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Phyll, There is currently no consensus how large the effect size should be to overcome concerns of bias ( and random error). Paul Glasziou has suggested 10 times differences, GRADE suggests multiple studies with effects size 2-5 times as large ( going in the same directions). We have been trying to answer this question empirically, but so far this has been hampered by lack of funding... Hope this helps Best Ben Sent from my iPad ( please excuse typos & brevity) > On Jul 26, 2014, at 8:41 AM, "Phyll Buchanan" <[log in to unmask]> wrote: > > Any thoughts on how to decide whether the effect sizes are so large they should overcome these concerns?