the complex ethics of academic-industry collaborations ross mckinney, jr, md duke university school...
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THE COMPLEX ETHICS OF ACADEMIC-INDUSTRY COLLABORATIONS Ross McKinney, Jr, MD
Duke University School of Medicine
Outline
What is Conflict of Interest? (COI) Areas of Concern Federal rule changes Duke processes
Don’t get the wrong message
In health care, almost no good idea will affect significant number of patients if it isn’t commercialized
Pharmaceutical & device companies don’t take care of patients – they need advice from people who do
Conflict of interest isn’t intrinsically bad – it’s a normal part of life
At Duke, we encourage working with industry (as distinct from for industry)
But…
Professionalism means putting the interests of your patients above your own self-interest
In research, professionalism means putting your science above your self-interests Economic (promotion, salary, grants) Social (status) Identification with an idea
We need to educate, but we should do so without marketing (e.g. CME v. speakers bureaus)
Definition - COI
A conflict of interest exists when a primary interest or responsibility is (unduly) affected by a secondary interest or responsibility
Real World Examples
Dental work Devils and Tar Heels
Key to the Example
Our perception is flavored by pre-set expectations and rationalizations of which we may not be aware
The whole crowd saw the same data, but drew very different conclusions
COI is part of every day life
Human beings are very aware of COIs Every sales encounter All fee-for-service medical encounters
The Human Response
We consider the paradigm, past history We consider the secondary influences we
can identify Can we trust the provider? If we break that trust as medical
providers, what happens? Decreased adherence / worse outcomes Poor word-of-mouth Malpractice cases
Be Aware
The public is paying increasing attention to examples of physicians appearing to act in self interest instead of the best interest of their patients
Should we collectively care?
A few industries
Airlines Pharmaceuticals Banking (71% trust in 2008 to 25% in
2011)
If people don’t respect and value physicians, will Congress use Medicare (i.e. physician payments) to balance the budget?
Areas of Concern
Clinical Research Clinical Care Education Commercialization of ideas
Concerns: In Clinical Research In science, reproducibility is the key test
for validation In clinical research, trials are often too
expensive to reproduce Don’t want to put people at risk
unnecessarily Primary means of validation is audit Audit is not generally effective as a means
to identify bias
Goals of COI Management in Research
Protect research subjects from biased decisions by conflicted investigators
Scientific integrity Do not want clinical decisions based on
data from biased studies Don’t want conflicted investigators
interpreting data Role of the Academic as the fair-broker
Free of bias (at least financial)
JAMA – 2003 – Als-Nielsen, et al 370 randomized trials Considered: 1) Outcome of trial; 2)
Sponsor Non-profit Sponsor - 16% recommended
experimental drug as treatment of choice Funding not reported: 30% Mixed funding: 35% For-profit organization: 51%
Difference significant (p<0.001)OR: 5.3; 95% CI 2.0-14.4)
NEJM Study - 2008
Studies of 12 anti-depressants, 12,564 patients
38 studies with positive FDA results, of which 37 were published, 1 not published
36 with negative FDA results 3 published, 22 not published 11 published with data selection to appear
positive In literature, 94% of publications were
positive Turner: NEJM 2008;258:252-260
Merck’s ADVANTAGE study - 2003
ADVANTAGE study: Assessment of Differences between Vioxx and Naproxyn to Ascertain Gastrointestinal Tolerance and Efficacy
After 3 months, 27% more people stopped taking Naproxyn than Vioxx
Discontinued
% Discontinued
Brief Illustration
After 3 months, 27% more people stopped taking Naproxyn Of course, that was 5.9% vs 8.1%
5
7.5
10
5.9
8.1
Discontinued
% Discontinued
Brief Illustration
After 3 months, 27% more people stopped taking Naproxyn Of course, that was 5.9% vs 8.1%
0
2.5
5
7.5
10
5.9
8.1
Discontinued
% Discontinued
Brief Illustration
or better, 94% vs 92% tolerance
0
25
50
75
100
94.1 91.9
Discontinued
% Remaining on original Rx
Seeding Study
ADVANTAGE was designed by the marketing department at Merck
Real subjects were the MDs Did use of study increase prescription rate? Complimented enrolling doctors Used many primary care sites, rather than
a few high enrolling centers
Brief Illustration
Personal experience – cost difference to me was 30x ($150 vs $5) [actually Celebrex vs ibuprofen]
Points like this have Congress’s eye as potential cost savings & unnecessary expenses
Migrate decision making from physicians to non-experts because of failure of physicians to perform the work of an expert adequately
The Complicated Question
Bayh-Dole Act of 1980 Inventions
Personal and institutional conflict Safety concerns increase in import The “rebuttable presumption” Where’s the right balance?
