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Module 2: Topic 1
Dr Amirul Islam
Semester 1, 2015
Module 2: Topic 1
Contents
11
12
12
13
14
15
Revision Exercises
17
20
References
22
Semester 1, 2015
Module 2: Topic 1
Note: Some of the materials are adapted from standard texts and guides (see references).
Semester 1, 2015
Module 2: Topic 1
Semester 1, 2015
Module 2: Topic 1
A study in which the researcher observes and records what has already happened is called
an observational approach. On the other hand, an experimental study or trial is initiated
by a researcher. In an "ideal" experiment, the researcher manipulates the independent
variable (s), holds all other variables constant, and observes the changes in the dependent
variable. In experimental studies or trials we determine which experimental units receive
which treatment, whereas in observational studies we have to take what is observed.
Observational studies often show an association between two variables, but they cannot in
themselves prove cause and effect.
For example, consider the hypothesis:
"Driving ability varies with blood alcohol level".
The researcher would manipulate the amount of alcohol given to the drivers and then
observe changes in their driving skills. If all other variables are held constant, then any
changes in driving skill must be caused by the effects of the alcohol.
Consider an alternative means of collecting data. The researcher stands outside the pub
on Friday night and asks for volunteers leaving the pub. Each volunteer undergoes a
driving test and also has his/her blood alcohol level measured. The researcher then
compares the driving skills of volunteers with zero blood alcohol level to the driving
skills of those drivers whose alcohol level is over .05. This is an observational design.
The researcher is merely observing the blood alcohol level of each subject, rather than
controlling or manipulating it.
Experiment
An experiment is the device or the means of getting the answer to the problem under
investigation, e.g. comparison of different manures or fertilizers, different varieties of a
crop, different cultivation processes, or different diets or medicines in a dietary or medical
experiment.
An experiment is a planned inquiry to discover new facts, or to confirm or deny the
results of previous investigations (Petersen, 1985).
Nuisance variables
Nuisance variables are associated with variation in an outcome (dependent variable) that
is extraneous to the effects of independent variables that are of primary interest to the
researcher. In our description of an "ideal" experiment, we stated that "all other variables"
should be held constant. If, for example, we are interested in the effects of alcohol on
driving ability, then any other variable which may influence driving ability is known as a
nuisance variable. Such things as the type of car, the driving course, temperature,
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Module 2: Topic 1
humidity, time of day, and the driver's, age, reflexes and level of experience would all
have an influence on a driving test score. These are all referred to as nuisance variables.
Confounding variables
Variables that are not controlled for that systematically change experimental results, they
are called confounding variables. A confounding variable has two properties. First, a
confounding variable is related to the explanatory (independent) variable in the sense that
individuals who differ due to the explanatory variable are also likely to differ for the
confounding variable. Second, a confounding variable affects the response (dependent)
variable.
Suppose we are interested in the effects of alcohol on driving ability. If all of the zero
alcohol level driving tests were performed in the morning, and all of the .05 alcohol level
driving tests were completed in the evening, we could not tell if the resulting differences
in driving abilities were due to differences in the alcohol level, or if they were due to
differences in the time of day of the test. In this case, "time of day" is known as a
confounding factor, because it literally confounds our interpretation of the experiment.
Treatments
Various objectives of comparison in a comparative experiment, are known as treatments,
e.g., in field experimentation different fertilizers or different varieties of crop or different
methods of cultivation are treatments.
A treatment is one or a combination of categories of the explanatory variable(s) assigned
by the experimenter. The plural term treatments incorporates a collection of conditions,
each of which is one treatment.
Experimental Units
The individuals in an experiment are referred to as experimental units. The smallest
division of the experimental material, to which we apply the treatments and on which we
make observations on the variable under study, is termed an experimental unit.
Experimental units can be people, animals, batteries, etc. In field experiment the plot of
land is the experimental unit. In other examples may be a patient in a hospital, pigs in a
pen, or a batch of seeds. With animal trials, an experimental unit can be a paddock of
animals, a single animal, or even part of an animal.
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Blocks
In agricultural experiments, most of the time we divide the whole experimental unit
(field) into relatively homogenous sub-groups (shown in the following diagram) or strata.
These strata, which are uniform amongst themselves, are known as blocks. That means, a
block is a group of experimental units that are similar in a way that is expected to affect
the response to the treatments. A group of homogenous experimental units is called a
block.
The term blocking was first used by R. A. Fisher in agronomic experiments (1920). In the
statistical theory of the design of experiments, blocking is the arranging of experimental
units in groups (blocks) that are similar to one another. Typically, a blocking factor is a
source of variability that is not of primary interest to the experimenter. Blocking is
sometimes used for nuisance factors that can be controlled. Nuisance factors are those
that may affect the measured result, but are not of primary interest. For example, in
applying a treatment, nuisance factors might be the specific operator who prepared the
treatment, the time of day the experiment was run, or the room temperature. All
experiments have nuisance factors. The experimenter will typically need to spend some
time deciding which nuisance factors are important enough to keep track of or control if
possible, during the experiment.
Replication
Replication means the repetition of a test or an experiment more than once. In other
words, the repetition of treatments under investigation is known as replication.
Precision
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The reciprocal of the variance of the mean is termed as the precision, or the amount of
information of a design. Thus for an experiment replicated r times, the precision is given
by
1
r
= 2
var( x )
Experimental Error
Let us suppose that a large homogenous field is divided into different plots (of equal
shape and size) and different treatments are applied to those plots. If the yields from some
of the treatments are more than those of the others, the experimenter is faced with the
problem of deciding if the observed differences are really due to treatment effects or they
are due to chance (uncontrolled) factors. In field experiments, it is a common experience
that the fertility gradient of the soil does not follow any systematic pattern but behaves in
an erratic fashion. Experience tells us that even if the same treatment is used on all the
plots, the yields would still vary due to the differences in soil fertility. Such variation
from plot to plot, which is due to random (or chance or non-assignable) factors beyond
human control, is spoken of as experimental error. It may be pointed out that the term
error used here in not synonymous with mistake but is a technical term which includes
all types of extraneous variations due to:
(i)
the inherent variability in the experimental material to
which treatments are applied,
(ii)
the lack of uniformity in the methodology of conducting the
experiments, or in other words failure to standardise the
experimental technique, and
(iii)
lack of representativeness of the sample to the population
under study.
Blind Experiment
The blind method is a part of some scientific methods, used to prevent research outcomes
from being influenced by either the placebo effect or the observer bias. In a blind
experiment, the subjects do not know whether they are in the treatment group or the
control group. The idea is that the groups studied, including the control, should be
unaware of the group they are placed in. In medicine, when researchers are testing a new
medicine, they ensure that the placebo looks, and tastes, the same as the actual medicine.
There is strong evidence of a placebo effect with medicine, where, if people believe that
they are receiving a medicine, they show some signs of improvement in health. A blind
experiment reduces the risk of bias from this effect, giving an honest baseline for the
research, and allowing a realistic statistical comparison.
Ideally, the subjects should not be told that a placebo was being used at all, but this is
regarded as unethical.
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since these differences persist from year to year, the pattern of variability can be
mapped with a uniformity trial
Randomisation
Replication, and
Local Control or Error Control or Blocking.
The roles they play in data collection and interpretation are discussed below.
Randomisation
By randomisation we mean that both the allocation of the experimental material and the
order in which the individual runs or trials of the experiment to be performed, are
randomly determined. After the treatments and the experimental units are decided the
treatments are allotted to the experimental units at random to avoid any type of personal
or subjective bias which may be conscious or unconscious. This brings to the
experimenter the question of allocation of treatments to experimental units so that each
treatment gets an equal chance of showing its worth. In the absence of prior knowledge of
the variability of the experimental material, this objective is achieved through
randomisation, a process of assigning the treatments to various experimental units in a
purely chance manner. The following are the main objectives of randomisation:
(i)
To eliminate bias,
(ii)
To ensure independence among the observations.
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1. Unpredictability
Each participant has the same chance of receiving any of the interventions.
Allocation is carried out using a chance mechanism so that neither the
participant nor the investigator will know in advance which will be
assigned.
2. Balance
Treatment groups are of a similar size & constitution; groups are alike in all
important aspects and only differ in the intervention each group receives.
3. Simplicity
Easy for investigator/staff to implement.
Replication
As pointed out earlier, replication means the execution of an experiment more than once.
In other words, the repetition of treatments under investigation is known as replication.
An experimenter resorts to replication in order to average out the influence of the chance
factors on different experimental units. Thus, the repetition of treatments results in a more
reliable estimate than is possible with a single observation. Replication is necessary to
increase the accuracy of estimates of the treatment effects. Although, the more the
number of replications the better the estimate is, it cannot be increased indefinitely as it
increases costs of experimentation.
Replication serves a number of purposes in an experimental design:
(i)
(ii)
(iii)
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random within each block. The process of reducing the experimental error by dividing the
relatively heterogenous experimental area (field) into homogenous blocks is known as
local control.
Example 1.1
Consider the very simple agricultural problem of comparing two varieties of tomatoes.
The purpose of the comparison is to find the variety which produces the greater quantity
of marketable quality fruit from a given area for large scale commercial planting. What
should we do? A simple approach would be to plant a block of land of each variety and
measure the total weight of marketable fruit produced. However, there are some obvious
difficulties. The variety that cropped most heavily may have done so simply because it
was growing in better soil. There are a number of factors which affect growth: soil
fertility, soil acidity, irrigation and drainage, wind exposure, exposure to sunlight
(e.g. shading, north-facing or south-facing hillside). Unfortunately no one knows exactly
to what extent changes in these factors affect growth. So unless the two blocks of land are
comparable with respect to all of these features, we won't be able to conclude that the
more heavily producing variety is better as it may just be planted in a block that is better
suited to growth.
If it was possible (and it never will be) to find two tracts of land that were identical in
these respects, using just those two blocks for comparison would result in a fair
comparison but the differences found might be so special to that particular combination of
growing conditions that the results obtained were not a good guide to full scale
agricultural production anyway.
Why randomise? Let us think about it another way. Suppose we took a large block of
land and subdivided it into smaller plots by laying down a rectangular grid. By using
some sort of systematic design to decide what variety to plant in each plot, we may come
unstuck if there is a feature of the land like an unknown fertility gradient. We may still
end up giving one variety better plots on average. Instead, let's do it randomly by
numbering the plots and randomly choosing half of them to receive the first variety. The
rest receive the second variety. We might expect the random assignment to ensure that
both varieties were planted in roughly the same numbers of high fertility and low fertility
plots, high pH and low pH plots, well drained and poorly drained plots etc.
In that sense we might expect the comparison of yields to be fair. Moreover, although we
have thought of some factors affecting growth, there will be many more that we, and even
the specialist, will not have thought of. And we can expect the random assignment of
treatments to ensure some rough balancing of those as well!
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Module 2: Topic 1
because of the small variation in the fertility of the land we were using, the only thing that
we thought mattered greatly was drainage. We could then try and divide the land into two
blocks, one well drained and one badly drained. These would then be subdivided into
smaller plots, say 6 plots per block. Then in each block, 3 plots are assigned at random to
the first variety and the remaining 3 plots to the second variety. We would then only
compare the two varieties within each block so that well drained plots are only compared
with well drained plots, and similarly for badly drained plots. This idea is called blocking.
By allocating varieties to plots within a block at random we would provide some
protection against other extraneous factors.
Marketing Problems
Eventually, the primary aim of marketing is to calculate the upcoming market share net
sales, or profitability of an offering, thus, allowing a company to:
Foretell customer buying tendency
Boost customer retention
Ascertain trade-off strategies during contract negotiation
Ascertain competitive pricing
Predict sales
Control brand equity
Devise product elements
Establish price sensitivity
Forecast and reduce customer switch rates
Ascertain best market position for new product introductions.
Sample Survey
Experimental Design
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Module 2: Topic 1
Take measurements.
Allocate treatments.
Take measurements.
Experimental Design
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Pre-experimental planning.
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Module 2: Topic 1
Step 1: The first step for designing an experiment is to develop all ideas about the
objectives of the experiment. It is usually helpful to prepare a list of specific problems or
questions that are to be addressed by the experiment. A clear statement of the problem
often contributes substantially to better understanding of the phenomenon being studied
and the final solution of the problem. It is also important to keep an overall objective in
mind; for example, is this a new process or system-in which case the initial objective is
likely to be characterization or factor screening-or is it a mature or reasonably wellunderstood system that has been previously characterized-in which case the objective may
be optimization.
Step 2: In selecting the response variable, the experimenter should be certain that this
variable really provides useful information about the process under study. Most often, the
average or standard deviation (or both) of the measured characteristic will be the response
variable. Multiple responses are not unusual. It is usually critically important to identify
issues related to defining the responses of interest and how they are to be measured before
conducting the experiment.
Step 3: When considering the factors that may influence the performance of a process or
system, the experimenter usually discovers that these factors can be classified as either
potential design factors or nuisance factors. The potential design factors are those factors
that the experimenter may wish to vary in the experiment. Nuisance factors are often
classified as controllable, uncontrollable, or noise factors. Once the experimenter has
selected the design factors, he or she must choose the ranges over which these factors will
be varied and the specific levels at which runs will be made. We reiterate how crucial it is
to bring out all points of view and process information in steps 1 through 3. We refer to
this as pre-experimental planning.
