Letter re: stratification by quality is not recommended in meta-analysis.

Abstract

We read with interest the letter by Page et al. [1] who disagree with the conclusions of our paper, “Stratification by quality induced selection bias in a meta-analysis of clinical trials” [2]. Page et al. [1] critique the directed acyclic graph (DAG) we presented and suggest that conditioning on quality stratum does not imply that the results within strata defined by quality ranking are biased. We believe that bias occurs when studies are selected into strata such that systematic differences between larger and smaller studies emerge (where none initially existed), as shown in the funnel or Doi plot (Figures 2–4 in our published article [2]). The association develops solely because of selection of studies into a quality stratum and does not imply that all the results within strata defined by quality ranking are biased, and this is a situation akin to publication bias [3], [4]. Page et al. next state that within stratum bias would only be the case if results in smaller studies were biased and less precise. On the contrary, selection bias would occur through conditioning on a quality stratum if studies selected into the stratum are either biased or less precise (not necessarily both) as in our DAG [2].