a novel method to adjust efficacy estimates for uptake of other active treatments in long-term clinical trials一个新颖的方法来调整效果估计吸收其他积极的治疗长期的临床试验.pdfVIP

A Novel Method to Adjust Efficacy Estimates for Uptake of Other Active Treatments in Long-Term Clinical Trials 1 1 1 2 3 4 John Simes *, Merryn Voysey , Rachel O’Connell , Paul Glasziou , James D. Best , Russell Scott , 1 1 5 6 1 Christopher Pardy , Karen Byth , David R. Sullivan , Christian Ehnholm , Anthony Keech , for the FIELD Study Investigators 1 National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia, 2 Centre for Evidence-Based Medicine, University of Oxford, Oxford, United Kingdom, 3 Faculty of Medicine, University of Melbourne, Melbourne, Australia, 4 Lipid and Diabetes Research Group, Christchurch Hospital, Christchurch, New Zealand, 5 Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, Australia, 6 Biomedicum Helsinki, National Public Health Institutes, Helsinki, Finland Abstract Background: When rates of uptake of other drugs differ between treatment arms in long-term trials, the true benefit or harm of the treatment may be underestimated. Methods to allow for such contamination have often been limited by failing to preserve the randomization comparisons. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, patients were randomized to fenofibrate or placebo, but during the trial many started additional drugs, particularly statins, more so in the placebo group. The effects of fenofibrate estimated by intention-to-treat were likely to have been attenuated. We aimed to quantify this effect and to develop a method for use in other long-term trials. Methodology/Principal Findings: We