Step 4: If the above pre-experimental planning activities are done correctly, this step is
relatively easy. Choice of design involves consideration of sample size (number of
replicates), selection of a suitable run order for the experimental trials, and determination
of whether or not blocking or other randomisation restrictions are involved. In Topic 2 we
discusses some of the important types of experimental designs for a wide variety of
problems. In selecting design, it is important to keep the experimental objectives in mind.
Step 5: When running the experiment, it is vital to monitor the process carefully to ensure
that everything is being done according to plan. Errors in experimental procedure at this
stage will usually destroy experimental validity. Up-front planning is crucial to success. It
is easy to underestimate the logistical and planning aspects of running a designed
experiment in a complex manufacturing or research and development environment. This
step suggests re-visiting the decisions made in steps 1-4, if necessary.
Step 6: Statistical methods should be used to analyse the data so that results and
conclusions are objective rather than judgemental in nature. If the experiment has been
designed correctly and performed according to the design, the statistical methods required
are not elaborate. Remember that statistical methods cannot prove that a factor (or
factors) has a particular effect. They only provide guidelines as to the reliability and
validity of results.
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Module 2: Topic 1
Step 7: Once the data have been analysed, the experimenter must draw practical
conclusions about the results and recommend a course of action. Graphical methods are
often used in this stage, particularly in presenting the results to others. Follow-up runs and
confirmation testing should also be performed to validate the conclusions from the
experiment.
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Revision Exercises
1.
2.
3.
4. In 1930, it was decided to carry out an experiment in Lanarkshire schools to assess the
possible beneficial effects of giving the children free milk during the school day. Twenty
thousand children took part and over the course of five months, February to June, half of
them had three-quarters of a pint of either raw or pasteurised milk while the remainder
did not have milk. All the children were weighed and had their heights measured before
and after the experiment, but contrary to expectation the average increase for the children
who had not had milk exceeded that for the children who had milk. This unexpected
result was later attributed to unconscious bias in the formation of the groups being
compared. In each school the division of the children into a "milk" or a "no-milk" group
was made either by ballot or by using an alphabetic system, but if the outcome appeared
to give groups with an undue preponderance of well-nourished or ill-nourished children,
some arbitrary interchange was carried out in an effort to balance them. In this
interchange the teachers must have unconsciously tended to put a preponderance of illnourished children into the group receiving milk. The results of the experiment were
further complicated by the fact that the children were weighed in their clothes and this
probably introduced a differential effect as between winter and summer and children from
poorer and wealthier homes. Because of the deficiencies in design the results of the
experiment were ambiguous despite the very large sample of children concerned.
(a)
(b)
(c)
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(d)
Module 2: Topic 1
5. From the shelf of a fresh juice shop, all the bottles of a certain brand of orange
juice on the shelf on a particular day were taken and analysed to observe the
vitamin C in orange juice. There were 21 bottles, and their vitamin C readings
(mg/100gm) were as follows:
15, 21, 20, 21, 18, 17, 15, 17, 13, 22, 23, 16,
13, 19, 23, 20, 25, 14, 26, 22, 23.
(a)
(b)
(c)
(d)
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Module 2: Topic 1
(A) What is the explanatory variable (IV) and what is the response variable
(DV)?
(B) Is this study an observational study or an experiment?
(C) Name one confounding variable that was controlled for in this study.
(D) Give two reasons why we must sometimes use an observational study
instead of an experiment.
10. A common mistake made by the media, the general public, and some researchers,
is to think that a link between two variables in any study implies that one variable
causes the other. Explain what is wrong with this automatic conclusion.
11. How can a researcher try to address the problem of confounding variables when
designing an observational study?
12. Explain why each of the following is used in experiments:
a) Placebo treatments
b) Blinding
c) Control groups.
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Module 2: Topic 1
Plant
Row-1
Row-2
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Row-3
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Single replication
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Module 2: Topic 1
Row-1
Row-2
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Row-3
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
3 replications
7. (C) This result is not valid because there was no control group for comparison.
8. Why randomisation?
The basic benefits of randomisation include
i. Elimination of selection bias.
ii. Formation of basis for statistical tests, a basis for an assumption-free statistical test of
the equality of treatments.
In general, a randomised trial is an essential tool for testing the efficacy of the treatment.
9. (A) Explanatory variable is Block Colour and response variable is Playing Time.
(B) An experiment.
(C) Any of the following: age, time of the day, other toys, interaction with other children
etc.
(D) 1) It is unethical or impossible in certain situations to assign people to receive a
specific treatment (such as smoking); 2) certain explanatory variables, such as left vs.
right handedness, are inherent traits and cannot be randomly assigned.
10. If the link is based on an observational study, there is simply no way to rule out all
potential confounding factors, so cause and effect cannot be established.
11. Measure all the potential confounding variables he/she can think of and include them
in the ANALYSIS to see whether they are related to the response variable; or use a casecontrol study and choose the controls to be as similar as possible to the cases.
12. a) The power of suggestion may lead to changes in the participants, and those changes
would be mistakenly attributed to the treatment or drug.
b) Participants are kept blind so they don't alter their behavior or outcome to please the
experimenter. Those collecting the measurements are kept blind so they don't
inadvertently bias the measurements in the desired direction.
c) Control groups are used to compare the effect of the treatment with what would have
happened under similar circumstances without the treatment.
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Module 2: Topic 1
References
Box G.E.P., Hunter W.G. & Hunter J.S. (2005). Statistics for Experimenters: Design,
Innovation and Discovery. 2nd edition. New York: Wiley.
Cox D.R. (1958). Panning of Experiments. New York: Wiley.
Das M.N. & Giri N.C. (1986). Design and Analysis of Experiments. 2nd edition. New
Delhi: Wiley Eastern Ltd.
Dawson B. & Trapp R.G. (2004). Basic and Clinical Biostatistics. New York: McGrawHill.
Edwards T. (2008). Research Designs and Statistics. New York: McGraw-Hill.
Gupta S.C and Kapoor V.K. (1984). Applied Statistics. Sultan Chand & Sons, New Delhi.
Hinkelmann, K. and Kempthorne, O. (2008). Design and Analysis of Experiments, John
Wiley & Sons, Inc.
Jones B. & Kenward M.G. (2003). Design and Analysis of Crossover Trials. 2nd edition.
London: Chapman & Hall.
Montgomery D.C. (2005). Design and Analysis of Experiments. 6th edition. New York:
Wiley.
Petersen, R.G. (1985). Design and Analysis of Experiments. New York: Marcel Dekker,
INC.
Utts J.M. (2005). Seeing Through Statistics. Third Edition. Brooks/Cole Cengage
Learning, CA, USA.
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Module 2: Topic 2
Dr Amirul Islam
Module 2: Topic 2
Contents
14
17
19
20
Revision Exercises
21
22
References
23
Note: Some of the materials are adapted from standard texts and guides (see references).
Module 2: Topic 2
Module 2: Topic 2
Method 1:
1. Obtain 20 identical pieces of paper (this is the experimental unit). Label five of
them Treatment A, five of them Treatment B, five of them Tret C and five
of them Tret D.
2. Place the pieces of paper in a box and mix thoroughly.
3. Pick a piece of paper at random. The treatment named on this piece is assigned to
experimental unit 1.
4. Without returning the first piece of paper to the box, select another piece. The
treatment named on this piece is assigned to experimental unit 2.
5. Continue this way until all 20 pieces of paper have been drawn.
6. This is just an example, the allocation will vary according to what you get
randomly.
Treatment
Experimental Unit
Treatment A
Treatment B
10
Treatment C
11
12
13
14
15
Treatment D
16
17
18
19
20
Module 2: Topic 2
Values
Data
Sort
Experimental Unit
Total 5 units
in each
treatment
Treatment A
20
16
13
Treatment B
10
12
19
17
Treatment C
15
Treatment D
Module 2: Topic 2
18
14
11
2.3.1 Analysis
A completely randomised design provides a one-way classified data according to levels of
a single factor, treatment. The data from this design can be analysed by a one-way
analysis of variance (ANOVA). The ANOVA results help us to answer the following:
How much variation is due to differences between treatments?
How much variation is due to differences within each set of observations for the
same treatment?
It provides solution of the hypotheses to test if there is any difference across the
treatments, i.e., Treatment A vs. Treatment B and so on.
yij = + i + eij ;
Where yij is the yield or response from the jth unit receiving the ith treatment, is the
general mean effect, i is the effect due to the ith treatment, and eij is the error component
due to chance. The error components are assumed to be independently and normally
distributed with 0 mean and constant variance 2.
The general form of the ANOVA table for a completely randomised design with p
treatments each replicated r times with N (rp) experimental units is given below.
Table 2.1: ANOVA for CRD
Source of
variation (SV)
Degrees of
freedom (df)
Sum of
Mean square
squares (SS) (MS)
F Statistic
Treatment
p-1
SST
MST=SST/(p-1)
FT=MST/MSE
Error
N-p [N-1-p+1,
i.e., total df
treatment df]]
SSE
MSE=SSE/(N-p)
Total
SSTot
N-1
SST= Between treatments sum of squares (or between groups sum of squares) which is
the sum of squares of the differences between the treatment means and the overall mean.
Module 2: Topic 2
SSE= Residual sum of squares or error sum of squares (or within groups sum of squares)
which is the sum of the squares of the differences between the observations and their
respective treatment means.
SSTot= Total sum of squares which is the sum of the squares of the differences between
the observations and the overall mean. Note that SSTot=SST+SSE.
In this design the total variation is partitioned into two components:
(a) Variation among treatment means (treatments).
(b) Variation among units within treatments (error).
Example 2.1
The following table shows some of the results of an experiment on the effect of
applications of sulphur [S3, S6, S12] in reducing scale disease of potatoes. The object in
applying sulphur is to increase the acidity of the soil since scale does not thrive in very
acid soil. In addition to untreated plots which serve as controls [O]- 3 [F3, F6, F12]
amounts of dressing are compared-300, 600 and 1200 lb. per acre. Both a spring and fall
application of each treatment was tested so that in all there were seven distinct treatments.
Field plan and scale indices for a completely randomized experiment on potatoes
F3
S6
F12
S6
S12
S3
F6
12
18
10
24
17
30
16
S3
F12
F6
S3
S6
10
10
21
24
29
12
F3
S12
S6
F6
S12
F3
F12
18
30
18
16
16
S3
S12
S6
F12
F3
18
17
19
32
26
F3
S3
F6
S6
F12
S12
12
30
30
16
18
10
17
10
18
10
24
24
32
16
21
18
12
16
29
26
18
19
17
Totals
181
38
67
62
73
23
57
Means
22.6
9.5
16.8
15.5
18.2
5.8
14.2
Module 2: Topic 2
Figure 2.1: Mean (acidity level) plots for Sulphur (S3, S6 and S12:treatment) and
controls (O, F3, F6 and F12)
The figure shows the highest mean acidity level for control O but in general application
of sulphur increased the acidity level, especially the mean deferences were higher in case
of S3 vs F3 and S12 vs F12.
Japanese
Chinese
14.20
12.85
14.15
14.30
13.65
13.90
15.00
13.40
13.65
14.60
14.20
13.60
14.55
12.75
13.20
15.15
13.35
13.20
14.60
12.50
14.05
14.55
12.80
13.80
Module 2: Topic 2
Total:
116.95
105.50
109.55
Mean:
14.619
13.188
13.694
Grant mean
13.83
d.f.
SS
MS
Race (Treatment)
3-1=2
8.43
4.21
23.39
Error
24-3=21
3.84
0.18
Total
24-1=23
12.27
Calculations:
Error sum square calculation
(14.2-14.619)2+..+(14.55-14.619)2+(12.8513.188)2+..+(13.80-13.694)2= 3.84
Sum square total = (14.2-13.83)2+(13.80-13.83)2=12.27
In this case, (every treatment units grant total)2
Sum square treatment = SS total SS error = 12.27-3.84 = 8.43.
In case of CRD, the total variation is due to treatment and error.
Module 2: Topic 2
If we do the analysis in SPSS, then the data entry should be like this.
df
Mean Square
Between Groups
8.428
4.214
Within Groups
3.841
21
.183
12.268
23
Total
F
23.041
Sig.
.000
10
Module 2: Topic 2
Descriptives
Headwidth
N
Mean
Std. Deviation
Caucasian
14.6188
.31953
Japanse
13.1875
.56553
13.6938
.35601
24
13.8333
.73035
Chinese
Total
The design is very flexible. Any number of treatments can be used and
different treatments can be used unequal number of times without unduly
complicating the statistical analysis in most of the cases. The number of
replications need not be the same from one treatment to another, although
comparisons are most precise when the treatments are equally replicated.
(ii)
The statistical analysis remains simple if some or all the observations for
any treatment are rejected or lost or missing for some purely random
accidental reasons. Moreover the loss of information due to missing data
is smaller in comparison with any other design.
(iii) The design provides maximum degrees of freedom for the estimation of
the error variance, which increases the sensitivity or the precision of the
experiment for small experiments, i.e., for experiments with small
number of treatments.
(iv) This design results in the maximum use of the experimental units since all
the experimental material can be used.
11
Module 2: Topic 2
(ii)
(iii) This design may be useful for experiments in which the total number of
units is limited.
12
Module 2: Topic 2
improvement of CRD obtained by providing error control measures. The error control
measures in RBD consist of making the units in each of these blocks homogenous.
