Clinical epidemiology
Clinical Epidemiology
Prof. Hong SU
Department of Epidemiology and Statistics
suhong5151@sina.com
Hippocratic oath
 Classical Version
 an oath historically taken by physicians, one of the most
widely known of Greek medical texts
 Modern Version
 I will respect the hard-won scientific gains of those
physicians in whose steps I walk, and gladly share such
knowledge as is mine with those who are to follow.
 I will apply, for the benefit of the sick, all measures are
required, avoiding those twin traps of overtreatment and
therapeutic nihilism.
What is clinical epidemiology program?
 It is designed to develop both clinical researchers
and practitioners by teaching the skills needed to
generate high-quality clinical research, as well as
the skills to locate, appraise, interpret and apply the
best clinical research evidence to patient care.
 Clinicians and researchers will learn the principles
of clinical epidemiology – the science of finding and
applying best evidence in clinical practice.
Clinical epidemiology is known as basic
science of clinical medicine.
Clinical epidemiology is just the methodology
to guide the clinical practice with scientific
evidence.
Why is clinical epidemiology important?
 Patients and clinicians need health care
solutions that are founded on the highest-
quality research evidence.
 Clinicians require the skills to undertake and
disseminate high-quality clinical research.
 Health practitioners need the skills to locate,
evaluate and apply best research evidence to
patient care.
Schedule
 Lecture 1—Introduction to clinical epidemiology
 Lecture 2—Common Design schemes for clinical
research
 Lecture 3—Design scheme for clinical research
(1)-descriptive study
 Lecture 4—Design scheme for clinical research
(2)-analytic study
 Lecture 5—Design scheme for clinical research
(3)- experimental study
 Lecture 6—Diagnostic and screening test
 Lecture 7—Disease cause and causal inference
 Lecture 8—Review
1

Introduction to Clinical
Epidemiology
Questions？
Clinical epidemiology is just the
methodology to guide the clinical practice
with scientific evidence.
• What is scientific thoughts and methods？
Story of Pontiac tell us：
Observation guided by scientific
thinking are still the best safeguard
against baloney and superstition.
Outline of presentation
 Definition of clinical epidemiology
 Application of clinical epidemiology
Story of Pontiac
 Phenomenon (The appearance by own eyes )
 Pontiac car is allergic to vanilla ice cream.
Information collection and analysis
The used time is shorter while buying vanilla ice cream
compared with other ice cream.
 Truth
 Cooling of atomization device in car need enough time
to launch again.
The appearance by own eyes might hide the truth !
What is the scientific thinking
 On the problems of human health and disease: many
times we met the similar story.
 Now clinical disease is not caused by a single factor,
it need to be investigated systematically to find the
cause or risk factors.
 Clinical epidemiology can provide us with
scientific thoughts and methods.
2
 1. smoking & lung cancer How to select the Controls?
 Control group
Design pattern of case -control study  Healthy controls: general population
 Other patients (Non-lung cancer)
smokers
Lung cancer  Non-respiratory diseases (fracture,etc)
non smokers
 chronic bronchitis (inflammation of windpipe)
smoking information resulting in chronic bronchitis
smokers Non-Lung
effect was partially offset
cancer
non smokers  Notice
Controls cannot be selected based on known or
Smoking rates of the two groups were compared unknown association with exposure

How to select the Controls?

How to select the Controls?
The diagnosis of ECG exercise experiment on
2、The diagnosis of ECG exercise experiment on coronary heart disease (CHD)
coronary heart disease (CHD) Non-
 Control group
CHD CHD Total
gold standard: coronary angiography ECG TEST
 Healthy controls
(+) A B A+B
Expensive, traumatic, cumbersome, many scholars  Other patients (Non-CHD)
ECG TEST
want to use other methods instead. (–) C D C+D  Not from department
of cardiology:
 to evaluate the diagnostic value of ECG Total A+C B+D A+B+C+D
Fracture patients
 case control study--to compare the  to compare the  from cardiology
consistence between ECG and coronary angiography consistence between ECG (Cardiomyopathy)
and angiography

