Highly-cited biomarker studies tend to report larger effect estimates for associations than subsequent meta-analyses do, says a literature review published in the Journal of the American Medical Association. John Ioannidis and Orestis Panagiotou combed through the ISI Web of Science to find studies that had been cited more than 400 times and had been published in a highly cited journal, and they searched for meta-analyses of those studies. From this, they evaluated 35 highly cited associations. "For 30 of the 35 (86%), the highly cited studies had a stronger effect estimate than the largest study; for 3 the largest study was also the highly cited study; and only twice was the effect size estimate stronger in the largest than in the highly cited study," Ioannidis and Panagiotou write. Ioannidis tells [email protected] that "the key message is that results that seem spectacular are very interesting, but researchers need to wait for further validation from independent research teams and large-scale evidence."