![Page 1: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/1.jpg)
Levels of Evidence, Recommendations & Phases of Clinical Trials
Dr SD sanyal Lt Col Priyaranjan
Cl Spl Surg & GI Surgeon
![Page 2: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/2.jpg)
Levels of Evidence
![Page 3: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/3.jpg)
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”.
![Page 4: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/4.jpg)
Levels of Evidence
![Page 5: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/5.jpg)
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
![Page 6: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/6.jpg)
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
![Page 7: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/7.jpg)
Grades of Recommendation
![Page 8: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/8.jpg)
![Page 9: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/9.jpg)
Clinical Trials & Phases
![Page 10: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/10.jpg)
• Definition• Purpose of trials• Phases of trial• RCT• Case control studies• Cohort Studies• Case studies and case reports• Systematic review• Meta-analysis
![Page 11: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/11.jpg)
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
![Page 12: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/12.jpg)
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
![Page 13: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/13.jpg)
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
![Page 14: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/14.jpg)
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
![Page 15: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/15.jpg)
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
![Page 16: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/16.jpg)
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
![Page 17: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/17.jpg)
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
![Page 18: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/18.jpg)
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
![Page 19: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/19.jpg)
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
![Page 20: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/20.jpg)
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
![Page 21: Levels of evidence, recommendations & phases of](https://reader035.vdocuments.mx/reader035/viewer/2022062823/58787bd91a28ab466c8b5185/html5/thumbnails/21.jpg)
THANK YOU