Of mice and men: problems with animal studies highlighted in a new light

John Ioannidis of Stanford and colleagues published an important paper in PLoS Biology, “Evaluation of Excess Significance Bias in Animal Studies of Neurological Diseases.” Summary:

“Studies have shown that the results of animal biomedical experiments fail to translate into human clinical trials; this could be attributed either to real differences in the underlying biology between humans and animals, to shortcomings in the experimental design, or to bias in the reporting of results from the animal studies. We use a statistical technique to evaluate whether the number of published animal studies with “positive” (statistically significant) results is too large to be true. We assess 4,445 animal studies for 160 candidate treatments of neurological disorders, and observe that 1,719 of them have a “positive” result, whereas only 919 studies would a priori be expected to have such a result. According to our methodology, only eight of the 160 evaluated treatments should have been subsequently tested in humans. In summary, we judge that there are too many animal studies with “positive” results in the neurological disorder literature, and we discuss the reasons and potential remedies for this phenomenon.”

PLoS blogger Roli Roberts wrote:

“…the key take-home is that more than twice as many studies as expected appeared to have statistically significant conclusions – something known as excess significance bias.

What’s the explanation for this anomaly? Rather than wilful fraud, the authors of the PLOS Biology study suggest that this excess significance comes from two main sources. The first is that scientists conducting an animal study might analyse their data in several different ways, but ultimately tend to pick the method that gives them the “better” result. The second arises because scientists usually want to publish in higher profile journals that tend to strongly prefer studies with positive, rather than negative, results. This can delay or even prevent publication, or relegate the study to a low-visibility journal, all of which reduce their chances of inclusion in a meta-analysis.”

The Ioanndis et al paper raises new concerns about journals’ positive publication bias(non-publication of neutral/negative results) and points to problems elsewhere in the system – involving research paper authors, their institutions, funders and the journals.

The paper, so far, has, predictably, received very little news coverage by the mainstream news media which so often tout the findings from animal studies without proper caveats and explanation of limitations. An exception is the Los Angeles Times, which offered a crisp analysis, “Animal studies riddled with bias, report finds.”


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