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Negative Results: A Crucial Piece of the Scientific Puzzle

Scientific advance relies on transparency, rigour and reproducibility. At PLOS ONE we have always supported the publication of rigorous research, in all its forms, positive or negative, as showcased in our earlier Missing Pieces Collection. In this 10th Anniversary Collection, A Decade of Missing Pieces Senior Editor Alejandra Clark revisits this important theme and highlights a decade of null and negative results, replication studies and studies refuting previously published work.

When Evidence Says No, but Doctors Say Yes

According to Vinay Prasad, an oncologist and one of the authors of the Mayo Clinic Proceedings paper, medicine is quick to adopt practices based on shaky evidence but slow to drop them once they’ve been blown up by solid proof. As a young doctor, Prasad had an experience that left him determined to banish ineffective procedures. He was the medical resident on a team caring for a middle-aged woman with stable chest pain. She underwent a stent procedure and suffered a stroke, resulting in brain damage. Prasad, now at the Oregon Health and Sciences University, still winces slightly when he talks about it. University of Chicago professor and physician Adam Cifu had a similar experience. Cifu had spent several years convincing newly postmenopausal patients to go on hormone therapy for heart health—a treatment that at the millennium accounted for 90 million annual prescriptions—only to then see a well-designed trial show no heart benefit and perhaps even a risk of harm. "I had to basically run back all those decisions with women," he says. "And, boy, that really sticks with you, when you have patients saying, 'But I thought you said this was the right thing.'" So he and Prasad coauthored a 2015 book, Ending Medical Reversal, a call to raise the evidence bar for adopting new medical standards. "We have a culture where we reward discovery; we don’t reward replication," Prasad says, referring to the process of retesting initial scientific findings to make sure they’re valid.

Cancer scientists are having trouble replicating groundbreaking research

Take the latest findings from the large-scale Reproducibility Project: Cancer Biology. Here, researchers focused on reproducing experiments from the highest-impact papers about cancer biology published from 2010 to 2012. They shared their results in five papers in the journal ELife last week — and not one of their replications definitively confirmed the original results. The findings echoed those of another landmark reproducibility project, which, like the cancer biology project, came from the Center for Open Science. This time, the researchers replicated major psychology studies — and only 36 percent of them confirmed the original conclusions.

Why Should Scientific Results Be Reproducible?

Since 2005, when Stanford University professor John Ioannidis published his paper “Why Most Published Findings Are False” in PLOS Medicine, reports have been mounting of studies that are false, misleading, and/or irreproducible. Two major pharmaceutical companies each took a sample of “landmark” cancer biology papers and only were able to validate the findings of 6% and 11%, respectively. A similar attempt to validate 70 potential drugs targets for treating amytrophic lateral sclerosis in mice came up with zero positive results. In psychology, an effort to replicate 100 peer-reviewed studies successfully reproduced the results for only 39. While most replication efforts have focused on biomedicine, health, and psychology, a recent survey of over 1,500 scientists from various fields suggests that the problem is widespread. What originally began as a rumor among scientists has become a heated debate garnering national attention. The assertion that many published scientific studies cannot be reproduced has been covered in nearly every major newspaper, featured in TED talks, and discussed on televised late night talk shows.

The State of Reproducibility: 16 Advances from 2016

2016 saw a tremendous amount of discussion and development on the subject of scientific reproducibility. Were you able to keep up? If not, check out this list of 16 sources from 2016 to get you up to date for the new year! The reproducibility crisis in science refers to the difficulty scientists have faced in reproducing or replicating results from previously published scientific experiments. Although this crisis has existed in the scientific community for a very long time, it gained much more visibility in in the past few years. The terms “reproducibility crisis” and “replicability crisis” were coined in the early 2010s due to the growing awareness of the problem.