Cohort Study

John M. Last's Dictionary of Epidemiology defines a cohort as "any designated group of

individuals who are followed or traced over a period of time" (A Dictionary of
Epidemiology, ed. by J.M.Last, 4th ed., 2001). As a leading type among observational study
designs, it most closely resembles the gold standard among epidemiological study designs,
randomized controlled trials. To fully appreciate its advantages and limitations, we suggest
you start with studying the learning objectives for this exercise outlined in Step 1 and then
go through the successive 7 steps, taking advantage of interactive and media-based features.
The background information for this case study is given in Step 2: Student Role.

Multiple-choice questions in Step 3: Study Design and Step 4: Data Collection require
you to demonstrate your knowledge of epidemiological terminology and concepts. In Step
5: Data Analysis you will perform calculations of the measures of effect and explain your
findings. Select what you think is the best answer for each question. At the same time, read
carefully through the explanations of both correct and incorrect answers.

After data analysis proceed to the discussion questions in Step 6: Discussion Questions
found at the end of the exercise. Bring your answers to your seminar section and be
prepared to discuss them in class. Finally, in Step 7: Quiz you are asked to answer multiple-
choice questions, the answers to which will be submitted via the Internet to your seminar
leader. The deadline for submitting your answers is 9 am on Wednesday. They will be
graded pass/fail. These questions are designed to assess your knowledge of the topic. Your
responses will be used by your seminar leaders to tailor their teaching plans to address any
misconceptions or problems you might have.

Good luck and have fun!

Step 1: Learning Objectives

A. Learn to apply the main features of cohort studies to design a new study:
1. Formulate research hypotheses
2. Define population at risk for disease
3. Define eligibility criteria for study participants
4. Define exposure
Induction time
Characterization of exposure
Selection of exposed and unexposed populations
5. Define outcome
 Timing of outcome classification
Ascertainment of outcome
6. Types of cohort studies based on the timing of events
Prospective
Retrospective
Ambidirectional
B. Employ steps in data analysis of cohort studies to analyze the data:
1. Administrative procedures before start of the study
2. Calculate relative risk based on simple counts
Interpret your estimate
3. Calculate relative rate from person-year information
Interpret your estimate
4. Calculate relative risk in exposure subgroups
Interpret your estimate
5. Calculate standardized incidence ratio
Interpret your estimate
C. Explain your findings and discuss problems in data analysis:
1. Reconcile the differences between relative risk and relative rate estimates
2. Give your suggestions for carrying out this retrospective cohort study
3. Analyze results of exposure subgroup analysis and suggest how they
influence our certainty about the results of the study
4. Discuss the value of age standardization
5. Compare the values of crude and age-adjusted relative rates with
standardized incidence ratio and explain the difference
6. Design a prospective cohort study which would investigate the relationship
between exposure and outcome
7. Discuss the value of statistical data analysis for conclusions about causality of
the exposure-outcome relationship
Step 2: Student Role - Your Plan of Action
Susser Syndrome, a rare and debilitating neurological disease, is striking the people
of Epiville!
Your internship at the Epiville Department of Health is progressing well, albeit uneventful.
After the initial investigative work connected with the outbreak of SARS in Epiville, youve
been mostly assigned to desk work and are now looking forward to getting some real world
Epi experience. Your supervisor, head of the Epiville Department of Health Dr. Morissa
Zapp, has been called in to investigate the possible causes of the sudden increase in Susser
Syndrome cases. She calls you into her office and asks to do some preliminary investigative
work and report back to her with the results. Her goal is to design and conduct a cohort
study looking at the possible causes of Susser Syndrome. Armed with your trusty Epi
textbooks and your love of epidemiology, you decide upon a plan of action. But first, you
turn to do a little investigative work on the net, after all, this is the age of new media
technologies!

Your first clues come from the recent newsreports about the outbreak. Listen to the WEPI1
newscast which provides some background information to your investigation (text of the
newscast is also available). WEPI1 video and text.

