Course Introduction & Background on Attorney Generals’ F.L.I.P. Grant and Neurontin Case Gordon...
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Transcript of Course Introduction & Background on Attorney Generals’ F.L.I.P. Grant and Neurontin Case Gordon...
Course Introduction & Background on
Attorney Generals’ F.L.I.P. Grant and Neurontin Case
Gordon Schiff MDDirector Clinical Quality Research & Improvement
Dept of Medicine Cook County Professor of Medicine Rush University
MODULE/LECTURE 1
1. Introduction: Description FLIP Project & Course – Why this course and our project is unique– Larger/current contexts: estrogen, vioxx
2. Neurontin Case Study– Patterns of use --Detailing example – Historical timeline ---Details of problems
3. Class Activity:– Annals Internal Med Article; Trigger questions
4. Orientation to Course; Syllabus – Topics, Projects, FLIP Tools, Grading Rules
OUTLINE of TODAY’S CLASS
Gabapentin (Neurontin) $430 Million Settlement
● States Attorney Generals and Dept of Justice alleged Parke Davis (Warner-LambertPfizer) deceptively promoted Neurontin:– Conducted CME lacking balance, expensive “perks” to attending
physicians.– “Publication strategies:” produced & distributed non-scientific,
anecdotal reports for off-label uses.– ”Research payments” to prescribers, in effect, kickbacks for off-
label prescribing.– Provided incomplete info to Drugdex reference, formulary
committees
Neurontin- GabapentinManufactured Unproven Illegal Claims
● Claims for un-approved uses– Bipolar disorder, migraine headaches, chronic pain
● Metamorphosis of 2nd line epilepsy drug into blockbuster– Elaborately orchestrated by senior Parke Davis officials.
● Total sales 2003- $2.7 billion – ~ 90% usage for indications lacking valid evidence
– Neurontin costs to consumers >$200/month
Goal: To improve prescribing practices by: 1) educating health professionals at all levels of training about the drug development and approval process;
2) making health professionals aware of pharmaceutical industry marketing practices and assisting them in developing the knowledge and skills to evaluate those marketing techniques; and
3) providing examples and strategies for evaluating existing sources of drug information, and for accessing unbiased sources of information about drugs.
Atty Genl Consumer and Prescriber Grant Program RFP 8/05
Researchers at John H. Stroger Jr. Hospital of Cook County and the University of Illinois at Chicago have been awarded a two-year $400,000 grant to educate health professionals about the safety of prescribing prescription medications, according to a release from UIC.
Gordon Schiff of the Department of Medicine at Stroger Hospital and associate professor of medicine at Rush Medical School, and Bruce Lambert, associate professor in the UIC College of Pharmacy, will collaborate on the project, designed to assist hospital formulary committees (a group that approves medications) evaluate the risks and benefits of new medications, and educate physicians and pharmacists about how to choose them, the release said
”
Restoring Healthy Balance
● How could #1 drug prescribed for women (HRT) turn out to not work for claimed benefits (incl lower heart risk) and cause more harm than good (breast, endometrial cancer, heart dis)?
Restoring Healthy Balance ● How could #1 drug prescribed for women (HRT)
turn out to not work for claimed benefits (incl lower heart risk) and cause more harm than good (breast, endometrial cancer, heart dis)?
● How could #1 drug prescribed for HBP (amlodipine (Norvasc)) turn out to be more harmful and less beneficial than inexpensive diuretic?
● How could most commonly prescribed arthritis med (rofecoxib (Vioxx)) be so heavily promoted and prescribed (100 million scripts worldwide) despite evidence of 2 to 4 x risk of heart attacks?
U.S. Deaths from Vioxx More than Vietnam War
● 1/1999--9/2004: 106.7 million rofecoxib prescriptions in US
– 17·6% were high-dose, mostly to older patients
● In 2 Merck-sponsored randomised trials: 2,25 relative risks for AMI
– 5x for high-dose rofecoxib and 2x for the standard dose
– Background rate AMI control NSAID users varied from 7·9 per 1000 person-years in CLASS1 to 12·4 per 1000 person-years in TennCare.
● Using Merck studies relative risks w/ these background rates 88,000– 140,000 excess cases serious coronary disease in US
● Using US national case-fatality rate-44%,suggests thousands of deaths attributable to rofecoxib use (~38,000-61,000)
Graham Lancet 2005
Restoring Healthy BalanceRe-balancing
Overselling/Misrepresenting Benefits
Minimizing/Hiding Risks
Drug pricing
One-Sided Source of Education
● In 2004, > $2 billion was spent on CME Pharmaceutical manufacturers paid for more than half
● Firms that manufacture FDA-regulated products (primarily pharmaceuticals) provided 74.7% of the income of medical education and communication companies (MECCs).
