Using metaanalysis and computer simulation we studied the effects of attrition in experimental research on cancer and stroke. The results were published this week in the new meta-research section of PLOS Biology. Not surprisingly, given the small sample sizes of preclinical experimentation, loss of animals in experiments can dramatically alter results. However, effects of attrition on distortion of results were unknown. We used a simulation study to analyze the effects of random and biased attrition. As expected, random loss of samples decreased statistical power, but biased removal, including that of outliers, dramatically increased probability of false positive results. Next, we performed a meta-analysis of animal reporting and attrition in stroke and cancer. Most papers did not adequately report attrition, and extrapolating from the results of the simulation data, we suggest that their effect sizes were likely overestimated.
And these were our recommendations: Attrition of animals is often unforeseen and does not reflect willful bias. However, there are several simple steps that the scientific community can use to diminish inferential threats due to animal attrition. First, we recommend that authors prespecify inclusion and exclusion criteria, as well as reasons for exclusion of animals. For example, the use of flowcharts to track animals from initial allocation until analysis, with attrition noted, improves the transparency of preclinical reporting. An added benefit of this approach lies in the ability to track systemic issues with experimental design or harmful side effects of treatment. Journal referees can also encourage such practices by demanding them in study reports. Finally, many simple statistical tools used in medicine could be adopted to properly impute (and report) missing data. Overall, compliance with ARRIVE guidelines will aid in most, if not all, of the issues inherent to missing data in preclinical research and help structure a better standard for animal use and reporting. (Click here to access the full article, and here for Bob Siegerink’s blog post about it).
Nature ran a feature on the article, which was massively covered by the lay press, in interviews, and in blogs. For example:
here is a Hungarian one
and a Spanish
and an Argentinan:
or a Swiss (Italian)