Some Progress and Problems in Meta-Analysis of Clinical Trials

Abstract

We report progress on some methodological issues in meta-analysis. Evidence continues to accumulate that randomized trials show smaller gains than nonrandomized trials when innovations are compared to standard therapies. Quality scores for randomized clinical trials show that reporting has improved about 27% in three decades, to a quality level slightly over 50%. Although quality scoring could be useful, in principle, for adjusting estimates of gain from innovations, a substantial study has not found a statistical relation between gains and quality. We describe a method of blinding papers to reduce the bias of readers doing meta-analyses. For combining data for fixed effects, Greenland and Salvan recommend using Mantel-Haensztel, weighted least squares or maximum likelihood methods. For random effects, Larholt, Tsiatis and Gelber have improvements for the DerSimonian and Laird method. Eddy and his colleagues have prepared software and book-length works on Bayesian methods for technology assessment using meta-analysis. Louis has a valuable review article on Bayesian approaches. The annoying difficulties in combining $2 \times 2$ tables when some cells have zeros has been largely overcome by exact calculation methods. From diagnostic data acquired from several independent investigations, new methods have appeared for estimating receiver operating characteristic curves. An update on meta-analyses of randomized clinical trials shows about 16 meta-analyses per year in journals during 1983-1990. We expect much more methodologic work as new issues appear and findings point us toward fresh solutions.