Improving risk/benefit estimates in new drug trials Shortcomings in the way res

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Improving risk/benefit estimates in new drug trials

Shortcomings in the way researchers interpret pre-clinical studies may be

creating inflated expectations about new drugs

http://www.eurekalert.org/pub_releases/2011-03/mu-ire030211.php

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

Kimmelman, associate professor at McGill's Biomedical Ethics Unit and

Department of Social Studies of Medicine, and 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 development.

" 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. "