Layout of RBD: In the RBD the experimental units are first grouped into blocks or
strata. Treatments are then randomly assigned to the units within the blocks. A separate
randomisation is used in each block. To illustrate the procedure, suppose we want to run
an experiment with five treatments (A, B, C, D and E) replicated four times in an
agricultural field with a fertility gradient (see Petersen R.G, 1985, p. 36). We construct a
RBD using the following steps:
BLOCK
I
II
III
IV
Treatment A
Treatment B
Treatment C
Treatment D
Treatment E
GRADIENT
Figure 2.3: Assignment of numbers to units blocked to remove effects of a gradient
Step 1: Form four blocks of five plots each perpendicular to the gradient. Number the
plots from 1 to 5 within each bock as shown in Figure 2.3.
Step 2: Use a table of random numbers or some other procedure (e.g. using EXCEL), to
assign treatments to the units in the first block. To illustrate for
Block I:
Sequence Treatment
Random number
(generated in Excel)
Random No
sorted and
ranked the plot
Treatment
according to the
rank, e.g., 1=A,
2=B, 3=C, 4=D,
5=E
078 (smallest) =1
721 (largest)=5
13
Sequence
Module 2: Topic 2
Random number
Rank (plot)
Treatment
962
036
844
963
097
Block III
Sequence
Random number
Rank (plot)
Treatment
675
936
709
591
665
Block IV
Sequence
Random number
Rank (plot)
Treatment
230
981
687
604
454
Treatment
II
III
IV
14
Module 2: Topic 2
Figure 2.4: Final experimental plan with treatments randomly assigned to units within
blocks in a RBD
Example 2.3
Suppose we are interested in how weight gain (Y) in rats is affected by source of protein
(Beef, Cereal, and Pork) and by level of protein (High or Low). There are a total of 6
(3x2) treatment combinations of the two factors (Beef -High Protein, Cereal-High
Protein, Pork-High Protein, Beef -Low Protein, Cereal-Low Protein, and Pork-Low
Protein) . Suppose we have available to us a total of N = 66 experimental rats to which
we are going to apply the different diets based on the t = 6 treatment combinations. Prior
to the experimentation the rats were divided into n = 11 homogeneous groups of size 6.
The grouping was based on factors that had previously been ignored (Example - Initial
weight size, appetite size etc.). Within each of the 11 blocks a rat is randomly assigned a
treatment combination (diet). The weight gain (in grams) after six month is measured for
each of the test animals and is tabulated in the following table.
Block
1
107
(1)
96
(2)
112
(3)
83
(4)
87
(5)
90
(6)
98
(1)
72
(2)
101
(3)
82
(4)
70
(5)
94
(6)
102
(1)
76
(2)
101
(3)
85
(4)
95
(5)
97
(1)
70
(2)
93
(3)
65
(4)
109
(1)
79
(2)
101
(3)
101
70
(1)
(2)
Block
7
128
(1)
89
(2)
104
(3)
85
(4)
84
(5)
89
(6)
56
(1)
70
(2)
71
(3)
64
(4)
62
(5)
67
(6)
89
(6)
99
(1)
91
(2)
92
(3)
80
(4)
71
(5)
85
(6)
71
(5)
61
(6)
10
82
(1)
63
(2)
87
(3)
87
(4)
81
(5)
61
(6)
75
(4)
75
(5)
81
(6)
11
101
(1)
102
(2)
110
(3)
83
(4)
93
(5)
83
(6)
98
82
77
79
(3)
(4)
(5)
(6)
Example 2.4
A group of researchers are interested in comparing the effects of four different chemicals
(A, B, C and D) in producing water resistance (y) in textiles. A strip of material,
randomly selected from each bolt, is cut into four pieces (samples) the pieces are
randomly assigned to receive one of the four chemical treatments. This process is
replicated three times producing a Randomised Block (RB) design. Moisture resistance
(y) was measured for each of the samples. (Low readings indicate low moisture
penetration). The data is given below.
C
A
B
D
13.4
12.9
12.2
12.3
D
B
A
C
12.7
12.9
11.4
11.9
B
D
C
A
Completed Design
Course notes STA60004
15
Module 2: Topic 2
Example 2.5
An experiment was carried out on wheat. Three varieties of wheat A, B, C were tested for
their yield in four randomised blocks. Each of four blocks were divided into three plots
and plots of each block were assigned at random to the three varieties. The plan and yield
per plot in kg are given below:
Block 1
A
8
C
12
B
10
Wheat yield
A
B
C
Block 2
C
10
B
8
A
8
Block 3
A
6
B
9
C
10
Block 1
8
10
12
Block 2
8
8
10
Block 4
B
10
A
8
C
9
Block 3
6
9
10
Block 4
8
10
9
Example 2.6
A researcher is carrying out a study of the effectiveness of four different skin creams for
the treatment of a certain skin disease. He has eighty subjects and plans to assign them
into 4 treatment groups of twenty subjects each. Using a randomised block design, the
subjects are assessed and put in blocks of four according to how severe their skin
condition is; the four most severe cases are the first block, the next four most severe cases
are the second block, and so on to the twentieth block. The four members of each block
are then randomly assigned, one to each of the four treatment groups.
(Example taken from Valerie J. Easton and John H. McColl's Statistics Glossary).
2.4.1 Analysis
If in an RBD a single observation is made on each of the experimental units, then the data
from an RBD can be analysed by a two-way ANOVA. In this design the ANOVA enables
us to partition the total variation into blocks, treatments and error. A randomised block
experiment is assumed to be a two-factor experiment. The factors are blocks and
treatments.
An appropriate linear statistical model for RBD is
Response = general mean effect (overall mean)+ treatment effect + block effect + error
Course notes STA60004
16
Module 2: Topic 2
yij = + i + b j + eij ;
Where yij is the yield or response of experimental unit from ith treatment and jth block,
is the general mean effect, i is the effect due to the ith treatment, bj is the effect due to jth
block or replicate and eij is the error component due to chance. The error components are
assumed to be independently and normally distributed with 0 mean and constant variance
2 .
The general form of the ANOVA table with p treatments each replicated r times in a
randomised block design with r blocks of p units each, is given below.
Table 2.2: ANOVA for RBD
Source
of Degrees
variation (SV)
freedom (df)
of Sum
of Mean square (MS)
squares (SS)
Treatment
p-1
SST
MST=SST/(p-1)
Block
r-1
SSB
MSB=SSB/(r-1)
Error
(p-1)(r-1)
SSE
MSE=SSE/(p-1)(r-1)
Total
rp1
SSTot
F Statistic
FT=MST/MSE
Analysis output using SPSS from example 2.5 (four blocks and 3 varieties of wheat)
Analysis summary
17
Module 2: Topic 2
Between-Subjects Factors
Value Label
BLOCK
TREATNUM
18
Module 2: Topic 2
Squares
df
Mean Square
Sig.
Corrected Model
26.000
11
2.364
Intercept
972.000
972.000
BLOCK
TREATNUM
BLOCK *
TREATNUM
4.667
1.556
15.500
7.750
5.833
.972
Error
.000
Total
998.000
12
26.000
11
Corrected Total
19
Module 2: Topic 2
Row
1
2
3
1
A
B
C
Column
2
B
C
D
3
C
D
E
4
D
E
A
5
E
A
B
20
Module 2: Topic 2
4
5
D
E
E
A
A
B
B
C
C
D
Example 2.7
An experiment was conducted to compare the effectiveness of four types of food
supplements for increasing the milk yield of dairy cows in a farm. The supplements (A,
B, C and D) were given to four cows, and repeated in four successive time periods while
rotating the cows. Milk yields, in grams/day, are recorded. The cow (1, 2, 3 or 4) was one
blocking factor and the time period (I, II, III or IV) was the other. The plan and yields are
given in the following table:
Cow
I
A
882
B
1078
C
702
D
690
1
2
3
4
II
B
605
C
705
D
659
A
789
Time Period
III
C
947
D
712
A
824
B
930
IV
D
772
A
756
B
644
C
762
Example 2.8
An experiment was conducted to compare the effectiveness of five manorial treatments
A, B, C, D and E on the yield of sugarcane (in kg/plot). The following are the results of
the Latin Square experiment.
B
405
C
325
E
471
A
552
D
430
A
525
D
445
B
492
C
431
E
469
E
463
B
429
A
472
D
425
C
432
D
441
A
513
C
381
E
572
B
467
C
481
E
493
D
410
B
410
A
460
21
Module 2: Topic 2
measured. The experimental layout and strength measurements were as shown in the
following table:
Front
Top
Bottom
A
33.8
D
35.0
C
35.8
E
33.2
B
34.8
Back
B
33.7
E
28.8
D
35.6
A
37.1
C
39.1
D
30.4
B
33.5
A
36.9
C
37.4
E
32.7
C
32.7
A
26.7
E
26.7
B
38.1
D
37.4
E
24.4
C
33.4
B
35.1
D
34.1
A
36.4
2.5.1 Analysis
In Latin square design there are three factors: row, column and treatment. The data
collected from this design can be analysed by a three-way ANOVA.
An appropriate linear statistical model for the ith row, jth column and the pth treatment
is:
Response = general mean effect (overall mean) + row effect + column effect + treatment
effect + error
yijk = + ri + c j + k + eijk ;
i=j=k=1,2,,p.
Where yijk is the yield or response of experimental unit from ith row, jth column and kth
treatment, is the general mean effect, ri is the effect due to the ith row, cj is the effect
due to jth column and k is the effect due to kth treatment and eijk is the error component
due to chance. As usual the error components are assumed to be independently and
normally distributed with 0 mean and constant variance 2.
The general form of the ANOVA table for a Latin square design with p treatments is
presented in the following table.
Table 2.2: ANOVA for RBD
Source
of Degrees
variation (SV)
freedom (df)
of Sum
of Mean square (MS)
squares (SS)
F Statistic
Rows
p-1
SSR
MSR=SSR/(p-1)
FR=MSR/MSE
Columns
p-1
SSC
MSC=SSC/(p-1)
FC=MSC/MSE
Treatment
p-1
SST
MST=SST/(p-1)
FT=MST/MSE
Error
(p-1)(p-2)
SSE
MSE=SSE/(p-1)(p-1)
22
Total
P2--1
Module 2: Topic 2
SSTot
Degrees of freedom for Error: (P2-1) - (p-1) (p-1) (p-1) = (P2-1- p+1 p+1 p+1)
=(P2-p 2p +2) = p(p-1)-2 (p-1) = (p-1)(p-2) [common: p-1 p-2: uncommon]
23
Module 2: Topic 2
factors and also the interaction effects, i.e., the variation in the effect of one factor as a
result of different levels of other factors.
As a simple illustration let us consider two fertilizers (independent variables), say, Potash
(K) and Nitrogen (N). Let us suppose that there are three different varieties of Potash and
four different varieties of Nitrogen, three and four are termed as levels of the factors
Potash and Nitrogen respectively. To find the effectiveness of various treatments, e.g.,
different levels of Potash or Nitrogen we might conduct two simple experiments, one for
Potash and the other for Nitrogen. A series of experiments in which only one factor is
varied at a time would be both lengthy and costly and might still be unsatisfactory
because of systematic changes in the general background conditions. Moreover, these
simple experiments do not give us any information regarding the dependence or
independence of one factor on the other, i.e., they do not tell us anything about the
interaction effect (PotashNitrogen). The only alternative is to try to investigate the
variation in several factors simultaneously by conducting the above experiment as a 34
factorial experiment, where 3 and 4 are the levels of factors Potash and Nitrogen
respectively. Factorial experiments are ones in which two or more independent variables
are manipulated systematically.
In factorial experiments combinations of two ore more levels of more than one factor are
the treatments. For example, with two factors (i) nitrogen fertilizer at three levels,
denoted by n0, n1 and n2 and (ii) irrigation at two levels, I0 and I1 in an agricultural
experiment we can form the following six treatment combinations taking one level from
each factor I0n0, I0n1, I0n2, I1n0, I1n1 and I1n2. Such combinations form treatments in factorial
experiments.
Factorial designs have several advantages over single factor designs. It is more efficient to
collect information of the effects of two or three independent variables in one experiment,
rather than to run a separate experiment for each factor. Also factorial designs allow us to
investigate interactions between independent variables.
In factorial design each complete trial or replication of the experiment and all possible
combinations of the levels of the factors, are investigated. When factors are arranged in a
factorial design, they are often said to be crossed. The effect of a factorial design is
defined as the change in response produced by a change in the level of the factor which is
called the main effect. For example, consider the following simple experiment taken from
Montgomery (2009). This is a two-factor factorial experiment with both design factors at
two levels. We have called these levels low and high and denoted them - and +,
respectively.
+
(High)
30
+
(High)
52
40
12
20
50
Factor B
Factor B
(Low)
(Low)
20
40
(Low)
+
(High)
(Low)
Factor A
Course notes STA60004
+
(High)
Factor A
24
Module 2: Topic 2
The main effect of factor A in this two-level design can be thought of as the difference
between the average response at the low level of A and the average response at the high
level of A. Numerically, this is
A=
40 + 52 20 + 30
= 21 .
2
2
That is, increasing factor A from the low level to the high level causes an average
response increase of 21 units. Similarly, the main effect of B is
30 + 52 20 + 40
= 11 .
2
2
In some experiments, we may find that the difference in response between the levels of
one factor is not the same at all levels of the other factors. When this occurs, there is an
interaction between the factors.
