Shortcomings in the way researchers interpret pre-clinical studies may be creating inflated expectations about new drugs
Shortcomings in the way researchers interpret pre-clinical
studies may be creating inflated expectations about new
It’s all too familiar: researchers announce the discovery of a
new drug that eradicates disease in animals. Then, a few years
later, the drug bombs in human trials. In the latest issue of the
journal PLoS Medicine, ethics experts Jonathan Kimmelman, associate
professor at McGill's Biomedical Ethics Unit and Department of
Social Studies of Medicine, and Alex John London, associate
professor of philosophy at Carnegie Mellon University, argue that
this pattern of boom and bust may be related to the way researchers
predict outcomes of their work in early stages of drug
“We do a fairly good job of predicting the success of
interventions that make it to later stages of clinical research,"
said London, who also directs CMU’s Center for Ethics and Policy.
"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, in which a
narrow focus on the data about the performance of a new drug 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,” London said. “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,” says Kimmelman.
If researchers adopt Kimmelman and London’s recommendations for
improving the ways that they predict outcomes from preclinical
trials they suggest that the research participants, drug developers
and funding agencies will all be better equipped to make informed
decisions about clinical drug testing, the study suggests.
“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
Kimmelman and London are currently investigating the quality and
outcomes of studies as drugs advance from pre-clinical stages of
testing to clinical trials thanks to a recent grant from the
Canadian Institute of Health Research.
For an abstract of the paper:
Full study is available on request.