Based on your own research and the newscast, you decide to investigate Glop Industries.
The Epivilles Chamber of Commerce website provides you with the following information:
Information about Susser Sydrome from the Epiville Department of Health
Webpage
Information about Glop Industries which produces the suspected causal
agent SUPERCLEAN

Sitting in the office cubicle finally gets to you and you decide to get out into the real world
and do some investigative work of you own. Your first stop is at the Glop Industries,
located in the Epiville Industrial Park. Upon entering you flash the powerful Epiville
Department of Health Identification Card (being sure to cover the word "intern" with your
thumb), and ask to speak with the plant manager. You are immediately greeted by Ms.
Dolores Doll who is very responsive to your questions. Ms. Dolls video and text.

Step 3: Study Design

You proved yourself well and Dr. Zapp trusts you with developing an analytical plan of the
cohort study of Susser Syndrome among Glop Industry employees. As a first step, you want
to generate a solid hypothesis to guide the investigation. You second trip out of the office is
to the local hospital to inquire about the individuals with this illness. On initial review of the
cases, it does appear that a number of affected individuals did in fact work at the Glop
Industries manufacturing plant. However, other individuals, not associated with the factory,
are affected as well, albeit in smaller numbers. Since exposures occurred in the past, you
decide to design a retrospective cohort study.

1. Based on the facts as presented, especially the broad timing of the events,
which do you think is the best hypothesis to investigate in this retrospective cohort
study?
a. Those who develop Susser
Syndrome are at a higher risk of
having been involved in the
production of SUPERCLEAN than
those who did not develop Susser
Syndrome.

Incorrect
When conducting a cohort study, we
are interested in comparing outcomes
between exposed and non-exposed
groups and, thus, interested in
estimating the rate of disease
development. This proposed
hypothesis implies the comparison of
exposure states between the diseased
and non-diseased groups and would be
more appropriate for a case-control
study design.

b. Those who are exposed to

chemicals involved in the
production of SUPERCLEAN (via
direct exposure at the factory)
have a higher rate of developing
Susser Syndrome than those who
are not exposed.

Correct
When generating a hypothesis, we
need to be specific without being so
stringent as to limit study participation.
Here, we specify the exposure of
Interest, define exposure groups and indicate
that we wish to
estimate a rate of disease
development in the exposed and
unexposed.

c. Residents of Epiville have a higher rate of developing Susser Syndrome than the
residents of the neighboring community.

Incorrect
This hypothesis is too general and too
broad in scope. Findings of a study
based on this hypothesis would do little
to elucidate the cause of the current outbreak of Susser
Syndrome.

To simplify the study design (after all, you have just begun conducting epidemiological
studies!), you decide to enroll a cohort in which all study participants enter into the study
at the same time (September 1st, 2002). No individuals will be allowed to enter after the
start of the study. Obviously, some study participants will be followed for less than 2
years.

2. Based on the information about possible involvement of SUPERCLEAN in the

outbreak of Susser Syndrome, what would be the best way to define exposure?
a. provide all workers at the Glop Industries factory with individual air quality dosimeters
and compile their daily readings
Incorrect
While this is a wonderful attempt at careful measurement of exposures, it comes a little bit
too late in the game. We are interested in exposures which have occurred in the past to see
their effect on the development of Susser Syndrome.
b. ask workers about their professional activities at the factory and estimate their exposures
from these work histories
Incorrect
Since we have decided to conduct a cohort study, we need to have information about work-
related exposures to SUPERCLEAN which was recorded prior to the start of the follow-up
period. We said that our study starts on September 2002. Thus, interviewing workers in
September of 2004, at the end of the study, is not appropriate and may lead to erroneous
results, primarily due to the fact that those who developed a disease would be more inclined
to overreport their exposures.
c. look for sources of information at the factory which record individual worker exposures
throughout their employment
Correct
In retrospective studies all relevant events (both the exposures and the outcomes of interest)
have already occurred when the study is initiated. They depend on the routine availability of
relevant exposure data in adequate detail from pre-existing records. It is reasonable to
assume that the factory will keep track of exposures to harmful chemicals such as
SUPERCLEAN and would be interested in sharing this information with the investigators.

