Sadie Conway

PH2612
Introduction to Epidemiology for Majors
Spring 2010 (Instructor: Dr. Nettleton)

Homework-3
(Epidemiologic Study Designs)

Date of assignment: 2/08/09

Date homework due: 2/15/09
Total points possible: 10 points
Instructions:

1. Write your full name on the first page and initials on the subsequent pages.
2. Strive for accuracy, brevity, clarity, and neatness in your written answers.
3. SHOW YOUR WORK. For the ‘Calculations and Interpretations’ section, show all calculations legibly on the
answer sheet (i.e., show numerator, denominator, and units). Even if you make an arithmetical mistake, you will
get partial credit for having the correct method. A correct answer based on a faulty procedure gets NO POINTS.
Please round your answers to the nearest tenth, circle your final answer (after various procedures), and include
the units of the measurement in your answers.
4. Items will be scored independently of one another. For example, one item may ask you to calculate a statistic
and another to interpret that statistic. Even though the answer to the first item may be wrong, the answer to the
second item can still be correct if the statistic - whatever its value - is interpreted correctly.
5. Turn in your homework on time.

Questions 1-2. For each of the following studies, identify (2 points each
for Question 1&2)

a) study design

b) exposure variable

c) outcome variable

d) advantage of the study design that was used (in one sentence).
 Sadie Conway

1. Between 1963 and 1966, a total of 5,356 subjects were randomized to receive
the Bacillus Calmette Guerin (BCG) vaccine or saline inoculations. They were
examined for leprosy before the vaccination and Leprosy surveillance was
continued until 1979. BCG afforded 48% protection against clinical leprosy, being
most effective against borderline tuberculoid leprosy and in children vaccinated
when under 15 years old. Protection was evident within 12 months in those
vaccinated between the ages of 10 and 15 years but was delayed in other age
groups. There was evidence for accelerated manifestations of tuberculoid leprosy
in children vaccinated when under 5 years of age. Tuberculin sensitivity was more
likely to be sustained following multiple BCG inoculations; vaccines with sustained
tuberculin sensitivity had the lowest incidence of leprosy, but protection was also
evident in tuberculin negative vaccines. These results may have implications for
ongoing trials of leprosy vaccine incorporating BCG.

a) Randomized experimental trial – parallel (vaccination vs.

placebo), preventative, individual, simple

b) Bacillus Calmette Guerin (BCG)

c) Leprosy incidence

d) The randomization of the subjects seems to have balanced the

treatment and control groups’ populations, thereby allowing
comparisons of the efficacy of different treatments on specific age
groups.
 Sadie Conway

2. In a study of 630 women taking oral contraceptives, subjects were followed for 2
years along with 945 women matched on age using methods of contraception other
than oral contraceptives. Information on the method of contraception was gathered
every 6 months using mailed a questionnaire. Development of hepatic adenoma (a
non cancerous tumor in liver) was assessed by ultrasound of the liver in all of the
women at the end of year 1 and at the end of year 2.

a) Prospective cohort – exposure based

b) Oral contraceptives

c) Hepatic adenoma incidence

d) Assuming that this study was motivated by existing evidence

suggesting an association between the development of hepatic
adenoma and the use of oral contraceptives (the exposure of
interest), the prospective cohort design allowed researchers to
collect data specific to that research hypothesis and draw a
temporally-based conclusion on whether exposure proceeded the
development of the condition.
 Sadie Conway

3. A study was designed to look at the association between the risk of bacteriuria
and use of oral contraceptives (OC). Among 2390 women aged 16-49 years who
were free from bacteriuria, 482 were OC users at the initial survey in 1973; 1,908
were not OC users. At a second survey in 1976, 27 of the OC users had developed
bacteriuria, as had 77 of the non OC users. (1.5 points total)

a) Construct a 2x2 table (0.25 points)

1976 Bacteriuria – Bacteriuria – Totals

has (+) does not have

(-)

Oral 27 455 482

contraception –

uses

Oral 77 1831 1908

contraception –

does not use

Totals 104 2286 2390

b) Identify the following for the above study (0.25 points for each below)

i) Exposure of interest: Oral contraceptives

ii) Outcome of interest: Bacteriuria incidence

iii) Study design: Prospective cohort – exposure based

iv) Measure of association: Relative risk

v) Calculate the measure of association and interpret it (use the blank

side the page for calculations if space is not enough):

The relative risk of developing bacteriuria for women who used

oral contraceptives compared to women who did not use oral
 Sadie Conway

contraceptive was 1.4. Because the relative risk was greater

than 1, women who used oral contraceptives had a 40% higher
incidence rate of bacteriuria than women who did not use oral
contraceptives.

