Methodology Score: 3.5/5
Usefulness Score: 3.5/5
Sprung CL, et al. CORTICUS Study Group. N Engl J Med. 2008 Jan 10;358(2):111-24
This Multicenter, double-blind, parallel-group, placebo-controlled RCT of 499 septic shock patients found that hydrocortisone did not improve survival or reversal of shock, either overall or in patients who did not have a response to corticotrophin (RR1.09;0.77 to 1.52). The group recognized the trial was under-powered, had questionable external validity and an extended enrolment time of 72hrs; an unplanned post hoc analysis showed a mortality benefit in those with a high SAPSII score indicating a potential benefit in this patient population.
By: Dr. Robert Ohle
Pre-specified and Post-hoc Subgroup Analyses
Subgroup analyses involve splitting all the participant data into smaller subsets of subjects (e.g. males and females), so as to make comparisons between them. A pre-specified subgroup analysis is one that is planned and documented before any examination of the data, preferably in the study protocol. Post-hoc analyses are those planned only after examination of the results. Such analyses are of particular concern because it is often unclear how many were undertaken and whether some were motivated by inspection of the data (data-dredging). However, both pre-specified and post-hoc subgroup analyses are subject to inflated false positive rates arising from multiple testing. Subgroup analyses are often under-powered and are best used to generate new hypotheses that can be tested in future trials.
By: Dr. Ian Stiell