Aim: to conduct a survey of current meta-epidemiological studies to identify additional trial design
characteristics that may be associated with significant over/under estimation of the treatment effect
and to use such identified characteristics as basis for the formulation of new CQS appraisal criteria.
Materials and methods: We retrieved eligible studies from two systematic reviews on this topic
(latest search May 2015) and searched the databases PubMed and Embase for further studies from
June 2015 – March 2022). All data were extracted by one author and verified by another. Sufficiently
homogeneous estimates from single studies were pooled using random-effects meta-analysis. Trial
design characteristics associated with statistically significant estimates from single datasets (which
could not be pooled) and meta-analyses were used as basis to formulate new or to amend existing
CQS criteria.
Results: A total of 38 meta-epidemiological studies were identified. From these, seven trial design
characteristics associated with statistically significant over- or under estimation of the true
therapeutic effect were found.
Conclusion: One new criterion concerning double blinding was added to the CQS and the original
criteria for concealing the random allocation sequence and for minimum sample size amended.