Mount Kenya University

Kenya

P.O. Box 342-01000 Thika

Email: info@mku.ac.ke

Web: www.mku.ac.ke

SCHOOL OF PUBLIC HEALTH

COURSE CODE: MPH5202

COURSE TITLE: APPLIED EPIDEMIOLOGY

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MPH 5202: APPLIED EPIDEMIOLOGY

CONTACT HOURS: 42

PRE-REQUISITE: FOUNDATIONS OF EPIDEMIOLOGY

Purpose

This unit is designed to enable the student to acquire skills, knowledge and attitudes on
applied epidemiology

Expected Learning Outcomes

By the end of the course unit, the learner should be able to:

i. Describe and use descriptive studies: case series, cross-sectional surveys,

retrospective and prospective studies
ii. Describe and use analytical studies: case-control, cohort, experimental study
designs, randomized, controlled trials (clinical and community trials)
iii. Explain the uses of measures of association/risk: Relative risk, odds ratio and
attributable risk
iv. Discuss monitoring and modeling for diseases
v. Describe the mantel hanzel procedure and its application.
vi. Explain disease surveillance and disease control strategies

Week/Lesson/ Topic/Sub topic Intended Learning Outcomes: Activities

Dates/Hours The students will be able to:
Week 1 Introduction  Definitions  Lectures
 Uses of epidemiology;  Assignments
 primary goals of  Discussion
epidemiology  Research
assignments
Week 2 Types of  Types of epidemiological  Lectures
epidemiological studies i.e (i)Descriptive  Assignments
studies: case series, cross-  Discussion
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 studies sectional surveys,  Research
retrospective and prospective assignments
studies
Week 3 Analytical (ii) Analytical studies i.e  Lectures
studies: case-control, cohort,  Assignments
 Discussion
 Research
assignments
Week 4 Experimental  Features of experimental  Lectures
study designs study designs  Assignments
 Types of experimental study  Discussion
designs  Research
 Advantages and assignments
disadvantages of the designs
 Confounding
Week 5 Randomized  Tne the Steps/ protocol  Lectures
clinical/communit involved in RCTS  Assignments
y trials  Discuss  Discussion
Randomization/blinding  Research
 Identify Sources of biases assignments
Week 6 CAT ONE 
Week 7 Exposure and risk  Measures of association/risk:  Lectures
in studies; case control, cohort  Assignments
 Discussion
 Research
assignments
Week 8 Relative risk,  Relative risk, odds ratio and  Lectures
odds ratio and attributable risk  Assignments
attributable risk.  Adjusted/standardized  Discussion
relative risks  Research
 Application in studies assignments
Week 9 Monitoring and  Rationale of monitoring and  Lectures
modeling for modeling for diseases  Assignments
diseases.  Types of Models  Discussion
 Importance of disease Research
modelling assignments

Week 10 The mantel  Steps in mantel hanzel  Lectures

hanzel procedure  Assignments
 Explain its application in  Discussion
studies  Research
assignments
Week 11 Disease  Types and methods of  Lectures
surveillance disease surveillance  Assignments
 Sources of Surveillance data  Discussion
 Process of Establishing a  Research
surveillance system assignments
 Process/steps/Evaluation of
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 CAT II surveillance system
 Output of surveillance
 Uses of surveillance data
Week 12 Disease control  Describe disease control  Lectures
strategy strategies i.e  Assignments
o Health Education and  Discussion
promotion  Research
o Good nutrition assignments
o Immunization
o Proper personal and
environmental hygiene
Week 13 Disease control o Vector control  Lectures
Strategy  Assignments
 Discussion
 Research
assignments
Week 14 Disease control o Adequate Health care delivery  Lectures
Strategy system  Assignments
 Discussion
 Research
assignments
Week 15 & 16 EXAMS
Teaching and Lectures, Assignments, Discussion, Research assignments
learning
methodologies
Instructional Textbooks, Chalkboard/Whiteboard, Handouts,
materials and Newspaper and Magazines
equipment
Recommended  Foundation of Epidemiology 
Text Books
Textbooks for  
Further
Reading

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LECTURE ONE: INTRODUCTION TO APPLIED EPIDEMIOLOGY

1.1 LECTURE OVERVIEW

The World Health Organization defines epidemiology as ―the study of the distribution and
determinants of health-related states or events (including disease), and the application of this
study to the control of diseases and other health problems‖ Epidemiology is a science that
involves surveillance, data collection and analysis, and the use of data to create interventions
that improve the health of the target population. All public health activities hinge on the work
of epidemiologists in the field and in the laboratory as they collect data and generate
meaningful, comparable health statistics.

On a global scale, epidemiology is dependent on the standardization of data across countries.

The International Classification of Diseases (ICD) is the classification system that aims to
standardize diagnoses globally. The WHO compiles health measurement data from many
surveillance systems worldwide, and this collected data is analyzed and reported in their
―World Health Statistics‖publication

By the end of this lecture, you should be able to:

i. Define terms used in applied Epidemiology
ii. Highlight the uses of Epidemiology
iii. Outline the goals of epidemiology

1.2 Epidemiology Terms and Definitions

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Epidemiology is a science that encompasses extensive and diverse material.

The word epidemiology comes from the Greek words epi, meaning on or upon, demos,
meaning people, and logos, meaning the study of. In other words, the word epidemiology has
its roots in the study of what befalls a population. Many definitions have been proposed, but
the following definition captures the underlying principles and public health spirit of
epidemiology:
Epidemiology is the study of the distribution and determinants of health-related states or
events in specified populations, and the application of this study to the control of health
problems.
Key terms in this definition reflect some of the important principles of epidemiology.

Study

 Epidemiology is a scientific discipline with sound methods of scientific inquiry at its

foundation.
 Epidemiology is data-driven and relies on a systematic and unbiased approach to the
collection, analysis, and interpretation of data.
 Basic epidemiologic methods tend to rely on careful observation and use of valid
comparison groups to assess whether what was observed, such as the number of cases
of disease in a particular area during a particular time period or the frequency of an
exposure among persons with disease, differs from what might be expected.
 However, epidemiology also draws on methods from other scientific fields, including
biostatistics and informatics, with biologic, economic, social, and behavioral sciences.
 In fact, epidemiology is often described as the basic science of public health, and for
good reason.
o First, epidemiology is a quantitative discipline that relies on a working
knowledge of probability, statistics, and sound research methods.
o Second, epidemiology is a method of causal reasoning based on developing
and testing hypotheses grounded in such scientific fields as biology, behavioral
sciences, physics, and ergonomics to explain health-related behaviors, states,
and events. However, epidemiology is not just a research activity but an
integral component of public health, providing the foundation for directing
practical and appropriate public health action based on this science and causal
reasoning.

Distribution
Epidemiology is concerned with the frequency and pattern of health events in a population:
Frequency refers not only to the number of health events such as the number of cases of
meningitis or diabetes in a population, but also to the relationship of that number to the size of
the population. The resulting rate allows epidemiologists to compare disease occurrence across
different populations.
Pattern refers to the occurrence of health-related events by time, place, and person. Time
patterns may be annual, seasonal, weekly, daily, hourly, weekday versus weekend, or any
other breakdown of time that may influence disease or injury occurrence. Place patterns
include geographic variation, urban/rural differences, and location of work sites or schools.
Personal characteristics include demographic factors which may be related to risk of illness,
injury, or disability such as age, sex, marital status, and socioeconomic status, as well as

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behaviors and environmental exposures. Characterizing health events by time, place, and
person are activities of descriptive epidemiology,

Determinants

 Epidemiology is also used to search for determinants, which are the causes and other
factors that influence the occurrence of disease and other health-related events.
 Epidemiologists assume that illness does not occur randomly in a population, but
happens only when the right accumulation of risk factors or determinants exists in an
individual.
 To search for these determinants, epidemiologists use analytic epidemiology or
epidemiologic studies to provide the ―Why‖ and ―How‖ of such events. They assess
whether groups with different rates of disease differ in their demographic
characteristics, genetic or immunologic make-up, behaviors, environmental exposures,
or other so-called potential risk factors. Ideally, the findings provide sufficient
evidence to direct prompt and effective public health control and prevention measures.

Health-related states or events

 Epidemiology was originally focused exclusively on epidemics of communicable
diseases but was subsequently expanded to address endemic communicable diseases
and non-communicable infectious diseases.
 By the middle of the 20th Century, additional epidemiologic methods had been
developed and applied to chronic diseases, injuries, birth defects, maternal-child
health, occupational health, and environmental health.
 Then epidemiologists began to look at behaviors related to health and well-being, such
as amount of exercise and seat belt use.
 Now, with the recent explosion in molecular methods, epidemiologists can make
important strides in examining genetic markers of disease risk.
 Indeed, the term health related states or events may be seen as anything that affects the
well-being of a population. Nonetheless, many epidemiologists still use the term
―disease‖ as shorthand for the wide range of health-related states and events that are
studied.

Specified populations

 Although epidemiologists and direct health-care providers (clinicians) are both

concerned with occurrence and control of disease, they differ greatly in how they view
―the patient.‖
 The clinician is concerned about the health of an individual; the epidemiologist is
concerned about the collective health of the people in a community or population.
 In other words, the clinician‘s ―patient‖ is the individual; the epidemiologist‘s
―patient‖ is the community. Therefore, the clinician and the epidemiologist have
different responsibilities when faced with a person with illness.
 For example, when a patient with diarrheal disease presents, both are interested in
establishing the correct diagnosis.
 However, while the clinician usually focuses on treating and caring for the individual,
the epidemiologist focuses on identifying the exposure or source that caused the
illness; the number of other persons who may have been similarly exposed; the
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 potential for further spread in the community; and interventions to prevent additional
cases or recurrences.

Application
 Epidemiology is not just ―the study of‖ health in a population; it also involves applying
the knowledge gained by the studies to community-based practice.
 Like the practice of medicine, the practice of epidemiology is both a science and an art.
To make the proper diagnosis and prescribe appropriate treatment for a patient, the
clinician combines medical (scientific) knowledge with experience, clinical judgment,
and understanding of the patient.

Similarly, the epidemiologist uses the scientific methods of descriptive and analytic
epidemiology as well as experience, epidemiologic judgment, and understanding of local
conditions in ―diagnosing‖ the health of a community and proposing appropriate, practical,
and acceptable public health interventions to control and prevent disease in the community

Incidence: number of new cases that occur in a population during a certain time period; can
also be called an attack rate (especially when used during an epidemic)

Prevalence: number of cases that exist in a population during a certain time period (point
prevalence is number of cases at a single point in time)

Mortality rate: number of deaths in a population during a specific time interval

Years of Potential Life Lost (YPLL): the number of years lost due to premature mortality;
measures the effect of premature death on a population

Disability-Adjusted Life Year (DALY): the number of years lost due to disability, illness, or
premature death; measures the burden of a disease in a population

Adjusted rates: when rates are statistically modified to eliminate the effect of certain
characteristics of the population on the data (like age, sex, or race). For example, higher death
rates in one city may be due to a higher proportion of elderly people in the area, so this
mortality data might be age-adjusted to account for differences in age when comparing it with
data from other cities.

Crude rates: non-adjusted rates

Case-fatality rate (CFR): the proportion of cases that die from a particular disease/health
issue (number of cause-specific deaths over number of incident cases)

Cluster: when cases of a disease or health condition are closely tied by time and place
(particularly important when looking at cancers, birth defects, and outbreaks)

Endemic: the usual incidence or prevalence of a certain disease in a population; the baseline
or expected number of cases in a population; can vary between geographic areas

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Epidemic: when the number of cases of a disease rises above endemic levels in a specific area
or among a specific population over a particular time period

Pandemic: an epidemic occurring over several countries or continents and usually affecting a
large proportion of the population

Health indicator: measurement that reflects the health state of people in a population; infant
mortality rate is often used as a health indicator of entire countries because it is influenced by
multiple factors such as maternal health, environmental conditions, education levels, and
access to medical care

Validity: the degree that a measurement accurately measures what it purports to measure

Vital statistics: information about births, marriages, divorces, and deaths in a population that
comes from their systematic registration by local health authorities

Sensitivity: the proportion of people with the disease that a test finds positive; a highly
sensitive test has a low rate of false negatives (an ideal test is 100% specific and 100%
sensitive)

Specificity: the proportion of people without the disease that a test finds negative; a highly
specific test has a low rate of false positives (an ideal test is 100% specific and 100%
sensitive)

1.3Goals in Epidemiology

Epidemiology is conceptually goal oriented and purposeful. As such, it focuses on three

distinct objectives, viz. therapeutic, preventive, health maintenance and promotion.

1. Maintenance and promotion of the healthy state.

2. Preventive action - to inhibit the transition from healthy to the unhealthy state by avoiding
and/or minimizing exposure to risk factors.
3. Curative (therapeutic) - increasing recoveries from unhealthy to the healthy state and thus
minimizing mortalities.

. You have come to the end of lecture one. In this lecture you have
learnt the following; definition of terms used in epidemiology, goals and uses
of epidemiology

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 Now take a break and reflect on some of the issues we
have discussed today. After your break, answer the following questions:
1. Define the following terms as used in applied epidemiology
i. Study
ii. Prevalence
iii. Crude rate
iv. Agent
2. Account for this statement, ― Epidemiology is the basic science of Public
Health‖_____________________________________________________
______________
3. Highlight the uses of
epidemiology_____________________________________

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LECTURE TWO: TYPES OF EPIDEMIOLOGY STUDIES

LECTURE OVERVIEW

Epidemiological studies may deal merely with the distribution of diseases/conditions in

human populations (descriptive surveys), and/or with the factors influencing the
distribution and the frequency of diseases (analytic surveys: cross-sectional, case-control,
cohort, quasi-experiment and experimental studies).

By the end of this lecture, you should be able to:

i. Classify epidemiological studies
ii. Differentiate between observational and experiment
studies
iii. Identify types of descriptive studies
iv. Describe the advantages and disadvantages of
descriptive studies

2. 1 Observational Studies: Descriptive & Analytical Types

Observational studies involve no intervention other than asking questions and carrying
out medical examinations and simple laboratory tests or X-ray examinations. In
epidemiology, observational studies are more common than experimental ones,
particularly if an investigator wants to determine whether an agent or exposure causes
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cancer in humans.

2.1Descriptive Studies

Descriptive studies tend to be simpler and easier to conduct than analytical or

experimental studies but they are nonetheless quite important. Descriptive studies can
provide the background from which analytical studies emerge. They help to generate
hypotheses, as opposed to testing them.

Advantages:

 A large range of outcomes because no subgroups are studied

 A large range of potential predictors again because no subgroups are studied

Disadvantages:

 Not possible to study subgroups

 No control for confounding as data is in aggregate form
 Not able to reproduce/replicate results as data was not collected in an experiment
with defined perimeters.

i. Cross-Sectional Comparison Studies: "Am I like my neighbors?"

Cross-sectional design is referred to as non-directional or one point in time survey, where

data is collected on both outcome and exposure status of the individuals under study.
Such studies are useful to describe characteristics of study population and can generate
new ethiological hypothesis. This study design involves disease prevalence. Cross-
sectional studies can evaluate the impact of changes in health services during an
intervening period. Cross-sectional studies compare data that are combined from smaller
groups as opposed to very large descriptive studies. These studies focus on observations
made at only one point in time so they are quickly completed and relatively inexpensive.
But they cannot reveal a sequence of events over time since they sample data only once.

Cross-sectional studies often simply compare the rate of a particular cancer in one place
versus another place.

Advantages of cross-sectional studies

1. Describe the distribution of both exposure and outcome in a population
(particularly useful for studying frequent outcomes of long duration).
2. Provide estimates of the magnitude of a disease problem in a community, which
might be very important for planning of health services.
3. Compared with other studies are relatively quick and inexpensive. Often, involve
only one-time survey.
4. Largely applicable: provision of health care services as well as generation of
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 ethiological hypothesis.

Disadvantages of cross-sectional studies

1. Do not measure risk, because this would require incidence data.
2. Can not determine cause-effect relationship.
3. Current exposure status may be due to changes that have occurred as a result of the
disease rather than having led to the disease.
Diseases of short duration may be missed. Thus, cross-sectional studies are best applied
to the study of chronic or persistent conditions.

2. Correlation (Ecologic) Studies: "What if I am exposed to this?"

Ecologic studies look at diet and cancer at the population level, think of this as the view
from 30,000 feet. These types of studies represent a transition to analytical studies since
they compare cancer rates of populations in relation to risk factors. They do not include
outcome so they aren't considered analytical.

Examples:

 The diet-cancer correlation

 Following populations as they migrate to compare cancer rates

Advantages:

Ecologic studies can provide powerful clues pointing in a particular direction, especially
when they compare large populations with different diets.

Disadvantages:

 Ecologic studies can't prove cause and effect.

 Scientists need more evidence from other studies to help prove the connection that
ecologic studies point to

Below is a flow chart to help you understand how study types are classified. Each type is
then discussed individually so you can learn more about its purpose.

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Chart adapted from "MedPage Tools: Guide to Biostatistics"

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 .

Image courtesy of American Institute of Cancer Research

. You have come to the end of lecture one. In this lecture

you have learnt the following
i. Classification of epidemiological studies
ii. Differences between observational and experimental studies
iii. types of descriptive studies
iv. The advantages and disadvantages of descriptive studies

Now take a break and reflect on some of the issues we have

discussed today. After your break, answer the following questions:
1. Differentiate between descriptive and analytical studies
2. Give the advantages of descriptive studies______________________
3. Highlight the advantages and disadvantages of descriptive
studies______________

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LECTURE THREE: ANALYTICAL STUDY

3.1 LECTURE OVERVIEW

The key feature of analytic epidemiology is a comparison group. Consider a large outbreak of
hepatitis A that occurred in Pennsylvania in 2003. Investigators found almost all of the case-
patients had eaten at a particular restaurant during the 2–6 weeks (i.e., the typical incubation
period for hepatitis A) before onset of illness. While the investigators were able to narrow
down their hypotheses to the restaurant and were able to exclude the food preparers and
servers as the source, they did not know which particular food may have been contaminated.
The investigators asked the case-patients which restaurant foods they had eaten, but that only
indicated which foods were popular. The investigators, therefore, also enrolled and
interviewed a comparison or control group — a group of persons who had eaten at the
restaurant during the same period but who did not get sick. Of 133 items on the restaurant's
menu, the most striking difference between the case and control groups was in the proportion
that ate salsa (94% of case-patients ate, compared with 39% of controls). Further investigation
of the ingredients in the salsa implicated green onions as the source of infection. Shortly
thereafter, the Food and Drug Administration issued an advisory to the public about green
onions and risk of hepatitis A. This action was in direct response to the convincing results of
the analytic epidemiology, which compared the exposure history of case-patients with that of
an appropriate comparison group.

By the end of this lecture, you should be able to:

i. Describe descriptive epidemiology
ii. Classify analytical epidemiological studies
iii. Describe the advantages and disadvantages of
descriptive studies
iv. Differentiate between cohort and case control
studies

When investigators find that persons with a particular characteristic are more likely than those
without the characteristic to contract a disease, the characteristic is said to be associated with
the disease. The characteristic may be a:

 Demographic factor such as age, race, or sex;

 Constitutional factor such as blood group or immune status;
 Behavior or act such as smoking or having eaten salsa; or
 Circumstance such as living near a toxic waste site.

Identifying factors associated with disease help health officials appropriately target public
health prevention and control activities. It also guides additional research into the causes of
disease.
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Thus, analytic epidemiology is concerned with the search for causes and effects, or the why
and the how. Epidemiologists use analytic epidemiology to quantify the association between
exposures and outcomes and to test hypotheses about causal relationships. It has been said that
epidemiology by itself can never prove that a particular exposure caused a particular outcome.
Often, however, epidemiology provides sufficient evidence to take appropriate control and
prevention measures.

Cohort study. A cohort study is similar in concept to the experimental study. In a cohort study
the epidemiologist records whether each study participant is exposed or not, and then tracks
the participants to see if they develop the disease of interest. Note that this differs from an
experimental study because, in a cohort study, the investigator observes rather than determines
the participants' exposure status. After a period of time, the investigator compares the disease
rate in the exposed group with the disease rate in the unexposed group. The unexposed group
serves as the comparison group, providing an estimate of the baseline or expected amount of
disease occurrence in the community. If the disease rate is substantively different in the
exposed group compared to the unexposed group, the exposure is said to be associated with
illness.

The length of follow-up varies considerably. In an attempt to respond quickly to a public

health concern such as an outbreak, public health departments tend to conduct relatively brief
studies. On the other hand, research and academic organizations are more likely to conduct
studies of cancer, cardiovascular disease, and other chronic diseases which may last for years
and even decades. The Framingham study is a well-known cohort study that has followed over
5,000 residents of Framingham, Massachusetts, since the early 1950s to establish the rates and
risk factors for heart disease. The Nurses Health Study and the Nurses Health Study II are
cohort studies established in 1976 and 1989, respectively, that have followed over 100,000
nurses each and have provided useful information on oral contraceptives, diet, and lifestyle
risk factors. These studies are sometimes called follow-up or prospective cohort studies,
because participants are enrolled as the study begins and are then followed prospectively over
time to identify occurrence of the outcomes of interest.

