Thursday, June 02, 2011

An Epidemic of False Claims

Competition and conflicts of interest distort too many medical findings

By John P. A. Ioannidis, writing in SciAm

False positives and exaggerated results in peer-reviewed scientific studies have reached epidemic proportions in recent years. The problem is rampant in economics, the social sciences and even the natural sciences, but it is particularly egregious in biomedicine. Many studies that claim some drug or treatment is beneficial have turned out not to be true. We need only look to conflicting findings about beta-carotene, vitamin E, hormone treatments, Vioxx and Avandia. Even when effects are genuine, their true magnitude is often smaller than originally claimed.

The problem begins with the public’s rising expectations of science. Being human, scientists are tempted to show that they know more than they do. The number of investigators—and the number of experiments, observations and analyses they produce—has also increased exponentially in many fields, but adequate safeguards against bias are lacking. Research is fragmented, competition is fierce and emphasis is often given to single studies instead of the big picture.

Much research is conducted for reasons other than the pursuit of truth. Conflicts of interest abound, and they influence outcomes. In health care, research is often performed at the behest of companies that have a large financial stake in the results. Even for academics, success often hinges on publishing positive findings. The oligopoly of high-impact journals also has a distorting effect on funding, academic careers and market shares. Industry tailors research agendas to suit its needs, which also shapes academic priorities, journal revenue and even public funding.

The crisis should not shake confidence in the scientific method. The ability to prove something false continues to be a hallmark of science. But scientists need to improve the way they do their research and how they disseminate evidence.

First, we must routinely demand robust and extensive external validation—in the form of additional studies—for any report that claims to have found something new. Many fields pay little attention to the need for replication or do it sparingly and haphazardly. Second, scientific reports should take into account the number of analyses that have been conducted, which would tend to downplay false positives. Of course, that would mean some valid claims might get overlooked. Here is where large international collaborations may be indispensable. Human-genome epidemiology has recently had a good track record because several large-scale consortia rigorously validate genetic risk factors.

The best way to ensure that test results are verified would be for scientists to register their detailed experimental protocols before starting their research and disclose full results and data when the research is done. At the moment, results are often selectively reported, emphasizing the most exciting among them, and outsiders frequently do not have access to what they need to replicate studies. Journals and funding agencies should strongly encourage full public availability of all data and analytical methods for each published paper. It would help, too, if scientists stated up front the limitations of their data or inherent flaws in their study designs. Likewise, scientists and sponsors should be thorough in disclosing all potential conflicts of interest.

Some fields have adopted one or several of these mechanisms. Large international consortia are becoming commonplace in epidemiology; journals such as Annals of Internal Medicine and the Journal of the American Medical Association instruct authors to address study limitations; and many journals ask about conflicts of interest. Applying the measures widely won’t be easy, however.

Many scientists engaged in high-stakes research will refuse to make thorough disclosures. More important, much essential research has already been abandoned to the pharmaceutical and biomedical device industries, which may sometimes design and report studies in ways most favorable to their products. This is an embarrassment. Increased investment in evidence-based clinical and population research, for instance, should be designed not by industry but by scientists free of material conflicts of interest.

Eventually findings that bear on treatment decisions and policies should come with a disclosure of any uncertainty that surrounds them. It is fully acceptable for patients and physicians to follow a treatment based on information that has, say, only a 1 percent chance of being correct. But we must be realistic about the odds.


Scientists test cancer drug that might heal a broken heart

Scientists are testing a drug that can mend a broken heart. Experiments found the medicine, which is usually used to treat cancer, shrank enlarged and diseased hearts back down to near normal size, allowing them to work properly again. Now the drug is about to be given to human heart patients for the first time.

In the future, it could be used to prevent and treat heart failure – one of the biggest causes of hospital admissions and death.
Living on the edge: More than 750,000 in the UK suffer from heart disease - with 40 per cent dying within a year of diagnosis

Living on the edge: More than 750,000 in the UK suffer from heart disease - with 40 per cent dying within a year of diagnosis

The drug’s powerful effect could provide a godsend for some of the millions worldwide suffering from heart failure, in which a weakened heart struggles to pump blood around the body.

Caused by heart attacks, high blood pressure and other conditions, more than 750,000 people live with it in the UK alone, with everyday tasks such as eating, dressing and getting out of bed leaving many sufferers breathless and exhausted.

Treatments range from drugs to transplants but with up to 40 per cent of those affected dying within a year of diagnosis, it has a worse survival rate than many cancers.

The medicine tested belongs to a family of drugs called histone deacetylases, which are already used to treat tumours.

But research from the University of Texas’s Southwestern heart centre shows that they also temper autophagy, a process in which cells eat their own proteins.

Autophagy allows cells to tidy up unwanted debris. But when it gets out of control, too many vital parts are eaten and the cells die. In hearts, this can further damage those which are already diseased.

This inflammation results in biological changes that can damage the heart and increase the risk of a heart attack, says a report in the European Heart Journal.

The researchers gave the drug to mice with high levels of autophagy and enlarged hearts that could fail, with incredible results. Joseph Hill, the heart centre’s chief of cardiology, said: ‘The heart decreased back to near its normal size, and heart function that had previously been declining went back to normal. That is a powerful observation where disease regression, not just disease prevention, was seen.’

He hopes the drug could be used to repair hearts damaged by heart attacks and other forms of disease. Dr Hill told the Daily Mail: ‘There is a huge need for new treatments for heart failure. ‘The final common pathway for most types of heart disease, high blood pressure, heart attacks or valve disease is heart failure and it is sky-rocketing.’

He is about to start small, preliminary tests on heart patients. If successful, larger-scale trials will follow.

The tests that led to the breakthrough began ‘decades ago’ on yeast, said the researchers, but only now does it seem likely it can be adapted to the human heart.

Dr Hill said: ‘This is one of those exciting, but rare, examples where an important finding made originally in yeast moved into mouse models and is soon moving to humans.’

Last night, Professor Jeremy Pearson, the charity’s associated medical director, said: ‘This is an intriguing study which suggests that an anti-cancer drug can, unexpectedly, be beneficial in heart failure – a condition which urgently needs new medicines to help treat it.’


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