3. hypertension & stroke

Design pattern of case-control study
systolic
diastolic
High blood
pressure Stroke
Clinical Epidemiology
patient
Normal pressure

High blood
pressure
control
How to guide clinical practice
Normal pressure

Proportion of cases with the exposure is significant greater than…

with scientific evidence？
Direction of inquiry: retrospective temporal priority
Conclusion: statistical association

3
 Significance of Improve the efficiency of diagnosis
clinical scientific research
How to diagnose correctly?
 Improve the efficiency of diagnosis  To collect many information----Diagnostic test

 Improve the effectiveness of treatment  The detailed medical history

 Results of physical examination

 ……
 Results of laboratory examination
 Improve the ability of causal inference
 To explain all of the results of Diagnostic tests
correctly

Improve the efficiency of diagnosis Improve the efficiency of diagnosis

The best clinical decision-making for diagnosis  Systemic Lupus Erythematosus (SLE)
 With the least amount of diagnostic tests for  A chronic inflammatory disease that has protean

the best judgment in the disease manifestations and follows a relapsing and remitting course.
 More than 90% of cases of SLE occur in women, frequently
 When faced with a suspicious patient, we can not let
starting at childbearing age.
him/her to experience all of the diagnostic tests at the
 The diagnosis of SLE is based on a combination of clinical
same time. findings and laboratory evidence.
 Every additional test should be selected based on the  Malar rash/Discoid rash

previous result of diagnostic test.  Many antibodies: Antinuclear antibodies, dsDNA, anti-Smith, etc.

Improve the efficiency of diagnosis Improve the efficiency of diagnosis

 How to diagnose correctly? To explain the result
How to diagnose correctly? To explain the result
accurately?
accurately?
 Scientific design, measure and evaluation of diagnostic test
 Malar rash--------------------------------------likely?
 Positive predictive value (PPV): probability that the disease
 Antinuclear antibody Obscure is present when the test is positive. quantitative data
 Result: positive
hypothesis
 Can I be diagnosed as SLE? ---------------very likely?
 Malar rash---------------------------------likely?
 dsDNA anibody  PPV: 20% The probability of having SLE is 20% for her with malar
 Result: positive rash.

 Can I be diagnosed as SLE? ---------------very very likely?  Antinuclear antibody---------------------very likely?

 PPV: 50%
 anti-Smith, etc. Negative?
 dsDNA antibody-----------------very very likely?
4 of the 11 American College of Rheumatology (ACR) criteria  PPV: 80%

4
 Clinical epidemiological methods Improve the effectiveness of treatment
 Scientific design, measure and evaluation of Based on the correct diagnosis, the next question is
diagnostic test
how to treat the patient correctly.
 To analyze of the sensitivity, specificity, likelihood
We should give a proven effective treatment for the
ratio, positive predictive value and receiver-operating
patients.
characteristic curve (ROC) of various diagnostic tests,
Clinical intervention: drugs and surgical intervention,
so as to provide scientific methods for clinical
etc.
practice.

Improve the effectiveness of treatment

Improve the effectiveness of treatment
new drug for a cold ? effective
A new drug for treating a common cold is  Disease pattern
developed recently.  Common cold is a self-limited disease. higher rate of self recovery
 It has a high rate of spontaneous recovery.
 It is used to treat 1000 cold patients from Affiliated
 Physical condition
Hospital of Anhui Medical University.  Age…
The effective rate is 95%  Immunity

 It is also applied to cure 1000 patients from Anhui  Placebo effect

a fake treatment, can sometimes improve a patient's condition simply
Provincial Hospital. because the person has the expectation that it will be helpful.
The effective rate is 96%  ……
 New drug
Is this new drug for a cold effective?

What is clinical epidemiology?

Basic principles of clinical trials
 Clinical epidemiology is just the methodology of

Randomization clinical medicine.

