Identifying the Study Design

1
Identifying the Study Design
When reading a paper, it isnt always clear what
the study design is. Sometimes there is a
combination of strategies. However, you should
think about what the predominant design features
are.

• Provides a framework for thinking about the
  study.
• Alerts you to weaknesses in some study designs.

2
Identifying the Study Design
Is it based on information about individuals?
Or averages in populations?
Correlational (Ecologic)
3
Identifying the Study Design
8 people with bird flu
Is there just one group? Did all subjects have
the disease? (Case Series)
X
X
X
X
X
X
X
X
X
Did they evaluate presence of disease and risk
factors at the same point in time?
(Cross-sectional Survey)
Do you have heart disease? Are you active?
4
Identifying the Study Design

• Two or more groups being compared?
• How were they selected? Did they find people with
  disease cases and then find a comparison group
  without disease controls? (Case-Control)
• Identify non-diseased people group them by risk
  factor status? Then follow them longitudinally to
  compare incidence? (Cohort Study)

X
X
X
X
X
X
X
X
Compare past exposures
X
X
X
X
Compare incidence over time
5
In prospective cohort studies conception, design,
enrollment occur before anyone develops the
outcome.
Enroll non-diseased subjects collect baseline
exposure data
Prospective
Follow up at intervals to get accurate outcome
data.
Obese
Lean
Retrospective
Identify a cohort retrospectively (e.g. tire
manufacturing workers vs. desk employees. Look at
what subsequently happened to them.
Exposed
Not Exposed
6
Identifying the Study Design
Did the investigators assign subjects to a
treatment or intervention and follow them to
compare outcomes? (Clinical Trial)
Aspirin
X
Compare incidence over time
X
X
Placebo
X
7
What kind of study was this?
Oral Contraceptives Liver Cancer. Previous
case reports of liver cancers in women on OCs.
The authors contacted all cancer registries
collected information on all females with liver
tumors.

1. Case series
2. Case-control study
3. Retrospective cohort
4. Prospective cohort
5. Randomized clinical trial

8
What kind of study is this?
State Annual per capita Tobacco Sales Lung Cancer Mortality Rate in 1965/100,000 pop.
Alabama 600 92
Florida 450 75
Georgia 500 80
North Carolina 550 66
Virginia 400 45
Alaska 200 35
Massachusetts 150 33
New York 175 20
New Jersey 200 23
Rhode Island 250 22

1. Case series
2. Case-control
3. Retrospective cohort
4. Cross-sectional survey
5. Correlational (ecologic)

9
1830 Villerme notes that mortality varies among
districts in Paris. He tried to correlate
mortality with the distance of the arrondissement
from the Seine River, the relationship of the
streets to the prevailing winds, the
arrondissement's source of water and local
climatological factors such as soil type,
exposure to the sun, elevation and inclination of
the arrondissement.
10
Villerme found that mortality correlated closely
with the degree of poverty in the arrondissement
(estimated as the of people exempted from tax).
The findings did not spark action.
poorest
wealthiest
11
What kind of study was this?
Villerme found that mortality correlated closely
with the degree of poverty in the arrondissement
(estimated as the of people exempted from tax).
The findings did not spark action.
poorest
wealthiest

1. Case series
2. Case-control
3. Retrospective cohort
4. Cross-sectional survey
5. Correlational (ecologic)

12
Median Household Income Premature Deaths /100,000
Lynn 38000 470
Lowell 40000 466
Springfield 30000 459
Newton 89000 218
Brookline 68000 233
Barnstable 47000 275
13
What kind of study was this?
Investigators in Bergen, Norway sent
questionnaires about respiratory health,
allergies, smoking habits, and occupational
respiratory exposures to a random sample of
residents between the ages of 15-70. After two
reminders, 2,819 responses were obtained. Of
these, 1,646 reported exposure to tobacco smoke
from other members of their immediate family.

1. Case series
2. Case-control
3. Retrospective cohort
4. Cross-sectional survey
5. Correlational (ecologic)

14
What kind of study was this?
A study in N. Engl. J. Med. examined whether
eating a Mediterranean diet had any association
with mortality in Greek adults. A baseline
questionnaire was used to determine how closely
the subjects followed a traditional Mediterranean
diet, and the group was followed for 2 years,
during which they determined the cause of death
among all subjects who died.
Mediterranean Diet Score Deaths in 2 yrs Alive Total
High (close adherence) 44 2586 2,630
Medium 61 3747 3,808
Low (poor adherence) 74 2383 2,457

1. Case-control
2. Retrospective cohort
3. Prospective cohort
4. Randomized clinical trial

15
What kind of study?
Bacteremia, Fever, and Splenomegaly Caused by a
Newly Recognized Bartonella Species. Eremeeva, et
al. N Engl J Med 20073562381-7. A 43-year-old
American woman developed a fever after traveling
in Peru for 3 weeks. She visited Lima and Nazca
and then traveled to the Sacred Valley of
Urubamba, followed by Cuzco and Machu Picchu,
where she hiked. She received numerous insect
bites. Sixteen days after returning to the US she
developed fever, insomnia, muscle aches, nausea,
headache, and mild cough. At the hospital she was
found to have anemia and an enlarged spleen
(splenomegaly). Laboratory tests determined that
her blood was infected with a genus of bacterium
called Bartonella.

