Sample Problems ADVANCED EPID/BIOS

PROBLEM SESSION #1 (DR GERTRUDE KALANDA, MONDAY 4th JUNE 2012, 3PM)

1. Convert the following:

Prob = 0.15 Odds =

Prob = 0.65 Odds =

Odds = 0.25 Prob =

Odds = 8:1 Prob =

Odds = 30:4 Prob =

2. Investigator A decides to measure the occurrence of homicides in Raleigh (a city in North Carolina).
She has available to her the medical examiner’s data base and the census data for 1990. In Raleigh,
there were 23 homicides in 1989 and 36 homicides in 1990. The population of Raleigh was 356,000
people in 1990.

What measure of frequency should she use?

What is the value of this measure for 1989; for 1990; for the two years combined?
What assumptions is she making?
What kind of study is this?

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Sample Problems ADVANCED EPID/BIOS

3. Investigator B decides to examine anxiety among patients with asthma. Over the course of one
month, he examines 250 patients attending the pulmonary clinic. Of the 250 patients, 50 have anxiety
disorder.

What measure of frequency should he use to report this finding? Calculate it.
What kind of study is this?

4. Over the course of 2 years, Investigator C examines the incidence of diarrhea among the infants of
500 women who are unable to breast feed their infants. At the six week follow-up, 45 infants have
had one episode of diarrhea.

Calculate an appropriate measure of frequency.

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Sample Problems ADVANCED EPID/BIOS

5. In another study, Investigator C identifies another 300 infants. She schedules weekly follow-up
visits for first 6 weeks. In the first week, 10 infants have diarrhea. In the second week, 12 infants
have diarrhea and 2 withdraw from the study. In the 3rd week, 5 infants have diarrhea and 1 infant
withdraws. In the 4th week, 8 infants have diarrhea and 3 withdraw. In the 5th week, 20 infants have
diarrhea and in the 6th week, 30 have diarrhea.

What would be the preferred measure of frequency?

Calculate both cumulative incidence and incidence rate for these data.

6. Investigator D is the principal investigator of a large study investigating child abuse. Over the
course of 1 year, her staff interviews 10000 children in 100 schools. 459 children provide self-reports
consistent with child abuse.

What measure should she report? Calculate it.

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Sample Problems ADVANCED EPID/BIOS

7. You conduct a study to evaluate a new diagnostic test. A total of 1200 persons are enrolled in the
study. The results are shown below.

Disease Status
Test Result () ()
() 254 66 320
() 20 860 880
Total 274 926 1200

Determine the:

a. Sensitivity

b. Specificity

c. Accuracy

d. Positive predictive value for the study population

e. Negative predictive value for the study population

f. If the test is applied in a population with a prevalence of 8%, will the positive predictive value
increase, decrease or remain the same?

g. If the test is applied in a population with a prevalence of 8%, will the negative predictive value
increase, decrease or remain the same?

h. Calculate the positive predictive value for a prevalence of 8%

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Sample Problems ADVANCED EPID/BIOS

8. After completing her first study, Investigator A becomes convinced that a “mentoring” program is a
potential beneficial intervention in preventing HIV infection among at risk youth. Through her
extensive contact network, she identifies 2000 at risk youth. She randomly assigns 1000 to the
intervention and 1000 to no intervention. The youth are then followed for 3 years. In the intervention
group, there are 3 cases of HIV infection (0 in year 1, 2 in year 2, 1 in year 3). In the no intervention
group, there are 34 cases of HIV infection (12 in year 1, 15 in year 2 and 7 in year 3).

What is the cumulative incidence in the two groups?

What is the “average” incidence rate over the three years for the two groups?
What is the incidence rate for year 2 alone for the two groups?
What is the “best estimate” incidence rate over the three years for the two groups?
What kind of study is this?

9. After his first study, Investigator B hypothesizes that anxiety disorder leads to an increased
frequency of asthma flares. He assembles two cohorts, one with anxiety disorder and one without,
each consisting of 500 persons. Over the course of a three month follow-up period, there are 65
asthma events in the anxiety disorder group occurring in 45 different people (10 persons had 2
events; 5 persons had 3 events). In the group of persons without anxiety disorder, there were 40
asthma events occurring in 33 different people ( 5 persons had 2 events, 1 person had 3 events).

What is the preferred measure of frequency for these data?

What is the cumulative incidence in the 2 groups?
What is the incidence rate in the 2 groups (Assume each event lasts 5 days and there are 30 days in
a month.)?