(calculations on attached sheet)

 Sadie Conway

4. An international, multicenter, double-blind, randomized trial was carried out to

determine if the use of folic acid prior to pregnancy reduced neural tube defect
(NTD) recurrence risk. The study population included 1,195 women who had
previously had an NTD-affected pregnancy. The women were randomly allocated to
one of 4 groups: (1.5 points)

a) Folic Acid only – Group A

b) Other vitamins – Group D

c) Both folic acid and vitamins – Group B

d) Neither folic acid and vitamins – Group C

This table shows the results of the study:

Group Folic Acid Other Vitamins NTD

cases/pregnancies

A + - 2/298

B + + 4/295

C - - 13/300

D - + 8/302

a) Calculate the cumulative incidence of NTD in the patients who received

folic acid and those who did not receive folic acid. (0.50 points)
cumulative incidence, folic acid recipients: 10.1 per 1,000 women
receiving folic acid

cumulative incidence, no folic acid: 34.9 per 1,000 women not

receiving folic acid

(calculations on attached sheet)

b) What is the measure of association used for this study? (0.25 points)
Relative risk

c) Calculate the measure of association for patients who received folic acid.
(0.25 points)

The relative risk of a recurrent neural tube defect in pregnant

women receiving folic acid compared to pregnant women who did
not receive folic acid was 0.3.
 Sadie Conway

(calculation on attached sheet)

d) Interpret the measure of association you calculated above in one

sentence. (0.5 points)

Because the relative risk was less than 1, pregnant women

receiving folic acid had a 71% lower incidence of recurrent neural
tube defects than women who did not take folic acid during
pregnancy.
 Sadie Conway

5. Please read the original research article referenced below:

Jenkins DJ, Kendall CW, McKeown-Eyssen G, Josse RG, Silverberg J, et al. Effect of a
low-glycemic index or a high-cereal fiber diet on type 2 diabetes: A randomized
trial. JAMA. 2008; 300(23):2742-2753. [posted on the course website]

Based on this article, please answer the following questions: (3 points total; 0.5
pts each)

a. State the study design, main exposure, and primary outcome.

The study was a randomized, parallel study design. The exposure of

interest was the effect of a low-glycemic index diet on patients with
type 2 diabetes being controlled by antihyperglycemic medications.
(Additionally, the population of comparison also had a dietary
intervention in the form of high-cereal fiber dietary advice.) The
primary outcome measure was the absolute change in glycated
hemoglobin A1c (HbA1c).

b. How were the subjects allocated to study groups? What are the
advantages of this method of subject allocation? Was this subject allocation
method successful in this study? Explain your answer.

Following recruitment efforts and eligibility screenings, subjects

were stratified by sex and HbA1c levels. Subjects were then
randomly assigned to one of two groups: (1) a group advised to
follow a high-cereal fiber diet or (2) a group advised to follow a low-
glycemic index diet. Randomly assigning each subject to a study
group eliminated the self-selection of dietary practices by the
subjects. In addition, randomization following stratification
distributed potential confounders (in this case, sex and HbA1c levels)
evenly between the two groups, thereby eliminating them as
confounders. This subject allocation method was successful because
the results of the study revealed the independent effect of glycemic
index on HbA1c. Further, this study design allowed for a comparison
of two dietary regimens rather than a single dietary change group
compared to a control group that underwent no dietary change.
 Sadie Conway

c. What measure of association was used in this study? Was there a

significant difference in glycemic control between the intervention groups?
Was this result significant?

Attributable risk difference was the primary measure of association

used in this study. (This was measured by determining the relative
changes in the absolute values of the average HbA1c levels of the
low-glycemic index and high-cereal fiber diet groups over the six-
month period of the study, after which the difference between the
two groups’ changes was calculated.) In the data analysis, average
HbA1c decreased by 0.50% on the low-glycemic index diet compared
to a decrease of 0.18% on the high-cereal fiber diet. As a result,
there was a 0.33% HbA1c treatment difference, which was significant
(P≤ .002) even after controlling for other factors; the authors
characterized the difference as “modest,” but one that “has clinical
relevance” (pg. 2750).

d. The authors acknowledge that one potential limitation to the study was
that it was conducted at one site (in Canada). Why might these results not be
generalizable to a broader population?

Physiological, cultural, and behavioral characteristics all play a role

in the generalizability of a study to a broader population. Because
the study was conducted at a single site, it is possible that certain
rick factors may be unique to this location. In addition, this study’s
original eligibility criteria restricted the reference population
according to disease status (type 2 diabetes positive) and
medication use (taking antihyperglycemic medications), which
potentially limits the generalizability to that of the reference
population rather than a broader, more general population. Further,
the individuals who chose to participate in this study – in which they
were expected to alter their eating habits in order to adhere to
guidelines being provided by the researchers – may not be broadly
characteristic of the reference population or the general population.

e. What was the conclusion of this study (in terms of primary outcome)?

The researchers concluded that patients with type 2 diabetes who

consumed a low-glycemic index diet for six months had moderately
lower HbA1c levels compared to type 2 diabetes patients who
consumed a high-cereal fiber diet.
 Sadie Conway

f. Further analyses indicate that nearly half of the group who received a high-
cereal fiber diet poorly adhered to the diet and instead consumed large
amounts of “junk food” (candy, sodas, etc). The group who received the low-
glycemic index diet did not have the same “junk food” problem and adhered
well to the intervention diet. Generally speaking, how might this new
“evidence” change your interpretation of the results? Explain your answer.

If further analyses revealed that dietary adherence had been an

issue for the high-cereal fiber group, it would cast doubt on whether
the low-glycemic index nature of the diet was the most significant
factor in the reduction of patients’ HbA1c levels. Instead, issues such
as the more nutritious nature of the low-glycemic index diet (when
compared with a diet high in “junk food”) would become possible
explanations for the greater decrease in HbA1c levels that were
measured in that group. The lack of dietary adherence for the high-
cereal fiber group would become a confounder in this study.