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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.
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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?
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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.
