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.

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.

A pharmaceutical industry perspective on the economics of treatments for alcohol and opioid use disorders.

Individuals with alcohol and/or drug use disorders often fail to receive care, or evidence-based care, yet the literature shows health economic benefits. Comparative effectiveness research is emerging that examines approved approaches in terms of real, total healthcare cost/utilization. Comprehensive retrospective insurance claims analyses are few but tend to be nationally distributed and large. The emerging pattern is that, while treatment in general is cost effective, specific therapeutics can yield different health economic outcomes. Cost/utilization data consistently show greater savings with pharmacotherapies (despite their costs) versus psychosocial treatment alone. All FDA-approved addiction pharmacotherapies (oral naltrexone, extended-release naltrexone, acamprosate, disulfiram, buprenorphine, buprenorphine/naloxone, and methadone) are intended for use in conjunction with psychosocial management, not as stand-alone therapeutics; hence, pharmacotherapy costs must offer benefits in addition to abstinence alone or psychological therapy. Patient persistence is problematic, and (despite its cost) extended-release pharmacotherapy may be associated with lower or no greater total healthcare cost, mostly due to reduced hospitalization. The reviewed studies use rigorous case-mix adjustment to balance treatment cohorts but lack the randomization that clinical trials use to protect against confounding. Unlike trials, however, these studies can offer generalizability to diverse populations, providers, and payment models--and are of particular salience to payers.

A literature review of cost-benefit analyses for the treatment of alcohol dependence.

The purpose of this study was to conduct a literature review of cost-benefit studies on pharmacotherapy and psychotherapy treatments of alcohol dependence (AD). A literature search was performed in multiple electronic bibliographic databases. The search identified seven psychotherapy studies from the USA and two pharmacotherapy studies from Europe. In the psychotherapy studies, major benefits are typically seen within the first six months of treatment. The benefit-cost ratio ranged from 1.89 to 39.0. Treatment with acamprosate was found to accrue a net benefit of 21,301 BEF (528 €) per patient over a 24-month period in Belgium and lifetime benefit for each patient in Spain was estimated to be Pta. 3,914,680 (23,528 €). To date, only a few studies exist that have examined the cost-benefit of psychotherapy or pharmacotherapy treatment of AD. Most of the available treatment options for AD appear to produce marked economic benefits.

Alcohol dependence treatments: comprehensive healthcare costs, utilization outcomes, and pharmacotherapy persistence.

OBJECTIVES: To determine the healthcare costs associated with treatment of alcohol dependence with medications versus no medication and across the 4 medications approved by the US Food and Drug Administration (FDA). STUDY DESIGN: Retrospective claims database analysis. METHODS: Eligible adults with alcohol dependence were identified from a large US health plan and the IMS PharMetrics Integrated Database. Data included all medical and pharmacy claims at all available healthcare sites. Propensity score-based matching and inverse probability weighting were applied to baseline demographic, clinical, and healthcare utilization variables for 20,752 patients, half of whom used an FDA-approved medication for alcohol dependence. A similar comparison was performed among 15,502 patients treated with an FDA-approved medication: oral acamprosate calcium (n = 8958), oral disulfiram (n = 3492), oral naltrexone (NTX) hydrochloride (n = 2391), or extended-release injectable naltrexone (XR-NTX; n = 661). Analyses calculated 6-month treatment persistence, utilization, and paid claims for: alcoholism medications, detoxification and rehabilitation, alcohol-related and nonrelated inpatient admissions, outpatient services, and total costs. RESULTS: Medication was associated with fewer admissions of all types. Despite higher costs for medications, total healthcare costs, including inpatient, outpatient, and pharmacy costs, were 30% lower for patients who received a medication for their alcohol dependence. XR-NTX was associated with greater refill persistence and fewer hospitalizations for any reason and lower hospital costs than any of the oral medications. Despite higher costs for XR-NTX itself, total healthcare costs were not significantly different from oral NTX or disulfiram, and were 34% lower than with acamprosate. CONCLUSION: In this largest cost study to date of alcohol pharmacotherapy, patients who received medication had lower healthcare utilization and total costs than patients who did not. XR-NTX showed an advantage over oral medications in treatment persistence and healthcare utilization, at comparable or lower total cost.

The effect of alcohol treatment on social costs of alcohol dependence: results from the COMBINE study.

