A few years ago scientists at Amgen, an American drug company, tried to replicate 53 studies that they considered landmarks in the basic science of cancer, often co-operating closely with the original researchers to ensure that their experimental technique matched the one used first time round. According to a piece they wrote last year in Nature, a leading scientific journal, they were able to reproduce the original results in just six. Months earlier Florian Prinz and his colleagues at Bayer HealthCare, a German pharmaceutical giant, reported in Nature Reviews Drug Discovery, a sister journal, that they had successfully reproduced the published results in just a quarter of 67 seminal studies.
The governments of the OECD, a club of mostly rich countries, spent $59 billion on biomedical research in 2012, nearly double the figure in 2000. One of the justifications for this is that basic-science results provided by governments form the basis for private drug-development work. If companies cannot rely on academic research, that reasoning breaks down. When an official at America’s National Institutes of Health (NIH) reckons, despairingly, that researchers would find it hard to reproduce at least three-quarters of all published biomedical findings, the public part of the process seems to have failed.
Academic scientists readily acknowledge that they often get things wrong. But they also hold fast to the idea that these errors get corrected over time as other scientists try to take the work further. Evidence that many more dodgy results are published than are subsequently corrected or withdrawn calls that much-vaunted capacity for self-correction into question. There are errors in a lot more of the scientific papers being published, written about and acted on than anyone would normally suppose, or like to think.
Various factors contribute to the problem. Statistical mistakes are widespread. The peer reviewers who evaluate papers before journals commit to publishing them are much worse at spotting mistakes than they or others appreciate. Professional pressure, competition and ambition push scientists to publish more quickly than would be wise. A career structure which lays great stress on publishing copious papers exacerbates all these problems. “There is no cost to getting things wrong,” says Brian Nosek, a psychologist at the University of Virginia who has taken an interest in his discipline’s persistent errors. “The cost is not getting them published.”
First, the statistics, which if perhaps off-putting are quite crucial. Scientists divide errors into two classes. A type I error is the mistake of thinking something is true when it is not (also known as a “false positive”). A type II error is thinking something is not true when in fact it is (a “false negative”). When testing a specific hypothesis, scientists run statistical checks to work out how likely it would be for data which seem to support the idea to have come about simply by chance. If the likelihood of such a false-positive conclusion is less than 5%, they deem the evidence that the hypothesis is true “statistically significant”. They are thus accepting that one result in 20 will be falsely positive—but one in 20 seems a satisfactorily low rate.
Understanding insignificance
In 2005 John Ioannidis, an epidemiologist from Stanford University, caused a stir with a paper showing why, as a matter of statistical logic, the idea that only one such paper in 20 gives a false-positive result was hugely optimistic. Instead, he argued, “most published research findings are probably false.” As he told the quadrennial International Congress on Peer Review and Biomedical Publication, held this September in Chicago, the problem has not gone away.