Here, we take a closer look at the clinical trial and teach you critical appraisal methods.

1. Study Designs:
Observational Studies &
Randomized Controlled
Trials
Day 2
Ashish Advani, PharmD
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2. Objectives
Participants should be able to:
 Evaluate different types of primary
literature for specific limitations
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3. Evaluating Primary Literature
 Author
 Should have no:
 Preconceived notions about agent evaluated
 Conflict of interest
 Writing should be free of opinions or
reflections of author’s attitude
Smith, GH, Norton LL, Ferrill, MJ. Evaluating Drug Literature. ASHP Clinical Skills Program.
Bethesda, MD: American Society of Hospital Pharmacists, Inc.; 1995: p. 1-202.
“clearly superior”
“remarkable improvement”
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4. Evaluating Primary Literature
 Introduction
 Literature review
should be accurate
and balanced
Smith, GH, Norton LL, Ferrill, MJ. Evaluating Drug Literature. ASHP Clinical Skills Program.
Bethesda, MD: American Society of Hospital Pharmacists, Inc.; 1995: p. 1-202.
 Abstract
 Should fairly
represent the
study design,
objective,
methods, and
results
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5. Evaluating Primary Literature
 Methods
 Design should:
 Address study
objective
 Allow for support or rejection
of null hypothesis
 Control: active or placebo
 Parallel vs. crossover design
 Use appropriate analysis:
intent to treat vs. per protocol
Smith, GH, Norton LL, Ferrill, MJ. Evaluating Drug Literature. ASHP Clinical Skills Program.
Bethesda, MD: American Society of Hospital Pharmacists, Inc.; 1995: p. 1-202.
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6. Evaluating Primary Literature
 Methods
 Intent to treat analysis- how to handle missing
data?
Hollis S et al. BMJ. 1999; 319: 67-674.
Sándor PS et al. Neurology. 2005;64:713-5.
 Last observation
carried forward
(LOCF)
 Extreme case
analysis
 Complete case
analysis
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7. Evaluating Primary Literature
 Methods
 Group selection should represent population and
minimize selection bias
 Outcome measures should be clinically relevant
 Treatment selection should represent standard of
care
 Trial should extend over sufficient timeframe
Smith, GH, Norton LL, Ferrill, MJ. Evaluating Drug Literature. ASHP Clinical Skills Program.
Bethesda, MD: American Society of Hospital Pharmacists, Inc.; 1995: p. 1-202.
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8. Evaluating Primary Literature
 Methods
 Group selection should represent population and
minimize selection bias
 Outcome measures should be clinically relevant
Kastelein JJ et al. Am Heart J . 2005;149:234-9.
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9. Evaluating Primary Literature
 Results
 Should follow Objectives section and outcome
measures presented in Methods section
 Safety should be addressed
Rigotti NA et al. Circulation 2010;121:221-9.
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10. Evaluating Primary Literature
 Discussion
 Interpretation of data- statistical and
clinical significance should be considered
 Treatment benefits vs. risk should be fairly
assessed
 Number Needed to Treat (NNT) and
Number Needed to Harm (NNH)
Smith, GH, Norton LL, Ferrill, MJ. Evaluating Drug Literature. ASHP Clinical Skills Program.
Bethesda, MD: American Society of Hospital Pharmacists, Inc.; 1995: p. 1-202.
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11. Evaluating Primary Literature
 Conclusions
 Should be supported by information in the
report
Smith, GH, Norton LL, Ferrill, MJ. Evaluating Drug Literature. ASHP Clinical Skills Program.
Bethesda, MD: American Society of Hospital Pharmacists, Inc.; 1995: p. 1-202.
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