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.

The use of orlistat in combination with a calorie-controlled diet for the treatment of overweight and obese patients.

Treatment.

Cost-utility analysis.

The study population comprised a hypothetical cohort of average adult patients with a body mass index (BMI) corresponding to overweight or obesity. The inclusion criteria were a BMI of at least 28 kg/m2, age 18 years or older, no diagnosed Type 2 diabetes mellitus (T2DM), and the ability to lose 2.5 kg during the introductory period.

The setting appears to have been primary care. The study was carried out in Ireland.

The effectiveness data were gathered from 5 clinical studies published between 1998 and 2000. The price year was 2003.

The effectiveness data were derived from a review or synthesis of published studies.

A decision analysis tree was constructed. The main outcome measure used in the model was the cost per quality-adjusted life-year (QALY). The model incorporated the relationships between weight loss and quality of life gain, and weight loss and reduction in risk of T2DM, to estimate the impact of weight loss on QALYs gained and on the onset of T2DM. A time horizon of 11 years was selected in order to capture the effects of treatment on diabetes incidence and associated costs.

The main outcomes estimated from the review of the literature were:

the percentage who responded at 3 months (ie, lost 5% of initial weight);

the percentage change from initial weight (for responders and nonresponders after 3 months);

the change in BMI after 12 months (for responders and nonresponders after 3 months);

the change in utility per unit of BMI reduction;

the sustainability of weight loss following a 12-month treatment period; and

the correlation between BMI and the annual incidence of T2DM.

Five international randomised, placebo-controlled, multi-centre trials with a similar study design were selected. All trials were at least 12 months in duration. The inclusion criteria for the patients specified adults with a BMI of at least 28 kg/m2, not diagnosed with T2DM, and with the ability to lose 2.5 kg in weight during the introductory trial period (4 weeks).

Not stated.

Not stated.

Not stated.

Approximately 7 studies were included in the review. Five clinical trials and 2 published studies were used to derive estimates on the impact of changes in BMI on patient utility and the correlation between BMI and annual incidence of T2DM.

A meta-analysis was carried out to combine the results of the 5 clinical trials. No further details were provided.

Not stated.

At 3 months, there were 48.79% responders with orlistat and 26.29% responders with diet alone.

The percentage change from initial weight was -15.50% (95% confidence interval, CI: 14.81 to 16.18) for responders in the orlistat group compared with -13.22% (95% CI: 12.19 to 14.24) for the comparator group. For nonresponders, the percentage change was -6.54% (95% CI: 6.02 to 7.06) for the orlistat group compared with -5.22% (95% CI: 4.72 to 5.83) for the diet only group.

The change in BMI after 12 months was 5.64 for responders in the orlistat group versus 4.79 for the comparator group. For nonresponders after 3 months, the change was 2.38 for the orlistat group compared with 1.89 for the diet only group.

The change in utility per unit of BMI reduction was estimated to be 0.017. The patients were assumed to regain their original weight at a uniform rate over the following 3 years.

Finally, the authors estimated that a 10% reduction in BMI would reduce the annual incidence of T2DM by approximately 30%.

These data formed the principal effectiveness or outcome parameters used in the analysis.

The outcome measures used were the QALYs gained. The QALYs were obtained using change in BMI as a surrogate outcome, incorporating the relationship between weight loss and quality of life gain and reduction in risk of T2DM using secondary literature. The benefits were discounted at a rate of 3%.

The direct costs reported were those of the health service. The key resource use categories included were medication costs, the cost of the dietary programme per month (including frequency of general practitioner and dietician visits) and diabetes related-costs (both monitoring and treatment costs). The quantities and the unit costs were reported separately. The authors relied on estimates from published literature on the burden of diabetes in Ireland and their own assumptions on the frequency of visits. The costing appears to have been based completely on actual data. The costs were discounted at a rate of 3%. The price year was 2003.

The methods used for the statistical analysis of the costs were not reported in this paper. The costs seem to have been treated deterministically.

The indirect costs were not considered in the economic study. A rationale for their exclusion was not provided.

Euros (EUR).

The authors explored the uncertainty around a number of key parameters in order to assess the robustness of their analysis using deterministic, one-way, sensitivity analyses (the method used to select the ranges was not reported). In particular, they used 1-year effectiveness data from a single more recent study, varied the number of years of sustained weight loss, and varied the daily dose of orlistat and the discount rate.

For the base-case analysis, the net utility gain in the orlistat group was 0.028 in comparison with the diet only group. Compared with patients on the diet alone, orlistat responders gained 0.090 after a 12-month treatment period, over a 4-year time horizon.

For orlistat responders, a reduction in diabetes disease-years was associated with savings of EUR 353 in diabetes-related costs over a time horizon of 11 years, compared with EUR 119 for orlistat nonresponders and EUR 179 for the comparator group.

For the base-case analysis, the incremental cost associated with the average orlistat-treated patient was EUR 478.

The incremental cost-effectiveness ratios (ICERs) were estimated as the extra cost per additional QALY gained for 12-month orlistat treatment over a calorie-controlled diet alone.

The ICER for orlistat was EUR 16,954 per QALY gained. The sensitivity analysis demonstrated an incremental cost per QALY in the range of EUR 11,000 to EUR 35,000 under a variety of assumptions.

The most influential parameters were the duration of sustained weight loss after treatment and the daily dose of orlistat.

Orlistat is effective and cost-effective in obese patients if, after 3 months of treatment, only treatment responders continue treatment.

A placebo plus a calorie-controlled diet alone was used as the comparator. This approximates usual therapy. You should decide whether this could be a valid comparator in your own setting.

The effectiveness evidence was derived from a meta-analysis of 5 international randomised controlled trials. It was unclear whether the review of the literature was systematic. The authors appropriately discussed the limitations of not using clinical data from an Irish setting. The clinical evidence appears to have been good.

The main measure of benefit was the number of QALYs gained. This measure has the potential to capture a range of health effects. The authors described the source of the quality of life estimates.

The authors explicitly identified the perspective adopted in the analysis. It seems that all the categories of cost relevant to the perspective adopted were included. However, the authors did not report the total costs for each intervention, which would have been helpful. The price year was reported.

Generalisability to the Irish setting was addressed and the results of the analysis were compared with those obtained for other countries. The authors do not appear to have reported their results selectively. It should be noted that the main author is a consultant to a pharmaceutical company. A more detailed explanation of the main benefits and cost results for both analyses would have been helpful. The authors appropriately discussed the main limitations of their study.

Although there is no stated willingness to pay threshold in Ireland, according to the conventional threshold used by the National Institute for Clinical Excellence in the UK, orlistat could be considered cost-effective. All the different scenarios tested in the sensitivity analyses proved the robustness of this result.

None stated.

Finer N, James WP, Kopelman PG, et al. One year treatment of obesity: a randomised double-blind, placebo controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor. Int J Obes Relat Metab Disord 2000;24:306-13.

Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. A randomised control trial. JAMA 1999;281:235-42.

Sjostrom L, Rissanen A, Andersen T, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet 1998;352:167-73.

Rossner S, Sjostrom L, Noack R, et al. Weight loss, weight maintenance and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. Obes Res 2000;8:49-61.

Hill JO, Hauptman J, Anderson JW, et al. Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-year study. Am J Clin Nutr 1999;72:221-31.