Concerns: In Clinical Care
The fee for service model Note articles about inappropriate use of
open breast biopsies (vs. needle), stenting of chronic stable angina, of spine surgery, of in-house diagnostic and treatment devices, of infusion therapies where the primary beneficiary seems to be the infuser rather than the infused
Insertion of flawed devices by physician developers and advocates
Routine procedures with reimbursement (EKGs, etc)
Concerns: In Education
FDA Rules about talking off label Speaker’s bureaus If you know someone is being paid to
give a talk, does it change your perception of the message?
Concerns: In Education
FDA Rules about talking off label Speaker’s bureaus If you know someone is being paid to
give a talk, does it change your perception of the message?
What if it’s true, but you don’t know?
Physician Sunshine Act
Section 6002 of the Affordable Care Act As of January 2012, pharmaceutical and
device manufacturers must report all gifts and payments to physicians and teaching hospitals to a federal database
Threshold is $10 per item, or $100 per year
Results will be published in 2013 in a web based, searchable format
Public awareness
What will the ramifications be of public disclosure?
An example, using the fact Minnesota has had a public database for several years
New York Times article
Front Page – May 10, 2007 “Psychiatrists, Children and Drug
Industry’s Role” “When Anya Bailey developed an eating
disorder after her 12th birthday, her mother took her to a psychiatrist at the University of Minnesota who prescribed a powerful antipsychotic drug called Risperdal.”
The problem
Anya gained weight but within two years developed a crippling knot in her back. She now receives regular injections of Botox to unclench her back muscles. She often awakens crying in pain.
The COI
In 2003, the year Anya came to his clinic, Dr. Realmuto earned $5,000 from Johnson & Johnson for giving three talks about Concerta.
The COI
In 2003, the year Anya came to his clinic, Dr. Realmuto earned $5,000 from Johnson & Johnson for giving three talks about Concerta.
However, not clever to say – “Academics don’t get paid very much. If I
was an entertainer, I think I would certainly do a lot better.”
The COI
In 2003, the year Anya came to his clinic, Dr. Realmuto earned $5,000 from Johnson & Johnson for giving three talks about Concerta.
However, not clever to say – “Academics don’t get paid very much. If I
was an entertainer, I think I would certainly do a lot better.”
(Dr. Realmuto’s university salary is $196,310.)
Minnesota case
Was it really the result of COI? Amount of money was small Adverse events happen
Perception of outsiders may differ from our own
Malpractice attorneys eagerly awaiting the federal database
The role of gifts
Duke rules prohibit gifts, including meals, from pharmaceutical and device reps Unrestricted educational grants to the
institution are allowed True CME can be supported – no quid pro
quo allowed Gifts are a part of relationship building
Reps goal is to convert the relationship from a business one to a personal one
Airline example
NIH Rules Recently Changed
$5,000 threshold for management and reporting to the NIH All cases of FCOI of $5K or more.
Must report all sponsored travel (other than government, universities, and medical centers)
Require review of all personal FCOIs prior to any NIH grant expenditures (even on renewal)
Web site to post all FCOIs linked to grants (perhaps)
Process
Annual report in March Review (in order) Review each grant application Review IRB submissions Review each grant award Now consider purchasing, research, and
(to a degree) clinical issues
Limits
Require annual reporting of all relationships >$600/year (likely to except universities, academic medical centers, government, and research institutes)
As of January 1, management at $5K/year if there is an overlap with research
At $25K/year, can no longer be PI on related research
Other limits
Treat equity as if it’s payments ($20,000 in stock is the same as $20,000 in payments)
Non-publically traded equity is treated as >$25K
Stock options are treated as >$25K We look at royalty arrangements case-
by-case
Summary
Conflict of Interest is present in everyday life
Providing transparency is critical Public perception may different from the
insider’s view If we want to remain professionals, we
need to maintain the interests of our patients first