B=
No baking powder
Baking powder
0%
3.9
3.3
3.5
3.7
4.1
3.9
3.8
4.1
5%
4.1
4.0
4.3
4.4
4.2
4.2
3.9
4.5
10%
4.3
4.4
4.5
4.6
4.4
4.5
4.3
4.6
15%
4.7
4.6
4.7
5.0
4.5
4.5
4.4
4.7
25
Module 2: Topic 2
Example: Suppose we have five different machines making the same part and each
machine has two operators, one for the day shift and one for the night shift. We take five
samples from each machine for each operator to obtain the following data:
Machine
1
Advantages of nested design: A nested design is recommended for studying the effect of
sources of variability that manifest themselves over time. Data collection and analysis are
straightforward, and there is no reason to estimate interaction terms when dealing with
time-dependent errors. Nested designs can be run at several levels. In nested designs,
carry over effects are not a problem, as individuals are measured only once.
26
Module 2: Topic 2
Example
An educational psychologist was interested in examining the effects of a program
designed to improve the attentiveness of children in primary school classes. In a random
sample of 120 primary school aged children, attentiveness was measured at the start of the
year (before the program started), and on three other occasions throughout the year after
3 months, after 6 months and after 12 months. The psychologist expected that
attentiveness would improve after the program commenced, and would continue to
improve throughout the year. Attentiveness was measured on a metric scale taking values
from 0 to 50, with higher values representing greater attentiveness.
27
Module 2: Topic 2
Revision Exercises
1. To test the effect of small proportions of coal in sand for manufacturing concrete,
several batches were mixed under particularly identical conditions except for the
variation in the percentage of coal. From each batch, several cylinders were made
and tested for breaking strength. The results obtained are shown below. (Taken
from Gupta & Kapoor (1984)).
.00
1690
1580
1745
1685
(i)
(ii)
(iii)
(iv)
0.05
1550
1445
1645
1545
Percentage of coal
0.10
1625
1450
1510
-
0.50
1725
1550
1430
1445
1.00
1530
1545
1665
1520
2. A plum orchard has 24 trees set aside for an experiment which aims to examine
the effect of mulching on tree growth. There are 4 mulching treatments: (A)
Control (no mulch); (B) Wood chips; (C) garden compost; and (D) Clippings from
own collection. The trees are in a 46 rectangle. The ground slopes down from the
left to the right.
What is the experimental unit?
(i)
(ii)
What type of design is used?
(iii)
If it is a randomised block design, state the blocking factor.
28
Module 2: Topic 2
(v)
(i) The experimental unit is a participant.
(ii) Repeated measures design.
(iii) Participants practiced the task until they had reached a consistent level of
performance. Also, participants performed the three conditions in different orders.
(iv) Noise condition affects the number of errors made on a perceptual task.
29
Module 2: Topic 2
References
Box, G.E.P., Hunter, W.G. & Hunter J.S. (2005). Statistics for Experimenters: Design,
Innovation and Discovery. 2nd edition. New York: Wiley.
Cox, D.R. (1958). Panning of Experiments. New York: Wiley.
Das, M.N. & Giri, N.C. (1986). Design and Analysis of Experiments. 2nd edition. New
Delhi: Wiley Eastern Ltd.
Dawson, B. & Trapp, R.G. (2004). Basic and Clinical Biostatistics. New York: McGrawHill.
Jones, B. & Kenward, M.G. (2003). Design and Analysis of Crossover Trials. 2nd edition.
London: Chapman & Hall.
Mead, R. (1988). The Design of Experiments. Cambridge University Press, Cambridge.
Montgomery, D.C. (2005). Design and Analysis of Experiments. 6th edition. New York:
Wiley.
Petersen, R.G. (1985). Design and Analysis of Experiments. New York: Marcel Dekker,
INC.
30
Module 2: Topic 3
Dr Amirul Islam
Semester 1, 2015
Module 2: Topic 3
Contents
3.3 Definitions
Revision exercises
12
16
References
19
Note: Some of the materials are adapted from standard texts and guides (see references).
Semester 1, 2015
Module 2: Topic 3
3.3 Definitions
Some key health statistics definitions are as follows. Note that there is a
distinction between rate and risk which are often confused. A risk is a
proportion and a rate is a measure over time.
In morbidity statistics, there are both measures of risks and rates.
Numerator
Population
Morbidity
Mortality
Death
Risk (%)
Semester 1, 2015
Module 2: Topic 3
Rate
Ratio
Number of cases/population
Mid-year population
Time measure
Further Notes
A proportion is a dimensionless number between 0.0 and 1.0 (if a probability) or,
equivalently, between 0% and 100% (if a percentage) consisting of one count as
the numerator divided by another count as the denominator. Note that for
consistent, unbiased interpretation, 1) all the individuals in the numerator must
also be included in the denominator, 2) each individual in the denominator must
be at risk of being in the numerator, and 3) all the individuals at risk of being in
the numerator in a group must be in the denominator.
A ratio is a value obtained by dividing the numerator by the denominator. The
numerator and denominator do not have to be related to each other. For example,
if there were 10 smokers and 500 non-smokers in a factory, then the ratio of
smokers to non-smokers would be 10/500 = 0.02 or 1:50. Similarly, the ratio of
females and males in a classroom of 25 boys and 5 girls is 25: 5 or 5: 1.
Semester 1, 2015
Module 2: Topic 3
Cause is the combination of necessary and sufficient factors (e.g., attributes and
exposures) the presence of which, alone or in combination, at some time during an
individuals life, inevitably result in disease in that individual.
Surveillance
Surveillance is a continuous and systematic process of collection, analysis,
interpretation and dissemination of descriptive information for monitoring health
problems (World Health Organisation). Surveillance systems are networks of
people and activities that maintain this process and may function at a range of
levels, from local to international.
There are essentially three types of surveillance system:
Semester 1, 2015
Module 2: Topic 3
Incidence
Incidence is the number of new cases of disease within a defined population
during a specified time period. Examples of incidence is the number of new cases
of lung cancer diagnosed in Australia in year 2003; or number of new cases of
HIV positives diagnosed in Victoria in year 2003.
The incidence rate (IR) is defined as the number of newly reported cases of a
given disease in a Calendar year, divided by the mid year population, the quotient
being multiplied by a convenient factor, usually 1000, 100,000, or 1,000,000.
People talk of two different types of incidence:
Cumulative incidence and
Incidence density
The difference between them relates to the way in which they are
measured.
Cumulative incidence (CI)
Defined as the total number of people who became diseased during a specified
period of time. Cumulative incidence provides an estimate of the probability or
risk that an individual will develop a disease during a specified period of time.
CI =
The cumulative incidence assumes that the entire population at risk has been
followed for the entire specified period of time. For example, if 1000 coal miners
were followed-up for 10 years and 200 of them were found to develop lung
cancer, then the cumulative incidence for lung cancer would be (200/1000) = 20%
over a 10 year observation period (note that the period of observation is
specified). However, not all studies are designed like this. For instance, most
participants in follow-up studies enter the study over a period of time, often over
several years. Others will become lost to contact during the follow-up period so
Semester 1, 2015
Module 2: Topic 3
that their information is not available at the end of the study. The length of time of
the study or follow-up will therefore not be the same for each participant.
Incidence density (ID)
Incidence density accounts for the varying time periods of follow-up and thus
maximizes whatever data is available for each person to examine the occurrence
of new disease. Incident density is given by the formula:
ID =
Example:
90
91
92
93
94
95
96
97
98
99
Sub A
Time
at risk
6.0
Sub B
6.0
Sub C
11.0
Sub D
9.5
Sub E
Total years at risk
00
5.0
37.5
Time followed
Disease onset
The figure provides data concerning five subjects who have a given disease in a
defined population. Each person is followed-up for varying periods of time
between 1990 and 2000, with two people developing the disease of interest.
Subject A was followed-up for 6 years (1990 to 1995), subject B for 6 years (1992
to 1997) until diagnosed with the disease, subject C for 11 years, subject D for 9.5
years and subject E for 5 years before being diagnosed. Therefore, the incidence
density is:
ID =
2 new cases
37.5 disease_free yrs
(person_yrs of observation)
Semester 1, 2015
Module 2: Topic 3
Prevalence
Prevalence is defined as the number of affected persons in the population at a
specific time divided by the number of persons in the population at that time. It is
given by the formula:
Examples include the percentage of children with skin cancer when tested at
school entry in 2003 and proportion of people with lung cancer in Australia.
There are two types of prevalence.
Point prevalence
Defined as the number of persons (old and new) in a defined population who have
a specified outcome (e.g. disease) at a single point in time. Example: number of
women in a maternity ward in The Royal Childrens Hospital giving birth right
now!!!.
Period prevalence
Defined as the number of persons who had the disease at any time during the
specified time interval. Example: number of women in the maternity ward giving
birth at any time during the month December 2003.
Note that the period prevalence is the combination of point prevalence and
incidence. Some articles in the literature will discuss period prevalence which is
the sum of the point prevalence at the beginning of the interval plus the incidence
during the interval.
Semester 1, 2015
Module 2: Topic 3
Type
Disease
Measure
Definition
Risk
Existing
Point
prevalence
Risk
New
Cumulative
incidence
Risk
Existing
and new
Period
prevalence
Rate
New
Incidence
rate (or
density)
Tell us how many times more likely it is that someone who is exposed to a risk
factor will experience a particular health outcome than someone who is not
exposed
Do not tell us anything about the actual amount of disease occurring in either
group
IRe
Incidence Rate in exposed
=
Incidence Rate in unexposed
IRo
Cumulative Incidence in exposed
Risk Ratio =
=
Cumulative Incidence in unexposed
Pe
Prevalence in exposed
Prevalence Ratio =
=
Prevalence in unexposed
Po
Rate Ratio
3.8
CI e
CI o
Semester 1, 2015
Module 2: Topic 3
Tells us how much extra disease is occurring among those exposed to something
compared to those who are unexposed
How much disease among those who are exposed that could potentially be
prevented by removing the exposure
Attributable Risk
Attributable Fraction
Tells us the proportion of disease in those exposed that can be attributed to the
exposure
Attributable Risk
100
Incidence in exposed
IRe
IRo
330
30
= 11.0
Semester 1, 2015
10
Module 2: Topic 3
The rate ratio tells us the rate of type-2 diabetes is 11 times higher among people
who are obese than among non-obese people
Crude Birth Rate (CBR): This rate reflects the number of births in a defined
population during a specified periodusually a yeardivided by the midyear
(July 1) population, the quotient being multiplied by 1000. Because of variations
in age composition and other factors, crude rates are seldom useful for
comparisons.
For example: In 1986 the mid-year (July 1) Australian population was
15,602,156 and 243,408 live birth were recorded. So, crude birth rate
CBR=
243, 408
1000
15, 602,156
=15.6 live births per 1000 population per year.
General Fertility Rate (GFR): The general fertility rate is defined as the
number of live births in a calendar year, divided by the number of women ages
15-44 (or 15-49) at midyear, the quotient being multiplied by 1000.
For example: In US, 1987-live births: 3,829,000; number of women aged
15-44: 58,012,000; neonatal deaths: 2780.
GFR= 3829000 1000
58012000
=66 live births per 1000 women ages 15-44 per year.
This rate is more sensitive than CBR.
Semester 1, 2015
11
Module 2: Topic 3
Example: In a specific state in US, 36,000 live births in 2008 among state
resident women who are 20-24 years old and 310,000 state resident women who
are 20-24 years old in 2008. The age-specific birth rate (ASBR) for the age group
20-24 is (36,000/310,000) x 1000 = 116.1 live births per 1000 state resident
women who are 20-24 years old in 2008.
Birth in
2000
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
300*
11,000
20,000
22,000
20,000
10,000
2,000
500*
Female
Population in 2000
165,000
179,000
192,000
222,000
213,000
212,000
210,000
200,000
(grossly rounded)
ASBR
1.8
61.5
104.2
99.1
93.9
47.2
9.5
2.5
Semester 1, 2015
12
Module 2: Topic 3
Revision Exercise
2. Indicate which type of measure of disease frequency best describes each of the
following scenarios?
i. Percentage of students enrolled in a postgraduate course who
developed influenza during the mid-term exam.
ii. Percentage of students enrolled in an epidemiology class who had
sore throats on the first day of class
iii. Percent of breast cancer patients who underwent mastectomy
during year 2003.
iv. Percent of men found to have high cholesterol level at their yearly
physical examination.
v. Number of newly diagnosed cases of SARS in a year per 1 million
persons.
vi. Percent of drivers found to be legally drunk at the time of their car
accident.
vii. A group of 1000 children who were free of asthma were followedup for 5 years. The rate of developing asthma in this group was 10
per 1000 person years.
viii. A study was carried out to examine the health status of the elderly
in the Ivanhoe nursing home on the 10th of June 2003. 13% of the
subjects in the nursing home had high blood pressure.
3. Suppose that you want to estimate the average duration of a disease from its onset
to death or cure. Which two measures of disease frequency do you need to know
in order to calculate your estimate?
Semester 1, 2015
13
Module 2: Topic 3
4. A study was carried out to compare the risk of coronary heart disease (CHD)
between pre- and post-menopausal women and the results are tabulated below.
Post-menopause
Pre-menopause
(a)
Cases
32
10
Calculate the risk of CHD in both pre- and post -menopause groups.
(c)
(b)
(c)
6. Questions 6 & 7 are taken from Morton RF, Hebel, JR & McCarter RJ (2001). A
Study Guide to Epidemiology and Biostatistics, 5th ed.