1. Case report
2. Case series
3. Case-control
4. Retrospective cohort
5. Clinical trial
6. Ecologic

16
Study type?
In 2003 a mass immunization against cholera was
conducted in Beira, Mozambique. The following
year there was an outbreak of El Tor Ogawa
cholera in Beira. To assess the usefulness of the
vaccine investigators compared the frequency of
vaccination between persons with
culture-confirmed cholera severe enough to have
prompted them to seek treatment and age- and
sex-matched neighborhood controls who did not
have diarrhea.

1. Case series
2. Cross-sectional
3. Case-control study
4. Retrospective cohort
5. Prospective cohort
6. Clinical trial

17
What kind of study?
Risk of kidney failure associated with the use of
acetaminophen, aspirin, and nonsteroidal
antiinflammatory drugs. Perneger TV, et al.
People who take analgesic drugs frequently may be
at increased risk of chronic kidney failure.
These authors used a kidney dialysis registry to
find 716 patients with kidney failure they
randomly selected 361 subjects without kidney
disease from the same geographic area. They used
phone interviews to estimate their cumulative
past use of analgesics and compared the two
groups.

1. Case series
2. Case-control
3. Retrospective cohort
4. Prospective cohort
5. Clinical trial

18
Type of study?
Adiposity as Compared with Physical Activity in
Predicting Mortality among Women. Hu et al. N
Engl J Med 20043512694-703. In 1976 the Nurses
Health Study enrolled 121,700 female RNs who
completed a mailed questionnaire regarding their
medical history lifestyle. The women have
returned follow up information every two years.
This study grouped them by exercise level BMI
and compared mortality rates among different
levels of these two risk factors.

1. Cases series
2. Case-control
3. Retrospective cohort
4. Prospective cohort
5. Clinical trial

19
Glucosamine, Chondroitin Sulfate, and the Two in
Combination for Painful Knee Osteoarthritis.
Clegg, et al. N Engl J Med 2006354795-808. Gluc
osamine and chondroitin sulfate are orally
administered substances that have been used for
years to treat joint problems in horses. Since
they are relatively non-toxic there has been
increasing interest in them for treating
osteoarthritis, but there is controversy about
their efficacy. These investigators randomly
assigned 1583 patients with symptomatic knee
osteoarthritis to receive 1500 mg of glucosamine
daily, 1200 mg of chondroitin sulfate daily, both
glucosamine and chondroitin sulfate, 200 mg of
celecoxib daily, or placebo for 24 weeks. The
primary outcome measure was a 20 percent decrease
in knee pain from baseline to week 24. The
primary outcome measure was whether the patient
achieved a 20 percent decrease in pain as
measured by the WOMAC pain subscale, a
standardized, previously validity tool for
assessing joint pain.
What kind of study is this?
20
Type of study?
These investigators randomly assigned 1583
patients with symptomatic knee osteoarthritis to
receive 1500 mg of glucosamine daily, 1200 mg of
chondroitin sulfate daily, both glucosamine and
chondroitin sulfate, 200 mg of celecoxib daily,
or placebo for 24 weeks. They compared the groups
with respect to decrease in knee pain from
baseline to week 24 using the WOMAC pain
subscale, a standardized, previously validity
tool for assessing joint pain.

1. Case series
2. Case-control
3. Retrospective cohort
4. Prospective cohort
5. Clinical trial

21
The frequency of new cases of tuberculosis in
Boston during a given calendar year is

1. Prevalence
2. Cumulative incidence
3. Incidence rate
4. None of the above

22
The of deceased males who are found to have
prostate cancer at autopsy?

1. Prevalence
2. Cumulative incidence
3. Incidence rate
4. None of the above

23
The of people who have malaria that is
resistant to treatment with chloroquine?

1. Prevalence
2. Cumulative incidence
3. Incidence rate
4. None of the above

24
The number of newly diagnosed brain tumors in a
calendar year per 100,000 Massachusetts children?

1. Prevalence
2. Cumulative incidence
3. Incidence rate
4. None of the above

25
The number of previously healthy women who had a
stroke during 40,000 person-years of follow up?

1. Prevalence
2. Cumulative incidence
3. Incidence rate
4. None of the above

26
In General

• Express prevalence and cumulative incidence as
  or per 1,000 or 10,000, etc.
• Express incidence rate as per 1,000 person-yrs
  or 10,000 person-years, etc.
• Remember to state the time period of observation
  for cumulative incidence.

