Improving Drug Trials
Too often what seems to be a promising drug winds up failing in human trials.
Carnegie Mellon University ethics expert Alex London says the pattern may be related to the way researchers predict the outcomes of their work.
In the latest issue of the journal PLoS Medicine, London and co-author Jonathan Kimmelman argue the pattern may be related to the way researchers predict outcomes of their work in the early stages of drug development.
"We do a fairly good job of predicting the success of interventions that make it to later stages of clinical research," said London, an associate professor of philosophy at CMU.
He added, "But when it comes to the leap from animal studies to the first trials in humans, there are serious problems."
Kimmelman and London suggest that the interpretation of pre-clinical results may suffer from a kind of myopia.
They say a narrow focus on drug performance data in pre-clinical studies produces overly optimistic predictions.
"Clearly we need to look at the pre-clinical evidence about a new intervention when estimating its likely benefits and burdens in people," said London, who also directs CMU's Center for Ethics and Policy.
"But we also need to look at how similar interventions have fared in the past. If drugs that work on the same principle have failed development, there may be good grounds for tempering our expectations."
Kimmelman and London also question whether researchers are doing enough to minimize any factors that interfere with measuring a drug's true effects.
They suggest that some of the techniques, such as randomization and blind testing that are common in clinical tests involving human subjects, should also be used at the pre-clinical stage.
"Medical researchers do a lot to control bias in drug trials with humans. We think if these measures were taken up by researchers who test drugs in animals, we would have a better basis for designing human trials," said Kimmelman, an associate professor at McGill University's Biomedical Ethics Unit and Department of Social Studies of Medicine.
If researchers adopt their recommendations, the co-authors suggest that the research participants, drug developers, and funding agencies will all be better equipped to make informed decisions about clinical drug testing.
"Pre-clinical studies provide a useful starting place for determining whether a new drug is clinically promising," Kimmelman said.
"We think we can — and should — be doing more to ensure predictions about clinical activity rest on a more complete and sound evidence base."
The research was funded by the Canadian Institutes of Health Research.