Philosophy of EBM

Evidence-Based Medicine (EBM)

Definition:

 The conscientious, explicit and judicious use of current best

evidence in making decisions about the care of the individual
patient

 It means integrating individual clinical expertise with the best

available external clinical evidence from systematic research
Why is EBM important ?
 Medical knowledge and accepted practice change rapidly
 Volume of research articles is expanded exponentially
 Integrating the evidence into your practice regularly makes it easier to
find and apply the evidence during busy clinical schedules
 It allows you to blend patient’s preferences with the research,
resulting in patient-centered care
EBM
Steps in the Process

1. identify a patient
2. formulate an appropriate clinical questions
3. conduct a literature search
4. select the key articles
5. critically appraise the articles
6. apply the results of the search to your patient
EBM matrix
What are clinical circumstances?
• Clinical question (PICO)
Can I believe in the results?
• Are the results valid? – methods -> internal validity
• Risk of bias (systematic error)?
• Quality of evidence?
What are the results?
• Size of the effect?
• Precision of estimation? – confidence interval
• Statistical significance? – p-value
Can I apply the results to my patient?
Clinical significance? External validity (directness, generalizability)?
5. Use clinical 1. A question
expertise to integrate arises during care
applicable evidence Apply AS5e5$ of a patient.
with attention to
patient values. I UL 1

4. Evaluate Appraise Ask 2. Completely

the evidence articulate all
for walidity parts of the
and clinical question.
applicability. Acquire

3. Conduct a thorough focused search

and select the highest quality evidence.
67 years old male with severe COPD

 with pronounced resting dyspnoea

 using home oxygen therapy due to chronic respiratory insufficiency
with CO2 retention(pCO2ca. 70-75 mmHg)

 Real-life question: does this patient need chronic non-invasive

ventilation?
clinical questions
 Does a patient with COPD need mechanical ventilation? 
 Does a patient with stable COPD and respiratory failure with hypercapnia need
mechanical ventilation? 
 Does a patient with stable COPD and respiratory failure with hypercapnia need
prolonged-invasive mechanical ventilation?
 In patients with stable COPD and respiratory failure with hypercapnia------is
prolonged on-invasive mechanical ventilation effective------compared with usual
care?
 In patients with stable COPD and respiratory failure with hypercapnia----does
prolonged non-invasive mechanical ventilation----improve survival----compared
with usual care?
Ask
Types of Questions
 Background questions:
o about the condition
o 5W questions (who, what, when, why, where, how)
o general knowledge
o look up the answers in textbooks
 Foreground questions
o about the options
o specific information
o look up the answers in the literature (articles)
Ask
The relationship between foreground and background questions
and clinicians’ experience
Elements of a specific clinical question (PICO)
• Patient, Problem, Population (How would you describe a group of patients
P
similar to you? What are the most important characteristics of the patient?)

• Intervention, Prognostic Factor, Exposure (What main intervention are you

I considering? What do you want to do with this patient? What is the main
alternative being considered?)

• Comparison (Can be None or placebo.) (What is the main alternative to

C compare with the intervention? Are you trying to decide between two drugs, a
drug and no medication or placebo, or two diagnostic tests?)

• Outcome (What are you trying to accomplish, measure, improve or affect?

O
Outcomes may be disease-oriented or patient-oriented.)
Patients’ values and preferences (tradition, law, religion,
ethics, culture, opportunities)
Is the evidence of efficacy enough?
• 40-year-old woman, with metastatic cancer of the stomach. Unable to eat. Would you
expect to introduce a feeding tube?
• The same woman. A few weeks later. The feeding tube in the stomach blocked. The only
way to put a feeding tube is through the abdominal wall directly to the bowel. Would you
expect it / suggest it?
• A few weeks later. All feeding tubes blocked. Patient in constant discomfort. The only way
to feed is intravenously. Would you expect it / suggest it?
• A few weeks later. Unable to swallow. In severe pain. Aspiration. The way to prolong life
is to use breathing machine Would you expect it/suggest it?
• A few weeks later. On respirator. Sedated due to constant severe discomfort. No urine
output. The only way to prolong life is to use dialysis. Would you expect/suggest it?
• A few weeks later. Unable to maintain blood pressure. About to have a cardiac arrest.
Would you expect resuscitation (CPR, electric shocks) if she has a cardiac arrest?
What are the types of clinical studies?