Your supervisor assembles a team to begin the investigation. After a little groundwork, you
find that the employee health clinic at Glop Industries keeps records of comprehensive
annual medical examinations of all employees beginning with their hiring date. You also
learn that the factory's human resources department has records of each worker's
employment history, which you can use as a source of information about exposure to
chemicals involved in the SUPERCLEAN production. Among the 40 job positions at the
factory, only 5 positions work directly with the production of SUPERCLEAN and can be
considered potentially "exposed." You are presented with the job descriptions and Glop
Industries factory air monitoring records.
 Job Category Maximum allowable level of exposure to Number of
SUPERCLEAN workersa
A 120-150 ppmb 800

B 150-175 ppm 200

C 175-200 ppm 500

D 200-225 ppm 150

E >=225 ppm 250

a
exposure to SUPERCLEAN for at least 6 months, started working at Glop Industries on
or before September 2002
b
ppm, parts per million
Additionally, after talking with some environmental experts and epidemiologists, you believe
that an individual needs to have been exposed for a minimum of 6 months before a
sufficient dose of the harmful chemical accumulates and any physiological changes can take
place leading to the possible development of Susser Syndrome. Your Epi books call this
period the induction time.

Intellectually curious? Learn more about induction time here.

Induction time is the time between exposure and disease development during which a
number of causes have to occur to result in the disease. Thus, Susser Syndrome cannot
occur until a susceptible individual is exposed to enough chemical which triggers the casual
sequence of events leading to the development of the disease. This process may take months
or even years. Individual susceptibility varies based on specific biological/ physiological
factors.
This accumulation of harmful factors takes time which is called induction period. Any
occurrence of disease within this induction period cannot be attributed to that particular
exposure. Often, the induction period in an individual is unknown and we are forced to
make educated guesses. In our case, the exact process leading to Susser Syndrome is poorly
understood.

Based on expert opinion, you are assuming a minimal induction period of 6 months.
Exposure to SUPERCLEAN production chemicals of less than 6 months will not lead to
Susser Syndrome.
Following some deliberations with your colleagues about definitions of exposed and
unexposed groups (collaborative work is never easy!), you decide to define the exposed and
unexposed groups as follows:
Exposed
 Light exposure (working in job categories A or B for at least 6 months).
Medium exposure (working in job categories C or D for at least 6 months).
High exposure (working in job category E for at least 6 months).
Unexposed
not working in one of the 5 positions directly involved in SUPERCLEAN
production.
having worked less than 6 months in one of these 5 positions during the two-year
follow-up period.
You now have the basic framework of your retrospective cohort study. You have redefined
your hypothesis to incorporate your assumptions about the induction period and you have
clearly defined your exposure variable and the underlying population to be sampled. You are
obviously excited to get out there and begin collecting data but you have not yet finished
designing the study. You must first determine who is eligible for the study.

3. How would you define eligibility criteria for study participants? [Aschengrau]
a. everyone working at the factory is eligible
Incorrect
These eligibility criteria will include
workers who have been on the job for
less than 6 months; also, remember that we
decided to enroll only those who already
worked at the factory as of September
1st, 2002.

b. only those who have worked at

the factory for at least two years
AND who were shown to be
healthy at their initial or annual
health check-ups (mandatory for
all employees of the factory) as
indicated by employee medical
records
Correct
We only want to capture incident cases
- those who develop the disease for the
first time after the exposure starts and
the study begins. It is important to
include only new cases of disease and
not pre- existing, prevalent cases, as it
may lead to spurious findings. We also
want to enroll only those who already
worked at the factory as of September
1st, 2002)
c. exclude workers who in the last
three months exhibited
symptoms of the disease

Incorrect
We need to exclude people who were
sick at the start of follow-up, not those
who became sick during the follow-up
period.

