New initiatives in critical care: distinguishing hype from hope

Abstract

Recent viewpoints on critical care have expressed frustration at the slow development of new therapeutic agents and the failure of investigator-initiated trials. Several new directions have been proposed: personalised medicine and the embracing of "omic" technologies, resolving the heterogeneity of treatment effects, and adaptive trial designs. We examine these approaches in the context of analysis of randomised controlled trials (RCTs). The curse of treatment effect heterogeneity is found not only in critical care but also in cancer oncology. We find the uncritical appeal to personalised medicine to be misplaced because such treatments are not identified at the personal level, but at the group or stratified level. The analysis of RCTs has foundered over the problem of accounting for the centre effect and rejecting the random effects approach. Enthusiasm for adaptive trial designs has been articulated at the rhetorical, not the substantive, level.