We look at evidence-based medicine and the clinical trials that comprise it, including the gold standard, the randomized controlled trial (RCT).

1. Study Designs:
Observational Studies &
Randomized Controlled
Trials
Day 1
Ashish Advani, PharmD
1

2. Objectives
Students should be able to:
 Describe the hierarchy of drug literature
and identify general limitations of primary,
secondary, and tertiary literature
2

3. Categories of Drug Literature
Primary literature
• Evaluative
• Descriptive
Secondary literature
Tertiary literature
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.
3

4. Self Assessment
 How would you categorize a meta analysis
or systematic review article?
 Primary literature
 Secondary literature
 Tertiary literature
4

5. Primary Literature→ Evaluative→
 Experimental
studies
 Clinical trial
 Pharmaceutical
research
 Educational
assessment
 Observational
studies
 Case control
 Cohort
 Follow-up
 Cross-sectional
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.
5

6.  Case report
 Pharmaceutical practice
 Clinical series
 Program
 Population
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.
Primary Literature→ Descriptive→
6

7. Limitations of Primary Literature
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.
 Bias
 Author
 Subject
 Journal
 Results only applicable to similar population with
same inclusion and exclusion criteria
 Results could be due to chance
 Retrospective studies only show association
7

8. Limitations of Primary Literature
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.
 Bias
 Author
 Subject
 Journal
 Results only applicable to similar population with
same inclusion and exclusion criteria
 Results could be due to chance
 Retrospective studies only show association
8

9. Limitations of Primary Literature
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.
 Bias
 Author
 Subject
 Journal
 Results only applicable to similar population with
same inclusion and exclusion criteria
 Results could be due to chance
 Retrospective studies only show association
9

10. Limitations of Primary Literature
Journal (Publication Bias)
FDATrial Data JournalsTrial Data
Possibility for drug companies to:
(1) not report data
(2) selectively report data
FDA= Food and Drug Administration
10

11. Limitations of Primary Literature
Journal (Publication Bias)
 1994-1996 Zoloft® study published in
May 2007 finding that drug was no
better than placebo
 Zoloft® went off patent in summer 2006
 1997 published Prozac® study had no
mention of suicide, however according
to FDA report…
http://www.fda.gov/cderfoi/nda/2003/18936S064_Prozac%20Pulvules_medr.pdf
Freidman, MJ. J Clin Psychiatry. 2007; 68 (5): 711-720.
Emslie, GJ. Arch Gen Psychiatry. 1997; 54 (11): 1031-1037.
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12. Limitations of Primary Literature
Journal (Publication Bias)
 Trial registration
 International Committee of Medical Journal Editors (2005)
 FDA Revitalization Act (September 2007)
Drazen, J. NEJM. 2007; 357 (17): 1756-1757.
http://clinicaltrials.gov/show/NCT00220636
Clinicaltrials.gov Linked Journal Publication
Hellerstein DJ. Prog Neuropsychopharmecol Bio Psychiatry. 2004; 28 (8): 1347-1348.
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13. Limitations of Primary Literature
Journal (Publication Bias)
 “Selective Publication of Antidepressant Trials and
Its Influence on Apparent Efficacy”
 Identified phase 2 and phase 3 studies for 12
antidepressants approved by FDA from 1987-2004
(12,564 adult patients) Compared with matched
data from journal articles, if published
 Extracted:
 Efficacy data on all randomized, double-blind, placebo-
controlled studies
 FDA regulatory decisions on data→ positive, negative,
or questionable
Turner, EH. NEJM. 2008; 358 (3): 252-260.
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14. Limitations of Primary Literature
Journal (Publication Bias)
Studies (74 total)
Patients (N=12,564)
11 (15%) 23 (31%)
40 (54%)
1,843 (15%)
3,449 (27%)
7,272 (58%)
Turner, EH. NEJM. 2008; 358 (3): 252-260.
14

15. Limitations of Primary Literature
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.
 Bias
 Author
 Subject
 Journal
 Results only applicable to similar population with
same inclusion and exclusion criteria
 Results could be due to chance
 Retrospective studies only show association
15

16. Limitations of Primary Literature
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.
 Bias
 Author
 Subject
 Journal
 Results only applicable to similar population with
same inclusion and exclusion criteria
 Results could be due to chance
 Retrospective studies only show association
16

17. 17
Self Assessment
 Which limitation from this presentation applies here?

18. 18