Nature Medicine | Spoonful of Medicine

EDITORIAL: Drug targets slip-sliding away

Papers trumpeting new drug targets are a staple of biomedical journals such as Nature Medicine, but their claims are viewed skeptically by many drug development professionals. This skepticism has only been reinforced by a recent attempt to put some numbers on the reproducibility of such reports in a real-world setting (Nat. Rev. Drug Discov. 10, 712, 2011). The authors, from Bayer Healthcare, surveyed their in-house scientists tasked with experimentally validating publications on new drug targets. For only 21% of the 67 cases examined did they find results considered to be completely in line with the literature.

A reproducibility rate of 21% seems remarkably low, and the Bayer authors didn’t find any obvious trends to explain this. Given the limited information provided in their report, it’s difficult to make an independent evaluation of their findings, and a more fine-grained look at each of the cases might yield further insights. Notably, 70% of the cases examined involved oncology drug targets, so the situation might be different in other therapeutic areas.

Why should published research on new drug targets be so challenging to replicate? Although it doesn’t seem plausible that outright fraud could account for a high fraction of the failure rate, less serious forms of bias—so-called ‘questionable research practices’, such as selective presentation of data—are likely a more pervasive problem (see PLoS ONE 4, e5738, 2009). Statistical errors made by authors, such as the use of insufficient sample sizes, may arise simply from ignorance but have the potential to undermine the conclusions of many papers. Even a basic statistical procedure—comparing the difference between two experimental effects—is widely botched (Nat. Neurosci. 14, 1105, 2011).

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