Case Study 2

Jill Marshall
MPH 510 Applied Epidemiology

Case Study Cigarette Smoking and Lung Cancer
June 8, 2013
A causal relationship between cigarette smoking and lung cancer was first suspected in the 1920s on
the basis of clinical observations. To test this apparent association, numerous epidemiologic studies
were undertaken between 1930 and 1960. Two studies were conducted by Richard Doll and Austin
Bradford Hill in Great Britain. The first was a case-control study begun in 1947 comparing the smoking
habits of lung cancer patients with the smoking habits of other patients. The second was a cohort
study begun in 1951 recording causes of death among British physicians in relation to smoking habits.
This case study deals first with the case-control study, then with the cohort study.
Data for the case-control study were obtained from hospitalized patients in London and vicinity over a
4-year period (April 1948 - February 1952). Initially, 20 hospitals, and later more, were asked to notify
the investigators of all patients admitted with a new diagnosis of lung cancer. These patients were
then interviewed concerning smoking habits, as were controls selected from patients with other
disorders (primarily non-malignant) who were hospitalized in the same hospitals at the same time.
Data for the cohort study were obtained from the population of all physicians listed in the British
Medical Register who resided in England and Wales as of October 1951. Information about present
and past smoking habits was obtained by questionnaire. Information about lung cancer came from
death certificates and other mortality data recorded during ensuing years.
Question 1: What makes the first study a case-control study?
The first study is a case-control study.It meets the definition of a case-control study as defined by Friis
and Sellers: an analytic study of persons diagnosed with the disease of interest and a suitable control
group of patients without the disease (Friis and Sellers, 2014). In this case, this was study of persons
diagnosed with lung cancer (with the disease of interest) and patients of other disorders who were
hospitalized at the same time (a suitable control group of patients without the disease).
References:
Friis R.H. and Sellers T. A. (2014) Epidemiology for Public Health Practice, Fifth Edition. Jones and Bartlett
Learning, LLC. Page 303.
Question 2: What makes the second study a cohort study?
The second study is a cohort study. It meets the definition of a cohort study as defined by Friis and
Selers: a population group or subset therof (distinguished by a common characteristic), that is followed
over a period of time (Friis and Sellers, page 325, 2014). In this case , this was a study of the past
smoking habits of persons who resided in England and Whales (population) as of October 1951 and died
during the ensuing years (period of time).
References:
Page 1 of 12
Jill Marshall
June 8, 2013
The remainder of Part I deals with the case-control study.
Question 3: Why might hospitals have been chosen as the setting for this study?
According to Friis and Sellers, a preferred approach is to conduct case-control studies in which cases and
controls are population based. They explain, when the selection of population-based study groups are
not feasible, cases may need to be derived from one or more major hospitals. They also explain that
although hospital-based studies are inherently subject to greater potential for errors than population
based studies, their use is certainly justified when little information has be reported about a particular
exposure-disease association or when a population based case registry is not available (Friis and Sellers,
page 308, 2014). In this case, there was little information and no population based case registry
available, so the use of the hospital was justified.
References:
Question 4: What other sources of cases and controls might have been used?
According to Friis and Sellers, the ideal situation is to identify and enroll all incident cases in a defined
population in a specified time period is using a disease registry or a complete listing of all available cases
