CURRENT ISSUES

'Cheers' to acamprosate in reducing the costs of alcoholism

- Carlene Todd-

A camprosate is one of the few drugs for treating alcoholism that has been shown in very large clinical trials to reduce relapse rates among 'weaned' patients. However, because

acamprosate is an expensive agent, there is a need to look beyond its efficacy to determine whether the drug represents economic value. At the recent inaugural European conference of the International Society for Pharmacoeconomics and Outcomes Research [Cologne, Gennany; December 1998], Mr Lieven Annemans from research organisation Health Economics and Disease Management in Mechelen, Brussels, presented an economic study of acamprosate ['Campral'; Merck KGaA] in maintaining abstinence in alcohol-dependent patients.

The results of the study showed that, under conser­vative conditions, acamprosate saved a minimum of BeF22 000/patient* over a 2-year period compared with no treatment, representing a national cost saving ofBeF70 million-BeF75 million in Belgium.

The objectives of the study, conducted by Mr Annemans and colleague Ms Nancy Vanoverbeke, were to develop an epidemiological and economic model to ascertain the value of acamprosate in maintaining abstinence in weaned patients with alcoholism, as well as identify the main cost drivers among such patients. To do this, they assessed the medical literature for data on acamprosate relapse rates compared with placebo, th~ types of relapse, and detoxification success rates.

Fewer relapses with acamprosate The researchers used data on relapse rates from

a large randomised clinical trial of 448 patients with alcoholism who received 1 year's treatment with either acamprosate or placebo.

Data for the placebo group were used as a proxy for no treatment. Mr Annemans pointed out that, although not accurate, this was the only alternative and fortunately formed a conservative standpoint due to the potential for a placebo effect.

At the end of treatment period, 18.3% of acamprosate recipients and 7.1% of placebo recipients were continu­ously abstinent.** After an additional12 months' follow-up without active treatment, the rates of continuous abstinence in these 2 treatment groups were 11.9 and 4.9%, respectively. Mr Annemans noted that the data from this clinical trial were chosen for the economic model, as the study contained few restrictions and therefore had good external validity.

The economic modelling study also used data on first-line treatment, referral patterns and resource use for alcoholism. which were obtained from a survey of 129 general practitioners (GPs) conducted by the Institute of Hygiene and Epidemiology in Belgium. Data on type of relapse, second-line resource use, and complications related to alcoholism, were obtained from a prospective, phase IV Belgian trial of 582 patients with alcoholism who received either acamprosate or placebo.

The economic analysis was conducted from the health insurer perspective and direct unit costs were

1173-5503199/0201-0003/$01 ooc Adielnternetionel Limited 1999. All rights reserved

obtained from official listings and hospital statistics in Belgium.

What happens after relapse?

The clinical data were incorporated into a Markov state transition model to reproduce the clinical results over a 2-year period. Mr Annemans noted that in general, clinical trials of acamprosate only include patients until relapse and do not assess what happens to patients over the subsequent years after relapse.

The 2-year model comprised 24 one-month stages, and during this period, patients could be in any of the following 6 states: ambulatory follow-up; ambulatory detoxification; institutional detoxification; institutional rehabilitation/follow-up; lost to follow-up; and death.

Mr Annemans commented that in the model, patients could revert to previous states, not just progress to subsequent states as tends to be the case in 'pure' Markov models. The probability of moving from one state to another over the period of a month, and the cost of being in one state during a month, were applied to the model.

Hospitalisation costly

The total monthly per-patient cost associated with ambulatory follow-up was estimated to be BeF91 0, the majority of which was due to GP and psychiatrist visits. In contrast, ambulatory detoxification required more intensive GP visits and biochemistry tests resulting in a total monthly per-patient cost of BeF2031.

Hospital detoxification cost an estimated BeF140 628/patient/month primarily due to the 10 days of stay at a cost of BeF7948/day. 54% of patients who are hospitalised for detoxification require in-hospital follow-up at a cost of BeF122 644/patient/ month.

Therefore. by reducing the number of alcoholic relapses acamprosate reduces the need for hospital detoxification and hospital follow-up, which subsequently reduces the direct costs of treating alcoholism.

*Belgian francs * * Relapse was defined as lapsing (drinking for 1 day), hinging (drinking for no more than 2-3 days), a 'real relapse' (starting to drink again continuously), or missing a consultation visit with the study investigator.

PharmacoEconom•cs & Outcomes News 27 Feb 1999 No. 201

3

4 CURRENT ISSUES

Acamprosate reduces the costs of alcoholism- continued

Acamprosate vs no treatment for alcoholism: per-patient costs• over 2 years Direct costa AcemDfQUte No treatment Acamprosate acquisition~ 34 712 0

Other drugs 3367 3378

Physician visits and examinations 17653 17695

Acute hospitalisation 48735 79063 (detoxification)

Long-tenn hospitalisation 107047 132 263 (follow-up)

Uver complications 472 887

Total 211 988 233287

• Belgian francs (BeF)

•• The 2-year acquisition cost of acamprosate represents a dally cost of BeF78.68/patient assuming that 22% of patients receive a dally dosage of 1332mQ and 78% receive 1998ma.

Furthermore, evidence shows that 2 years of abstinence from alcohol can reduce the likelihood of liver complications. Therefore, acamprosate not only reduces the proportion of patients who relapse, but also avoids liver complications.

The average per-patient cost of liver complications is estimated to be BeF436 000, based on per-patient costs of BeF383 000 for ascites, BeF527 000 for oesophageal varices, BeF229 000 for hepatic encepha­lopathy and BeF406 000 for hepatocellular carcinoma.

PharmacoEconomics & Outcomes News 27 Feb 1999 No. 201

Saving of BeF22 000/patient By combining the probabilities and costs of being

in each of the 6 health states, the researchers calculated the average healthcare costs over 2 years for a patient receiving acamprosate versus no treatment [see table].

Under conservative conditions, it was estimated that total direct per-patient costs over a 2-year period were BeF211 986 and BeF233 287 for acamprosate and no treatment, respectively. The acquisition cost for acamprosate was offset by savings from hospitalisations avoided. Therefore, institutionalisation appears to be the main cost driver in alcoholic patients.

However, Mr Annemans pointed out that the cost savings with acamprosate only apply if the drug is used for a maximum of I year continuously, as in the clinical trial, and that after relapse it is discontinued during a 14-day period of detoxification.

Sensitivity analysis showed that the results of the economic study were robust to changes in several parameters, including the cost of acute hospitalisation and the rate of hospital follow-up. That is, acamprosate remained cost saving even when the cost of acute hospitalisation was reduced to 50% of the current cost and when the percentage of patients undergoing follow-up in hospital was reduced from 54 to 24% of those receiving hospital detoxification.

1173·5503199/0201·0004/$01 .00c Adis International Limited 1999. All rights reserved