• Understand evidence-based medicine

• Lean how to ask the proper research question in

studying a clinical trial

• Differentiate between phase I, II, III, and VI clinical

trials

• Recognize the different types of study designs in clinical

trials
A case of stage III ovarian cancer (omental
cakes, ascites), Ca 125 is over 500.
Would you proceed with :

- Upfront surgery ?

- NAC treatment?

- Palliative care ?
1980’s: McMasters University in Ontario, Canada
David Sackett and colleagues proposed Evidence Based
Medicine (EBM) as a new way of teaching, learning and
practicing medicine.

Sackett defines EBM as:

“…The conscientious, explicit, and judicious use of current best
evidence in making decisions about the care of individual
patients.”
It is a change in the way physicians practice medicine, teach and learn, and
handle research.

Clinical practice: Based on the best current evidence (not necessarily on how
it IS always been done)

Patient Care: Compassionate, patient-oriented (less authoritarian)

Learning & Teaching: Problem-based, problem-solving more investigative,

less know-it-all-by-yesterday

Research: More stringent approach, better proof criteria (more demanding

of proof, less room for error)

9
1. Clinical Question:
Patient-focused, problem-oriented.
2. Find Best Evidence:
Literary Search
3. Critical Appraisal:
Evaluate evidence for quality and usefulness.

4. Apply the Evidence:

Implement useful findings in clinical practice
5. Evaluate:
The information, intervention, and EBM process
• The researcher asks a very specific question
and tests a specific hypothesis.

• Broad questions are usually broken into

smaller, testable hypotheses or questions.

• These are often called objectives or aims, although

calling them questions tends to help with focusing the
hypothesis and thinking about how to find an answer.
• A question that matters to nobody, even you.
• Hoping that one emerges from routine
clinical records, but ..
• The records may be biased and confounded
they will lack information you need to answer your question
reliably, because they were collected for another reason
• Fishing expedition/data dredging–
gathering new data and hoping a
question will emerge
• Feasible
• Interesting
• Novel
• Ethical
• Relevant
• Literature search for previous evidence
• Discuss with colleagues
• Narrow down the question – time, place,
group
• What answer do you expect to find?
• Who am I collecting information from
• What kinds of information do I need?
• How much information will I need? *
• How will I use the information?
• How will I minimize chance/bias/confounding
factors?
• How will I collect the information ethically?
* sample size – ask a statistician for help
http://www.bmj.com/collections/statsbk/13.dtl
Chance - measurements are nearly always subject to random
variation. Minimize error by ensuring adequate sample size and
using statistical analysis of the play of chance

Bias - caused by systematic variation/error in selecting patients,

measuring outcomes, analyzing data – take extra care

Confounding factors- factors that affect the interpretation of

outcomes e.g. people who carry matches are more likely to develop
lung cancer, but smoking is the confounding factor – so measure
likely confounders too
• What information to give before seeking consent? Any
deviation from normal clinical practice?
• What burden will be imposed on participants? What risks will
participants/others be exposed to? What benefit might
participants or others receive?
• How might society/future patients benefit in time? Might
publication expose the patients’ identities?
 Test a potential therapy, procedure or drug for the first time in
human beings Test Safety
• Phase I trials are typically conducted in very small groups of
people (10-80).
• In addition to safety, Phase I research yields important
information on side effects, effectiveness of a chosen delivery
method (e.g., by mouth, injection, etc.) and appropriate dosage
levels.
 More comprehensively evaluate a treatment’s safety and
effectiveness

• Larger group of participants (usually 100 to 300).

Confirm a therapy’s effectiveness, monitor side effects and compare it
against the current standard treatments in a large group of people
(around 1,000 to 3,000)

• Phase III trials last longer, are usually conducted at multiple centers .

• They evaluate whether a treatment will benefit people and if the

benefits associated with a therapy outweigh the risks.
 They are conducted after a treatment has received FDA approval and
been brought to market.

• They help further evaluate long-term side effects and potential new
uses for other conditions.