THE LONG-TERM COST-EFFECTIVENESS OF IMPROVING ALCOHOL ABSTINENCE WITH ADJUVANT ACAMPROSATE

A. J. Palmer*, K. Neeser, C. Weiss, A. Brandt, S. Comte1 and M. Fox2

IMIB, Institute for Medical Informatics and Biostatistics, Riehen, Switzerland,
1 Merk–Lipha S.A., Lyon, France and
2 Department of Gastroenterology, Kent and Sussex Hospital, Tunbridge Wells, UK

Received 13 January 2000; in revised form 6 April 2000; accepted 19 April 2000


    ABSTRACT
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 ACKNOWLEDGEMENTS
 REFERENCES
 
A computer model was developed with decision analysis software to explore the long-term clinical and economic outcomes of alcohol abstinence maintenance with either standard counselling therapy or standard therapy plus 48 weeks of adjuvant acamprosate in detoxified alcoholic patients. Important complications of alcoholism were modelled using Markov processes, and included relapse (return to drinking), alcohol-related hepatic disease, acute and chronic pancreatitis, acute and chronic gastritis, oropharyngeal carcinoma, oesophageal carcinoma, alcoholic cardiomyopathy, alcohol-related peripheral neuropathy, alcoholic psychosis, accidental death, and suicide. Probabilities of developing complications were dependent on whether the patients within the cohort remained abstinent or had relapsed. Relapse rates, probabilities, and costs for acamprosate therapy and treatment of complications were taken from published literature. The analysis was performed from the German health insurance perspective. Life expectancy and total lifetime costs (costs of initial abstinence maintenance therapy plus costs of complications) were calculated for a typical male cohort with average age of 41 years, 80% with fatty liver, 15% with cirrhosis, 22% with chronic pancreatitis, and 1% with alcoholic cardiomyopathy at baseline. Life expectancy with and without acamprosate therapy was 15.90 and 14.70 years respectively, and discounted (5% per annum) average total lifetime costs per patient were DEM 46 448 and DEM 49 549 respectively. We conclude that, despite the acquisition costs of DEM 2177, adjuvant acamprosate therapy was both clinically and economically attractive under conservative assumptions.


    INTRODUCTION
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 ACKNOWLEDGEMENTS
 REFERENCES
 
In 1990, there were 1.5–2 million alcohol-dependent patients in western Germany, leading to direct and indirect costs of 1500 million and 4500 million German Marks (DEM) respectively (Banz et al., 1993Go; Brecht et al., 1996Go). The economic aspects of alcoholism have taken on increasing importance, due to rising health care costs, limited health care resources, and the potential to reduce the incidence, progression, and costs of complications if alcohol misuse can be minimized (Holder et al., 1992Go; Holder and Blose, 1992Go; Brecht et al., 1996Go; Schadlich and Brecht, 1998Go). Most clinical trials in alcoholism management focus on outcomes like short-term (<2 years) abstinence rates or changes in craving for alcohol. Improved alcoholism management often involves relatively high levels of short-term expenditure to avoid long-term complications (Schadlich and Brecht, 1998Go) with the overall effect on total long-term costs being difficult to quantify. Subsequently, techniques are required to forecast long-term outcomes based on existing data. Disease modelling is one method that allows long-term health and economic assessments in the absence of empirical data, based on the extrapolation of known data. The use of disease models in health care is increasingly accepted as a state of the art method for interpreting complex data and quantifying medical outcomes. It is cost-saving and expedient, compared to conducting long-term epidemiological and clinical studies, and may help to generate data for improved decision-making on intervention strategies. When outcomes are expressed in terms of a common unit such as costs per life year gained, the information generated by modelling can help decision-makers to choose from interventions competing for the same scarce resources [Mason et al., 1993; US Department of Health and Human Services, Public Health Service, 1996; Bundesamt für Sozialversicherung (Federal Office of Social Insurance), 1998].