From the data in the table below, compute the average duration, in
years, of the five chronic neurological conditions listed.
Table: Prevalence and incidence of selected Neurological diseases
in Rochester
Disease
Epilepsy
Multiple sclerosis
Parkinsons disease
Motor neuron disease
Central nervous system neoplasms
Semester 1, 2015
14
Module 2: Topic 3
7. Assume that the prevalence of coronary heart disease decreases after age 70,
while its incidence continues to increase with age. What is the most probable
explanation for the divergence of these rates?
Epidemiology, 3rd
(c) What was the cumulative incidence of disease during the 1year follow-up period?
9. Calculate the 1986 birth rate for the Australian population if 243,408 live births
were recorded and the mid-year population was 15,602,156.
Semester 1, 2015
15
Module 2: Topic 3
10. The following table gives the female population of an Indian city for the year
1975, together with the estimated number of births based on a special vital
statistics enquiry conducted in that city.
Number of women
(000)
Number of births
15-19
16.0
260
20-24
16.4
2244
25-29
15.8
1894
30-34
15.2
1320
35-39
14.8
916
40-44
15.0
280
45-49
14.5
145
Total
107.7
7059
Semester 1, 2015
16
Module 2: Topic 3
3. Suppose that you want to estimate the average duration of a disease from its
onset to death or cure. Which two measures of disease frequency do you need
to know in order to calculate your estimate?
Prevalence (P) = Incidence (I) x duration of disease (D). To solve for D, you need
P and I, since D = P/I.
4. (a)
Calculate the risk of CHD in both pre and post menopause groups.
(32 / 7524) x1000 = 0.00425 x1000= 4.25 per 1000 person-years (per
year) for the post-menopausal.
(10 / 9583) x1000 = 0.00104x1000 = 1.04 per 1000 per year for the premenopausal.
(b)
(c)
Semester 1, 2015
17
5. (a)
Module 2: Topic 3
(b)
(c)
7. Patients older than age 70 who develop coronary heart disease have shorter
survival times than the younger patients.
8. (a)
(b)
(c)
(d)
9. Calculate the 1986 birth rate for the Australian population if 243,408 live
births were recorded and the mid-year population was 15,602,156.
Crude birth rate:
Semester 1, 2015
18
Module 2: Topic 3
10.
Age group
(year)
15-19
20-24
25-29
30-34
35-39
40-44
45-49
Total
Number of
women (000)
G
F
16.0
R
16.4
=
7059 15.8
1000
107700 15.2
14.8
Number of
births
(ii)Age-Specific
Fertility Rate
(ASFR)
(per 1000)
260
(260/16000)x1000=16
2244
137
1894
120
1320
87
916
62
=
19
15.0
280
6
10
14.5
145
5
.
107.7
7059
451
5
(i) GFR=(7059/107700)*1000=66 (approx.) per thousand.
(iii) TFR= 5 (Sum of the ASFR)
=5451
=2251 per thousand.
Semester 1, 2015
19
Module 2: Topic 3
References
Dawson, B. and Trapp, R.G. (2001), Basic and Clinical Biostatistics, 3rd Edition
(international edition), Lange Medical Book/McGraw-Hill.
Gupta S.C. & Kapoor V.K. (1984). Fundamentals of Applied Statistics. Sultan
Chand & Sons. New Delhi.
Kuzma J.W. (1998), Basic Statistics for the Health Sciences, 3rd Edition, Mayfield
Publishing Company, Mountain View, California, USA.
Semester 1, 2015
20
Module 2: Topic 4
Dr Amirul Islam
Module 2: Topic 4
Contents
11
12
13
15
Revision exercises
18
22
References
25
Note: Some of the materials are adapted from standard texts and guides (see references).
Module 2: Topic 4
Module 2: Topic 4
Module 2: Topic 4
Autopsy
Hospital records
Occupational records
Financial records (e.g. insurance, pension funds)
(b)
Real
STA60004: Research Design
Module 2: Topic 4
Changes in survivorship
E.g. decreased mortality from ectopic pregnancy.
Module 2: Topic 4
Therefore the specific fertility rate was (94,575/648,677) x 1000 = 145 per
1000 women per year.
For epidemiological research studies, annual rates are often inappropriate
because periods of follow-up are not always whole years and recruitment
into studies can occur unevenly throughout years. Therefore, another
denominator used is person-years of observation.
Person-years of observation mean the total amount of time for which
people were observed to be disease-free during the time of follow-up. If
death occurs during the follow-up then individuals can be counted only if
they die from the cause under study, not if they die from another disease or
migrate away.
For example, a study follows 10 people from 1982 to 1992 and the
outcome of interest was the death from a particular disease. There were
three deaths recorded. The total person-years are the combined time of
people alive (disease-free) during the study. That is 8.5 + 10 + 5.5 + 10 +
+ 2.5 = 64.5 person-years.
The mortality rate for the study is (3/64.5) x 1000 = 46.5 per 1000 personyears.
Module 2: Topic 4
For example: A city contains 100,000 people (45,000 males and 55,000
females), and 1,000 people die per year (600 males and 400 females).
Crude mortality rate for that city
1000
CMR =
1000
100000
=10 deaths per 1000 population per year.
Merits of CMR:
It is simple to understand and calculate.
(i)
It is one of the most widely used of any vital statistics rates. As an
(ii)
index of mortality, it is used in numerous demographic and public
health problems.
(iii) Since the entire population of the region is exposed to the risk of
mortality, CMR is a probability rate indicating the probability that a
person belonging to the given population will die in the given
period.
Demerits of CMR: The most serious drawback of CMR is that it
completely ignores the age and sex distribution of the population.
Experience shows that mortality is different in different segments of the
population. Children, in the early ages of life, and the older generation are
exposed to higher risk of mortality as compared to younger people.
Moreover, mortality rate is also different for females, irrespective of age
groups, than their male counterparts.
Specific mortality rates (SMR) or specific death rates (SDR) are rates in
which some subdivision of the data has occurred. Here, a population is
divided into more homogeneous subgroups based on particular
characteristics of interest (e.g. age, sex, disease, and race) and rates are
calculated within these groups (age-specific rates, sex-specific rates,
disease-specific rates, race-specific rates, respectively). In order to arrive at
a more useful figure than CMR, we must take into account the fact that the
mortality pattern is different in different segments of the population.
Various segments may be sex, age, occupation, social status, etc. For
example, the people engaged in infant or child welfare work would be
interested to know the mortality condition in the age groups below one
year, 1-4 years, 5-9 years, etc. Those engaged in maternal health programs
would like to know the number of deaths occurring among women in the
reproductive period (usually 15 to 49 years); insurance authorities would
be interested in the mortality pattern at different ages of the population.
Mortality rate computed for a particular specified section of the population
is termed as specific mortality rate (SMR) or specific death rate (SDR).
Module 2: Topic 4
Merits of SMR:
(i)
(ii)
The death rates specific to age and sex overcome the drawback of
CMR, since they are computed by taking into consideration the age
and sex composition of the population. By eliminating the variation
in the death rates due to age-sex distribution of the population
SMRs provide more appropriate measures of the relative mortality
situation in the regions.
For general analytical purposes, the death rate specific for age and
sex is one of the most important and widely applicable types of
death rates. It also supplies the essential components required for
the construction of life table.
Demerits of SMR:
(i)
(ii)
ASMR=
57701 1000
43513000
= 1.3 deaths per 1000 population per year for the age group 25-34.
Module 2: Topic 4
CSMR=
94840 100000
243827000
253 100000
3829000
10
Module 2: Topic 4
Case Fatality Ratio (CFR): The case fatality ratio for a particular
condition is the number of deaths caused by the condition, divided by the
total number of identified cases of the condition in a specified population.
Although case fatality ratio is commonly used to describe the deaths
attributable to specific infectious diseases, it can also be used to describe
the deaths attributable to any condition (Ref. see Epidemiology,
Biostatistics and Preventive Medicine by Jekel et. all.).
Case Study:
11
Module 2: Topic 4
Age Yrs
Officers
Deaths
Person Rate
yrs
Nonofficers
Deaths
Person
yrs
Rate
15 19
500
0.0
126500
0.0
20 24
9000
0.0
226000
1.8
25 29
13000
0.0
10
164500
6.07
30 34
11500
0.0
26
88000
29.5
35 39
13500
14.8
36
60500
59.5
40 44
15000
40
19
21500
88.4
45 - 49
14
135000 103.7
11
5500
200
50 - 54
19
7500
1500
133.3
108
694000
15.6
253.3
41
83500 49.1
All ages
Notes: Rate per 100,000 person years
In the case study above, the crude mortality rate for officers (49.1 per
100,000 per year) is much higher than the crude rate for non-officers (15.6
per 100,000 per year). On the surface, it appears that the officers have a
greater risk of dying from heart disease than the non-officers.
However by comparing age specific rates, the rates are higher for nonofficers than the officers at almost every age. Remember the crude rates
ignore the age structure of the two populations. Officers are, on average,
much older than the non-officers and therefore their crude rate is greater.
But when like with like is compared, the officers are generally at lower risk
than the non-officers.
12
Module 2: Topic 4
Direct
Indirect
Population B
Young
1,000
0.001
4,000
0.002
Middle- 5,000
aged
50
0.010
5,000
100
0.020
Older
Total
400
451
0.100
1,000
10,000
200
308
0.200
4,000
10,000
13
Module 2: Topic 4
5,000
10,000
5,000
20,000
Population A
Population B
Young
5,000
0.001
5,000
0.002
10
Middle- 10,000
aged
0.010
100
10,000
0.02
200
Older
0.100
500
5,000
0.200
605
20,000
Total
5,000
20,000
1,000
1,210
14
Module 2: Topic 4
605
= 3.03%
20,000
1,210
= 6.05%
20,000
Thus although the CMR for Population A was higher (4.51%) than
That of Population B (3.08%), the age-adjusted rates indicate that
the risk of death is actually twice as high in Population B than in
Population A.
Age group
Young
Middle-aged
STA60004: Research Design
Proportion of people in
ref. population
0.40
0.30
Semester 2/SP 3 2015
Age-specific
mortality rate
0.0001
0.0010
15
Module 2: Topic 4
Older
0.30
0.0100
Males in reference
population
Age Proportion AgeObserved
group of ref.
specific death
size
death rate rate
Young 0.40 x
Number AgeObserved
of
specific death
workers death rate rate
0.0001 = 0.00004
2,000 x
= ?
3,000 x
= ?
Older
5,000 x
= ?
Total
1.00
0.00334
10,000
48
3. Multiply the age-specific death rates from each age group in the
reference population by the number of workers in the
corresponding age groups in the company. This gives the number
of deaths that would be expected in each age group of workers if
they had the death rates of the reference population.
Males in reference
population
Age Proportion AgeObserved
group of ref.
specific death
size
death rate rate
Number AgeObserved
of
specific death
workers death rate rate
16
Module 2: Topic 4
Young 0.40 x
0.0001 = 0.00004
Older
Total
1.00
0.00334
10,000
53.2
= (0.0048/0.00532) x 100
= 90%
Thus, males in the company actually had a death rate that was only 90% of
the value that would be expected, based on the death rates in the standard
population.
Note that if the employees in this example had an SMR of 140, it means
that their mortality was 40% greater than was expected on the basis of the
age-specific death rates of the reference population.
17
Module 2: Topic 4
Revision Exercises
White
1915-1919
1920-1924
1930-1934
1940
1950
1960
1970
1980
1987
92.8
73.3
55.2
43.2
26.8
22.9
17.8
11.0
8.6
African
American
150.4
117.3
90.5
72.9
43.9
44.3
32.6
21.4
17.9
a) What are some arguments that the time trends are real, not artifactual?
b) What effect would improved birth registration have on these data?
c) What effect would improved death registration have in these data?
d) What might explain the decline in infant mortality between 1915 and
1960?
e) What might explain the decline in infant mortality between 1960 and
1987?
f) What are three hypotheses that might explain the differences in infant
mortality between whites and blacks?
18
Module 2: Topic 4
2.
3.
Person
1
2
3
4
5
6
7
8
9
D
D
L
1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 Time
D = death, L = lost to follow up
4.
There are 10,000 individuals in City A, which is located in NSW. Eight young
individuals and 420 old individuals develop the flu over the course of a year.
(a)
Use these data to calculate the crude influenza rate per 1,000
individuals in City A.
(b)
19
Module 2: Topic 4
Age
group
Young
City A
40%
City B
50%
City C
80%
NSW
60%
Old
60%
50%
20%
40%
110
(c)
(d)
(e)
Age group
UK
60%
30%
10%
<30
30-55
>55
USA
30%
40%
30%
World
50%
30%
20%
UK
50
80
120
USA
75
150
400
(a) Calculate the crude rate of heart disease for each of the two
countries.
6.
(b)
Suppose that you want to compare the rate of heart disease in the
UK to that in the USA. Should you use the two crude rates to
compare the two countries? Why or why not?
(c)
(d)
Based on these answers, would you say that the age differences
between UK and the USA account for the entire difference in crude
heart disease rates between the two countries?
Taken from Morton RF, Hebel JR & McCarter RJ. (2001). A Study Guide to
Epidemiology and Biostatsitics, 5th ed.
A city contains 100,000 people (45,000 males and 55,000 females), and
1,000 people die per year (600 males and 400 females). There were 50
cases (40 males and 10 females) of lung cancer per year, of which 45 died
(36 males and 9 females). Compute:
20
Module 2: Topic 4
a.
b.
c.
d.
e.