● CME provided by medical schools is almost equally reliant on the pharmaceutical industry, which 63.8% of CME income to medical schools
● http://www.ama-assn.org/ama/pub/category/16260.html
● Professional and Consumer Education– Reform of Medical and Pharmacy Education
● Improved Evidence– Better Quality Critical Review Healthy Skepticism
● Industry reforms/codes● Regulatory Oversight● Legislation ● Litigation● Consumer and Professional Advocacy
– New Forms Pharmacy-Medicine-Consumer Collaboration
Restoring Healthy Balance Approaches
● Professional and Consumer Education– Reform of Medical and Pharmacy Education
● Improved Evidence– Better Quality Critical Review Healthy Skepticism
● Industry reforms/codes● Regulatory Oversight● Legislation ● Litigation● Consumer and Professional Advocacy
– New Forms Pharmacy-Medicine-Consumer Collaboration
Restoring Healthy Balance Approaches
Leveraging Formularies for Improved Prescribing
1. Venue for critical review new drug claims 2. Evaluation of comparative efficacy.3. Less bias and conflict in decision-making4. Cumulative expertise reviewing new drugs5. Experience with pitfalls and biases6. Identify/weigh potentials for overuse/misuse7. Weigh of cost benefit (for individual
drug/indication).8. Weigh institutional resource allocation (this
drug vs. alternatives).9. Raise/highlight safety concerns10. Dissemination vehicles and tools (guidance
and warnings).
More rational prescribing
Enhanced:1. Appropriateness 2. Safety3. Cost Effectiveness
Value-added role of formulary related to drug marketing
1866
Parke-Davis Founded
1970
Warner-Lambert buys Parke-Davis
1977
Patent for Gabapentin awarded to Warner-Lambert
1993
FDA approves Gabapentin for adjunctive treatment of partial complex seizures in adults
U.S. Gabapentin sales at $97.5m
May1996
Dr. David Franklin hired as Medical Science Liaison
Sept1996
Dr. Franklin files lawsuit against Warner-Lambert
Pfizer buys Warner-Lambert/Parke-Davis and all patents (including pregabalin)
July 2000
Oct2000
Aug1996
Dr. Franklin quits Warner-Lambert
Neurontin approved for adjunctive treatment of partial seizures in children
Nov2000
78% of Neurontin use is off-label (Pfizer documents)
U.S. Neurontin sales at $2.5b
Neurontin approved for Post Herpetic Neuralgia in adults
Pfizer pleads guilty to charges of false marketing and settles for for $430m
May 2002
May2004
Patent on Neurontin expiresGabapentin marketed as generic
March2005
June2005
Pregabalin campaign launched
Neurontin in top 10 U.S. drugsSales at $2.6b Neurontin sales
fall by 77%
Lyrica captures 7% of anti-epileptic market
Unapproved Indications for which Neurontin Illegally Promoted
• Bipolar disorder.
• Peripheral neuropathy,
diabetic neuropathy and
other pain syndromes.
• Epilepsy monotherapy.
• Reflex sympathetic
dystrophy.
• Attention deficit disorder.
• Restless leg syndrome .
• Essential tremor and periodic
limb movement disorder
(ETPMLD)
• Migraines
• Drug and alcohol withdrawal
Steinman, M. A. et. al. Ann Intern Med 2006;145:284-293
Prescriptions for Gabapentin by Diagnostic Category
0
10
20
30
40
50
60
70
80
Unapproved Uses
Approved Uses
44/115 (38%) Neurontin Detail Visits “Main Message” was Unapproved Uses
Steinman et al SGIM 5/2006
0
10
20
30
40
50
60
70
80
Unapproved Uses
Approved Uses
44/115 (38%) Neurontin Detail Visits “Main Message” was Unapproved Uses
Steinman et al SGIM 5/2006
After receiving the detail visit, 46% (50/108) of physicians reported the intention to increase their prescribing or recommendation of gabapentin in the future
Characteristics and impact of drug detailing for gabapentin.Steinman et al SGIM Abstract 5/2006
Steinman, M. A. et. al. Ann Intern Med 2006;145:284-293
1998 Promotion Budget for Gabapentin by Strategy and Tactical Category
Debate on Neurontin Marketing Practices Trigger Questions/Statements
● If the drug works, what’s wrong with it?
● So, what, it didn’t hurt anybody
● This is exceptional case, isolated problem that has now been fixed
● Drug companies need to do this to make money, so they can develop needed new drugs
● Everybody does it
● They did show that pregabalin (Lyrica) works
● This is only relevant to doctors (who do the prescribing), not to pharmacists
● I want to work for industry, this ties my hands
There is widespread agreement that commercial interestsshould not influence the clinical decisions that physiciansmake on behalf of their patients. As a result, a complexsystem has evolved to help manage these conflicts,focused primarily on disclosure and self-regulation by physicians, professional organizations, and the pharmaceutical industry. These efforts have been largely ineffective and the techniques used to promote gabapentin illustrate how commercial interests can intrude into thepractice of medicine in both visible and hidden ways.
Conclusion-Neurontin Promotion
Steinman, M. A. et. al. Ann Intern Med 2006;145:284-293
Course Game Plan – Topics
1. Introduction- Neurontin 2. Formularies 3. Historical examples
serious drug problems 4-5. Trial design
Statistical biases 6. Surrogate vs. outcome
end-points7. Comparative efficacy
8. Promotion, advertising 9. Indications creep
off label use10. FDA; regulatory issues11. Limited populations
exposed pre-marketing12. Cost effectiveness 13 Information sources 14. Principles of
conservative prescribing
Project
● Pick a drug● Literature Search on Chosen Drug
Look at Study DesignBegin to use FLIP Formulary Tools (2)
● Engage Surrogate and Comparatives Efficacy Issues
Project (con’t)
● Examine Promotional and Appropriate and Real life Use issue
● Policy issues raised by this drugPrepare formal presentation
● Presentations
FLIP Toolsfor next class
● Formulary Culture Survey– Complete on Blackboard before class– Do before doing the reading
● FLIP Formulary Checklist Tool
● Levels of Understanding Tool