However, for the exercises that follow and for
post class quiz 2, you will need to answer with
the specific numerator and denominator for some
questions, to make sure that you are including
and excluding the right subjects.
27
Study population of 1,000. Dashed line disease
present (Lung Cancer) Patients 1, 2, 3, 4) had
the disease before the study began. During the
year of the study, 6 new cases occur (start of
dashed lines). Among the total of 10 cases,
there were 6 deaths during the year The 990
other individuals in the study did not become ill
or die.
1994

1995 Jan Feb
Mar Apr May Jun Jul Aug
Sep Oct Nov Dec Jan 1lt------------
--------------------------------------------------
-------------------------------------------Alive 2
lt---------------------------------------Dead 3lt---
--------------------------------------------------
---------Dead 4lt-----Dead 5
--------------------------------------------------
--------------------------------------------------
-Alive 6 ----------------------------
Dead 7
--------------------------------------------------
-----------------------Alive 8
------------Dead 9

--------------------------------------------------
----------Alive 10

---------------------------------------Dead
X
X
X
X
X
X
Prevalence of disease on Jan. 1, 1994? July
1, 1994? Dec. 31, 1994?
28
Prevalence on Jan. 1, 1994?
1994

1995 Jan Feb
Mar Apr May Jun Jul Aug
Sep Oct Nov Dec Jan 1lt------------
--------------------------------------------------
-------------------------------------------Alive 2
lt---------------------------------------Dead 3lt---
--------------------------------------------------
---------Dead 4lt-----Dead 5
--------------------------------------------------
--------------------------------------------------
-Alive 6 ----------------------------
Dead 7
--------------------------------------------------
-----------------------Alive 8
------------Dead 9

--------------------------------------------------
----------Alive 10

---------------------------------------Dead

1. 0/1000
2. 4/1000
3. 6/1000
4. 4/996
5. 5/996
6. 6/996

29
Prevalence on July 1, 1994?
1994

1995 Jan Feb
Mar Apr May Jun Jul Aug
Sep Oct Nov Dec Jan 1lt------------
--------------------------------------------------
-------------------------------------------Alive 2
lt---------------------------------------Dead 3lt---
--------------------------------------------------
---------Dead 4lt-----Dead 5
--------------------------------------------------
--------------------------------------------------
-Alive 6 ----------------------------
Dead 7
--------------------------------------------------
-----------------------Alive 8
------------Dead 9

--------------------------------------------------
----------Alive 10

---------------------------------------Dead

1. 4/997
2. 4/1000
3. 6/1000
4. 4/996
5. 5/996
6. 5/997

30
Prevalence on Dec. 31, 1994?
1994

1995 Jan Feb
Mar Apr May Jun Jul Aug
Sep Oct Nov Dec Jan 1lt------------
--------------------------------------------------
-------------------------------------------Alive 2
lt---------------------------------------Dead 3lt---
--------------------------------------------------
---------Dead 4lt-----Dead 5
--------------------------------------------------
--------------------------------------------------
-Alive 6 ----------------------------
Dead 7
--------------------------------------------------
-----------------------Alive 8
------------Dead 9

--------------------------------------------------
----------Alive 10

---------------------------------------Dead

1. 4/1000
2. 4/996
3. 4/994
4. 6/1000
5. 6/996
6. 6/994

31
Study population of 1,000. Dashed line disease
present (Lung Cancer) Patients 1, 2, 3, 4) had
the disease before the study began. During the
year of the study, 6 new cases occur (start of
dashed lines). Among the total of 10 cases,
there were 6 deaths during the year The 990
other individuals in the study did not become ill
or die.
1994

1995 Jan Feb
Mar Apr May Jun Jul Aug
Sep Oct Nov Dec Jan 1lt------------
--------------------------------------------------
-------------------------------------------Alive 2
lt---------------------------------------Dead 3lt---
--------------------------------------------------
---------Dead 4lt-----Dead 5
--------------------------------------------------
--------------------------------------------------
-Alive 6 ----------------------------
Dead 7
--------------------------------------------------
-----------------------Alive 8
------------Dead 9

--------------------------------------------------
----------Alive 10

---------------------------------------Dead
X
X
X
X
X
X
What was the cumulative incidence during 1994?
32
Cumulative incidence in 1994?
1994

1995 Jan Feb
Mar Apr May Jun Jul Aug
Sep Oct Nov Dec Jan 1lt------------
--------------------------------------------------
-------------------------------------------Alive 2
lt---------------------------------------Dead 3lt---
--------------------------------------------------
---------Dead 4lt-----Dead 5
--------------------------------------------------
--------------------------------------------------
-Alive 6 ----------------------------
Dead 7
--------------------------------------------------
-----------------------Alive 8
------------Dead 9