BACKGROUND: The COMBINE (combined pharmacotherapies and behavioral intervention) clinical trial recently evaluated the efficacy of pharmacotherapies, behavioral therapies, and their combinations for the treatment of alcohol dependence. Previously, the cost and cost-effectiveness of COMBINE have been studied. Policy makers, patients, and nonalcohol-dependent individuals may be concerned not only with alcohol treatment costs but also with the effect of alcohol interventions on broader social costs and outcomes. OBJECTIVES: To estimate the sum of treatment costs plus the costs of health care utilization, arrests, and motor vehicle accidents for the 9 treatments in COMBINE 3 years postrandomization. RESEARCH DESIGN: A cost study based on a randomized controlled clinical trial. SUBJECTS: : The study involved 786 participants 3 years postrandomization. RESULTS: Multivariate results show no significant differences in mean costs between any of the treatment arms as compared with medical management (MM) + placebo for the 3-year postrandomization sample. The median costs of MM + acamprosate, MM + naltrexone, MM + acamprosate + naltrexone, and MM + acamprosate + combined behavioral intervention were significantly lower than the median cost for MM + placebo. CONCLUSIONS: The results show that social cost savings are generated relative to MM + placebo by 3 years postrandomization, and the magnitude of these cost savings is greater than the costs of the COMBINE treatment received 3 years prior. Our study suggests that several alcohol treatments may indeed lead to reduced median social costs associated with health care, arrests, and motor vehicle accidents.

Revisiting the cost-effectiveness of the COMBINE study for alcohol dependent patients: the patient perspective.

OBJECTIVE: Most cost and cost-effectiveness studies of substance abuse treatments focus on the costs to the provider/payer. Although this perspective is important, the costs incurred by patients should also be considered when evaluating treatment. This article presents estimates of patients' costs associated with the Combined Pharmacotherapies and Behavioral Interventions (COMBINE) alcohol treatments and evaluates the treatments' cost-effectiveness from the patient perspective. STUDY DESIGN: A prospective cost-effectiveness study of patients in COMBINE, a randomized controlled clinical trial of 9 alternative alcohol treatment regimens involving 1383 patients with diagnoses of primary alcohol dependence across 11 US clinic sites. We followed a microcosting approach that allowed estimation of patients' costs for specific COMBINE treatment activities. The primary clinical outcomes from COMBINE are used as indicators of treatment effectiveness. RESULTS: The average total patient time devoted to treatment ranged from about 30 hours to 46 hours. Time spent traveling to and from treatment sessions and participation in self-help meetings accounted for the largest portion of patient time costs. The cost-effectiveness results indicate that 6 of the 9 treatments were economically dominated and only 3 treatments are potentially cost-effective depending on patient's willingness to pay for the considered outcomes: medical management (MM) + placebo, MM + naltrexone, and MM + naltrexone + acamprosate. CONCLUSIONS: Few studies consider the patient's perspective in estimating costs and cost-effectiveness even though these costs may have a substantial impact on a patient's treatment choice, ability to access treatment, or treatment adherence. For this study, the choice of the most cost-effective treatment depends on the value placed on the outcomes by the patient, and the conclusions drawn by the patient may differ from that of the provider/payer.

Comparison of healthcare utilization among patients treated with alcoholism medications.

OBJECTIVES: To determine in a large claims database the healthcare utilization and costs associated with treatment of alcohol dependence with medications vs no medication and across 4 US Food and Drug Administration (FDA)-approved medications. STUDY DESIGN: Claims database analysis. METHODS: Eligible adults with alcohol dependence claims (n = 27,135) were identified in a commercial database (MarketScan; Thomson Reuters Inc, Chicago, Illinois). Following propensity score-based matching and inverse probability weighting on demographic, clinical, and healthcare utilization variables, patients who had used an FDA-approved medication for alcohol dependence (n = 2977)were compared with patients who had not (n =2977). Patients treated with oral naltrexone hydrochloride(n = 2064), oral disulfiram (n = 2076), oral acamprosate calcium (n = 5068), or extended-release injectable naltrexone (naltrexone XR) (n = 295) were also compared for 6-month utilization rates of alcoholism medication, inpatient detoxification days, alcoholism-related inpatient days, and outpatient services, as well as inpatient charges. RESULTS: Patients who received alcoholism medications had fewer inpatient detoxification days (706 vs 1163 days per 1000 patients, P <.001), alcoholism-related inpatient days (650 vs 1086 days, P <.001), and alcoholism-related emergency department visits (127 vs 171, P = .005). Among 4 medications, the use of naltrexone XR was associated with fewer inpatient detoxification days (224 days per 1000 patients) than the use of oral naltrexone (552 days, P = .001), disulfiram (403 days, P = .049), or acamprosate (525 days, P <.001). The group receiving naltrexone XR also had fewer alcoholism-related inpatient days than the groups receiving disulfiram or acamprosate. More patients in the naltrexone XR group had an outpatient substance abuse visit compared with patients in the oral alcoholism medication groups. CONCLUSION: Patients who received an alcoholism medication had lower healthcare utilization than patients who did not. Naltrexone XR showed an advantage over oral medications in healthcare utilization and costs.