from a source such as the Vital Statistics Bureau. They also explain that the best way to ensure that the
distribution of exposure among the controls represents the exposure levels in the population is to select
population-based controls. A suggested method to identify such controls is to obtain a list that contains
names and addresses of most residents in the same geographic area as the cases (Friis and Sellers, 2014)
References:
Learning, LLC. Page 305-307.
Question 5: What are the advantages of selecting controls from the same hospitals as cases?
The advantages to selecting controls from the same hospitals and cases include that the cases and
controls are from the same geographic area. Additionally, Friis and Sellers explains that other
advantages to selecting controls from the same hospital are that the study personnel who are already
in the hospital to interview cases may achieve time efficiency by also interviewing controls. The time
saving, plus the fact that hospital controls may be more likely than population controls to participate,
ultimately equates to cost savings (Friis and Sellers, pages 308-309, 2014).
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Jill Marshall
June 8, 2013
References:
Learning, LLC. Page 308-309.
Question 6: How representative of all persons with lung cancer are hospitalized patients with lung
cancer?
At the time of the study using hospitalized patients with lung cancer was probably fairly representative
of all persons with lung cancer, as outpatient treatments and diagnostic methods were not available.
Currently, there is more advanced knowledge of cancer including knowledge about the differing stages
of the disease that may not require hospitalization. Advancements in outpatient treatment coupled with
early identification may exclude those diagnosed with the disease from being represented by the cases
making the sample not very representative of all persons with lung cancer.
Question 7: How representative of the general population without lung cancer are hospitalized
patients without lung cancer?
Not very, as persons who are hospitalized generally have poorer health conditions than those of the
general population. They may also engage in more risk-taking behavior or high-risk activities such as
smoking, drinking, drug use, or working in situations where exposure to other carcinogens may increase
their propensity to develop lung cancer. Generally, people who engage in healthier activities stay out of
hospitals.
Question 8: How may these representativeness issues affect interpretation of the study's results?
Friis and Sellers explain that one of the major limitations of case-control studies is indeterminate
representativeness of the cases and controls. If the cases and controls are not representative of the
population, the results of the study will be biased. This would be a case of selection bias. Selection bias
occurs when the relation between exposure and disease is different from those participating and those
who would be theoretically eligible to participate but do not (Friis and Sellers, 2014).
References
Learning, LLC. Pages 316, 442.
Over 1,700 patients with lung cancer, all under age 75, were eligible for the case-control study. About
15% of these persons were not interviewed because of death, discharge, severity of illness, or inability
to speak English. An additional group of patients were interviewed but later excluded when initial
lung cancer diagnosis proved mistaken. The final study group included 1,465 cases (1,357 males and
108 females). The following table shows the relationship between cigarette smoking and lung cancer
among male cases and controls.
Page 3 of 12
Jill Marshall
June 8, 2013
Table 1. Smoking status before onset of the present illness, lung cancer cases and matched controls
with other diseases, Great Britain, 1948-1952.
Cigarette
smoker
Non-smoker
Total
Cases
Controls
1350
1296
7
1357
61
1357
Question 9: From this table, calculate the proportion of cases and controls who smoked.
Cigarette smoker
Non-smoker
Total
1350/1357 =
Proportion Smoked =
Cases
1350
7
1357
0.9948
99.5%
Controls
1296
61
1357
0.9550
95.5%
Proportion smoked, cases: 99.5%