In the absence of the toxic effects of alcohol in patients who remain abstinent, complications of alcoholism either will not occur in patients who do not have the complication, may be reversible, or have an improved survival outcome. A number of substances, including acamprosate, have been shown to reduce short- to medium-term relapse rates in detoxified alcohol-dependent patients (Pelc et al., 1994Go; Paille et al., 1995aGo,bGo; Sass et al., 1996aGo; Whitworth et al., 1996Go; Geerlings et al., 1997Go) but the long-term effects on incidence and progression of clinical complications, life expectancy and costs have not been assessed.

In this context, a computer simulation model was developed to estimate the lifetime medical and cost outcomes for a cohort of detoxified alcoholic patients following either standard counselling therapy, or standard counselling therapy with adjuvant acamprosate in the German setting (Sass et al., 1996aGo). The hypothesis tested was that adjuvant acamprosate therapy would decrease the incidence and progression of long-term complications of alcoholism, leading to an increase in life expectancy, with the costs of acamprosate therapy being offset by a reduction in costs due to complications avoided.


    METHODS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 ACKNOWLEDGEMENTS
 REFERENCES
 
An incremental cost-effectiveness analysis was performed in terms of total lifetime costs per life-year gained for a typical male cohort with an average age of 41 years, 80% with fatty liver, 15% with cirrhosis, 22% with pancreatitis, and 1% with alcoholic cardiomyopathy at baseline (Jacob et al., 1991Go; Saunders and Latt, 1993Go; Parent and Barkun, 1996Go; Sass et al., 1996aGo). The disease process was modelled using Markov processes, representing the development of important alcohol-related complications. The development of alcohol-related complications under a given clinical treatment strategy was interpreted as a series of events occurring over time (e.g. incidence of complications, mortality). Different treatment strategies change key clinical parameters and medical consequences, therefore changing the incidence of clinical events or regression/progression of the disease. The resulting history of events was combined with costs related to events or complications, in order to calculate total lifetime costs (Fig. 1Go).



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Fig. 1. Overview of the process of modelling long-term effects of interventions.

 
Probabilities for clinical events were retrieved from the published literature (Table 1Go). In the few cases where more than one source was available for a probability, data were taken preferentially from German studies published in peer-reviewed journals, with more recent studies preferred over older studies. The impact of different probability values was explored with sensitivity analysis, described in more detail below. Costs for each of the alternative intervention strategies and complications were calculated from published German sources (Table 2Go). The perspective of the German third party (health insurance) payer was taken, therefore only direct medical costs were considered. All costs were calculated in German Marks (DEM), expressed in 1996 values.


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Table 1. Summary of probabilities (P) used in the model
 

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Table 2. Cost items used in the model
 
Outcomes calculated were survival functions, life expectancy, and mean expected total lifetime costs per patient. The incremental cost-effectiveness ratio was calculated in comparison to standard therapy alone, using the formula , where TC = the mean expected total lifetime direct costs, LE = life expectancy from baseline age expressed in years, a = standard therapy plus acamprosate, s = standard therapy alone.

Both undiscounted and discounted costs and life years gained were calculated using a real discount rate of 5% per annum.

One-way sensitivity analysis on life expectancy and total lifetime costs for patients treated with adjuvant acamprosate was performed in order to identify factors exerting a major influence on these outcomes. Each probability and cost parameter was varied one at a time by ±10%, while holding all other parameters constant. Break-even analysis was performed on the costs of 48 weeks adjuvant acamprosate therapy. The acquisition costs of acamprosate were varied until the total lifetime costs (costs of therapy + costs of treating events) were equal to the total costs for standard therapy alone.

The full model structure was built up from a series of Markov submodels that simulate the progression of the important complications of alcoholism. The submodels were run in parallel, allowing the cohort to develop more than one complication concurrently, as has previously been applied in diabetes mellitus, another disease with multiple long-term complications (Palmer et al., 1996Go, 1999Go, 2000Go). Overall mortality was calculated by integrating complication-specific mortality calculated within each submodel with non-complication-specific mortality (Fig. 2Go) (Welch et al., 1996Go; Anonymous, 1996dGo). The model was programmed using TOM (Tools for Outcomes Modelling)TM software from IMIB (Basel/Riehen, Switzerland).



