Veterinary Epidemiology II

1
Objectives – Concepts
1. Understand the concept of probability and odds

2. Describe epidemiological study designs

3. Define, calculate and interpret “risk estimates and their uses RR,
RRR, ARR, OR, PAR, PARF

2
Fundamental Assumption in Epidemiology
 Disease doesn’t occur in a vacuum

 Disease is not randomly distributed throughout a population

 Epidemiology uses systematic approach to study the

differences in disease distribution in subgroups

 Allows for study of causal and preventive factors

3
Components of Epidemiology
 Measure disease frequency

 Assess distribution of disease

 Who is getting disease?

 Where is disease occurring?

 When is disease occurring?

 Quantify disease

 Formulation of hypotheses concerning causal and preventive factors

 Identify determinants of disease

 Hypotheses are tested using epidemiologic/statistical tools

4
Distinction between descriptive epidemiology and analytic
epidemiology

Descriptive epidemiology:

 seeks to measure the frequency in which diseases occur or collect

descriptive data on possible causal factors.

Analytic epidemiology:

 attempts to specify in more detail the causes of a particular

disease”

5
 Types of Studies
A. Experimental – study factor is manipulated by the investigator

1. Pure versus Quasi-experimental

2. Laboratory versus real world

B. Observational - no manipulation of study factor by the investigator

1. Descriptive versus Analytic

2. Retrospective versus Prospective

 Descriptive epidemiology:

 Analytic epidemiology:

6
 Epidemiologic study designs
Factors Important in Study Design

A. Specific testable hypotheses - Non specific search for information

B. Biases

1. Internal validity

 the validity of findings with the research study;

 the technical soundness of a study,

 particularly concerned with the control of extraneous influences that might

effect the outcome

 Or Indicates whether the independent variable was the sole cause of the
change in the dependent variable

7
 2. External validity

 The degree to which the findings can be inferred to the

population of interest or to other populations;

 The generalizability of the results

 Indicates the extent to which the results of the experiment are

applicable to the real world

8
Basic Question in Analytic Epidemiology-
 Are exposure and disease linked?

Exposure Disease
 Basic Questions in Analytic Epidemiology
 Look to link exposure and disease
 What is the exposure?
 Who are the exposed?
 What are the potential health effects?
 What approach will you take to study the relationship between
exposure and effect?

•Study designs direct/protocol how the investigation is conducted

9
What designs exist to identify and investigate factors in disease?

Descriptive Analytic

Case report Cohort study

RCT

Case series Case-Control

study
Descriptive
Epidemiology Cross-sectional
study

10
Timeframe of Studies
 Prospective Study - looks forward, looks to the future,
examines future events, follows a condition, concern or
disease into the future

time

Study begins here

11
 Timeframe of Studies
 Retrospective Study - “to look back”, looks back in time to
study events that have already occurred

time

Study begins here

12
Descriptive Studies
1. Case Reports
 Detailed presentation of a single case or handful of cases

 Generally report a new or unique finding

 e.g. previous undescribed disease

 e.g. unexpected link between diseases

 e.g. unexpected new therapeutic effect

 e.g. adverse events

13
2. Case Series
 Experience of a group of patients with a similar diagnosis

 Assesses prevalent disease

 Cases may be identified from a single or multiple sources

 Generally report on new/unique condition

 May be only realistic design for rare disorders

 Advantages

 Useful for hypothesis generation

 Informative for very rare disease with few established risk factors

 Characterizes averages for disorder

 Disadvantages

 Cannot study cause and effect relationships

 Cannot assess disease frequency 14

 3. SURVEY
 Surveys are conducted to estimate, with some specified precision, the
frequency and distribution of selected outcomes in defined populations.

 Provide data about the frequency of occurrence of a disease of interest in a

specific population.

 The two main design issues which need to be considered in designing a survey
are the sampling protocol to be used and the design of the data-collection
instrument

 If a survey collects information about both an outcome of interest and

potential exposures of interest, it then becomes a cross-sectional analytic
study, not a descriptive study because it can be used to evaluate associations
between exposures and outcomes.

