Health Care Governance, Leadership
and Ethics: A Physician’s View
Roy M. Poses MD
President
Foundation for Integrity and Responsibility in Medicine
Clinical Associate Professor
Alpert School of Medicine, Brown University
Original Session Description
• Governance of health care organizations is increasingly
unrepresentative of key constituencies, unaccountable,
opaque, and independent of ethical standards. The
leadership of health care organizations is increasingly illinformed, incompetent, self-interested, and corrupt. The
results include suppression and manipulation of clinical
research, transformation of medical education into
marketing, and distortion of health policy discussion. Yet it
has become politically incorrect to address these issues,
which are doubtless major causes of increasing health care
costs, and declining access, quality, and professional
morale.
Outline
•
•
•
•
•
•
•
•
Why are we miserable? – qualitative study
Case-study: AHERF
Conceptual model of health care dysfunction
Historical background
Conflicts of interest
Bad leadership
Case studies
What can be done?
A Continuous Health Care Crisis
• “Aura of inevitability” about health care reform in 80’s and
90’s in the US
• Reasons for reform then: cost, quality, access
• In the new century, after failed attempt at legislative
reform
– Costs still rising, e.g., increased costs of insurance, new
deductibles and co-pays
– Quality no better, e.g., IOM “Crossing the Quality
Chasm”
– Access worse, e.g., increasing numbers of uninsured,
Medicare fee cuts leading to physicians dropping
Medicare
Health Professional Dissatisfaction
• Unlike in 80’s and 90’s, physicians and other health care professionals
are increasingly dissatisfied
• Proportion of physicians who felt they make the wrong career choice:
– 1973 - 15%,
– 1995 - 40% (1)
• US Physicians 2006 (2)
– Low morale – 35%
– Depressed – 32%
– Burned out – 67%
– Considering leaving practice – 60%
1. Zuger A. NEJM 2004; 350: 69. 2. Steiger B. Phys Exec Nov 2006.
Introduction to the ABIM/ ACP-ASIM/ ESIM
New Physician Charter
• “Physicians today are experiencing frustration as changes in
the health care delivery systems in virtually all
industrialized countries threaten the very nature and
values of medical professionalism.”
– But the changes and how they threaten professionalism not further
defined
• “We share the view that medicine’s commitment to the
patient is being challenged by external forces of change
within our societies.”
– But the external forces not otherwise described
ABIM Foundation. Ann Int Med 2002; 136: 243
Background: A Qualitative Study of
Physicians’ Concerns about Health Care
• In 2002, motivated by a sense that health care was going
very wrong, but no one could quite their fingers on the
cause • Asked physicians open-ended questions about their
concerns
• Compiled and described their major themes in “A
Cautionary Tale: The Dysfunction of American Health
Care”
• Physicians raised many striking cases suggesting a
dysfunctional health care system was threatening
physicians’ core values
Poses RM. Eur J Int Med 2003; 14: 123.
Outline
•
•
•
•
•
•
•
•
Why are we miserable? – qualitative study
Case-study: AHERF
Conceptual model of health care dysfunction
Historical background
Conflicts of interest
Bad leadership
Case studies
What can be done?
The Allegheny Health Education and Research
Foundation (AHERF) Case: Background
• From Allegheny General Hospital in Pittsburgh (1968) to
largest health care system in Pennsylvania (1997)
• CEO was Sherif Abdelhak, called a “visionary,” “genius,”
• By 1995, Abdelhak earned $1.2 M, 3 times the median for a
health system CEO
• Abdehak gave John D. Cooper Lecture at AAMC (1996),
published in Academic Medicine
– “We will need to create new forms of organization that are more
flexible, more adaptive, and more agile than before”
– “Unleash the creativity and productive potential of every
individual and provide an environment that encourages teamwork”
The AHERF Case: Events
• In 1997, although Abdelhak was still publicly announcing
expansion plans, debt was soaring
• Losing $1 M / day, Abdelhak raided restricted endowments
• In 1998, Abdelhak fired, AHERF declared Chapter 11
bankruptcy, $1.2 billion in debt
– second largest bankruptcy in US at that time
• Allegheny University of Health Sciences downsized,
multiple hospitals closed, multiple lay-offs
• Multiple lawsuits filed
– Securities and Exchange Commission settled civil fraud charges
against AHERF ex-CFO McConnell and two Vice Presidents
– SEC filed suit against AHERF auditors
• Abdelhak sought plea bargain, sentenced to 11-23 months
The AHERF Case: Revelations and Responses
• Abdelhak revealed to have ruled by intimidation:
– Dominated board, forced admission of his wife to medical school and had dean who
protested fired
– Speech to faculty, “Don’t cross me or you’ll live to regret it.”