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Sample Problems ADVANCED EPID/BIOS

Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
1 D
2 ---- ------ ------ ------ ------ ------ ------ ----x
3 ---- ------ ------ ------ ------ ------ ----x
4 ---- ------ ----x W
5 ---- ------ ------
6 W
7 ---x
8 ---- ------ ------ ------ ----x
9 ---- ----x
10 ---- ------ ------ ------ ------ ----x
11 D
12 ---- ------ ------ ------ ------ ----x
13 ---x
14 ---- ------ ----x
15 W
16 ---- ------
17 ---- ------ ------ ------ ------ ------ ------ ----x
18 ---- ------ ------ ------ ------ ------ ----x
19 W
20 ---- ----x
21 ---- ------ ----x
22 ----
23 ---- ------ ------ ------
24 ---- ------ ----x W

10. An research award winning team has been investigating the recently discovered SMBHTM
syndrome (Stop, my brain hurts too much syndrome). They assembled a cohort of 103 persons in
October of this year and plan to start the study in January. Assume that each new case of SMBHTMS
begins on the first of the month. Each dot represents a new case. The dashed line indicates the
duration of the illness. After cure of the illness, the person is no longer at risk. W indicates
withdrawal from the study and D represents death from other causes.

What is the preferred measure of frequency in these data?

What is the prevalence on January 5?

What is the prevalence on March 28?
What is the cumulative incidence over 1 year (January - December)?
What is the incidence rate over 1 year (January - December)?

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Sample Problems ADVANCED EPID/BIOS

PROBLEM SESSION #2 (DR VICTOR MWAPASA, WEDNESDAY 6th JUNE 2012, 9AM)

1. Suppose a case-control study reports an OR of 4.00, since we know how to convert odds to
probabilities, can you calculate the RR for this study?

2. Being an opportunistic investigator, Investigator D decides to conduct a more in-depth study of the
children who reported abuse. She identifies 400 of the 459 children as having very strong evidence of
abuse. As a control group, she randomly selects 800 children from the remaining 9541 children.

What measure of frequency will she use in this study?

What type of study is this?
What measure of association will be reported?

3. You conduct a case control study. The observed results are shown below.

OBSERVED DATA:

Disease Status
Exposure Case Control
Status
Exposed 420 684 1104
Not Exposed 578 962 1540
Total 998 1646

a. What is the observed measure of association?

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Sample Problems ADVANCED EPID/BIOS

4. Surveillance data from Blantyre indicate that 90 cases of Disease X occured over a 2 year period.
60 of the cases occurred among persons of lower socioeconomic status and 30 among persons with
higher socioeconomic status.

What additional information is needed to calculate a rate ratio?

Assume the population of Blantyre includes 150000 persons of lower socioeconomic status and
250000 of higher socioeconomic status.

What is the incidence rate for persons with higher SES? The overall IR (both groups combined)?
What is the rate ratio?

5. An investigator identified a cohort of 600 women with HIV infection. Over a 6 months of follow-up,
she observes that the infants of 56 women that breastfed their infants (n = 200) have HIV infection
and infants of 24 women who did not breastfeed (n = 400) have HIV infection. Assuming no loss to
follow-up:

What is the risk ratio?

What is the OR?

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Sample Problems ADVANCED EPID/BIOS

6. In a study of HIV infection among African women (n = 1124), the cumulative incidence over 2 years
among women with stable partners was 1.8% (19/1030). Among single women the CI over 2 years
was 11.7% (11/94).

What is the risk ratio?

What is the odds ratio?

7. Cohorts of children with parents with and without alcoholism are identified. Each group has 10000
kids. Over the course of 1 year, 100 kids with alcoholic parents suffer abuse. 15 of the kids without
alcoholic parents are abused. In each group, 20 kids are lost to follow-up. In the second year, an
additional 130 kids in the “alcoholic” group are abused and 20 kids in the non-alcoholic group. In the
second year, 60 kids in the alcoholic group are lost to follow-up and 75 kids in the non-alcoholic group
move away.

What is the 2 year incidence rate?

What is the rate ratio?

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Sample Problems ADVANCED EPID/BIOS

8. You have conducted a randomized clinical trial of a therapeutic vaccine for the prevention of
complications in HIV infection. After two years, among persons in the vaccine group, 5% have
progressed. In the no vaccine group, 25% have progressed. How would you describe the effects of
the vaccine? How many persons would need to get the vaccine to prevent 1 case from progressing?

9. Over 10 years, you conduct a study investigating the effects of exposure to pesticides used on
coffee estates to the development of gastric carcinoma. Since only a small percent of the total
population is exposed to these pesticides, you enrich your sample for exposed persons (i.e. you
select more of them than if you were to take a random sample of the population). Your exposed group
includes 1000 persons and your unexposed group includes 4000 persons. You obtain the following
results:

Exposed Unexposed
Year Cases Withdrawals Cases Withdrawals
1 2 10 1 22
2 4 15 3 30
3 10 10 10 16
4 12 12 15 24
5 15 7 16 28
6 20 10 15 32
7 10 16 12 14
8 15 10 18 14
9 8 19 16 42
10 10 15 14 16

Use what you have learned to describe the increase in disease associated with this exposure. Also,
calculate a measure to make an argument for regulation of the pesticide use.

