John Ioannidis states that science is a noble but low-yield endeavor. For him, we should be very comfortable knowing that only a small percentage of medical research can lead to improvements in clinical outcomes and quality of life.

Most published biomedical research results are false. The statement was made by Greek-American John Ioannidis and made the scientist and researcher one of the most cited authors in the world.
The paradisiacal environment of the Greek island of Sikinos and his wife, Despina, served as inspiration for the first draft of the study. It was the summer of 2004 and the couple was enjoying what was just another calm night on the balcony. Ioannidis is enthusiastically relating ideas to his companion. Finally, after a period of ten years maturing in his mind, he managed to commit his reasoning to paper.
The result was the article “Why Most Published Research Findings Are False”, from 2005, which is currently the most downloaded and consulted PLoS Medicine journal. In 2014, when the study counted one million visits, Ioannidis confessed that the title of the article was a valuable help in capturing the attention of the medical and scientific community, but it took some time to reach the popularity it currently has. Ten years later, it still makes sense.
For him, the most surprising thing was seeing the impact and recognition that the article achieved over time. Since its publication until today, several colleagues have communicated to Ioannidis their ideas, opinions and visions regarding their areas of work, showing the discussion and reflection raised by the article in the scientific community not only in biomedicine but in the social sciences, psychology or economics. Many researchers are eager to work with him: he has published work with 1,328 different co-authors in 538 institutions in 43 countries, and annually receives invitations to speak at a thousand conferences and institutions around the world. Nowadays he is unable to meet the generous average of accepting around five invitations per month, after excessive travel has caused dizziness.
Ioannidis and Steve Goodman form the duo that runs Metrics (Meta-Research Innovation Center at Stanford), a center that aims to improve the efficiency of scientific research. One of the goals of the professor and scientist is to be able to say one day that the title of his work is no longer true and that it makes no sense to say that the majority of results in published articles are false in any scientific area.
In the 1990s, Ioannidis gathered a team and set up a base at the University of Ioannina. After detecting disturbingly high error rates in the medical literature, it was necessary to have solid data, clear reasoning and good statistical analysis to be able to identify the problem and, if possible, find a solution. “A recurring theme of ancient Greek literature is that you need to pursue the truth, no matter what the truth may be,” he said.
His critical and analytical spirit takes shape in his works, which continue to challenge the foundations of medical research.
Ioannidis proved mathematically that you are attracted to ideas that have a good chance of being wrong, you just need to be motivated to prove that you are right and have a little wiggle room in how you set up the proof and you will probably be able to prove that wrong theories are correct.
Ioannidis published a study in 2005 in the Journal of the American Medical Association (Jama) in which he declared that between a third and half of the instructions in biomedical investigations were not trustworthy.
Another implicit lesson to be learned from Ioannidis’ work is that the results obtained are the fruits of the isolated work of scientists, each trying to surpass the other, each seeking scope of value without sharing or combining information. Unfortunately, in most areas, the search for recognition, or even the Nobel Prize, makes the paradigm of the solitary and isolated investigator the dominant paradigm. The path of evidence-based medicine is the most correct, which leads doctors to use the best science available to practice their profession, instead of limiting themselves to applying what they learned in college.
It is necessary to filter out bad studies, it is necessary to carry out a quality peer review and for this it is not enough to have a minimum number of people who spend a minimum amount of time analyzing information, which is also minimal. Even when data exists — or remains rare — there is not enough time to analyze and select it. One procedure that may be useful is post-publication review. The simple act of commenting, raising questions or concerns can be constructive, but there is a lack of incentives for scientists and other stakeholders to develop a quality critical analysis or even try to replicate the studies carried out. It is important and necessary to find ways to reward people for this type of verification. It is urgent to rethink the way of “doing” science, as planned and conceiving scientific research, promoting team science, large collaborative studies instead of individual researchers with independent studies, a whole new process that would culminate in peer review.
The United States Effect
In 2013, he joined forces with Daniele Fanelli, from the University of Edinburgh, and published in the Proceedings of the National Academy of Sciences the results of a study in which they defend the existence of the “United States Effect”, that is, North American scientists are under great pressure to produce results in order to obtain research funding or get a promotion and move up the career ladder. Ioannidis does not suggest that scientists are intentionally falsifying results, he points out that some areas of research are more difficult to quantify than others, such as the behavioral sciences, compared to genetics, where there is no room for error, for example, in sequencing of genes.
“Research is a wonderful thing. It’s the best thing that ever happened to human beings. We need the investigation. we need science. we need better ways of doing things. We often know what the methods are, but we don’t know how to implement them,” said Ioannidis at the beginning of the year. He argues that, as in medicine and for doctors, research and scientists should also adhere to pay for performance. It is a paradigm shift that will promote the best methods and practices. Currently, explained, something is very wrong. “We cannot continue investing in proposals or publications that present extravagant arguments. What should be supported and encouraged is progress with good methods, good science and incremental results. Nowadays there are a large number of scientists who want to do research and they are generating important insights into the good and best application of scientific research. And this requires quality education. The failure is in education”, he concludes.
Status Quo of Medical Research
“Researchers and doctors often don’t understand each other; they speak different languages,” explains Ioannidis. Medical research is not especially plagued by inaccuracies. But everyone expects more from scientists, and especially from medical scientists, once we understand that we are betting our lives on their results, explains Ioannidis, who makes a point of having several doctors on his team.
A major dilemma in the meta-research community is the question of whether problems with medical research should be broadcast to the public. Not only because it can promote disenchantment among the most skeptical patients, but many researchers and doctors do not want to give reasons that affect research funding. Ioannidis dismissed those concerns. “If we don’t inform the public about these problems, then we are no better than the non-scientists who falsely claim they can cure,” he says.
Rigor or funding, this is the dilemma for many researchers, according to Ioannidis: “Some think there may be less funding because we stop claiming that we can prove that we have miracle treatments. But if we can’t actually provide these miracles, how long will we be able to fool the public? The scientific enterprise is probably the most fantastic achievement in human history, but that doesn’t mean we have the right to exaggerate what we are accomplishing.
Dispelling Myths
Ioannidis suggests a simple approach: ignore all the studies. “Studies have gone back and forth and spread doubt about how to choose between the divergent results. The logic is valid for all medical studies”, he adds. He also points the reason to drug studies, which are said to have an additional corrupting force of financial conflict of interest. “Often, the claims made by studies are so extravagant that you can cross-reference them immediately without needing to know much about the specific problems with the studies. Even when the evidence shows that a particular piece of research is wrong, if you have thousands of scientists who have invested their careers in it, they continue to publish articles about it,” he says, concluding that “it’s like an epidemic, in the sense that they are infected with these misconceptions, and they are spreading to other researchers through journals.”
We could solve much of the problem if the world would just stop waiting for scientists to know for sure. Being wrong in science is good, even necessary, as long as scientists recognize that they were wrong, report their mistake openly rather than disguising it as a success and then moving on to the next thing.
“Science is a noble endeavor, but it is also a low-yield endeavor,” he says. We know that only a very small percentage of medical research is likely to lead to major improvements in clinical outcomes and quality of life, says Ioannidis, who calmly assures us that we should be very comfortable with this fact.
Published on LinkedIn
Published on Portal DiagnósticoWeb
Published in Revista Diagnóstico