--------------------------------------------------
----------Alive 10

---------------------------------------Dead

1. 4/1000
2. 6/1000
3. 10/1000
4. 4/996
5. 6/996
6. 10/996

33
Study population of 1,000. Dashed line disease
present (Lung Cancer) Patients 1, 2, 3, 4) had
the disease before the study began. During the
year of the study, 6 new cases occur (start of
dashed lines). Among the total of 10 cases,
there were 6 deaths during the year The 990
other individuals in the study did not become ill
or die.
1994

1995 Jan Feb
Mar Apr May Jun Jul Aug
Sep Oct Nov Dec Jan 1lt------------
--------------------------------------------------
-------------------------------------------Alive 2
lt---------------------------------------Dead 3lt---
--------------------------------------------------
---------Dead 4lt-----Dead 5
--------------------------------------------------
--------------------------------------------------
-Alive 6 ----------------------------
Dead 7
--------------------------------------------------
-----------------------Alive 8
------------Dead 9

--------------------------------------------------
----------Alive 10

---------------------------------------Dead
X
X
X
X
X
X
What was the population mortality rate during
1994? (Use population at beginning of year for
calculation)
34
Population mortality rate in 1994?
1994

1995 Jan Feb
Mar Apr May Jun Jul Aug
Sep Oct Nov Dec Jan 1lt------------
--------------------------------------------------
-------------------------------------------Alive 2
lt---------------------------------------Dead 3lt---
--------------------------------------------------
---------Dead 4lt-----Dead 5
--------------------------------------------------
--------------------------------------------------
-Alive 6 ----------------------------
Dead 7
--------------------------------------------------
-----------------------Alive 8
------------Dead 9

--------------------------------------------------
----------Alive 10

---------------------------------------Dead

1. 4/10 or 40
2. 6/10 or 60
3. 4/1000 or 0.4
4. 6/1000 or 0.6
5. 6/996
6. 10/1000

35
Study population of 1,000. Dashed line disease
present (Lung Cancer) Patients 1, 2, 3, 4) had
the disease before the study began. During the
year of the study, 6 new cases occur (start of
dashed lines). Among the total of 10 cases,
there were 6 deaths during the year The 990
other individuals in the study did not become ill
or die.
1994

1995 Jan Feb
Mar Apr May Jun Jul Aug
Sep Oct Nov Dec Jan 1lt------------
--------------------------------------------------
-------------------------------------------Alive 2
lt---------------------------------------Dead 3lt---
--------------------------------------------------
---------Dead 4lt-----Dead 5
--------------------------------------------------
--------------------------------------------------
-Alive 6 ----------------------------
Dead 7
--------------------------------------------------
-----------------------Alive 8
------------Dead 9

--------------------------------------------------
----------Alive 10

---------------------------------------Dead
X
X
X
X
X
X
What was the case-fatality rate during 1994?
36
Case fatality rate?
1994

1995 Jan Feb
Mar Apr May Jun Jul Aug
Sep Oct Nov Dec Jan 1lt------------
--------------------------------------------------
-------------------------------------------Alive 2
lt---------------------------------------Dead 3lt---
--------------------------------------------------
---------Dead 4lt-----Dead 5
--------------------------------------------------
--------------------------------------------------
-Alive 6 ----------------------------
Dead 7
--------------------------------------------------
-----------------------Alive 8
------------Dead 9

--------------------------------------------------
----------Alive 10

---------------------------------------Dead

1. 6/10 or 60
2. 6/1000 or 6
3. 6/996
4. 4/996
5. 4/10

37
A new disease occurs with constant IR 3/1000
person-yr. Estimate the cumulative incidence over
5 years.

1. 0.03 over 5 yrs.
2. 0.010 over 5 yrs.
3. 0.015 over 5 yrs.
4. 0.030 over 5 yrs.

38
You should be able to calculate these measures of
disease frequency and measures of association
using a simple hand calculator. Epi_Tools.XLS
will also do them, but you need to be able to do
them without Epi_Tools for the exams.
39
What does one measure and compare in a
case-control study?

1. Cumulative incidence
2. Incidence rate
3. Risk of disease
4. Frequency of past exposures
5. Risk difference

40
In a cohort study one may measure the degree of
association between an exposure and an outcome by
calculating either a relative risk or an odds
ratio?

1. True
2. False
3. Im not sure

41
In a case-control study one may measure the
degree of association between an exposure and an
outcome by calculating either a relative risk or
an odds ratio.

1. True
2. False
3. I dont know.

42
When is an odds ratio a legitimate estimate of
relative risk?

1. Whenever one is conducting a case-control study.
2. When the exposure is relatively uncommon.
3. When the outcome is relatively uncommon.
4. When the sample size is large.