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Clinical Trials
(100 points)
Due April 21, 2011
1.
(50) A clinical trial to compare a cholesterollowering drug with placebo among
individuals with coronary disease or other occlusive disease, but with below
average levels of LDL cholesterol (the "bad" cholesterol) is planned.
The
investigators hypothesize that further lowering of cholesterol in this high risk
group is beneficial. The primary endpoint is total mortality and the planned
followup is 5 years.
It is expected that 10% of participants given placebo will
die in 5 years.
The cholesterol lowering treatment is estimated to lower the LDL
cholesterol level by 40 mg/dl more than placebo.
The full effect of this
cholesterol lowering treatment is assumed to result in 20% fewer deaths than
the placebo group.
It is assumed that the full effect of the treatment on mortality
will not be reached for 2 1/2 years.
It is also assumed that the nonadherence
rate to the capsules prescribed will be 30% in the group that receive the
cholesterollowering drug by the end of the 5year trial.
a. (5)
Using Halperin's model and Table 1 in his paper, what is the adjusted
value for p
e
?
b. (5)
What is the combined sample size required for this study based on your
estimate of p
e
in part a.
See 1
st
formula on slide #7 of Lecture 17).
Assume the type I error is 0.05 (2sided) and power = 0.90.
c. (5)
If there was no lag, what would the adjusted value of p
e
be (assume the
nonadherence rate to the capsules for the cholesterollowering drug is
30% as in part a.)?
d. (5)
If compliance was perfect (100%) in the cholesterollowering group, what
would the adjusted value of p
e
be if the lag was 2 1/2 years?
e. (5)
Would sample size be larger or smaller than the estimate in part b. if
compliance to the cholesterol lowering treatment was 100% (zero
dropouts in Halperin’s terminology)?
f. (5)
What would be the impact on sample size (larger or smaller than your
answer in part b.) for this study if the estimated death rate was 7.5% for
the placebo group instead of 10% (assume all other assumptions in the
study description above are the same)?
g. (5)
The investigators predict that 15% of patients assigned placebo will begin
taking a cholesterol lowering treatment during followup.
If this is taken
into account in the determination of sample size, what impact would it
have (just state larger, smaller, or no change in sample size estimated for
part b.)?
1
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 Spring '07
 ph7420

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