Proportion smoked, controls: 95.5%
Question 10: What do you infer from these proportions?
Smoking is a behavior that occurs in more than 95% of both the cases and controls.
Question 11a: Calculate the odds of smoking among the cases.
Cigarette smoker
Non-smoker
Total
1350/1357 =
Proportion Smoked =
smokers/non-smokers
Odds
Cases
1350
7
1357
0.9948
99.5%
192.9
192.9/1
Controls
1296
61
1357
0.9550
95.5%
21.2
21.2/1
The odds of smoking among the cases is 192.9/1

Page 4 of 12
Jill Marshall
June 8, 2013
Question 11b: Calculate the odds of smoking among the controls.
Cigarette smoker
Non-smoker
Total
1350/1357 =
Proportion Smoked =
smokers/non-smokers
Odds
Cases
1350
7
1357
0.9948
99.5%
192.9
192.9/1
Controls
1296
61
1357
0.9550
95.5%
21.2
21.2/1
The odds of smoking among the controls is 21.2/1

Question 12: Calculate the ratio of these odds. How does this compare with the cross-product ratio?
Cigarette smoker
Non-smoker
Total
1350/1357 =
Proportion Smoked =
smokers/non-smokers
Odds
[(smokers/nonsmokers)cases]/(smokers/nonsmokers)(controls)
Odds Ratio (OR)
The Odds Ratio is 9.1
Cases
1350
7
1357
0.9948
99.5%
192.9
192.9/1
Controls
1296
61
1357
0.9550
95.5%
21.2
21.2/1
9.1
9.1
Question 13: What do you infer from the odds ratio about the relationship between smoking and lung
cancer?
The Odds Ratio (OR) is 9.1 and according to Friis and Sellers the OR literally measures the odds for
exposure to a given disease (Friis and Sellers, page 310, 2014). In this case the OR is saying that persons
who smoke are 9X more likely to develop lung cancer than those who do not smoke
References
Page 5 of 12
Jill Marshall
June 8, 2013
Table 2 shows the frequency distribution of male cases and controls by average number of cigarettes
smoked per day.
Table 2. Most recent amount of cigarettes smoked daily before onset of the present illness, lung cancer
cases and matched controls with other diseases, Great Britain, 1948-1952.
Daily Number of
Cigarettes
Number of
Cases
Number of
Controls
0
1-14
15-24
25+
All smokers
7
565
445
340
1350
61
706
408
182
1296
Odds Ratio
referent
Question 14: Compute the odds ratio by category of daily cigarette consumption, comparing each
smoking category to nonsmokers.
Daily Number of
Cigarettes
Number of
Cases
Number of
Controls
Odds Ratio
0
1-14
15-24
25+
All smokers
7
565
445
340
1350
61
706
408
182
1296
referent
7.0
9.5
16.3
9.1
smokers (cases) *
non-smokers
(controls)
A
34465
27145
20740
82350
smokers
(controls) * nonsmokers (cases)
B
4942
2856
1274
9072
The Odds Ratio for 1-14 cigarettes is 7.0; 15-24 cigarettes is 9.5; 25+ cigarettes is 16.3; and all smokers is
9.1.
Question 15: Interpret these results.
These results could be interpreted to mean that the odds of developing lung cancer increases with the
number of cigarettes a person uses daily.
Although the study demonstrates a clear association between smoking and lung cancer, cause-andeffect is not the only explanation.
Page 6 of 12
A/B
7.0
9.5
16.3
9.1
Jill Marshall
June 8, 2013
Question 16: What are the other possible explanations for the apparent association?
There could be simply a correlation but not causation; chance; bias including selection, information, or
confounding, or investigator error.
The next section of this case study deals with the cohort study. Data for the cohort study were
obtained from the population of all physicians listed in the British Medical Register who resided in
England and Wales as of October 1951. Questionnaires were mailed in October 1951, to 59,600
physicians. The questionnaire asked the physicians to classify themselves into one of three categories:
1) current smoker, 2) ex-smoker, or 3) nonsmoker. Smokers and ex-smokers were asked the amount
they smoked, their method of smoking, the age they started to smoke, and, if they had stopped
smoking, how long it had been since they last smoked. Nonsmokers were defined as persons who had
never consistently smoked as much as one cigarette a day for as long as one year. Usable responses to
the questionnaire were received from 40,637 (68%) physicians, of whom 34,445 were males and 6,192
were females.
Question 17: How might the response rate of 68% affect the study's results?
This response rate could suggest selection bias and skew the results of the study.
The next section of this case study is limited to the analysis of male physician respondents, 35 years of
age or older. The occurrence of lung cancer in physicians responding to the questionnaire was
documented over a 10-year period (November 1951 through October 1961) from death certificates
filed with the Registrar General of the United Kingdom and from lists of physician deaths provided by
the British Medical Association. All certificates indicating that the decedent was a physician were
abstracted. For each death attributed to lung cancer, medical records were reviewed to confirm the
diagnosis. Diagnoses of lung cancer were based on the best evidence available; about 70% were from
biopsy, autopsy, or sputum cytology (combined with bronchoscopy or X-ray evidence); 29% were from
cytology, bronchoscopy, or X-ray alone; and only 1% were from just case history, physical
examination, or death certificate. Of 4,597 deaths in the cohort over the 10-year period, 157 were
reported to have been caused by lung cancer; in 4 of the 157 cases this diagnosis could not be
documented, leaving 153 confirmed deaths from lung cancer. The following table shows numbers of
lung cancer deaths by daily number of cigarettes smoked at the time of the 1951 questionnaire (for
male physicians who were nonsmokers and current smokers only). Person-years of observation
("person-years at risk") are given for each smoking category. The number of cigarettes smoked was
available for 136 of the persons who died from lung cancer.
Table 3. Number and rate (per 1,000 person-years) of lung cancer deaths by number of cigarettes
smoked per day, Doll and Hill physician cohort study, Great Britain, 1951-1961.
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Jill Marshall
June 8, 2013
Daily Number of
Cigarettes
0
1-14
15-24
25+
All smokers
Total
Deaths
3
22
54
57
133
136
Person-years at
Risk
42800
38600
38900
25100
102600
145400
Mortality Rate per

