L1 USE OF CLINICAL
EPIDEMIOLOGY
Epidemiology
➢ The study of disease distributions
and determinants
Clinical Epidemiology
➢ The science concerned with counting
clinical events occurring in intact
human beings and it uses
epidemiological methods to carry out
and analyse the count
FINAL 17/18, MT 18/19
Uses of Clinical Epidemiology
(Clinical setting)
1. To quantify the frequency and
distribution to the clinical events
2. To promote the critical analysis of
medical literature
3. To study the aetiology of the
disease
(Patient management)
1. To identify the aetiology and the
evolution of the disease,
determine the protective, risk and
prognostic factor
2. To evaluate intervention
measurement to find the best
option for treatment propose
3. To validate and propose the
rational use of laboratory and
therapeutic studies
4. To support and sustain decision
analysis
Use of Epidemiology as a Prevention
1. Health promotion
2. Specific protection
3. Early diagnosis and prompt
treatment
4. Disability limitation
5. Rehabilitation
Epidemiology in medical practice Y1
1. Normality (gauss distribution)
2. Diagnosis (association between
systolic murmur and mitral
regurgitation)
3. Frequency of disease (how
common)
4. Risk
5. Prognosis (survival rate)
6. Appropriate therapy (therapy with
drugs through trials)
7. Causal factors
MT 21/22
Function of epidemiology in finding
the etiology of disease
• Based on distribution, frequency
and probability,
• Epidemiology help us to discover
the factors that determine
susceptibility and
resistance of individual to the
disease
• To determine the predisposing (at
risk) population conditions to
the outbreaks
• Determine the source and
reservoir mechanism (how we
receive and give to
others) and period of
communicability for causative
agent
• Track mode of transmission of
infectious disease
Normal & Abnormality
Methods
➢ Gaussian
➢ Percentile
➢ Risk factor
➢ Diagnostic
➢ Therapeutic
➢ Culturally desirable
Diagnostic data interpretation
Sensitivity
Proportion of truly diseased people
categorised as abnormal by the test.
Specificity
Proportion of truly normal people
categorised as normal by the test.
Positive predictive value
Probability of disease in a patient with
an abnormal test result
Negative predictive value
Probability of a patient not having a
disease when the test result is negative
Source of Errors/Bias
➢ Random Error
Precision problem
MT 18/19
➢ Systematic Error
Validity problem
Selection bias
A distortion in the estimate of effect as
a result from loss of follow-up,
migration, death and misclassification
Information bias
A distortion in the estimate of effect as
a result of inaccurate measurement of
exposure or outcome
Confounding bias
As a result of influence from
extraneous factors causing mixed
effect
History of Medical Achievements
• In 1840’s, by conducting
experiment through nature, John
Snow prove the association of
Cholera with water.
• In 1870’s, Koch and Pasteur
manage to prove germs theory
through epidemiology study.
L2 ABNORMALITY
Normal
➢ Normal in statistics is defined as
fall within the bell shaped curve.
➢ The distribution of the sample of
the people fall within the
Gaussian bell shaped curve or
having Z value in the range of -
1.96<z<1.96 or within 95% CI
Abnormality
➢ Abnormal defined as not normal,
differing in any way from the
usual state, structure, condition or
rule.
Type of Abnormality
Physical Abnormality
Any unusual physical characteristic
that is visible or can be detected
through physical examination or
medical tests.
E.g. deformities, growths or tumours,
unusual facial features, and birth
defects.
Functional Abnormality
Any deviation from normal function or
behaviour.
E.g. difficulty in performing activities of
daily living, concentrating, or memory
problems.
Biochemical Abnormality
A deviation from normal biochemical
parameters in the body.
E.g. high blood glucose levels, high
cholesterol levels, or abnormal liver
function tests.
 Psychological Abnormality
Any deviation from normal
psychological function or behaviour.
E.g. depression, anxiety, or psychosis
Genetic Abnormality
Any deviation from normal genetic
makeup.
