Study Designs: Observational Studies & Randomized Controlled
Trials
Day 1Ashish Advani, PharmD
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ObjectivesStudents should be able to:Describe the hierarchy of
drug literature and identify general limitations of primary,
secondary, and tertiary literature2
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Categories of Drug LiteratureSmith, 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
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Self AssessmentHow would you categorize a meta analysis or
systematic review article? Primary literatureSecondary
literatureTertiary literature4
Primary Literature EvaluativeExperimental studiesClinical
trialPharmaceutical researchEducational assessmentObservational
studiesCase controlCohortFollow-upCross-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
5
Case reportPharmaceutical practiceClinical
seriesProgramPopulation
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
Descriptive6
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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.BiasAuthorSubjectJournal Results only applicable to
similar population with same inclusion and exclusion
criteriaResults could be due to chanceRetrospective studies only
show association 7
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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.BiasAuthorSubjectJournalResults only applicable to similar
population with same inclusion and exclusion criteriaResults could
be due to chanceRetrospective studies only show association 8
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.BiasAuthorSubjectJournalResults only applicable to similar
population with same inclusion and exclusion criteriaResults could
be due to chanceRetrospective studies only show association 9
9
Limitations of Primary Literature Journal (Publication Bias)
FDATrial Data
Journals
Trial Data
Possibility for drug companies to: not report data selectively
report dataFDA= Food and Drug Administration 10
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Limitations of Primary Literature Journal (Publication
Bias)1994-1996 Zoloft study published in May 2007 finding that drug
was no better than placeboZoloft went off patent in summer 20061997
published Prozac study had no mention of suicide, however according
to FDA report
http://www.fda.gov/cderfoi/nda/2003/18936S064_Prozac%20Pulvules_medr.pdfFreidman,
MJ. J Clin Psychiatry. 2007; 68 (5): 711-720.Emslie, GJ. Arch Gen
Psychiatry. 1997; 54 (11): 1031-1037.11
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Limitations of Primary Literature Journal (Publication
Bias)Trial registrationInternational 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.govLinked Journal PublicationHellerstein DJ. Prog
Neuropsychopharmecol Bio Psychiatry. 2004; 28 (8): 1347-1348.12
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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 publishedExtracted: Efficacy data on all randomized,
double-blind, placebo-controlled studiesFDA regulatory decisions on
data positive, negative, or questionable
Turner, EH. NEJM. 2008; 358 (3): 252-260.13
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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
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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.BiasAuthorSubjectJournalResults only applicable to similar
population with same inclusion and exclusion criteriaResults could
be due to chanceRetrospective studies only show association 15
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.BiasAuthorSubjectJournal Results only applicable to
similar population with same inclusion and exclusion
criteriaResults could be due to chanceRetrospective studies only
show association 16
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Self AssessmentWhich limitation from this presentation applies
here?
Questions?18
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Chart1234011
Sheet1UnpublishedPublished and agree with FDAPublished and
conflict with FDA234011