For the preceding problem, assume that 0.5% of the population is exposed to pesticides. What
proportion of gastric cancer in the overall population is attributable to pesticides?

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Sample Problems ADVANCED EPID/BIOS

Problem Session #3 (DRS KAMIJA PHIRI & ATUPELE KAPITO, THURSDAY 7th JUNE 2012, 3PM)

1. You conduct a case control study. The observed results are shown below.

OBSERVED DATA:

Disease Status
Exposure Case Control
Status
Exposed 420 684 1104
Not Exposed 578 962 1540
Total 998 1646

a. What is the observed measure of association?

The test used to measure the exposure performs with sensitivity and specificity of 0.90 and 0.85,
respectively, among cases. The sensitivity and specificity of the exposure measurement was 0.75 and
0.95, respectively, among controls.

b. What is your best estimate of the appropriate measure of association?

Disease Status
Exposure Case Control
Status

Exposed

Not Exposed

Total 998 1646

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Sample Problems ADVANCED EPID/BIOS

2. A randomized clinical trial was conducted over 5 years. In the group receiving the new drug
(N=3304), 116 experienced the primary endpoint (outcome). In the group receiving placebo
(N=3301), 183 experienced the primary endpoint.

a. Calculate a risk ratio for the primary endpoint.

b. How many people would need to be treated to prevent the outcome in one person?

In the same clinical trial, the cumulative incidence for the new drug group was 0.022 for a secondary
endpoint (outcome) and 0.031 in the placebo group at 3 years of follow-up.

c. Determine the relative risk reduction

d. Determine the number needed to treat

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Sample Problems ADVANCED EPID/BIOS

3. You conduct a clinical trial with four groups (arms). Patients randomized to Arm 1 receive Drug A at
a dose of 10 mg/d. Patients randomized to Arm 2 receive Drug A at a dose of 5 mg/d. Patients
randomized to Arm 3 receive Drug B at a dose of 20 mg/d and patients randomized to Arm 4 receive
placebo. A simple randomization scheme (no stratification, blocking, etc.) is used and all arms have
an equal probability of being selected. The trial is performed blinded (masked).

a. What is the probability that a patient receives Drug B?

b. What is the probability that a patient receives Drug A?

c. What is the probability that a patient has received Drug A or placebo?

d. If the clinical trial enrolls 500 subjects, how many subjects are expected to receive placebo?

e. When the randomization code is broken, Subject 25 was identified to be in Arm 1. Given that
Subject 25 was in Arm 1, what is the probability that Subject 26 was in any Arm other than 1?

f. If you consider 3 consecutive patients, what is the probability that all 3 patients received Drug B?

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Sample Problems ADVANCED EPID/BIOS

4. You conduct a case-control study. At the beginning of the study, you select all of your control group
from a defined study base (base population, target population). Over time, you identify all of the cases
that occur in the base population. These cases serve as your case group.

a. What type of control sampling is this?

b. What measure of association will the odds ratio estimate?

c. Some of the controls develop the disease being studied during the course of the study. What
will you do with these controls during the analysis?

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Sample Problems ADVANCED EPID/BIOS

5. In a cohort study, you use an imperfect diagnostic test. Among persons with the exposure, the
sensitivity of the test was 0.85. Among persons without the exposure, the sensitivity of the test is
0.75. For both groups, the specificity is 0.95. Using the truth given below, estimate the risk ratio and
risk difference for a study performed over 2 years.

Truth:

Outcome
Exposure () ()
() 862 9251
() 425 15987
Total

Outcome
Exposure () ()
() 10113

() 16412

Total

OBSERVED:

b. Is this differential or non-differential misclassification?

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Sample Problems ADVANCED EPID/BIOS

6. In a case-control study, you estimate the sensitivity of the exposure measurement in cases to be
0.95 and among controls, the sensitivity of the exposure measurement is 0.85. The specificity of the
exposure measurement is 0.95 among cases and 1.00 among controls.

OBSERVED DATA:

Disease Status
Exposure Case Control
Status
Exposed 218 211
Not Exposed 232 689
Total 450 900

CORRECTED:

Disease Status
Exposure Case Control
Status

Exposed

Not Exposed

Total 450 900

a. What is the observed crude OR?

b. Given the observed data, what is the effect of the misclassification (calculate a corrected OR)?

c. Is this differential or non-differential misclassification?

d. Briefly explain how recall bias could create this effect.

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Sample Problems ADVANCED EPID/BIOS

7. Data are collected for the city A in a large North American country. These data are shown below:

Age Study Study Standard

Group Cases/yr Population Population
0 – 24 200 200000 140000000
25 – 44 875 175000 55000000
45 – 64 340 85000 45000000
³ 65 85 40000 10000000
Total 1500 500000 250000000

Using the date given above, calculate an incidence rate for the study population.

Calculate an standardized incidence rate for the study population using the standard population.

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