4. On what would you base your definition of Susser Syndrome? [Aschengrau]

a. the neurological symptoms alone

Incorrect
Per information from the Epiville Department of Health, Susser Syndrome clinical findings
are not very specific. As a result, it has a broad spectrum of disorders with which it needs to
be differentiated.
Consequently, based on the neurological symptoms alone, some individuals who do not
actually suffer from the disorder may be
incorrectly classified as having Susser Syndrome These cases would be false
positives [Aschengrau, pg. ?] Alternatively,
not all Susser Syndrome cases will
present with the full panoply of
neurological symptoms. Thus, a number
of true cases may be missed. These
cases would be false negatives. [Aschengrau,
pg. 65]

b. the self-diagnosis of the

participants

Incorrect
Not only cannot Susser Syndrome be
self-diagnosed, but the accuracy of self-diagnosis
in general is suspect
and can lead to either over- or underestimate of associated risks.

c. combination of
neurological symptoms
and laboratory tests

Correct
This the most accurate and economical
diagnosis. Thus, only those symptomatic
individuals with appropriate blood test
findings should be considered as
suffering from Susser Syndrome. These cases would be called definite confirmed cases.
Step 4: Data Collection
Now that you have defined the appropriate variables and determined the information you
want to collect, you are ready to determine exactly how you are going to collect your data.
You need to collect information on the exposure and outcome variables.

5. What is the best source for assessing the outcome among exposed and unexposed?
[Aschengrau]
a. diagnosis of Susser Syndrome
identified from the hospital charts
of the local hospital and based on
the neurology consultation and
supported by lab results
Correct
We will not miss any cases as all
subjects with disorder will end up at the
local hospital and all cases
will be valid.

b. complaints of neurological
symptoms identified from the
records of the employee health
clinic

Incorrect
We might miss persons with the
syndrome who quit work at the factory
and might include persons whose
symptoms are not actually full-blown
Susser Syndrome.

c. complaints of neurological
symptoms based on information
provided by the human resources
department about medical leave of
absence

Incorrect
We might miss many legitimate cases
and obtain many invalid cases.

6. What is the best method of gathering information on the outcome variable?

[Aschengrau]
a. look through the records of the
local hospital dated from
September, 2002 to September,
2004 to identify those with disorder
and see if there is information in
the chart about their employment

Incorrect
This is not the best way of collecting the data because
employment information might be
missing from the charts; in addition,
subjects who had already quit their job
at the factory as a result of the illness
would be missed.

b. link a discharge
database from the local hospital with a computer database
containing a list of cohort members employed at the
Glop Industries

Correct
Modern linkage techniques allow for correct identification of approximately 95% of people
based on their name and birth date.
Because the local hospital treats all
potential cases, the only cases you are
likely to miss are those who moved out
of the area before treatment or those
patients discharged after the study end
date.

Your supervisor reads over your recommendations and agrees with the majority of them.
Before the study can begin and the data can be collected, however, your supervisor instructs
you of all the administrative work that must be in order. You must:
1. Obtain permissions from Glop Industries regarding use of their internal data.
2. Get approval of your study from your Institutional Review Board (IRB) - this will
ensure that the study adheres to the ethical principles of conducting public health
research and that the rights of study participants are protected.
3. Prepare a budget and get funding.
4. Develop an operations manual to be used by all study personnel which will describe
the standardized procedures for collecting and managing the data. Operations
Manual is critical in maintaining the proper quality control.
5. Design a consent form for study participants which clearly indicates its goals,
explains risks, benefits and expenses that participants might incur if they decide to
participate in the study, as well as states how participants would benefit from their
participation and how you plan to make use of the data once they are collected.
 6. Design a structured questionnaire that will be used to collect data from the study
participants.
7. Hire and train interviewers.
8. Design a data management plan (how and where paper forms will be stored, when
and how they will be entered into the computer database, how the data cleaning will
be performed, and how often checks of the data will be performed to spot possible
problems in the study).
9. Design data analysis plan and propose how you will publicize the findings.
Having received the necessary IRB approval, the study starts. The data begin to file back to
the Department of Health and must now be collated and carefully entered into the computer
database. Despite your leadership role, you are still the intern and, thus, have the inglorious,
yet crucial, responsibility of data entry. Once all of the data are entered, you can proceed to
the analysis stage where the associations proposed in your hypothesis are characterized and
tested.

