Date post: | 20-Dec-2015 |
Category: |
Documents |
View: | 215 times |
Download: | 0 times |
Marketing Tactics of the Pharmaceutical Industry
Gundy Sweet, PharmD, FASHPDirector, Drug Information Service
Clinical Associate ProfessorUniversity of Michigan
May 2009
2
Disclosure
Gundy Sweet discloses no relevant financial relationships with commercial interests
3
Objectives At the conclusion of this program, you
will be able to: Name 5 marketing tactics used by the
pharmaceutical industry Define 2 ways in which industry can
influence the published data State 2 reasons why the industry moved
towards physicians as speakers
4
Overarching Questions Why may doctors prescribe drugs that
are marginally effective?
Why are patients given drugs that have risky side effects when safer agents may be available?
Why are prescriptions written for costly agents when less costly agents are available?
5
Marginally Effective Drugs Lyrica for fibromyalgia
Placebo-controlled trials (2) 1-week Pb wash-in; 13*- or 14^-week DB treatment Outcomes
Change in pain score from baseline >30% improvement from baseline
Results Both studies showed a significant decrease in
pain score with L vs Pb Only the second trial showed a significant
difference in percent of patients who achieved >30% improvement
42-50% of those receiving L compared to 30% of those receiving Pb
16-33% of L discontinued due to adverse event
*Mease P et al. J Pain. 2008;9:792-805.^Arnold L et al. J Rheumatol. 2008;35:502-14.
6
Marginally Effective Drugs Lyrica for fibromyalgia
Durability trial 6 weeks of Lyrica to all to identify
optimum dose Responders (54%) randomized to
placebo (Pb) or Lyrica (L) for 26 weeks Primary outcome: loss tx response
(<30% decrease pain score) 60% receiving Pb and 30% receiving L 17% receiving L dropped out due to
adverse events
Crofford L et al. Pain. 2008;136:419-31.
7
Drugs with Safety Concerns Darvon (Lilly): came to market in 1957
Data Propoxyphene no better than aspirin or
acetaminophen for pain control Known problems with addiction/risk of death from
overdose Lilly continued to market the drug which
brought them $100 million/yr 1979 Natl Insti Drug Abuse – 1100
deaths/yr FDA then mandated educational campaign,
but it was too late for MDs and patients
8
Drugs with Cost Concerns Numerous drug classes have seen “new
and improved” versions of older drugs Non-sedating antihistamines PPIs
The newer agents typically come at an increased cost, some of which are sizeable
What do we get for our money? Increased efficacy? Increased safety? Nothing?
9
The journey of drug therapy…
MD prescribes
drug
Insurance/ patient pays
for drug
Patient consumes/ uses drug
Data sources include:- Drug reps- Published data- Colleagues
May end up paying for a higher cost drug when it was not needed.
May end up taking a drug for which safety data are not well known.
Pharmaceutical industry has
influence in all of these avenues
10
The journey of drug therapy…
MD prescribes
drug
Insurance/ patient pays
for drug
Patient consumes/ uses drug
Data sources include:- Drug reps- Published data- Colleagues
May end up paying for a higher cost drug when it was not needed.
May end up taking a drug for which safety data are not well known.
