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We hope you have enjoyed this limited-length demo
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1. Adaptive clinical trials: overview 1
- Prof. Yu Shyr
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2. Adaptive clinical trials: overview 2
- Prof. Yu Shyr
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3. Bayesian adaptive designs for clinical trials
- Prof. Benjamin Saville
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4. Adaptive clinical trial design: randomization
- Prof. Hao Liu
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5. Adaptive designs for phase I trials 1
- Prof. Anastasia Ivanova
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6. Adaptive designs for phase I trials 2
- Prof. Anastasia Ivanova
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7. Case studies of adaptive early phase trials
- Prof. Daniel Normolle
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8. Phase II clinical trials - traditional approaches
- Prof. Fei Ye
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9. Phase II clinical trials - Bayesian methods
- Prof. Fei Ye
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10. Seamless phase II/III trials
- Prof. Elizabeth Garrett-Mayer
- Mr. Nathaniel O’Connell
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11. Frequentist approaches: sample size in adaptive clinical designs
- Prof. Tatsuki Koyama
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14. Ethical issues in adaptive clinical trials
- Dr. Spencer Phillips Hey
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15. Implementation of adaptive methods in early phase clinical trials
- Prof. Gina Petroni
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16. Design early phase drug combination trials: methods
- Prof. Ying Yuan
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17. Design early phase drug combination trials: software
- Prof. Ying Yuan
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18. Adaptation in likelihood trials
- Prof. Jeffrey Blume
Printable Handouts
Navigable Slide Index
- Introduction
- What is an adaptive trial?
- Traditional randomized control trail
- A multiple arm study
- Adaptive clinical trials in the literature
- No rationale to further delay adaptive designs
- Are adaptive trials more ethical than randomized?
- Talk outline
- Background
- Why RCTs?
- Leaving therapy to chance
- Charles Fried (1974) and theoretical equipoise
- Theoretical equipoise
- Critique of theoretical equipoise
- Benjamin Freedman (1987) and clinical equipoise
- Clinical equipoise
- Advantages of clinical equipoise
- Critique of clinical equipoise
- Miller (2003) and the non-exploitation framework
- Advantages of non-exploitation framework
- Critique of non-exploitation framework
- Summing up
- Ethical challenges of adaptive design trials
- Adaptive trials: alter allocation ratio
- Adaptive trials: drop arms based on outcomes
- Ethical argument 1: patient-subject benefit
- Problems for argument 1
- Ethical argument 2: therapeutic misconception
- Problems for argument 2
- Ethical argument 3: efficiency
- Problems for argument 3
- Ethical argument 3.1: efficiency
- Ethical argument 3.1.1: efficiency
- Ethical argument 4: objection from injustice
- Conclusion
- Adaptive trials do offer ethical advantages
- Bibliography (1)
- Bibliography (2)
Topics Covered
- Purported ethical advantages of adaptive clinical trial designs
- Foundations of research ethics
- Ethical tensions in randomized controlled trials
- The concept(s) of equipoise
- Do adaptive designs enhance patient-subject benefit?
- The therapeutic misconception
- Efficiency
- Are adaptive randomized trials unjust?
Talk Citation
Hey, S.P. (2016, December 28). Ethical issues in adaptive clinical trials [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 6, 2024, from https://doi.org/10.69645/CVHK3727.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Spencer Phillips Hey has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Pharmaceutical Sciences
Transcript
Please wait while the transcript is being prepared...
0:00
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.
0:23
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?
0:58
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.