Step 5: Data Analysis

Before crunching the numbers, you quickly glance over the data and realize that there are a
number of ways to analyze your data. The most appropriate analysis of the data collected in
this study employs the use of person-years as a way of taking into account the fact that
subjects may be followed for varying amounts of time (see Aschengrau).

Intellectually curious? Learn more about person-year calculations here.

The most precise estimate of the impact of exposure in a population that utilizes all available
information is called the incidence rate. This is considered to be a measure of the
instantaneous rate of development of disease in a population and is defined as the number
of new cases of disease during the given period of time (usually one year) over the total
person-time of observation over the same period. The denominator presents the sum of
each individuals time at risk or the sum of the time that each person remained under
observation and free from the disease of interest. This allows the researcher to account for
those who dropped out of the study and no longer contribute to person-years at risk due to
a variety of reasons (moved away, refused to participate, died from unrelated causes, etc.). At
the end of follow-up period, all person-years are summed up to represent the cumulative
time at risk for disease. The time at risk for each person will be calculated from the time the
individual entered the study until the time he/she exits the study. interactive person-year
exercise here.
As previously stated, in our retrospective cohort study all individuals will enter the study at
the same moment in time (September 2002). However, not all will exit at the same time.
How can they exit the study? Any number of ways, including:
a. the development of Susser Syndrome (once they have the endpoint, they are no
longer at risk of developing it);
 b. death;
c. loss-to-follow-up, meaning subjects decided to stop their participation in the study.
Loss-to-follow-up presents the biggest challenge in epidemiological studies. It becomes
impossible to directly calculate their person-years. If we do not have regular contacts with
subjects, it may not be possible to estimate the last time we knew that particular subject was
free of the disease of interest. In these situations, epidemiologists may use simple counts of
subjects to calculate measures of effect. The effect estimate based on such calculations is
called relative risk (or risk ratio) while effect estimates based on person-year calculations are
called rate ratios. Relative risk provides an estimate of the true measure of effect, rate ratio.
Since this is your first real work as a budding epidemiologist, you decide to analyze the data
using both simple counts and person-years and then compare your results to see if there is
some truth to what Epi textbooks say. It is time to get to work!

7. Calculation of the rate ratio from person-year information. [Aschengrau]

The data collected by your team yield the following person-year information:
Number of exposed person-years of observation (PYO) 3,675, i.e.,
low exposure group 2,000 PYO
medium exposure group 1,225 PYO
high exposure group - 450 PYO
Number of unexposed person-years 14,000 PYO
Number of exposed cases - 74
Number of unexposed cases - 120

a. How would you present the

data in the 2x2 format?

Disease + Total person-years

over 2 years
Exposed 74 3,675
Unexposed 120 14,000

b. Calculate incidence rate among all exposed

number of cases among exposed during 2 years /total person-years of observation among
exposed over 2 years = 74/ 3,675 = 0.0200 (or 20
cases per 1,000 PYO)

c. Calculate incidence rate among unexposed

number of cases among unexposed during 2 years /total person-years of observation
among unexposed over 2 years = 120/ 14,000 = 0.0086 (or 9 cases per 1,000 PYO)

d. Calculate incidence rate ratio

Incidence rate in exposed / Incidence rate in unexposed = 0.0200/ 0.0086 = 2.33
e. Interpret your finding
Those who are exposed to chemicals involved in SUPERCLEAN production for at least 6
months have a 2.33 times higher rate of developing Susser Syndrome than those who are
not exposed to SUPERCLEAN production.