 The science of making predictions about individual

Control
patients by counting clinical events in similar
Blinding method
patients (population of patients ), using strong
scientific methods for studies of groups of patients to
ensure that the predictions are accurate.

5
How to understand the meaning of Clinical Epidemiology
Clinical medicine:
Answer clinical questions and guide
clinical decision making
deals with individuals
Epidemiological
Epidemiology:
Involved in methods used to
answer the questions
application deals with population

clinical
Clinical Epidemiology:
medicine
deals with a defined population to
answer the clinical questions

What is epidemiology？ What is epidemiology？

 The study of the distribution and determinants of health-
related states or events in specified population, and the EPI DEMOS LOGOS
application of this study to control of health problems.
[source: Last (ed.) Dictionary of Epidemiology, 1995] upon people study
 Determinants: physical, biological, social, cultural, and
behavioral factors that influence health. Epidemiology is not a body of knowledge.
 specified population: a group of people with the similar
feature Epidemiology is a philosophy, a strategy, a
 Health-related states or events: health status, diseases, death, methodology, a way of studying a health
other implications of disease such as disability, residual
dysfunction, complication, recurrence, but also causes of problem.
death, behavior, provision and use of health services.

What is clinical epidemiology? What is clinical epidemiology?

 Clinical epidemiology is the application of
epidemiological principles and methods to the practice
of clinical medicine.
 Used as an aid to clinical decision making
 Lead to valid conclusions by avoiding being misled by
bias and chance.
 Purpose: to develop and apply methods of clinical
observation that will lead to valid conclusions by
avoiding being misled by systematic error and chance.
 It is an important approach to obtain many kinds of
information, by which clinicians can make good
decisions in care of patients.

6
How to understand the meaning of Clinical Epidemiology Keywords of Clinical Epidemiology
With the progress of Clinical……
 DME：Design，Measure，Evaluation

 By using principle and methods of clinical

epidemiology, our research aims to improve

knowledge on etiology, diagnosis, prognosis and

treatment or prevention of clinical disease.

Features of clinical epidemiology Central concerns:

 The clinical medicine is the main body, bed-side
epidemiology.  Accuracy of diagnostic tests
 The object is the patient group, not a singer patient.
 The essence is to emphasize the quality control, and  Study of prognosis of disease
strive to ensure the study conclusions to be true and
 Effectiveness of treatment
reliable.
 To make clinical medicine change from experience  Prevention in clinical practice
into evidence-based medicine.

Accuracy of Diagnostic tests

Validity of Diagnostic Test (Accuracy)
- Sensitivity: Is the test detecting true cases of disease?
 Test properties: validity (sensitivity,
(Ideal is 100%: 100% of cases are positive)
specificity), precision, predictive value, etc.
Reflects the ability of recognizing the cases

-Specificity: Is the test excluding those without disease?

(Ideal is 100%: 100% of non-cases are negative)

Reflects the ability of recognizing the non-cases

7
 Accuracy of Diagnostic tests Accuracy of Diagnostic tests
Test properties DISEASE Test properties DISEASE
(+) (Š) Total
(+) (–) Total
TN: True positive (+) A B A+B TN: True positive
(+) A B A+B
FP: False positive FP: False positive
TEST (TP) (FP)
TEST (TP) (FP)
FN: False negative (Š) C D C+D FN: False negative
(–) C D C+D
TN: True negative TN: True negative
(FN) (TN)
(FN) (TN)
Total A+C B+D A+B+C+D
Total A+C B+D A+B+C+D
Sensitivity: Likelihood a diseased person will have a positive test Specificity: Likelihood a healthy person will have a negative test
Sensitivity = TP/All disease = A/(A+C) Specificity = TN/All healthy = D/(B+D)
Of 100 men with prostate cancer, 90 have (+) PSA. Of 100 healthy kids, 3 have a false (+) strep test. Specificity = 97%
Sensitivity=90%

