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Introduction
The sequence of events is all too familiar: banner headlines in the press announce the arrival of some miraculously effective new drug or treatment, but soon the early enthusiasm wanes as further research reveals that the benefits of treatment are rather more modest, that there are side effects, and that only some categories of patients are likely to benefit. Later, a systematic review of the evidence may suggest that the treatment was rather more effective than had been realised-as in the cases of, for example, streptokinase for acute myocardial infarction, 1 aspirin for the prevention and treatment of vascular disease, 2 tamoxifen and ovarian ablation for breast cancer 3 -or that it was more hazardous than realised, as in the case of routine antiarrhythmic prophylaxis after myocardial infarction. 4 Such systematic reviews may then be followed by large trials or "mega" trials to confirm or refute their findings.*RF 5-7*
Quantitative systematic reviews (meta-analyses) remain the best means of assessing the benefits of any health care intervention that has been tested in randomised controlled trials, particularly in areas in which many similar trials of the same intervention have been performed. 8 Such reviews will form the basis of most of the systematic reviews in the Cochrane Collaboration's database. 9 By combining the results of several studies, systematic reviews increase the numbers of outcome events available for comparison in the treatment and control groups and so reduce random errors. This is particularly important in assessment of treatments in which moderate random errors could obscure moderate, but potentially important, treatment effects. 8 Like all powerful tools, systematic reviews should be handled with care as injudicious use may lead to damagingly incorrect conclusions. In the same way that chance can influence the results of individual clinical trials, chance can also influence the results of a systematic review of those trials to a surprising extent, particularly if relatively few patients and outcome events are included in the overall analysis and if inappropriate subgroup analyses are performed. 8 In addition, publication bias-whereby studies with significant results are more likely to be published than those with null results-does exist 10 11 and may increase the risk of inappropriate conclusions in systematic reviews that are restricted to published studies. 12
As part...