Meta-analyses of chronic disease trials with competing causes of death may yield biased odds ratios.
OBJECTIVE
To study the odds ratio (OR) as measure of treatment effect in the context of mutually exclusive causes of death.


METHODS
As example we consider meta-analyses of randomized trials of implantable cardioverter defibrillator implantation (ICD). We compare the pooled OR to the pooled cause-specific hazard ratio (HR) for each of the mutually exclusive outcomes "sudden cardiac death" (SCD) and "death other than SCD."


RESULTS
The pooled OR and cause-specific HR for the reduction of SCD are similar (0.43 and 0.44, respectively) for nine included trials. However, the OR erroneously presumes a potential trend toward an adverse effect of the ICD on "death other than arrhythmia" (OR 1.11 [0.84-1.45]), whereas such an effect is small with the cause-specific HR (HR 1.03 [0.79-1.32]). In general, it is shown that a spurious association of treatment with "other death" may be seen when a substantial number of death from the cause of interest is postponed.


CONCLUSIONS
The OR should be used with caution to study effects of treatment on mutually exclusive causes of death. Practically this concern applies primarily to meta-analysis where the use of the cause-specific HR, whenever available, is recommended.
Koller
Michael T
MT
Basel Institute for Clinical Epidemiology, University Hospital Basel, CH-4031 Basel, Switzerland. kollerm@uhbs.ch
Stijnen
Theo
T
Steyerberg
Ewout W
EW
Lubsen
Jacobus
J
D015982:Bias; D002423:Cause of Death; D002908:Chronic Disease; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D006801:Humans; D015201:Meta-Analysis as Topic; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016896:Treatment Outcome