Ethical issues in adaptive clinical trials

Published on December 28, 2016   30 min

Other Talks in the Series: Adaptive Clinical Trial Design

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Hello. My name is Spencer Hey. I'm a research fellow in the Program on Regulation, Therapeutics and Law housed within the Division of Pharmacoepidemiology and Pharmacoeconomics at the Brigham and Women's Hospital in Boston, Massachusetts. I'm also a faculty member at the Harvard Center for Bioethics where I teach courses in research ethics and moral reasoning. Today, I will be talking about Ethical Issues in Adaptive Clinical Trials.
We begin with a very basic question. What is an adaptive trial? While there are many different kinds of adaptive trial designs, and a complete answer to this question is really a course unto itself. For the purposes here, we're going to keep it simple and just go with U.S. Department of Health and Human Services definition. According to the DHHS, an adaptive trial is a study that includes a prospectively planned opportunity for modification of one or more specified aspects of the study design and hypotheses based on analysis of data, usually interim data, from subjects in the study. Or to put it more simply, it's a study that modifies itself. But modifies itself how?
If you look at the structure of a traditional randomized controlled trial by which I mean a trial that is not adaptive, the participants are randomly allocated among the treatment arms in a fixed predetermined way. This is usually a ratio of one-to-one, i.e., every participant is equally likely to end up in either arm of the study. Then at the end of the trial, we compare the outcomes and draw conclusions about which therapy was better. In an adaptive trial, we don't wait to examine the outcomes until the end of the study. Instead, we examine and compare the outcomes either as they happen or at pre-determined points during the trial and then use this information to alter the structure of the trial. Frequently, this means altering the random allocation ratio. So let's say that the experimental therapy appears to be better than the control. That will make it more likely that a new subject will be allocated to the experimental therapy. In other words, as the study progresses and the outcomes start to roll in, the allocation ratio might shift toward two to one or three to one, sending more participants into the better performing arm. This is not the only kind of modification in adaptive design.