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Fig. 2. Model overview.

 
Abstinence submodel
The abstinence submodel simulates the abstinence rates under different therapies over time. The abstinence rates for standard therapy alone or with adjuvant acamprosate were taken from a 2-year study in the German setting (Sass et al., 1996aGo) and were extrapolated to 5 years using the trend analysis function of an Excel spreadsheet. After 5 years, it was assumed that abstinence rates remained constant, as has been found in previous long-term studies (Fig. 3Go) (Sass et al., 1996aGo; Whitworth et al., 1996Go). Patients who relapsed were considered as having alcohol dependence syndrome (Schadlich and Brecht, 1998Go) with its associated costs, and the increased clinical risks associated with continued alcohol misuse.



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Fig. 3. Two-year reported abstinence rates (Sass et al., 1996a) and projected abstinence rates.

 
Liver disease submodel
The liver submodel represents the progression from no alcohol-related liver disease, to fatty liver, acute hepatitis, cirrhosis with and cirrhosis without portal hypertension, and primary liver cell carcinoma (Fig. 4Go). The transition probabilities from one state of disease severity to another are dependent on whether or not patients within the cohort remain abstinent. The state of ‘fatty liver’ is considered to be reversible, i.e. if patients remain abstinent, fatty liver will resolve (Grant et al., 1988Go; Saunders and Latt, 1993Go). Annual mortality increases with increasing severity of liver disease (Imperiale and McCullough, 1990Go; Saunders and Latt, 1993Go; Gerhardt et al., 1996Go; Urbistondo et al., 1996Go; Tang et al., 1998Go). Patients may develop a number of cirrhosis-related complications, including ascites (non-infected and infected), hepatic encephalopathy, oesophageal varices, and primary liver cell carcinoma. While liver transplant has been modelled as a possible therapy option for end-stage hepatic failure (Gerhardt et al., 1996Go; Gerbes, 1997Go) in many countries, liver transplantation is rare for alcohol-induced liver failure (Kumar et al., 1990Go; Berlakovich et al., 1994Go). The effect of abstinence on survival following liver transplant is not clear (Gerhardt et al., 1996Go; Tang et al., 1998Go).



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Fig. 4. Liver disease submodel.

 
Gastrointestinal (GI) disease submodel
The GI submodel simulates the development of acute and chronic gastritis, acute and chronic pancreatitis, oropharyngeal carcinoma, and oesophageal carcinoma (Fig. 5Go). The probabilities of complications depend on whether or not patients within the cohort remain abstinent.



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Fig. 5. Gastrointestinal (GI) submodel.

 
Alcoholic cardiomyopathy submodel
The alcoholic cardiomyopathy submodel simulates the progression from no cardiomyopathy, to alcoholic cardiomyopathy, and possibly to heart transplant (Fig. 6Go). The transition probabilities depend on whether or not patients within the cohort remain abstinent. Alcoholic cardiomyopathy is reversible in some patients after cessation of alcohol misuse, and thus resolves in a certain proportion of abstinent patients (Demakis et al., 1974Go; Schwartz et al., 1975Go; Baudet et al., 1979Go; Agatston et al., 1986Go; Pavan et al., 1987Go; Milani et al., 1989Go; Jacob et al., 1991Go). Annual mortality increases with the onset of cardiomyopathy, although mortality may be improved in abstinent patients (Regan, 1984Go; Wahl et al., 1985Go). While heart transplant has been included in the model structure as a possible therapy option for terminal cardiac failure, in many countries heart transplantation is a rare treatment modality for alcoholic cardiomyopathy. In this study, it has been assumed that no patients received cardiac transplant for alcoholic cardiomyopathy (Prazak et al., 1996Go).