15
Analytic Epidemiology
 1. Observational Studies
 Cross-sectional
 Cohort
 Case-control

 Non-experimental

Observational because there is no individual intervention

Treatment and exposures occur in a “non-controlled” environment

Individuals can be observed prospectively, retrospectively, or

currently
16
 Ecological studies
 In an ecological study the unit of analysis is a group of individuals (such as
counties, states, cities, or census tracts).

 Summary measures of exposure and summary measures of outcome are

compared and inference is made at the individual level.

 Ecological studies are relatively quick and inexpensive to perform and can
provide clues to possible associations between exposures and outcomes of
interest.

 A major disadvantage of ecological studies is that of ecological fallacy:

 The assumption that an observed relationship in aggregated data will hold at

the individual level.

17
1. Cross-sectional studies
 An “observational” design that surveys exposures and disease status
at a single point in time (a cross-section of the population)

time
Study only exists at this point in time
18
Cross-sectional Design

factor present
No Disease
factor absent
Study
population
factor present
Disease
factor absent

time
Study only exists at this point in time
19
 Cross-sectional Studies
 Often used to study conditions that are relatively frequent with long duration of
expression (nonfatal, chronic conditions)

 It measures prevalence, not incidence of disease

 Not suitable for studying rare or highly fatal diseases or a disease with short duration
of expression

 Disadvantages

 Weakest observational design,

 The temporal sequence of exposure and effect may be difficult or impossible

to determine

 Usually don’t know when disease occurred

 Rare and quickly emerging disease a problem.

20
2. Case-Control Studies

 an “observational” design comparing exposures in disease cases

vs healthy controls from same population

 Exposure data collected retrospectively

 Most feasible design where disease outcomes are rare

21
factor present
Cases
factor absent (disease)
Study
population
factor present Controls
(no disease)
factor absent
present
past

time

Study begins here 22

 Case-Control Study
 Strengths

 Less expensive and less time consuming

 Efficient for studying rare diseases

 Limitations

 Inappropriate when disease outcome for a specific exposure is

not known at start of study

 Exposure measurements taken after disease occurrence

 Disease status can influence selection of subjects

23
Selection of a case

 Selection of a case include the

 definition of the disease

 the source of the cases, and

 whether to include only incident or both incident and prevalent cases

Both exclusion and inclusion criteria can be used for this purpose, and should
apply to both cases and potential controls

There are three approaches that might be used to ensure that cases and controls are
similar:

Exclusion or restricted sampling

Matching

Analytic control

24
Restricted sampling: If breed is a likely confounder you might only
select one breed in the study (the dominant breed in the source
population).

Matching: Each case is matched with a control that has identical (or at
least similar) values of the confounding variable (e.g. age and sex).

 This method provides direct control over known confounders and

under certain conditions the efficiency of the analysis is improved.

25
 Disadvantages:

 1. recruitment of suitable controls can be difficult (when it is difficult

to find a suitable match);

 2. you cannot quantify the effect of the matching variable on the risk
of disease

 3. analysis of the data must take into account the effect of matching;

 4. it is possible to overmatch, which decreases the efficiency of the

study and sometimes introduces bias.

Analytical control: Multivariable regression techniques may be applied

to remove the effect of known confounders.

26
 Selection of the controls
 One of the most difficult aspects of a case-control design

 It should be considered that controls are subjects that would have been cases if
the outcome had occurred

The major principles are:

 Controls should come from the same study base (population) as the cases

 Controls should be representative of the source population with respect to

exposure.

 In open populations controls should mirror the exposure time of the non-case
subgroup in the population.

 The time during which a non-case is eligible for selection as a control is the time
period in which it is also eligible to become a case if the disease should occur.