8. Calculation of the risk ratio based on simple counts. [Aschengrau]

The data collected by your team yield the following counts:
The data collected by your team yield the following counts:
Total number of exposed individuals - 1,900, i.e.
low exposure group 1,000
medium exposure group - 650
high exposure group - 250
Total number of unexposed individuals - 7,400
Number of exposed diseased (all people who develop Susser Syndrome among the
exposed) - 74
Number of unexposed diseased - 120

a. The first step is to tabulate the

data in the classic 2x2 table. How
would you do this?

Disease + Disease - Total

Exposed 74 1,826 1,900
Unexposed 120 7,280 7,400

b. Calculate cumulative incidence

among all exposed
Cumulative incidence in exposed = number of cases among exposed/total number of
exposed subjects= 74/ 1,900 =
0.0389 (or 39 cases per 1,000 exposed per 2
years or 20 cases per 1,000 exposed per year)

c. Calculate cumulative incidence

among unexposed
cumulative incidence in unexposed = number of cases among unexposed/total number of
unexposed subjects=120/7,400 = 0.0162 (or 16 cases per 1,000 unexposed per 2 years or 8
cases per 1,000 unexposed per year)

d. Calculate rate ratio

cumulative incidence in exposed / cumulative
incidence in unexposed = 0.0389/ 0.0162 = 2.40
e. Interpret your finding
Those who are exposed to chemicals involved
in SUPERCLEAN production for at least 6
months have a 2.4 times higher rate of
developing Susser Syndrome than those who
are not exposed to SUPERCLEAN production.

9. Calculation of rate ratio in exposure sub-groups. [Aschengrau]

Number of exposed person-years of observation (PYO) 3,675, i.e.,
low exposure group 2,000 PYO
medium exposure group 1,225 PYO
high exposure group - 450 PYO
Number of unexposed person-years 14,000 PYO
Number of exposed cases - 74
Number of unexposed cases - 120
Number of expose cases 75
o Low exposure group 32
o Medium exposure group 30
o High exposure group 12

a. There is too much information here to

present in the simple 2x2 format. How
would you present the data in the table
according to different exposure subgroups?

Exposure Low Medium High Unexposed

Group exposure exposure exposure
Number 32 30 12 120
of cases
PYO 2,000 1,225 450 14,000

b. Calculate incidence rate among

exposed by level of exposure
Incidence rate in exposed (Low exposure) =
32/2,000 = 0.0160 (or 16 cases per 1,000 PYO)
Incidence rate in exposed (Medium exposure) =
30/ 1,225 = 0.0245 (or 24 cases per 1,000
PYO)
Incidence rate in exposed (High exposure) =
12/450 = 0.0267 (or 27 cases per 1,000 PYO)

c. Calculate incidence rate among

unexposed
Incidence rate in unexposed =
120/ 14,000 =0.0086 (or 9 cases per 1,000 PYO)

d. Calculate rate ratio at each level of

exposure
Incidence rate in exposed / Incidence rate in unexposed (Low exposure) =
0.0160/0.0086 = 1.86
Incidence rate in exposed / Incidence rate in unexposed (Medium exposure) =
0.0245/0.0086 = 2.85
Incidence rate in exposed / Incidence rate in unexposed (High exposure) =
0.0267/0.0086 = 3.10

e. Interpret your finding

Those who are exposed to low levels of
exposure have a 1.9 times higher rate of
developing a neurological disorder than
those who are not exposed.

Those who are exposed to medium levels

of exposure have a 2.9 times higher rate
of developing a neurological disorder than
those who are not exposed.

Those who are exposed to high levels of

exposure have a 3.1 times higher rate of
developing a neurological disorder than
those who are not exposed.

f. What is this pattern of increase in the

rate ratio consistent with?

Taken together, these findings are

consistent with a dose-response
relationship. As the dose of exposure
increases, the rate of disease
development also increases.