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Fig. 6. Alcoholic cardiomyopathy submodel.

 
Other complications submodel
This submodel simulates relatively acute events, such as suicide, accidental death, alcoholic psychosis/delirium tremens, as well as simulating the development of alcoholic peripheral neuropathy (Fig. 7Go). The probabilities of events depend on whether or not the patients remain abstinent or relapse. In some patients, peripheral neuropathy will resolve if abstinence is maintained, particularly when disulfiram is avoided (Wetzel et al., 1989Go; Palliyath et al., 1990Go). The suicide rate among alcohol-misusing patients is 58–70-fold higher than among non-alcohol misusing patients (Kessel and Grossman, 1961Go; Kendell and Staton, 1966Go; Gillis, 1969Go; Lesch et al., 1986Go) and one-fifth to one-third of the increased death rate among alcoholics is explained by suicide. The suicide rate is related to the level of alcohol consumption (Berglund and Ojehagen, 1998Go). Successful treatment of alcoholics leads to decreased suicide rates compared to unsuccessfully or untreated patients (Kendell and Staton, 1966Go; Gillis, 1969Go). For the purposes of this study it was assumed that the suicide rate was reduced to the level of the general population in abstinent patients, and remained elevated in relapsed patients. Sensitivity analysis on this assumption was performed. The accidental death rate among alcohol-misusing patients is 4–5-fold higher than non-alcohol misusing patients (Gillis, 1969Go; Lesch et al., 1986Go) and, for the purposes of this study, was assumed to return to the level in the general population in abstinent patients.



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Fig. 7. Other complications submodel.

 

    RESULTS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 ACKNOWLEDGEMENTS
 REFERENCES
 
The mean expected total lifetime costs per patient, undiscounted (and discounted at 5% per annum) were DEM 75 081 (48 245) and DEM 76 942 (49 907) with and without adjuvant acamprosate therapy respectively. The acquisition costs of acamprosate are relatively minor in comparison to the costs of different complications (Table 3Go).


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Table 3. Mean total lifetime costs (non-discounted) with standard therapy alone or with adjuvant acamprosate, broken down by cost element (DEM, 1996 values)
 
The survival curve was shifted slightly to the right with adjuvant acamprosate therapy, due to the reduction in excess mortality from liver disease, acute pancreatitis, cardiomyopathy, suicide, and accidental death (Fig. 8Go). Life expectancy from baseline age 41 years increased from 14.70 to 15.90 years with adjuvant acamprosate, resulting in 1.20 (undiscounted) life-years gained (LYG), or 0.52 LYG when discounted at 5% per annum (p.a.).



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Fig. 8. Survival function, showing the percentage of the cohort alive over the simulation period.

Light squares = adjuvant acamprosate, dark circles = standard therapy alone.

 
Sensitivity analysis
One-way sensitivity analysis of life expectancy revealed that the probabilities relating to hepatic disease, suicide, and relapse rates had the greatest impact (Fig. 9Go). Due to the relatively large effects of the abstinence rates and the uncertainty surrounding the effects of abstinence on suicide, the impacts of these two factors were explored in more detail. If the abstinence rates with standard therapy alone and adjuvant acamprosate therapy were conservatively assumed to be equal after 2 years (i.e. after the second year, the abstinence rate of the adjuvant acamprosate-treated group dropped from 40% to 20%; Fig. 3Go), adjuvant acamprosate therapy resulted in 0.59 LYG (non-discounted), while cost savings were reduced to DEM 460 (discounted at 5% p.a.). The baseline analysis assumed that, if patients were abstinent, the risk of suicide would return to the level of the general population. If no effect of abstinence on suicide rate was assumed, i.e. the suicide rate remained at 60-fold that of the general population, adjuvant acamprosate therapy resulted in 0.75 LYG (non-discounted), while cost savings increased to DEM 2024 (discounted at 5% p.a.).



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Fig. 9. One-way sensitivity analysis of life expectancy for patients treated with adjuvant acamprosate therapy.

