Phase II Clinical Trial
Phase II clinical
trials are generally single-arm studies aimed at estimating the activity of a
new treatment. These “pilot” studies are commonly applied to anticancer drugs
to assess the therapeutic efficacy and toxicity of new treatment regimens.
Phase II trials decide whether the new treatment is promising and warrants
further investigation in a large-scale randomized Phase III clinical trial
based on an observed response rate that appears to be an improvement over the
standard treatment or other experimental treatments. Because the sample size is
small (generally less than 50 patients), Phase II clinical trials are only able
to detect a large treatment improvement, e.g. greater than 10%. To
detect a small difference in treatment, e.g. less than 5%, one would require a
much larger sample size, which is not possible in Phase II studies due to the
limited number of subjects eligible for the study and the large number of
treatments awaiting study. Phase II
studies are prominent in cancer therapeutics because new treatments frequently
arise from combinations of existing therapies or by varying dose or radiation
schedules.
There are three
main objectives in treating patients in Phase II clinical trials. The
primary objective is to test whether the therapeutic intervention benefits the
patient. The second objective is to screen the experimental treatment for the
response activity in a given type of cancer. The final objective is to extend
our knowledge of the toxicology and pharmacology of the treatment.
An important
characteristic of some Phase II trial designs is the use of early stopping
rules. If there is sufficient evidence that one of the treatments under
study has a positive treatment effect, then patient accrual is terminated and
this treatment is declared promising. Also, if a treatment is sufficiently
shown not to have a desirable effect, then patient accrual is terminated and
this treatment is declared not promising.
This program helps users to determine
sample sizes or decision rules for a Phase II clinical trial so that
the sample size needed for a standard Phase II clinical trial can be reduced.
If you don’t know which program to use, please feel free to check : User
guidance, definition and terminology
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Phase II
Clinical Trials 1. Fleming's Phase II Procedure 3. Simon’s Randomized Phase II
Design |
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Further
Information:
Difference between Fleming’s
procedure and Bayesian design of Phase II clinical trials
This section describes
both the hypotheses and design for Fleming’s and the Bayesian approach to single-arm
Phase II clinical trials. Both designs are used for Phase II clinical trials
with binary outcomes and continuous monitoring. The fundamental difference
between the two designs is the frequentist basis for
Fleming’s procedure only depends on the observed results whereas the Bayesian
approach uses prior information. The testing procedure for Fleming’s procedure
is based on the normal approximation to the binomial distribution of the
observed number of treatment responses. The resulting decision boundaries, rg and ag,
are solved analytically. The Bayesian design incorporates prior information
about the treatment being investigated with the observed results to yield
revised beliefs about the treatment. The testing procedure is based on the
posterior probability of the experimental treatment given the observed data.
The posterior probability is a conditional probability computed from a beta
distribution which results in the upper and lower decision boundaries, Un and Ln,
which are evaluated using numerical integration, namely “Simpson’s Composite
Algorithm”. Another difference
between the two designs is that Fleming’s procedure has only two outcomes at
the final recruitment stage, reject or accept H0, whereas the
Bayesian design traditionally allows for an inconclusive trial at the final
stage.
