Philippe Laramée

The Economic Burden of Alcohol Dependence in Europe

AIMS To determine the economic burden pertaining to alcohol dependence in Europe. METHODS Database searching was combined with grey literature searching to identify costs and resource use in Europe relating to alcohol dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) or the World Health Organisations International Classification of Diseases (ICD-10). Searches combined MeSH headings for both economic terms and terms pertaining to alcohol dependence. Relevant outcomes included direct healthcare costs and indirect societal costs. Main resource use outcomes included hospitalization and drug costs. RESULTS Compared with the number of studies of the burden of alcohol use disorders in general, relatively few focussed specifically on alcohol dependence. Twenty-two studies of variable quality were eligible for inclusion. The direct costs of alcohol dependence in Europe were substantial, the treatment costs for a single alcohol-dependent patient lying within the range €1591-€7702 per hospitalization and the annual total direct costs accounting for 0.04-0.31% of an individual countrys gross domestic product (GDP). These costs were driven primarily by hospitalization; in contrast, the annual drug costs for alcohol dependence were low. The indirect costs were more substantial than the direct costs, accounting for up to 0.64% of GDP per country annually. Alcohol dependence may be more costly in terms of health costs per patient than alcohol abuse. CONCLUSIONS This review confirms that alcohol dependence represents a significant burden for European healthcare systems and society. Difficulties in comparing across cost-of-illness studies in this disease area, however, prevent specific estimation of the economic burden.

The cost-effectiveness and public health benefit of nalmefene added to psychosocial support for the reduction of alcohol consumption in alcohol- dependent patients with high/very high drinking risk levels: a Markov model

Objectives To determine whether nalmefene combined with psychosocial support is cost-effective compared with psychosocial support alone for reducing alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels (DRLs) as defined by the WHO, and to evaluate the public health benefit of reducing harmful alcohol-attributable diseases, injuries and deaths. Design Decision modelling using Markov chains compared costs and effects over 5 years. Setting The analysis was from the perspective of the National Health Service (NHS) in England and Wales. Participants The model considered the licensed population for nalmefene, specifically adults with both alcohol dependence and high/very high DRLs, who do not require immediate detoxification and who continue to have high/very high DRLs after initial assessment. Data sources We modelled treatment effect using data from three clinical trials for nalmefene (ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941)). Baseline characteristics of the model population, treatment resource utilisation and utilities were from these trials. We estimated the number of alcohol-attributable events occurring at different levels of alcohol consumption based on published epidemiological risk-relation studies. Health-related costs were from UK sources. Main outcome measures We measured incremental cost per quality-adjusted life year (QALY) gained and number of alcohol-attributable harmful events avoided. Results Nalmefene in combination with psychosocial support had an incremental cost-effectiveness ratio (ICER) of £5204 per QALY gained, and was therefore cost-effective at the £20 000 per QALY gained decision threshold. Sensitivity analyses showed that the conclusion was robust. Nalmefene plus psychosocial support led to the avoidance of 7179 alcohol-attributable diseases/injuries and 309 deaths per 100 000 patients compared to psychosocial support alone over the course of 5 years. Conclusions Nalmefene can be seen as a cost-effective treatment for alcohol dependence, with substantial public health benefits. Trial registration numbers This cost-effectiveness analysis was developed based on data from three randomised clinical trials: ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941).

Risk of All-Cause Mortality in Alcohol-Dependent Individuals: A Systematic Literature Review and Meta-Analysis

Background Alcohol dependence (AD) carries a high mortality burden, which may be mitigated by reduced alcohol consumption. We conducted a systematic literature review and meta-analysis investigating the risk of all-cause mortality in alcohol-dependent subjects. Methods MEDLINE, MEDLINE In-Process, Embase and PsycINFO were searched from database conception through 26th June 2014. Eligible studies reported all-cause mortality in both alcohol-dependent subjects and a comparator population of interest. Two individuals independently reviewed studies. Of 4540 records identified, 39 observational studies were included in meta-analyses. Findings We identified a significant increase in mortality for alcohol-dependent subjects compared with the general population (27 studies; relative risk [RR] = 3.45; 95% CI [2.96, 4.02]; p < 0.0001). The mortality increase was also significant compared to subjects qualifying for a diagnosis of alcohol abuse or subjects without alcohol use disorders (AUDs). Alcohol-dependent subjects continuing to drink heavily had significantly greater mortality than alcohol-dependent subjects who reduced alcohol intake, even if abstainers were excluded (p < 0.05). Interpretation AD was found to significantly increase an individuals risk of all-cause mortality. While abstinence in alcohol-dependent subjects led to greater mortality reduction than non-abstinence, this study suggests that alcohol-dependent subjects can significantly reduce their mortality risk by reducing alcohol consumption.

