UNIVERSITY OF LONDON

FACULTY OF MEDICINE
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE

POSTGRADUATE DIPLOMA AND MSc EXAMINATION

for External Students

EPIDEMIOLOGY: PRINCIPLES AND PRACTICE

670 E101: Fundamentals of Epidemiology

Wednesday 1 June 2005 – 10.00-12.00

This paper MUST NOT be removed from the examination room.

Answer THREE questions. Use a SEPARATE answer book for each question.

Electronic calculators may be used. These should be of a hand-held type and must not be pre-
programmed. The name and model of calculator should be stated CLEARLY on the front of
each of your answer books.

Question 1

Between 1950 and 2000, the annual number of deaths from prostate cancer in a western
European country increased from 4,355 to 6,755. The male population of the country in these
two years was 27,455,000 and 29,877,000, respectively.

a) Calculate the death rates from prostate cancer in 1950 and 2000. (10 marks)

EP101 Solutions & marking guidelines

1. a) 1950: (4355/27,455,000)*100,000 =15.86 per 100,000 per year (5 marks. Give full marks if other
denominators are given, eg, per 1,000,000 per year, as long as they are stated clearly. : drop 1 if the
number of person-years are not stated clearly; and a further 1 if ‘person-years’ or ‘per year’ is not
stated clearly)
2000: (6755/29,877,000)*100,000 =22.61 per 100,000 per year. (5 marks. As above, drop up to 2 if
denominator is not stated clearly)

b) What was the proportional change in prostate cancer mortality between 1950 and 2000?
(10 marks)
Rate in 2000 / rate in 1950 = 1.425 or a 42.5% increase. (10 marks)

c) Describe FOUR possible explanations for this change. (40 marks)

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Give 5 marks for mentioning each point and a further 5 for the explanation.
a. Chance – unlikely, huge numbers, can be addressed by statistical testing
b. Bias – diagnosis or detection of prostate cancer improved over time, likely, would need to
make judgement based on literature etc
c. Confounding – population became older, likely, standardisation
d. Real increase – only if chance, bias and confounding are ruled out; it would mean that
prostate cancer became more common or survival decreased (unlikely)

In 2000, the standardised incidence ratios of breast cancer were similar in women with non-
manual and manual occupations but the standardised mortality ratio (SMR) was higher in
women with manual occupations (SMR 112) than in women with non-manual jobs (SMR
93).

d) Describe what an SMR is. (10 marks)

SMR: indicator of mortality, indirectly adjusted for age, compared with mortality in the national
(standard) population; ratio of observed vs expected numbers of cases

e) What information is needed to calculate the SMRs for women in different occupational
groups? (15 marks)

SMR: Total number of deaths (from breast cancer) in each occupational group (5 marks)
Age structure of each occupational group (5 marks)
Age-specific mortality rates (from breast cancer) in the national (standard) population (5
marks)

f) Give TWO possible explanations for why the SMRs were different but the standardised
incidence ratios were similar. (15 marks)

Survival is probably higher (and case-fatality lower) in women with non-manual occupations,
possibly due to better medical care. (10 marks)

Alternatively, it is possible that detection of incident cases is spuriously higher in women with non-
manual occupations (e.g. because of higher uptake of screening) and that this has included non-
malignant lesions and thus artificially increased incidence. (5 marks)

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Question 2

You wish to study whether hepatitis B vaccination in adults is associated with multiple
sclerosis, which is a rare disorder of the nervous system that occurs in the age range of 15
years to 50 years with peak incidence at 30 years. Hepatitis B vaccination in adults is given to
people occupationally exposed to the virus, for example health workers, and for travellers to
countries with high rates of infection. Describe the study design that you would use (20
marks). Explain your choice (20 marks). Describe three strengths and three weaknesses of the
design that you have chosen (60 marks).