– “Most faculty realized this was a dictatorship…. It was an organization run by fear and
reprisal.”
• Outrage by ex-AHERF Doctors:
– “colossal disaster that could have been avoided,” “obscene,” “an atocity,”
“repugnant”
– Abdelhak “never took responsibility for bringing the system down”
• Uwe Reinhardt, health economist: “the lunacy that is acceptable would make you
throw up”
• Tepid response of national organizations:
– CEO of AAMC: “unprecedented for a medical school to be caught up in this type of
bankruptcy”
– LCME: would help place students if AUHS bankrupt
– JCAHO: Hahnemann Hospital “not cited for any deficiencies”
– AMA, ACP, AAFP, other specialty organizations, ACGME, ABIM, other boards, DHHS
-?
The AHERF Case: in the Literature
• Burns et al article in Health Affairs, covered events through
mid-1999, but not outcome of most legal proceedings, and
concentrated on debt financing issues[1]
• Nothing in any large-circulation journal (including news
sections)
• Nothing in Academic Medicine since Abdelhak’s paper
– which has never been cited
• First article that mentioned Abdelhak’s conviction: Poses in
Euro J Int Med in 2003[2]
1. Burns LR. Health Affairs 2000; 19: 7. 2. Poses RM. Eur J Int Med
2003; 14: 123
AHERF Key Points
• Small group of insulated leaders, largely
unaccountable
– put their self-interest first
– intimidated professionals, suppressed dissent
• The organization’s governance structure failed to
inhibit them
• Bad results for patients, professionals, students, the
community,…
• Why did everyone believe the hype?
• Where was the outrage?
• Why is there still silence?
Outline
•
•
•
•
•
•
•
•
Why are we miserable? – qualitative study
Case-study: AHERF
Conceptual model of health care dysfunction
Historical background
Conflicts of interest
Bad leadership
Case studies
What can be done?
Hypothesized Causes of Dysfunction:
Organizational Process and Structure
• Health care is increasingly dominated by large organizations
• The organizations’ leadership may be:
–
–
–
–
–
–
–
Autocratic, “imperial”
Insulated
Uninformed about health care context, indifferent to health care values
Incompetent
Self-interested
Conflicted
Corrupt
• The organization’s governance structures enable such leadership
• The organization may use tactics including:
– Deception, delusion, disinformation
– Intimidation, coercion, perverse incentives, conflicts of interest
Organizational Structure
and Process
Organizational
Tactics
Poor
Governance:
Unrepresentative
Unaccountable
Delusion
Disinformation
Outcomes
Increased
Cost
Decreased
Access
Deception
Opaque
Not Subject to
Ethical Standards
Medical
DecisionMaking, Health
Care Process
Threats to
EvidenceBased
Practice
Poor Quality
Demoralized
Professionals
Poor Leadership:
Autocratic
Isolated
Uninformed, Indifferent
Incompetent
Self-Interested
Conflicted
Corrupt
Intimidation
Coercion
Perverse
Incentives
Conflicts of
Interest
Threats to
Core
Values,
Ethical
Practice
Suffering
Disability
Disease
Death
Conceptual Model
Outline
•
•
•
•
•
•
•
•
•
Why are we miserable? – qualitative study
Case-study: AHERF
Conceptual model of health care dysfunction
Historical background
Conflicts of interest
Anechoic effect
Bad leadership
Case studies
What can be done?
Historical Background
• From professional ethics and the missions
of not-for-profit organizations to laissez
faire (robber baron?) capitalism
Health Care Not a Free Market
• Arrow (1963) “argued that medical care cannot conform to
market laws because patients are not ordinary consumers
and doctors are not ordinary vendors. He said that sick or
injured patients must rely on physicians in ways
fundamentally different from the price-driven relation
between buyers and sellers in an ordinary market. This
argument implied that, contrary to the assumptions of
antitrust law, market competition among physicians cannot
be expected to lower medical prices. And since physicians
influence decisions to use medical services far more than
patients do, the volume and types of services provided to
patients—and hence total health costs—need to be
controlled by forces other than the market, such as
professional standards and government regulation.”