Systematic Randomized
Meta-analysis Cohort study
Review controlled trial

Case control Cross-

Case series
study sectional study
Hierarchy of evidence and study design
Type of questions / Type of study
 Diagnosis: How to select and evaluate diagnostic tests?
Cross-sectional study, prospective blind comparison to a gold standard
 Therapy: Is treatment effective?
A systematic review, randomized controlled trial or cohort study
 Prognosis: What is the patient’s likely clinical course over time?
Cohort study, case-control, case series
 Harm/Etiology: What caused this disease?
Cohort, Case-control, case series
 Case-based studies

, ,
Experimental Observational
Control group | No control group

Analytical Descriptive

i
Randomised | | I |
controlled Case- Cross-sectional Case Case
trials Cohort control survey series _ study

Stronger evidence Weaker evidence

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Case Report/Study
• Detailed report of the diagnosis, treatment, response to treatment,
and follow-up after treatment of an individual patient.
Case Series

 Group of case reports involving patients who were given similar

treatment.
 Case reports and case series usually contain demographic information
about the patient(s), for example, age, gender, ethnic origin.
 No comparator, no control
Case-control study
 Designed to help determine if an exposure is associated with an
outcome (i.e., disease or condition of interest).
 Identify the cases (a group known to have the outcome) and the
controls (a group known to be free of the outcome).
 Controls should be chosen who are similar in many ways to the cases.
The factors (e.g., age, sex, time of hospitalisation) chosen to define
how controls are to be similar to the cases are the ‘matching criteria’.
Cohort study

 Riskfactors, causes of diseases

 Longitudinal
 Mostly prospective, sometimes retrospective
 Expensive
 Strong evidence
 Framingham Heart Study

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Example of a research question:

is hypertension a risk factor for MI?
Cross-sectional study
Cross-sectional study
• Cross-sectional studies involve data collected at a defined time. They
are often used to assess the prevalence of acute or chronic
conditions, but cannot be used to answer questions about the causes
of disease or the results of intervention
• Population, or a representative subset,
• Exposure, health outcome population in a single point of time or a
period of time serial cross sectional (snap chat) quick, easy
Randomized Controlled Trial RCT
Cohort Study
Methods
 Randomized vs quasi-randomized vs non-RCT
 Randomization is performed after obtaining patient consent to enter the study
with the use of a central computer…physician does not know the allocation of
patients (concealed randomization)
 Allocation concealment -A technique used to prevent selection bias by
concealing the allocation sequence from those assigning participants to
intervention groups, until the moment of assignment. Allocation concealment
prevents researchers from (unconsciously or otherwise) influencing which
participants are assigned to a given intervention group
Methods of randomization

 Goal: comparable groups should be similar in respect to prognostic

factors
 Mechanism: each patient entering the experiment has the same
probability to enter experimental or control group as any other
patient entering study
Pseudo randomization
 Quasi randomization … we can predict ( chart, calendar)
Simple randomization
Imbalance of sample size between treatment arms due to simple randomization (coin toss)
in a small trial (n = 10).
Kang M, Ragan BG, Park JH. Issues in outcomes research: an overview of randomization techniques for clinical trials. J Athl Train. 2008;43(2):215-221. doi:10.4085/1062-6050-43.2.215
Block randomization
Block randomization
STEPS
(1) block size of 4 is chosen,
(2)possible balanced combinations with 2 C (control) and 2 T
(treatment) subjects are calculated as 6 (TTCC, TCTC, TCCT, CTTC, CTCT, CCTT),
(3) blocks are randomly chosen to determine the assignment of all 40
participants (eg, one random sequence would be [TTCC /TCCT / CTTC / CTTC / TCCT
/ CCTT / TTCC / TCTC / CTCT / TCTC]).
This procedure results in 20 participants in both the control and treatment groups
Stratified randomization
relatively simple and useful technique, especially for smaller clinical trials, it
becomes complicated to implement if many covariates must be controlled
Covariate Adaptive Randomization
Flowchart for selecting appropriate
randomization technique
Methods
 Open when the patient knows if he/she has been assigned to the experimental or
control treatment arm.
 Single-blind the patient does not know if he/she has been assigned to the
experimental or control treatment arm
 Double-blind neither the patient nor the investigator is aware of patients'
treatment assignment,
Blinding
Who can be ‘blinded’:

 person entering the patient to the study

 patient
 clinician
 outcome assessor
 person analyzing data
 author of the manuscript
Good blinding may reduce or eliminate experimental biases such
as confirmation bias, the placebo effect, the observer effect, and
others.
Placebo

 Power of placebo

 Placebo effect–effect associated with the knowledge of getting an

‘effective’ intervention

 Placebo controlled study vs. active-controlled /e.g. oncology

Systematic bias
 Selection bias

 Performance bias

 Detection bias

 Attrition bias
Intention to treat analysis
Methods
Completness of follow up
 Withdrawal

 Lost to follow up

 Theworst case scenario sensitivity analysis ( all analysed, no one

controll)
Methods
Outcomes/Endpoints

 Objective/hard vs. subjective/soft

 Clinically important/ patient-important vs. surrogate/substitute

 Primary vs secondary

 Composite outcomes
Confounders
 Factors influencing the outcome, confounders
Confounding variables
have an effect on the dependent variable influence the relationship between an exposure
and an outcome