Design: Case-control – 10 marks. Give an additional 5 marks for explaining what the cases
would be, and a further 5 marks for discussing control selection appropriately.
Cohort – 5 marks. Give an additional 5 for defining exposed and unexposed groups
appropriately, and a further 5 for a discussion of blinding of diagnosis.
Ecological – 5 marks
Cross sectional – 5 marks
RCT – 0 marks, since it is not feasible – this would deprive risk groups of vaccine protectio,
for example.

Explanation: use the table below: marks are given in brackets.

Case control Rare disease (10) Long latent period Other valid point (5)
(5)
Cohort Relatively rare Time relationship Other valid point (5)
exposure (5) (10)
Ecological Rare disease (10) Relatively rare Other valid point (5)
exposure (5)
Cross sectional Rapid study (10) Relatively cheap (5) Other valid point (5)
RCT Eliminates Other valid point (5)
confounding (15)

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Strengths and weaknesses: use the table below: marks are given in brackets.

Advantages Disadvantages
Case Relatively Other valid Relativel Bias Sample size Other
control rapid (10) point (10) y cheap likely(10) for relatively valid
(10) rare (10)
exposure(10
)
Cohort Time Good Other Cost (10) Sample size Time
sequence control of valid (10) (10 neede
clear (10) confoundin d (10)
g (10)
Ecologica Bias Minimal Other No control of Routine data Other
l unlikely (10) time (10) valid (10) counfoundin may not be valid
g (10) available (10)
(10)
Cross Rapid (10) Less Other Large Time Other
sectional potential valid (10) sample size sequence valid
bias than cc (10) unclear (10) (10)
(10)
RCT Confoundin Bias Other Sample size Ethical Other
g excluded minimized valid (10) very large issues (10) valid
(10) (10) (10) (10)

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Question 3

A study was carried out to examine the association between patterns of alcohol consumption
and stroke. It was performed over a period of 10 years in subjects aged 35-69 years in a town
in Australia. An attempt was made to identify all incident cases of stroke in the population
over the study period. 11,511 cases were identified. Information on the number of days per
week on which they drank alcohol, and the number of drinks consumed on each occasion was
obtained by questionnaire from the surviving cases, or from relatives of those who had died.
Information was obtained for 94% of surviving cases, and for 53% of those who had died.
Controls were selected randomly from the study population. Overall information was
obtained for 6,077 controls (65% of those invited to participate).

a) What type of study is this? Why were cases who had died included? (15 marks)

Population based case-control study (7 marks: 5 for ‘case-control study’ alone).

Cases who had died were included because if they were not included, any associations found would
only apply to non-fatal stroke, and might not be generalisable to stroke in general.(8 marks)

b) Describe FIVE possible sources of bias in this study. (30 marks)

Give 2 marks for mentioning a particular term, and up to 4 further marks for each clear explanation of
how it might arise, up to a maximum of 30 for this section. This solution uses the terminology from the
EPP CAL material: if students use other terminology that makes sense and is well explained, they
should not be penalised.

Recall bias [a type of reporting bias] The cases, or relatives of fatal cases, may have been
thinking about possible causes for the stroke and so may report alcohol consumption
differently from controls.

Response bias [a type of reporting bias]. In cases: while information was obtained from nearly
all the non-fatal cases, it could not be obtained for nearly half of the fatal cases. It is possible
that information may have been harder to obtain for heavy drinkers, who might have lost
touch with their relatives.

Response bias [a type of reporting bias]: In cases, information given by a relative may not be
as reliable as information given by the case. Alcohol intake is a subject people may feel
sensitive about, and is often underreported.

Response bias [a type of reporting bias]. In controls: 35% of those invited did not respond. It
is possible that heavy drinkers would have been less likely to respond.

Interviewer bias [a type of observer bias]: In both cases and controls, interviewers may have
been more likely to record certain drinking patterns according to their own interpretation of
what the interviewee actually said since they are not blinded to case control status.

Information bias; controls: Again, alcohol intake is a sensitive topic, and may be
underreported.

