This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.

Long term treatment with riluzole for patients with amyotrophic lateral sclerosis.

Treatment.

Cost-effectiveness analysis.

Patients suffering from amyotrophic lateral sclerosis.

Hospital. The economic study was carried out in Italy.

Effectiveness data related to the period 1994-96. Resource use data referred to 1994-98. The price year was 1996.

Effectiveness data were derived from a review of the literature.

Costing was undertaken retrospectively on the same patient sample as that used in the effectiveness study.

The following outcomes were assessed: survival curves for the two groups of patients, difference in survival between the two groups, relative death risks, and mean survival gain of treatment with riluzole compared with placebo.

The review included randomised placebo-controlled clinical trials, which evaluated survival or tracheostomy-free survival for patients with amyotrophic lateral sclerosis treated with riluzole plus standard supportive therapy versus placebo plus standard supportive therapy. To be included in the review the trials had to utilise a daily dose of 100mg riluzole. Only trials published in English were considered.

IOWA-IDIS (Iowa Drug Information System, Iowa City, USA) compact disc database and MEDLINE were searched.

Studies included had to conform to the following criteria: intention to treat approach in the effectiveness analysis, duration of follow-up between 18 and 21 months, and a RCT design.

Not stated.

Two primary studies were included in the review.

Individual patient data from the primary studies were combined using survival meta-analysis.

Not performed. The results of the survival meta-analysis showed that there was a significant difference in survival between the two groups (p<0.05); the relative death risks for riluzole versus placebo was 0.77 (95% CI: 0.62 - 0.96; p=0.022). The mean survival gain for patients treated with riluzole was 2.4 undiscounted months and 2.3 discounted months.

The benefit measure was lifetime survival per patient. Benefits were discounted.

Only the costs of health care resources were estimated. Cost and quantity data were derived from the literature review. Only drug costs were considered since follow-up costs were identical in the two groups. Costs were discounted. The price year was 1996.

Costs were not statistically analysed.

Not estimated.

US dollars ($).

Two sensitivity analyses were carried out: in the first, the effectiveness variable (relative death risk, survival gain) was varied between the lower and upper limits of the 95% confidence interval; and the second replaced the US price with the UK price for riluzole.

The mean lifetime survival per patient was 20.1 undiscounted months for riluzole therapy and 17.7 for the standard therapy without riluzole. The discounted lifetime survival values were respectively 19.7 and 17.4 months. The mean survival gain of treatment with riluzole was 2.4 undiscounted months or 2.3 discounted months.

The incremental cost of the riluzole therapy against the usual care without riluzole was $12,000 per patient.

Benefits and costs were combined using cost per life years gained as a cost-effectiveness ratio. Incremental analysis was performed. Incremental cost-effectiveness ratio of the riluzole therapy against the usual care without riluzole was $62,609 per life year gained (discounted costs per discounted years). In the first sensitivity analysis, the cost per life year gained varied between $13,458 and $205,714. In the second sensitivity analysis the cost per life-year gained was $45,048.

Since, as established in the literature, the upper border for acceptable values per life-years gained is $50,000, the results of the analysis show that riluzole has, in general, an unfavourable cost-effectiveness profile, being characterised as a border case. The range of costs per life years gained in the first sensitivity analysis was too wide (between $13,458 and $205,714) signifying that the effectiveness estimates were very important for the final outcomes.

The reason for the choice of the comparator, standard practice and placebo is clear.

The estimates of measure of benefit were derived from a systematic literature review that identified only two studies that satisfied the inclusion criteria. Although the study analysed a fairly large quantity of individual patient data, the riluzole survival advantage was characterised by a wide 95% confidence interval, which resulted in a wide range of costs per life year gained in the sensitivity analysis.

Adequate details of the methods of cost estimation were given. Drug costs were considered in the analysis only, as these were reported to be different between the groups. A discount rate of 3% was applied. Cost results were reported when UK and Italian prices were used instead of the US price of riluzole. Nevertheless, the results should be treated with a degree of caution as recommended discount rates differ across countries.

A series of sensitivity analyses was performed to explore the robustness of the findings and the generalisability to other countries.

Further studies are needed to confirm the clinical effectiveness of riluzole.

None stated.

Ginsberg G, Lev B. Cost-benefit analysis of riluzole for the treatment of amyotrophic lateral sclerosis. Pharmacoeconomics 1997;12:578-94.