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We hope you have enjoyed this limited-length demo
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- View the Talks
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1. Adaptive clinical trials: overview 1
- Prof. Yu Shyr
-
2. Adaptive clinical trials: overview 2
- Prof. Yu Shyr
-
3. Bayesian adaptive designs for clinical trials
- Prof. Benjamin Saville
-
4. Adaptive clinical trial design: randomization
- Prof. Hao Liu
-
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
-
7. Case studies of adaptive early phase trials
- Prof. Daniel Normolle
-
8. Phase II clinical trials - traditional approaches
- Prof. Fei Ye
-
9. Phase II clinical trials - Bayesian methods
- Prof. Fei Ye
-
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
-
14. Ethical issues in adaptive clinical trials
- Dr. Spencer Phillips Hey
-
15. Implementation of adaptive methods in early phase clinical trials
- Prof. Gina Petroni
-
16. Design early phase drug combination trials: methods
- Prof. Ying Yuan
-
17. Design early phase drug combination trials: software
- Prof. Ying Yuan
-
18. Adaptation in likelihood trials
- Prof. Jeffrey Blume
Printable Handouts
Navigable Slide Index
- Introduction
- Traditional clinical trial phases
- Adaptive clinical trial design
- ‘Seamless’ designs
- FDA guidelines for seamless designs
- A “seamless phase II/III” design (1)
- A “seamless phase II/III” design (2)
- Seamless phase II/III diagram
- Benefits of seamless phase II/III designs
- Potential drawbacks of seamless II/III designs
- Feasibility considerations (follow-up & endpoints)
- Feasibility considerations (logistics & resources)
- Ethical considerations
- Statistical considerations
- Conditions for a seamless trial
- Statistical methods
- Combination P-value
- Combination P-values (limitations & advantages)
- Group-sequential methods
- Group-sequential methods (extension)
- Conditional power/error
- Bayesian methods (1)
- Bayesian methods (2)
- General conclusions on seamless methods
- Additional methods
- Case studies
- Example 1: INHANCE (1)
- Example 1: INHANCE (2)
- Example 2: PURSUIT-SC (1)
- Example 2: PURSUIT-SC (2)
- Example 3: EORTC study 30986 (1)
- Example 3: EORTC study 30986 (2)
- References (1)
- References (2)
- References (3)
- References (4)
Topics Covered
- Background and settings appropriate for implementing seamless trial designs
- Benefits and potential drawbacks of seamless designs
- Real world examples of seamless trial designs in completed trials
Talk Citation
Garrett-Mayer, E. and O’Connell, N. (2016, December 29). Seamless phase II/III trials [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 12, 2024, from https://doi.org/10.69645/VJVG1737.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Elizabeth Garrett-Mayer has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
- Mr. Nathaniel O’Connell has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Methods
Transcript
Please wait while the transcript is being prepared...
0:00
Today, we are going to be talking about
Seamless Phase II/III Trials.
My name is Elizabeth Garrett-Mayer
and I'm an oncology biostatistician
at the Hollings Cancer Center
and the Department of Public Health Sciences
at the Medical University of South Carolina.
Along with me is Nathaniel O'Connell,
who is a graduate student
in the Department of Public Health Sciences.
I will be giving the beginning part
of this talk,
and then towards the end, we will switch over
and Nathaniel will finish the talk
by going through some case study examples.
0:35
There are traditionally
three phases of clinical trials.
The first phase is often called
a dose-finding study,
where the goal is to find the optimal dose.
These are commonly "first in man" trials
and there are a range of doses
that are evaluated to find the highest dose
that falls below,
or within, an acceptability threshold.
These trials usually have relatively
few patients
and are completed as the first part
of the clinical development of a drug.
Moving on from phase I, after an optimal dose
is found we go into the phase II setting.
At this stage, the safety of the drug
is further investigated
and the efficacy of the drug
is also investigated.
These are more exploratory in nature,
where we're looking to find
what the correct dose,
the regimen, or the schedule of the drug is.
And they may investigate early efficacy
across several dose levels,
or treatments, or even regimens,
or schedules.
In this phase is where we're looking
for the hint of efficacy
to see whether or not
the drug is showing sufficient promise
to be moved forward to the next phase,
which is phase III.
In phase II we often allow
relatively small sample sizes
recognizing that we need preliminary evidence
and it's not considered
a definitive phase of drug development.
The last phase of drug development
in most contexts is phase III.
In phase III it is a confirmatory stage
where efficacy is determined, often
versus a standard of care regimen.
In these trials there is a large sample size
relative to the phase II,
and they are very often multi-site studies.
Almost always are we going to be comparing
a treatment to some kind of control group;
And in this case we almost always have
relatively strict error rates,
meaning we need to have
high statistical power
and a low alpha level
also known as the type 1 error rate.
And this is because this stage is
when there is the opportunity to have
the drug approved by a federal agency,
such as in the United States,
the Federal Drug Administration.