E.g. Down Syndrome or sickle cell
anaemia
Immunological Abnormality
Any deviation from normal immune
function.
E.g. autoimmune disorders or
allergies
Normality and abnormality are not
seen as separable attributes
➢ The abnormal people with the
disease represent only a small
proportion compared to the whole
population.
➢ The curve represents abnormal
being swallowed up by the bigger
curve of normal people.
➢ Most of the distribution of the
clinical variables are not easily
divided into abnormal or normal.
This is because they are not
inherently dichotomous and do
not have two different peaks or
sharp breaks that can differentiate
between these two.
➢ Some of the abnormal behaviours
are statistically normal. Eg:
having a distinctively higher IQ
than 160 although is rare but it is
not dysfunctional.
➢ When two distributions are mixed,
the abnormalities are usually not
seen as separate because they
comprise such a small proportion
of the whole.
➢ The curve of people with disease
is “swallowed up” by the larger
curve for healthy, normal people.
Problem list Table
Criteria for Abnormality
Abnormal defined as not normal,
differing in any way from the usual state,
structure, condition or rule.
➢ Clinical needs to set a clear cut
point that will divide these two.
➢ 3 criteria that can be used:
Being unusual
• Normal is the most frequently
occurring.
• Abnormal is the less frequently
occurring.
• The frequency of a
characteristic in a population
expressed statistically to define
what’s normal and abnormal.
• Whenever the standard
deviations beyond 2 than the
mean, it is considered
abnormal.
• The frequency of a
characteristic can also be
represented in the normal
distribution graph (bell shape).
• However misleading may occur
when rely only on standard
deviation of data from mean to
classify the abnormality.
• For example one extreme value
can appear normal in different
setting regardless it being a
disease.
• Eg; obesity data in US that fall L3 SCREENING VALIDITY
within the normal mean
indicating that its not a disease,
while in other country it is.

Being sick
• Anyone having any disease and
is not in the best condition,
therefore that person is
abnormal.
• Can be any form of disease
whether a communicable or
non-communicable disease.
• Eg: disability, obesity and high
BMI increase risk of the CAD or L6 LIFE TABLE
even death.
Survival analysis
Being treatable ➢ A collection of statistical
• The end condition after being procedures for data analysis for
treated is the main interest which the outcome variable of
rather than mid condition interest is time until an event
• If treating the condition can lead occurs.
to a better outcome for that
diseased individual then they
Censored data
are classified as abnormal.
➢ Censoring is when we don’t
• This approach make particularly
good sense on asymptomatic know the exact survival time.
condition.
• Eg: hypertension can result in Life table
variety of disease and treating ➢ A mathematical model that
hypertension would prevent the portrays mortality condition at a
serious complication. particular time among a
population and provides a basis
for measuring longevity.
Uses of Life Table
1. Mortality
2. The probability of dying at each
age
3. Chances of survivorship
4. Average remaining years of life
5. The life expectancy of a
population at varying ages
6. To make predictions on
demographics or different
populations
L8 QUALITY OF LIFE
Definition
An evaluation of both positive and
negative aspects of people’s general
wellbeing and ability to function in daily
task.
Factors influencing QOL
• PSYCHOLOGICAL:
positive/negative feelings, self-
esteem, body image..
• PHYSICAL: general health,
mobility, pain & discomfort,
activities of daily living..
• SOCIAL RELATIONSHIPS:
personal relationship, sexual
activity, social support..
• ENVIRONMENT: physical safety
& security, home environment,
transport..
• SPIRITUALITY: faiths & beliefs,
religions..
• INDEPENDENCE: financial
resources, work satisfaction,
freedom..
L9 GOOD CLINICAL PRACTICE
Definition
An international ethical and scientific
quality standard for the designing,
conducting, recording and reporting of
clinical trials that involve the
participation of human subjects.
Principles of ICH GCP
Conduct trials according to GCP
1. Clinical trials should be conducted in
accordance with the ethical
principles that have their origin in the
Declaration of Helsinki, and that are
consistent with GCP and the
applicable regulatory requirement(s).