Interviewer bias [a type of observer bias]: In both cases and controls, interviewers may have
been more likely to record certain drinking patterns according to their own interpretation of
what the interviewee actually.

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c) The following table shows some of the results obtained for men in this study. What does
this show? Is frequency of drinking an effect modifier of the association between alcohol
and stroke? Justify your answer. (15 marks)

Number of days per Number of standard Average weekly Adjusted odds ratio
week when alcohol drinks consumed per number of standard (95% CI) compared
consumed session drinks consumed to non drinkers

1-2 9 or more 9-18+ 2.6 (1.1-6.2)

5-6 3-4 15-24 0.5 (0.3-0.8)

While similar amounts of alcohol are being consumed per week in each group, the group consuming
them over 1-2 days per week had a significantly increased odds of stroke compared to non drinkers,
whereas the group consuming them over 5-6 days per week had a significantly reduced odds of
stroke compared to non drinkers. This means that frequency of drinking is an effect modifier. Since
the effect is in opposite directions in the two groups, this is not likely to be due to confounding.

(5 marks for identifying effect modifier, up to 10 marks for further explanation)

d) List FIVE likely confounding factors in this study and explain why they are potential
confounding variables. (40 marks)

Possible confounders include;

Age
Sex (the results presented are for men only)
Social class
Smoking (?)
Other vascular disease e.g. MI or angina
Other illnesses, e.g. diabetes, which could affect drinking habits and raises the risk of stroke.

(4 marks for each potential confounder if justified, 4 marks for adequate justification up to 40 marks)

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Question 4

A study was conducted which aimed to measure the prevalence of visual impairment in
people aged 75 years and above in the UK. The study was conducted in 53 general practices
selected to be representative of the UK population. Visual acuity was available for 14,600
people out of 21,241 invited. The results of the study are shown below.

Men Women
Number Number visually Number Number visually
examined impaired examined impaired
Total 5620 513 8980 1290

a) What type of study is this? (10 marks)

Cross-sectional study (10 marks)

b) Calculate the overall prevalence of visual impairment in the population. (10 marks)

1803/14600*100 = 12.4% (10 marks)

c) Calculate the prevalence of visual impairment in men and women separately. Calculate a
summary measure to compare the prevalence in men and women and briefly comment on
your findings. (20 marks)

513/5620*100 (9.1%) in men (5 marks)

1290/8980*100 (14.4%) in women (5 marks)
Prevalence ratio 14.4/9.1 = 1.58 (5 marks)(Award 3 marks if ratio is correctly calculated from
wrong prevalences)
Women have a higher prevalence of visual impairment than men (5 marks)

d) The following table gives the prevalence of visual impairment by age for men and women
separately.

Age Men Women

Number Prevalence % Number Prevalence %
examined examined
75-79 2961 4.8 3652 7.2
80-84 1525 10.0 2531 12.9
85-89 632 19.2 1144 25.6
90+ 130 28.6 363 39.4

i) Describe briefly how visual impairment changes with age. (5 marks)

The prevalence or risk of visual impairment increases with increasing age (5 marks).

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 ii) Compare the prevalence of visual impairment in men and women in each age-group.
(10 marks)
The prevalence or risk of visual impairment is higher in women than men at all ages (5 marks). Add up
to 5 marks if they calculate prevalence ratios as below.
Age Prevalence ratio
75-79 1.52
80-84 1.29
85-89 1.33
90+ 1.38

iii) Discuss whether age is a possible confounder of the association between visual
impairment and gender. (20 marks)
There is still an increased risk of visual impairment in women even after stratifying by age i.e. the
higher prevalence of visual impairment in women is not entirely explained by age (10 marks)

There is some indication that the association is attenuated by stratifying by age i.e. the association
between visual impairment and gender is partly, but not totally, explained by the fact that there are
more older women in this cohort (5 marks).