The central vertical line represents the life expectancy of patients treated with adjuvant acamprosate, calculated using the baseline probability estimates (Table 1Go). Each parameter was varied one at a time by ±10%. The relative size of the impact on life expectancy is represented by the relative width of the corresponding horizontal bar. P = probability.

 
One-way sensitivity analysis of total lifetime costs per patient showed that the probability of relapse in the first year had the greatest impact, followed by probabilities and costs associated with alcoholic psychosis, the costs of alcohol dependence therapy when patients relapse, the costs of treating chronic pancreatitis, the probability of suicide at age 45 years, and various liver complications. Changes in the acquisition costs of acamprosate had a relatively minor impact on the total lifetime costs (Fig. 10Go). It was assumed that relapsers had alcohol-dependence syndrome, with its associated costs. The costs of alcohol-dependence syndrome were ranked as the factor with the fourth-highest single influence on costs. When it was assumed that relapsers had no associated increased costs due to alcohol-dependence syndrome, therapy with adjuvant acamprosate was cost neutral.



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Fig. 10. One-way sensitivity analysis of total lifetime costs per patient treated with adjuvant acamprosate therapy.

The central vertical line represents the total lifetime costs per patient treated with adjuvant acamprosate, calculated using the baseline probability and cost estimates (Tables 1 and 2GoGo). Each parameter was varied one at a time by ±10%. The relative size of the impact on total lifetime costs is represented by the relative width of the corresponding horizontal bar. c = costs; P = probability; DEM = German Marks.

 
The break-even point of the acquisition costs of 48 weeks therapy with acamprosate was DEM 4000 (Fig. 11Go). When the acquisition costs of acamprosate were below this point, adjuvant acamprosate therapy was likely to lead to cost savings over a patient's lifetime.



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Fig. 11. Break-even analysis of the acquisition costs of 48 weeks adjuvant acamprosate therapy.

The diagonal line represents total lifetime costs for patients treated with adjuvant acamprosate therapy as the acquisition costs of 48 weeks acamprosate therapy are varied from DEM 1000 to DEM 7000. The break-even point is DEM 4000, when the total lifetime costs of acamprosate treated patients will equal those of patients treated with standard therapy alone (dotted line).

 

    DISCUSSION
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 ACKNOWLEDGEMENTS
 REFERENCES
 
The use of adjuvant acamprosate therapy leads to cost savings and improved life expectancy. In this situation, an incremental cost-effectiveness analysis is not required, as there is no question as to whether the payer can afford the clinical benefits, because the intervention leads to overall cost savings.

Alcohol-dependent patients have increased morbidity and mortality in comparison to the general population (Gillis, 1969Go; Pell and D'Alonzo, 1973Go; Lesch et al., 1986Go; Piette et al., 1998Go). Abstinent patients retain considerable excess morbidity and mortality compared to the general population (Pell and D'Alonzo, 1973Go). Life expectancies calculated by the model for a male cohort of weaned alcohol-dependent patients were 55.7 and 56.9 years for standard therapy alone or adjuvant acamprosate therapy respectively. These results are similar to the results of an observational study in Austria that demonstrated total life expectancy of 50 years in previously hospitalized chronic alcoholic patients, compared to a control group with life expectancy of 73.9 years (Lesch et al., 1986Go). Other studies have also demonstrated that treatment of alcoholism/ abstinence maintenance may improve survival, and be cost-saving (Holder and Blose, 1992Go; Schadlich and Brecht, 1998Go). The improvements in life expectancy seen with adjuvant acamprosate therapy are substantial, even under conservative assumptions, when compared to other interventions commonly used in modern medicine, such as thrombolytic therapy for myocardial infarction (15 months gained in comparison to no thrombolytic therapy), routine beta-blocker therapy for prophylaxis against recurrent myocardial infarction (1.2–5.6 months gained) ticlopidine compared to aspirin for patients at high risk of stroke (0.6 months), or interferon therapy in patients with chronic hepatitis B (37 months) (Wright and Weinstein, 1998Go).