1,000 personyears
0.07
Rate Ratio
referent
Rate difference
per 1000 personyears
referent
Question 18: Compute lung cancer mortality rates, rate ratios, and rate differences for each smoking
category. What do each of these measures mean?
Daily Number of
Cigarettes
0
1-14
15-24
25+
All smokers
Total
Deaths
3
22
54
57
133
136
Person-years at
Risk
42800
38600
38900
25100
102600
145400
Mortality
Rate per
1,000
personyears
0.07
0.57
1.39
2.25
1.30
0.94
Rate Ratio
referent
8.10
19.80
32.40
18.60
Rate difference
per 1000 personyears
referent
0.50
1.32
2.20
1.23
These results could be interpreted to mean that mortality rates increase with the number of cigarettes a
person uses daily.
Question 19: What proportion of lung cancer deaths among all smokers can be attributed to smoking?
What is this proportion called?
The proportion of lung cancer deaths among all smokers that can be attributed to smoking is 94.6%. This
proportion is called Absolute Risk.
Page 8 of 12
Jill Marshall
June 8, 2013
Absolute Risk = [(1.30/0.07)/1.30]*100 = 94.6
Rate difference
Daily Number of
Person-years at Mortality Rate per 1,000
per 1000 personCigarettes
Deaths
Risk
person-years
Rate Ratio
years
0
3
42800
0.07
referent
referent
1-14
22
38600
0.57
8.10
0.50
15-24
54
38900
1.39
19.80
1.32
25+
57
25100
2.25
32.40
2.20
All smokers
133
102600
1.30
18.60
1.23
Total
136
145400
0.94
Question 20: If no one had smoked, how many deaths from lung cancer would have been averted?
Based on the proportion in the previous question, 95 percent of deaths from lung cancer can be
attributed to smoking. Using this information, approximately 126 deaths of the 133 could have been
averted if no one had smoked.
The cohort study also provided mortality rates for cardiovascular disease among smokers and
nonsmokers. The following table presents lung cancer mortality data and comparable cardiovascular
disease mortality data.
Table 4. Mortality rates (per 1,000 person-years), rate ratios, and excess deaths from lung cancer and
cardiovascular disease by smoking status, Doll and Hill physician cohort study, Great Britain, 1951-1961.
Smokers
Lung Cancer
Cardiovascular
Disease
Mortality rate per 1,000 person-years

Excess deaths
Non-smokers
All
Rate Ratio per 1000 personyears
Attributable risk
percent among
smokers
1.3
0.07
0.94
18.5
1.23
95%
9.5
7.32
8.87
1.3
2.19
23%
Question 21: Which cause of death has a stronger association with smoking? Why?
Deaths resulting from lung cancer have a stronger association with smoking. The rate ratio
demonstrates that there is a higher association between smoking and lung cancer at 18.5 than there is
between smoking and cardiovascular disease at 1.3.
In calculating the attributable risk percent, the excess lung cancer deaths attributable to smoking is
expressed as a percentage of all lung cancer mortality among all smokers. The attributable risk
Page 9 of 12
Jill Marshall
June 8, 2013
percent of 95% for smoking may be interpreted as the proportion of lung cancer deaths among
smokers that could have been prevented if they had not smoked. A similar measure, the population
attributable risk ercent expresses the excess lung cancer deaths attributable to smoking as a
percentage of all lung cancer mortality among the entire population. From a prevention perspective,
the population attributable risk percent for a given exposure can be interpreted as the proportion of
cases in the entire population that would be prevented if the exposure had not occurred. The
population attributable risk percent is often used in assessing the cost-effectiveness and costbenefit
of community-based intervention programs. One formula for the population attributable risk percent
is: PAR% = (Incidence in entire population * Incidence in unexposed) / Incidence in entire population.
Question 22: Calculate the population attributable risk percent for lung cancer mortality and for
cardiovascular disease mortality. How do they compare? How do they differ from the attributable risk
percent?
Smokers
Mortality rate per 1,000 person-years

Excess deaths
Non-smokers
All
Rate Ratio per 1000 personyears
Lung Cancer
1.3
0.07
Cardiovascular
9.5
7.32
Disease
PAR = (All *Non-smokers)/All*100
Attributable risk
percent among
smokers
0.94
18.5
1.23
95%
8.87
1.3
2.19
23%
PAR for Lung Cancer is 92.5%

