Meta-analysis of the literature or of individual patient data: is there a difference?

The use of meta-analyses or overviews to combine formally the results of related randomised clinical trials is becoming increasingly common. However the distinction between analyses based on information extracted from the published literature and those based on collecting and reanalysing updated individual patient data is not clear. We have investigated the difference between meta-analysis of the literature (MAL) and meta-analysis of individual patient data (MAP) by comparing the two approaches using randomised trials of cisplatin-based therapy in ovarian cancer. The MAL was based on 788 patients and the MAP on 1329 and estimated median follow-ups were 3.5 and 6.5 years, respectively. The MAL gave a result of greater statistical significance (p = 0.027 vs p = 0.30) and an estimate of absolute treatment effect three times as large as the MAP (7.5% vs 2.5%). Publication bias, patient exclusion, length of follow-up, and method of analysis all contributed to this observed difference. The results of a meta-analysis of the literature alone may be misleading. Whenever possible, a meta-analysis of updated individual patient data should be done because this provides the least biased and most reliable means of addressing questions that have not been satisfactorily resolved by individual clinical trials.