Do trials that report a neutral or negative treatment effect improve the care of critically ill patients? No

Excerpt

Randomized controlled trials (RCTs) with appropriate question selection, careful subject enrollment, adequate powering and assiduous execution of a well-designed protocol can provide convincing data that improve the strength of the evidence base guiding practice. However, many RCTs conducted in intensive care medicine have resulted in no significant differences in primary outcomes between the tested groups. This is particularly true for trials targeting mortality. Because patients in RCTs in critical care medicine—and patients in intensive care units (ICUs)—have wide variability in their risk of death, these patients will also have wide variability in the absolute benefit that they can derive from a given therapy. If the adverse effects of the therapy are not perfectly aligned with the treatment benefits, this will result in heterogeneity of the treatment effect, wherein different patients experience quite different and often unexpected results from therapy. As a consequence, in a negative RCT, there are patients who experience benefit and others who experience harm, all merged into the global result. Therefore, the results do not provide a definitive answer to the study question or enable reliable guidance or recommendations to be developed. Indeed, these negative clinical trials seldom convey useful information beyond that stemming from an examination of their subgroups, their possibly inopportune assumptions and their deficiencies of design. …