Influence of Pilot and Small Trials in Meta-Analyses of Behavioral Interventions: A Meta-epidemiological Study

Abstract Background: Pilot/feasibility or studies with small sample sizes may be associated with inflated effects. This study explores the vibration of effect sizes (VoE) in meta-analyses when considering different inclusion criteria based upon sample size or pilot/feasibility status. Methods: Searches were conducted for meta-analyses of behavioral interventions on topics related to the prevention/treatment of childhood obesity from 01-2016 to 10-2019. The computed summary effect sizes (ES) were extracted from each meta-analysis. Individual studies included in the meta-analyses were classified into one of the following four categories: self-identified pilot/feasibility studies or based upon sample size (N≤100, N>100, and N>370 the upper 75 th of sample size). The VoE was defined as the absolute difference (ABS) between the re-estimations of summary ES restricted to study classifications compared to the originally reported summary ES. Concordance (kappa) of statistical significance between summary ES was assessed. Fixed and random effects models and meta-regressions were estimated. Three case studies are presented to illustrate the impact of including pilot/feasibility and N≤100 studies on the estimated summary ES. Results: A total of 1,602 effect sizes, representing 145 reported summary ES, were extracted from 48 meta-analyses containing 603 unique studies (avg. 22 avg. meta-analysis, range 2-108) and included 227,217 participants. Pilot/feasibility and N≤100 studies comprised 22% (0-58%) and 21% (0-83%) of studies. Meta-regression indicated the ABS between the re-estimated and original summary ES where summary ES were comprised of ≥40% of N≤100 studies was 0.29. The ABS ES was 0.46 when summary ES comprised of >80% of both pilot/feasibility and N≤100 studies. Where ≤40% of the studies comprising a summary ES had N>370, the ABS ES ranged from 0.20-0.30. Concordance was low when removing both pilot/feasibility and N≤100 studies (kappa=0.53) and restricting analyses only to the largest studies (N>370, kappa=0.35), with 20% and 26% of the originally reported statistically significant ES rendered non-significant. Reanalysis of the three case study meta-analyses resulted in the re-estimated ES rendered either non-significant or half of the originally reported ES. Conclusions: When meta-analyses of behavioral interventions include a substantial proportion of both pilot/feasibility and N≤100 studies, summary ES can be affected markedly and should be interpreted with caution.