Weigh risk vs benefits
2. Before a trial is initiated, foreseeable
risks and inconveniences should be
weighed against the anticipated
benefit for the individual trial subject
and society. A trial should be initiated
and continued only if the anticipated
benefits justify the risks.
Subjects wellbeing exceed the
science
3. The rights, safety, and well-being of
the trial subjects are the most
important considerations and should
prevail over interests of science and
society.
Have adequate info to justify trial
4. The available nonclinical and clinical
information on an investigational
product should be adequate to
support the proposed clinical trial.
Write a sound protocol
5. Clinical trials should be scientifically
sound, and described in a clear,
detailed protocol.
Receive IRB/IEC approval
6. A trial should be conducted in
compliance with the protocol that has
received prior institutional review
board (IRB)/ independent ethics
committee (IEC) approval/favourable
opinion.
Conducted by qualified
7. The medical care given to, and
medical decisions made on behalf of,
subjects should always be the
responsibility of a qualified physician
or, when appropriate, of a qualified
dentist.
Conducted by qualified & trained
support staff
8. Each individual involved in
conducting a trial should be qualified
by education, training, and
experience to perform his or her
respective task(s).
Obtain informed consent
9. Freely given informed consent
should be obtained from every
subject prior to clinical trial
participation.
Record info appropriately
10. All clinical trial information should
be recorded, handled, and stored in
a way that allows its accurate
reporting, interpretation and
verification.
Confidentiality & data protection
11. The confidentiality of records that
could identify subjects should be
protected, respecting the privacy and
confidentiality rules in accordance
with the applicable regulatory
requirement(s).
Handle investigation products
appropriately (GMP)
12. Investigational products should be
manufactured, handled, and stored
in accordance with applicable good
manufacturing practice (GMP). They
should be used in accordance with
the approved protocol.
Quality assurance
13. Systems with procedures that
assure the quality of every aspect of
the trial should be implemented.
IRB Responsibilities
➢ Safeguard the rights, safety, and
well-being of all trial subjects
➢ Review the documents such as
trial protocol and consent forms
➢ Review a proposed clinical trial
within a reasonable period of time
and document its views in writing
including approvement,
modifications, disapprove,
termination.
➢ Consider the qualifications of the
investigator
➢ Conduct continuing review of
each ongoing trial at intervals
appropriate to the risk of to
human subjects, but at least once
a year
➢ Request more information
➢ Non-therapeutic trial protocol
review
➢ Reviews situations where consent
is not possible to ensure that
ethical concerns are addressed
➢ Review amount and method of
payment to subjects to ensure
neither presents problems of
coercion (threat) or undue
influence on the trial subjects
L12 META-ANALYSIS
Forest plot
The following figure is drawn a Forest plot
of 5 studies showing the effect of Statin on
Death and Myocardial Infarction. L12
a) Comment on the weight of the studies
and their significance. (3)
• The square boxes in each study
show their respective weight.
• Ideal and TNT have more weight
than others which is 37% and 31%
respectively.
• This is because they have larger
sample size (ideal test has sample
size of 8888 and TNT has sample
size of 10001).
• Prove- It test and A to Z test has
lesser weight due to its smaller
sample size.
• Out of 4 studies only TNT was
significance (since its risk ratio
 and confidence interval),
indicating that statin reduce the
risk of getting myocardial
infarction by 20% (??) - wafa
• The overall risk ratio is 0.85
indicating significance of all 4
study (statin able to reduce risk of
myocardial infarction by 15%)
b) Explain the potential therapeutic effect of
Statin on death and myocardial infarct
based upon the above findings. (2)
• Statin dose has therapeutic effect
on death and myocardial
infarction.
• The study is significant because
the rhomboid shape, which is the
summary of all combined studies,
does not encompass on the line
of no difference which is 1 and
p=0.000 which is smaller than
0.05.