11
History of Pharmaceutical Marketing Pharmaceutical marketing is not a
new industry practice Reps started calling on MDs in the mid-
1800s Building relationships with MDs with the
goal of selling product
12
Effects of Reps Starts Early
Pharmaceutical industry influence starts early in MD training:* first stethoscope free lunches during educational programs textbooks weekend trips to ideal locations to
hear talks about new drugs financial incentives to attend educational
programs (fancy dinner and an honorarium)
*Note that 2009 PhRMA Guidelines will stop some of this
13
Power of the Sales Force Sales force increased
1995: 38,000 reps 2005: 100,000 reps
2.6 fold increase in 10 years 1 rep: 6 MDs (1 rep: 2.5 targeted MDs)
MDs were swamped by reps and began to feel justified in accepting gifts for lost time with patients
14
Power of the Sales Force New generation reps evolved in 1990s
“Older” reps needed to be savvy and resourceful to get prescribing data
New reps had electronic prescribing data handed to them
Marketing firms (eg, IMS) collect the data on prescriptions written in pharmacies and sell the data to pharmaceutical industry
Sale of data sent $44 million to AMA in 2005 Reps now knew exactly who prescribed
what products, how much, and how often
15
Techniques Used Prescribing incentive programs (e.g.,
Inderal LA) Unrestricted educational grants Samples or vouchers
Only provided for most promoted, usually most costly drugs
Allows rep to gain access to MDs Research money
Pharmaceutical industry funds >70% of research (vs 30% 30 years ago)
Power of funding influences prescribing
16
The journey of drug therapy…
MD prescribes
drug
Insurance/ patient pays
for drug
Patient consumes/ uses drug
Data sources include:- Drug reps- Published data- Colleagues
May end up paying for a higher cost drug when it was not needed.
May end up taking a drug for which safety data are not well known.
17
Industry Effect on Published Data For FDA-approved drugs, public disclosure
of trials is available through: FDA Summary Basis of Approval document Study summaries in the package insert Published literature in peer-reviewed journals
37% of clinical trial abstracts never get published
Clinicians need full access to data to make informed decisions for patient care
But does that happen?
18
Industry Control of Journal Content Betty Dong and levothyroxine
1986: Synthroid (Knoll Pharmaceuticals) and
UCSF investigators (Betty Dong/Francis Greenspan)
Study to compare Synthroid to other forms of levothyroxine (4 products studied)
Dong signed a contract with Knoll Included a clause stating that results were
confidential and could not be released without consent from the manufacturer
19
Industry Control of Journal Content
1990: Results: 4 products were equivalent Manuscript accepted by JAMA Knoll threatened lawsuit if published
1995: Modified report published by Knoll - products
not equivalent - Dong not an author 1997:
Dong article was published (JAMA. 1997;277:1205) Suppression of findings by Knoll impacted clinical
practice and cost of treatment for many years
20
Selective Publication Selective publication of trials
Evaluated 12 antidepressants All phase II and III studies registered with
FDA between 1987-2004 Compared outcomes in FDA analysis to
matching publications 74 studies were identified in the FDA
database 51 (69%) studies were published
Turner et al. N Engl J Med 2008;358:252-60.
21
Selective Publication
Study Outcome by FDA Analysis
Published agrees with FDA decision
Published conflicts with FDA decision
Study not published
Positive (n=38)
37 (97%) 1 (3%)
Questionable (n=12)
6 (50%) 6 (50%)
Negative (n=24)
3 (12%) 5 (21%) 16 (67%)
N Engl J Med 2008;358:252-60.
22
Selective Publication Does selective publication happen across the
board? All 90 new molecular entities approved, 1998-
2000 Purpose: how often trials are published 909 studies in the FDA Summary Documents 43% of these studies were published
32% published prior to FDA approval 92% published within 3 years of approval
Characteristics of published studies larger sample size, good study design (randomized,
blinded), and favorable study outcomes
Lee K. PLoS Medicine. 2008;5:1348-56.
23
Selective Publication Does selective publication happen across the
board? All 90 new molecular entities approved, 1998-2000 909 studies in the FDA Summary Documents 43% of these studies were published
32% published prior to FDA approval 92% published within 3 years of approval
Characteristics of published studies larger sample size, good study design (randomized,
blinded), and favorable study outcomes Conclusions
Publication of favorable outcomes consistent with findings seen for select reviews
Concern – healthcare professionals do not have access to the true risks/benefits of new drugs without seeing all available data
Lee K. PLoS Medicine. 2008;5:1348-56.
24
Controlling Content of Journals
UCSF investigators assessed: Extent of publication Whether or not concurrence with FDA
analysis Outcomes and conclusions
All NME approved in 2001-2002 (n=33) All trials submitted to FDA that had a
comparator group (n=164)
Rising K et al. PLoS Medicine. 2008;5:1561-70.