7. Match the term with its definition. Each term may be selected once, more than
once, or not at all.
Age-specific death rate
case fatality ratio
cause-specific death rate
crude birth rate
direct standardization
incidence rate
indirect standardization
infant mortality rate
prevalence rate
standardized mortality ratio
standardized rate
(a)
(b)
(c)
(d)
(e)
(f)
This is useful for studying trends in the causes of death over time.
(g)
(h)
(i)
21
Module 2: Topic 4
What might explain the decline in infant mortality between 1960 and
1987?
Between 1960 and 1987 hospital-based technology reduced the mortality
for many high-risk infants including those born prematualy, born at low or
very low birth weight and those with congenital malformations
(f)
What are three hypotheses that might explain the differences in infant
mortality between whites and blacks?
Some hypotheses are:
o Black infants have genetically determined lower survival rates
o Black mothers are less likely to have access to medical care during
pregnancy
o Black mothers are more likely to be of lower socioeconomic class
than white mothers
o Deaths of white infants are less likely to be recorded than deaths of
black infants
o Births of black infants are less likely to be recorded than are births
of white infants.
2. Calculate the 1986 age-sex specific mortality rate for Australian men
aged 65-74 years if 17,032 deaths were recorded and the mid-year
population for this group was 463,802.
Age-specific mortality rate:
22
Module 2: Topic 4
3. (a)
Number of deaths = D = 3
(b)
(c)
Mortality rate:
3/65 = 0.046 per person years or 4.6 per 100 person per year.
(c)
(d)
(e)
5. (a)
(b)
NO. Should not compare the crude rates because the age
distributions of the two countries are very different and age is a
confounder for heart disease.
23
(c)
Module 2: Topic 4
(d)
162.5
per
Age does not account for all of the difference between the USA and
the UK. The age-adjusted rates are quite different; in fact; the USA
adjusted rate is more than twice the adjusted rate for the UK.
(b)
(c)
(d)
(e)
7. (a)
(b)
(c)
(d)
(e)
(f)
(g)
(h)
(i)
Direct standardization
Incidence rate
Indirect standardization
Prevalence rate
Standardized mortality ratio
Cause-specific death rate
Case fatality ratio
Crude birth rate
Age-specific death rate
Revision questions/Activity
Activity 1:
The population of Australia in 2005 was 20,395,000 with 10,128,000 males and
10,267,000 females. At the end of 2004, 654,977 living persons had been
diagnosed with cancer at some time in the last 23 years. During 2005, 22,017
males and 17,080 females died from cancer, 1119 males and 1062 females were
24
Module 2: Topic 4
diagnosed with pancreatic cancer and 964 males and 1062 females died from
pancreatic cancer.
References
Dawson, B. and Trapp, R.G. (2001), Basic and Clinical Biostatistics, 3rd Edition
(international edition), Lange Medical Book/McGraw-Hill.
Gupta, S.C. & Kapoor V.K. (1984). Fundamentals of Applied Statistics. Sultan
Chand & Sons. New Delhi.
Jekel, F.J., Katz, D.L. and Elmore, J.G. (2001). Epidemiology, Biostatistics, and
25
Module 2: Topic 4
Kuzma J.W. (1998), Basic Statistics for the Health Sciences, 3rd Edition, Mayfield
Publishing Company, Mountain View, California, USA.
Lilienfeld, D.E. and Stolley, P.D. (1994). Foundations of Epidemiology, 3rd ed.
New York : Oxford University Press.
Morton, R.F., Hebel, J.R. & McCarter, R.J. (2001). A Study Guide to
26
Analytical studies
Cross-sectional
studies
Observational
studies
Experimental
studies
Longitudinal
studies
Cross-sectional
studies
Randomised
controlled trials
Cohort studies
Community or
cluster trials
Case-control studies
Ecological studies
1
Analytic studies
Analyse associations between factors
Including cause and effect
Descriptive studies
Describe a health state or event in a defined
population
Provide measures of prevalence or incidence,
eg: How common is obesity among people who eat first
food?
Analytic studies
Designed to answer questions:
Is there any (causal) association?
How strong is an association?
Study factor
the factor (or factors) that we are interested in, that may be
PAST
FUTURE
PRESENT
Retrospective
Prospective
Crosssectional
Time
Ecological studies
In most epidemiological studies individuals are
counted and analysed in terms of their exposure and
outcome status
Ecological studies analyse aggregates of individuals or
other larger units
Usually because aggregate data is all that is available
10
Ecological studies
11
Ecological studies
12
Ecological studies
Source: Gertsman BB. 2003. Epidemiology kept simple. Hoboken, New Jersey, Wiley-Liss
13
Ecological studies
Source: Gertsman BB. 2003. Epidemiology kept simple. Hoboken, New Jersey, Wiley-Liss
14
Ecological studies
Strengths for answering questions on associations ie
CAUSE and EFFECT questions
Can use existing data collected for different purposes
or area level, eg
15
Module 2: Topic 5
Semester 2, 2014
Module 2: Topic 5
Contents
5.1 Randomised clinical trials
5.1.3
Suggested Reading
5.1.4
5.1.5
Major Concepts
5.1.6
Discussion Point
5.1.7
Extra readings
14
14
14
15
15
16
5.2.6
16
Major Concepts
17
17
18
20
Revision exercises
21
24
References
32
Note: Some of the materials are adapted from standard texts and guides (see references).
Semester 2, 2014
Module 2: Topic 5
Identify the major epidemiologic study designs and which types are classified as
experimental or observational
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Module 2: Topic 5
Study Population
RANDOMIS
ED
Control group
Treatment group
Improved
Not improved
Improved
Not improved
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Module 2: Topic 5
Interventional trials (also called treatment trials) are clinical trials which set out
to test treatments or combinations of treatments which have not yet been
officially approved. For example, a pharmaceutical company may have developed
a new drug which it believes would be effective in the treatment of Alzheimers
disease but must first test it on human volunteers in accordance with strict and
rigorous guidelines in order to ensure that it is safe and effective. Some drugs
Semester 2, 2014
Module 2: Topic 5
Diagnostic and screening trials are aimed at finding new ways to detect and
diagnose medical conditions (e.g. a better test, a more effective procedure or a
more sophisticated tool).
Clinical trials can also be classed according to whether they are considered therapeutic
or non-therapeutic.
Evidence from approved RCTs is required for medications to receive marketing approval
by the Therapeutic Goods Administration (TGA) in Australia.
Placebo Effects
A well-known phenomenon in medicine is that patients given only inert substance (e.g.
sugar pills) will often show subsequent clinical improvement when compared with
similar untreated patients. This phenomenon, termed the placebo effect, must be taken
into account in clinical trial design if effects in the intervention group are to be ascribed to
the intervention itself and not to the generic effect of being treated. The usual method to
accomplish this is to use an inert treatment that is indistinguishable from the primary
intervention in the control group. Thus, the only difference between groups is the specific
intervention under study.
Semester 2, 2014
Module 2: Topic 5
The National Health and Medical Research Council has developed guidelines for the
organisation and conduct of human research ethics committees to review research
involving humans. This involves the provision of plain language information to potential
study participants so that they are truly informed of all aspects of the trial and can thus
give written, informed consent. In the case of minors, a parent or legal guardian can give
consent provided the minor agrees to participate. Further information is available from
the National Health and Medical Research Council in Canberra.
II.
Obligations to society:
to avoid conflicts of interest
to avoid partiality
to widen the scope of epidemiology
to pursue responsibilities with due diligence
to maintain pubic confidence
The basis of this obligation is the accurate interpretation and reporting of research results.
These concepts will be discussed in more detail in future topics.
III.
Oftentimes, epidemiologists do research for third parties and are obliged not to reveal
proprietary information.
IV.
Obligations to colleagues:
to report methods and results
to confront unacceptable behaviour and conditions
to communicate ethical requirements
Semester 2, 2014
Module 2: Topic 5
These obligations occur in two common situations: who should be included as authors on
articles and the necessity to report negative results. It has been shown that research
articles that comprise statistically significant results are more likely to be published than
non-significant results. When this occurs, further resources may be expended to prove
something that has already been shown not to be significant.
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Module 2: Topic 5
Know the types of summary rates calculated with data from cohort studies
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14
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Module 2: Topic 5
Exposed
Disease
Population
People without
disease
No disease
Unexposed
Disease
No disease
Source: The above are figures are for prospective cohort studies: Medical research library
of Brooklyn
http://servers.medlib.hscbklyn.edu/ebm/2400.htm
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Module 2: Topic 5
Exposure Assessment
The two key elements in the identification of relative risks associated with the
development of new disease are the measurement of exposure and outcome. Recall from
an earlier topic the components of screening. Tools to measure exposures and disease
must be both reliable and valid. One of the potential problems in cohort studies is that the
measure of exposure or outcome can change over the study period. For example, a new
International Classification of Disease may be implemented half way through a 10-year
cohort study. If the investigators were tracking death certificates for certain disease
classifications, they may have difficulties.
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Module 2: Topic 5
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18
Module 2: Topic 5
ethically safe;
Disadvantages:
blinding is difficult;
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19
Module 2: Topic 5
Outcome
Variable
Binary or
categorical
(e.g.
fracture,
yes/no)
Correlated
Chi-square
test:
compares proportions
between more than two
groups
Relative risks: odds
ratios or risk ratios
Logistic regression:
multivariate technique
used when outcome is
binary;
gives
multivariate-adjusted
odds ratios
Alternative to the
chi-square test if
sparse cells:
Fishers
exact
test:
compares
proportions
between
independent
groups when there are
sparse data (some cells
<5).
McNemars exact test:
compares
proportions
between correlated groups
when there are sparse data
(some cells <5).
Semester 2, 2014
20
Module 2: Topic 5
unexposed group. More simply, we calculate the percentage of patients who developed
disease in the exposed and unexposed groups, then divide the percentage for the exposed
group by that of the unexposed group. This will give the required RR.
The relative risk may be defined as the ratio of the incidence of disease among an
exposed groups relative to the incidence of disease among a non-exposed groups.
RR =
Incidence in exposed
.
Incidence in nonexposed
The data resulting from a prospective study in which the outcome variable and the risk
factor are both dichotomous may be displayed in a 2 2 table as given below.
Table 5.1: General representation of two nominal characteristics
Risk Factor Develop disease Do not develop disease Total
a
b
a+b
Exposed
c
d
c+d
Unexposed
a+c
b+d
a+b+c+d
Total
From the above table, a out of (a + b) patients who developed the disease in the
exposed group, thus the proportion of patients who developed disease in the exposed
group is
a /(a + b). Similarly, the proportion of patients who developed disease
in the unexposed group is c /(c + d).
Thus, the relative risk can be represented symbolically as
a
a (c + d )
RR = a + b =
c
c ( a + b)
c+d
A RR ranges between zero to some positive values. However, in general we encounter the
following three possibilities.
A RR of 1 or very close to 1 indicates that the patients in the exposed and unexposed
groups have the same risk.
If the RR is greater than 1, patients in the exposed group are at increased risk compared
to those in the unexposed group.
If the RR is less than 1, patients in the exposed group are at lower risk than the patients
in the unexposed group.
Note: To test the hypothesis (null) of no association between the factors (exposure and
disease) we use the (chi-squared test) and to obtain an estimate of the magnitude of the
association between exposure and disease we use RR (cohort study) or OR (case-control
study).
Semester 2, 2014
21
Module 2: Topic 5
UTI at an initial survey in 1973, there were 482 OC users and the remaining 1908 were
not OC users. At a second survey in 1976, 27 of the OC users had developed UTS, as
had 77 of the non-users.
Outcome
Exposure
UTI
No UTI
Total
OC use
27
455
482
No OC use
77
1831
1908
Total
104
2286
2390
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Module 2: Topic 5
A simple comparison between these two studies is presented in the following figure.
Observational Study
Experimental Study
Population
Population
Other-Than-Random Allocation
(e.g. Self Selection)
Random Allocation
Group A
Group B
Group A
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Group B
23
Module 2: Topic 5
Revision Exercises
Intervention:
Preventive:
2. In an RCT to assess the effectiveness of a new type of open heart surgery, could the
trial be single blind, double blind or triple blind? Why?
Risk Factor
Disease
osteoporosis
lung cancer
6. What are some potential means of keeping subjects enrolled in clinical trials?
Analysis of the Results
7 If you discover that, by chance, the baseline characteristics of your study groups in a
clinical trial are significantly different, what are some possible solutions?
8. Read the following supplementary article:
Course notes STA60004
Semester 2, 2014
24
Module 2: Topic 5
Shackel NA, Day RO, Kellett B, Brooks PM. Copper-salicylate gel for pain relief
in osteoarthritis: a randomised controlled trial. Med J Aust 1997; 167:134-136.
Can be downloaded from the website:
http://espace.library.uq.edu.au/eserv/UQ:10099/copper.pdf
A pdf copy of this article also attached with Topic 5 notes on Blackboard.
(i). Were people in the treatment group in the supplementary article significantly
more likely to withdraw during the trial? How could this affect the results of the
clinical trial?
(ii). Recalculate the chi-square and p-value associated with the number of patients
in each group that reported adverse events during the trial.
9. Why is randomisation essential and what does it accomplish?
Discussion Point
10. Would a randomised clinical trial be an appropriate epidemiologic study methodology
to evaluate the effect of polio vaccination versus a placebo on life expectancy? Why or
why not?
