Muzun

Homework 3

1) Review the E3200 Protocol and answer the following:

a) Were any surrogate variables used as outcomes in this study?
While there is no mentioned for surrogate variable , but based on what mentioned on “6. Measurement
of Effect page 25 “
We could consider the "Solid Tumor Response Criteria (RECIST) 6.1.1 Malignant Disease Evaluation."
Mainly measurements of tumor response using RECIST criteria is often used as a surrogate endpoint in
oncology clinical trials.

b) Were the surrogate variables part of the primary objective or part of the secondary objectives?
Seems to be as apart of the 1ry objective , while it evaluates the “response , time till event , survival “

c) Read over the eligibility criteria in section 3 of the protocol. Summarize the main
eligibility factors for entry into this study.
Confirmed cases – type of disease , no prior Oxaliplatin , adequate renal and liver function + blood
count
Determined criteria for INR + PTT must met + ECOG 0 -2
No history for thrombotic or hemorrhagic disorders , not treating with anticoagulation.

Which eligibility factors lead to heterogeneity of the population and which factors lead to homogeneity?
Heterogeneity (Advanced disease Stage – adequate liver and kidney function – had a treatment history
Aged over 18 – ECOG from 0 -2 – using of contraception)
Homogeneity (excluding certain historical trearment , In-eligiiblity criteria , excluding for lactating
women and pregentent- no aspirin in the last 10 days or surgical in previous 28 )

d) Given your answer to part c) above, would you consider this study to have broad
eligibility or narrow eligibility?
Inclusion Criteria limit the pool of eligible participants to those who meet these specific criteria,
resulting in a more focused and homogeneous study population

e) Now look at the E3200 Giantonio et al. JCO paper. Were any of the eligibility criteria that would lead to
heterogeneity reported in the manuscript? Were the treatment arms well balanced across these variables?

Stratification Factors
4.1.5.1 ECOG Performance Status: 0 vs.

1, 2 4.1.5.2 Prior Radiation Therapy: Yes vs. No

These stratification factors suggest that the randomization process consider a patient's performance
status (how well they can function) and whether they have previously received radiation therapy

By stratifying based on these factors, this study aims to ensure a balanced distribution of these
characteristics across the different treatment groups

This helps control for these factors when analyzing and interpreting research results
Muzun

2) Review the Calès et al. 2001 NEJM paper (in my lecture 8 Readings on BB) and
answer the following:
a) How was loss to follow-up handled in the statistical analysis for the primary endpoint?

1-Intention to treat analysis

2-Chi2 + Fisher exact + Mann-Whitney test

3-Treatment success calculations

The rate of treatment success, which is the sum of five-day survival and bleeding control, was
computed for the primary endpoint. Among the patients who did not respond to treatment were those
who were lost to follow-up on day 5 or earlier. This method makes sure that individuals who left
treatment early are counted and are regarded as having failed the program.

b) What was the primary method of analysis for the rate of treatment success?

was based on the intention-to-treat (ITT) principle , includes all randomized participants in their
originally assigned groups, regardless of whether they completed the intervention or were lost to
follow-up.

c) Was there provision for evaluating potential confounding factors for the rate of
treatment success?

Yes , they used different method as M-H + Berslow-day test to test for counfounding effect

d) How was the secondary endpoint of survival to day 42 handled in the analysis?

Kaplan–Meier analysis, log-rank tests

e) Were any methods used to conduct an adjusted analysis of survival to day 42?

Multivariate Analysis consider for Vapreotide+ Adjustment for Beta-Blocker Administration

3) Muscle strength declines with advancing age. Preliminary evidence suggests that part of this loss of muscle
strength might be due to progressive deficiency of dehydroepiandrosterone (DHEA). Investigators plan a
randomized trial to administer DHEA or an identical placebo for 6 months to elderly participants and then
measure muscle strength. Previous studies have reported a mean grip strength in elderly persons of 20 kg with
a standard deviation of 8 kg. Assuming alpha (two-sided) = 0.05 and beta = 0.10,
a) How many participants would be required to demonstrate an increase of at least 2 kg in the grip strength in
the treated group compared to the control group ? 168
3.24 ∗ 8 !
𝑛=# * = 12.96! = 167.7
2
. db sampsi
Muzun
. sampsi 20 22, sd1(8) sd2(8) alpha(0.05) power(0.10)

Estimated sample size for two-sample comparison of means

Test Ho: m1 = m2, where m1 is the mean in population 1

and m2 is the mean in population 2
Assumptions:

alpha = 0.0500 (two-sided)

power = 0.1000
m1 = 20
m2 = 22
sd1 = 8
sd2 = 8
n2/n1 = 1.00

Estimated required sample sizes:

n1 = 15
n2 = 15
b) How many participants would be needed if beta = 0.20?
(1.96 + 0.48) ∗ 8 !
𝑛=# * = 11.2! = 125
2
. db sampsi

. sampsi 20 22, sd1(8) sd2(8) alpha(0.05) power(0.20)

Estimated sample size for two-sample comparison of means

Test Ho: m1 = m2, where m1 is the mean in population 1

and m2 is the mean in population 2
Assumptions:

alpha = 0.0500 (two-sided)

power = 0.2000
m1 = 20
m2 = 22
sd1 = 8
sd2 = 8
n2/n1 = 1.00

Estimated required sample sizes:

n1 = 41
n2 = 41