25
Controlling Content of JournalsExtent of publication 128 (78%) of trials in NDA were published
Active controls & favorable outcomes 80% had 1 author & 15% had all authors with ties to
industry
Concurrence with FDA analysis 43 outcomes in FDA documents did not favor NME
20 (47%) not included in published report 5 of remaining 23 changed in published data
10 conclusions in FDA documents did not favor NME
9 of these conclusions changed in publication to favor test drug
Rising K et al. PLoS Medicine. 2008;5:1561-70.
26
Controlling the Journal
Australasian Journal of Bone and Joint Medicine
•Published by Elsevier (credible)
•2003-2005
Elsevier•No disclosure of Merck funding in journal•Printed excerpts of peer-reviewed articles or summarized articles•Emphasis on studies favorable for Vioxx and Fosamax
Advisory Brd
•“Honorary”•Australian rheumatologist •Never rec’d single paper for peer review
Merck•Phony journal that resembled peer-reviewed journal•Used as a marketing piece
27
The journey of drug therapy…
MD prescribes
drug
Insurance/ patient pays
for drug
Patient consumes/ uses drug
Data sources include:- Drug reps- Published data- Colleagues
May end up paying for a higher cost drug when it was not needed.
May end up taking a drug for which safety data are not well known.
28
Colleagues as Educators Industry has many different
relationships with healthcare providers: Advisory board memberships Involvement with speakers programs Paid to be thought leaders for ghost written
articles Industry is major source of funding for
CME Accreditation Council for CME - in 2003,
90% of the $1 billion spent on CME came from industry
29
Colleagues as Educators 2005: industry profits leveled off
Pharmaceutical sales force saw cuts Industry hired more MDs as speakers
Thought leaders or key opinion leaders Purpose – to persuade colleagues to use the new
drugs Result….
Industry paid MD to give a talk
Audience of MDs, sometimes paid to listen
And sometimes, also a great meal for all
30
Colleagues as Educators Relationships with industry became
lucrative for MDs Some MDs were found to have
incredible incomes from industry Estimated that 25% of MDs participate in
speakers bureaus Reports of earning >$300K/yr
Recent report of a world-renown psychiatrist receiving $1.6 million in consulting fees over 7 yearsAre disclosure laws
needed?
31
Increased Transparency
Several states have implemented laws mandating disclosure of payments to healthcare professionals by the pharmaceutical industry
Disclosures are publicly available in some states……..……….or are they?
32
Increased Transparency Study to determine:
Magnitude of payments (>$100) in Vermont and Minnesota
Accessibility and quality of data available to the public
Ross JS et al. JAMA. 2007;297:1216-23.Ross JS et al. JAMA. 2008;300:1998-2000.
33
Ease of access to the data Vermont
Payment disclosures available from Office of Attorney General
Web-based annual summaries, aggregate data
Drug companies can declare payments as trade secrets
61% of reports had missing data Only 10% of original reports had usable MD data
Freedom of Information Act request (took 1 year) and Public Citizen lawsuit against Attorney General (took 2 years) to get full disclosure
34
Ease of access to the data Minnesota
Payment disclosures from Board of Pharmacy
Only available in original paper submission forms, filed by year
Data were not available as a public report
35
So is transparency working? The laws in place are a start, but they
are inadequate Incomplete disclosure and insufficient
access Changes are needed to improve the
system Disallow trade secret exception Require state agency enforcement Appoint responsible party for collecting
and providing data in a usable format
36
Why Colleagues as Educators?
Benefits of using MDs Talks by MDs generate 4x more
prescriptions than those by reps ROI was 2x
Lucrative marketing tactic for off-label uses (which is illegal for reps)
But it all came to a head in 2004…………..
