In meta-analysis of clinical trials, often meta-regression analyses are performed to explain the heterogeneity in treatment effects that usually exist between trials. A popular explanatory variable is the risk observed in the control group, the baseline risk. The relationship between the treatment effect and the baseline risk is investigated by fitting a linear model that allows randomness on the true baseline risk by assuming a normal distribution with unknown mean and variance. However, the normality assumption could be too strong to adequately describe the underlying distribution. Therefore, we developed a new semi-parametric method that relaxes the normality assumption to a more flexible and general distribution. We applied a penalized Gaussian mixture distribution to represent the baseline risk distribution. Furthermore, a bivariate hierarchical model is formulated in order to take into account the correlation between the baseline and treatment effect. To fit the proposed model, a penalized likelihood function is maximized by an Expectation Maximization (EM) algorithm. We illustrate our method on a number of simulated data sets and on a published meta-analysis data set. Copyright

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doi.org/10.1002/sim.3066, hdl.handle.net/1765/35874
Statistics in Medicine
Erasmus MC: University Medical Center Rotterdam

Ghidley, W, Lesaffre, E.M.E.H, & Stijnen, Th. (2007). Semi-parametric modelling of the distribution of the baseline risks in meta-analysis. In Statistics in Medicine (Vol. 26, pp. 5434–5444). doi:10.1002/sim.3066