Relman A. NY Rev Books, July 2, 2009
Professional Ethical Standards Through the
1970s
• Through the 1970s, the ethical code of the AMA
said:
– “in the practice of medicine a physician should limit the
source of his professional income to medical services
actually rendered by him, or under his supervision, to
his patients”
– “the practice of medicine should not be commercialized,
nor treated as a commodity in trade”
The Demise of Professional Ethical
Standards
• Health care economists regarded “professional norms as
monopolistic constraints on contractual possibility.”(1)
• “The 1975 Supreme Court ruling that the professions were
not protected from anti-trust law undermined the
traditional restraint that medical professional societies had
always placed on the commercial behavior of
physicians….”(2)
• “In 1980, after medical organizations lost some costly
antitrust trials, in which they were accused of such offenses
as limiting doctor fees or denying staff privileges, the
AMA changed its ethical guidelines, declaring medicine to
be both a business and a profession. This lowered the
AMA's barriers to the commercialization of medical
practice….”(3)
1. Bloche MG. J Health Politics Policy La2 2001; 26:1099. 2. Relman
AS. JAMA 2007; 298: 2668. 3. Relman A. NY Rev Books, July 2,
2009
Breaking the Medical “Guild”
• Enthoven, the architect of “managed competition,” one of
the leaders of Jackson Hole, published a book in Europe in
which he
– identified physicians as members of a tightly-knit guild
that was responsible for high health care costs
– so to control health care costs, his main goal was “to
break up the guild,” and transfer physicians’ supposed
power to managers
Enthoven A. Theory and Practice of Managed Competition in Health
Care Finance. Amsterdam: North-Holland, 1988.
A Plague of Managers
2500
2000
1500
1983
1990
2000
in K
1000
500
0
Physicians
Nurses
Managers
Health Care Not-for-Profits Become
Like Businesses
• First, in the time of Enron, Worldcom, Global
Crossing, etc
– which were run by “morally challenged executives,” (1)
– from a culture of “infectious greed,” (2)
1. Sen. John McCain 2. Alan Greenspan, Chair, Fed Reserve
Health Care Not-for-Profits Become
Like Businesses
• Now, in the time of AIG, Bear Stearns,
Fannie Mae, Freddie Mac, Lehman
Brothers, Merrill Lynch, etc, etc, etc
Health Care Not-for-Profits Became Like
Businesses
• Now, in the time of Bernie Madoff, Alan Stanford,
etc, etc,
Health Care Not-for-Profits Became Like
Businesses
• “The filthy rich … are different. It is not just that they’re
rich but that there’s something about being extremely rich
that blurs ordinary perspective in all but the most
exceptional people. Power may corrupt, but extreme wealth
blinds and deafens.”(1)
• “Much of the financial engineering, the fancy new
derivatives and balance-sheet legerdeman, was part of a
bubble that would one day burst…. Many of these hustlers,
gamblers and pugilists were helping to misallocate capital
on a fantastic scale…. They were telling America just what
they thought of it.”(2)
1. Marrin M. Times (UK), March 1, 2009. 2. Frank T. Wall Street
Journal, Feb 11, 2009
How Academic Medicine’s Leaders Forgot Its
Mission
• Academic health centers (AHCs) became dependent on
huge cash inflows from Medicare and commercial insurance
• Cost rises lead to cost containment
• In response, medical schools and AHCs “were content to go
where the money was....”
• So, “financial success, the measure of the marketplace,
has become the dominant standard of measurement of
‘value’ for most academic medical centers.”
Ludmerer KM. Time to Heal. New York: Oxford University Press,
1999
Academic Medicine’s Leaders Forgot Its Mission II
• Furthermore, “hospital administrators increasingly had
M.B.A degrees.... assumed business titles..., demanded and
received corporate levels of compensation, and retained
hordes of management consultants.”
• Thus, “medical school and hospital officials approached
academic medical centers much as if those institutions
were making cars or breakfast cereals. They applied the
same management strategies to medical centers that were
widely being used in other ‘industries.’”
Ludmerer KM. Time to Heal. New York: Oxford University Press,
1999
AAMC Redefines the Academic Mission
• Research universities must respond to “societal demands that they
become engines of economic development….”
• “Academic medicine… finds itself struggling to create a precarious
equipoise between the world and values of commerce and those of
traditional public service….”
• “In our capitalistic economy the pathway by which research invention
becomes beneficial application is often totally dependent on venture
capital, the availability of which commonly demands the active
participation of academic inventors in the commercial venture; put
simply, no participation, no money. It is this demand … that has
driven the dramatic increase in medical faculty entrepreneurship.”
Korn D. JAMA 2000; 284: 2234.
Academic Medical Centers: “Show Me the
Money”
• The medical school mission is to teach medicine, and in doing so,
provide excellent patient care and perform excellent research, but…
• Lee Goldman (interview in April, 2007, SGIM Forum) divided faculty
into:
– “Taxpayers” who generate more than they cost
– “Hired workers” who get paid to do a job
– “Loss leaders” who get short-term investments in the expectations they will
become taxpayers
– “Welfare recipients” - faculty with more tenuous status.
• “Bottom line, you should strive to be a 'taxpayer.‘”
• The primary criterion of success in academic medicine is now how
much money faculty bring in, from clinical practice or external grants,
not quality of teaching or academic work
Goldman L et al. SGIM Forum, April, 2007.