10. Calculation of rate ratio in different age strata. [Aschengrau]

The crack team of field agents has presented you with the data on the age
distribution of all subjects in the cohort, detailed as follows:

Group Exposed Unexposed

Number of PYO Number of PYO
cases cases
20-25 17 994 30 4,120
25-30 26 1,194 45 4,854
30-35 21 994 40 4,448
35-40 10 493 5 578
Total 74 3,675 120 14,000

a. Calculate incidence rate

among exposed in each age
group

Incidence rate in exposed = 17/ 994 = 0.0171 (or 17 cases

per 1000 PYO) in the age group younger 20-25
Incidence rate in exposed = 26/ 1,194 = 0.0218 (or 22 cases
per 1000 PYO) in the age group 25-30
Incidence rate in exposed = 21/ 994 = 0.0211 (or 21 cases
per 1000 PYO) in the age group 30-35
Incidence rate in exposed = 10/ 493 = 0.0201 (or 20 cases per
1000 PYO) in the age group 35-40

b. Calculate incidence rate

among unexposed in each
age group

Incidence rate in unexposed = 30/ 4,120 = 0.0073 (or 7 cases

per 1000 PYO) in the age group 20-25
Incidence rate in unexposed = 45/ 4,854 = 0.0093 (or 9 cases
per 1000 PYO) in the age group 25-30
Incidence rate in unexposed = 40/ 4,448 = 0.0090 (or 9 cases
per 1000 PYO) in the age group 30-35
Incidence rate in unexposed = 5/ 578 = 0.087 (or 9 cases
per 1000 PYO) in the age group 35-40

c. Calculate rate ratio in each

age group

Incidence rate in exposed / Incidence rate in unexposed = 0.0171/0.0073 = 2.35 in the age
group 20-25
Incidence rate in exposed / Incidence rate in unexposed = 0.0218/0.0093 = 2.35 in the age
group 25-30
Incidence rate in exposed / Incidence rate in unexposed = 0.0211/0.0090 = 2.35 in the age
group 30-35
Incidence rate in exposed / Incidence rate in unexposed = 0.0202/0.0087 = 2.35 in the age
group 35-40

d. Interpret your findings

Incidence rate in the age group 20-25 is 2.4 times higher among those that are exposed
compared to those unexposed.
Incidence rate in the age group 25-30 is 2.4 times higher among those that are exposed
compared to those unexposed.
Incidence rate in the age group 30-35 is 2.4 times higher among those that are exposed
compared to those unexposed.
Incidence rate in the age group 35-40 is 2.4 times higher among those that are exposed
compared to those unexposed.

e. Does the association

between exposure and
outcome seem to vary by
age group?

No. Risk are similar in all age categories.

Intellectually curious? Learn more how to calculate standardized

incidence ratio here.

Calculation of standardized incidence ratio (extra credit). [see Aschengrau]

You have data available from the local department of health on the annual
incidence rate of the neurological disorders in Epiville. These data would allow you
to calculate the standardized incidence ratio (indirect method) to determine if the
incidence among SUPERCLEAN employees is higher than the incidence in the
general population. Because the age distribution of the general population is quite
different from the age distribution of the working population you have to take into
account the age structure of the respective groups.

Age group Incidence rate in the general populationa

20-25 0.00039
25-30 0.00052
30-35 0.00047
35-40 0.00062
a
annual incidence rate.

1. Calculate observed
cases and
PYO in each age
Strata (total among exposed and
unexposed)
Age group Observed Casesa Observed PY
20-25 47 5,114
25-30 71 6,048
30-35 61 5,442
35-40 15 1,071
a
observed over 2 years.
2. Calculate the
number of expected
cases in each strata
Age group Incidence rate in Observed PYb Expected Casesc
the general
populationa
20-25 0.00039 5,114 2
25-30 0.00052 6,048 3
30-35 0.00047 5,442 3
35-40 0.00062 1,071 1
Total 17,675 8
a
annual rate
b
PYO accumulated over 2 years
c
Expected cases=Incidence rate in the general population x Observed PY

3. Calculate
standardized
incidence ratio (SIR)
SIR=194/9=21.6

4. How do you interpret

your findings?
Factory employees exposed to SUPERCLEAN have a more than 20
times higher incidence rate of Susser Syndrome than the
general population of Epiville.

