshold of $100 000/QALY and 62% certain at $200 000/QALY. At 78 weeks, the cost-effectiveness probabilities are 59% at $100 000/QALY and 76% at $200 000/QALY. We can be 95% confident that the intervention would be considered 'good value' at $90 000/abstinent year at 25 weeks and $500/abstinent year at 78 weeks. CONCLUSIONS: While extended-release naltrexone appears to be effective in increasing both quality-adjusted life-years (QALYs) and abstinence, it does not appear to be cost-effective using generally accepted value thresholds for QALYs, due to the high price of the injection.

NIDA Clinical Trials Network CTN-0051, Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment (X:BOT): Study design and rationale.

INTRODUCTION: For opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays. Long-term abstinence is rarely achieved; many patients relapse and overdose after detoxification. Methadone, buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) can prevent opioid relapse but are underutilized. This study is intended to develop an evidence-base to help patients and providers make informed choices and to foster wider adoption of relapse-prevention pharmacotherapies. METHODS: The National Institute on Drug Abuse's Clinical Trials Network (CTN) study CTN-0051, X:BOT, is a comparative effectiveness study of treatment for 24weeks with XR-NTX, an opioid antagonist, versus BUP-NX, a high affinity partial opioid agonist, for opioid dependent patients initiating treatment at 8 short-term residential (detoxification) units and continuing care as outpatients. Up to 600 participants are randomized (1:1) to XR-NTX or BUP-NX. RESULTS: The primary outcome is time to opioid relapse (i.e., loss of persistent abstinence) across the 24-week treatment phase. Differences between arms in the distribution of time-to-relapse will be compared (construction of the asymptotic 95% CI for the hazard ratio of the difference between arms). Secondary outcomes include proportions retained in treatment, rates of opioid abstinence, adverse events, cigarette, alcohol, and other drug use, and HIV risk behaviors; opioid cravings, quality of life, cognitive function, genetic moderators, and cost effectiveness. CONCLUSIONS: XR-NTX and BUP-NX differ considerably in their characteristics and clinical management; no studies to date have compared XR-NTX with buprenorphine maintenance. Study design choices and compromises inherent to a comparative effectiveness trial of distinct treatment regimens are reviewed. CLINICAL TRIAL REGISTRATION: NCT02032433.

Access to Addiction Pharmacotherapy in Private Health Plans.

BACKGROUND: An increasing number of medications are available to treat addictions. To understand access to addiction medications, it is essential to consider the role of private health plans. To contain medication expenditures, most U.S. health plans use cost-sharing and administrative controls, which may impact physicians' prescribing and patients' use of addiction medications. This study identified health plan approaches to manage access to and utilization of addiction medications (oral and injectable naltrexone, acamprosate, and buprenorphine). METHODS: Data are from a nationally representative survey of private health plans in 2010 (n=385 plans, 935 products; response rate 89%), compared to the same survey in 2003. The study assessed formulary inclusion, prior authorization, step therapy, overall restrictiveness, and if and how health plans encourage pharmacotherapy. RESULTS: Formulary exclusions were rare in 2010, with acamprosate excluded most often, by only 9% of products. Injectable naltrexone was covered by 96% of products. Prior authorization was common for injectable naltrexone (85%) and rare for acamprosate (3%). Step therapy policies were used only for injectable naltrexone (41%) and acamprosate (20%). Several medications were often on the most expensive tier. Changes since 2003 include fewer exclusions, yet increased use of other management approaches. Most health plans encourage use of addiction pharmacotherapy, and use a variety of methods to do so. CONCLUSIONS: Management of addiction medications has increased over time but it is not ubiquitous. However, health plans now also include all medications on formularies and encourage providers to use them, indicating that they value addiction pharmacotherapy as an evidence-based practice.

The Cost Effectiveness of Nalmefene for Reduction of Alcohol Consumption in Alcohol-Dependent Patients with High or Very High Drinking-Risk Levels from a UK Societal Perspective.

AIM: To evaluate costs and health outcomes of nalmefene plus psychosocial support, compared with psychosocial intervention alone, for reducing alcohol consumption in alcohol-dependent patients, specifically focusing on societal costs related to productivity losses and crime. METHODS: A Markov model was constructed to model costs and health outcomes of the treatments over 5 years. Analyses were conducted for nalmefene's licensed population: adults with both alcohol dependence and high or very high drinking-risk levels (DRLs) who do not require immediate detoxification and who have high or very high DRLs after initial assessment. The main outcome measure was cost per quality-adjusted life-year (QALY) gained as assessed from a UK societal perspective. Alcohol-attributable productivity loss, crime and health events occurring at different levels of alcohol consumption were taken from published risk-relation studies. Health-related and societal costs were drawn from public data and the literature. Data on the treatment effect, as well as baseline characteristics of the modelled population and utilities, came from three pivotal phase 3 trials of nalmefene. RESULTS: Nalmefene plus psychosocial support was dominant compared with psychosocial intervention alone, resulting in QALYs gained and reduced societal costs. Sensitivity analyses showed that this conclusion was robust. Nalmefene plus psychosocial support led to per-patient reduced costs of £3324 and £2483, due to reduced productivity losses and crime events, respectively. CONCLUSION: Nalmefene is cost effective from a UK societal perspective, resulting in greater QALY gains and lower costs compared with psychosocial support alone. Nalmefene demonstrates considerable public benefits by reducing alcohol-attributable productivity losses and crime events in adults with both alcohol dependence and high or very high DRLs who do not require immediate detoxification and who have high or very high DRLs after initial assessment.

The Cost-Effectiveness of the Integration of Nalmefene within the UK Healthcare System Treatment Pathway for Alcohol Dependence.