Academic Medical Centers As
“Cash Cows”
• At Virginia Commonwealth University:
– Approximately 1/8 of students are in health
sciences
– Approximately 2/3 of university president’s
salary comes from health sciences and
“private” sources
VCU News, Feb 20, 2009
Summary per Dr Arnold Relman
• “Endangered are the ethical foundations of medicine,
including the commitment of physicians to put the needs of
patients ahead of personal gain, to deal with patients
honestly, competently, and compassionately, and to avoid
conflicts of interest that could undermine public trust in the
altruism of medicine.”
• Threats arise from the “growing commercialization of the
US health care system.”
• We have come a long (and the wrong) way from an era
(1980) when the AMA said, “the practice of medicine
should not be commercialized, nor treated as a commodity
in trade.”
Relman AS. JAMA 2007; 298: 2668.
Outline
•
•
•
•
•
•
•
•
•
Why are we miserable? – qualitative study
Case-study: AHERF
Conceptual model of health care dysfunction
Historical background
Conflicts of interest
Anechoic effect
Bad leadership
Case studies
What can be done?
Conflicts of Interest
• The web that holds it all together
Background: Conflicts of Interest in
Academic Medicine
• Increasing concern about conflicts of interest
• Most attention to small gifts to physicians: pens,
coffee mugs, free lunches, reimbursement for
travel to educational meetings
• Brennan et al suggested banning even such small
gifts from pharmaceutical/ biotechnology/ device
companies
• Ban to be enforced by medical school leadership
Brennan TA et al. JAMA 2006; 295: 429-433
Conflicts of Interest – the Prevailing
Dogma (Brown U version)
• “[Conflicts of interest] are not unusual; they do not imply
wrong-doing or inappropriate activities. Rather, research
universities encourage interactions and the establishment of
relationships between faculty and business and industry.
The experience and knowledge gained through outside
consulting and service on advisory committees is valued for
its synergistic return to both research and student training.
Commercialization of faculty inventions and discoveries
through technology transfer brings the benefits of university
research to the public good. Faculty often play an important
role in successful commercialization efforts as scientific
consultants and in continuing research development
projects.
The Prevailing Dogma - II
• “[There is] increasing collaboration between industry and
research universities, the expectation that the universities
can and should be involved in the economic development of
their region and state, and the increasing interest of the
faculty in participation in entrepreneurial endeavors….”
• “Conflicts of interest often arise at the intersection of two
fundamental missions: to push the boundaries of knowledge
and to transfer that knowledge to the private sector for the
benefit of the public. With pro-active technology transfer
comes increasingly close relationships between industry and
university
The Prevailing Dogma – Conflicts
of Interest as Inevitable
• Interest of faculty in entrepreneurial
activities
• Synergies between commercial and
educational activities
• Need for technology transfer and
commercialization of discoveries
• Regional economic development
Alternative Definition – Individual
Conflict of Interest
• A individual conflict of interest occurs when a person with
entrusted responsibility has another interest that may
conflict with the proper exercise of that authority.
– Examples of people with entrusted responsibility:
• Physician responsible for putting the care of individual patients before all
other interests
• Teacher responsible for honestly imparting information, skills, judgment
• Researcher responsible for searching for and disseminating the truth
• Administrator responsible for fulfilling the mission of the organization
Compare and Contrast – Transparency
International’s Definition of Corruption
• Abuse of entrusted power for private
gain
What Individuals Have Conflicts?
• Physicians
• Other health care professionals
• Medical and health sciences school faculty, staff,
administration, leadership
• Staff and leadership of not-for-profit (NGO) organizations
–
–
–
–
Medical and health care societies
Health related charities
Research institutions
Disease advocacy groups, etc
• Staff and leadership of government agencies
• Employees and leaders of for-profit health care corporations
Alternative Definition – Institutional
Conflict of Interest
• A institutional conflict of interest exists
when an organization has an interest that
conflicts with its fundamental mission.
What Institutions Have Conflicts?
•
•
•
•
•
Medical and health science schools
Medical and health care societies
Health care charities
Research institutions
Disease advocacy groups
Who Are the Counter-Parties?
