Meta-analysis of clinical trials as a scientific discipline. I: Control of bias and comparison with large co-operative trials.

Meta-analysis is an important method of bridging the gap between undersized randomized control trials and the treatment of patients. However, as in any retrospective study, the opportunities for bias to distort the results are widespread. Attempts must be made to introduce the controls found in prospective studies by blinding the selection of papers and extraction of data and making blinded duplicate determinations. Informal and personalized methods of obtaining data are probably more liable to error and bias than employing only published data. Publication bias is a serious problem requiring further research. There also need to be more comparisons of meta-analysed small studies with large co-operative trials.