11. If investigators find no statistically significant relationship between a new medication
and mortality in a clinical trial, what are two possible explanations for this finding?
3. How might you measure exposure to second-hand cigarette smoke in a cohort study of
the effects of second-hand smoke on the incidence of asthma in children?
4.
A common measure of dietary intake is the 24-hour food recall. Write down every
thing that you had to eat and drink in the last 24 hours. Do you think that those 24
hours were representative of your usual food intake? Usually, a series of random
24-hour recalls are undertaken to classify a persons usual dietary intake.
Semester 2, 2014
25
Module 2: Topic 5
6.
The following table shows a hypothetical cohort study of 3,000 cigarette smokers
and 5,000 nonsmokers to investigate the relation of smoking to the development
of coronary heart disease (CHD) over a 1-year period.
CHD develops
Total
Smoke cigarettes
84
2916
3000
87
4913
5000
Yes
212
465
677
No
1313
3912
5225
Semester 2, 2014
Total
1525
4377
5902
26
Module 2: Topic 5
What is the relative risk (RR) of reportedly seeing a ghost for one group compared to the
other? Write a sentence to explain your answer in a form that could be understood by
someone who knows nothing about statistics.
1.
2. In an RCT to assess the effectiveness of a new type of open heart surgery, could
the trial be single blind, double blind or triple blind? Why?
Single blinding would involve the patient (subject) being unaware of which type of
surgery (s)he experienced. This would not be difficult to achieve. Double blinding would
involve the observer of the subject not being aware of the type of surgery the subject has
received. This would not be possible if the observer were the surgeon (as would most
likely be the case) or a member of theatre staff. Triple blinding is not possible if double
blinding is not achieved. In many cases the person reviewing the data is the statistician
whose responsibility it is to arrange and manage double blinding.
3.
Risk Factor
Disease
osteoporosis
Semester 2, 2014
food poisoning
lung cancer
27
Module 2: Topic 5
smoke
Appealing to their altruism (their desire to help others with the disease)
Promising that should they be assigned to the control group they will be given the new
treatment after the trial, if it proves effective
7. If you discover that, by chance, the baseline characteristics of your study groups in a
clinical trial are significantly different, what are some possible solutions?
If the discovery is made before the trial is in progress you could reallocate subjects
randomly to groups after stratifying on key variables that are possibly related to the
outcome.
Randomly discard subjects with certain characteristics (the ones showing imbalance)
from one or other of the groups. This strategy may be viable in very large studies.
Include the variables showing imbalance in the analysis as covariates so as to
statistically control for them.
8. Read the following supplementary article:
Shackel NA, Day RO, Kellett B, Brooks PM. Copper-salicylate gel for pain relief in
osteoarthritis: a randomised controlled trial. Med J Aust 1997;167:134-136.
Semester 2, 2014
28
(i)
Module 2: Topic 5
Yes, people in the treatment group were significantly more likely to withdraw during the
trial. This could affect the results by decreasing the power of the study and increasing the
likelihood of a type II error.
(ii) Recalculate the chi-square and p-value associated with the number of
patients in each group that reported adverse events during the trial.
The two-by-two table to test the association between the report of adverse events and the
groups is shown below (note that intention-to-teat analyses are assumed and all 58 people
in each group have been included). These data were obtained from Table 2. Note that the
information in Table 1 relates to people who withdrew from the trial due to their adverse
events, not the total number of adverse events.
Observed
Reported adverse
event
Yes
No
Total
Copper-salicylate
gel
48
10
58
Placebo
Total
29
29
58
77
39
116
Expected
Reported adverse
event
Yes
No
Total
Copper-salicylate
gel
38.50
19.50
58
Placebo
Total
38.50
19.50
58
77
39
116
2 = (O-E)2/E
2 = [(48 38.5)2 / 38.5] + [(10 19.5)2 / 19.5] + [(29 38.5)2 / 38.5] +
[(29 19.5)2 / 19.5]
2 = 2.3441 + 4.6282 + 2.3441 + 4.6282
2 = 13.9 on one degree of freedom has a p-value is less than 0.001.
9. Why is randomisation essential and what does it accomplish?
Semester 2, 2014
29
Module 2: Topic 5
Randomisation is essential because then and only then can the difference in outcome
between the groups be ascribed to the treatment applied. If randomization is omitted, the
difference in outcome may be due to differing characteristics in the competing groups.
Randomisation achieves an unbiased distribution of risk factors (e.g. age, sex, severity of
disease). This principle is the underlying concept on which randomised clinical trials are
based.
10. Would a randomised clinical trial be an appropriate epidemiologic study
methodology to evaluate the effect of polio vaccination versus a placebo on life
expectancy? Why or why not?
No, because it would involve the withholding of an effective vaccine from some people at
risk of contracting polio, thereby exposing them to a possibly disabling disease which
would reduce permanently the quality of their lives.
However, it would be ethical to compare the effect of polio vaccination using a new
vaccine with the polio vaccines that are currently used.
11. If investigators find no statistically significant relationship between a new
medication and mortality in a clinical trial, what are two possible explanations for
this finding?
(i)
(ii)
Women of childbearing age (say 20-25 years) could be followed for (say) 20 years to
assess how maternal diet affects the birth weight of children. A difficulty would be
in defining the exposures (diet during what time period, how is diet assessed or
measured?).
Children with asthma could be followed over time to assess the relative effectiveness
of various treatments or treatment regimes.
Semester 2, 2014
30
Module 2: Topic 5
3. How might you measure exposure to second-hand cigarette smoke in a cohort study
of the effects of second-hand smoke on the incidence of asthma in children?
Since the children will spend much of their time at home, the exposure could be measured
by the amount of smoking done by their parents. Other sources of second-hand smoke
would be difficult to associate with individual children.
4. A common measure of dietary intake is the 24-hour food recall. Write down every
thing that you had to eat and drink in the last 24 hours. Do you think that those 24
hours were representative of your usual food intake? Usually, a series of random 24hour recalls are employed to classify a persons usual dietary intake.
You need to think how to do this yourself. Try to write down what you see as the
problems associated with this kind of recall measurement.
5. Supplementary reading:
Crofts N, Aitken CK. Incidence of bloodborne virus infection and risk behaviours in a
cohort of injecting drug users in Victoria, 1990-1995. Med J Aust. 1997;167:17-20.
Use this formula and the information in tables 3 in the article to estimate the
overall duration in years for people with the Hepatitis C virus.
Prevalence = No. with positive HCV serostatus/Total population at risk
Prevalence = (49 + 52 + 43)/202 = 144/202
Prevalence = 0.71
Semester 2, 2014
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Module 2: Topic 5
Duration = Prevalence/Incidence
Duration = 0.71/0.115
Duration = 6.2 years
(ii) Calculate the chi-square value for the relationship between reports of
sharing of needles and syringes, and HCV serostatus in table 3 of the article.
How many degrees of freedom are there? How is this chi-square value
interpreted?
Observed
Reports of sharing
50%
< 50%
None
Total
+
49
52
43
144
HCV serostatus
14
21
23
58
Total
63
73
66
202
+
44.91
52.04
47.05
144
HCV serostatus
18.09
20.96
18.95
58
Total
63
73
66
202
Expected
Reports of sharing
50%
< 50%
None
Total
2 = (O-E)2/E
2 = [(49 - 44.91)2 / 44.91] + [(52 - 52.04)2 / 52.04] + [(43 - 47.05)2 / 47.05] +
[(14 - 18.09)2 / 18.09] + [(21 - 20.96)2 / 20.96] + [(23 - 18.95)2 / 18.95]
2 = 0.3725 + 0 + 0.3486 + 0.9247 + 0 + 0.8656
2 = 2.5114 (which corresponds with the value in the paper)
Degrees of freedom = (r - 1) (c - 1) = 2 x 1 = 2
Interpretation:
2 < 5.99, the critical 2 value at the 0.05 level. Therefore, do not reject the null
hypothesis. There is no significant association between the frequency of reporting shared
use of needles and syringes and HCV serostatus
6. The Following table shows a hypothetical cohort study of 3,000 cigarette smokers
and 5,000 nonsmokers to investigate the relation of smoking to the development of
coronary heart disease (CHD) over a 1-year period.
Course notes STA60004
Semester 2, 2014
32
Module 2: Topic 5
CHD develops
Total
Smoke cigarettes
84 (a)
2916 (b)
3000
(a+b)
87 (c)
4913 (d)
5000
(c+d)
RR =
a (c + d ) 84 5000
=
c(a + b) 87 3000
=1.61 (approx).
Thus the risk of developing CHD for smoker is 1.6 fold higher than that for the nonsmoker.
7. (a) The 2x2 Table:
Exposure
Transfusion
No transfusion
Total
No Hepatitis
Hepatitis
75 (a)
16 (c)
91
520 (b)
696 (d)
1216
Total
595 (a+b)
712 (c+d)
1307
Semester 2, 2014
33
Module 2: Topic 5
References
Dawson, B. and Trapp, R.G. (2001), Basic and Clinical Biostatistics, 3rd Edition
(international edition), Lange Medical Book/McGraw-Hill.
Crofts N, Aitken CK (1997). Incidence of blood borne virus infection and risk
behaviours in a cohort of injecting drug users in Victoria, 1990-1995. Med J Aust;
167:17-20.
Can be downloaded from the website:
http://www.mja.com.au/public/issues/jul7/crofts/crofts.html
Friedman LM, Furberg CD, DeMets DL (a985). Fundamentals of Clinical Trials.
Littleton, Massachusetts: PSG Publishing Company.
Gordis, L., (2013), Epidemiology, 5th Edition, Elsevier/Saunders, Chapters 7-8
(available at Swinburne Bookshop and students may buy this book).
Jekel, F.J., Katz, D.L. and Elmore, J.G. (2001). Epidemiology, Biostatistics, and
Preventive Medicine, 2nd Ed., W.B. Saunders Company, New York.
Methods in Observational
Lilienfeld, D.E. and Stolley, P.D. (1994). Foundations of Epidemiology, 3rd ed.
New York: Oxford University Press.
Morton, R.F., Hebel, J.R. & McCarter, R.J. (2001). A Study Guide to
Epidemiology and Biostatsitics, 5th Edn.
Shackel NA, Day RO, Kellett B, Brooks PM (1997). Copper-salicylate gel for
pain relief in osteoarthritis: a randomised controlled trial. Med J Aust; 167:134136.
Semester 2, 2014
34
Module 2: Topic 6
Topic 6: Case-Control
Studies
Semester 1, 2014
Module 2: Topic 6
Contents
6.1 Topic background
6.6
6.5.3
6.5.4
6.5.5
Revision exercises
10
17
References
23
Note: Some of the materials are adapted from standard texts and guides (see references).
Semester 1, 2014
6.1
Module 2: Topic 6
Background
6.2
Learning Objectives
6.3
Suggested Reading
Semester 1, 2014
Module 2: Topic 6
6.4
In a case- control study subjects are selected on the basis of whether or not they have the
disease of interest. Cases (those with disease) are then compared to controls (those
without disease) in terms of their history of exposure to a hypothesised causal factor. This
is illustrated in Figure 5.1 (Source: Beaglehole et al., 1993).
Time
Direction of inquiry
Exposed
Start with:
Cases (people
with disease)
Not exposed
Population
Controls (people
without disease)
Exposed
Not exposed
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Module 2: Topic 6
6.5
Major Concepts
Semester 1, 2014
Module 2: Topic 6
Semester 1, 2014
Module 2: Topic 6
Exposed
Non-exposed
Develop disease
a
c
Odds Ratio,
Course notes STA60004
Semester 1, 2014
Module 2: Topic 6
OR=
ad
.
bc
Similar to the RR, the value of the OR ranges from zero to some positive numbers. In
real life we encounter one of the three possibilities.
An OR of one: This indicates that the odds of cases is the same in the exposed
and unexposed groups.
An OR of greater than one: This shows that the odds of cases is higher in the
exposed group than the odds of cases in the unexposed group.
An OR of less than one. This means that the odds of cases in the exposed
group is less than that in the unexposed group.
Example: Consider a case control study that investigates the association of bronchial
carcinoma and asbestos exposure in the Canadian chrysolite mines and mills, the data is
given in Table 8.4. Calculate an appropriate measure of association between carcinoma
and asbestos exposure and comment.
Cases
Controls
Total
Exposed
148
372
520
Unexposed
75
343
418
Total
223
715
938
From the above table we have: a = 148, b = 372, c =75 and d = 343. Thus the OR =
(ad)/bc) = (148343) / (37275) =1.83. This means that the odds of developing
bronchial carcinoma is 1.83 fold in the asbestos exposed group compared to the odds of
developing bronchial carcinoma in the unexposed group.
6.6
Advantages:
They are relatively quick and cheap to undertake compared to other analytic
designs.
Odds ratios can be calculated from this type of study which is a good
approximation of the relative risk.
Disadvantages:
Semester 1, 2014
6.7
Module 2: Topic 6
Discussion Point
In a study of a rare type of cancer, do you think that it would be best to design a
cohort study or a case control study? Think not only of the study rigour, but also
the implications for resources.
Semester 1, 2014
Module 2: Topic 6
Revision Exercises
State in words the meaning of an odds ratio, remembering that the data about risk
factors are collected retrospectively.
3. In a study to examine the association between smoking and drinking and the
development of head and neck cancer, from where would you source cases and controls?