•
•
•
•
•
•
•
•
Pharmaceutical companies
Biotechnology companies
Medical device companies
Contract research organizations
Medical education and communication companies
Health insurers/ managed care companies
Health care information technology companies
Consulting firms
Grading Physicians’ and Medical
Faculty Conflicts of Interest
• Low level, most common – small gifts, meals,
trips to students, house-staff, faculty from industry
• Mid level, common – speaking fees, consulting
fees, royalties, advisory board memberships
(grants?) to “thought-leaders”
• High level, less common – service on for-profit
health care corporations’ boards of directors (plus
fees and stock options) for senior faculty, medical
school and university leaders
Prevalence of Conflicts of Interest:
Campbell Physician Study
• Surveyed random sample of US physicians in primary care
(GIM, family practice, pedi) and cardiology, general
surgery, and anesthesiology
• Asked about financial interactions with “drug, device, or
other medically related companies”
–
–
–
–
Drug samples
Gifts (food or beverages in the workplace, event tickets
Reimbursements (meeting admission or expenses)
Payments (consulting, speakers’ honoraria, advisory board, trial
enrollment)
• Response rate = 52%
Campbell EG et al. NEJM 2007; 356: 1742
Prevalence of Conflicts of Interest:
Campbell Physician Study
90
80
70
60
%
50
40
30
20
10
0
Samples
Gifts
Meetings
Payments
Prevalence of Conflicts of Interest:
Campbell Physician Study
• Odds ratio for university or medical school
practice as predictor of receiving payments
– 3.31 (95% CI 1.56- 7.05)
• This suggests that majority of academic
physicians are drug, biotech, or device
consultants, speakers, advisors, etc
Prevalence of Conflicts of Interest:
Campbell Department Chair Survey
• Surveyed chairs of medicine, psychiatry, two other clinical
departments, microbiology, one other nonclinical
department at all medical schools and 15 largest
independent teaching hospitals
• Asked about specific kinds of industry relationships of
individual chairs
–
–
–
–
–
–
Executive of company
Member of board of directors
Paid consultant
Member of scientific advisory board
Member of speakers’ bureau
Founder of company
Campbell EG et al. JAMA 2007; 298: 1779-1786.
Prevalence of Conflicts of Interest:
Campbell Department Chair Survey
Percentage
30
25
20
15
10
5
0
un
er
r
de
k
ea
ry
iso
dv
Non-Clinical
Fo
Sp
t
A
ic
n
lta
t if
ie n
Sc
u
ns
Co
or
ct
re
Di
e
iv
ut
ec
Ex
Clinical
Prevalence of Conflicts of Interest:
Campbell Department Chair Survey
• “60% of department chairs had some
form of personal relationship with
industry”
Selling Them the Rope:
Prevalence of For-Profit Health Care
Corporate Directors Among
Academic Medical Leaders
Roy M. Poses(1), Wally R. Smith(2),
Robert Crausman(3), Russell
Maulitz(4)
1. Foundation for Integrity and Responsibility in Medicine; 2.
Virginia Commonwealth University; 3. Brown University; 4. Drexel
University
Methods
• Cross-sectional prevalence study
• Population of corporations: 164 “pure”
public for-profit health care corporations
among the Standard & Poors (S&P) 1500
• Data: public biographies of board members
from proxy statements, annual reports or
web-sites, end of 2005
Results: Number of Corporate
Directors at Individual Schools
• Schools with any corporate directors:
65/125 (52%)
• Schools with 1-2 directors: 34
• Schools with 3-5 directors: 19
• Schools with 6-10 directors: 9
• Schools with >10 directors: 3
Results: Corporate Directors As Top
Operational Medical School Leaders
• 7 schools’ parent university presidents
• 11 university vice-presidents of health
affairs
• 5 medical school deans
• 11 academic medical center CEOs
• 22 (17.6%) of 125 schools had health care
corporate directors as top leaders
Results: Corporate Directors On Medical
School and University Boards
• 36 (28.8%) medical schools’ parent
universities’ boards of trustees included at
least one for-profit corporate health care
director
• 12 medical schools’ own boards of trustees
included at least one for-profit corporate
health care director
Psychology of Conflicts of Interest
• Conflicts of interest create mental confusion,
obscuring what we ought to talk about
• Fear of offending your conflicted colleagues or
supervisors
“People who have conflicts of interest often find
giving clear advice (or opinions) particularly
difficult.”
– Joe Collier, “The Price of Independence”
Collier J. BMJ 2006; 332: 1447.
Psychology of Board of Directors Level
Conflicts
• Service as a director requires “a duty of care,”
that is, “unyielding loyalty” to the
corporation’s stockholders
• Directors of a for-profit corporation have legally
enforceable fiduciary responsibilities to its
stock-holders for the corporation’s direction
and financial viability, including its
profitability
Monks RAG, Minow N. Corporate Governance, 3rd Ed. Blackwell:
2003
Effects of Conflicts of Interest
•
•
•
•
Practice, Clinical Decision Making
Medical Education
Clinical Research
Health Care Policy
Outline
•
•
•
•
•
•
•
•
Why are we miserable? – qualitative study
Case-study: AHERF
Conceptual model of health care dysfunction
Historical background
Conflicts of interest
Bad leadership
Case studies
What can be done?