PAR for Cardiovascular disease is 17.4%
The compare in that death as a result of lung cancer and cardiovascular disease can be attributed to
smoking. They differ in that a much higher percentage of deaths from lung cancer (92.5 percent) can be
attributed to smoking than they can be for cardiovascular disease (at 17.4 percent).
Question 23: How many lung cancer deaths per 1,000 persons per year are attributable to smoking
among the entire population? How many cardiovascular disease deaths?
Lung Cancer: 0.87 deaths per 1,000 person-years (PAR*All)
Cardiovascular Disease: 1.54 deaths per 1.000 person-years (PAR*All)
The following table shows the relationship between smoking and lung cancer mortality in terms of the
effects of stopping smoking.
Table 5. Number and rate (per 1,000 person-years) of lung cancer deaths for current smokers and exsmokers by years since quitting, Doll and Hill physician cohort study, Great Britain, 1951-1961.
Page 10 of 12
Jill Marshall
June 8, 2013
Cigarette Smoking
Status
Lung
Cancer
Deaths
Rate per
1000 personyears
Rate
Ratio
Current smokers
133
1.3
18.5
For ex-smokers,
years since
quitting
< 5 years
5-9
10-19
20+
5
7
3
2
0.67
0.49
0.18
0.19
9.6
7
2.6
2.7
non-smokers
0.07
Question 24: What do these data imply for the practice of public health and preventive medicine?
The data implies that smokers are the highest risk group for lung cancer and while quitting reduces the
risk, those who never smoke are in the lowest risk group. Public health initiatives and preventive
medicine efforts to prevent people from smoking would have the most benefit. Additionally, educating
those who smoke to quit smoking will help to reduce deaths from lung cancer.
As noted at the beginning of this case study, Doll and Hill began their case-control study in 1947. They
began their cohort study in 1951. The odds ratios and rate ratios from the two studies by numbers of
cigarettes smoked are given in the table below.
Table 6. Comparison of measures of association from Doll and Hills 1948-1952 case-control study and
Doll and Hills 1951-1961 physician cohort study, by number of cigarettes smoked daily, Great Britain.
Daily number of
Cigarettes Smoked
Rate Ratio from

Cohort Study
0
1-14
15-24
25+
All Smokers
1.0 (ref)
8.1
19.8
32.4
18.5
Odds Ratio from

case-control
study
1.0 (ref)
7
9.5
16.3
9.1
Question 25: Compare the results of the two studies. Comment on the similarities and differences in
the computed measures of association.
Page 11 of 12
Jill Marshall
June 8, 2013
Both studies demonstrate that lung cancer deaths are associated with smoking. Both studies also
demonstrate that the risk of a lung cancer death increases with the daily number of cigarettes smoked.
The difference is in comparing the rate ratio to the odds ratio. The odds ratios from the case-control are
not as strong (high of a number) as the rate ratios from the cohort study.
Question 26: What are the advantages and disadvantages of case-control vs. cohort studies?
Answer 26
Sample size
Costs
Study time
Case-control
smaller/ disadvantage
inexpensive/advantage
quick/advantage
Cohort
larger/advantage
expensive/disadvantage
lengthy/disadvantage
Rare disease
Rare exposure
Multiple exposures
Multiple outcomes
good for this/advantage

not good for this/disadvantage

Progression,
spectrum of illness
Disease rates


Recall bias
potential for bias/disadvantage
Loss to follow-up
Selection bias
less potential for loss/advantage

potential for bias/disadvantage
less potential
for bias/advantage
potential for loss/disadvantage
less potential for
bias/advantage
Question 27: Which type of study (cohort or case-control) would you have done first? Why? Why do
a second study? Why do the other type of study?
I would have conducted a case-control study first especially if there were an accessible disease registry
available. A case-control study is cost effective and less time consuming than a cohort study. I might do
a cohort study if there is evidence to support the findings from the case-control study.
Question 28: Which of the following criteria for causality are met by the evidence presented from
these two studies?
Answer 28
Strong association
Consistency among studies
Exposure precedes disease
Dose-response effect
Biologic plausibility
Page 12 of 12
Yes
X
X
X
X
No

Case Study 2

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Jill Marshall

MPH 510 Applied Epidemiology

Proportion smoked, cases: 99.5%

The odds of smoking among the cases is 192.9/1

The odds of smoking among the controls is 21.2/1

Mortality Rate per

Mortality rate per 1,000 person-years

Mortality rate per 1,000 person-years

PAR for Lung Cancer is 92.5%

Rate Ratio from

Odds Ratio from

good for this/advantage

not good for this/disadvantage

not good for this/disadvantage

good for this/advantage

potential for bias/disadvantage

less potential for loss/advantage

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