Professional Documents
Culture Documents
an Academic Perspective
YuYu-Xiao Yang, MD, MSCE, FACP
Division of Gastroenterology Center for Clinical Epidemiology and Biostatistics University of Pennsylvania 2011
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Who am I?
Th P l The Perelman S h l of M di i at th School f Medicine t the University of Pennsylvania
S i scholar at th C t f Cli i l E id i l Senior h l t the Center for Clinical Epidemiology and Biostatistics (CCEB) Gastroenterologist Clinical Epidemiologist
Pharmacoepidemiology Cancer epidemiology
Editorial roles
Pharmacoepidemiology and Drug Safety Annals of Internal Medicine
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Outline
Historical perspective Drug Safety Regulation and Surveillance
Pre-marketing Pre Post-M k ti Post P t-Marketing
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1938
Food Drug, and Cosmetic Act Food, Drug Manufacturer provide safety data FDA to review safety data in 60 days No proof of efficacy required
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1950 1951
1952
1st textbook of adverse drug reaction published AMA Registry on Blood Dyscrasias established
later incorporated into the spontaneous reporting system of the U.S. FDA
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1962
Kefauver-Harris Amendment to FD&C Act Kefauver Extensive preclinical testing required Proof of efficacy (i.e., RCT) required (i e Mandatory reporting of ADRs I Increased ti d time and cost of drug approval d t fd l process Drug Efficacy Study Implementation for prepre-1962 drugs
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1992
Prescription Drug User Fee Act (PDUFA)
Drug manufacturers pay fees to allow the FDA to assign more resources to the drug review and approval process Drug review time cut from ~30 months to ~15 months E t d d b 1997 FDA Modernization Extended by M d i ti Act
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2006
Institute of Medicine Review of FDA
Major deficiencies revealed Called for an increase in the regulatory powers, g funding, and independence of the FDA
2007
PDUFA 4
Increased policing power for FDA Increase in user fee ($1-1.8 million per NDA in 2012) $ $702,172,000 f FY 2012 for
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Diabetes Drug Avandia Should Be Removed F R d From th M k t Public the Market, P bli Citizen Tells FDA Advisory Committee July 30 2007 30,
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Transplant Mild chronic portal inflammation, fibrosis , death Death Death NA Massive necrosis with collapse of architecture, cirrhosis NA
5 CCEB
26
NA
NA
NA
36
Death
Outline
Historical perspective Drug Safety Regulation and Surveillance
Pre-marketing Pre Post-M k ti Post P t-Marketing
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Years
~3.5
~1
~2
~3
~2.5
~10-12 Total
Test Population
20 to 80 healthy volunteers
1000 to 3000 patient volunteers Verify effectiveness, monitor adverse reactions from long-term use
Purpose p
Success Rate
5 enter trials
1 approved
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Premarketing
FDA Approval
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Expedited safety reports sent to IRB and the FDA is the norm
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Premarketing
FDA Approval
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Postmarketing Surveillance
Adverse event reporting systems Formal studies (will discuss tomorrow)
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Fax, mail, phone or web report VAERs (Vaccine Adverse Event Reporting System) Only vaccines y
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The plural of At times sufficient for regulatory decisions anecdote is Vital for hypothesis g yp not data generation
Disproportionality measures
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Disproportionality Analysis
Significant signal g g
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Outline
Historical perspective Drug Safety Regulation and Surveillance
Pre-marketing Pre Post-M k ti Post P t-Marketing
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Current Status
Rapidly expanding pharmacopoeia Medications widely used Where we can monitor, the rates of adverse events appear t be hi h d t to b high
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NDAs
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Approvals
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This figure illustrates the number of reports received (solid bars) and entered (checkered bars) into AERS by type of report since the year 2000 until the end of 2010.
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Recent Withdrawals
1999 - troglitazone 2000 - cisapride i id 2001 alosetron 2005 rofecoxib and valdecoxib 2005 natalizumab 2007 tegaserod
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Outline
Historical perspective Drug Safety Regulation and Surveillance
Pre-marketing Pre Post-M k ti Post P t-Marketing
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CERTs
Increase awareness of the benefits and harms of drugs, medical devices, devices and biological products through education and research 14 Collaborating Centers
Emphasis Health information technology Therapies for CV disorders Population-based delivery system Mental health therapeutics MS disorders Therapeutics for the elderly Pediatric therapeutics Anti-infective therapeutics Consumer education Therapeutic medical devices Clinical and economic issues Tools f optimizing prescribing for Therapeutics for vulnerable populations Drug interactions Center Brigham Duke HMO Research Network Rutgers UAB U Iowa Cincinnati Childrens U Penn U of Texas Cornell U of Chicago U of Illinois f Vanderbilt U Arizona CCEB
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Thank you!
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