- Title
- LDL-cholesterol differences predicted survival benefit in statin trials by the surrogate threshold effect (STE)
- Creator
- Johnson, Kent R.; Freemantle, Nick; Anthony, Danielle M.; Lassere, Marissa N. D.
- Relation
- Journal of Clinical Epidemiology Vol. 62, Issue 3, p. 328-336
- Publisher Link
- http://dx.doi.org/10.1016/j.jclinepi.2008.06.004
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2009
- Description
- Objective: We describe a new statistical method called the surrogate threshold effect (STE) that estimates the threshold level of a surrogate needed in a clinical trial to predict a benefit in the target clinical outcome. In this article, we apply this method to the LDL-cholesterol biomarker surrogate and survival benefit-target outcome in statin trials. Study Design and Setting: We identified randomized trials comparing statin treatment to placebo treatment or no treatment and reporting all-cause and cardiovascular mortality. Trials with fewer than five all-cause deaths in at least one arm were excluded. Multiple regression modeled the reduction in all-cause and cardiovascular mortality as a function of LDL-cholesterol difference. The 95% confidence and 95% prediction bands were calculated and graphed to determine the minimum LDL-cholesterol difference (the surrogate threshold) below which there would be no predicted survival benefit. Results: In 16 qualifying trials, regression analysis yielded an all-cause mortality model whose prediction bands demonstrated no overall survival gain with LDL-cholesterol difference values below 1.5 mmol/L. The cardiovascular mortality model yielded prediction bands that demonstrated no cardiovascular survival benefit with LDL-cholesterol difference values below 1.4 mmol/L. Conclusions: In a multitrial setting, the STE approach is a promising yet straightforward statistical method for evaluating the surrogate validity of biomarkers.
- Subject
- statins; forecasting; surrogate; biomarker; levels of evidence; LDL-cholesterol
- Identifier
- uon:7588
- Identifier
- http://hdl.handle.net/1959.13/808052
- Identifier
- ISSN:0895-4356
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