Medical Research Council Biostatistics Unit, Cambridge, UK. thomas.nye@mrc-bsu.cam.ac.uk|Medical Research Council Biostatistics Unit, Cambridge, UK. thomas.nye@mrc-bsu.cam.ac.uk|Medical Research Council Biostatistics Unit, Cambridge, UK. thomas.nye@mrc-bsu.cam.ac.uk|Medical Research Council Biostatistics Unit, Cambridge, UK. thomas.nye@mrc-bsu.cam.ac.uk|Medical Research Council Biostatistics Unit, Cambridge, UK. thomas.nye@mrc-bsu.cam.ac.uk