A Cochrane Collaboration review that found just over half of new treatments to be more effective than their established equivalents in comparative clinical trials is good news for trial ethics, the researchers say.

In the systematic review published by The Cochrane Library, a research team led by Benjamin Djulbegovic of USF Health Clinical Research and the H Lee Moffitt Cancer Center & Research Institute at the University of South Florida in Tampa, US looked at evidence from 743 publicly funded, randomised trials enlisting 297,744 patients in total.

The studies involved new, experimental treatments for cancer and neurological disorders as well as a range of other diseases. When these therapies were compared with established treatments for the same conditions, very slightly more than half on average of the new treatments performed better than the established treatments.

For the researchers, this was a welcome outcome. In a randomised trial, they explained, patients are allocated randomly to different treatment groups to ensure that like is compared with like.

Ethical dilemma

When the trial involves a new treatment, the hope or expectation is that it will prove better than the established treatment it is compared with, Djulbegovic et al noted. However, this presents an ethical dilemma.

If the researchers already know one treatment is better than the other, they are knowingly allocating some of the trial participants to an inferior treatment, the researchers pointed out. So if randomised trials are to be properly ethical, only half of new treatments should turn out to be better than existing ones.

“When we compared the effects of new treatments to established ones, the pattern was almost symmetrical,” Djulbegovic commented. “This is good news, because it means researchers genuinely don’t know whether new treatments are going to be any better.”  

The researchers found the same pattern in trials going back five decades. Fifteen years ago, they noted, Iain Chalmers – a Cochrane Collaboration founders and one of the authors of the latest review – posed the question in a letter to the British Medical Journal: ‘What is the prior probability of a proposed new treatment being superior to established treatments?’