An alternative type of cohort study is a retrospective cohort study. In this type of study both
the exposure and the outcomes have already occurred. Just as in a prospective cohort study,
the investigator calculates and compares rates of disease in the exposed and unexposed groups.
Retrospective cohort studies are commonly used in investigations of disease in groups of
easily identified people such as workers at a particular factory or attendees at a wedding. For
example, a retrospective cohort study was used to determine the source of infection of
cyclosporiasis, a parasitic disease that caused an outbreak among members of a residential
facility in Pennsylvania in 2004. The investigation indicated that consumption of snow peas
was implicated as the vehicle of the cyclosporiasis outbreak.

Case-control study. In a case-control study, investigators start by enrolling a group of people

with disease (at CDC such persons are called case-patients rather than cases, because case
refers to occurrence of disease, not a person). As a comparison group, the investigator then
enrolls a group of people without disease (controls). Investigators then compare previous
exposures between the two groups. The control group provides an estimate of the baseline or
expected amount of exposure in that population. If the amount of exposure among the case
group is substantially higher than the amount you would expect based on the control group,
then illness is said to be associated with that exposure. The study of hepatitis A traced to green
onions, described above, is an example of a case-control study. The key in a case-control study
17
is to identify an appropriate control group, comparable to the case group in most respects, in
order to provide a reasonable estimate of the baseline or expected exposure.

From an analytic viewpoint the cross-sectional study is weaker than either a cohort or a case-
control study because a cross-sectional study usually cannot disentangle risk factors for
occurrence of disease (incidence) from risk factors for survival with the disease. (Incidence
and prevalence are discussed in more detail in Lesson 3.) On the other hand, a cross-sectional
study is a perfectly fine tool for descriptive epidemiology purposes. Cross-sectional studies are
used routinely to document the prevalence in a community of health behaviors (prevalence of
smoking), health states (prevalence of vaccination against measles), and health outcomes,
particularly chronic conditions (hypertension, diabetes).

In summary, the purpose of an analytic study in epidemiology is to identify and quantify the
relationship between an exposure and a health outcome. The hallmark of such a study is the
presence of at least two groups, one of which serves as a comparison group. In an
experimental study, the investigator determines the exposure for the study subjects; in an
observational study, the subjects are exposed under more natural conditions. In an
observational cohort study, subjects are enrolled or grouped on the basis of their exposure,
then are followed to document occurrence of disease. Differences in disease rates between the
exposed and unexposed groups lead investigators to conclude that exposure is associated with
disease. In an observational case-control study, subjects are enrolled according to whether they
have the disease or not, then are questioned or tested to determine their prior exposure.
Differences in exposure prevalence between the case and control groups allow investigators to
conclude that the exposure is associated with the disease. Cross-sectional studies measure
exposure and disease status at the same time, and are better suited to descriptive epidemiology
than causation.

Now take a break and reflect on some of the issues we have

discussed today. After your break, answer the following questions

Classify each of the following studies as:

1. Experimental
2. Observational cohort
3. Observational case-control
4. Observational cross-sectional
5. Not an analytical or epidemiologic study

1. ____ Representative sample of residents were telephoned and asked how much they
exercise each week and whether they currently have (have ever been diagnosed with)
heart disease.
2. ____ Occurrence of cancer was identified between April 1991 and July 2002 for
50,000 troops who served in the first Gulf War (ended April 1991) and 50,000 troops
who served elsewhere during the same period.
3. ____ Persons diagnosed with new-onset Lyme disease were asked how often they walk
through woods, use insect repellant, wear short sleeves and pants, etc. Twice as many
18
 patients without Lyme disease from the same physician's practice were asked the same
questions, and the responses in the two groups were compared.
4. ____ Subjects were children enrolled in a health maintenance organization. At 2
months, each child was randomly given one of two types of a new vaccine against
rotavirus infection. Parents were called by a nurse two weeks later and asked whether
the children had experienced any of a list of side-effects.

References

1. Kannel WB. The Framingham Study: its 50-year legacy and future promise. J
Atheroscler Thromb 2000;6:60-6.
2. Centers for Disease Control and Prevention. Asthma mortality — Illinois, 1979–1994.
MMWR. 1997;46(MM37):877–80.
3. Centers for Disease Control and Prevention. Hepatitis A outbreak associated with
green onions at a restaurant–Monaca, Pennsylvania, 2003. MMWR 2003;
52(47):1155–7.
4. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA,
Nathan DM, Diabetes Prevention Program Research Group. Reduction in the incidence
of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med
2002;346:393–403.
5. Colditz GA, Manson JE, Hankinson SE. The Nurses' Health Study: 20-year
contribution to the understanding of health among women. J Women's Health
1997;49–62.
6. Centers for Disease Control and Prevention. Outbreak of Cyclosporiasis associated
with snow peas—Pennsylvania, 2004. MMWR 2004;53:876–8.

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LECTURE FOUR: COHORT EPIDEMIOLOGIC STUDIES

4.1 LECTURE OVERVIEW

The "What will happen to me?" study follows a group of healthy people with different levels
of exposure and assesses what happens to their health over time. It is a desirable design
because exposure precedes the health outcome — a condition necessary for causation — and
is less subject to bias because exposure is evaluated before the health status is known. The
cohort study is also expensive, time-consuming and the most logistically difficult of all the
studies. It is most useful for relatively common diseases. To assess suitability, we find out the
commonality of the disease we wish to study.

By the end of this lecture, you should be able to:

i. To differentiate the types of cohort studies
ii. Identify the steps in conducting cohort studies
iii. Highlight the advantages and disadvantages of cohort
studies
iv. Describe biases in cohort studies

4.2 Types of Cohort Studies

I. Prospective Cohort Study.
II. Concurrent Cohort Study
The cohort is assembled now (i.e. in the present), and followed into the future. Data collection
is more satisfactory in the concurrent cohort study. Such studies are often called Prospective
Cohort Studies.
III. Historical Cohort Study. The cohort is identified from past records and followed
forward from that time to present. A good example is the Dutch famine study. During
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 the Second World War a period of acute food shortage occurred in Holland. All the
women who were pregnant at the time were identified.
When their infants were born anthropometric measurements were made on the infants to see
the effects of food shortage in the mother occurring at different stages of pregnancy. The
babies form a cohort which has been followed into adulthood to study the long term effects of
food deprivation during foetal life. In the case of historical cohorts the data has to be
sufficiently robust for obtaining meaningful answers.
Retrospective Cohort Study
The relevant events viz. exposure and outcome have already taken place. This type of study is
in contrast to prospective cohort studies where the relevant exposure may or may not have
occurred at the time of commencement, but the outcomes have certainly not yet occurred.
Cohort studies can be distinguished from case-control studies by the important characteristic
that they classify subjects by presence or absence of exposure whereas in case-control studies
classification is by outcome.
In a given situation the selection of case-control or cohort design will depend on the research
question being asked (hypothesis being tested), the resources available and the current state of
knowledge. The objective is to choose a design that would yield the most reliable and
informative answer.
In the case of cohort studies the choice of a prospective or retrospective design depends on the
research question as well as logistical considerations. Retrospective designs can be conducted
relatively quickly and cheaply because all relevant events have already happened. They are
commonly employed for studying diseases with long latency periods for outcomes to happen.
The drawback is that relevant information about exposure may not be very reliable because it
was recorded in the past. Similarly, information about confounders may not be available
because they were not thought of at the time of recording the information. These drawbacks
are overcome in prospective studies, but the cost is also proportionately greater.
4.3 Criteria for Conducting Cohort Studies
Two criteria must be fulfilled in conducting any type of a cohort study:
 Observation must take place over a meaningful period of time so that the outcome
under study has a reasonable time to occur. One should also bear in mind that the
longer the period of follow-up the greater is the potential for drop-outs to occur.
 All members of the cohort should be observed over the full period of follow-up. Drop-
outs can distort the study, especially if the reasons for dropping out are related to the
outcome.
4.4 Advantages and Disadvantages of Cohort studies
Advantages:
1. If the study groups have been properly selected they allow direct calculation of
incidence or morbidity rates rather than an odds ratio. Cohort designs are a powerful
strategy for measuring incidence.
2. They allow the most unambiguous determination of a temporal sequence. A potential
cause gets measured before the outcome, and so there is less likelihood of bias.
Moreover, all important variables can be measured carefully instead of depending on
memory.
3. A study can be designed such that several different kinds of outcomes can be
determined at the same time e.g. anxious attachment in infancy and educational, social
and emotional outcomes in late childhood. Measure incidence and thus permit direct
estimation of risk of disease.
4. Do not rely on memory for information about exposure status, hence avoid bias due to
selective recall.

21
 5. Since cohort studies begin with people free of disease, potential bias due to selective
survival is eliminated.
6. Cohort studies provide a logical approach to studies of causation or effects of
treatment.
7. Cohort approach can yield information on associations of exposure with several
diseases.

Cohort studies are the best available observational studies as substitutes for true experimental
studies.
Disadvantages:
1. The main disadvantage is that if the outcome is infrequent, a large number of people
must enter the study and be followed for a long time before results become available.
This has implications for costs with regard to staff, transportation and time. Cohort
studies are more efficient for outcomes which are common, and not so good for rare
diseases.
Cohort studies work best when the exposure factor is relatively rare but has a high attack rate
e.g. a study of the sequelae of serious head injury. A large number of controls without such a
history can be assembled easily; on the other hand those with serious head injury are very
likely to show some sequelae in a reasonably short time. Non-concurrent cohort studies avoid
some of the constraints in tracking subjects. On the other hand there is a likelihood of bias
similar to case-control studies in eliciting past exposure.
2. The second disadvantage is that the condition being studied may be present at the
beginning but asymptomatic and goes clinically undiagnosed. Require large samples to
yield the same number of cases that could be studied more efficiently in a case-control
study.
3. Particularly inefficient for studies of rare diseases.
4. Logistically difficult – long follow-up period, often serious attrition to study subjects.
5. Direct observation of participants may cause changes in health behavior.
6. Possible bias in ascertainment of disease due to changes over time in criteria and
methods.
7. Very costly.

The design of a cohort study is sketched below:

Exposed
No disease
People without

the disease
Population
“at risk”

Disease
22

Not exposed
4.5 Steps in Planning a Cohort Study
• Assemble the initial cohort with the defined baseline characteristics.
• Devise a scheme for tracking the cohort's members, making sure that no biases are operating
that could influence the determination of exposure, and that exposure did take place. A major
difficulty arises from the fact that subjects have freedom of movement and of lifestyle. A great
deal of time and effort gets expended in keeping track of them.
• Develop objective outcome criteria.
• Develop an unbiased method of ascertaining outcome status.
• Determine ways of measuring other factors (confounders) that may influence the outcome.
Selection of Subjects
The selection of subjects is determined by the frequency of exposure and the need to obtain
complete and reliable information about both exposure and outcome on all the study subjects.
For relatively common exposures like cigarette smoking, alcohol consumption, bottle feeding
and so on, a sufficiently large number of subjects can be enrolled from a variety of sources. In
the case of rare exposures, special groups may need to be considered, for example, exposure to
lead or to radiation or industrial toxins, and so on. Such special exposure cohorts allow the
evaluation of rare conditions.
Sometimes subjects are chosen because of the ease with which reliable and detailed
information about exposure and outcome data can be collected. Professions like nurses,
doctors, teachers, civil servants, workers in different industries, and similar well defined
groups make ideal subjects for cohort study designs.
4.6 Selection of Comparison Groups
A careful choice is as important as in the case of case-control studies, the main principle being
that the two groups should be as similar as possible in all respects except for the exposure
factor being studied. If there is no association between exposure and the disease then the
disease rates between the two populations would be similar.
If there is one single cohort initially being recruited then its members can be categorized by
degree of exposure and comparison be made of disease rates between different categories of
exposure.
The rates of mortality and disease occurrence in the general population may be used for
comparison with the corresponding rates in a special cohort e.g. rates of a disease in the
general population and amongst workers in a chemical plant. Such a comparison will
underestimate the true association between exposure and disease because in such cases a part
of the general population is in fact exposed. There are also other issues which muddy the
results. The general population happens to contain people who are ill or disabled and therefore
unable to work, and disease rates among them are generally higher than in the working
population. Moreover, other factors like lifestyle, smoking, diet, housing, and so on may be
different between the groups being compared. To overcome these difficulties a comparison
cohort is selected from the general population which is closely matched with the study cohort
except for the exposure factor. Sometimes several comparison cohorts are enrolled. If study
results show similar levels of association between exposure and disease for several
comparison groups the case for validity is that much stronger.
In all cohort studies followup of cohort members is the main challenge. The larger the number
and the longer the period of follow-up the greater are the chances of drop-outs.
Information about Exposure
23
The use or pre-existing records saves time and cost. But the amount of detail may not be
sufficient for the study. Nor are the details of possible confounding factors likely to be
adequately recorded. In most situations details obtained from pre-existing records would need
to be supplemented by interviews, questionnaires, physical examination and laboratory tests.
The information gathered at the time of enrollment about changes in employment, work
patterns, life-style, diet and so on, needs to be updated at each follow-up.
Information about Outcome
In all cohort studies the goal is to obtain complete and unbiased information about the
outcome in every subject. Hospital records, physical examination, and laboratory tests at end-
point, questionnaires and interviews are the common methods of recording outcomes. The
important issue is that whatever the procedures used for recording outcome they should be
applied equally to all the groups, exposed and unexposed.
Analysis of Data

Activity 4.1
Discuss the how you will analyse cohort studies
________________________________________________________
________________________________________________________
_________________________________________________________

1). Retrospective Cohort Studies.

A cohort is assembled. Medical records are studied to obtain data about base-line
measurements and personal characteristics. The cohort is followed up for observing outcome.
For example, a cohort of children less than 3 years old and presenting with asthma and
bronchitis is assembled. Data about feeding in infancy, family history of atopy, and any
serious respiratory illness in the past are obtained.
The cohort is then observed for studying the outcome (e.g. spontaneous remission).
The advantages are:
 Predictor variables preceded the outcome, and observations are made before the
outcome is known.
 Hence there is less likelihood of bias.
 Cost is reduced since the subjects are already assembled, and base-line measurements
are all made.
 All with and without the outcome are from the same population.
The disadvantages are:
 There is no quality control over measurements.
 The data about past history may be incomplete.
2). Nested Case-Control Study
This is so called because it is a case-control study 'nested' within a cohort study. Within an on-
going cohort first an outcome is defined. All the members of the cohort who have developed
the outcome are identified. From amongst those who have not developed the outcome a
random sample is taken. Medical records of both groups before the outcome occurred are
studied and predictor variables are compared between the two groups. For example, a cohort
of children who were referred to hospital for febrile convulsions is assembled. In this cohort
all those who go on to develop non-febrile recurrent seizures are compared with a random
sample of those who do not develop this complication for defined predictor variables like birth

24
history, family history, characteristics of associated illness at the time of first febrile
convulsion, type of convulsion, and so on.
3). Double Cohort Study.
Two distinct cohorts are assembled on the basis of exposure to a risk factor like Exposed / Not
Exposed / or Low Level Exposure. For example, two cohorts of children one comprising those
who received orally a traditional medicine containing lead, and another made of those who
had traditional cosmetics containing lead (kohl) applied to the eyes or cheeks are compared for
signs of lead toxicity with healthy children not exposed to lead.
This type of study design is not to be confused with case-control design. The samples are
chosen by exposure
. In case-control design samples are chosen by outcome.
4.7 Choosing Cohort study Designs
Cohort studies are best suited for the following situations:
 For accurately describing the incidence or natural history of a condition.
 Often they are the only way of firmly establishing the temporal sequence.
 They are useful in studying rapidly fatal diseases.
 One advantage of cohort studies is that several outcome variables may be studied
simultaneously. For example, smoking causes not only heart disease but also chronic
respiratory disease, lung cancer, and is associated with peptic ulcer. As different types
of events accumulate it is possible to study several outcomes.
Because of their costs and the time taken to answer the research question cohort studies are
undertaken when less expensive approaches fail to answer the research question satisfactorily.
Deciding about the type of cohort design will depend upon both practical and scientific
considerations. If the research question can be answered by the data already existing a
retrospective cohort design may suffice. On the other hand if the research question is about
outcomes which are frequent in occurrence a prospective cohort design may be more fruitful.
With regard to subjects, if the research question is about describing the natural history of a
condition the sample must closely resemble the target population to which the results would be
applied.
4.8 Bias in Cohort Studies
Bias can arise in cohort studies because of a number of reasons:
 The degree of accuracy with which subjects have been classified with respect to
exposure and disease status.
 Information bias.
 Accuracy in diagnosing the outcome.
 Drop-outs or loss to follow-up. This may be due to causes related to exposure,
outcome, or both.
 Non-participation. Those who agree to participate are likely to differ from those who
refuse with
 regard to motivation, attitude towards health, risk factor status etc.

Confounding bias.
 In general, the likelihood of selection bias is much less in cohort compared to case-
control studies. In prospective cohort studies exposure is assessed before the
occurrence of the disease. Hence it is very unlikely that outcome would influence
classification of exposure. This pitfall happens in retrospective studies where exposure
and outcome have already taken place at the commencement of the study. If
knowledge of outcome is to influence classification of exposure then selection bias
may result in the same manner as it does in case-control studies.

25
  Inaccurate classification with regard to exposure or disease status can be the major
source of error in cohort studies. Careful definitions at the planning stage can help to
avoid this problem.
 Drop-outs are another cause of bias. Cohort studies require following individuals for a
sufficient length of time to allow the outcomes to happen. By then it is inevitable that
some of the subjects may have changed their address, some may have lost interest,
moved away or died. If loss to follow up is in excess of 30 to 40 per cent the results
would be biased. Hence choice of a stable population at the design stage of the study is
important. For the drop-outs a knowledge of their backgrounds like occupation,
education, income, ethnicity, life-style, and so on is helpful. If it can be shown that
those who dropped out of the study are not very different from those who stayed, then
the results are more valid. Another approach is to first assume that all drop-outs
developed the outcome and calculate rates accordingly. Next assume that they did not,
and again estimate the results. The two results provide a range between which the
actual results lie.
Refusal to respond poses yet another kind of problem. If non-response is related to exposure
status the results would under estimate the strength of the association.

. You have come to the end of lecture one. In this lecture you have
learnt the following; types of cohort studies, prospective and retrospective
cohort, steps involved in the conduct of cohort studies, advantages and
disadvantages of cohort studies

Now take a break and reflect on some of the issues we

have discussed today. After your break, answer the following questions:
i. Differentiate between prospective and historical cohort
studies__________________________________________
ii. Describe the steps in the conduct of cohort
studies____________________________________________
__
iii. Identify biases in cohort studies and describe how they can be
prevented
iv. Highlight the disadvantages in cohort studies

26
Modern Epidemiology, 2nd Ed Rothman, K. J. and Greenland, S Lippincott, Philadelphia 0-
7216-6181-5-51985

Essentials of Epidemiology in Public Health by Ann Aschengrau and George R. Seage III,
Jones and Bartlett Publishers, Boston and London

The UFAW Handbook on The Care & Management of Laboratory Animals, Trevor Poole
(Ed). Longman Scientific & Technical

LECTURE FIVE : CASE CONTROL EPIDEMIOLOGIC STUDIES

5.1 LECTURE OVERVIEW

The "why me?" study investigates the prior exposure of individuals with a particular health
condition and those without it to infer why certain subjects, the "cases," become ill and others,
the "controls," do not. The main advantage of the case-control study is that it enables us to
study rare health outcomes without having to follow thousands of people, and is therefore
generally quicker, cheaper and easier to conduct than the cohort study.