It was assumed that the suicide rate of abstinent patients returned to the level of the general population. However, due to underlying psychological co-morbidity (Kessel and Grossman, 1961Go; Driessen et al., 1998Go), this may overestimate the reduction in suicide rates seen with abstinence. Due to the uncertainty surrounding the effect of abstinence on suicide, more detailed sensitivity analysis was performed, which revealed that, even when no effect of abstinence on suicide was assumed, acamprosate still led to savings of both lives and costs.

Sensitivity analysis revealed the importance of abstinence rates, liver disease, and suicide in alcoholism therapy. Interventions that improve abstinence rates are likely to have a critical impact on the outcomes of alcoholic patients who have been detoxified.

Limitations
The validity of health economics analyses is limited by the availability of appropriate medical and cost data. The data available from the literature are themselves limited by the aims, populations, and methodology of the clinical trials that generate the data. Prevalence rates of complications were reasonably well reported, but incidence rates of complications including peripheral neuropathy, alcoholic cardiomyopathy in alcohol-dependent patients generally, and in abstinent (recovering) patients specifically have been poorly documented. Every attempt was made to apply probabilities from the German setting, but data from studies performed in other countries were sometimes applied. Although not ideal, in the absence of other information, this solution allows the filling of data gaps until more country-specific information becomes available.

Measures of dispersion of the results were not calculated. For an accurate estimation of confidence intervals, each probability and cost item needs to be defined as a distribution. In reality, it is difficult to find probabilities and costs even as single (point value) numbers, and distributions are rarely reported. Therefore, distributions must be artificially created or assumed, leading to the calculation of artificial confidence intervals that may or may not reflect reality. Thorough sensitivity analysis is the preferred method of quantifying uncertainty (Siegel et al., 1996Go; Weinstein et al., 1996Go).

Quality of life changes were not explicitly assessed in the analysis, although improved quality of life is implicit in a reduction in severity of complications. Quality-adjustment of LYG would allow a cost-utility analysis. In the case where adjuvant acamprosate therapy has lower costs and higher effectiveness (life expectancy), adjustment for quality of life improvements would increase the dominance of adjuvant acamprosate in comparison to standard therapy.

In most of the clinical trials of acamprosate, the primary efficacy assessment until now has been absolute abstinence. Although this endpoint is relatively clear-cut, the effect of acamprosate on reduction in craving and reduced levels of alcohol consumption has not been taken into account, and the improvements in morbidity and mortality due to lower levels of alcohol consumption (Lelbach, 1975Go; Pequignot et al., 1978Go; Becker et al., 1996Go; Almela et al., 1997Go; Gronbaek et al., 1998Go) may have been underestimated in this study.

Not every possible alcohol-related complication was modelled. Other alcohol-related problems, such as skeletal myopathy (Fernandez-Sola et al., 1995Go) autonomic neuropathies, (Monforte et al., 1995Go), other carcinomas (Pell and D'Alonzo, 1973Go), alcohol-related dementia and Korsakoff syndrome (Kendell and Staton, 1966Go), para-suicide (Chignon et al., 1998Go; Driessen et al., 1998Go), and non-fatal accidents (Piette et al., 1998Go), were not taken into account. Additionally, not every possible alternative alcoholism therapy, such as outpatient long-term intensive therapy for alcoholics (Ehrenreich et al., 1997Go) or adjuvant naltrexone therapy (O'Malley et al., 1992Go, 1996aGo,bGo; Volpicelli et al., 1992Go, 1995aGo, bGo, 1997Go; Mason et al., 1994Go; O'Brien et al., 1996Go) was included in this analysis. Brief intervention therapy was also not considered, as this generally applies to a different population of patients identified as problem drinkers (not abstinent alcoholics) with the intention of reducing levels of alcohol consumption to safer levels (Anonymous, 1996bGo; Edwards and Rollnick, 1997Go; Higgins-Biddle et al., 1997Go; McIntosh et al., 1997Go; Senft et al., 1997Go; Wilk et al., 1997Go; Cordoba et al., 1998Go; Dyehouse and Sommers, 1998Go; Marlatt et al., 1998Go; Wright et al., 1998Go). While other interventions that improve abstinence maintenance or reduce the level of alcohol consumption are likely to improve clinical outcomes, they too will need to be subject to assessment of their efficiency (i.e. balance of costs versus effectiveness).

