Meta-analysis in epidemiology, with special reference to studies of the association between exposure to environmental tobacco smoke and lung cancer: a critique.

Meta-analysis, a set of statistical tools for combining and integrating the results of independent studies of a given scientific issue, can be useful when the stringent conditions under which such integration is valid are met. In this report we point out the difficulties in obtaining sound meta-analyses of either controlled clinical trials or epidemiological studies. We demonstrate that hastily or improperly designed meta-analyses can lead to results that may not be scientifically valid. We note that much care is typically taken when meta-analysis is applied to the results of clinical trials. The Food and Drug Administration, for example, requires strict adherence to the principles we discuss in this paper before it allows a drug's sponsor to use a meta-analysis of separate clinical studies in support of a New Drug Application. Such care does not always carry over to epidemiological studies, as demonstrated by the 1986 report of the National Research Council concerning the purported association between exposure to environmental tobacco smoke and the risk of lung cancer. On the basis of a meta-analysis of 13 studies, 10 of which were retrospective and the remaining 3 prospective in nature, the Council concluded that non-smokers who are exposed to environmental tobacco smoke are at greater risk of acquiring lung cancer than non-smokers not so exposed. In our opinion, this conclusion in unwarranted given the poor quality of the studies on which it is based.