A Bayesian Re-analysis of the Steroids to Reduce Systemic Inflammation after Infant Heart Surgery (STRESS) Trial

BackgroundProphylactic steroids are often used to reduce the systemic inflammatory response to cardiopulmonary bypass in infants undergoing heart surgery. The STRESS trial found that the likelihood of a worse outcome did not differ between infants randomized to methylprednisolone (n=599) versus placebo (n=601) in a risk-adjusted primary analysis (adjusted odds ratio [OR], 0.86; 95% CI, 0.71 to 1.05; P=0.14). However, secondary analyses showed possible benefits with methylprednisolone. To ensure that a potentially efficacious therapy is not unnecessarily avoided, we re-analyzed the STRESS trial using Bayesian analytics to assess the probability of benefit. MethodsOur Bayesian analysis used the original STRESS trial primary outcome measure, a hierarchically ranked composite of death, transplant, major complications and post-operative length of stay. We evaluated probability of benefit (OR<1) versus harm (OR>1) by comparing the posterior distribution of the OR assuming a neutral probability of benefit versus harm with weak prior belief strength (nearly non-informative prior distribution). Reference results were calculated under the vague prior distribution. To convey magnitude of effect we used model parameters to calculate a predicted risk of death, transplant or major complications for methylprednisolone and placebo. Analyses consisted of 10 Markov Chain Monte Carlo simulations, each consisting of 2000 iterations with a 1000 iteration burn-in to ensure proper posterior convergence. Sensitivity analyses evaluated pessimistic (5%-30% prior likelihood of benefit), neutral and optimistic (70%-95%) prior beliefs, and controlled strength of prior belief as weak (30% variance), moderate (15%) and strong (5%). ResultsIn primary analysis, the posterior probability of benefit from methylprednisolone was 91% and probability of harm was 9%. Composite death or major complication occurred in 18.8% of trial subjects with an absolute risk difference of -2% (95% CI -3%, +1%) associated with methylprednisolone. Each of 9 sensitivity analyses demonstrated greater probability of benefit than harm in the methylprednisolone group with 8 of 9 demonstrating >80% probability of benefit and [&ge;]1% absolute difference in risk of death, transplant or major complications. ConclusionProbability of benefit with prophylactic methylprednisolone is high and harm is unlikely. This more in-depth analysis of the data expands the initial clinical evaluation of methylprednisolone provided by the STRESS trial.