11. After putting an exhaustive effort into data analysis, you present your findings to
your supervisor. What should you tell her?
a. It looks like we were chasing a red
herring. In my opinion, there does
not appear to be any relationship
between working with
SUPERCLEAN and the
development of Susser Syndrome.
Let's looks at another source of
exposure.

Incorrect
The consistently elevated risks do
support our hypothesis that
SUPERCLEAN production is
associated with Susser Syndrome.

b. The exposure to SUPERCLEAN

production is the definite cause of
Susser Syndrome. Those elevated
rates are very convincing.

Incorrect
SUPERCLEAN appears to be
associated with the development of
Susser Syndrome. However, as
detailed in Aschengrau, to move from association to
causation requires a substantial
amount of epidemiological evidence
as well as biological plausibility. At this
stage in the investigation, we are far
from having enough data to arrive at such a conclusion.

c. The data clearly suggest an

association between exposure to
SUPERCLEAN at the Glop Industries factory and
successive development of Susser
Syndrome. I think we might want
to explore other potential
exposure sources as
well as try to improve exposure measurement.

Correct
The data do suggest an association;
however, we need to check the
statistical significance of these findings
as they may be due to chance.
Furthermore, it is important to rule out
other potential exposures as they may
confound the findings.

Step 6: Discussion Questions

Carefully consider the following questions related to your work above. Write down your
answers and be prepared to discuss them during the seminar session.
1. How and why the results of Q7 are different from the results of Q8? Give examples
of the events that could have influenced the results.
2. What would you have done to improve the design of this retrospective cohort study?
3. What does the crude rate ratio tell us?
4. What does the monotonic increase in rate ratio among various exposure groups in
Q9 tell us? How does it influence our certainty about the results of this study?
5. Why do we need to look at the age distribution of risks in the cohort (see Q10) and
how should we interpret our findings?
6. Propose how you will design a prospective cohort study which would investigate the
relationship between exposure to SUPERCLEAN and Susser Syndrome. Use
 information from the Step 3: Study Design section to guide yourself through the
necessary steps.
7. Do you think the results of this cohort study are suggestive or conclusive about the
effect of the SUPERCLEAN on Susser Syndrome?
8. Is there a need to conduct further studies?

Questions for the Intellectually Curious

1. What does SIR tell us? What is the purpose of looking at SIRs in cohort studies?
2. Let us assume that Susser Syndrome was a reportable disease. In other words,
physicians and hospitals would be required to report all patients diagnosed with
Susser Syndrome to the Epiville Department of Health (this is a form of passive
surveillance). How would your data collection methods change if this were the case?
What are the advantages and disadvantages of such change vis-a-vis hospital
discharge data?

Step 7: Quiz
This part of the homework is graded with a Pass/Fail grade. Type your name in the space
provided and select your seminar leaders name from the list below. Choose the best answer
to the three multiple choice questions and click the "Submit" button found on the bottom of
the page. Your answers will be sent automatically to your seminar leader who will use them
to assess the content areas that are well understood and those that are less well understood
and to adjust the teaching plans for this weeks seminar session accordingly.

1. Which of the following is the main design feature of cohort studies?

a. number of people in the exposed and unexposed groups should be equal
b. exposed and unexposed groups are representative of the general population
c. exposed and unexposed groups come from the same source population
2. Retrospective cohort studies are more suitable than prospective cohort studies for
the following:
a. Study of rare and occupational exposures
b. Study of common exposures
c. Study of multiple exposures
3. Which of the following measures of risk will be closest to the
true measure of effect in a cohort study with some losses to
follow-up:
a. Relative risk based on the risks among exposed and unexposed
b. Incidence rate ratio based on the rates calculated from the person-year
follow-up information
c. Odds ratio based on the ratio of odds of disease among exposed and
unexposed