27
By the end of this lecture, you should be able to:

i. Identify the steps in conducting case control

5.2 Types of Case Control designs
- Nested case-control study – primary based, within a fully enumerated cohort.
- Case-cohort – same control group representing every person in a cohort – used
with multiple case series. Produces risk ratios. Unable to implement density
sampling in this way, because sampling at the time of case occurrence (risk-set
sampling) requires a different control sample for each case series.
- Density case-control study – density sampling and risk set sampling are two
approaches to sampling that provide control series representative of the person-
time experience of the source population.
- Cumulative case-control studies – where sampling begins after all the cases
have occurred – e.g.: epidemic of diarrheal illness. Results in OR, which may
be equal to RR or IR if R < 0.10. More sensitive to bias from exposure-related
LTFU, since the entire cohort was not enumerated to begin with

5.3 Control selection – exposure distribution among the controls must be the same as it
is in the source population of cases. This need only be true within strata, and not
between strata, as long as stratification is taken into account.
- Represented by the relationship, r = B1/T1 = B0/T0, for a source population
defined with respect to person-time.
- In a cohort study, I1 = A1/T1 and I0 = A2/T2.
- But we replace the denominator with the control series, so that I1 = A1/B1 and I0
= A0/B0. These are pseudo rates, which may be related to the true rates if the
control sampling rate, r, is known.
- Even if r is not known, if control selection correctly sampled from the source
population, then B = r*T and the ratio of pseudo-rates is equal to the incidence
rate ratio.
- The ratio of pseudo-rates, often called the cross-product ratio, is also
commonly thought of as the exposure odds ratio (i.e.: (A1/A0)/(B1/B0)) – the
ratio of odds of being exposed among cases versus controls.
- Does not require rare disease assumption.
5.4 Defining the source population
Primary base or population-based study – cases selected from a precisely defined
and identified population, and controls directly sampled from same population.
Random sampling is most desirable.
Secondary base studies – not possible to identify the source population explicitly,
and simple random sampling not feasible. Must select controls so that they would
28
 simulate the exposure distribution in the source population. E.g.: Patients treated
for severe psoriasis at the Mayo Clinic – come from all over the world – unable to
identify folks who would attend the Mayo Clinic if they had psoriasis).
5.5 Case selection
May be incomplete, so long as the case sampling rate is equal for exposed and non-
exposed cases.
5.6 Control selection
Must be selected from same population that gives rise to study cases, or a
population with an identical exposure distribution.
Within strata of stratification factors, controls should be selected independently of
their exposure status.
Controls may represent person-time if the sampling probability of any control is
proportional to the amount of person-time that person spends at risk of disease in
the source population (incidence-density sampling) – allows estimation of rates –
density case control study.
Controls may represent those at cohort entry if each subject in the source
population has an equal chance of selection as a control, regardless of time spent at
risk / under follow-up, and including those that ultimately acquire disease – case-
cohort study – allows estimation of RR.
Controls may represent those without disease at the end of follow-up – cumulative
case-control study – allows estimation of incidence OR.
For density sampling or for estimation of risk ratios, a person may be selected as a
control and yet remain eligible to become a case – or may even be selected as a
control more than once – corresponds to person contribution multiply to person-
time and to both numerators and denominators in cohort studies.
Fallacies – Do not restrict controls to those at risk for exposure. These subjects
would be part of the unexposed portion of the source population and would be
included in the corresponding cohort study.
Neighborhood controls: Used out of convenience. E.g.: service area of a hospital.
However, may be misleading – e.g.: VA hospitals – patients different from individuals in
the neighborhood – military experience. Possibly poor recall as well – unmotivated.
Dead controls: Great, so long as causes of death are not related to exposure. May enhance
comparability of information if cases are dead.
Random-digit dialing: Must distinguish commercial from residential, ensure that each
residence may has an equal probability of contact and response/enrollment. Expensive –
recent developments mean phone numbers may not be linked to geographic areas. Possibly
poor recall as well – unmotivated.
Hospital- or clinic-based controls
Premise: Source population of cases in a given clinic is composed of those who
would seek medical care at that clinic, which may be represented by those who do
seek medical care at that clinic.
Problem: Source population is actually those who would seek medical care at that
clinic if they had the given disease, which may be different for other diseases.
Problem: Exposure distribution may differ from those of the source population –
exposure may be related to hospitalization generally, or may be associated with
other diseases, or both. Over-representing exposure prevalence in the control series
will attenuate the study OR. E.g.: smoking and leukemia. Use of controls with
cardiovascular and respiratory diseases.
Solution: Exclude from the control series those hospitalized with diseases known to
be related to smoking. Exclude liberally – if wrong, the series simply becomes
29
 more homogeneous. But make sure there is some diversity in the series, just in case
one of the included sources does happen to be related to exposure – a variety of
diagnoses dilutes the biasing effects.
Exposure related to hospitalization – Berkson‘s bias – cannot be remedied.
Friend controls
Uses individual matching – pros and cons.
Friends and cases may be more likely to share similar exposure history.
Alternatively, friends of cases may be less likely to share exposures – e.g.: having
learning problems, disliking school. Exposure history of socially active people
more likely to be represented.
Strengths: relatively quick and inexpensive, appropriate for rare outcomes, conducted with
moderate numbers of subjects, examine multiple exposures (this is accomplished by cohort
studies as well).
Weaknesses: Incidence rates / risks cannot be estimate (without knowing the sampling rate
of cases and controls), not appropriate for rare exposures, subject to recall biases if
retrospective, difficulty assembling a correct control series.
- Associations are statistical findings.
- Associations may be of three types:
 Spurious – false – Sampling error or bias. E.g.: False positives due to multiple
comparisons. E.g.: Confounding.
 Non-causal associations. Real associations that are not causal. E.g.: Prevention
of death causes an increase in time at risk for car accident, giving rise to a non-
causal association between therapy and car accidents.
 Causal – See Bradford Hill criteria. Those in which changes in the exposure
produce changes in the outcome.

- Accuracy = value of the parameter is estimated with little error.

- Errors = random or systematic.
- Systematic errors = biases. Opposite of bias = validity. Systematic error has a non-zero
expected value, regarding its departure from the true value of an association.
- Opposite of random error = precision. Random error has an expected value of zero,
regarding its departure from the true value of an association.
- Internal validity – violations – confounding, selection bias, and information bias.
- Confounding
- Mixing of effects. Apparent effect of the exposure is distorted.
- When the measure of association does not equal the measure of effect, because of
differences in variables other than the exposure.
- Surrogates can stand in for confounders – e.g.: age as a surrogate for aging.
- Confounder must be an extraneous risk factor for the disease under study, where
extraneous means apart from the exposure. I.e.: it must be exposed with the disease in
the unexposed group. E.g.: Pizza consumption is a confounding factor for the beer –
rectal cancer relationship? No, pizza consumption is associated with rectal cancer only
because of its association beer consumption. In fact, the pizza-rectal cancer
relationship is confounded by beer. For case control studies, must look at the control
series / source population, not the case series. The confounder might not actually be a
risk factor for the disease – but then it must be a surrogate for one. Judging this criteria
requires external knowledge – one would not want to over-adjust, or adjust the
estimate for a random error.
- Confounder must be associated with the exposure in the source population. For cohort
30
 studies, the cohort is the source population – just check the data. For case-control
studies, check the controls, if the control series is sufficiently large. May need external
information. Nested case-control studies – check the cohort.

Exposed

Cases

Not exposed

Population

Exposed
Controls

Not exposed

DIRECTION OF INQUIRY

Advantages of case-control studies

1. Highly informative compared to other designs: several exposures or potential causal
agents can be examined.
2. Efficient designs (low cost per study) primarily because few subjects are needed to
obtain stable estimate of RR.
3. Particularly appropriate for studies of rare diseases (e.g. a case-control study with 100
cases of a disease having an annual incidence of 1/1000. A cohort design for this disease
would require 1000 persons to be followed up for 100 years or 10000 persons to be
followed up for 10 years in order to yield the same number of cases).
Disadvantages of case-control studies
1. The absolute frequency of a disease can not be determined. No counts are made of
population at-risk, thus there are no denominators available to obtain the incidence rates.
Lacking absolute risks, it‘s not possible to compare disease rates among different studies,
31
 nor is it possible to estimate the attributable risk.
2. Particularly subject to bias: selection bias in choosing controls and recall bias (cases
may recall better prior exposures than controls).
3. ―Philosophically‖ difficult to interpret: the antecedent-consequent relationship
(exposure-outcome) is subject to considerable uncertainty.
- Selection bias
- Distortions that result from procedures used to select subjects and from factors that
influence study participation. The relation between exposure and disease is different
for those who participate and for all those who theoretically should have been eligible
for the study.
- Self-selection bias. Volunteer bias. Response bias.
- Healthy worker effect. Membership bias.
- Prevalence-incidence bias – mild, resolved, or fatal cases are excluded from the case
group. Available cases may have a different exposure distribution than all cases.
- Survivor bias or immortal time bias.
- Berksonian bias
 Occurs when both the exposure and the disease affect selection.
 E.g.: Estrogens causing endometrial cancer. Horwitz and Feinstein suggested
that estrogens were merely advancing diagnosis, because estrogens induce
bleeding, which would cause women to seek medical attention. As it turns out,
this reasoning is flawed because endometrial cancer is still diagnosed (serious
disease, inevitably becomes symptomatic), even if the time of diagnosis varies
for unexposed patients. Anyways – proposed solution – control series of
women with benign gynecologic diseases. But administration of estrogen
would cause the diagnosis of benign conditions that otherwise may not have
been detected, so exposure prevalence over-estimated for source population.
 Alternative solution – restrict cases and controls to women with vaginal
bleeding. However, estrogen causes bleeding, and endometrial cancer causes
bleeding. By restricting to those who bleed, we introduce a negative association
between endometrial cancer and estrogen use, because if you are bleeding and
you do not have endometrial cancer, you probably have some other cause of
bleeding, like estrogen use.
- Some of the above examples are really forms of confounding, because they relate to
third variables that can be captured and adjusted for (theoretically, at least). E.g.:
health status, fitness. They may not be measured though, so removal of confounding
may require restriction.

You have come to the end of lecture one. In this lecture you have
learnt the following; types of case control studies, case selection, control
selection, types of controls, biases in case control studies, advantages and
disadvantages of case control studies

32
 Now take a break and reflect on some of the issues we
have discussed today. After your break, answer the following questions:
i. Account for the role of bias in case control
studies___________________________________________
ii. Highlight the advantages and disadvantages of case control
studies____________________________________________

REFERENCES

Rothman KJ, Greenland S, Lash TL. Chapter 9: Validity in epidemiologic studies. Modern
Epidemiology: 2008.

Salas M, Hofman A, Stricker BH. Confounding by indication: an example of variation in the

use of epidemiologic terminology. American Journal of Epidemiology, 149(11): 1999.

LECTURE SIX: EXPERIMENTAL STUDY

LECTURE OVER VIEW

The investigators intervene in the natural history by actively altering one of the variables and
then making inference on the relationship between the variables based on the outcomes

By the end of this lecture, you should be able to:

1. Identify reasons for experimental studies

2. Highlight the advantages and disadvantages
3. Describe biases and confounding in
experimental studies

33
- An experiment is a set of observations, conducted under controlled circumstances, in
which the scientist manipulates the conditions to ascertain what effect, if any,
manipulation has on the observations.
- Experimental studies in epidemiology – investigator manipulates the exposure
assigned to participants in the study. E.g.: clinical trials, field trials, community
intervention trials.
 Randomization – allocation of subjects is unrelated to the extraneous factors
that affect the outcome, so any association produced between treatment
allocation and extraneous factors is random. This process converts the effect of
potential biasing factors into random noise for the purpose of statistical
analysis, and is therefore a fundamental assumption of standard statistical
methods which assume all residual variance is random.
 Quasi-randomization – random allocation that does not meet quality standards
of full randomization (See SR section).
 Ethical problems with randomization – treatment assignment independent of
patient characteristics, therefore designed to assist study validity instead of
patient well-being.
 Ethical problems with experiments – requirement of equipoise may not be met.
 Clinical trial – an experiment with patients as subjects.
 Patient-blinded.
 Double-blinded = assessor and patient are blinded to treatment
assignment.
 Triple-blinded = patient, assessor, and individual making the treatment
assignment unaware – alternatively, data analyst unaware.
 Field trial – Subjects are not defined by the presence of disease or by
presentation to clinical care – focus is on initial occurrence of disease. E.g.:
studies of vitamin C to prevent common cold.
 Consider selecting patients to increase R0. But reduces generalizabiltiy.
E.g. MRFIT study – selected high risk patients for AMI. Could also
have looked at patients who had already experienced an AMI.
 Community intervention and cluster randomized trials
 Is the intervention implemented separately for each individual?
 Required for convenience (e.g.: diet and households), or to examine
environmental interventions with widespread effects.
 Cluster-randomization – larger the size of each group (and therefore the
smaller the number of groups) relative to total study size, the less is
accomplished by randomization.
- Non-experimental studies
 Unethical for investigators to expose persons to potential causes of disease
simply to learn about etiology. But people do this willingly or unwillingly to
themselves!
 Unable to assign exposure. Must rely on selection of subjects to achieve
comparability between groups and valid treatment of residual variance as
random.
 Gold standard – the natural experiment – e.g.: Snow‘s study of cholera in
London, with the water supply of the Southwark and Vauxhall Company (water
pumped from the Thames) geographically intermixed with that of the Lambeth
Company, which had obtained a supply of water free of London sewage by

34
 switching the collection point from opposite Hungerford Market to Thames
Ditton.

6.2 Why Experimental Study

a. As they provide better evidence of the effect or the outcome that cannot be
obtained with any other observational method.
b. The variation is minimized and bias is controlled , hence more valid and
their results speak truth
c. Enjoying maximum confidence just like any other scientific laboratory
experiment
d. Providing maximum amount of assurance
e. Fastest and safest way to find treatments that work in people and ways to
improve health

WHAT ARE ITS OBJECTIVES?

a. Intervention trials determine whether experimental treatments or trials
are safe and effective under controlled environments

b. Observation trials address health issues in large groups of people in

natural settings.

6.3 WHEN THEY ARE DONE

When the laboratory and animal studies yield the most promising results of the
intervention, those results are tested by clinical trials

When the margin of the expected benefit or the outcome of an intervention is

doubtful or very narrow (10to30%) only.
When the margin is large, obvious and beyond doubt, it will be unnecessary to
conduct clinical trials.
6.4 WHAT ARE ITS TYPES?

 Treatment trials
 Prevention trials
 Diagnostic trials
 Screening trials
 Quality of life trials

TREATMENT TRIALS

They test
New treatments
New combination of drugs

35
 New approaches to Surgery
New Radiation therapy

PREVENTION TRIALS

They try to find better ways to prevent disease in people and to prevent disease
recurrence using
Medicines
Vaccines
Vitamins
Minerals
Life style changes

DIAGNOSTIC TRIALS

To find better tests for diagnosis of a disease

To find better procedures for diagnosis of a disease

SCREENING TRIALS

• To find out the best way to detect certain diseases or conditions

PHASES OF CLINICAL TRIALS

Phase -I trials
Phase -II trials
Phase -III trials
Phase -IV trials

PHASE-I TRIALS

FIRST TIME TESTING

IN A SMALL GROUP OF 20-80
PURPOSE IS
TO EVALUATE SAFETY
TO DETERMINE A SAFE DOSAGE RANGE
RECTIFY SIDE EFFECTS

PHASE-II TRIALS

TESTED IN LARGE GROUP OF 100-300 PEOPLE

PUROSE IS TO FURTHER EVALUATE
SAFETY
EFFECTIVENESS

PHASE –III TRIALS

36
STILL LARGE GROUP 1000-3000 PEOPLE ARE TESTED
PURPOSE IS TO CONFIRM
 ITS EFFECTIVENESS
 MONITOR SIDE EFFECTS
 COMPARE WITH COMMONLY USED TREATMENTS
 TO GATHER INFORMATION REGARDING SAFE USE

PHASE-IV TRIALS
Post marketting studies
To know about
Drug risks
Benefits
Optimal use

PROTOCOL (STUDY PLAN

Study plan is carefully designed

1. to safeguard the health of the participants and
2. to answer the specific research question

6.5 BIAS IN EPIDEMIOLOGY

Bias is any trend in the collection, analysis, interpretation, publication or review of data that
can lead to conclusions that are systematically different from the truth. Also deviation of
results or interference‘s from the truth, or processes leading to such deviation are bias.

Bias can occur during any stage of a study:

 during the literature review of the study question

 during the selection of the study sample
 during the measurement of exposure and outcome
 during the analysis of data
 during the interpretation of the analysis
 during the publication of the results

Various forms of bias had been described and defined. Most of them however can be
categorised in one of three general types:

37
  Selection bias
 Information bias
 Confounding bias
Some biases are specific to a particular type of analytical study whereas others can be found in
all basic study designs (cross-sectional, case control and cohort).

Selection bias

Selection bias can occurs in the design phase of studies. It may also occur during the
execution of study when some subjects are included and not others, based on the procedures
used to select subjects. Errors in the estimation of effect happens when characteristics of the
subjects selected for the study are systematically different from those in the target population,
a distortion of the measured effect will then result.

Many varieties of selection bias have been described. Admission bias, prevalence/incidence
bias detection bias, volunteer bias and loss to follow-up bias are common forms of this type of
bias. Admission bias occurs when case control and cross sectional studies are done
exclusively in hospital settings where the population studied not accurately reflects the target
population.

Prevalence/incidence bias happens when mild or asymptomatic cases as well as fatal short
disease episodes are missed when studies are performed late in disease process. Volunteer
bias occurs when those who volunteer to participate in a study differ systematically with
regard to either exposure or disease status from those who did not volunteer.

The common element of such biases is that the relation between exposure and disease is
different for those who participate in study and those who would be theoretically eligible for
the study but do not participate.

Selection bias is a theoretical possibility whenever correlates of the outcome capable of

influencing study participation are existent in some individuals at the beginning of the study.
These correlates may be unmeasured or even unrecognised by the investigator.

Information (observation) bias

38
Information bias occurs in the data collection stage of studies. It happens when estimated
effect is distorted either by an error in measurement or by misclassifying the subject for
exposure and/or outcome variables.

The most common types of information bias include interviewer bias, questionnaire bias,
recall bias, diagnostic suspicion bias and exposure suspicion bias.

Interviewer bias results when systematic differences occur in the soliciting, recording, or
interpreting of information from study subjects. Questionnaire bias results when leading
questions or other flaws in questionnaire result in a difference in accuracy between compared
groups. Recall bias happens e.g. when people, having had adverse health outcomes, remember
and report past exposure differently from those who did not experience any adverse health
outcome.

Activity 6.1
1. Discuss the role of bias in experimental studies and how
you can control them_____________________________
2. Describe the effects of confounding in epidemiology

6.7 Confounding

Confounding, is a distortion in the degree of association between an exposure and an outcome

due to a mixing of effects between the exposure and an incidental factor, which is known as
the confounding factor or confounder for short.

We call such variables confounding variables or confounders. A simple definition of

confounding would be the confusion, or mixing, of effects

This definition implies that the effect of the exposure is mixed together with the effect of
another variable, leading to a bias.

Like bias, confounding represents systematic error and threatens the internal validity of an
epidemiologic study since it can lead to false conclusions regarding the true relationship
between an exposure and outcome.

39
Confounding can either overestimate or underestimate the true magnitude of the measure of
association between an exposure and outcome. When the effect of a confounder overestimates
the magnitude of a measure of association, it is said to be a positive confounder. Conversely, if
the confounding factor leads to underestimation of the magnitude of the measure of
association, it is said to be a negative confounder.

Depending on the nature of its relationship with the exposure and outcome, a confounder can
even distort associations to such an extent that a positive association appears negative or no
association appears as an association.

For an incidental factor to be a confounder, it must satisfy the following conditions:

 it must be associated with the exposure,

 it must be an independent risk factor for the outcome,
 it must not be an intermediate step in the causal chain between the
exposure and outcome, and
 it must be present to a greater or lesser degree in the study group versus
the comparison group.
 With regard to the last requirement, it is important to understand that
confounding occurs because the confounder is unequally distributed
between the study and comparison groups.

If the factor is equally distributed between the groups, no confounding will take place, even if
the first three requirements are met. It is also possible that an incidental factor may cause
confounding in one study but not in another.

This is because the distribution of the variable may differ from one study to another.
Because we normally do not know what factors actually will confound any given association,
many epidemiologists suggest that all suspected or known risk factors for the outcome,
especially if they are known to be associated with the exposure, should be considered potential
confounders. In any event, as was the case with rate adjustment, it is only after the fact that we
learn whether or not confounding was present and to what degree.

If adjusting the measure of association for a potential confounder alters its magnitude, then the
factor must have been a confounder.

The degree of confounding is indicated by the extent to which the magnitude of the measure of
association is affected. If there is no effect, then there is no confounding.

Because the topic of confounding can itself be confounding in the more common use of the
term, it should help to provide an example before we go any further. Several studies have
shown a positive association between cigarette smoking and motor vehicle injuries. A
potential confounder of this association, however, is alcohol consumption. Cigarette smoking
and alcohol consumption are associated with each other as any trip to a bar will substantiate
(unless there is legislation prohibiting smoking), and alcohol consumption is a well-
documented independent risk factor for motor vehicle injuries. Furthermore, it is unlikely that
alcohol consumption is part of a causal chain between cigarette smoking and motor vehicle
injuries based on current knowledge. Therefore, alcohol consumption is considered a potential

40
confounder. Now, assume a case-control study finds a positive association between cigarette
smoking and motor vehicle injuries. If the case group contains significantly more drinkers than
the control group, we cannot be sure whether the association is really due to cigarette
smoking.

Part or all of the association between cigarette smoking and motor vehicle injuries could be
due to alcohol consumption.

Even if cigarette smoking is not associated with vehicle injuries, it could appear to be so
because of its association with alcohol consumption.

On the other hand, even if cigarette smoking is associated with vehicle injuries, the association
could be overstated because of an excess number of drinkers among the case group. In fact,
when alcohol consumption is controlled in studies of the association between cigarette
smoking and motor vehicle injuries, the measure of association decreases but still remains
significant. Thus, alcohol appears to be a positive confounder (i.e. one that overstates the
magnitude of the measure of association).

Confounding: a recap Potential confounding variables always have to be considered in the

design and analysis of epidemiological studies. Confounding occurs when a confounding
variable, C, is associated with the exposure, E, and also influences the disease outcome, D.