What factors would you match for? What data would you collect and how would the data
be obtained?
4. A case-control study of bladder cancer was undertaken in a region with a large dye
manufacturing plant. Newly diagnosed cases of bladder cancer in that region were
identified from the state cancer registry. Controls were identified by telephone sampling
in the region and matched for age and sex. Exposures to chemicals, dyes, dietary factors
and smoking were assessed and odds ratios for these exposures were assessed. During
this process, the investigators learned that the dye plant had recently begun a medical
surveillance program for its employees that included screening for bladder cancer. A few
subclinical cases of bladder cancer were detected through the medical surveillance
program and were included among the case group. Could the differential medical
surveillance of the dye manufacturing workers bias the results of this study? If so, why?
5. A case-control study of lung cancer used identified cases of newly diagnosed lung
cancer and age/sex matched controls diagnosed with other conditions in the same
hospital. Rather than interviewing cases and controls, investigators reviewed the medical
histories to collect data on exposures. The medical charts of the lung cancer cases were
8.5 times more likely to mention a history of asbestos exposure compared with the
medical histories of the controls. Is this differential or non-differential misclassification?
What impact might this have had on the outcome of the study?
6. Compare the use and interpretation of a relative risk and an odds ratio.
7. How would you explain to someone the difference between an absolute and a relative
risk?
8. Why cannot you calculate an incidence rate from a case-control study?
9. Why is it easier to study a rare disease with a case-control study than with a cohort
study?
10. Read the following supplementary article (extra reading):
Siskind V, Green A, Bain C, Purdie D. Breastfeeding, menopause, and epithelial
ovarian cancer. Epidemiology 1997;8:188-191.
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Module 2: Topic 6
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Module 2: Topic 6
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12
Module 2: Topic 6
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13
Module 2: Topic 6
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14
Module 2: Topic 6
(i)
How were the cases and controls selected? What potential biases could
have been introduced by this selection method?
(ii)
How was the exposure measured? How could this method have biased the
results?
(iii) What information was provided about the non-participants? Based on this
information, do you think that it is likely that non-participation could have
influenced the results?
(iv) Calculate the unadjusted odds ratio that measures the association between
unsupplemented breastfeeding and epithelial ovarian cancer for all women. (N.B.
the data will need to be extracted from Table 1 on page 190). Interpret this odds
ratio.
(v) How would you interpret the overall results of this study for a lay person? Do
you trust the results of this one study?
11.
Cases
Controls
Total
Exposed
148
372
520
Unexposed
75
343
418
Total
223
715
938
12. A case-control study of myocardial infarction gave results for prior alcohol
consumption as shown. Calculate the odds ratio for each category of drinkers compared
with the non-drinkers. Does the table show a positive or negative association between
alcohol consumption and myocardial infarction?
Standard drinks per day
0 (Nondrinkers)
2
3-5
6
Total
Cases
136
202
42
11
391
Controls
110
238
46
24
418
13.
In a study of risk factors for congenital defects of the neural tube, maternal
deficiency of folate was found in 15 out of a total of 100 mothers of cases and 10 out of a
total of 200 mothers of controls. Calculate the odds ratio for exposure and interpret the
result.
Course notes STA60004
Semester 1, 2014
15
Module 2: Topic 6
14. The data given in the following table are reproduced from a Case Study and represent
employees laid off by the U.S. Department of Labor (taken from Utts J.M. seeing through
statistics, p238).
Laid Off?
% Laid Off
Ethnic Group
Yes
No
Total
African
130
1382
1512
8.6
American
87
2813
2900
3.0
White
217
4195
4412
Total
a) Compute the odds of being retained to being laid off for each ethnic group.
b) Use your results in part (a) to compute the odds ratio. Write a sentence to explain
your answer in a form that could be understood by someone who knows nothing
about statistics.
Semester 1, 2014
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Module 2: Topic 6
2. State in words the meaning of an odds ratio, remembering that the data about
risk factors are collected retrospectively.
The odds ratio is an approximation of the relative risk of disease in those exposed to a
risk factor compared with those who were not exposed to the risk factor. The odds ratio
is calculated by dividing the odds of an exposed person having the disease by the odds of
a non-exposed person having the disease.
3. In a study to examine the association between smoking and drinking and the
development of head and neck cancer, from where would you source cases and
controls? What factors would you match for? What data would you collect and
how could the data be obtained?
Cases could be selected from newly diagnosed patients attending a particular hospital
over a specified time period for treatment of cancer of the head and neck. Controls could
be sourced from the general population in the catchment area of the hospital through
electoral roles or alternatively, from patients attending the same hospital for the treatment
of disease not related to smoking or alcohol intake.
The subjects should be matched for age (in 5-10 year groups) and sex.
Details of sex, age, tobacco consumption, alcohol consumption, education and occupation
could be collected. This data could be obtained through medical records or through
interviewing the subjects using a pre-designed questionnaire. The latter would be
preferred as medical records are often incomplete and a poor source of information on
exposure.
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Module 2: Topic 6
4. A case-control study of bladder cancer was carried out in a region with a large
dye manufacturing plant. Newly diagnosed cases of bladder cancer in that region
were identified from the state cancer registry. Controls were identified by telephone
sampling in the region and matched for age and sex. Exposures to chemicals, dyes,
dietary factors and smoking were assessed and odds ratios for these exposures were
assessed. During this process, the investigators learned that the dye plant had
recently begun a medical surveillance program for its employees that included
screening for bladder cancer. A few subclinical cases of bladder cancer were
detected through the medical surveillance program and were included among the
case group. Could the differential medical surveillance of the dye manufacturing
workers bias the results of this study? If so, why?
Yes, the results would be biased because subclinical cases of bladder cancer would have
gone undetected among individuals in the community who were not dye workers. These
subclinical cases would not have been included in the study.
5. A case-control study of lung cancer used identified cases of newly diagnosed lung
cancer and age/sex matched controls diagnosed with other conditions in the same
hospital. Rather than interviewing cases and controls, investigators reviewed the
medical histories to collect data on exposures. The medical charts of the lung cancer
cases were 8.5 times more likely to mention a history of asbestos exposure compared
with the medical histories of the controls. Is this differential or non-differential
misclassification? What impact might this have had on the outcome of the study?
This represents differential misclassification, since the misclassification of asbestos
exposure is different between the cases and controls.
This can produce bias in either direction, raising or lowering the estimation of risk.
Because most physicians are aware of the relationship between asbestos and lung cancer,
they are likely to ask lung cancer patients if they had ever been exposed to asbestos. For
most other patients, they are unlikely to ask about asbestos or other occupational
exposures and asbestos exposure is less likely to be noted for the controls, compared with
the cases. This is another illustration of medical records being a poor source of data on
exposure!
6. Compare the use and interpretation of a relative risk and an odds ratio.
A relative risk measures the likelihood of developing the disease in the exposed group
relative to those who are unexposed. Relative risk is used to measure the association
between exposure and outcome for data collected in a cohort study or randomised clinical
trial.
For a case control study, the risk ratio is meaningless. Instead, the odds ratio is used
which compares the odds of exposure to a risk factor among cases with that among
controls. However, for a rare condition, the odds ratio approximates the relative risk.
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Module 2: Topic 6
7. How would you explain to someone the difference between an absolute and a
relative risk?
Absolute risk is the risk of having a disease. Eg If the incidence of a disease is 1 in 1000,
then the absolute risk is 1 in 1000 or 0.1%.
Relative risk is the risk of the outcome of interest in the exposed group relative to the risk
of the outcome in the unexposed group. Eg Relative risk = 3.0 the risk of the outcome
in the exposed group is three times that of the unexposed group.
9. Why is it easier to study a rare disease with a case-control study than with a
cohort study?
Both cohort (prospective) and case-control (retrospective) studies can be utilised to
examine associations between risk factors and disease. However to study a rare disease,
cohort studies will require a very large sample size and extensive follow-up of subjects
over time. Thus, many persons must be studied over a long period to obtain even a few
cases that develop the end-point of interest. In contrast, a case-control study utilises
existing cases and requires a much smaller sample size. Case-control studies are
therefore cheaper to carry out and provide results much faster.
(i) How were the cases and controls selected? What potential biases could
have been introduced by this selection method?
Histologically confirmed incident cases of epithelial ovarian cancer were recruited from
the gynaecologic oncology treatment centres in Victoria, New South Wales, and
Queensland. The controls were randomly selected from the electoral rolls to be similar to
the anticipated age and geographic distribution of the cases. Misclassification should not
be a problem with the cases, but may exist with the controls. As with any case control
study, recall bias is a potential problem with the cases.
(ii)
How was the exposure measured? How could this method have
biased the results?
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Module 2: Topic 6
Breastfeeding history was obtained through interview with both the cases and the
controls. Again, recall bias is a potential problem with self-report of exposure.
(iii)
Breastfed
Did not breast feed
Total
Cases
450
168
618
Controls
569
155
724
Total
1,019
323
1,342
OR = ad/bc
= (450 x 155) / (569 x 168)
= 69,750 / 95,592
= 0.72
ie. The unadjusted odds ratio of 0.72 for all women indicates that women with a history
of breastfeeding have a 28% lower risk of developing epithelial ovarian cancer than
women without a history of breastfeeding.
(iv)
How would you interpret the overall results of this study for a lay
person? Do you trust the results of this one study?
In this case control study, breastfeeding was found to be protective for epithelial ovarian
cancer in pre-menopausal women, but the protective effect was not present for postmenopausal women. Before it is accepted that breastfeeding provides protection against
epithelial ovarian cancer, the results of this study would need to be reproduced by other
larger studies in a range of population groups.
11.
ad 148 343
=
= 1.82
bc 372 75
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Module 2: Topic 6
The odds of developing bronchial carcinoma among the asbestos exposure is 1.82 times
than those who are un-exposed.
12. A case-control study of myocardial infarction gave results for prior alcohol
consumption as shown. Calculate the odds ratio for each category of drinkers
compared with the nondrinkers. Does the table show a positive or negative association
between alcohol consumption and myocardial infarction?
Standard drinks per day
0 (Nondrinkers)
2
3-5
6
Total
Cases
136
202
42
11
391
Controls
110
238
46
24
418
a) Odds ratio for the 2 standard drinks group compared with the non-drinkers:
OR = (202 x 110)/(238 x 136) = 0.69
b) Odds ratio for the 3 - 5 standard drinks group compared with the non-drinkers:
OR = (42 x 110)/(46 x 136) = 0.74
c) Odds ratio for the 6 standard drinks group compared with the non-drinkers:
OR = (11 x 110)/(24 x 136) = 0.37
Alcohol consumption appears to have a protective effect against acute myocardial infarct.
The likelihood of having an AMI appears to decrease with increasing alcohol
consumption.
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Module 2: Topic 6
13. In a study of risk factors for congenital defects of the neural tube, maternal
deficiency of folate was found in 15 out of a total of 100 mothers of cases and 10 out of
a total of 200 mothers of controls. Calculate the odds ratio for exposure and interpret
the result.
Maternal folate
deficiency present
Maternal folate
deficiency absent
Total
Odds ratio
Cases
15
Controls
10
Total
25
85
190
275
100
200
300
= ad / bc
= (15 x 190) / (10 x 85)
= 2,850 / 850
= 3.4
Babies whose mothers had a folate deficiency were 3.4 times more likely to suffer a
congenital defect of the neural tube compared with babies whose mothers were not folate
deficient.
14. The data given in the following table are reproduced from a Case Study and represent
employees laid off by the U.S. Department of Labor (taken from Utts J.M. seeing through
statistics, p238).
Laid Off?
% Laid Off
Ethnic Group
Yes
No
Total
African
130
1382
1512
8.6
American
87
2813
2900
3.0
White
217
4195
4412
Total
a) Compute the odds of being retained to being laid off for each ethnic group.
The odds are 1,382 to 130 or about 10.6 to 1 for African Americans and 2,813
to 87 or about 32.3 to 1 for Caucasians.
b) Use your results in part (a) to compute the odds ratio. Write a sentence to explain
your answer in a form that could be understood by someone who knows nothing
about statistics.
Odds ratio is (2,813/87) (1,382/130) = 3.04. That means the odds of being laid
off compared with being retailed are 3 times higher for African American than
for white.
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Module 2: Topic 6
References
Beaglehole, R., Bonita, R., and Kjellstrom, T. (1993). Basic Epidemiology. WHO,
Geneva.
Dawson, B. and Trapp, R.G. (2001), Basic and Clinical Biostatistics, 3rd Edition
(international edition), Lange Medical Book/McGraw-Hill.
Gordis L (2013). Epidemiology (5th ed.). Chapters 10, 11, 13.
Siskind V, Green A, Bain C, Purdie D (1997). Breastfeeding, menopause, and epithelial
ovarian cancer. Epidemiolog, Vol. 8, pp. 188-191.
Kelsey JL, Thompson WD, Evans AS (1986). Methods in Observational Epidemiology.
New York: Oxford University Press.
Rosner B (2006). Fundamentals of Biostatistics, 6th Edn.Thomson, Australia.
Schlesselman JJ. (1982). Case-Control Studies: Design, Conduct, Analysis. Oxford:
Oxford University Press.
Applications of the Case-control Method. Epidemiologic Reviews. 1994, Vol. 16, pp.1164.
Utts J.M. (2005). Seeing Through Statistics. Third Edition. Brooks/Cole Cengage
Learning, CA, USA.
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