Note;
at line = no therapeutic effect
P value < than 0.05 = high impact / high
effectiveness
A systematic review and meta-analysis was
conducted to examine the efficacy of
hydroxychloroquine (HCQ) compared to control
groups without use of HCQ in patients with
COVID-19. The outcome of the review is shown
in the figure below.
B. Interpret and conclude the meta-
Source:
https://doi.org/10.1016/j.dsx.2020.08.033
A. State the reasons for performing the
test of heterogeneity and interpret the
result above. (2.5) (why do meta-
analysis)
• Increase power and precision
• Narrower confidence
interval
• Quantify effect size and their
uncertainty
• Reduce problems of
interpretation due to
sampling variation
• Assess homogeneity or
heterogeneity of result
• Settle controversies arising from
conflicting studies
• Generate new hypothesis
• Assess the variability across
studies in order to make sensible
decisions
• See if the result is statistically
significant
• See if the result reject null
hypothesis
analysis findings. (2.5)
• Those who use
hydroxychloroquine (HCQ)
compared to control groups
without use of HCQ in patients
with covid 19 have the same
outcome
• Confidence interval include the
value of 1, the study is
statistically significant
• I2 is a more sensitive tool
• It is less than 50%
• Indicate homogenous
• For studies that are homogenous,
can used either fixed or random
effect model
➢ Square box represent weight due
to larger sample size
➢ Less than 50% = homogenous
➢ Homogenous can use fixed or
random effect model
➢ Heterogenous can only use
➢ Confidence inter include value of
1 = statistically significant
➢ Rhomboid shape (summary) does
not encompass on the life of no
difference which is 1 and p-
value=.0000 which is smaller than
0.05
SLP1 JOURNAL CRITIQUE
A critique is a systematic way of
objectively reviewing a piece of
research to highlight both its strength
and weaknesses and its applicability to
practice
HOW?
Critical reviews for research are
systematic. It is useful to ask yourself
questions about the purpose of each
component of the article.
1. TITLE
➢ Clearly indicate what the research
is about without being too long or
short to be informative
➢ Variables and theoretical issues
stated
2. AUTHOR
➢ Indicate author’s professional and
academic qualifications
3. KEYWORDS
➢ To help identify main areas of
focus
➢ Informative and relevant
4. ABSTRACT
➢ To provide a succinct summary of
the contents of the article
➢ Should be informative to enable
reader to decide whether the
article is of interest to them or not
5. INTRODUCTION
➢ Should orientate the reader to
study by:
o Giving a firm sense of what
was done in the study
o Introducing the
question/problem
o Developing the background
of the study
o Stating the purpose of
research
6. LITERATURE REVIEW
➢ Gives an overview of the
available literature which
surrounds the problem being
researched
➢ Should look at similarities and
differences between the literature
along with the strengths and
limitations
➢ Illustrates how the current study
fits into the existing framework of
research
7. AIM
➢ Must be clearly stated
➢ Focuses on one main idea and
conveys the main purpose of
study.
8. RESEARCH DESIGN
➢ Clearly state what the researcher
did and how it was done, allowing
reader to evaluate the methods
used, consistency, reliability,
validity and whether it is
replicated.
➢ Sample: the number of
participants, their characteristics
and selection process used
➢ Ethics clearance: the process of
obtaining ethics clearance and
how ethical standards were
maintained should be made clear
➢ Use of apparatus: briefly identified
and described, and its function in
the research explained
➢ Procedure: each steps should be
explained
9. DATA ANALYSIS
➢ Detailed summary of the data
collected and the main results
and findings
➢ Tables and figures for clear
representation of data
10. DISCUSSION
➢ Implications of research results
are evaluated and interpreted
➢ Contain a clear statement of
support, otherwise of the original
hypothesis.
➢ Include any suggestions for
improvements of further research
made here

11. CONCLUSION
➢ Should summarise the main
points and indicate the
usefulness of the research
➢ Should not include any new
information
➢ Areas for future research may
be suggested

12. REFERENCES
➢ List of all sources referred are
cited clearly