A Workshop from the Program in Wise Prescribing PHARmACeUTiCAl ComPAny PresCriber Marketing

Pharmaceutical Company Prescriber Marketing
A Workshop from the Program in Wise Prescribing
The Program in Wise Prescribing is a University of Vermont initiative
funded by the Attorney General Consumer and Prescriber Grant
Program. The impact of drug company marketing strategies on
consumer and prescriber behavior is well understood. However,
the proper approach for limiting marketing’s negative impact
on inappropriate and needlessly expensive use of medications
remains controversial. The Program in Wise Prescribing approach
centers on raising awareness about the methods and effectiveness
of pharmaceutical marketing.
Appendix 1: Neurontin Settlement
Objectives
1. Understand drug development
history and the rationale
for detailing pharmaceuticals
to prescribers
2. Understand the potential
advantages and disadvantages
of industry-prescriber
interactions
3. Raise awareness of research
evidence on industry-prescriber
interactions
4. Recognize and respond
appropriately to strategies
used by industry representatives
5. Review less biased resources for
therapeutic options
Pharmaceutical companies seeking FDA approval for a new
medication must specify the intended use of that product and
support claims for that use with research. The medication may
not be marketed or promoted for any other uses without further
FDA approval.1 While clinicians may prescribe medications for
off-label use, drug companies may not market drugs to influence
off-label prescribing.
Contact information:
Insert your contact information here
On May 13, 2004, Warner-Lambert, a division of Pfizer, Inc., entered
into an Assurance of Voluntary Compliance/Discontinuance with
the Attorneys General of 50 States and the District of Columbia
to settle allegations that Warner-Lambert conducted an unlawful
marketing campaign for the drug Neurontin1. The unlawful
campaign consisted of the combination of misleading strategies
and illegal promotion of Neurontin for off-label uses.
Although Warner-Lambert only received FDA approval for
adjunctive therapy in the treatment of partial complex seizures
in patients over age 12, they promoted off-label use of Neurontin
for a variety of conditions including:1
• Bipolar disorder
•Migraines
• ALS
• Neuropathic pain • First line Rx of seizures
• ADD
Warner-Lambert accomplished this using multiple strategies:
• Detailing by pharmaceutical representatives including false
or misleading statements about Neurontin’s efficacy and FDA
approval for off-label uses.1
• Hiring influential doctors as speakers for Neurontin in
exchange for generous honoraria, stipends, and grants.2
• Organized teleconferences using moderators encouraged
to steer the discussion toward off-label use.2
• Influenced unrestricted educational programs to increase
sales for off-label use.2
• Organized advisory boards and consultant meetings that
included “hard hitting” educational sessions promoting
Neurontin.2
• Withholding negative studies from publication.2
• Ghost writing review articles, and letters to the editor
promoting Neurontin and having a professor sign as
the author.2
OFFICE OF PRIMARY CARE
University of Vermont College of Medicine Office of Primary Care www.med.uvm.edu/opc
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Appendix 2: FDA Drug Approval Process
According to FDA estimates, it takes approximately eightand-a-half years to study and test a new drug before it
can be approved for the general public. This estimated
timeframe includes early laboratory and animal testing,
as well as later clinical trials with human subjects.
Overview of New Drug Development Process
Pre-Clinical
Research
Clinical studies
phase
Synthesis &
Purification
Investigational
New Drug (IND)
Application
Submitted
1
phase
animal
testing
Clinical use
New Drug
Application
(NDA)
Submitted
2
phase
3
drug
approval
PostMarketing
Surveillance
Phases of the New Drug Development Process
HumansN
Purpose
Synthesis and Purification
NoN/A
To identify a chemical compound that can achieve a desirable result.
Animal Testing
No
Two or more species (one rodent, one non-rodent) To study pharmacokinetics (absorption,
distribution, metabolism, excretion) and
pharmacodynamics (what the drug does
to the body, including drug toxicity).
Phase 1
Yes
20-80 healthy
volunteers
To determine the pharmacokinetics and dynamics of the drug in humans and the side effects associated with increasing doses.
Phase 2
Yes
Several hundred patients To obtain data on the drug’s effectiveness
and safety for a particular indication(s) in
patients with the disease or condition.
Phase 3
Yes
Hundreds-
thousands of patients To gather the additional effectiveness and safety information needed to evaluate the overall benefit-risk ratio for the drug. Phase 3 studies also provide an adequate
basis for extrapolating the results to the
general population and transmitting that
information in the physician labeling.
Post-Marketing Surveillance
Yes
As many To assess risks and side effects not seen in
as possible earlier phase studies.
