To the Editor: In their meta-analysis, Dr Ioannidis
and colleagues1 found that randomized and
nonrandomized studies often reach similar conclusions, although nonrandomized
studies may yield larger estimates of the effect size. I agree with the authors
that nonrandomized evidence can help explore clinical questions. However,
analyzing sources of heterogeneity among randomized and nonrandomized trials
might be more informative than simply pooling treatment results from only
randomized clinical trials. Especially in the case of an unclear treatment
effect, all available information should be used to resolve the uncertainty
in outcome between studies. Important information from nonrandomized clinical
trials should not be ignored; instead, heterogeneity in design, data collection,
and analysis should be explored. Even in randomized clinical trials, the method
of randomization might lead to differences in outcomes.
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