This document discusses levels of evidence and phases of clinical trials. It defines evidence-based medicine as using current best evidence from systematic research to make decisions about patient care. Levels of evidence are ranked from 1A to 5 based on study design, with systematic reviews and randomized controlled trials ranked highest. Clinical trials progress through four phases to test safety, efficacy, and optimal use of new drugs or devices. Phase 1 assesses safety, phase 2 establishes efficacy, phase 3 confirms safety and efficacy in larger groups, and phase 4 studies monitor risks and benefits after marketing.

1. Levels of Evidence,
Recommendations & Phases of
Clinical Trials
Dr SD sanyal
Lt Col Priyaranjan
Cl Spl Surg & GI Surgeon

2. Levels of Evidence

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”.

4. Levels of Evidence

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

7. Grades of Recommendation

9. Clinical Trials & Phases

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

21. THANK YOU