27
 In most cases the case-control studies in veterinary medicine has
been a risk-based (cumulative incidence) design

 In this approach, the controls are selected from among those animals
that did not become cases up to the end of the risk period

 An individual can be selected as a control only once

 This design is appropriate if the population is closed and the risk

period for the outcome in an individual has ended before subject
selection begins

28
Example of case-control study

29
3. Cohort Studies
 an “observational” design comparing individuals with a

known risk factor or exposure with others without the

risk factor or exposure

 looking for a difference in the risk (incidence) of a

disease over time

 best observational design

 data usually collected prospectively (some

retrospective) 30
 disease
Factor
Study present no disease
population
free of
disease Factor disease
absent
no disease
present
future

time
Study begins here 31
 Cohort Study
 Strengths

 Exposure status determined before disease detection

 Subjects selected before disease detection

 Can study several outcomes for each exposure

 Limitations

 Expensive and time-consuming

 Inefficient for rare diseases or diseases with long latency

 Loss to follow-up

32
Experimental Studies
 Treatment and exposures occur in a “controlled” environment

 planned research designs

 Clinical trials are the most well known experimental design.

 Randomized Controlled Trials (RCTs)

 a design with subjects randomly assigned to “treatment” and

“comparison” groups

 provides most convincing evidence of relationship between exposure

and effect

 the “gold standard” of research designs

 Community trials use non-random data

33
The Possible Clinical Trial Designs
• Blinded: Participants do not know if in experimental or control
group.

• Double Blinded: Participants and staff do not know group

assignment.

• Placebo: Inactive pill w/no therapeutic value

• Crossover Trial: In this design each experimental unit receives all
treatments
• Withdrawal trial: Withdrawal- refers to the withdrawal of treatment
during one or more phases of a study to demonstrate the effects that
it has on the target behavior
34
RANDOMIZATION outcome
Intervention
no outcome
Study
population
outcome
Control
no outcome
baseline
future

time
Study begins here (baseline point) 35
Randomized Controlled Trials

 Disadvantages

 Very expensive

 Not appropriate to answer certain types of questions

 it may be unethical, for example, to assign animals to

certain treatment or comparison groups

36
Study Design Sequence
Hypothesis formation

Descriptive
Case reports Case series
epidemiology

Analytic Animal Lab

epidemiology study study
Clinical
trials Hypothesis testing

Cohort Case- Cross-

control sectional
37
 Measures of association
Association : A statistical relationship between two or more
variables

 Risk is the probability that an event will happen with its consequence.

 So, a characteristic or factor that influences whether or not an

event occurs, is called a risk factor (hazard).

 We study the associations between putative risk factors (exposures)

and an outcome (a disease) which are investigated using analytical
observational studies.
38
 Association between exposure & Disease
 Question:
Is there an excess risk associated with a given exposure?

Three main categories of analysis: • Measures of strength

– Risk ratio
• (1) measures of strength – Incidence rate ratio
• (2) measures of effect – Odds ratio

• (3) measures of total effect

39
Measures of association
 Both exposure and outcome are binary variables (yes or no), the
results can be presented in a 2 × 2 table.

Diseased Non- Total

diseased
Exposed a b a+b
Non- c d c+d
exposed
Total a+c b+d a+b+c+d

40
 Measure of association
1. Cross-sectional study
 Individuals are tested for the presence of disease and risk factor at
same time.
And the prevalence is the measure of disease.

41
Example
 If a cross-section study is performed on a random sample of 300
animals the frequencies would look like the following

Diseased Non-diseased Total

Exposed 60 40 100
Non-exposed 40 160 200
Total 100 200 300

=3

So, the prevalence is 3 times more likely in exposed group

42
 Case-control study
• Diseased (a+c) and non diseased (b+d) are intentionally chosen.

• To check whether exposure is more common in the disease group,

odds ratio is the measure of association
OR is the odds of disease, given exposure.
Case Control
Exposed a b
Non-exposed c d
Total a+c b+d

43
 Cont…
 Odds of disease in the exposed population:

 Odds of disease in the non-exposed population:

Odd ratios (OR)

Odds ratio is then, the ratio of two odds and given as:

Case Control
Exposed 90 30
Non-exposed 60 120 Exposure is 6 times more common in
cases than in control
Total 150 150
44
 Cohort study
 Two groups followed over time:
 One exposed
 The other non exposed
 Follows in chronological order (the effect of exposure on disease
occurrence)

• Incidence risk in the exposed population is give as :

 Incidence risk in the non-exposed population:

• Incidence risk in the total population:

45
 Cont.

From this; the disease odds ratio can also be calculated

diseased No disease Total

Exposed 90 60 150
Non- 30 120 150
exposed
300
46
Another example
 In vaccine trials (in foxes), vaccine efficacy is defined as the
proportion of disease prevented by the vaccine in vaccinated
individuals which is the attributable fraction.
 The following results were obtained:
Rabies + Rabies - Total
Vaccination - 18 30 48
Vaccination + 12 46 58
Total 30 76 106

The odds of rabies in the unvaccinated group was 2.3 times the odds of
rabies in the vaccinated group (OR = 2.3).