Ethics and Leadership Issues: 2008
• Drugs, devices, biotech
– Neurosurgeon pleaded guilty to accepting kickbacks from device manufacturers
– Pfizer pulls Lipitor advertisements after “Dr” Jarvik found not to have medical
license
– Merck pays more than $600M to settle case alleging health care fraud and that it
bribed doctors
– Kyphon (Medtronic) submits to corporate integrity agreement
– Biovail pleads guilty to kickbacks and conspiracy
– GlaxoSmithKline and Novartis convicted of Medicaid fraud in Alabama
– Pfizer accused of suppressing and manipulating results of Neurontin studies
• Insurance / Managed Care
– HealthNet ordered to pay $9M damages for cancelling coverage after patient got
cancer
– Amerigroup settles charges of Medicaid fraud
– Anthem BC/BS and Wellpoint pay fines for revoking insurance policies after
policy-holders became ill, filed claims
– UnitedHealth settles lawsuit alleging it backdated stock options to benefit its
former CEO
Ethics and Leadership Issues II: 2008
• Academic Medicine
– West Virginia University leaders ousted after reports they gave pharma executive degree
without fulfilling requirements
– University of Florida Dean ousted after admitting politically connected, but dubiously
qualified medical school applicant
– Virginia Commonwealth University President retires early after secret grant from Philip
Morris, and his membership on tobacco wholesaler Universal Corp board revealed
– UCLA put Japanese Yakuza leaders at head of liver transplant line after they donated
money, journalist who reported story got death threats
– Stanford Chair of Psychiatry removed as PI of federal grant after his large stock holdings
in Corcept, the manufacturer of the drug the project was studying, revealed
– St Louis University settled case alleging its public health school overcharged federal
grants
– Dean of UMDNJ, politician who had part-time job there convicted of fraud, bribery
– Partners Healthcare denied knowledge that drug company funded research center was
created for marketing purposes
– Bernie Madoff resigns from Yeshiva University board, university admits large losses
from investments in his “Ponzi scheme”
– Flordia based fund raiser for Dana-Farber Cancer Center revealed to have marketed
Madoff funds
– Yale University settles charges it mismanaged federal grant funds
Ethics and Leadership Issues III: 2008
• Hospitals
– Financial director of Shriners Hospital for Children (St Louis) pleads guilty to mail fraud
– FBI raids Los Angeles hospitals, arrests CEO, alleging scheme that recruited homeless as
fake patients
– Memorial Regional Hospital (FL) resigns after his time in Navy brig revealed
– Staten Island University Hospital (NY) settles fraud charges
• Government
– Allegedly conflicted institute director leaves NIH
– Maryland outsourced cancer registry to Macro International, whose employees fabricated
data
– NIH reprimanded adminstrator who advocated transparency about conflicts of interest
• Not-for-profit
– Former financial director of Institute for Cancer Prevention pleaded guilty to lying to
federal investigators
• Other
– National Century Financial (health care financing company) CEO convicted of fraud
Ethics and Leadership Issues: 2nd Quarter 2009
• Bernie Madoff, former member of Yeshiva U board, convicted
• Quest Diagnostics settles case alleging sale of misbranded test kits
• NJ legislator guilty who lobbied for Hackensack Medical Center found guilty of
fraud
• Merck hired Elsevier to create fake “peer-reviewed” journals
• Wellcare accepts deferred prosecution for defrauding Florida Medicaid
• Synthes settles, will stop paying clinical trial investigators with stock shares
• Novo Nordisc settles charges it paid kickbacks to Saddam Hussein
• Medtronic consultant found to have falsified study results
• Sanofi Aventis settles charges it cheated Medicaid
• Chair of Partners board failed to disclose he owned medical education and
communications company which hired Partners faculty
• Lilly provided handbook for Zyprexa ghost-writers
• CVS pharmacy benefit manager helped to market Zyprexa
• Former HealthSouth CEO owes $2.88 billion in damages
American College of Physician Executives
Survey
How concerned are you about:
Gifts to executives
Conflicted executives
Gifts to board members
Conflicted board members
Unethical business practices
0
10
20
30
40
%
Slightly
Moderately
Weber DO. Physician Executive, March-April, 2005.
Very
50
60
American College of Physician Executives
Survey
Who is Involved in Unethical Business Practices in
Your Organization?
Physician
Executive
Board member
0
5
10
15
20
%
25
30
35
Transparency International’s Global
Corruption Report
• Corruption - alongside poverty, inequity, civil conflict,
discrimination and violence - is a major issue that has
not been adequately addressed.... It leads to the skewing
of health spending priorities and the leaching of health
budgets, resulting in the neglect of diseases and those
communities affected by them; it also means that poor
people often decide against life-saving treatment, because
they cannot afford the fees charged for health services that
should be free. Corruption in the health care sector
affects people all over the world.
