This is a commentary on a 2011 Cochrane Review that found substantial differences between studies that were adequately randomized and those that were not adequately randomized. The direction of the difference was not predictable, however, meaning that there was not a consistent bias on average towards overstating the treatment effect or a consistent bias on average towards understating the treatment effect. This leads the authors of the Cochrane review to conclude that “the unpredictability of random allocation is the best protection against the unpredictability of the extent to which non-randomised studies may be biased.” The authors of the commentary provide a critique of this conclusion on several grounds.
Howick J, Mebius A. In search of justification for the unpredictability paradox. Trials. 2014;15(1):480. doi:10.1186/1745-6215-15-480. Available at http://www.trialsjournal.com/content/15/1/480/abstract.