37
The Neurontin Story Neurontin (gabapentin, Warner-
Lambert) was approved in 1993 for seizures
Allegations of off-label use began in 1996 by a whistle-blower (Dr. Franklin, MSL)
Aggressive, elaborate, complex, organized, $40M marketing strategy Extensive off-label promotion for multiple
indications pain, migraine, bipolar disorder, ADD,
monotherapy for epilepsy, restless leg syndrome
•For many of these indications, there were no data to support the use•For some indications, there were data showing that Neurontin was no better than placebo
38
The Neurontin Story Tactics
Targeted key MDs Used MD-champions for peer-to-peer selling Paid MDs to attend ‘consultant meetings’ or
‘advisory boards’ Paid MDs to moderate teleconferences Sponsored ‘independent’ CME through
unrestricted educational grants Paid MDs to allow rep-preceptorships Created speakers bureaus using influential
MDs Provided ‘grant’ money for ‘research’
•Frequent RXers of anticonvulsants•MDs with potential to influence others
“One of the most effective ways” for off-label marketing
•…but they weren’t providing any advice•Received generous honorarium, expensive meals, paid trip•Heard talks on off-label use
Rep spent the day with the MD, seeing patients, and ‘offering advice’
•STEPS trial – Neurontin titration to effectiveness•Uncontrolled, open-label design•MDs told to increase dose until seizure free, up to 3600 mg/d•Over 700 MDs participated, ave of 3 patients per MD, rec’d $300/pt•Published paper said evaluated effectiveness•Internal documents said goal was to teach MDs to push the dose higher to clinical effect
39
The Neurontin Story Did the plan work?
1995 sales – $97.5 million 2003 sales - $2.5 billion 2000 – 78% of sales were for off-label
indication In 2004, 8 years after the suit was
initially filed, Pfizer pleaded guilty to fraudulent marketing and violating FDCA
Coincidentally, the patent on Neurontin expired in 2004
40
The Neurontin Story Settlement with Pfizer was for $430
million Criminal fine, civil liabilities for fraud,
fines to consumer protection agencies, and $27 million to whistle blower
But was it worth it? Neurontin generated $2.5 billion in
2003 alone compared to $98 million in 1995
Steinman MA et al. Ann Intern Med. 2006;145:284-93.
…and in January 2009 Eli Lilly agreed to pay $1.42 billion for off-label promotion of Zyprexa….and recently, Pfizer settled for $2.3 billion to stop an investigation into their off-label promotion of Bextra and other drugs
41
Lessons Learned The Neurontin case greatly increased
awareness of MDs and the public to the marketing tactics and deceit being used by the industry….
…. led to changes that we are still seeing today.
42
What can you do???????
43
Ways to Regulate Influence Realize that the pharmaceutical
industry is a business They have a fiduciary responsibility to
their shareholders
44
Ways to Regulate Influence Understand that the information which comes
from reps/industry is often biased or distorted Know how to sort through the data Realize that published reports tend to favor
studies with positive outcomes Be familiar with guidelines on ethical interactions
from AMA, ACCP and PhRMA New push for tighter controls between
Professional Medical Associations and PhRMA funding (JAMA. 2009;301:1367)
45
On An Institutional Level Consider policies that restrict access
of pharmaceutical reps in health systems: Require an appointment to conduct
business Don’t allow food for meetings Don’t allow gifts of any sort Don’t allow samples and require approval
of vouchers
46
When reviewing new drugs Require disclosure of potential conflict
of interest for those involved with drug selection/purchasing decisions
Review published literature carefully Pull FDA Summary Document to
identify data that may be missing Review clinicaltrials.gov to see all
hypothesis-testing studies conducted and a synopsis of the results
47
On A Personal Level Be aware of the realities of the
business world Don’t cave in to marketing pressures Maintain high ethical and moral
standards Know and understand the limitations
of the published literature and educate others accordingly
48
And remember, the industry will always come out with something new……..
EXCEDRIN® EXPRESS GELS™ YOUTUBE VIDEO CONTEST
The Contest (Fall 2008):• Make a short video about an amazing feat of speed • Submit your video and you could win the grand prize of $15,000