Clinical relevance of nalmefene versus placebo in alcohol treatment: reduction in mortality risk.

Reduction of long-term mortality risk, an important clinical outcome for people in alcohol dependence treatment, can rarely be established in randomized controlled trials (RCTs). We calculated the reduction in all-cause mortality risk using data from short-term (6 and 12 months) double-blind RCTs comparing as-needed nalmefene treatment to placebo, and mortality risks from meta-analyses on all-cause-mortality risk by reduction of drinking in people with alcohol dependence. A reduction in drinking in the RCTs was defined by shifts in drinking risk levels established by the European Medicines Agency. Results showed that the reduction of drinking in the nalmefene group was associated with a reduction in mortality risk by 8% (95% CI: 2%, 13%) when compared to the placebo group. Sensitivity analyses confirmed a significant effect. Thus comparing the difference between nalmefene and placebo in reduction in drinking levels with results on all-cause mortality risk from meta-analyses indicated a clinically relevant reduction in mortality risk. Given the high mortality risk of people with alcohol dependence, abstinence or a reduction in drinking have been shown to reduce mortality risk and should be considered treatment goals.

A Predictive Microsimulation Model to Estimate the Clinical Relevance of Reducing Alcohol Consumption in Alcohol Dependence

Background: Alcohol consumption is one of the most important factors for disease and disability in Europe. In clinical trials, nalmefene has resulted in a significant reduction in the number of heavy-drinking days (HDDs) per month and total alcohol consumption (TAC) among alcohol-dependent patients versus placebo. Methods: A microsimulation model was developed to estimate alcohol-attributable diseases and injuries in patients with alcohol dependence and to explore the clinical relevance of reducing alcohol consumption. Results: For all diseases and injuries considered, the number of events (inpatient episodes) increased with the number of HDDs and TAC per year. The model predicted that a reduction of 20 HDDs per year would result in 941 fewer alcohol-attributable events per 100,000 patients, while a reduction in intake of 3,000 g/year of pure alcohol (ethanol) would result in 1,325 fewer events per 100,000 patients. Conclusion: The potential gains of reducing consumption in alcohol-dependent patients were considerable.

Alcohol Dependence and Mortality: Implications for Treatment —Authors' Reply

We would like to thank Cook for her commentary (Cook, 2015) in this issue of EBioMedicine, which deals with not only our findings (Laramee et al., 2015) but also the implications for treatment and setting up a treatment system. While generally agreeing with Cook, we differ in one aspect that alcohol use disorders in general and alcohol dependence specifically are not recognized. A recent large-scale study in 6 European countries showed that GPs did recognize alcohol dependence, in fact, they identified more severe cases than standardized instruments such as the CIDI (Rehm et al., 2015a, Mitchell et al., 2012). This implies that recognition is not the main reason why alcohol dependence is having a low treatment rate. One problem here seems to be that most countries see no role for treatment at the primary health care level; the leading paradigm recommends screening, brief advice/interventions for alcohol problems and referral to specialized treatment for alcohol dependence (Babor et al., 2007; http://pathways.nice.org.uk/pathways/alcohol-usedisorders/brief-interventions-for-alcohol-use-disorders). In other words, GPs are restricted to non-treatment roles, i.e., roles outside the core professional identity. Moreover, referral is not too popular with patients, who believe that they can cope with the problem themselves (Probst et al., 2015), and because of stigmatization tend to postpone interventions until they are unavoidable (Rehm et al., 2015b). Moreover, a recent review did not see much evidence for this kind of referral (Glass et al., 2015). In conclusion, only if the role of primary health care is redefined, including but not limited to remuneration of treatment, there seems to be reasonable hope to reduce the treatment gap. It has been proposed that GPs should address alcohol use and alcohol dependence analogously to blood pressure and hypertension (Nutt and Rehm, 2014), and this strategy may prove to be the way forward.