Adverse Event Reporting System (AERS):
www.fda.gov/cder/aers/default.htm
MedWatch: www.fda.gov/medwatch
USP-ISMP Medication Errors Reporting Program: www.ismp.org/orderforms/
reporterrortoISMP.asp
Appendix 3: Impact & perceptions of
pharmaceutical advertising on prescribers
Data on influence
Receiving a free meal was independently associated with
self-reported change in prescribing practices.3
Physicians who requested that drugs be added to their hospital
formulary were more than 10 times as likely as their colleagues
to have received financial support from the companies that
manufactured those drugs.4
The cost of prescriptions a physician writes is correlated with the
availability and use of information provided by drug representatives.5
Prescriber impressions
67% of faculty members surveyed, and 77% of residents, thought physicians could be compromised by accepting gifts.6
61% of residents thought gifts influenced other physicians, but only 16% thought gifts influenced their own behavior.7
90%of physicians feel they have received insufficient training
on interacting with drug company representatives.6
Patient impressions
70%of patients believe that when physicians receive gifts,
it affects prescribing.8
47%of patients believe it is inappropriate for a physician to
accept a dinner.7
31%of patients believe a drug pen influences prescribing.9
2
Adapted from: The New Drug Development Process: Steps from Test Tube to New Drug Application Review. Available at: www.fda.gov/cder/handbook/develop.htm. Accessed: March 21, 2007.
Appendix 4: Pharmaceutical representative marketing tactics
Research has shown pharmaceutical representatives use various
techniques meant to subconsciously influence prescribers. Many
of the most common strategies are listed below:
Pharmaceutical Representative Marketing Tactics
Strategy
What is it Reciprocity or Giving a gift
Gifts10
11
How it worksExamples
Possible responses
When someone receives a gift
they feel indebted to return the
favor; the bigger the gift, the
greater the sense of indebtedness.
Don’t accept gifts.
Pens, toys, food, tickets
to events, vacations
Appeals to Referring to a Many feel at least a little insecure
“Dr. Jones from the pain Authority11,10
local expert about their medical knowledge
clinic uses this medication
in the field
and want to be as up-to-date as on many of his patients.”
possible on the latest treatments. As a result, experts can carry a lot of influence. The companies invest
significantly in getting an expert to use
their product and spread the word.
Recognize both the
tactic and the fact that
the pharmaceutical
industry may have
influenced the expert.
Social Validation11 or the Bandwagon Effect10
Recognize the tactic
and seek alternative
evidence for the
prescribing decision.
Referring to
what other prescribers are doing
This is essentially peer pressure,
making you feel like you are out
of the loop if you aren’t using this
drug too. “Most of the physicians I have talked
to have stopped prescribing short acting
narcotics and switched to Dolornil for
out-patient pain management.”
Misinformation 12,13 Providing false Consciously or not, pharmaceutical 11% of statements made by drug
information representatives spread inaccurate reps are false; 25% of the studies
to promote a and misleading information through featured in marketing brochures
product
verbal presentations and written provided by drug company
promotional material. representatives contain invalid data.
Be skeptical and careful
about the information, and
check other sources. STEP
(Safety, Tolerability, Efficacy,
Price) is a recommended
method for discussing
medications with reps.10
Friendship/
Liking 11
Decide how sincere it
is when a drug rep
remembers your birthday
or favorite movie.
Consciously divisive or not, the drug reps
develop or feign a
friendship with
the prescribers
and staff.
Remembering birthdays, and
other personal information that
they will raise at future visits.
Through the relationship that
unfolds, they may have better
access to you and be able to
discuss products they are selling.
A drug rep was seen recording
personal information into a
database on physicians they
had just seen.
Commitment/
PharmaceuticalYou are asked a series of leading
REP: Do you have patients with
Consistency11
representatives get questions about how you practice urinary incontinence?
your commitment medicine and then ask you to tryMD: Yes
to try their
their medication. Questions are
REP: Do they find this embarrassing?
medication by
posed in such a manner thatMD: Yes
implying that not you’d feel wrong not to agree.
REP: Wouldn’t you like to help them
doing so would be Prescribers who make such avoid that embarrassment?
inconsistent with verbal commitments are much MD: Yes
your practice.
more likely to make changes in REP: If you use my new product, your
their practice. patients won’t have to go through that
embarrassment. It has been shown to
reduce urinary incontinence by 90%.
Wouldn’t you like to try this with your
patients?
MD: Yes
OFFICE OF PRIMARY CARE
University of Vermont College of Medicine Office of Primary Care www.med.uvm.edu/opc
Recognize the tactic and
resist making a commitment
statement – Instead, say
something like: “I don’t
prescribe new medications
until they have been on the
market for a year.” “This
sounds promising; I would
like to read more about it
first.” Ask a question about
the medicine, rather than
simply saying, “yes.”
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Appendix 5: comparison of sources for prescribing
The Cochrane Database of Systematic Reviews
www.cochrane.org
This online database of meta-analyses has been assembled by a
collaborative who set the standard for meta-analyses. The only role
bias may play in these reviews is the authors’ interpretation of the
findings. No information is available for writing prescriptions.
UpToDate
www.UpToDate.com
This peer reviewed and easy to read online text book contains
efficacy and prescribing information. There is a disclosure process
where authors must share any significant financial affiliation
they have with industry. There is no reported methodology by
which the authors review the literature and report the findings.