AIMS: To assess the cost-effectiveness of integrating nalmefene within the treatment pathway for alcohol dependence recommended by the National Institute for Health and Care Excellence in the UK. METHODS: A Markov model, taking a UK NHS perspective, followed a cohort with alcohol dependence and high/very high drinking risk levels (HVHDRLs), who do not require immediate detoxification and who continue at HVHDRLs after initial assessment, for 5 years. Costs and quality-adjusted life years (QALYs) from treatment with nalmefene plus psychosocial support versus psychosocial support alone were modelled. The consequent incidence of alcohol-attributable harmful events and disease progression, with the possibility of requiring other options or recurrent treatment, were captured. RESULTS: Nalmefene plus psychosocial support dominated psychosocial support alone, with lower costs and increased QALYs after 5 years. Savings are driven by the higher response to nalmefene, and the subsequent lower cost accumulation for alternatives. CONCLUSIONS: Nalmefene represents a highly cost-effective treatment option in this population. The analysis shows that integrating nalmefene within the current UK clinical treatment pathway for alcohol dependence could reduce the economic burden on the NHS by limiting harmful events and disease progression.

Extended-Release Naltrexone: A Qualitative Analysis of Barriers to Routine Use.

The Medication Research Partnership (a national health plan and nine addiction treatment centers contracted with the health plan) sought to facilitate the adoption of pharmacotherapy for alcohol and opioid use disorders. Qualitative analysis of interviews with treatment center change leaders, individuals working for the manufacturer and its technical assistance contractor, and health plan managers extracted details on the processes used to order, store, bill for, and administer extended-release naltrexone. Qualitative themes were categorized using domains from the Consolidated Framework for Implementation Research (intervention characteristics, outer setting, inner setting, and provider characteristics). Characteristics of XR-NTX that inhibited use included the complexity of ordering and using the medication; cost was also a barrier. Outer setting barriers reflected patient needs and external health plan policies on formulary coverage, benefit management, and reimbursement. Program structures, the lack of physician linkages, a culture resistant to the use of medication, and unease with change were inner setting elements that limited use of XR-NTX. Patient stereotypes and a lack of knowledge about XR-NTX affected practitioner willingness to treat patients and prescribe XR-NTX. The Consolidated Framework for Implementation Research provided a useful lens to understand and interpret the processes affecting access to XR-NTX.

Nalmefene for Reducing Alcohol Consumption in People with Alcohol Dependence: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company (Lundbeck) marketing nalmefene (Selincro) to submit evidence of its clinical and cost effectiveness for reducing alcohol consumption in people with alcohol dependence. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG) and to produce a critical review of the company's submission to NICE. The clinical evidence was derived from three phase III, company-sponsored, randomised, double-blind, placebo-controlled trials in adults with a diagnosis of alcohol dependence comparing nalmefene, taken on an as-needed basis, in conjunction with psychosocial support with placebo in conjunction with psychosocial support. Psychosocial support was provided in the form of BRENDA, an intervention of lower intensity than that recommended in NICE Clinical Guideline 115 (NICE CG115). Post-hoc subgroup analyses were conducted in people who were drinking at high or very high risk levels at baseline and maintained this level of drinking during the screening phase prior to randomisation. This subgroup forms the licensed population. There were a number of limitations and uncertainties in the clinical evidence base which warrant caution in its interpretation. In particular, the post-hoc subgroup analyses and high dropout rates in the three nalmefene studies meant that the inference of treatment effects might be confounded. The company's economic evaluation showed that use of nalmefene in conjunction with psychosocial support in the form of BRENDA dominated the use of BRENDA in conjunction with placebo, providing more quality-adjusted life-years (QALYs) at a reduced cost. However, this evaluation did not meet the final scope issued by NICE, which specified that the comparator should be psychological intervention as defined in NICE CG115. The ERG produced alternative cost per QALY values for the comparison undertaken by the company and suggested three further comparisons deemed relevant: (1) nalmefene with psychological intervention as defined in NICE CG115; (2) delayed use of nalmefene in those who did not respond to psychological intervention as recommended in NICE CG115 alone; and (3) use of naltrexone outside of its marketing authorisation. The ERG thought it probable that using nalmefene in only those people who do not respond to psychological intervention alone was likely to be more cost effective compared with its immediate use in the entire licensed population. The Appraisal Committee accepted the comparison with psychosocial support in the form of BRENDA and believed that the most plausible cost per QALY was likely to be below £5100. Therefore, the Appraisal Committee concluded that nalmefene in conjunction with psychosocial support was a cost effective use of NHS resources compared with psychosocial support alone for treating people with alcohol dependence drinking at a high risk level, without physical withdrawal symptoms and not requiring immediate assisted withdrawal from alcohol.

Cost-Effectiveness of Injectable Extended-Release Naltrexone Compared With Methadone Maintenance and Buprenorphine Maintenance Treatment for Opioid Dependence.

BACKGROUND: The aim of this study was to estimate the cost-effectiveness of injectable extended-release naltrexone (XR-NTX) compared with methadone maintenance and buprenorphine maintenance treatment (MMT and BMT, respectively) for adult males enrolled in treatment for opioid dependence in the United States from the perspective of state-level addiction treatment payers. METHODS: A Markov model with daily time cycles was used to estimate the incremental cost per opioid-free day in a simulated cohort of adult males aged 18-65 over a 6-month period from the state health program perspective. RESULTS: XR-NTX is predicted to be more effective and more costly than methadone or buprenorphine in our target population, with an incremental cost per opioid-free day gained relative to the next-most effective treatment (MMT) of $72. The cost-effectiveness of XR-NTX relative to MMT was driven by its effectiveness in deterring opioid use while receiving treatment. CONCLUSIONS: XR-NTX is a cost-effective medication for treating opioid dependence if state addiction treatment payers are willing to pay at least $72 per opioid-free day.