Cost and cost-effectiveness of the COMBINE study in alcohol-dependent patients.

CONTEXT: The COMBINE (Combined Pharmacotherapies and Behavioral Intervention) clinical trial recently evaluated the efficacy of medications, behavioral therapies, and their combinations for the outpatient treatment of alcohol dependence. The costs and cost-effectiveness of these combinations are unknown and of interest to clinicians and policy makers. OBJECTIVE: To evaluate the costs and cost-effectiveness of the COMBINE Study interventions after 16 weeks of treatment. DESIGN: A prospective cost and cost-effectiveness study of a randomized controlled clinical trial. SETTING: Eleven US clinical sites. PARTICIPANTS: One thousand three hundred eighty-three patients having a diagnosis of primary alcohol dependence. INTERVENTIONS: The study included 9 treatment groups; 4 groups received medical management for 16 weeks with naltrexone, 100 mg/d, acamprosate, 3 g/d, or both, and/or placebo; 4 groups received the same therapy as mentioned earlier with combined behavioral intervention; and 1 group received combined behavioral intervention only. MAIN OUTCOMES MEASURES: Incremental cost per percentage point increase in percentage of days abstinent, incremental cost per patient of avoiding heavy drinking, and incremental cost per patient of achieving a good clinical outcome. RESULTS: On the basis of the mean values of cost and effectiveness, 3 interventions are cost-effective options relative to the other interventions for all 3 outcomes: medical management (MM) with placebo ($409 per patient), MM plus naltrexone therapy ($671 per patient), and MM plus combined naltrexone and acamprosate therapy ($1003 per patient). CONCLUSIONS: To our knowledge, this is only the second prospective cost-effectiveness study with a randomized controlled clinical trial design that has been performed for the treatment of alcohol dependence. Focusing only on effectiveness, MM-naltrexone-acamprosate therapy is not significantly better than MM-naltrexone therapy. However, considering cost and cost-effectiveness, MM-naltrexone-acamprosate therapy may be a better choice, depending on whether the cost of the incremental increase in effectiveness is justified by the decision maker.

Availability of addiction medications in private health plans.

Health plans have implemented cost sharing and administrative controls to constrain escalating prescription expenditures. These policies may impact physicians' prescribing and patients' use of these medications. Important clinical advances in the pharmacological treatment of addiction highlight the need to examine how pharmacy benefits consider medications for substance dependence. The extent of restrictions influencing the availability of these medications to consumers is unknown. We use nationally representative survey data to examine the extent and stringency of private health plans' management of naltrexone and disulfiram for alcohol dependence, and buprenorphine for opiate dependence. Thirty-one percent of insurance products excluded buprenorphine from formularies, whereas 55% placed it on the highest cost-sharing tier. Generic naltrexone is the only substance dependence medication that is both rarely excluded from formularies and usually placed on a lower cost-sharing tier. These findings demonstrate that pharmacy benefits have an impact on access to medications for substance abuse.

Measuring economic outcomes of alcohol treatment using the Economic Form 90.

OBJECTIVE: This article assesses the ability of the economic outcome measures in the Economic Form 90 to detect differences across levels of alcohol dependence as measured by the Alcohol Dependence Scale. METHOD: We used baseline data from the Combining Medications and Behavioral Interventions (COMBINE) Study, a large, multisite clinical trial, to assess the extent to which the economic items on the Economic Form 90 instrument can detect differences across levels of alcohol dependence. RESULTS: After adjusting for differences in demographic characteristics, the Economic Form 90 can detect significant differences across a range of dependence severity levels for the economic outcomes of inpatient medical care, emergency-department medical care, behavioral health care, being on parole or probation, and missed workdays, conditional on being employed. We did not detect significant differences across dependence severity for employment status, outpatient medical care, other criminal justice involvement, or motor vehicle accidents. CONCLUSIONS: The Economic Form 90 can identify differences in many economic outcomes associated with differing levels of alcohol dependence. This suggests that the Economic Form 90 may be useful in assessing changes in economic outcomes that result from changes in alcohol dependence.

Economic evaluation of interventions for problem drinking and alcohol dependence: cost per QALY estimates.

AIMS: To compare the performance of competing and complementary interventions for prevention or treatment of problem drinking and alcohol dependence. To provide an example of how health maximising decision-makers might use performance measures such as cost per quality adjusted life year (QALY) league tables to formulate an optimal package of interventions for problem drinking and alcohol dependence. METHODS: A time-dependent state-transition model was used to estimate QALYs gained per person for each intervention as compared to usual care in the relevant target population. RESULTS: Cost per QALY estimates for each of the interventions fall below any putative funding threshold for developed economies. Interventions for problem drinkers appear to offer better value than interventions targeted at those with a history of severe physical dependence. CONCLUSIONS: Formularies such as Australia's Medicare should include a comprehensive package of interventions for problem drinking and alcohol dependence.