Add up to 5 marks if they refer back to the prevalence ratio for the total population in question (c)
above and/or compare the age distribution in men and women to justify their answer.

Note: Up to 5 marks may be given for each other sensible comment (up to a maximum of 20 marks)
eg, that it is difficult to assess whether the risk is higher in women without confidence intervals or that
would need to combine the age-specific prevalence ratios into an overall prevalence ratio to compare
to the unadjusted figure.

e) The investigators also collected data on smoking in this study. They found that people
who smoked had a higher risk of visual impairment due to age-related macular
degeneration (AMD) than people who had never smoked. Give up to five criteria for
deciding whether smoking in this study is a cause of AMD. (25 marks)

Odds ratio for AMD 95% confidence

adjusted for age and sex interval
Never smoked 1
Ex-smoker 1.13 0.88 to 1.44
Current smoker 2.33 1.61 to 3.37

Give 5 marks each for the following criteria (maximum 25) 3 marks for mentioning the criteria and 2
marks for further comment
 Temporality – cross-sectional study so difficult to establish temporality
 Strength of the association – over two-fold increased odds, could possibly be explained by
confounding or bias
 Consistency - would need information from other studies to assess how consistent the
finding is
 Biological gradient – some indication of a biological gradient but odds ratio for ex-smoker
category is not statistically significant
 Specificity – cannot assess with the information available
 Plausibility/coherence – plausible hypothesis as smoking has vascular and oxidative effects
that could cause retinal disease

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Question 5

a) Explain the meaning of the incubation period of an infectious disease. (5 marks)

The period from the time of infection to the development of symptoms.

b) What is the latent period of an infectious disease? How does this differ from a non-
infectious disease? (15 marks)

For ID the latent period is the period from the time of infection to the onset of infectivity (7 marks).
For a non-ID it is the period from exposure to an aetiological agent to the onset of disease (8
marks).

There was an outbreak of measles in a small primary school with a single classroom and 23
children, all of whom were susceptible to measles. A single case occurred, with onset of rash
on day 0, and other cases followed with onset of rash on days 8, 9 (3 cases), 10 (3 cases), 11
(2 cases), 12 (3 cases), 13, 14, 15 and 22.

c) The normal range of the serial interval for measles is 7 to 18 days. Define a serial
interval. For measles it is measured using the day of rash onset – why do you think this
is? (30 marks)

The serial interval is the time from a specific point (here onset of rash) in the natural history of the
infection in a primary case to the same point in the natural history of a secondary case (15 marks)
Day of rash onset is used because it is a clearly definable day and is remembered reasonably well
(15 marks)

d) The secondary attack rate (SAR) is often used to measure the probability of transmission
of an infectious disease. It is defined as:

number of exposed susceptible individuals who develop disease

------------------------------------------------------------------------------------------
total number of exposed susceptible individuals

Calculate the SAR for this measles outbreak. Give at least one assumption made when the
SAR is used to measure the probability of transmission. (25 marks)

SAR = 15 / 22 = 68%. (10 marks) note the last case is outside the range of the serial interval
& is therefore not part of the chain or a tertiary case

Assumptions: All secondary cases are due to contact with the primary case. The children mix
randomly and are equally susceptible. (5 marks for each of these making 15).

e) The basic reproductive rate is the average number of secondary cases produced by each
infective case in a totally susceptible population. Calculate the basic reproductive rate for
the measles outbreak described above. What is the minimum proportion of this population
that would have to be immune to measles in order to eradicate the disease? (25 marks)

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There was one primary case, and there were 15 secondary cases, so the basic reproductive
rate (R0) is 15. (10 marks)

The minimum proportion of this population that would have to be immune to measles in order
to eradicate the disease is the herd immunity threshold or HIT, which is (R 0 – 1) / R0, which is
14/15 or 93%. (5 marks for the stating the formula and a further 10 for the correct HIT. Award
5 marks if the HIT is wrong but correct given the value of R 0. used.)

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