 Figure 1: Situation in which C may confound the affect of the E to D association.

An epidemiological study wishes to investigate the E to D relationship, but the E to C and C to

D associations may bias the estimate of the E to D association unless they are considered in
the design or analysis. An example of confounding: When examining the relationship between
alcohol consumption (E) and heart disease (D), smoking (C) would be an important
confounding factor, since smoking is correlated with alcohol consumption and smoking is
associated with heart disease.
Confounding is essentially a mixing of effects that occurs when a factor (confounder)
associated with the exposure of interest is also associated with development of the disease or

41
outcome of interest independently of exposure. Therefore, a distorted estimate of the exposure
effect results because the exposure effect is mixed with the effect of extraneous variables.

A confounder must be predictive of disease occurrence independent of its association with the
exposure of interest, but cannot be an intermediate in the casual chain of association between
exposure and disease development. The confounding variable can effect the association
between exposure and disease positively or negatively; the distorted estimate resulting from
confounding can overestimate or underestimate the true effect or even change the apparent
direction of effect.

To be confounding, and extraneous variable must have the following characteristics:

 It must be a risk factor for disease

 It must be associated with the exposure under study in the population studied
 It must not be an intermediate step in the casual path between the exposure and the
disease
In epidemiological studies an investigator would like to minimise both systematic error (bias)
and random error (chance). Reducing systematic errors lead to an increase in the validity of
the study, while reducing random errors increase the power of the study. Knowledge of
systematic error (bias0 therefore become an important issue in epidemiological studies.

Example of Confounding

42
Rothman (2002, p.101) provides a classic example of confounding, which is the relation
between birth order and the occurrence of Down syndrome.

1.8
Affected Babies per 1000 Live Births

1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
1 2 3 4 5+
Birth Order

These data suggest that the prevalence of Down syndrome is associated with (perhaps
―causally‖) birth order.

The effect of birth order, however, is a blend of whatever effect birth order has by itself and
the effect of another variable that is closely correlated with birth order.

The other variable is the age of the mother.

9
Affected Babies per 1000 Live Births

8
7
6
5
4
3
2
1
0
<20 20-24 25-29 30-34 35-39 40+
Maternal Age

This figure gives the relation between mother‘s age and the occurrence of Down syndrome
from the same data.

It indicates a much stronger relationship (8.5 per 1000 for the highest category vs 1.7 per 1000
for the highest category from the previous graph—notice difference in scale of Y axis).

43
Because birth order and the age of the mother are highly correlated, we can expect that
mothers giving birth to their fifth baby are, as a group, considerably older than mothers giving
birth to their first baby.

Thus, the birth order effect is mixed with the mother‘s age effect. We call this mixing of
effects confounding. In this example, the birth order effect is confounded with maternal age.

We can resolve this confounding by consider both effects simultaneously.

44
In this graph, we see a striking trend with maternal age (cases increase for each birth order),
while there is no trend with birth order (cases essentially constant for each maternal age).

This last graph is an example of a stratified display, in contrast to the previous graphs which
are examples of a crude display.

The stratified display reveals that the erroneous birth order effect was due to confounding with
maternal age

Diagrammatically, the two necessary associations for confounding are:

Confounder

association association

Exposure Disease

Confounded effect

There is also a third requirement.

A factor that is an effect of the exposure and an intermediate step in the causal pathway from
exposure to disease will have the above associations, but causal intermediates are not
confounders; they are part of the effect that we wish to study.

Thus, the third property of a confounder is as follows:

3) A confounder must not be an effect of the exposure.

Rothman (2002, p.164) points out that the degree of confounding is not dependent upon
statistical significance, but rather upon the strength of the associations between the confounder
and both exposure and disease. He advocates that a better way to evaluate confounding is to
statistically control for the potential confounder, using stratification or regression analyses,
and determine whether the unconfounded result (adjusted model) differs from the potentially
confounded result (the unadjusted model). If they differ, then confounding is present in the
unadjusted model.

Example (Stoddard’s hypothetical data)

45
A researcher wants to study the association of a diet high in pizza and the disease outcome
skin acne. The following data are collected using a cross-sectional study design:

Eat Pizza

(at least twice per month)

Noticeable Skin Acne Yes No

Yes 80 40

No 120 149

Odds Ratio = 2.48 , p < 0.001

Thus, an association between pizza consumption and skin acne is observed in this crude
analysis.

One might consider, however, if the association is confounded by age. The data are stratified
and these are the results:

Teenager (age 13-19)

Eat Pizza

at least twice per month

Noticeable Skin Acne Yes No

Yes 60 10

No 20 4

Odds Ratio = 1.20 , p = 0.78

Adult (age 20+)

Eat Pizza

at least twice per month

46
 Noticeable Skin Acne Yes No

Yes 20 30

No 100 145

Odds Ratio = 0.97 , p = 0.91

Now we see that the association does not hold in either age group.

Since the crude display gives a different result than the stratified display of the data, the result
is confounded. That is, the pizza-acne association observed in the crude display is confounded
by age.

Filling in the labels to our diagram,

Confounder

association association

Exposure Disease

confounded effect

Age

Association Association

Pizza Acne

confounded effect

There is an association between age and pizza, as 80/94, or 85%, of teenagers eat pizza
regularly, while 120/295, or 41%, of adults eat pizza regularly. This ―imbalance‖ represents
an ―association‖ (as age increases, pizza eating decreases).

Age

47
 Pizza Acne

confounded effect

There is a well-known assocation between age and acne, acne being mostly a teenager disease.
In these data, 70/94, or 74%, of children have acne, while only 50/295, or 17%, of adults have
acne. This imbalance represents an association (as age increases, acne decreases).

Age

85% vs 41% 74% vs 17%

Pizza Acne

confounded effect

We therefore have the two assocations that must be present for age to be a confounder

1) A confounder must be associated with the disease (age-acne association)

2) A confounder must be associated with exposure (age-pizza association)

We also satisfied the third property of a confounder:

3) A confounder must not be an effect of the exposure.

(This holds, since eating pizza does not cause a person to be a teenager.)

This example illustrates what is usually the case in a confounded relationship. What we
consider to be the putative cause of the disease is simply a surrogate for something else, the
confounder, that is the cause, or more directly related to the cause, of disease.

That is, pizza is a surrogate for teenager, since teenagers are the big pizza consumers; and
something that occurs in the teenage years produces acne, perhaps related to rising hormonal
levels.

Control of Confounding

Controlling for confounding A number of methods can be applied to control for potential
confounding factors, both at the design stage and in the analysis of epidemiological studies.
The aim is to make the groups as similar as possible with respect to the confounder. At the
48
design stage, potential confounding factors may be identified based on previous studies or
because the factor may be considered as biologically plausible.

Methods used for controlling for confounding at the design stage

Restriction is a method that limits participation in the study to individuals who are similar in
relation to the confounder. For example, a study restricted to non-smokers only will eliminate
any confounding effect of smoking. However, a disadvantage of restriction is that it may be
difficult to generalize to the rest of the population based on a homogeneous study group

Matching in case control studies Matching involves selecting controls so that the distribution
of potential confounders among them will be similar to those of the cases.

Randomization (random allocation) Involves the random allocation (e.g. using a table of
random numbers) of individuals to exposure categories. Therefore, the distribution of known
and unknown confounding variables will be similar for each of the groups being compared.
This method may only be used in clinical trials.

Methods used for controlling for confounding during analysis

Methods to detect the presence of confounding The presence or magnitude of confounding
in epidemiological studies is evaluated by observing the degree of discrepancy between the
crude and adjusted estimates. One method to assess for the presence of confounding is to
calculate the crude relative risk (without controlling for confounding) and compare this
measure with the relative risk adjusted for the potential confounder. If the relative risk has
changed and there is little variation between the stratum specific rate ratios, then there is
evidence of confounding Note that it is inappropriate to use statistical methods to test for the
presence of confounding.

Stratification Stratification allows the association between exposure and outcome to be

examined within different strata of the confounding variable. For example by age, sex or
alcohol consumption.
If we were conducting a study to examine the association between lung cancer and urban
atmospheric pollution, controlling for smoking, the population could be stratified according to
smoking status. The association between air pollution and cancer can then be assessed
separately within each stratum
Stratification allows for the assessment of modifying effects as well as controlling for
confounding factors; e.g. stratification makes it possible to examine the effect of smoking on
the association between atmospheric pollution and lung cancer.
The problem with simply creating strata is that in general, strata with more individuals will
tend to have a more precise estimate of the association (with a smaller standard error) than
strata with fewer individuals. Therefore we calculate a weighted average where greater weight
is given to the strata with more data. The most common weighting scheme used is the Mantel-
Haenszel method.
When using the Mantel-Haenszel method, an overall estimate of the relative risk adjusted for
the potential confounder can be calculated by pooling the stratum specific rates. This gives us
an overall summary measure of effect
Mantel-Haenszel estimates can be calculated using all of the usual statistical packages. See
related links for a relevant chapter on stratifying results using the Mantel-Haenszel method in
a user friendly statistics textbook, and a link to a textbook that can help you to use these
methods in a popular statistics package.
49
Standardisation The methods of direct and indirect standardisation are commonly used to
control for the confounding affects of age and sex.

Multivariate analysis As the number of confounders that can be controlled for

simultaneously is limited, and particularly since this may lead to small numbers in some strata,
statistical modelling (e.g. logistic regression) is commonly used to control for more than one
confounder at the same time.

Beyond confounding

Effect modification (Interaction) Effect modification occurs when the effect of an exposure
is different among different subgroups. For instance, if we were examining the relationship
between obesity and mortality then we could say that gender or ethnicity are effect modifiers,
since the effect of obesity on mortality varies according to gender and ethnicity. Another
example could be immunisation status as an effect modifier on the relationship between
exposure to a pathogen and outcome
Another term for effect modification is interaction. Interaction occurs when the direction or
magnitude of an association between two variables differs due to the effect of a third variable.
It can reflect a cumulative effect of multiple risk factors that are not acting independently, and
can produce a greater or lesser effect than the sum of the effects of each factor acting on its
own.
When using Mantel-Haenszel methods for stratification, an important assumption is made,
namely that there is no effect modification occurring. If effect modification is occurring then
there is little point in combining the weighted strata to achieve an overall measure, and a more
sophisticated method of stratification should be used.

Role of chance, bias and confounding in epidemiological studies

The interpretation of study findings or surveys is subject to debate, due to the possible errors
in measurement which might influence the results. This section introduces you to various
errors of measurement in epidemiological studies..

Resource text

While the results of an epidemiological study may reflect the true effect of an exposure(s) on
the development of the outcome under investigation, it should always be considered that the
findings may in fact be due to an alternative explanation.

Such alternative explanations may be due to the effects of chance (random error), bias or
confounding, which may produce spurious results, leading us to conclude the existence of a
valid statistical association when one does not exist, or alternatively the absence of an
association when one is truly present.

Observational studies are particularly susceptible to the effects of chance, bias and
confounding, and these need to be considered at both the design and analysis stage of an
epidemiological study so that their effects can be minimized.

50
Confounding, interaction and effect modification

Confounding involves the possibility that an observed association is due, totally or in part, to
the effects of differences between the study groups (other than the exposure under
investigation) that could affect their risk of developing the outcome being studied.

Confounding occurs when the effects of two associated exposures have not been separated,
resulting in the interpretation that the effect is due to one variable rather than the other. The
consequence of confounding is that the estimated association is not the same as the true effect.

You have come to the end of lecture one. In this lecture you have
learnt the following; Experimental studies, experimental designs, why carry out
experimental designs, Bias and confounding, Strengths and weakness of
Experimental designs.

Now take a break and reflect on some of the issues we have

discussed today. After your break, answer the following questions:
i. Account for the role of bias in experimental designs
___________________________________________
ii. Highlight the advantages and disadvantages of case Experimental
studies____________________________________________
iii. How would you control confounding in experimental studies

References

1. Pocock SJ. Clinical Trials: a Practical Approach. Chichester: Wiley; 1983.

2. Altman DG, Bland JM. Treatment allocation in controlled trials: why randomise? Br
Med J 1999; 318:1209. | ChemPort |
51
 3. Begg C, Cho M, Eastwood S, et al. Improving the quality of reporting randomized
controlled trials: the CONSORT statement. J Am Med Assoc 1996; 276:637–
639. | Article | C
4. 1. Hennekens CH, Buring JE. Epidemiology in Medicine, Lippincott Williams &
Wilkins, 1987.
5. Kendall JM. Designing a research project: Randomised Controlled trials and their
principles, Emerg Med J. 2003, March;20(2)164-168.
3. Hollis S, Campbell F, What is meant by intention to treat analysis? Survey of
published randomised controlled trials. BMJ 1999; 319;670-74.

6. Pocock SJ. Clinical Trials: A practical approach, Chichester, Wiley, 1984.

Sibbald B, Roland M, Understanding

LECTURE SEVEN: RANDOMISED CONTROLLED TRIALS

7.1 LECTURE OVERVIEW

The randomised controlled trial is considered as the most rigorous method of determining
whether a cause-effect relationship exists between an intervention and outcome [2]. The
strength of the RCT lies in the process of randomisation that is unique to this type of
epidemiological study design.

Generally, in a randomised controlled trial, study participants are randomly assigned to one of
two groups: the experimental group receiving the intervention that is being tested and a
comparison group (controls) which receives a conventional treatment or placebo. These
groups are then followed prospectively to assess the effectiveness of the intervention
compared with the standard or placebo treatment.

The random allocation of subjects is used to ensure that the intervention and control groups
are similar in all respects (distribution of potential confounding factors) with the exception of
the therapeutic or preventative measure being tested. The choice of comparison treatments
may include an existing standard treatment or a placebo (a treatment which resembles the
intervention treatment in all respects except that it contains no active ingredients).

52
 By the end of this lecture, you should be able to:
1. Identify the steps in conducting RCTs
studies
2. Highlight the advantages and
disadvantages of RCTs studies
3. Describe biases in RCTS
4. Describe the general outline of the
protocol in RCTs

7.2 Definition. A study design that randomly assigns participants into an experimental group
or a control group. As the study is conducted, the only expected difference between the
control and experimental groups in a randomized controlled trial (RCT) is the outcome
variable being studied.

The study designs described previously in this series have focused on observational studies,
where outcome measures have been recorded either at one specific timepoint (cross-sectional)
or repeatedly over time (longitudinal). Information may be collected at an aggregate level
(ecological) and may be gathered prospectively (cohort study) or retrospectively (case–control
study).

Randomised controlled trials (RCT), or randomised clinical trials, are experimental studies
where the effect of an intervention is assessed by collecting data before and after an
intervention has taken place. RCT are used to compare an intervention with one or more other
interventions or with no intervention. Interventions are often clinical treatments but may also
be educational interventions such as health promotion leaflets.

7.3 What are the two main features of the RCT?

1. They are comparative

In RCT, an intervention is investigated by comparing one group of people who receive the
intervention with a control group or control arm who do not (Figure 1, below). The control
group receives the usual or no treatment and their outcome measure, or the change in measure
from the starting point or baseline, is compared with that of the intervention group.

53
Figure 1.

Diagrammatic representation of a randomised controlled trial

2. They are designed to minimise bias

i. Allocation bias

Allocation bias occurs when the measured treatment effect differs from the true treatment
effect because of how participants were selected into the intervention or control groups. In
RCT, once the participants are entered into the study, they are randomised to either an
intervention group or the control group. Randomisation ensures that characteristics that might
affect the relationship between intervention and outcome measures will be roughly equal
across all arms of the study, minimising potential bias.

ii. Performance bias

Even after randomised allocation, bias can occur. Performance bias occurs when participants'
response to the treatment is affected by knowledge of the group to which they are assigned, or
when health professionals administer treatments differently between treatment arms.

iii. Assessment bias

Health professionals assessing the outcome of treatment relative to alternative or placebo

interventions may record outcome measures biased by the knowledge of the group to which
the participant has been assigned. Over- (or under-) estimation of the effects of an
intervention, even if subconscious, is known as assessment bias. Alternatively there might be a
54
systematic difference in measuring the outcomes between the two groups because of the
method of recording used. For example, where the control group is assigned to one
practitioner and the intervention group to another, or where groups are assessed at different
times of the day, there may be a systematic difference between groups in the mean outcome
measure recorded. Bias will be minimised where a standardised method of evaluation is used
across both groups. Subjective measures to assess the effectiveness of a treatment will be more
prone to bias.

iv. Attrition bias

Attrition bias (also call loss-to-follow-up bias) occurs when patients drop out of the study from
one or other of the study groups preferentially. For example, if halfway through a study the
treatment has been successful participants may drop out, and information about the success of
the treatment is then lost. Conversely, participants in the control group may be unhappy with
their lack of progress and may drop out of the study in order to seek alternative help.

v. Allocation concealment

Bias will be minimised where the allocation schedule is concealed of whom is assigned to
which group. Blinding (also known as masking) helps to prevent systematic differences
between comparison groups in prognosis or responsiveness to treatments (allocation bias).
Blinding of both participants and practitioners prevents performance and assessment bias by
ensuring that participants, treatment administrators and those measuring outcomes do not
know which treatment was given. Where possible, it is recommended that RCT participants
are blind to the treatment they receive. In order to do this it is sometimes appropriate for the
control group to receive a placebo. This enables the RCT to be blind and overcomes the
placebo effect, where it is the action of taking medication and not the medication itself that
results in a positive outcome.

Why carry out RCT?

RCT are prospective longitudinal studies, allowing the investigation of causal associations
between interventions and outcomes. The random selection of participants into each arm and
the controlled way in which the trial is carried out mean that all factors other than the
intervention are considered equal. Although associations may be investigated under
observational studies, causality cannot be inferred. If possible, it is always preferable to
choose RCT over other study designs when assessing the impact of one or more interventions.

Note that ethical constraints limit the choice of comparison treatments.

Figure 1. General outline of a two armed randomised controlled trial.

55
56
7.4 Basic outline of the design of a randomised controlled trial

1. Development of a comprehensive study protocol. The study protocol will include:

- Aim and rationale of the trial

- Proposed methodology/data collection
- Definition of the hypothesis
- Ethical considerations
- Background/review of published literature
- Quality assurance and safety
- Treatment schedules, dosage, toxicity data etc.

2. Formulation of hypothesis.

3. Objectives of the trial.

4. Sample size calculations.

5. Define reference population.

6. Choice of a comparison treatment - placebo or current available best treatment.

7. Selection of intervention and control groups, including source, inclusion and exclusion
criteria, and methods of recruitment.

8. Informed consent procedures.

9. Collection of baseline measurements, including all variables considered or known to affect

the outcome(s) of interest.

10. Random allocation of study participants to treatment groups (standard or placebo vs. new).

11. Follow-up of all treatment groups, with assessment of outcomes continuously or

intermittently.

12. Monitor compliance and losses to follow-up.

13. Interim analysis.

14. Analysis - comparison of treatment groups.

15. Interpretation (assess the strength of effect, alternative explanations such as sampling
variation, bias).

16. Publication.

57
 Activity 7.1
Discuss the design pitfalls
________________________________________________________
________________________________________________________
_________________________________________________________

7.5 Randomisation

The aim of randomisation is to ensure that any observed differences between the treatment
groups are due to differences in the treatment alone and not due to the effects of confounding
(known or unknown) or bias. That is, that the groups are similar in all respects with the
exception of the intervention under investigation.

Methods of random allocation are used to ensure that all study participants
have the same chance of allocation to the treatment or control group, and that the likelihood of
receiving an intervention is equal regardless of when the participant entered the study.
Therefore, the probability of any participant receiving the intervention or the standard
treatment/placebo is independent of any other participant being assigned that treatment.

The assignment of study subjects to each intervention is determined by formal chance process
and cannot be predicted or influenced by the investigator or participant. In a well designed
RCT, random allocation is determined in advance.

Methods of randomisation - allocation of subjects to intervention and control groups

1. Simple randomisation

For example, computer generated random number tables. Simple randomisation is rarely used.

2. Block randomisation

Block randomisation is a method used to ensure that the numbers of participants assigned to
each group is equally distributed and is commonly used in smaller trials.

3. Stratified randomisation

Stratified randomisation is used to ensure that important baseline variables (potential

confounding factors) are more evenly distributed between groups than chance alone may
assure. However, there are a limited number of baseline variables that can be balanced by
stratification because of the potential for small numbers of subjects within each stratum.
58
4. Minimized randomisation

This method may be used when the study is sufficiently small and simple randomisation will
not result in balanced groups.
Note that deterministic methods of allocation such as by date of birth or alternate assignment
to each group are not considered as random.

Advantages of randomisation

 Eliminates confounding - tends to create groups that are comparable for all factors that
influence outcome, known, unknown or difficult to measure. Therefore, the only
difference between the groups should be the intervention.
 Eliminates selection bias.
 Gives validity in statistical tests based on probability theory.
 Any baseline differences that exist between study groups are attributable to chance
rather than bias. Though this should still be considered as a potential concern.