A critical review of pharmacoeconomic studies of acamprosate.

AIMS: This review assessed the published data on the cost-effectiveness of acamprosate for the treatment of alcohol dependence. METHODS: Four Markov modelling studies have assessed the therapeutic benefit and economic impact of acamprosate on the treatment of alcohol dependence. These have evaluated both short-term and long-term outcomes and have used German, Belgian, and Spanish costings. A fifth prospective cohort study collected real outcomes and data on expenditure during a 1 year study follow-up period. RESULTS: All five studies have produced consistent results, showing the use of acamprosate, which enhances abstinence rates, to reduce the total costs of treatment and thus be dominant over other rehabilitation strategies not involving pharmacotherapy. In all of the studies, the principal cost-driver is hospitalization. Although there is a short-term increase in treatment costs associated with drug acquisition, these are recovered from long-term savings attributable to reduced hospitalization and rehabilitation costs.

Acamprosate for the adjunctive treatment of alcohol dependence.

OBJECTIVE: To review the literature related to the treatment of alcohol dependence with acamprosate, a synthetic compound structurally similar to the naturally occurring amino acid, homotaurine. DATA SOURCES: Primary literature and review articles were identified by MEDLINE search (1966-June 2003). Abstracts from recent meetings were also reviewed. DATA SYNTHESIS: Acamprosate has been marketed in 24 countries. Although the precise mechanism of acamprosate in the treatment of alcohol-dependent patients is unclear, it may restore the balance between inhibitory and excitatory neurotransmission in the central nervous system. European trials have shown consistent increases in abstinence rates compared with placebo when acamprosate use was paired with appropriate psychosocial and behavioral therapies. Decreased direct and indirect healthcare costs associated with acamprosate treatment have also been reported. CONCLUSIONS: Acamprosate is a promising medication for the treatment of alcohol dependence in the US.

Cost-effectiveness of adjuvant treatment with acamprosate in maintaining abstinence in alcohol dependent patients.

An open prospective cohort study was performed in Germany in order to evaluate the costs of treating alcohol dependence under real-world conditions. Eight hundred and fourteen recently detoxified alcohol-dependent patients were provided with psychosocial rehabilitation support. In addition, 540 alcohol-dependent patients treated with adjuvant acamprosate therapy were compared with 274 patients without pharmacotherapy. Real costs were assessed over a period of one year. Of the patients who were treated with acamprosate, 33.6% remained abstinent compared to only 21.1% in the standard cohort. The mean total costs per patient treated with acamprosate were EUR 1,631.49 per year. In the standard cohort, total costs were EUR 2,068.83. This difference is highly significant (p = 0.012). Direct costs amounted to 76.9% of the total costs, with a 27% difference between the cohorts (p < 0.001). There was no difference in indirect costs between the two groups (p = 0.324). This real-cost study confirms the favourable cost-effectiveness of acamprosate previously suggested by pharmaco-economic modelling studies.

[Adjuvant drug treatment of alcoholism with acamprosate: between sectoral budgets and disease management]. / Die adjuvante Arzneimitteltherapie der Alkoholkrankheit mit Acamprosa--Zwischen sektoraler Budgetierung und Disease Management.

OBJECTIVE: On the basis of several controlled clinical investigations the cost-effectiveness of acamprosate as adjuvant therapy of alcohol-dependent patients has yet been evaluated. These optimal conditions cannot be found in the daily ambulant practice and results in asking which of the alternatives, "standard plus acamprosate" or "standard without acamprosate", is more cost-effective in maintaining abstinence in alcohol dependent patients under realistic conditions. PATIENTS AND METHODS: In an open multi-centre study, medical care, costs and therapeutic outcome was prospectively documented. Prior to enrolling, all patients were obliged to undergo a detoxification procedure. At a mean age of 45 years the patients suffered an average of ten years from alcohol dependence. 521 patients were documented in the acamprosate cohort and 265 patients in the cohort "other therapy" over one year. Two thirds of the participating patients were male. RESULTS: At 33.6 % the rate of abstinence was remarkably higher in the acamprosate cohort in comparison to the cohort "other" at 21.1 % abstinent patients. The mean total costs per patient and year amounted to DM 3191 in the acamprosate-cohort and were significantly lower than in the cohort "other" with DM 4046. Effectiveness-adjusted costs of DM 9500 per successfully treated patient in the acamprosate-cohort were superior to the cohort "other", amounting to DM 19 148 per successfully treated patient. CONCLUSION: The described economic benefits may be utilised under conditions of an adequate disease management.