FEW scandals in science are more chilling than those in which patients have been subjected to risky medical experiments without their knowing it. It鈥檚 a scenario that seems almost unthinkable in these days of ethics boards, oversight committees and whistle-blowers. Yet new research has lifted the lid on just such a scandal, and one that has been running for decades in many countries. It is now clear that tens of thousands of patients have been subjected to pointless, unethical and potentially lethal medical experiments in hospitals around the world.
The experiments are of the type known as randomised controlled trials (RCTs), which are widely and rightly acknowledged as the acid test of the effectiveness of new therapies. Over the years, RCTs have identified countless life-saving therapies, from new surgical techniques to cancer drugs. Patients who take part are randomly divided into two groups. One is prescribed the new treatment, the other a 鈥渃ontrol鈥� such as a placebo. By comparing the success rates of the two groups, doctors can gauge the effectiveness of a new treatment. Their conclusions have been confirmed by years of experience on wards. No one seriously doubts that therapies identified in this way work.
No one, that is, apart from the many researchers who insist on carrying out RCTs on proven therapies. In dividing their patients into treatment and control groups, they are denying half of them access to the already proven therapy. At best, these patients have their health unjustifiably jeopardised. At worst, they could be receiving a death sentence.
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It seems incredible that such trials could escape the notice of the ethics committees who vet RCTs, the journals that publish the results and the numerous physicians already using the therapies. Yet this is what a team led by Dean Fergusson of the Ottawa Health Research Institute has shown in a study published in the June issue of the journal Clinical Trials (vol 2, p 218).
They focused on the RCTs for aprotinin, a protein which first showed promise in the 1980s as a way of combating blood loss during surgery. By June 1992 it had been tested on more than 2000 patients in a dozen RCTs, and the evidence was unequivocal: aprotinin radically reduces the need for blood transfusions in heart surgery. It won approval from the US Food and Drug Administration in 1993, and was soon in use in hospitals worldwide.
Yet dozens of research teams recruited yet more patients for yet more RCTs. Fergusson and his colleagues tracked down no fewer than 50 subsequent trials, together involving more than 5000 patients. All confirmed that aprotinin reduces the need for blood transfusions in heart surgery. In gathering this superfluous data, thousands of patients ended up as controls, and were thus denied access to the proven therapy, with potentially life-threatening results.
Aprotinin is by no means an isolated case. As long ago as the mid-1970s, RCTs of clot-buster drugs like streptokinase had shown they could save the lives of heart-attack patients. Even so, researchers persisted with a dozen further RCTs over the following decade testing the clot-busting ability of streptokinase compounds, needlessly denying effective treatment to tens of thousands of patients.
鈥淭hese patients have their health jeopardised. At worst, they could be receiving a death sentence鈥�
It is not always patients in the control group whose health is jeopardised. During the mid-1970s, trials proved conclusively that certain drugs used to combat the effects of heart attacks did more harm than good. Even so, a decade later patients were still being recruited into trials, the results of which only confirmed what was already known.
What leads researchers to carry out such pointless studies? One possibility is the publish-or-perish syndrome, which drives academics to churn out essentially worthless research to boost their portfolio of published work. Another possibility is that pharmaceutical companies offer to fund RCTs as a way of getting their latest drugs onto wards.
The truth may be far simpler, but no less scandalous. Fergusson and his colleagues found that the academic papers that reported the additional trials of aprotinin were astonishingly thin on references to previous studies. Typically, they mentioned references to just four previous RCTs 鈥� and usually the same ones. This is a classic sign of references simply being cribbed from previous papers, rather than located through rigorous literature searches.
True, literature searches were not easy without online databases. But that was never an excuse for failing to carry them out. What Fergusson and his colleagues appear to have found is that the health of thousands of patients is being threatened by researchers who do not know that their trials are pointless because they cannot be bothered to do the necessary checks.
These researchers, the ethics committees who approved their trials and the journals that published the results can no longer ignore this scandal. For it cannot be long before some of the patients discover what was done to them 鈥� and start asking awkward questions.