Blinding in randomised controlled trials

Blinding is a process where the critical information on allocation of treatment is hidden either
from the patients, or from observer or the evaluator in the study. The method of blinding in
RCT is used to ensure that there are no differences in the way in which each group is assessed
or managed, and therefore minimize bias. Bias may be introduced, for example, if the
investigator is aware of which treatment a subject is receiving, as this may influence
(intentionally or unintentionally) the way in which outcome data is measured or interpreted.
Similarly, a subject's knowledge of treatment assignment may influence their response to a
specific treatment.

Blinding also involves ensuring that the intervention and standard or placebo treatment
appears the same.

Double blinding is when neither the investigator nor the study participant is aware of treatment
assignments. However, this design is not always possible.

A single blind RCT is when the investigator but not the study participants know which
treatment has been allocated.

Strengths of a randomised controlled trial

 A well designed randomised control trial provides the strongest evidence of any
epidemiological study design that a given intervention has a postulated effectiveness
and is safe.
 A RCT provides the best type of epidemiological study from which to draw
conclusions on causality.
 Randomisation provides a powerful tool for controlling for confounding, even by
factors that may be unknown or difficult to measure. Therefore, if well designed and
59
 conducted, a RCT minimizes the possibility that any observed association is due to
confounding.
 Clear temporal sequence - exposure clearly precedes outcome.
 Provides a strong basis for statistical inference.
 Enables blinding and therefore minimizes bias.
 Can measure disease incidence and multiple outcomes.

 Good randomization will ―wash out‖ any population bias

 Easier to blind/mask than observational studies
 Results can be analyzed with well known statistical tools
 Populations of participating individuals are clearly identified

Weaknesses of a randomised controlled trial

 Ethical constraints - for example, it is not always possible or ethical to manipulate

exposure at random.
 Expensive and time consuming.
 Requires complex design and analysis if unit of allocation is not the individual.
 Inefficient for rare diseases or diseases with a delayed outcome.
 Generalisability - subjects in a RCT may be more willing to comply with the treatment
regimen and therefore may not be representative of all individuals who might be given
the treatment.
 Does not guarantee comparable groups as differences in confounding variables may
arise by chance
 For a descriptive overview it may be cheaper and easier to use an observational design.
 Prior knowledge is required about the level of improvement that is clinically
meaningful and the expected variation of improvement in the sample in order to
calculate the RCT sample size. These facts are often not known
 Expensive in terms of time and money
 Volunteer biases: the population that participates may not be representative of the
whole
 Does not reveal causation
 Loss to follow-up attributed to treatment

7.6 Factors to be considered when carrying out RCT

Sample size

The size of the sample required when carrying out RCT is dependent upon the power of the
test and what size of intervention impact is considered meaningful. It also depends on the type
of hypothesis the RCT is testing. The smaller the magnitude of difference between groups that
is to be detected and the greater the variability in outcomes, the larger the sample size that will
be required.

Stratification

Very large trials are likely to have a good balance of patients within each arm. When the
samples are small, however, treatment groups may by chance end up with different
60
characteristics, which may affect the outcome of the trial. Stratification is a way of ensuring
the treatment groups are balanced on characteristics that are likely to alter the relationship
between treatment and outcome.

Crossover design

Crossover trials are another way of overcoming differences in groups by keeping the patients
as matched as possible. Instead of having different patients in each treatment group, patients
receive first one treatment and then the other, in a random order, with a washout period in
between. Within-patient differences are then compared. Thus each patient effectively becomes
their own 'test' and 'control'.

Between group contamination

Educational interventions, in particular, are prone to contamination where, for example, a

member of the control arm is a friend of a patient receiving the oral health advice-sheet
intervention. Information may then pass between the two arms of the trial, and thus alter the
results.

One way to overcome this is to use cluster sampling so that natural clusters such as geographic
areas or dental practices are randomised rather than individuals.

Ethical issues

RCT are not always possible because of ethical issues when assigning patients to study arms.

If one group of patients receives treatment thought to be effective, while another group does
not, the ethics of a trial may be brought into question. Similarly, there are some trials that
cannot be carried out because they may actively encourage unhealthy practices such as
smoking; people cannot be randomised into smoking and nonsmoking groups.

Analysis of data

RCT are experiments set up to test hypotheses. The null hypothesis (H0) is that the
intervention will have no impact on the outcome measure (ie, that the outcome of interest will
be similar in both the test and control groups). The alternative to the null hypothesis (H1) is
that the intervention will have a meaningful effect and that this effect will be statistically
significant. The statistical method required to test this hypothesis will depend on the nature of
the outcome of interest. Comparing the proportions of patients achieving a 'successful
outcome' between treatment groups (eg, those satisfied with their treatment) will require a
different approach from investigating average differences between groups (eg, average
probing pocket depths).

Fictitious Example

To determine how a new type of short wave UVA-blocking sunscreen affects the general
health of skin in comparison to a regular long wave UVA-blocking sunscreen, 40 trial
participants were randomly separated into equal groups of 20: an experimental group and a
control group. All participants' skin health was then initially evaluated. The experimental

61
group wore the short wave UVA-blocking sunscreen daily, and the control group wore the
long wave UVA-blocking sunscreen daily.

After one year, the general health of the skin was measured in both groups and statistically
analyzed. In the control group, wearing long wave UVA-blocking sunscreen daily led to
improvements in general skin health for 60% of the participants. In the experimental group,
wearing short wave UVA-blocking sunscreen daily led to improvements in general skin health
for 75% of the participants.

You have come to the end of lecture one. In this lecture you have
learnt the following; Definition of Randomised clinical Trials, features of
RCTs, why carry out RCTs, basic outline of the design of Randomised Control
Trials, Methods of randomization, Strengths and weakness of Randomised
Control trials

Now take a break and reflect on some of the issues we have

discussed today. After your break, answer the following questions:
i. Account for the role of bias in Randomised clinical trials
___________________________________________
ii. Highlight the advantages and disadvantages of case RCTs
studies____________________________________________
iii. How would you control confounding in RCTs

References

7. Pocock SJ. Clinical Trials: a Practical Approach. Chichester: Wiley; 1983.

8. Altman DG, Bland JM. Treatment allocation in controlled trials: why randomise? Br
Med J 1999; 318:1209. | ChemPort |
9. Begg C, Cho M, Eastwood S, et al. Improving the quality of reporting randomized
controlled trials: the CONSORT statement. J Am Med Assoc 1996; 276:637–
639. | Article | C
62
 10. 1. Hennekens CH, Buring JE. Epidemiology in Medicine, Lippincott Williams &
Wilkins, 1987.
11. Kendall JM. Designing a research project: Randomised Controlled trials and their
principles, Emerg Med J. 2003, March;20(2)164-168.
3. Hollis S, Campbell F, What is meant by intention to treat analysis? Survey of
published randomised controlled trials. BMJ 1999; 319;670-74.

12. Pocock SJ. Clinical Trials: A practical approach, Chichester, Wiley, 1984.
Sibbald B, Roland M, Understanding

LECTURE EIGHT: MEASURES OF ASSOCIATION

By the end of the lecture you should be able to:

i. Define Attributable risk
ii. Calculate attributable risks, relative risks and odds ratio
iii. Describe the applications of Attributable Risk, Odds Ratio, and
Relative Risk in Epidemiology.

ATTRIBUTABLE RISK (AR)

8.1 Lecture overview

Many diseases are caused by more than one exposure. For example, lung cancer is caused
by exposure to smoking, asbestos, radiation or some chemical products. Public health
programs to prevent disease are directed toward reducing or eliminating such causal
exposures.

Epidemiologic research not only focuses on the identification and assessment of risk factors
but also is concerned with planning and evaluating public health interventions or control
measures to reduce the incidence of disease in the population. Being able to predict the
impact of remov- ing a particular exposure on the risk of developing a disease is an
important public health con- sideration. It allows those who are responsible for protecting
the public‘s health to make deci- sions about allocating scarce resources (time, energy,
money and political capital) where they will have the most impact. It helps them answer
the following questions:
1. What amount of the risk of developing a disease is attributable to a particular
exposure?

2. By what percent would the risk of developing disease be reduced if the exposure
63
 were eliminated?

If smoking were eliminated, what would happen to the incidence of lung cancer? Would
smokers‘
risk of lung cancer disappear if they stopped smoking?

For public health decision-making purposes, it is valuable to be able to answer these

questions from two perspectives: from the perspective of the impact of eliminating the
exposure on only those who are exposed and from the perspective of the impact of
eliminating the exposure on the entire population, those who are exposed and those who
are not exposed.

Note that for purposes of this teaching unit risk and incidence rate (or incidence) can
be considered interchangeable. Strictly speaking, however, incidence rate (or incidence)
denotes
the rate of new cases per unit time whereas risk denotes the rate of new cases in a fixed
interval of time.

8.2Measures of Attributable Risk in the Exposed

Attributable risk (AR): AR is the portion of the incidence of a disease in the exposed
that is due to the exposure. It is the incidence of a disease in the exposed that would be
eliminated if exposure were eliminated.

The AR is calculated by subtracting the incidence in the unexposed (Iu) from the
incidence in the exposed (Ie):

AR = Ie − Iu
Attributable risk percent (AR%): AR% is the percent of the incidence of a disease in the
exposed that is due to the exposure. It is the proportion of the incidence of a disease in the
exposed that would be eliminated if exposure were eliminated.

The AR% is calculated by dividing the attributable risk (AR) by the incidence in the exposed (Ie)
and then multiplying the product times 100 to obtain a percentage:

Ie − I
AR% = × 100
u
Ie
or
AR
AR% = × 100
Ie

8.3Measures of Attributable Risk in the Population

64
Population attributable risk (PAR): PAR is the portion of the incidence of a disease in the pop-
ulation (exposed and nonexposed) that is due to exposure. It is the incidence of a disease in the
population that would be eliminated if exposure were eliminated.

The PAR is calculated by subtracting the incidence in the unexposed (Iu) from the incidence in
total population (exposed and unexposed) (Ip):

PAR = Ip − Iu

Population attributable risk percent (PAR%): PAR% is the percent of the incidence of a dis-
ease in the population (exposed and nonexposed) that is due to exposure. It is the percent of
the incidence of a disease in the population that would be eliminated if exposure were eliminated.

The PAR% is calculated by dividing the population attributable risk (PAR) by the incidence in the
total population and then multiplying the product times 100 to obtain a percentage:

Ip − I
PAR% = × 100
u
Ip
or

PAR
PAR% = × 100
I p

65
Example

The preventive advantages of eating fish have been reported in numerous studies. A recent
cohort study1 reported that not eating fish increased the risk for stroke. The table below
shows the results of this study:

Eating Fish and Stroke

Cases Noncases
Eating Fish of Stroke of Stroke Total
Never 82 (a) 1,549 (b) 1,631
Almost daily 23 (c) 779 (d) 802
Total 105 2,328 2,433

Incidence in the exposed (Ie): a/a b 82/1,631 0.0503, or 5.03 per 100
Incidence in the unexposed (Iu): c/c d 23/802 0.0287, or 2.87 per 100
Incidence in both combined (Ip): a c/(a b c d) 105/2,433
0.0432, or 4.32 per 100
Incidence in the exposed a/a + b
RR = =
Incidence in the unexposed c /c + d
a(c + d )
RR = = 5.03/2.87 = 1.75
c(a+ b)

Applying the formulas above to these data (and disregarding the fact that some members of the
population may eat fish more than ―never‖ and less than ―almost daily‖) results in the following
measures of attributable risk.

AR Ie − = 5.03 − 2.87 = 2.16 per 100

Iu
AR% = (AR /I e ) 100 (2.16/5.03) 100 = 43%
=
PAR = I p − I u = 4.32 − 2.87 = 1.45 per 100
PAR% = (PAR /I p ) = (1.45/4.32) 100 = 33.6%
100
Assuming that this and many other studies present enough evidence about the preventive advan-
tages of eating fish to reduce stroke, we could interpret the above data as follows:

• Those who never eat fish have 1.75 times as much risk (higher incidence) as those who eat

66
fish almost daily (RR = 1.75).

67
 • If those who do not eat fish change their eating habits and begin to eat fish almost
daily, their incidence of strokes will decrease by 2.16 per 100 individuals (AR = 2.16 per
100), which would represent a 43% reduction of their stroke incidence (AR% = 43%).

• A reduction of 1.45 new cases of stroke per 100 population (exposed and unexposed)
is expected if everybody eats fish almost daily (PAR = 1.45 per 100). Such reduction
represents a 33.6% reduction of the incidence in the population (PAR% = 33.6%).

8.5 Relative risk

In statistics and epidemiology, relative risk or risk ratio (RR) is the ratio of the probability of
an event occurring (for example, developing a disease, being injured) in an exposed group to the
probability of the event occurring in a comparison, non-exposed group. Relative risk includes
two important features: (i) a comparison of risk between two "exposures" puts risks in context,
and (ii) "exposure" is ensured by having proper denominators for each group representing the
exposure.

Disease status
Risk
Present Absent

Smoker

Non-smoker

Consider an example where the probability of developing lung cancer among smokers was 20%
and among non-smokers 1%. This situation is expressed in the 2 × 2 table to the right.

Here, a = 20, b = 80, c = 1, and d = 99. Then the relative risk of cancer associated with smoking
would be

Smokers would be twenty times as likely as non-smokers to develop lung cancer.

68
The alternative term risk ratio is sometimes used because it is the ratio of the risk in the exposed
divided by the risk in the unexposed.

Relative risk contrasts with the actual or absolute risk, and may be confused with it in the media
or elsewhere.

8.6 Statistical use and meaning

Relative risk is used frequently in the statistical analysis of binary outcomes where the outcome
of interest has relatively low probability. It is thus often suited to clinical trial data, where it is
used to compare the risk of developing a disease, in people not receiving the new medical
treatment (or receiving a placebo) versus people who are receiving an established (standard of
care) treatment. Alternatively, it is used to compare the risk of developing a side effect in people
receiving a drug as compared to the people who are not receiving the treatment (or receiving a
placebo). It is particularly attractive because it can be calculated by hand in the simple case, but
is also amenable to regression modelling, typically in a Poisson regression framework.

In a simple comparison between an experimental group and a control group:

 A relative risk of 1 means there is no difference in risk between the two groups.
 An RR of < 1 means the event is less likely to occur in the experimental group than in the
control group.
 An RR of > 1 means the event is more likely to occur in the experimental group than in
the control group.

Activity 8.1 Read carefully and answer the following question

A cohort study was conducted in Kabondo Division, Homabay County to investigate the
association between Lung cancer and mortality. A random sample of villagers aged 15 years and
over (about 3600 males and 5000 female) was questioned about their smoking habits. Deaths
were ascertained and follow up surveys conducted 3years later and thereafter annually for
10years. Mortality rates in female are shown in the table below:

69
 Crude Age standardized
Rate Relative risk Rates Relative risk
Tobacco chewers 6.5 6.7 10.8 1.7 P<0.001
Non chewers 2.3 3.0 8.2 1.0
a) Differentiate between for the difference between crude and Age standardized relative
risks

b) What would the sources and effects be of loses to follow up on the study results.

c) Account for the Difference between Age standardized relative risk and relative

From the table deduce explicitly the association between the alcohol drinking and the risks of
dying

8.7 ODD RATIO

Definition

The Odds Ratio is a measure of association which compares the odds of disease of those exposed
to the odds of disease those unexposed.

Formulae

 OR = (odds of disease in exposed) / (odds of disease in the non-exposed)

Example

I often think food poisoning is a good scenario to consider when interpretting ORs: Imagine a
group of 20 friends went out to the pub – the next day a 7 were ill. They suspect that it may have
been something they ate, maybe the fish casserole… here are the numbers:

70
 Cases Controls
Total
(ill) (not ill)
Exposed
5 3 8
(ate fish)
Unexposed
2 10 12
(didn‘t eat fish)
7 13 20

 Odds of exposure in cases = a/c = 5/2 = 2.5

 Odds of exposure in controls = b/d = 3/10 = 0.3
 Odds Ratio = (a/c) / (b/d) = 2.5/0.3 = 8.33

Interpretation: What does this mean?

 OR of 1 would suggests that there is no difference between the groups; i.e. there would
be no association between the suggested exposure (fish) and the outcome (being ill)
 OR of > 1 suggests that the odds of exposure are positively associated with the adverse
outcome compared to the odds of not being exposed
 OR of < 1 suggests that the odds of exposure are negatively associated with the adverse
outcomes compared to the odds of not being exposed. Potentially, there could be a
protective effect

In the example above, we can conclude that those who ate the
fish casserole (exposure) were 8.3 times more likely (OR = 8.3) to be ill (outcome), compared to
those who did not eat the fish casserole. Of course this is an entirely ficticious example, and I
have nothing against fish

Advantages

 Appropriate to analyse associations between groups from case-control and prevalent (or
cross-sectional) data.
 For rare diseases (or diseases with long latency periods) the OR can be an approximate
measure to the RR (relative risk)
 Doesn‘t require denominator (i.e. total number in population) unlike measuring risk
 Good method to estimate the strength of an association between exposures and outcomes

Disadvantages

71
  Association does not infer causation! *epidemiology golden rule

You have come to the end of another lecture where we discussed about definition
,calculations and applications of attributable risk, odds ratio and Relative Risks.

Outline the applications of attributable risk in Epidemiology.

______________________________________________________________________________
______________________________________________________________________________
Differentiate between relative risk and attributable risk---------------------------------------------------
---------------------------------------------------------------------------------------------------------------------

. Sauvaget C, Nagano J, Allen N, et al. Intake of animal products and stroke mortality in the
Hiroshima/Nagasaki Life Span Study. International Journal of Epidemiology. 2003;32:536–
543.

Last JM, ed., et al. A Dictionary of Epidemiology. 4th ed. New York: Oxford University Press;
2000.
Gordis L, Epidemiology. 2nd ed. Philadelphia: WB Saunders; 1996.

72
LECTURE NINE :MANTEL HAENZSEL PROCEDURE
9.1 LECTURE OVERVIEW
The Mantel test, named after Nathan Mantel, is a statistical test of the correlation between two
matrices. The matrices must be of the same rank, in most applications they are matrices of
interrelations between the same vectors of objects.

By the end of this lecture, you should be able to:

i. Describe the steps in mantel Haenzsel procedures
ii. Apply the procedure in epidemiological study
iii. Identify the importance of Mantel haenzsel procedure

iv. Describe biases in cohort studies

9.2 Steps of Mantel Haenzsel Procedure

Step One
Calculate a crude OR or RR by summing all the cells of a, b, c and d across all the strata (or from
the entire dataset if not already stratified).
OR = cross product ratio = ad/bc
RR = a (a+b) / c(c+d)

Step Two
Stratify for the suspected confounder or effect modifier if this has not already been done and
calculate the OR or RR for each strata.
Then, compare the crude measure of effect versus the measure of effect for each stratum. How
similar do they look? There will always be some random variation.

Step three
Then test for interaction by performing a Chi-square calculation (is there a significant difference
between observed and expected?).

If the Χ2 term is non-significant then there is no interaction from the term stratified for and we
can proceed.

73
If you don‘t have interaction, there may still be confounding factors.
If the Χ2 term is significant then you stop analysis at this point and report the interaction found in
the data.
Step Four
Now consider the MH estimate of effect (OR or RR) and its confidence intervals.
The H0: that the RRMH or ORMH is equal to 1.
This tests whether or not there is an association between rows and columns i.e. did the risk factor
increase or decrease the incidence if disease?

Step six
Compare the crude estimator of effect to the Mantel Haenszel estimator of effect.
As a rule of thumb –if there is a +/-10% difference between crude and MH then there is likely to
be confounding

Application of Mantel Haenszel procedure in epidemiological research

 The mainstay of epidemiological analyses
 Allows for evaluation of, and control of, confounding factors
 Also allows the evaluation of biological interaction between two factors
 The test is commonly used in ecology, where the data are usually estimates of the
"distance" between objects such as species of organisms. For example, one matrix might
contain estimates of the genetic distances (i.e., the amount of difference between two
different genomes) between all possible pairs of species in the study, obtained by the
methods of molecular systematics; while the other might contain estimates of the
geographical distance between the ranges of each species and every other species.
 If there are n objects, and the matrix is symmetrical (so the distance from object a to
object b is the same as the distance from b to a) such a matrix contains n(n − 1)/2
 The procedure adopted is a kind of randomization or permutation test. The correlation
between the two sets of n(n − 1)/2 distances is calculated, and this is both the measure of
correlation reported and the test statistic on which the test is based. In principle any
correlation coefficient could be used, but normally the Pearson product-moment
correlation coefficient is used.
 helps overcome the problems arising from the statistical dependence of elements within
each of the two matrices, use of the permutation test means that no reliance is being
placed on assumptions about the statistical distributions of elements in the matrices.