Agency for Healthcare Research Quality Evidence Based
Practice Centers (ARHQ)
www.ahrq.gov/clinic/epcquick.htm
Like Cochrane, this collaborative performs meta-analyses using
a systematic, reproducible process. The only significant risk for
bias lies in the interpretation and conclusions sections.
The Medical Letter
http://medlet-best.securesites.com/index.html
This is a product of a not-for-profit organization. While there
is not an explicit method for collecting drug review articles,
an extremely rigorous peer review process should ensure all
relevant articles and opinions are raised.
Clinical Evidence
www.clinicalevidence.com
This peer reviewed and easy to read resource from the BMJ
organization looks for the latest systematic reviews and any
subsequent RCTs and relevant work. They include Cochrane
and AHRQ and comment on how these systematic reviews
may be integrated.
Micromedex
www.micromedex.com
This is a proprietary product. While specifics on the literature
surveillance and review process are not fully disclosed, the
drug information detail is second to none.
Other
Some other common sources used for prescribing include:
Epocrates, the PDR, and pocket drug information handbooks.
While these can be useful for medication dosages, most of these
products do not have any efficacy information. These sources
are written with the assumption the prescriber knows a certain
medication is the most appropriate treatment for a condition.
ResourceElectronic impartialRx ease
hhh
hhh
hhh
hhh
h
hh hh
Cochrane Collaborative
Yes
AHRQ
Yes
The Medical Letter
Yes
Clinical Evidence
Yes
Drug Representatives
No
UpToDate
Yes
Micromedex
Yes
Epocrates
Yes
Yes
PDR
Yes
No
Some
Varies
Drug Info Handbooks
Definition of the ratings
Impartial: Based on whether there is peer review and
reproducible systematic data collection, analysis, and
reporting, i.e measures to reduce the chance that bias is
influencing the information.
Rx Ease: Information is availabe for writing a prescription.
No
No
No
No
No
Yes
Yes
cost
w
w
hh
hhh
w
hhh
hhh
w
w
h
hhhHigh
hh Med
h Low
w Free
h $50/year
hh $51-200/year
hhh >$200/year
1. U.S. Department of Justice. Warner-Lambert to pay $430 million to resolve criminal & civil health care liability relating to off-label promotion. Accessed at www.usdoj.gov/opa/pr/2004/May/04_civ_322.htm.
on March 3, 2005.
2. Narrative Review: The promotion of Gabapentin: An analysis of internal industry documents. Steinman MA, Bero LA, Chren M, Landefeld CS. Ann intern Med. 2006;145:284-293.
3. Lurie N, Rich EC, Simpson DE, et al. Pharmaceutical representatives in academic medical centers: Interaction with faculty and housestaff. J Gen Intern Med. 1990;5:240-243.
4. Chren MM, Landefeld CS, Physicians behavior and their interactions with drug companies: a controlled study of physicians who requested additions to a hospital drug formulary. JAMA 1994;271:684-689.
5. Caudill TS, Johnson MS, Rich EC, McKinney WP. Physicians, pharmaceutical sales representatives, and the cost of prescribing. Arch Fam Med. 1996;5:201-206.
6. McKinney WP, Schiedermayer DL, Lurie N, Simpson DE, Goodman JL, Rich EC. Attitudes of internal medicine faculty and residents towards professional interaction with pharmaceutical sales
representatives. JAMA. 1990;264:1693-1697.
7. Steinman MA, Shlipak MG, McPhee SJ. Of principles and Pens: Attitudes and practices of medicine housestaff towards pharmaceutical industry promotions. Am J Med. 2001;110:551-557.
8. Blake RL, Early EK. Patients’ attitudes about gifts to physicians from pharmaceutical companies. J Am Board Fam Pract. 1995;8:457-464.
9. Gibbons RV, Landry FJ, Blouch DL, et al. A comparison of physicians’ and patients’ attitudes toward pharmaceutical industry gifts. J Gen Intern Med. 1998;13:151-154.2. Narrative Review: The promotion of
Gabapentin: An analysis of internal industry documents. Steinman MA, Bero LA, Chren M, Landefeld CS. Ann intern Med. 2006;145:284-293.
10.Shaughnessy and Slawson. Pharmaceutical representatives. BMJ 1996;312:1494.
11. Roughead EE, KJ Harvey, AL Gilbert. Commercial detailing techniques used by pharmaceutical representatives to influence prescribing. Aust NZ J Med 1998;28:306-310.
12. Ziegler MG, Lew P, BC Singer. The accuracy of drug information from pharmaceutical sales representatives. JAMA 1995;273:1296-1298.
13. Cardarelli R, Licciardone JC, Taylor LG. A cross-sectional evidence-based review of pharmaceutical promotional marketing brochures and their underlying studies: is what they tell us important and true? BMC
University of Vermont College of Medicine Office of Primary Care www.med.uvm.edu/opc
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