• Corruption might mean the difference between life and
death for those in need of urgent care. It is invariably the
poor in society who are affected most by corruption
Transparency International’s Global
Corruption Report II
• But the scale of corruption is vast in both rich and poor
countries. Corruption deprives people of access to health
care and can lead to the wrong treatments being
administered.
• Corruption in the health sector is not exclusive to any
kind of health system. It occurs in systems whether they
are predominantly public or private, well funded or poorly
funded, and technically simple or sophisticated.
No other sector has the specific mix of uncertainty,
asymmetric information and large numbers of dispersed
actors that characterise the health sector. As a result,
susceptibility to corruption is a systemic feature of health
systems
Outline
•
•
•
•
•
•
•
•
Why are we miserable? – qualitative study
Case-study: AHERF
Conceptual model of health care dysfunction
Historical background
Conflicts of interest
Bad leadership
Case studies
What can be done?
Examples: Case Studies
• Distortion of the clinical evidence-base
• Pay for what sort of performance?
The Evidence Based Medicine Process
• Pick important clinical problem that affects defined
population
• Identify possible management options, and their possible
outcomes
• Systematic search for the best possible evidence
• Critical review of each study
• Assess outcome probabilities (for each option)
• Assess values (utilities) of possible outcomes
• Combine probabilities and values to determine option with
most favorable benefit vs harm, or highest expected utility
Threats at Each Stage of the EBM Process
• Pick important clinical problem that affects defined
populations
– Stealth marketing
• Identify possible management options, and their possible
outcomes
– Stealth marketing
•
•
•
•
•
Systematic search for the best possible evidence
Critical review of each study
Assess outcome probabilities (for each option)
Assess values (utilities) of possible outcomes
Combine probabilities and values to determine option with
most favorable benefit vs harm, or highest expected utility
Stealth Marketing Campaigns
• Pharma and other organizations orchestrate elaborate
marketing campaigns to sell products or services
• Goals include:
–
–
–
–
Increasing awareness of the relevant disease or problem
Making the problem appear more salient or more important
Emphasizing short-comings of existing approaches and treatments
Then, emphasizing advantages of the new product or service
• Often executed in part by medical education and
communication, or medical information companies
(MECCs or MICs)
• Elements of these campaigns may be covert, failing to
identify the sponsoring organization
Wyeth Fenfluramine-Phenteramine (Fen-Phen) Stealth
Marketing Campaign Case
• Marketed obesity as a serious health issue using slogans like:
– “Obesity – the Public Health Crisis”
– “Obesity – a Chronic Disease”
• Gave grants to
– Professional organizations, e.g., American Academy of Family Physicians,
American Society of Bariatric Physicians
– Disease-oriented not-for-profit organizations, e.g., American Diabetes
Association, North American Society for the Study of Obesity, Shape Up
America
• Established Key Opinion Leaders (KOLs) and an advisory board:
– JoAnn Munson (Harvard) and Gerald Faich (U Penn) wrote favorable opinion
articles that did not reveal their conflicts of interest[2]
– George Blackburn (Mass Med Soc) helped lift state ban on Fen-Phen
– Louis Lasagna (Tufts) testified on behalf of Fen-Phen to FDA
1. Elliott C. Hastings Center Rep 2004; 34: 18. 2. Manson JE et al.
NEJM 1996; 335: 659.
Wyeth Fenfluramine-Phenteramine (FenPhen) Stealth Marketing Campaign Case II
• Hired Excerpta Medica, a subsidiary of Reed Elsevier, to
ghost-write 10 articles in Reed Elsevier journals
– Only two published before Fen-Phen withdrawn, did not reveal
true authors
– Authors did not disclose payments from Excerpta Medica
• After fen-phen withdrawn, spent another $100 million to
minimize the fallout
– Expert panel of cardiologist KOLs
– “Very Important Visiting Professor” program
Elliott C. Hastings Center Report 2004; 34: 18
Pfizer Sertaline (Zoloft) Stealth Marketing
Campaign Case
• Pfizer engaged Current Medical Directions (CMD) to
orchestrate marketing of sertaline (Zoloft)
• CMD drafted 85 articles by 1998, of which 55 were
published
– Topics included depression, dysthymia, panic disorder, posttraumatic stress disorder, differentiation between selective
serotonin reputake inhibitors (SSRIs), use of sertaline in children,
etc
– Appeared in J Clin Psychiatr, J Psychopharmacology, Am J Psych,
JAMA, Arch Gen Psych, etc
– CMD ghost-written articles outnumbered conventionally written
articles in medical literature, and had five times as many citations
Healy D. Br J Psych 2003; 183: 22.