9.3 Application of Mantel Haenszel procedure in epidemiological research

74
 The mainstay of epidemiological analyses
 Allows for evaluation of, and control of, confounding factors
 Also allows the evaluation of biological interaction between two factors
 The test is commonly used in ecology, where the data are usually estimates of the
"distance" between objects such as species of organisms. For example, one matrix might
contain estimates of the genetic distances (i.e., the amount of difference between two
different genomes) between all possible pairs of species in the study, obtained by the
methods of molecular systematics; while the other might contain estimates of the
geographical distance between the ranges of each species and every other species.
 If there are n objects, and the matrix is symmetrical (so the distance from object a to
object b is the same as the distance from b to a) such a matrix contains n(n − 1)/2
 The procedure adopted is a kind of randomization or permutation test. The correlation
between the two sets of n(n − 1)/2 distances is calculated, and this is both the measure of
correlation reported and the test statistic on which the test is based. In principle any
correlation coefficient could be used, but normally the Pearson product-moment
correlation coefficient is used.
 helps overcome the problems arising from the statistical dependence of elements within
each of the two matrices, use of the permutation test means that no reliance is being
placed on assumptions about the statistical distributions of elements in the matrices.

. You have come to the end of lecture one. In this lecture you have
learnt the following; steps involved in Mantel Haenzsel procedure and its
application in epidemiology

Now take a break and reflect on some of the issues we

have discussed today. After your break, answer the following questions
i. Describe the steps involved in mantel haenzel
procedure___________
ii. Highlight the uses of epidemiology_____________

75
LECTURE TEN: DISEASE MODELLING

10.1 LE CTURE OVERVIEW

Today, infectious diseases are causing more and more health problems. Just in the last few years,
we've seen many new infectious outbreaks, including SARS, West Nile virus, hantavirus, and
now H1N1 influenza.

In the 1960s and 1970s, we thought we'd licked the problem of infectious diseases with new
vaccines and treatments. It turns out that this conclusion was wildly optimistic. Now, we tend to
think more about managing infectious diseases than ridding the world of them. We want to limit
the impact of these diseases on our lives by reducing the number of people who get sick and by
giving people strategies to protect themselves.

Managing an infectious disease starts with learning as much as you can about the disease and
how it spreads. How does the virus or bacterium infect people--through the nose, in body fluids
like saliva or blood, or through a vector like mosquitoes or ticks? How soon after being infected
do people get sick? How fast do they recover? What groups of people are most affected? What is
the natural host of a disease-causing organism--birds, farm animals, mice? Does human behavior
affect how the disease spreads? Does weather play a role?

Then you need to consider all the interventions you can use. Is there a vaccine? How effective is
it? Will people be willing to be vaccinated? Are there drugs, like antivirals or antibiotics, that
help? Are they readily available? Are they expensive? Are there behavioral or social
interventions? For example, using bed nets can protect people from malaria-carrying mosquitoes,
but will people use nets? Closing schools might protect people from influenza, but is it worth the
cost? What about face masks or hand washing?

By the end of this lecture, you should be able to:

i. Define a model
ii. Explain why we model
iii. Describe The SIR Model for Spread of Disease
- The Differential Equation Model
iv.

10.2 What is a model?

76
A model is a representation of reality, almost always simplified in some way. In technical
language, a model is a representation of a ‗system‘. A system is defined as a collection of
components which work together to produce some kind of output. In real life the system reacts to
various external influences through its components so that the output is modified.
With simple systems it is often possible to predict the effect of external influences on the output
without the need for a model, e.g. vaccination on an individual animal will produce the effect of
protection from a given disease. But as systems become more complex it is no longer possible to
guess exactly how the system will behave in different circumstances, e.g. what would be the
effect on disease incidence of vaccination of only certain classes of livestock within a large
population? The boundaries of the system have been cast wider so that more interacting
components have to be considered simultaneously in order to predict the effect of vaccination –
in this case these components include the structure of the population and its dynamics. Models of
complex systems are made in order to understand the effect of external influences on output
through representation of the interactions between the component parts of the system, i.e. to
answer the questions, ―what might happen if...?‖, and sometimes also, ―why or how does the
effect come about?‖.

10.3 Why make models?

The prediction of the outcome of a particular action on a system is not the only use to which
models may be put. Models can have several uses. In addition to using models:
 to predict the effects of changing or modifying different components in the system;
 models may also be used:
 to test (verify) and improve our understanding of a system;
 to analyse and explain behaviour of a complex system, and;
 to determine the relative importance of different components of the system.
Models can therefore be used as an aid to understanding, rather than being an end in themselves.
Teclaw (1979) says

10.3 Why do we model infectious diseases?

1. Gain insight into mechanisms influencing disease spread, and link individual scale ‗clinical‘
knowledge with population-scale patterns.
2. Focus thinking: model formulation forces clear statement of assumptions, hypotheses.
3. Derive new insights and hypotheses from mathematical analysis or simulation.
4. Establish relative importance of different processes and parameters, to focus research or
management effort.
5. Thought experiments and ―what if‖ questions, since real experiments are often logistically or
ethically impossible.
6. Explore management options
.
Note the absence of predicting future trends.
Models are highly simplified representations of very complex systems, and parameter values are
difficult to estimate.
Æ quantitative predictions are virtually impossible

10.4 The SIR Model for Spread of Disease - The Differential Equation Model

77
As the first step in the modeling process, we identify the independent and dependent variables.
The independent variable is time t, measured in days. We consider two related sets of
dependent variables.

The first set of dependent variables counts people in each of the groups, each as a function of
time:

S = S(t) is the number of susceptible individuals,

I = I(t) is the number of infected individuals, and

R = R(t) is the number of recovered individuals.

The second set of dependent variables represents the fraction of the total population in each of
the three categories. So, if N is the total population (7,900,000 in our example), we have

s(t) = S(t)/N, the susceptible fraction of the population,

i(t) = I(t)/N, the infected fraction of the population, and

r(t) = R(t)/N, the recovered fraction of the population.

It may seem more natural to work with population counts, but some of our calculations will be
simpler if we use the fractions instead. The two sets of dependent variables are proportional to
each other, so either set will give us the same information about the progress of the epidemic.

1. Under the assumptions we have made, how do you think s(t) should vary with time?
How should r(t) vary with time? How should i(t) vary with time?
2. Sketch on a piece of paper what you think the graph of each of these functions looks like.
3. Explain why, at each time t, s(t) + i(t) + r(t) = 1.

Next we make some assumptions about the rates of change of our dependent variables:

 No one is added to the susceptible group, since we are ignoring births and immigration.
The only way an individual leaves the susceptible group is by becoming infected. We
assume that the time-rate of change of S(t), the number of susceptibles,1 depends on the
number already susceptible, the number of individuals already infected, and the amount
of contact between susceptibles and infecteds. In particular, suppose that each infected
individual has a fixed number b of contacts per day that are sufficient to spread the
disease. Not all these contacts are with susceptible individuals. If we assume a
homogeneous mixing of the population, the fraction of these contacts that are with
susceptiblesis s(t). Thus, on average, each infected individual generates b s(t) new
infected individuals per day. [With a large susceptible population and a relatively small

78
 infected population, we can ignore tricky counting situations such as a single susceptible
encountering more than one infected in a given day.]
 We also assume that a fixed fraction k of the infected group will recover during any
given day. For example, if the average duration of infection is three days, then, on
average, one-third of the currently infected population recovers each day. (Strictly
speaking, what we mean by "infected" is really "infectious," that is, capable of spreading
the disease to a susceptible person. A "recovered" person can still feel miserable, and
might even die later from pneumonia.)

Let's see what these assumptions tell us about derivatives of our dependent variables.

4. The Susceptible Equation. Explain carefully how each component of the differential
equation

(1)

5.
follows from the text preceding this step. In particular,

o Why is the factor of I(t) present?

o Where did the negative sign come from?

Now explain how this equation leads to the following differential equation for s(t).

(2)

6. The Recovered Equation. Explain how the corresponding differential equation for r(t),

(3)

7. Follows from one of the assumptions preceding Step 4.

8. The Infected Equation. Explain why

(4)

9. What assumption about the model does this reflect? Now explain carefully how each
component of the equation

(5)

79
 10. follows from what you have done thus far. In particular,

o Why are there two terms?

o Why is it reasonable that the rate of flow from the infected population to the
recovered population should depend only on i(t) ?
o Where did the minus sign come from?

Finally, we complete our model by giving each differential equation an initial condition. For this
particular virus -- Hong Kong flu in New York City in the late 1960's -- hardly anyone was
immune at the beginning of the epidemic, so almost everyone was susceptible. We will assume
that there was a trace level of infection in the population, say, 10 people.2 Thus, our initial values
for the population variables are

S(0) = 7,900,000
I(0) = 10
R(0) = 0
In terms of the scaled variables, these initial conditions are

s(0) = 1
i(0) = 1.27 x 10- 6
r(0) = 0

(Note: The sum of our starting populations is not exactly N, nor is the sum of our fractions
exactly 1. The trace level of infection is so small that this won't make any difference.) Our
complete model is

(6)

We don't know values for the parameters b and k yet, but we can estimate them, and then
adjust them as necessary to fit the excess death data. We have already estimated the average
period of infectiousness at three days, so that would suggest k = 1/3. If we guess that each
infected would make a possibly infecting contact every two days, then b would be 1/2. We
emphasize that this is just a guess. The following plot shows the solution curves for these choices
of b and k.

80
 7. In steps 1 and 2, you recorded your ideas about what the solution functions should look
like. How do those ideas compare with the figure above? In particular,

o What do you think about the relatively low level of infection at the peak of the
epidemic?
o Can you see how a low peak level of infection can nevertheless lead to more than
half the population getting sick? Explain.

10.5 Major decisions in designing a model

Even after compartmental framework is chosen, still need to decide:

 Deterministic vs stochastic

 Discrete vs continuous time

 Discrete vs continuous state variables

 Random mixing vs structured population

 Homogeneous vs heterogeneous(and which heterogeneities to include?)

Deterministic vs stochastic models

Deterministic models
 Given model structure, parameter values, and initial conditions, there is no variation in
output.
Stochastic models
 incorporate chance.

81
  Stochastic effects are important when numbers are small, e.g. during invasion of a new
disease
 Demographic stochasticity: variation arising because individual outcomes are not certain
 Environmental stochasticity: variation arising from fluctuations in the environment (i.e.
factors not explicitly included in the model)

10.6 Important classes of stochastic epidemic models

Monte Carlo simulation
 Any model can be made stochastic by using a pseudo-random number generator to ―roll
the dice‖ on whether events occur.
Branching process
 Model of invasion in a large susceptible population
 Allows flexibility in distribution of secondary infections, but does not account for
depletion of susceptibles

Chain binomial
 Model of an epidemic in a finite population.
 For each generation of transmission, calculates new infected individuals as a binomial
random draw from the remaining susceptibles.
Diffusion
 Model of an endemic disease in a large population.
 Number of infectious individuals does a random walk around its equilibrium value
 quasi-stationary distribution

Continuous vs discrete time Continuous-time models (ODEs, PDEs)

 Well suited for mathematical analysis
 Real events occur in continuous time
 Allow arbitrary flexibility in durations and residence times
Discrete-time models
 Data often recorded in discrete time intervals
 Can match natural timescale of system, e.g. generation time or length of a season
 Easy to code (simple loop) and intuitive
 Note: can yield unexpected behaviour which may or may not be biologically relevant
(e.g. chaos).

Continuous vs discrete state variables

 Continuous state variables arise naturally in differential equation models.
 Mathematically tractable, but biological interpretation is vague (sometimes called
‗density‘ to avoid problem of fractional individuals).
 Ignoring discreteness of individuals can yield artefactual model results (e.g. the ―atto-
fox‖ problem).
 Quasi-extinction threshold: assume that population goes extinct if continuous variable
drops below a small value

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  Discrete state variables arise naturally in many stochastic models, which treat individuals
(and individual outcomes) explicitly

Individual ―clinical‖ data

• Latent period: time from infection to transmissibility
• Infectious period: duration (and intensity) of shedding infectious stages
• Immunity: how effective, and for how long?
Population data
• within and between population groups
Epidemiological data
• Transmissibility (
- density dependence, seasonality
Time series
Incidence: number of new cases
Prevalence: proportion of population with disease
Seroprevalence / sero-incidence:
shows individuals‘ history of exposure.
 Age/sex/spatial structure, if present.
e.g. mean age of infection

Cross-sectional data
 Seroprevalence survey (or prevalence of chronic disease)
endemic disease-at steady state

 insight into mixing

 epidemic disease-outbreak size, attack rate, and risk groups

Potential roles of models with respect to Disease control

Modelling can contribute in all of the following areas:
 retrospective analysis of epidemics and evaluation of different control strategies;
 contingency planning – exploration of the effect of different strategies in hypothetical
 epidemics;
 resource planning – exploration of the resource requirements of different strategies in
hypothetical epidemics;
 training – the use of models to provide ‗virtual‘ experience of epidemic combat;
 surveillance targeting – in particular the use of risk assessments to identify priority areas;
 Tactical decision support – limited use of models during epidemics.
10.7 Validation of models
There are no simple rules to follow when validating models. Several key issues are
identified; These are:
 Valid models should make biological sense;
 Valid models should mimic real life;
 Valid models should be fit for the use they are designed for;

83
  Sensitivity analysis should be carried out to assess the influence of uncertain parameters
on the model outcome.

You have come to the end of lecture one. In this lecture you have learnt
the following; definition of disease modeling, why model diseases, types of models, SEIR
model, the role of data in disease modeling.

Now take a break and reflect on some of the issues we

have discussed today. After your break, answer the following questions:
i. Highlight reasons for disease modelling_______________
ii. Describe the role of data in disease
modeling______________________________________
iii. Highlight the types of stochastic models used in
epidemiology___________________________________
iv. Differentiate between discrete time and continuous
models__________________________________________

Modern Epidemiology, 2nd Ed Rothman, K. J. and Greenland, S Lippincott, Philadelphia 0-7216-

6181-5-5 1985

Essentials of Epidemiology in Public Health by Ann Aschengrau and George R. Seage III, Jones
and Bartlett Publishers, Boston and London

The UFAW Handbook on The Care & Management of Laboratory Animals, Trevor Poole (Ed).
Longman Scientific & Technical

84
LECTURE TWELVE: DISEASE SURVEILLANCE

11.1 LECTURE OVERVIEW

Disease surveillance has been a part of public health protection since the 1200s during the
investigations of the bubonic plague in Europe. During the 1600s John Grant developed the
fundamental principles of public health including surveillance and outbreak investigation, and in
the 1700s rhode Island passed the first public health laws to provide for the protection of health
and care of the population of the state. In the eighteenth century, Farr introduced the modern
version of surveillance and along with the United States, Italy, and Great Britain began required
reporting systems for infectious diseases. By 1925 the United States began national reporting of
morbidity causes. By 1935 the first national health survey had been conducted, and in 1949 the
National Office of Vital Statistics published weekly mortality and morbidity statistics in the
Journal of Public Health Reports. this activity was later transferred to the Centers for Disease
Control and Prevention, who began publishing the
Morbidity and Mortality Weekly Report in 1961. Laws, regulations, reporting mechanisms, and
data collections are all essential to surveillance and disease outbreak investigations.

By the end of this lecture, you should be able to:

1. Define public health surveillance
2. Highlight the features and uses of Surveillance
3. Describe the plannining of surveillance system
4. Discuss the evaluation of surveillance system
11.2 DISEASE SURVEILLANCE
Definitions and Importance
Disease surveillance is ―the ongoing systematic collection, analysis, interpretation and
dissemination of specific health data for use in public health‖ (teutsch and Churchill,
2000). Surveillance provides a means for nurses to monitor disease trends in order to reduce
morbidity and mortality and to improve health.
Surveillance is a critical role function for nurses practicing in the community. A comprehensive
understanding and knowledge of the surveillance systems and how they work will help nurses
improve the quality and the usefulness of the data collected for making decisions about needed
community services, community actions, and public health programming . Surveillance is
important because it generates knowledge of a disease or event outbreak patterns (including
iming, geographic distribution, susceptible populations). the knowledge can be used to intervene
to reduce risk or prevent an occurrence at the most appropriate points in time and in the most

85
effective ways. Surveillance is built on understanding of epidemiologic principles of agent,
host, and environmental relationships and on the natural history of disease or conditions.
Surveillance systems make it possible to engage in effective continuous quality improvement
activities within organizations and to improve quality of care. Surveillance focuses on the
collection of process and outcome data.

Process data focus on what is done, i.e. services provided or protocols for health care.
Outcome data focus on changes in health status. the activities generated by analyses of these data
aim to improve public health response systems. an example of process data is collection of data
about the proportion of the eligible population vaccinated against influenza in any one year.
Outcome data in this case are the incidence rates (new cases) of influenza among the same
population in the same year. although surveillance was initially devoted to monitor ing and
reducing the spread of infectious diseases, it is now used to monitor and reduce chronic diseases
and injuries, and ―environmental and occupational exposures‖ (Ching, 2002) as well as personal
health behaviors. Surveillance systems help nurses and other professionals monitor emerging
infections, and bioterrorist outbreaks (Pryor and Veenema, 2003). Bioterrorism is one example
of an event creating a critical public health concern that involves environmental exposures that
must be monitored. This event also requires serious planning in order to be able to respond
quickly and effectively.
Biological terrorism is defined as ―an intentional release of viruses, bacteria, or their
toxins for the purpose of harming or killing . . . citizens‖ (CDC, 2001a).
Chemical terrorism is the intentional release of hazardous chemicals into the environment for the
purpose of harming or killing (CDC, 2001a). In the event of a bioterrorist attack, imagine how
difficult it would be to control the spread of biological agents such as botulism or anthrax or
chemical agents such as sarin or ricin if no data were available about these agents, their resulting
di eases or symptoms, and their usual incidence (new cases)

11.3 Features of Surveillance

 Is organized and planned
 Is the principle means by which a population‘s health status is assessed
 Involves ongoing collection of specific data
 Involves analyzing data on a regular basis
 Requires sharing the results with others
 Requires broad and repeated contact with the public about personal health issues
 Motivates public health action as a result of data analyses to:
 Reduce morbidity
 Reduce mortality
 Improve health

11.4 Uses of Public Health Surveillance

Public health surveillance can be used to facilitate the following (CDC, 2004):
 Estimate the magnitude of a problem (disease or event).
 Determine geographic distribution of an illness or symptoms.
86
  Portray the natural history of a disease.
 Detect epidemics; define a problem.
 Generate hypotheses; stimulate research.
 Evaluate control measures.
 Monitor changes in infectious agents.
 Detect changes in health practices.
 Facilitate planning

11.5 Types of Surveillance

1. Active- e.g. notifications, COVER

2. Senitel - i.e. sample surveillance

3. Passive -

11.6 Planning a Surveillance System

1. Establish Objectives

2. Develop case definitions

3. Determine data source or data collection mechanism

4. Develop data collection instruments

5. Field test methods

6. Data analysis and interpretation

7. Dissemination and feedback

8. Evaluation

1. Establish Objectives

Identifying high priority health events

Disease related:

87
Frequency (incidence, prevalence, mortality, morbidity)

Severity (case fatality, hospitalisation rate, QALYs)

Cost to society

Preventability

Communicability

Society related:

International obligations

Public & mass media interest

Political will to prevent

Availability of data

2. Establish case definitions

Criteria - i.e. person, place, time, clinical or laboratory diagnosis, epidemiological features

3. Sources of data

1. Lab reports

2. Statutory notifications

3. Hospital episode statistics

4. Clinical reporting - sentinel reporting system

5. COVER

6. Other clinical reports - e.g. BPSU, AIDS/HIV, KC60

88
7. Death certs

Evaluation of a System

1. Describe the public health importance of the health event under surveillance consider:

Total numbers of cases, incidence and prevalence

Indices of severity (death rate, case fatality ratio)

Can it be prevented?

2. Describe the surveillance system to be evaluated

List its objectives (see purposes & uses of surveillance system)

Describe the health event under surveillance

Describe the components and operation of the system:

a. What information is collected?

b. Who collects the data?

c. Time to collect the data

d. Mode of data transfer and storage

e. Who analyses data?

f. How is it disseminated?

g. Who is it disseminated to?

3. Discuss validity and repeatability of case definitions in various types of surveillance data

89
4. Indicate the level of usefulness by describing the actions taken as a result of data
collected by the surveillance system

5. Describe cost/resources needed to run surveillance

6. Evaluate the quality of the surveillance system by assessing its attributes

Flexibility

Representativeness

Acceptability

Timeliness

Sensitivity

Simplicity

7. List conclusions and recommendations

8. Ways to improve the system

Improve awareness of disease by increasing education

Simplify reporting

Frequent feedback

Use multiple sources and methods

Active surveillance

Sentinel surveillance

Computerisation

11.7 Characteristics of a Surveillance System

Feedback (distinguishes it from a database)

Rapidity

90
On-going

Standardised nature

Ease

11.8 Limitations of a Surveillance System

Completeness

Accuracy

Relevance and/or representiveness

Timeliness

11.9 Sources of Specific Surveillance data

TB

1. Statutory notifications

2. Lab reports

3. Death certs

4. Mycobnet

5. Enhanced tuberculosis surveillance

Nosocomial

1. Hospital Episodes Statistics

2. Nursing, doctor notes

3, Lab reports and local lab based surveillance (MRSA, Clostridium difficile)

4. Surgical Site Infection Surveillance Service

Seasonal Flu

1. Royal College of General Practitioners scheme

91
2. Mortality statistics

3. Lab reports

4, Hopsital Episodes Statistics

Legionnaires' Disease

Incidence estimated from hospital admissions for unspecified community acquired pneumonia
(CAP)

'Gold standard' surveillance

Monitoring trends - (1) annual data sets (UK/EWGLNET countries) (2) age groups (3) sex
distribution (4) severity of illness and proportion of deaths (5) case type (6) method of diagnosis
(urinary, serological, culture)

Local, regional, national and European surveillance [European Working group for Legionella
Infections, Annual European report of all legionella cases (travel/nontravel) (EWGLI),
International surveillance of travel associated legionnaires' diseases (EWGLINET)]

Five Principles of Surveillance

1. Systematic collection of data

2. Analyses of data to produce statistics (by time, person, place)

3. Interpretation to provide information (be aware of timeliness, completeness, representation)

4. Distribution of information to those who require action e.g. CDR weekly

5. Continuing surveillance to evaluate action

You have come to the end of lecture one. In this lecture you have
learnt the following; definition of disease surveillance, features and uses of

92
 surveillance, principle of surveillance, establishing a surveillance system,
evaluation of surveillance and limitation of surveillance system.