Accuracy of Diagnostic tests Accuracy of Diagnostic tests

Test properties DISEASE Test properties DISEASE
(+) (Š) Total (+) (Š) Total

(+) A B A+B (+) A B A+B

TEST TEST

(Š) C D C+D (Š) C D C+D

Total A+C B+D A+B+C+D Total A+C B+D A+B+C+D

Predictive value of (+): Likelihood that a person with a Predictive value of (–): Likelihood that a person with a
positive test actually has the disease negative test is free of the disease
Cases identified / all positive tests
PV(+)=TP/All positives=A/(A+B) Noncases identified / all negative tests
PV(–)= TN/All negatives = D/(C+D)
Two-thirds of patients with a (+) Exercise Stress Test will have
coronary heart disease PV(+)=66% 99 of 100 patients with a (–) syphilis test are free of syphilis
PV(–)=99%

Study of Prognosis Some end points in the course of disease

 Prognosis：the prediction of the future  Cure

 Death
course of a disease and is expressed as the
 Response (Percent of patients showing some
probability that a particular event will evidence of improvement following an
occur in the future. intervention).
 Remission (Percent of patients entering a phase in
 Knowledge of the likely prognosis is helpful which disease is no longer detectable)
in determining the most useful treatment.  Recurrence (Percent of patients who have return
of disease after a disease free interval)

8
Some end points in the course of disease
 Case Fatality - Percent of patients with a disease
who die of it.
 Five-year survival - Percent of patients
surviving 5 years from some point in the course of
the disease.
 Median survival time - Time at which 50% of
patients still alive.
 Observed survival - Life tables or Kaplan Meier
plots.
Study of Prognosis
 Clinical epidemiology is necessary to provide sound
predictions on prognosis and outcome.
 The assessment of prognosis should include
measurement of all clinically relevant outcomes.
 Prognosis in terms of mortality is measure as case-
fatality rate or probability of survival.
 Life-table analysis:

Survival curves Differences between risk and prognositic factors

100  A distinction should be made between factors

80
associated with an increased risk of
Probability
60
of survival
40
Line 1 developing a disease (risk factor) and those
(%)

20 that predict a worse prognosis once the

0
disease is present (prognostic factors).
Time (years)

Myocardial infarction Effectiveness of treatment

 Risk factors
 Age  Usually the effects of most treatment or
 Male
 Prognostic factors
interventions require research to establish
 Age
 Cigarette smoking
 Male their value.
 Hypertension
 Anterior infarction
 LDL/HDL  The specific interventions must be shown to
 Hypotension
increase risk of
developing a disease  Ventricular arrhythmia do more good than harm among patients who
predict a worse prognosis use them.
once the disease is present

9
 Interventions that Can Be Evaluated
„
New drugs and new treatment of diseases
„
New medical and health care technology
„
New methods of primary prevention
„
New programs for screening
„
New ways of organizing and delivering
health services
„
New community health programs
„
New behavioral intervention programs
Clinical Trials-Phases
 Phase III - Is it any better?
 Large groups of patients for statistical
confirmation of effect and incidence of
side-effects
 Phase IV - Does it work in the community?
 Post marketing studies. Fine tuning and
new rare findings from a very large
population
Effectiveness of treatment
Design pattern of Randomised controlled trial
new treatment
group 1
population inclusion/
exclusion
group 2
control treatment
Effectiveness of treatment
Clinical Trials-Phases
 Phase I - Does it hurt the Patient?
 Usually in normal volunteers, small groups
for safety testing
 Phase II - Does it help the Patient?
 On patients to confirm the effectiveness of
the drug
56
Randomized Clinical Trial
 A trial is an experiment
 A
„ clinical trialis a controlled experiment having a
clinical event as an outcome measure, done in a
clinical setting, and involving persons having a
specific disease or health condition
 „A randomized clinical trial is a clinical trial in
which participants are randomly assigned to
separate groups that compare different treatments
57
Thanks!
Outcome
Outcome
10