Issues relating to study design and risk of bias when including non-randomized studies in systematic reviews on the effects of interventions

Non-randomized studies may provide valuable evidence on the effects of interventions. They are the main
source of evidence on the intended effects of some types of interventions and often provide the only
evidence about the effects of interventions on long-term outcomes, rare events or adverse effects.
Therefore, systematic reviews on the effects of interventions may include various types of non-randomized
studies. In this second paper in a series, we address how review authors might articulate the particular
non-randomized study designs they will include and how they might evaluate, in general terms, the extent
to which a particular non-randomized study is at risk of important biases. We offer guidance for describing
and classifying different non-randomized designs based on speci¿c features of the studies in place of using
non-informative study design labels. We also suggest criteria to consider when deciding whether to
include non-randomized studies. We conclude that a taxonomy of study designs based on study design
features is needed. Review authors need new tools speci¿cally to assess the risk of bias for some
non-randomized designs that involve a different inferential logic compared with parallel group trials.
Copyright © 2012 John Wiley & Sons, Ltd.