Now take a break and reflect on some of the issues we

have discussed today. After your break, answer the following questions:
i. Highlight role of surveillance in
epidemiology_______________
ii. Describe how one can establish a surveillance
system______________________________________
iii. Highlight the output of surveillance epidemiology_______
iv. Differentiate between Active and Passive
surveillances______________________________________
____

1. World Health Organization. (2012). Epidemiology.Retrieved May 18, 2012.

2. The WHO Family of International Classifications. (2012). Retrieved May 18, 2012, from
World Health Organization.
3. World Health Organization. (2012). World Health Statistics 2012.Retrieved May 18,
2012.
4. Columbia University.(n.d.).Glossary of Epidemiology Terms.Retrieved May 18, 2012.
5. Centers for Disease Control and Prevention. (2011, February 28). International Outbreak
Investigations.Retrieved May 18, 2012.
6. Office of Surveillance, Epidemiology, and Laboratory Services. (2004, November 17).
Steps of an Outbreak Investigation.Retrieved May 18, 2012, from Centers for Disease
Control and Prevention.

93
LECTURE 12.1 DISEASE CONTROL STRATEGIES

12.1 LECTURE OVERVIEW

These public health strategies are important to prevent the spread of disease among persons at
risk. For example, outreach programs, in the community and on the streets, make available to
persons who use drugs prevention and risk reduction, testing, and referral services.
Recommended approaches, immunizations and screening, can protect the health of a person
who uses drugs through medical interventions, while evidence-based behavioral interventions
help prevent sexual and injection transmission by addressing risky behaviors. In this discussion
we will focus mainly on Nutrition, vector control, Health education and Promotion and
Immunization.

By the end of this lecture, you should be able to:

1. Describe factors in eradicating disease
2. Discuss nutrition and infectious disease control
3. Discuss the role of vector control in disease
control
4. Describe immunization and disease control
5. Discuss the rolr of health promotion in disease

12.2 Key Factors in Eradicating a Disease

Scientific feasibility and political support are the two primary factors determining whether a
disease can be eradicated.

Conditions that make it scientifically feasible to eradicate a disease include:

 Epidemiologic vulnerability. A disease could be considered vulnerable if it: does not

spread easily; there is a natural cyclical decline in prevalence; there is a naturally induced
immunity; it is easily diagnosed; and the duration of any relapse potential is short.

 Availability of an effective and practical intervention. Such interventions could include a

vaccine or other primary preventive measure, a curative treatment, or a means of
eliminating vectors. Ideally, intervention should be effective, safe, inexpensive, long-
lasting, and easily deployed.

 Demonstrated feasibility of elimination. A disease that has been documented to have

been eliminated from an island or other geographic unit could be a candidate for
eradication.

94
Even if it is scientifically feasible to eradicate a disease, there are nonscientific conditions that
must be considered, such as:

 Perceived burden of the disease

 Expected cost of eradication

 Synergy of eradication efforts with other interventions

 Necessity for eradication rather than control

12.3 NUTRITION AND INFECTIOUS DISEASE CONTROL

 The interaction of infection and nutrition as a cause of mortality and severe morbidity in
children is well documented, and has a disproportionately high impact on lower socio-
economic groups. Addressing infectious disease is thus a second essential part of actions
to improve nutrition. Malnutrition and infection form a cycle. Here, nutrition actions as
they affect infectious disease in terms of prevention and management are discussed in
some detail. Infectious disease control itself is so important - both in its own right and in
relation to nutrition - that it is also included under this heading.
 Because malnutrition and infection interact and are closely linked, it is relevant to talk
about a "malnutrition-infection complex". Of the about 13 million infants and children
who currently die each year in developing countries, most of the deaths are due to
infections and/or parasitic disease, and many if not most of the children die
malnourished. The malnutrition and infection complex remains the most prevalent public
health problem in the world today21.
 The principles underlying malnutrition and infection can be summarized as follows.
Inadequate dietary intake leads to low nutritional reserves, which are manifested as
weight loss or failure of growth in children. Depleted nutritional reserves are associated
with a lowering of immunity, probably with almost all nutrient deficiencies. Particularly
in protein-energy and vitamin A deficiencies there may be progressive damage to
mucosa, lowering resistance to colonization and invasion by pathogens. Lowered
immunity and mucosal damage are the major mechanisms by which defences are
compromised. Under these circumstances, the incidence, severity, and duration of
diseases may be increased. The relative importance of these three factors is not fully
worked out under all conditions. The disease processes themselves exacerbate loss of
nutrients, both by the host's metabolic response, and by physical loss from the intestine.
These factors themselves worsen the malnutrition, leading to further damage to defence
mechanisms. At the same time, many diseases are associated with a loss of appetite, and
other possible disabilities, cycling back to further lower the dietary intake. While other
relationships play a part, these are some of the most important, and account for much of
the high morbidity and mortality under circumstances of high exposure to infectious
disease and inadequate diet, characterizing many poor communities.
 Control of infectious disease, and dietary/nutrition interventions to promote this process,
are thus of major importance in cutting into the cycle of malnutrition and infection.
Controlling infectious disease through primary health care is a major priority of the

95
 health sector. Concern for nutrition only reinforces this priority. It is worth noting that
prevention and management of infection is particularly important in malnourished
communities: for example, measles immunization would be expected to save more lives
in malnourished communities than in those better off.
 Dietary interventions during and immediately after infectious disease can affect the
course and effects of the disease, and reduce the extent to which nutritional status suffers.
Nutrition is thus relevant to disease management. Adequate nutrition maintains immunity
and other protection against disease, so that nutritional or dietary interventions can be
important in prevention; indeed, it has been claimed that longer-term trends (over
decades) towards improved health in many countries are basically due to the preventive
effect of better nutrition22.
 Interventions during management of infection often fall naturally within the existing
concerns of the health sector - as examples in combating anorexia, and in maintaining
dietary intake during persistent diarrhoea. Nutritional interventions for prevention may or
may not be through the health sector; for example the social services are responsible in
some countries.
 In sum, policies to improve nutrition necessarily include control of infectious disease.
Often, they will reinforce priorities that are already accepted: for example, the prime
importance of breastfeeding needs to be promoted through the health and other sectors.
Equally, nutrition considerations would support the priority given to environmental
sanitation, housing, as well as measures such as immunization, oral rehydration, parasite
control, etc. Within these conventional health measures, nutrition considerations may
have a part to play in terms of targeting and monitoring and evaluation of outcomes.
 Concern with nutrition improvement may be particularly usefully translated into action
by emphasis on feasible, usually incremental, actions incorporated within services. These
are stressed here, not least because of their obvious relation to nutritional concerns, and
the fact that they may get lost sight of in sectoral planning. The scope for action is
discussed later as specific strategies for tackling malnutrition and infection in the context
of primary health care and its support systems, under three main headings:

 Dietary management of infection dietary prevention of infection

- infectious disease control to improve nutrition.
 Growth monitoring is important for all three aspects and should be promoted for
individual problem detection, for communication with mothers and communities, for
assessing progress, and for other reasons23.
 Setting for Action
 While the control of infectious diseases is accorded a high priority within health
departments, effective programmes are complex, costly and difficult to implement.
Furthermore, to be most effective they require substantial contributions from sectors
other than health. Financing of the health sector is traditionally assigned a low priority in
developing countries with market economies. Within limited health budgets, a high
proportion of funds is allocated to hospital-based curative care, involving major capital
and recurrent costs and leaving only minor resources for the development of preventive
programmes. Limitations of health infrastructure result in low overall coverage which in
turn limits the reach of primary health care programmes and their infectious disease
control components.

96
 The control and prevention of infection should be central to health policy in developing
countries where infectious disease morbidity is the major component of hospital
admission. Primary health care programmes give clear priority to a range of services and
activities designed to reduce the incidence and severity of common infections. While
infectious disease is a clear priority for the health sector, a number of the principal
interventions for its control are the responsibility of other sectors. Adequacy and safety of
water supply, sanitation and housing are usually substantially determined by public works
departments and local authorities.
The interaction between infection and malnutrition has an overwhelming impact on those
who are poorest in social, economic and environmental terms and is the major cause of
death, sickness and disability in infants and young children as well as being an important
contributor to ill-health and reproductive problems of their mothers. Its occurrence is the
single most powerful expression of the biological consequences of poverty and
disadvantage. Reduction of the frequency and severity of infection in the long-term
requires addressing poverty and deprivation within the broader framework of economic
growth and social development. In the context of this paper, such an approach includes
the improvement of household food security, environmental hygiene, child caring
capacity, and the empowerment of women. These are discussed in sections B and D.
Micronutrient deficiency control programmes are covered further in section E.

12.4 Dietary Management of Infection

Dietary management seeks to modify the course and outcome of infection by the
improvement of food intake during disease and recovery, particularly in young children.
This is applied principally through education programmes enabling mothers and carers to
acquire and apply the necessary food resources and skills in an effective manner. The
education may be formal, through the school system for example, but importantly
includes information and counselling through health care workers. Under a number of
circumstances, supplementary food, micronutrient supplements, and technologies such as
for fermented and amylase-rich foods may be supplied as part of the services. A brief list
of possible actions, related as appropriate to specific common diseases follows.
i) Continuation of breastfeeding during infections This applies to all infections, but with
particular force to diarrhoea, measles, respiratory tract infections, and malaria. In children
up to four to six months of age, exclusive breastfeeding is recommended. During
episodes of diarrhoea, continued exclusive breastfeeding (with increased frequency and
duration of feeds if possible) is the most important nutritional aspect of management. If
such infants nonetheless become dehydrated, rehydration therapy may be required. When
breastfeeding is maintained during diarrhoea, the growth faltering commonly associated
with diarrhoea is rarely seen, and the risk of death is minimized. Continued breastfeeding,
as required with increased frequency, is also central to the management of other acute
infections, such as measles and acute respiratory tract infections, of which pneumonia is
the most serious. In children older than four to six months, continued partial
breastfeeding is of similar importance, and its continuation during episodes of infection
should be emphasized.
ii) Maintenance of diet during infection, especially persistent diarrhoea, including both
active and recovery (catch-up) phases Maintaining supplementary foods in young
children (above four to six months of age) during the course of infection, and increasing

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 intake during the recovery period, is essential. This is made more difficult by the anorexia
that commonly accompanies infectious disease, and by the low energy density of many
weaning foods. The mistaken view that is still prevalent in some communities that dietary
intake should be restricted during infection is particularly pernicious, and needs to be
vigorously counteracted. In this context, not only is encouragement to continue feeding
required, but promotion of methods that increase the energy density of palatable diets
should be stressed - there is considerable potential for use here of fermented foods (often
along traditional lines) and use of amylase-rich flours to reduce bulk. Supply of
supplementary foods may also be a means of increasing food intake during these critical
periods.
iii) Administration of vitamin A in the management of measles, acute respiratory
infections, etc.24In areas where vitamin A deficiency exists particularly during and in the
immediate post-infection phases of measles and respiratory tract infections, vitamin A
supplementation has been shown to be effective in reducing case-fatality, preventing
further infection and promoting recovery. This may be accomplished by counselling for
vitamin A-rich foods in the diet, and often can also be effectively achieved by direct
provision of vitamin A supplements.
iv) Use of oral rehydration therapy in treatment of acute diarrhoeaThis intervention is
well known and widely applied, and has relevance to nutrition not only in the
management of the disease itself, but very possibly in counteracting anorexia, thus
enabling more successful application of the interventions mentioned here. Home-
prepared fluids (e.g. gruels) for treating dehydration may be considered.
v) Dietary support in chronic infections With diseases such as tuberculosis, leprosy and
AIDS, attention to maintaining adequate dietary intake forms an important part of the
management. Methods in young children are similar to those discussed above, including
continuation of breastfeeding, and provision of higher energy density and palatable foods,
and emphasis on frequency of feeding.
 vi) Iron and malaria Malaria is frequently associated with iron-deficiency anaemia, and
the interactions are complex. However, current evidence is that oral administration of
iron during the treatment of malaria, in moderate doses, is valuable. This will help
enhance immunity, and the benefits of oral supplementation are considered to outweigh
the risks which are peculiar to malaria since the parasite requires iron for multiplication.
 vii) Other micronutrient deficiencies Multiple micronutrient deficiencies are commonly
associated with infectious disease and have particularly been implicated in acute
respiratory infections (notably zinc, iron, and possibly vitamin D). Due attention to
micronutrient status during management is appropriate.
 viii) Intestinal parasites Infection with intestinal parasites is frequently associated with
malnutrition, and the potential for integrating parasite control and nutrition programmes
is clear. In this context, where intestinal parasite infestation is prevalent, parasite control
programmes may usefully include food supplementation, and vice versa.
 ix) Effective nursing/caring during sickness in the family In effect, many of the
interventions discussed here depend upon family members and helpers. To be effective
these may need counselling and support to care for sick children during infection, and
importantly in the nutritional context to promote their rapid catch-up during the recovery
phase. Emphasis on providing the appropriate information through all available channels

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 is required, because this aspect is frequently overlooked in the delivery of health and
nutrition programmes.

12.5 Dietary Prevention of Infection

 Dietary prevention seeks to reduce the frequency and severity of infection by ensuring a
safe and nutritionally adequate diet and limiting energy expenditure, to protect nutritional
status. Good nutritional status prevents infection by a number of mechanisms, notably
through the immune system and maintaining the integrity of epithelial tissues. Again,
education and information are important means of implementation. Specific interventions
through the health system may also be needed. Dietary prevention of infection includes
promoting or ensuring the following.
 i) Exclusive breastfeeding for four to six months Exclusive breastfeeding helps to prevent
diarrhoea by minimizing the infant's exposure to diarrhoeal pathogens, which are
common in other foods and in water. At the same time, breast milk provides anti-bacterial
activity in the infant's gut, reducing the risk of disease if contaminants should be
ingested. Similarly, breastfeeding has direct benefits in preventing other diseases, from
acquired passive immunity from the mother. It also probably prevents malnutrition, not
only secondarily to diarrhoea, through the cycle of suckling promoting production of
maternal milk.
 ii) Continued breastfeeding into the second year of life Continued breastfeeding promotes
prevention of disease through protection of nutritional status, as well as some continuing
direct protection against infectious disease. Indirect effects are also important, through
birth spacing.
 iii) Satisfactory quality and intake of complementary foods A number of issues arise here,
concerning energy density, nutritional value, and food hygiene. It is essential to promote
frequent feeding of foods of adequate energy density (including use of amylase-rich
flours). Microbial contamination may be reduced using fermented foods. Good feeding
practices may be promoted through education, and in some circumstances, perhaps
notably in urban areas, special weaning foods may be marketed.
 iv) Vitamin A status in relation to measles and respiratory tract infections Vitamin A
supplements are indicated in all populations at high risk from measles where vitamin A
deficiency exists. Measles precipitates vitamin A deficiency, and the disease is worsened
in the deficient individual. There is also accumulating evidence that vitamin A deficiency
increases risks of developing respiratory diseases, and that children who are vitamin A
deficient are more likely to suffer from chronic ear infections. Thus prevention of vitamin
A deficiency is particularly important to reduce the incidence and severity of respiratory
tract infections, of which pneumonia is the most serious. In general terms, preventing
vitamin A deficiency by dietary improvement, fortification and/or supplementation is
expected to ameliorate infectious disease, through effects on immunity and on epithoreal
tissues.
 v) Prevention of low birth weight Improving women's nutritional status, especially pre-
and during pregnancy, is important not only for the nutrition of women but in preventing
low birth weight (especially intra-uterine growth retardation) and subsequent likely
higher risks of malnutrition, morbidity and mortality in the offspring. A number of
interventions to improve women's nutrition are mentioned in section D, and those that are
particularly relevant in this context include maternal supplementation, reduction of

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 energy expenditure, and family planning, with particular reference to adolescent mothers.
Low birth weight infants are considered to be at particular risk of respiratory tract
infections, thus reducing low birth weight may have this specific benefit of reducing
RTIs.
 vi) Iron and malaria As for management of malaria and anaemia, there are complex
issues concerning iron supplementation in malaria endemic areas. In general, oral iron
should be administered to all pregnant women under malaria chemoprophylaxis; however
this issue does not arise for the population in general, since malaria chemoprophylaxis is
no longer recommended on a population basis, at least for young children, in situations
where there is inadequate assurance that it can be maintained in the long-term. Where
malaria chemoprophylaxis cannot be administered systematically, it is nonetheless
expected that iron supplementation under these conditions would be of benefit, due to the
immune effect relating to malaria, as well as through improving anaemia. In general,
assuring adequate iron status will have widespread public health benefits, reducing
anaemia and improving immunity.

12.6 Infectious Disease Control

 Control of infectious diseases which will improve nutrition and have other benefits, is
widely described. The main point to emphasize here is that concern for nutrition
inevitably includes priority for infectious disease control.
 Controlling infectious diseases involves improving the health environment, and assuring
access to adequate health services - indeed all the factors encompassed under the concept
of primary health care. In the context of child malnutrition, particular emphasis may be
appropriate to programmes of immunization (EPI), controlling respiratory infections,
malaria, schistosomiasis, and intestinal parasites. At the same time, promoting the early
diagnosis and treatment of infection in children and mothers (especially during
pregnancy) by primary care services has a central role. Of the specific disease
programmes in relation to malnutrition and young children, those that address diarrhoeal
disease, not only acute diarrhoea for which rehydration is important, but also persistent
diarrhoea for which dietary management is of particular importance, must be stressed.

12.7 Measurement Issues

 Malnutrition and infection can be measured by well-established methods, including
anthropometry often as growth monitoring26. Assessing the processes outlined in this
section is also relatively straightforward in principle, from service or administrative
sources in some cases, otherwise from household surveys. Some relevant indicators are
proposed below; those generally only available from household surveys are designated
(S), although data availability (and reliability) from service or administrative sources will
vary greatly and may also require special surveys.
 For assessing management of infectious diseases, the following indicators (usually as
percentages) may be important: case fatality rates by disease (e.g. diarrhoea, pneumonia,
measles; measles cases given vitamin A; individuals with chronic diseases given food
and/or micronutrient supplements; proportion of mothers breastfeeding during child's
illness (S); feeding patterns and frequency during child's illness (S); aspects of child care
during illness including use of oral rehydration therapy (S).

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  For assessing prevention,the following indicators should be considered: incidence of low
birth weight; age at first pregnancy; proportion of short birth intervals (e.g. less than 24
months); contraceptive prevalence rates. Other important information may be obtained
from such data as: proportion of infants exclusively breastfed for four to six months (S);
feeding frequency, weaning food preparation, with respect to both quantity and quality
(S); vitamin A supplementation and disease-specific mortality (S).
 Infectious disease control is assessed by a number of standard methods, generally
involving household or individual surveys, which would include: immunization coverage
rates; coverage of programmes for control of diarrhoeal disease, acute respiratory
infections, parasites; proportion of individuals receiving effective primary treatment of
infections.
Related Policies
 The prevention and control of malnutrition/infection requires substantial inputs from
other sectors than health to be effective. The priorities of those sectors may not be
compatible with those of the health sector in terms of nature, area, targeting or timing;
some examples follow. Physical planning and housing policies determine the adequacy of
the physical (and often social) environment and the degree of overcrowding. The re-
development of urban slums is a costly and sometimes disruptive process, and the
extension of water and sanitation to temporary settlements often conflicts with longer
term plans for permanent developments. Crowded education curricula may not permit the
introduction of health education within official school hours and teaching staff may not
live in the community. Agricultural policy which encourages commercial cash cropping
may have adverse effects on nutrition if income increases are not translated into
improved diet and better quality care. Irrigation schemes can markedly extend the
distribution of schistosomiasis. Changes in agricultural patterns resulting in greater
involvement of women and children can affect health care and exposure to infectious
diseases (e.g. malaria, hookworm). Development of a more stable society and
infrastructure can have a direct effect on infectious disease transmission (e.g. STDs).

12.8 Improving Your Eating Habits

When it comes to eating, we have strong habits. Some are good ("I always eat breakfast"), and
some are not so good ("I always clean my plate"). Although many of our eating habits were
established during childhood, it doesn't mean it's too late to change them.

