Broadly speaking, studies at high or unclear risk of bias should be given reduced weight in meta-analyses, compared with studies at low risk of bias (Spiegelhalter 2003). However, formal statistical methods to combine the results of studies at high and low risk of bias are not sufficiently well developed that they can currently be recommended for use in Cochrane reviews (see Section 8.8.4.2). Therefore, the major approach to incorporating risk of bias assessments in Cochrane reviews is to restrict meta-analyses to studies at low (or lower) risk of bias.