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: CONCLUSIONS/SIGNIFICANCE: This novel application of a penalized Cox model for adjustment of a trial estimate of treatment efficacy incorporates evidence-based estimates for other therapies, preserves comparisons between the randomized groups, and is applicable to other long-term trials. In the FIELD study example, the effects of fenofibrate on the risks of coronary heart disease and cardiovascular disease events were underestimated by up to one-third in the original analysis. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN64783481.
|
Authors | John Simes, Merryn Voysey, Rachel O'Connell, Paul Glasziou, James D Best, Russell Scott, Christopher Pardy, Karen Byth, David R Sullivan, Christian Ehnholm, Anthony Keech, FIELD Study Investigators |
Journal | PloS one
(PLoS One)
Vol. 5
Issue 1
Pg. e8580
(Jan 08 2010)
ISSN: 1932-6203 [Electronic] United States |
PMID | 20072614
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
|
Topics |
- Data Interpretation, Statistical
- Diabetes Mellitus
(drug therapy)
- Fenofibrate
(therapeutic use)
- Humans
- Placebos
- Proportional Hazards Models
- Randomized Controlled Trials as Topic
- Treatment Outcome
|