Systematic Reviews: Obtaining data from randomised controlled trials: how much do we need for reliable and informative meta-analyses?

Abstract

Minimising biases and random errors Complete identification of published and unpublished trials The most important step in the conduct of any systematic review of randomised controlled trials is to identify and include all (or nearly all) of the relevant trials. This is needed whether the review is to be based on aggregate or individual patient data; the process of trial identification has already been described in this series.8 Meta-analyses based on individual patient data always require direct contact with trialists (as do some reviews based on aggregate data), so these provide an additional means of identifying trials - enlisting the help and knowledge of those trialists. For example, neither of two important reviews of randomised trials comparing melphalan and prednisone with combination chemotherapy in the treatment of multiple myeloma9,10 found the unpublished Italian M-80 randomised trial of these drugs versus vincristine plus melphalan, cyclophosphamide, and prednisone. This study was also unknown to the secretariat of an ongoing overview of such trials until the Italian group was contacted for patient data from its other trials. Similarly, direct contact with trialists identified two unpublished trials previously unknown to the secretariat of a meta- analysis of advanced ovarian cancer11; these had not been identified by a meta-analyses based on the published literature.