What is the appropriate outcome for studies of treatments for out-of-hospital cardiac arrest?
Resuscitation · 2006-09-20 · Method & validation
Abstract
BACKGROUND: A good outcome following out-of-hospital medical care for cardiac arrest is survival to hospital discharge. Because a large number of patients are required to detect a minimum clinically important difference in survival, an intermediate outcome such as hospital admittance is commonly used. For an intermediate outcome to be a useful surrogate, the survival rate conditional on achieving the intermediate outcome should not depend upon the field treatment. If so, an advantage of the intermediate outcome may be a smaller sample size. However, recent trials demonstrate that survival conditional on admittance may depend upon the field treatment. Even if the resources are available to power a study for survival, is survival the right outcome? For example, no increase in survival and a large increase in admittance could be considered a bad result, as it represents a substantial waste of resources. Similarly no increase in mortality and a decrease in admittance should be considered a good result, as it represents a substantial cost savings without any sacrifice of life. Both admittance and survival are important outcomes and need to be considered jointly, that is, as a bivariate outcome. METHODS: Cost-effectiveness concepts are used to distinguish between a good and bad (bivariate) outcome. Simulations are conducted to compare the impact of the univariate and the bivariate outcomes in a variety of trial scenarios. A table of sample sizes is computed for the bivariate outcome across a range of trial scenarios. RESULTS: The bivariate outcome outperforms both univariate outcomes for most alternatives. The required sample size for the joint outcome of admittance and survival may be substantially, over 50%, less than that for the survival outcome alone. CONCLUSION: Use of the bivariate outcome could provide more informed decision making about resuscitation strategies and at less cost then the current gold standard of hospital survival.