Making sudden, radical changes to eating habits such as eating nothing but cabbage soup, can
lead to short term weight loss. However, such radical changes are neither healthy nor a good
idea, and won't be successful in the long run. Permanently improving your eating habits requires
a thoughtful approach in which you Reflect, Replace, and Reinforce.

 REFLECT on all of your specific eating habits, both bad and good; and, your common
triggers for unhealthy eating.
 REPLACE your unhealthy eating habits with healthier ones.
 REINFORCE your new, healthier eating habits.

Reflect, Replace, Reinforce: A process for improving your eating habits

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1. Create a list of your eating habits. Keeping a food diary for a few days, in which you
write down everything you eat and the time of day you ate it, will help you uncover your
habits. For example, you might discover that you always seek a sweet snack to get you
through the mid-afternoon energy slump. It's good to note how you were feeling when
you decided to eat, especially if you were eating when not hungry. Were you tired?
Stressed out?
2. Highlight the habits on your list that may be leading you to overeat. Common eating
habits that can lead to weight gain are:

 Eating too fast

 Always cleaning your plate
 Eating when not hungry
 Eating while standing up (may lead to eating mindlessly or too quickly)
 Always eating dessert
 Skipping meals (or maybe just breakfast)

3. Look at the unhealthy eating habits you've highlighted. Be sure you've identified all
the triggers that cause you to engage in those habits. Identify a few you'd like to work on
improving first. Don't forget to pat yourself on the back for the things you're doing right.
Maybe you almost always eat fruit for dessert, or you drink low-fat or fat-free milk.
These are good habits! Recognizing your successes will help encourage you to make
more changes.
4. Create a list of "cues" by reviewing your food diary to become more aware of when and
where you're "triggered" to eat for reasons other than hunger. Note how you are typically
feeling at those times. Often an environmental "cue", or a particular emotional state, is
what encourages eating for non-hunger reasons.

Common triggers for eating when not hungry are:

 Opening up the cabinet and seeing your favorite snack food.

 Sitting at home watching television.
 Before or after a stressful meeting or situation at work.
 Coming home after work and having no idea what's for dinner.
 Having someone offer you a dish they made "just for you!"
 Walking past a candy dish on the counter.
 Sitting in the break room beside the vending machine.
 Seeing a plate of doughnuts at the morning staff meeting.
 Swinging through your favorite drive-through every morning.
 Feeling bored or tired and thinking food might offer a pick-me-up.

5. Circle the "cues" on your list that you face on a daily or weekly basis. Going home
for the Thanksgiving holiday may be a trigger for you to overeat, and eventually, you
want to have a plan for as many eating cues as you can. But for now, focus on the ones
you face more often.

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 6. Ask yourself these questions for each "cue" you've circled:

 Is there anything I can do to avoid the cue or situation? This option works best for
cues that don't involve others. For example, could you choose a different route to work to
avoid stopping at a fast food restaurant on the way? Is there another place in the break
room where you can sit so you're not next to the vending machine?
 For things I can't avoid, can I do something differently that would be healthier?
Obviously, you can't avoid all situations that trigger your unhealthy eating habits, like
staff meetings at work. In these situations, evaluate your options. Could you suggest or
bring healthier snacks or beverages? Could you offer to take notes to distract your
attention? Could you sit farther away from the food so it won't be as easy to grab
something? Could you plan ahead and eat a healthy snack before the meeting?

7. Replace unhealthy habits with new, healthy ones. For example, in reflecting upon your
eating habits, you may realize that you eat too fast when you eat alone. So, make a
commitment to share a lunch each week with a colleague, or have a neighbor over for
dinner one night a week. Other strategies might include putting your fork down between
bites or minimizing other distractions (i.e. watching the news during dinner) that might
keep you from paying attention to how quickly — and how much — you're eating.
Here are more ideas to help you replace unhealthy habits:

 Eat more slowly. If you eat too quickly, you may "clean your plate" instead of paying
attention to whether your hunger is satisfied.
 Eat only when you're truly hungry instead of when you are tired, anxious, or feeling an
emotion besides hunger. If you find yourself eating when you are experiencing an
emotion besides hunger, such as boredom or anxiety, try to find a non-eating activity to
do instead. You may find a quick walk or phone call with a friend helps you feel better.
 Plan meals ahead of time to ensure that you eat a healthy well-balanced meal.

8. Reinforce your new, healthy habits and be patient with yourself. Habits take time to
develop. It doesn't happen overnight. When you do find yourself engaging in an
unhealthy habit, stop as quickly as possible and ask yourself: Why do I do this? When did
I start doing this? What changes do I need to make? Be careful not to berate yourself or
think that one mistake "blows" a whole day's worth of healthy habits. You can do it! It
just takes one day at a time!

12.10 VECTOR CONTROL

Vector control is any method to limit or eradicate the mammals, birds, insects or other
arthropods (here collectively called "vectors") which transmit disease pathogens. The most
frequent type of vector control is mosquito control using a variety of strategies. Several of the
"neglected tropical diseases" are spread by such vectors.

In the United States, cities or special districts are responsible for vector control. For example, in
California, the Greater Los Angeles County Vector Control District is a special district set up by
the state to oversee vector control in multiple cities.[1]

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Methods of Control

Vector control focuses on utilizing preventative methods to control or eliminate vector

populations. Common preventative measures are:

Habitat/Environmental Control

Removing or reducing areas where vectors can easily breed can help limit population growth.
For example, stagnant water removal, destruction of old tires and cans which serve as mosquito
breeding environments and good management of used water can reduce areas of excessive vector
incidence.

Reducing Contact

Limiting exposure to insects or animals that are known disease vectors can reduce infection risks
significantly. For example, bed nets, window screens on homes, or protective clothing can help
reduce the likelihood contact with vectors. To be effective this requires education and promotion
of methods among the population to raise the awareness of vector threats.

Chemical Control

Insecticides, larvicides, rodenticides, Lethalovitraps and repellents can be used to control

vectors. For example, larvicides can be used in mosquito breeding zones; insecticides can be
applied to house walls or bed nets, and use of personal repellents can reduce incidence of insect
bites and thus infection. The use of pesticides for vector control is promoted by the World Health
Organization (WHO) and has proven to be highly effective.

Biological Control

The use of natural vector predators, such as bacterial toxins or botanical compounds, can help
control vector populations. Using fish that eat mosquito larvae or reducing breeding rates by
introducing sterilized male tsetse flies have been shown to control vector populations and reduce
infection risks.

Importance of vector control

However, even for vector-borne diseases with effective treatments the high cost of treatment
remains a huge barrier to large amounts of developing world populations. Despite being
treatable, malaria has by far the greatest impact on human health from vectors. In Africa, a child
dies every minute of malaria; this is a reduction of more than 50% since 2000 due to vector
control. In countries where malaria is well established the World Health Organization estimates
countries lose 1.3% annual economic income due to the disease. Both prevention through vector
control and treatment are needed to protect populations.

As the impacts of disease and virus are devastating, the need to control the vectors in which they
carried is prioritized. Vector control in many third world areas can have tremendous impacts as it

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increases mortality rates, especially among infants.Because of the high movement of the
population, disease spread is also a greater issue in these areas.

As many vector control methods are effective against multiple diseases, they can be integrated
together to combat multiple diseases at once.The World Health Organization therefore
recommends "Integrated Vector Management" as the process for developing and implementing
strategies for vector control.

Vector Control Program

The San Diego County Vector Control Program (VCP) is a countywide program that monitors
vectors and the diseases that they carry. A "vector" is an animal or insect capable of transmitting
the causative agent of human disease. "Vector" also includes eye gnats. Some examples of
vectors in San Diego County are mosquitoes, ticks, and rodents. The VCP has been reducing and
controlling mosquitoes since the 1930‘s.

The VCP:

1. Protects public health by surveying for diseases carried by vectors.

2. Reduces peoples‘ exposure to vectors and human diseases.

3. Responds to public requests for vector inspections.

4. Educates the public about mosquitoes and other vectors to help residents protect themselves
from the diseases vectors can carry.

Activity 12.1
1. Discuss immunization and its role in disease
prevention and control
________________________________________________________
2. Discuss Proper hygiene( Personal and Environmental)
and its role in disease control and prevention-

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 ________________________________________

12.11 HEALTH PROMOTION

Health promotion refers to "The process of enabling people to increase control over their health
and its determinants, and thereby improve their health."

This conception reflects the World Health Organization conception of health as "the extent to
which an individual or group is able to realize aspirations and to satisfy needs, and to change or
cope with the environment. This is a dynamic model, in which health is seen not only as a state,
but as a resource for everyday life. It is a positive concept emphasizing social and personal
resources as well as physical capacities". (World Health Organization. Health promotion: a
discussion document on the concept and principles.

Health promotion is a general concept, while illness prevention refers specifically to an illness
or disease: "measures not only to prevent the occurrence of illness, such as risk factor reduction,
but also to arrest its progress and reduce its consequences once established."

Activity 12.2
Using PRECEDE-PROCEED Model describe how you will implement
effective Health Promotion programme
________________________________________________________
________________________________________________________
_________________________________________________________

By comparison, health protection refers to "ensuring safe food and water supplies, providing
advice to national food and drug safety regulators, protecting people from environmental threats,
and having a regulatory framework for controlling infectious diseases in place. Ensuring proper
food handling in restaurants and establishing smoke-free bylaws are examples of health
protection measures."

From these definitions you will see that health promotion differs from prevention or risk
reduction interventions by being broader and non-specific:

 Health promotion does not target a single risk factor or disease, but tries to enhance each person‘s
ability to improve their own health.

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  A central goal is to create environments that support healthiness, from which came the metaphor
of ‗upstream‘ and ‗downstream‘ interventions:.
o A passer-by sees a body floating down a river, and calls 911. Firemen arrive and haul the
body out, and paramedics start resuscitation and rush the victim to the ER where the
hospital PR director proudly announces that the highest quality care is being delivered to
deal with the situation. By contrast, health promotion would focus upstream to figure out
what is causing people to fall into the water, and correct it. Health promotion aims to
prevent disease by modifying the social determinants of health or ‗upstream‘ factors.
 Beyond preventing disease, health promotion also seeks to create a context in which health can
evolve spontaneously. Health promotion often seeks to support neighbourhood groups in taking
charge of local issues that affect health: food choices in the school cafeteria; setting up exercise
groups; arranging for volunteers to assist elderly people, etc.
 A well-known discussion of health promotion approaches is given in the Ottawa Charter.

The Ottawa Charter for Health Promotion.

Ottawa was the venue for an international conference on health promotion in 1987. The
resulting Ottawa Charter proposed action "to achieve health for all" by the year 2000. It included
the following strategies:

 Building healthy public policy. This puts health on the agenda for all policymakers,
directing them to be aware of the health consequences of their decisions
 Creating supportive environments. (e.g. encouraging a family to support their relative
who is trying to lose weight) This recognized the importance of environment for health,
and proposed a socio-ecological approach to health
 Strengthening community action. Health promotion requires community empowerment
and involvement in setting priorities, planning and implementing strategies to achieve
better health
 Developing personal skills. Health promotion supports personal and social development
through providing information and enhancing life skills
 Reorienting health services. Health promotion argues for shifting health resources
towards a more equal distribution between health care and preventing disease.
Essentially, health services should be expanded to include the four strategies above in
addition to conventional medical care. Responsibility for health promotion services
should be shared among individuals, community groups, health professionals, health
services and governments.

Values in Health Promotion

Health promotion is implicitly based on several values:

• equity and social justice

• a holistic definition of health

• covers the full range of health determinants

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 • recognizes the influence of environment on health

• empowers people and builds individual and collective capacity

• seeks to enhance people's social participation

• involves intersectorial collaboration.

3. Additional Information

Some other definitions of health promotion:

"Health promotion includes strengthening the skills of individuals to

encourage healthy behaviours and it also includes building the healthy
social and physical environments to support these behaviours." "Health
promotion is any combination of health education and related
organizational, economic and political interventions designed to facilitate
behavioral and environmental changes conducive to health

Green also described health promotion as ―the combination of educational and

environmental supports for actions and conditions of living conducive to
health‖

"Health promotion is the process of helping people to take control over their
lives so that they can choose options that are health giving rather than
those that are health risky." (Vetter N, Matthews I. Epidemiology and
public health medicine. Churchill Livingstone, 1999: 216)

Population Health Promotion

Population health and health promotion were seen as being in competition, so in 1996 Health
Canada released a report that tried to reconcile the two. While the Ottawa Charter offered ideas
on "how" to intervene, Health proposed a population health promotion (PHP) model which
applies these intervention approaches to different targets ("who"): Individuals, Families,
Communities, Sectors (such as the educational system), and Society as a whole. This extends
health promotion beyond the individual level and emphasizes multiple levels of involvement.
Next, PHP proposes "what" the interventions should address: the nine determinants of health
previously identified by Health Canada.

There are many ways to apply this model, but as an example, if the goal is to prevent the spread
of AIDS, community interventions could include needle exchange programs; educational
institutions can include healthy sexuality in educational curricula; the health system can make
opportunities for HIV testing more accessible; social marketing campaigns can raise awareness
of safe sex practices.

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The PHP model offers a systematic and comprehensive way to think about strategies to influence
health, many of which lie outside the health sector.

Developing a Population Health Promotion Model

In building a model that can help guide our actions to improve health, three questions are critical.
"On WHAT should we take action?" "HOW should we take action?", and "WITH WHOM
should we act?" The documents discussed above help answer these questions. Strategies for
Population Health points out that action must be taken on the full range of health determinants
(the WHAT). The Ottawa Charter on Health Promotion calls for a comprehensive set of action
strategies to bring about the necessary change (the HOW). Both documents affirm that, in order
for change to be accomplished, action must be taken at various levels within society (the WHO).
Taking these questions and the answers as a starting point, we can begin to construct an action
model.

Figure 12. 1

The Population Health Promotion Action Model figure is a cube which addresses three critical
questions, which are identified on the three visible faces of the cube. The action model can help
guide our actions to improve our health.

The question of "what" should be done to improve population health is addressed on the front
face of the cube. The response to the question of "what" should be done to improve population
health, is to take action on the full range of health determinants

The question of "how" should we take action is on the side face of the cube. The Population
Health Promotion cube directs that action should be taken using on comprehensive action
strategies, as laid out in the Ottawa Charter for Health Promotion.

The third question of "who" (with whom should we act) appears on the top face of the cube. This
face provides guidance on the various levels to which interventions can be directed from
individual, through to societal levels.

For the purposes of this image, it should be noted that although a square does have more than
three sides, the image only uses three sides to address their questions of "what", "how" and
"who".

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To develop the details of the three dimensions in the model, we can turn to Strategies for
Population Health for a summary of the evidence on the range of health determinants and The
Ottawa Charter for a description of comprehensive action strategies. We can also turn to
communication theory for an explanation of the various levels within society at which action can
be taken: the individual; family and friends; community (people linked by a common interest or
geographic setting such as a neighbourhood, school or workplace); sector/system (education,
income support, housing, etc.); and society as a whole. For example, to promote the health of
school-aged children we can help young people develop a positive self-image; involve families
in the education of their children; ensure that schools, as communities, are healthy places to be;
develop polices within the educational system that support the realization of one's full potential;
and promote the value of learning and education throughout the society as a whole.

Using the findings of these documents, which have been accepted nationally and internationally,
the model has been completed as shown below. We are calling the model a Population Health
Promotion (PHP) model because it explains the relationship between population health and
health promotion. It shows how a population health approach can be implemented through action
on the full range of health determinants by means of health promotion strategies.

Figure12. 2

This model also illustrates the need for evidence-based decision-making to underpin the
development of population health promotion activities. Evidenced-based decisions are required
to ensure that policies and programs focus on the right issues, take effective action and produce
sound results. When assembling the evidence required, three sources should be consulted:

 Research studies that have systematically studied health issues, the underlying factors, the
interventions and their impact, both intended and unintended.

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  Experiential knowledge that has been gained through practice and synthesized in ways that can
guide practice and policy-making.
 Evaluation studies (formative and summative) of policies, programs and projects.

These sources provide evidence based on an examination of past activities. In addition, trends
can be analyzed to identify emerging issues and visioning can be done to create preferred
scenarios for the future. Evidence-based decision-making is thus, an art and a science where
collective wisdom and vision, along with empirically derived knowledge, play worthwhile roles.

The decision-making process must be made explicit. It must draw upon a broad base of evidence,
involve all the key stakeholders, clarify who exercises the final decision-making authority and be
supported by effective technological support systems. Information technologies are increasingly
available to assist with decision-making processes. Technologies can help gather and synthesize
information, conduct stakeholder consultations and perform meta-analysis across studies to help
us reach key conclusions. Such decision support systems, in conjunction with explicit
assumptions underpinning the decision-making process will help us reach the best possible
decisions as to what to act on, how to act and with whom.

Values and Assumptions Underlying the Population Health Promotion Model

The PHP model is based on the following assumptions:

 Policy and program decision makers agree that comprehensive action needs to be taken
on all the determinants of health using the knowledge gained from research and practice.
 It is the role of health organizations to analyze the full range of possibilities for action, to
act on those determinants that are within their jurisdiction and to influence other sectors
to ensure their policies and programs have a positive impact on health. This can best be
achieved by facilitating collaboration among stakeholders regarding the most appropriate
activities to be undertaken by each.
 Multiple points of entry to planning and implementation are essential as demonstrated by
the examples in the following section. However, there is a need for overall co-ordination
of activity.
 Health problems may affect certain groups more than others. However, the solution to
these problems involves changing social values and structures. It is the responsibility of
the society as a whole to take care of all its members.
 The health of individuals and groups is a combined result of their own health practices
and the impact of the physical and social environments in which they live, work, pray and
play. There is an interaction among people and their surroundings. Settings, consisting of
places and things, have a physical and psychological impact on people's health.
 In order to enjoy optimal health, people need opportunities to meet their physical, mental,
social and spiritual needs. This is possible in an environment that is based on the
principles of social justice and equity and where relationships are built on mutual respect
and caring, rather than power and status.
 Health care, health protection and disease prevention initiatives complement health
promotion. Comprehensive approaches will include a strategic mix of the different
possibilities for action. Meaningful participation of people in the development and

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 operationalization of policies and programs is essential for them to influence the
decisions that affect their health.

How To Work with the Population Health Promotion Model: Some Possibilities

To operationalize the model, it is helpful to visualize it as consisting of many interior cubes each
providing a potential blueprint for action. While the model may appear static, it becomes
dynamic when used as a planning tool. Organizations may use the model from different entry
points. For example, one can begin with the health determinant that one intends to influence, the
action strategy to be used, or the level at which action is to be taken. Alternatively, the model can
be used to plan a comprehensive range of actions on emerging health issues or issues related to
the health of a particular priority group.

Example 1: If You Would Like to Focus on the Determinants of Health

Collectively, stakeholders should address the full range of health determinants in adopting a
population health approach. Particular organizations, however, may wish to focus on specific
determinants. This example shows how the model can be used to identify possibilities for
influencing the various determinants:

Addressing the Health Concerns of At Risk Groups

In addressing the question of risk, it is important to consider both risk factors and risk conditions.
Risk factors are elements often behaviour patterns which tend to predispose people to poorer
health. Risk Conditions are general circumstances, over which people have little or no control,
that are known to affect health status. An example of risk conditions would be a deprived
neighbourhood where the housing is substandard, there are few recreational facilities,
community spirit is weak and there are feelings of danger and insecurity. Risk conditions are
usually a result of public policy and are modified through collective action and social reform.

The Population Health Promotion Model can contribute to the discussion of risk in three ways:

 It moves the discussion away from victim blaming and calls for action on the full range
of factors and conditions that determine health.
 It provides an analytical tool to help develop a clearer picture of those likely to be most at
risk. Who are they? People who, by virtue of their economic and social situation, are
isolated and without access to resources and opportunities to participate in their
communities. People with few life skills and, who consequently, feel little sense of
control over their lives and their environments. People who, for a variety of reasons,
engage in negative lifestyles and people who do not have access to appropriate primary
care and preventive health services.
 It provides a planning tool and may be used to address the health concerns of identified
groups at risk, as illustrated in the next example.

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 You have come to the end of lecture one. In this lecture you have
learnt the following; Disease control strategies including, proper nutrition, Public
health promotion, vector control methods and programmes.

Now take a break and reflect on some of the issues we

have discussed today. After your break, answer the following questions:
ii. Highlight role types of immunization in
epidemiology_______________
iii. Describe how nutrition help in contro of diseases
______________________________________
iv. Describe how you can work with population Health promotion
model_______

1. Modern Epidemiology, 2nd Ed Rothman, K. J. and Greenland, S Lippincott,

Philadelphia 0-7216-6181-5-5 1985
2. Essentials of Epidemiology in Public Health by Ann Aschengrau and George R.
Seage III, Jones and Bartlett Publishers, Boston and London

3. World Health Organization. (2012). Epidemiology.Retrieved May 18, 2016.

4. The WHO Family of International Classifications. (2012). Retrieved May 18,
2012, from World Health Organization.
5. World Health Organization. (2012). World Health Statistics 2012.Retrieved May
18, 2012.

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