Risk related therapy in meta-analyses of critical care interventions: Bayesian meta-regression analysis

Purpose: The relationship between treatment efficacy and patient risk is explored in a series of meta-analyses from the critical care domain, focusing on mortality outcome.

Methods: Systematic reviews of randomized controlled trials were identified by electronic search over the period 2002 to July 2018. A Bayesian meta-regression model was employed, using the risk difference metric to estimate the relationship between mortality difference and control arm risk, and estimate the mortality difference with and without adjusting for control arm risk. 

Results: Of 780 initially identified published systematic reviews, 113 had appropriate mortality data comprising 123 analysable groups. The 123 meta-analyses were pharmaceutical therapeutic (59.3%), non-pharmaceutical therapeutic (24.4%) and nutritional (16.3%), with a 25% overall average control arm mortality. In 25/123 (20%) analyses, meta-regression indicated significant baseline risk (Bayesian 95% credible intervals excluding zero). In all analyses, the relationship between risk-difference and control arm risk was negative indicating a positive treatment effect with increasing control arm risk. Adjusted estimates identified six studies with significant positive treatment effects, not evident until after adjustment for control arm risk.

Conclusion: Underlying risk-related therapy is apparent in meta-analyses of the critically-ill and identification is of importance to both the conduct and interpretation of these meta-analyses.