3. Evidence Based Medicine
• Dr. David Sackett is the most cited proponent and
author regarding the topic of evidence-based
medicine (EBM)
• Definition:
- “Evidence based medicine is the conscientious,
explicit, and judicious use of current best
evidence in making decisions about the care of
individual patients. The practice of evidence-
based medicine means integrating individual
clinical expertise with the best available external
clinical evidence from systematic research”.
5. Levels of Evidence
• The levels of evidence outlined by Sackett and his colleagues in
2000:
• 1A = Systematic Review of Randomized Controlled Trials (RCTs)
• 1B = RCTs with Narrow Confidence Interval
• 1C = All or None Case Series
• 2A = Systematic Review Cohort Studies
• 2B = Cohort Study/Low Quality RCT
• 2C = Outcomes Research
• 3A = Systematic Review of Case-Controlled Studies
• 3B = Case-controlled Study
• 4 = Case Series, Poor Cohort, Case Controlled
• 5 = Expert Opinion
6. Levels of Evidence
• As defined by Hadorn and colleagues
• Level A:
- Well conducted RCT with 100 or more patients (including
meta-analysis)
• Level B:
- Well-conducted case-control study
- Poorly controlled or uncontrolled RCT with one or more
major or
three or more minor methodological flaws
-Observational studies with high potential for bias
- Case series or case reports
• Level C:
- Expert opinion
10. • Definition
• Purpose of trials
• Phases of trial
• RCT
• Case control studies
• Cohort Studies
• Case studies and case reports
• Systematic review
• Meta-analysis
11. Clinical Trials
• Clinical trials are sets of tests in medical research and
drug development that generate safety and efficacy
data
• Generate information about adverse drug reactions
and adverse effects of other treatments for health
interventions e.g.,
- drugs
- diagnostics
- device
- therapy protocols
12. Purpose of trials
• Assess the safety and effectiveness of a new medication or device
on a specific kind of patient
• Assess the safety and effectiveness of a different dose of a
medication than is commonly used
• Assess the safety and effectiveness of an already marketed
medication or device for a new indication
• Assess whether the new medication or device is more effective for
the patient's condition than the already used, standard medication
or device
• Compare the effectiveness in patients with a specific disease of
two or more already approved or common interventions for that
disease
13. Phases of trials
• Phase 0: Pharmacodynamics and
Pharmacokinetics
• Phase 1: Screening for safety
• Phase 2: Establishing the efficacy of the drug,
usually against a placebo
• Phase 3: Final confirmation of safety and
efficacy
• Phase 4: Sentry studies during sales
14. Phases of trials
• Phase 0 trials :
- First-in-human trials
- Single sub-therapeutic doses of the study drug are given to a small
number of subjects (10 to 15) to gather preliminary data on the
agent's pharmacodynamics and pharmacokinetics
• In Phase 1 trials:
- Researchers test an experimental drug or treatment in a small
group of people
(20-80) for the first time to evaluate - its safety
- determine a safe dosage range
- identify side effects
• In Phase 2 trials:
- The experimental treatment is given to a larger group of people
(100-300) to see if it is effective and to further evaluate its safety
15. Phases of trials
• In Phase 3 trials:
- The treatment is given to large groups of
people (1,000-3,000) to confirm its:
a. Effectiveness
b. Monitor side effects
c. Compare it to commonly used treatments
d. Collect information that will allow it to be used
safely
• In Phase 4 trials:
- Postmarketing studies delineate additional information:
- including the treatment's risks
- benefits
- optimal use
16. Randomized Control Trials
• Study involves the randomization procedure
• Subjects in the study are randomly allocated to each group included
in the study
• Each subject has an equal chance of being assigned into an
intervention group, a control group, a placebo group or a sham
treatment group
• Eliminates the over-representation of any one characteristic in one
group
• It eliminates any bias in the assignments of individuals to
• Randomized controlled trials are known to be the ‘GoldStandard’
for establishing the effects of a treatment
17. Case Control Studies
• This design involves choosing 2 patients or 2
groups of patients who were exposed to 2
different interventions
• The investigator retrospectively looks back to
which group or patient achieved a better
outcome
18. Cohort Studies
• This design is also called a prospective study, or a
longitudinal study
• It involves the selection of a large population of
people who have the same condition and/or
receive a specific intervention
• They are followed over time and compared to a
group not affected by the condition
• This study employs observation as the research
methodology
• The interventions are not manipulated
19. Case Series & Case Reports
• Case series:
- Reports on a series of patients with a pre-
identified problem
• Case reports:
- This involves a report on the intervention
and outcome for a single patient
20. Systematic review
• Systematic review is usually restricted to RCTs
• A group of reviewers search the available literature via
bibliographic databases and retrieve copies of all the
articles written on a specific topic
• Critical evaluation of the methodologies and content
• The final product is a synthesis of the properly
completed and meaningful research into information
that is relevant to practicing medical
practitioners/clinicians
• Meta-analysis:
- A subset of systematic reviews that use statistical
methods to combine analyze multiple investigations