The side-effects of adjuvant acamprosate therapy were not considered in the analysis, as acamprosate is generally well-tolerated, and the side-effects that occur are mild, short-lived, reversible, and not significantly different from those occurring in placebo-treated patients (Paille et al., 1995aGo,bGo; Sass et al., 1996aGo,bGo; Whitworth et al., 1996Go; Geerlings et al., 1997Go; Pelc et al., 1997Go; Poldrugo, 1997Go).

Although indirect costs were not included in this analysis, the indirect costs due to alcoholism have previously been estimated at DEM 4422 million in west Germany in 1990, DEM 2284 million from premature mortality, DEM 1150 million from inability to work, and DEM 988 million from premature retirement. This was more than triple the direct costs (DEM 1150 million). If indirect costs had been considered in this analysis, it is possible that the savings from a societal perspective could be considerably greater.

Finally, the abstinence rates for the acamprosate-treated cohort used in this analysis were taken from a single long-term study (Sass et al., 1996aGo). The results from this study were used in the model because acamprosate was given in addition to counselling and/or psychotherapy, reflecting the real-life management of alcohol abstinence in the German setting. Another long-term study (2 years to 1 year drug therapy plus 1 year no-drug follow-up, 448 patients) in Austria (Whitworth et al., 1996Go) also showed significantly superior 2-year abstinence rates, compared to placebo. However, the absolute abstinence rates for both the placebo and acamprosate groups were lower, and the difference between abstinence rates at 2 years for the placebo and acamprosate groups was less than those reported in the German trial. When the abstinence rates taken from the Austrian trial were simulated in the model, adjuvant acamprosate therapy was still life-saving (0.55 LYG discounted at 5% p.a.), and cost neutral (both groups with total lifetime costs of ~DEM 53 200 per patient, discounted at 5% p.a.). However, a French study showed a significant difference in abstinence rates at 6 months, but not at 12 or 18 months, although a positive trend in favour of acamprosate was seen (Paille et al., 1995aGo,bGo). A formal meta-analysis could provide more definitive estimates of the long-term effectiveness of acamprosate, although combining results from studies with heterogeneous patient populations, drug doses, severity of illness, and differences in psychological support/counselling and other concomitant therapy would be difficult.


    CONCLUSIONS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 ACKNOWLEDGEMENTS
 REFERENCES
 
In conclusion, an attempt has been made to quantify the long-term clinical and economic implications of improved abstinence rates after alcohol detoxification using the example of adjuvant acamprosate therapy in the German setting. The methodology employed allowed the estimation of prognoses based on available data and in the absence of population trials or observational studies. Tentative conclusions may be drawn. Interventions that lead to improved abstinence rates may have an important impact on long-term outcomes, such as life expectancy and costs of complications due to alcoholism. In the case of adjuvant acamprosate therapy, the improved abstinence rates lead to reduced total lifetime costs from the German health insurance perspective, despite the additional acquisition costs of DEM 2177, and an improvement in life expectancy, even under conservative assumptions.


    ACKNOWLEDGEMENTS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 ACKNOWLEDGEMENTS
 REFERENCES
 
The authors would like to thank Lipha S.A., Lyon, France, for their support of this project.


    FOOTNOTES
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 ACKNOWLEDGEMENTS
 REFERENCES
 
* Author to whom correspondence should be addressed at: Rheingasse 66, 4058 Basel, Switzerland. Back


    REFERENCES
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 ACKNOWLEDGEMENTS
 REFERENCES
 
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