47
If RR = 1 : risk of disease in the exposed and non-exposed groups are
equal.

If RR < 1 : exposure reduces the risk of disease and exposure is said to

protective

If RR > 1 : exposure increases the risk of disease

RR range between 0 and infinity.

It cannot be estimated in case-control study

48
Incidence rate ratio (IRR)

Exposed Non exposed

No of cases 50 25 75
Time at risk 500 400 900
49
 Measures of effect in the exposed population
• The measure of effect indicates to what extent the event is
prevented if the risk factor is avoided.
• The measures are:
– Attributable risk (rate)
– Attributable fraction

Attributable risk (AR) (Risk difference)

• AR is defined as the increase or decrease in the risk (or rate) of
disease in the exposed group that is attributable to exposure.

diseased No disease Total

This means that the risk in the

Exposed 15 45 60 Exposed group associated
Non-exposed 8 72 80 exclusively with exposure is500.15
Attributable fraction (AF)
 Attributable fraction (the attributable proportion in
exposed subjects) is the proportion of disease in the
exposed group that is due to exposure.
𝐴𝑅
AF=
𝐶𝑜𝑚𝑚𝑢𝑙𝑎𝑡𝑖𝑣𝑒 𝐼𝑛𝑐𝑖𝑑𝑒𝑛𝑐𝑒 𝑖𝑛 𝑡ℎ𝑒 𝑒𝑥𝑝𝑜𝑠𝑒𝑑

Or

This figure is the proportion of

exposed cases that could have been
Prevented if the exposure had not been
present

51
To make AF more clear

(CIR-1)/CIR~(2.5-1)/2.5=0.6

52
 Vaccine example
• In vaccine trials (in foxes), vaccine efficacy is defined as the proportion of disease
prevented by the vaccine in vaccinated individuals which is the attributable fraction.
The following results were obtained:

Rabies + Rabies - Total

Vaccination - 18 30 48
Vaccination + 12 46 58
Total 30 76 106
The odds of rabies in the unvaccinated group was 2.3 times the odds of rabies in
the vaccinated group (OR = 2.3). Fifty six percent of rabies cases in unvaccinated
foxes was due to not being vaccinated (AF = 0.56).
An approximation with OR.

53
 Measures of effect in the total population
• Population attributable risk or rate (PAR) is the increase or decrease
in risk (or rate) of disease in the population that is attributable to
exposed.
• The incidence in the population minus incidence in the unexposed
group.
• To calculate this factor, the population incidence should be known

diseased No disease Total

Exposed 15 45 60
This means the incidence of disease
Non-exposed 8 72 80 in the population associated with
23 117 140 the factor is 0.064
54
 Measures of effect in the total population
• Population attributable fraction (PAF) is the proportion
of disease in the population that is due to the exposure.

diseased No disease Total

Exposed 15 45 60
Non-exposed 8 72 80
39% percent of cases in the
23 117 140 population was due to exposure
(PAF = 0.39).
It will be also easily calculate as number of excess cases divided to the total number
of cases; 9/23=0.39 or (the AF times proportion of cases that is exposed 0.6*15/23
=0.39) 55
Epidemiologic measures of association for independent proportions in 2 × 2
tables.
Parameter Case-control Cohort Cross-sectional
Measures of strength:
RR No yes yes (prevalence RR)
IRR no yes no
OR yes yes yes (prevalence OR)
Measures of effect:
AR No yes yes
AF No yes yes

Measures of effect in population (total effect):

yesα yes
PAR no
yesα yes
PAF no

α If an estimate of the prevalence of exposure or disease incidence for the population is

available from another source.
56
57