The pattern of boom-and-bust in bringing novel therapeutics to market may have something to do with the way researchers translate their results from preclinical to clinical studies, two ethicists suggest.
Researchers may "have too narrow of a view" when it comes to predicting how their work will progress from animal studies into human ones, according to Jonathan Kimmelman, PhD, of McGill University, and Alex John London, PhD, of Carnegie Mellon University.
They attempt to raise awareness of the need for a more cautious translational process between preclinical and clinical studies in an essay in PLoS Medicine.
"We don't always see additional uncertainty reflected in the way [researchers] think about first-in-human studies," London told MedPage Today. "There's always this boom-and-bust of heightened expectation for promising programs. But time goes by and there's disappointment. It seems to happen with some regularity."
Now, London said, there's a "methodological question -- how can we keep that from happening?"
London says many researchers do take proper caution when approaching their early findings and how they will translate to human studies. However, there is a public face and a private face to research, he says.
Researchers are happy to talk about limitations, "insofar as there's a public face ensuring enthusiasm for novel research programs."
"That's where the public face can get ahead of what's warranted by science," he said.
One of the main concerns derived from this is that the translational predictions are used for a host of reasons in human trials, such as ensuring that risk-benefit ratios are reasonable, that informed consent is truly informed.
Kimmelman and London offered some suggestions for improving the translational process, including adding randomization and blinded comparison to early studies.
They caution that animal studies can't enable reliable causal inference and clinical generalization because they don't address important threats to internal, construct, and external validity.
Decision makers should also use evidence that sheds light on the reliability of causal claims embedded with a proposed trial, they wrote. For instance, evidence can be gathered from outcomes of previous trials involving agents targeting related biological pathways.
In fact, one of their next steps towards investigating ways to improve the translational process will be to look at the arc of compounds that have and haven't succeeded in translation, to identify possible clues.
"There may be many ways forward," London said, "with researchers in different disciplines coming up with different proposals."
