Predicting Harms and Benefits in Translational Trials

PLoS Medicine
(Accessed 13 March 2011)

Predicting Harms and Benefits in Translational Trials: Ethics, Evidence, and Uncertainty Jonathan Kimmelman, Alex John London Essay, published 08 Mar 2011

Summary Points
– Ethical judgments about risk, benefit, and patient eligibility in clinical trials hinge on predictions about harm, therapeutic response, and clinical promise.

– Predictions for novel interventions in preclinical stages of development suffer from two problems: insufficient attention to threats to validity in preclinical research and a reliance on an overly narrow base of evidence that includes only animal and clinical studies of the intervention in question (“evidential conservatism”).

– To improve ethical and scientific decision-making in early phase studies, decision-makers should explicitly attend to reporting quality and methodological features in preclinical experiments that address threats to internal, construct, and external validity.

– Decision-makers should also use evidence that sheds light on the reliability of causal claims embedded within a proposed trial. This evidence can be gathered from outcomes of previous trials involving agents targeting related biological pathways (“reference classes”).