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.
11
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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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