Retractions in the medical literature: how many patients are put at risk by flawed research?

Background Clinical papers so flawed that they are eventually retracted may put patients at risk. Patient risk could arise in a retracted primary study or in any secondary study that draws ideas or inspiration from a primary study. Methods To determine how many patients were put at risk, we evaluated 788 retracted English-language papers published from 2000 to 2010, describing new research with humans or freshly derived human material. These primary papers -- together with all secondary studies citing them -- were evaluated using ISI Web of Knowledge. Excluded from study were 468 basic science papers not studying fresh human material; 88 reviews presenting older data; 22 case reports; 7 papers retracted for journal error and 23 papers unavailable on Web of Knowledge. Overall, 180 retracted primary papers (22.8%) met the inclusion criteria. Subjects enrolled and patients treated in 180 primary studies and 851 secondary studies were combined. Results Retracted papers were cited over 5000 times, with 93% of citations being research related, suggesting that ideas promulgated in retracted papers can influence subsequent research. Over 28 000 subjects were enrolled -- and 9189 patients were treated -- in 180 retracted primary studies. Over 400 000 subjects were enrolled -- and 70 501 patients were treated -- in 851 secondary studies which cited a retracted paper. Papers retracted for fraud (n=70) treated more patients per study (p<0.01) than papers retracted for error (n=110). Conclusions Many patients are put at risk by retracted studies. These are conservative estimates, as only patients enrolled in published clinical studies were tallied. [ABSTRACT FROM AUTHOR]