Design of a cost-effectiveness study within a randomized trial: The LIPID trial for secondary prevention of IHD

The Long-term Intervention with Pravastatin in Ischemic Heart Disease (LIPID) trial is a double-blind, randomized, placebo-controlled trial evaluating the long-term effect of pravastatin on coronary mortality in patients with a previous myocardial infarction or unstable angina - ischemic heart disease (IHD). It is planned to run for at least five years with 9,014 patients from 85 centers in Australia and New Zealand. The trial will monitor cause-specific mortality and major clinical events associated with each treatment. Running in parallel with the main study is a prospective economic analysis, the objectives of which are (1) to estimate the effectiveness of pravastatin compared with placebo in terms of survival, quality of life (QOL), and quality-adjusted life-years (QALY); (2) to estimate the resource usage associated with pravastatin compared with placebo - in particular, to study whether it alters resource usage through prevention of disease progression; and (3) to use this information for a cost-utility analysis with cost per quality-adjusted life-year as the unit of analysis. A novel aspect of the design is the use of a preliminary cost-effectiveness analysis, based on 'best-guess' values, and a sensitivity analysis over plausible ranges to guide the choice of subsample size. Some data, such as mortality, days spent in hospital, major clinical events, and drug use, are being collected within the main LIPID trial. However, additional subsamples for the cost-effectiveness study will include information on quality of life, time off work, and resources used, such as time in hospital, procedures, and medications taken. The methods and sample sizes for these substudies have been a crucial issue in validity and feasibility.