The influence of mortality time-points on pooled effect estimates in critical care meta-analyses

Article type
Authors
Roth D1, Herkner H1
1Medical University of Vienna, Department of Emergency Medicine, Austria
Abstract
Background: There is an on-going debate among meta-analysis methodologists and statisticians whether it is appropriate to pool mortality estimates from clinical trials that use mortality outcomes ascertained at different time-points. If the relative effects vary over time, which might especially be the case in critical care, standard pooling of studies with different follow-up times within one meta-analysis would not be justifiable. Current Cochrane guidelines propose pooling of short-, middle-, and long-term effects as a potential solution, but include no specific guidelines.
Objectives: Describe the current practice of dealing with different mortality time-points and analyze the influence of different time points on pooled effect estimates in actual Cochrane critical care meta-analyses.
Methods: The CDSR was searched for critical care-reviews. Review characteristics including strategy for dealing with different follow-up times and study characteristics were extracted. Meta-analyses were recalculated using all described strategies and influence of such strategies on deviation of pooled effect estimates compared to a "use last time-point available" approach was analyzed using meta-regression and multilevel mixed-effects linear regression.
Results: We evaluated 835 reviews, and included 80 meta-analyses of 298 studies, representing 107,605 patients. 49 (61%) reviews did not state any strategy, 9 (11%) used separate analyses for each time-point, 9 (11%) used the last available, 6 (8%) used a closest to defined time-point, 3 (4%) performed separate analyses for last and predefined, 2 (3%) mixed some, 1 (1%) computed predefined time-points from study-data, and 1 (1%) pooled all but performed a sensitivity analysis. Among 388 recalculated meta-analyses no influence of the strategies "pool short-, middle-, long-term", "use closest to defined" and "separate" on effect estimates was found compared to "use last available".
Conclusions: Reviews use a large variety of strategies to deal with different mortality time-points, however more than 50% do not report any strategy. We found no influence of different strategies on effect estimates in critical care reviews.