AN EMPIRICAL-STUDY OF THE EFFECT OF THE CONTROL RATE AS A PREDICTOR OF TREATMENT EFFICACY IN METAANALYSIS OF CLINICAL-TRIALS

If the control rate (CR) in a clinical trial represents the incidence or the baseline severity of illness in the study population, the size of treatment effects may tend to vary with the size of control rates. To investigate this hypothesis, we examined 115 meta-analyses covering a wide range of medical applications for evidence of a linear relatio nship between the CR and three treatment effect (TE) measures: the ris k difference (RD); the log relative risk (RR), and the log odds ratio (OR). We used a hierarchical model that estimates the true regression while accounting for the random error in the measurement of and the fu nctional dependence between the observed TE and the CR, Using a two st andard error rule of significance, we found the control rate was about two times more likely to be significantly related to the RD (31 per c ent) than to the RR(13 per cent) or the OR (14 per cent). Correlations between TE and CR were more likely when the meta-analysis included 10 or more trials and if patient follow-up was less than six months and homogeneous. Use of weighted linear regression (WLR) of the observed T E on the observed CR instead of the hierarchical model underestimated standard errors and overestimated the number of significant results by a factor of two. The significant correlation between the CR and the T E suggests that, rather than merely pooling the TE into a single summa ry estimate, investigators should search for the causes of heterogenei ty related to patient characteristics and treatment protocols to deter mine when treatment is most beneficial and that they should plan to st udy this heterogeneity in clinical trials. (C) 1998 John Wiley & Sons, Ltd.