prevention, reduction, or mitigation of drug-related toxicity. This new
agent is to be tested against a placebo in a double-blind randomized
trial among patients with mestastatic breast cancer who receive weekly
paclitaxel. The rate of neurotoxicity over the period of the trial is esti-
mated to be about 40% in the placebo group, and the hypothesis is that
this new agent lowers the toxicity rate by one-half, to 20%. Find the
total sample size needed using a two-sided level of significance of 0.05
and the assumption that the hypothesis would be detectable with a
power of 80%.12.24 In the study on metastatic breast cancer in Exercise 12.23, the investi-
gator also focuses on tumor response rate, hoping to show that this rate
is comparable in the two treatment groups. The hypothesis is that
addition of the new agent to a weekly paclitaxel regimen would reduce
the incidence of neurotoxicity without a compromise in its e‰cacy. At
the present time, it is estimated that the tumor response rate for the
placebo group, without the new agent added, is about 70%. Assuming
the same response rate for the treated patients, find the margin of error
of its estimate using the sample size obtained from Exercise 12.23.
12.25 The primary objective of a phase III trial is to compare disease-free
survival among women with high-risk operable breast cancer following
surgical resection of all known disease and randomized to receive as
adjuvant therapy either CEF or a new therapy. CEF has been estab-
lished successfully as a standard adjuvant regimen in Canada; the aim
here is to determine whether the addition of a taxane (to form the new
regimen) can improve survival outcome over CEF alone. The five-year
disease-free survival rate for women receiving CEF alone as adjuvant
therapy was estimated at about 60%, and it is hypothesized that the
newly formed regimen would improve that rate from 60% to 70%. Find
the total sample size needed using a two-sided test at the 0.05 level of
significance and a statistical power of 80%.
12.26 Ovarian cancer is the fourth most common cause of cancer deaths in
women. Approximately 75% of patients present with an advanced
stage, and because of this, only a minority of patients will have sur-
gically curable localized disease, and systematic chemotherapy has
become the primary treatment modality. A randomized phase III trial
is considered to compare paclitaxel–carboplatin versus docetaxel–
carboplatin as first-line chemotherapy in stage IV epithelial ovarian
cancer. Suppose that we plan to use a statistical test at the two-sided 5%
level of significance and the study is designed to have 80% power to
detect the alternative hypothesis that the two-year survival rates in the
paclitaxel and docetaxel arms are 40% and 50%, respectively. Find the
total sample size required.
480 STUDY DESIGNS