Competing risk and heterogeneity of treatment effect in clinical trials - PubMed (original) (raw)

Editorial

Competing risk and heterogeneity of treatment effect in clinical trials

David M Kent et al. Trials. 2008.

Abstract

It has been demonstrated that patients enrolled in clinical trials frequently have a large degree of variation in their baseline risk for the outcome of interest. Thus, some have suggested that clinical trial results should routinely be stratified by outcome risk using risk models, since the summary results may otherwise be misleading. However, variation in competing risk is another dimension of risk heterogeneity that may also underlie treatment effect heterogeneity. Understanding the effects of competing risk heterogeneity may be especially important for pragmatic comparative effectiveness trials, which seek to include traditionally excluded patients, such as the elderly or complex patients with multiple comorbidities. Indeed, the observed effect of an intervention is dependent on the ratio of outcome risk to competing risk, and these risks - which may or may not be correlated - may vary considerably in patients enrolled in a trial. Further, the effects of competing risk on treatment effect heterogeneity can be amplified by even a small degree of treatment related harm. Stratification of trial results along both the competing and the outcome risk dimensions may be necessary if pragmatic comparative effectiveness trials are to provide the clinically useful information their advocates intend.

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Figures

Figure 1

Figure 1

Relative and Absolute Benefits for Implantable Cardiac Defibrillators (ICDs) Stratified by Total Mortality Risk: These graphs show the relative (A) and absolute (B) benefit for ICDs assuming that the devices are 75% effective in preventing sudden cardiac death (SCD) but not at all effective in preventing pump failure. The risk ratio of SCD to pump failure death was empirically observed [30]. Note that both relative risk reduction decreases monotonically. Absolute risk reduction demonstrates a U-shaped benefit; benefit is low in low risk groups whose risk of SCD is low and in high risk groups who are suffer pump failure.

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