Parke-Davis Neurontin Stealth Marketing
Campaign Case
• “Medical education drives this market!”
• Speakers bureaus to “identify and train strong Neurontin advocates
and users to speak locally….”
• Lecture series to increase “the volume of Neurontin new
prescriptions.”
• Use of Medical Education and Communication Companies (MECCs)
to develop “educational” programs to support “growth opportunities”
for off-label use.
• Consultants’ meeting attendees told “we would like to develop a close
business relationship with you.”
• Publications strategy so that “all articles submitted will include a
consistent message … with particular interest in proper dosing and
titration as well as emerging [off-label] use”
Steinmann MA et al. Ann Intern Med 2006; 145: 284
Parke-Davis Neurontin Stealth Marketing Campaign Case: Structure
Steinman, M. A. et. al. Ann Intern Med 2006;145:284-293
Key Opinion Leaders
• “Key opinion leaders were salespeople for us….”
• 'There are a lot of physicians who don’t believe what we as
drug representatives say. If we have a KOL [key opinion
leader] stand in front of them and say the same thing, they
believe it.'
• They become an integral part of the company’s marketing,
education, and research strategies. 'When these people are
receiving a fee, they are in one sense in the employment of
the company,…’
• "These people are paid a lot of money to say what they say.
I’m not saying the key opinion leaders are bad, but they are
salespeople just like the sales representatives are."
Moynihan R. BMJ 2008; 336: 1402
“Dr. Drug Rep”
• NY Times article by Dr Daniel Carlat, a physician who used
to give lectures for pharma
• Recruited by Wyeth rep to “give talks to other doctors about
using Effexor XR for treating depression” at $500 each
(excluding travel)
• “Faculty development program” he attended (and was paid
for) included “officially sanctioned slide deck”
– “I knew this was hardly impartial medical education, and that we
were being fed a marketing line. But when you are treated like
the anointed, wined and dined in Manhattan and placed among
the leaders of the field, you inevitably put some of your critical
faculties on hold.”
Carlat D. NY Times, November 25, 2007.
“Dr Drug Rep” II
• “The drug rep who arranged the lunch was always there,
usually an attractive, vivacious woman with platters of
gourmet sandwiches….”
• “The day after my talks, I would get a call … from the
drug rep saying that I did a great job….”
• “As the reps became more comfortable with me, they
began to see me more as a sales colleague.”
• After some doctors criticized his talks, “I realize… I was
blithely minimizing the hypertension risks….”
• Revised his talks to become more balanced, then district
manager said “you weren’t as enthusiastic about our
product at your last talk,” and asked “Have you been
sick?”
• That’s when he quit
Summary: Stealth Marketing Key
Elements
• Recruitment of “key opinion leaders” – via
speakers’ bureaus, consulting arrangements,
etc
• Marketing message injected into
“educational” programs
• “Publication strategy” involving
manipulation of journal articles, including
ghost-writing and guest-authorship
Threats at Each Stage of the EBM Process
• Pick important clinical problem that affects defined
populations
• Identify possible management options, and their possible
outcomes
– Traditional Advertising and Marketing
•
•
•
•
•
Systematic search for the best possible evidence
Critical review of each study
Assess outcome probabilities (for each option)
Assess values (utilities) of possible outcomes
Combine probabilities and values to determine option with
most favorable benefit vs harm, or highest expected utility
Is Detailing Just Advertising? – Built
on False Friendship
• “Drug reps are selected for their presentability and outgoing natures,
and are trained to be observant, personable, and helpful.”
• “Trained to assess physicians' personalities, practice styles, and
preferences, and to relay this information back to the company.”
• “Reps scour a doctor's office for objects … that can be used to
establish a personal connection with the doctor”
• “Drug reps provide respite and sympathy; they appreciate how hard
doctor's lives are, and seem only to want to ease their burdens.”
• “Every word, every courtesy, every gift, and every piece of
information provided is carefully crafted, not to assist doctors or
patients, but to increase market share for targeted drugs.”
Fugh-Berman A et al. PLoS Medicine 4(4):e150.
Is Detailing Just Advertising? –
Buying Friendship
• “Gifts create both expectation and obligation.”
• “Pharmaceutical gifting, however, involves carefully
calibrated generosity.”
• Many prescribers receive pens, notepads, and coffee
mugs, all items kept close at hand, ensuring that a
targeted drug's name stays uppermost in a physician's
subconscious mind.”
• “High prescribers receive higher-end presents….”
• “'The essence of pharmaceutical gifting is ‘bribes that
aren't considered bribes’”
The Life of a Drug Rep: per Shahram Ahari
• His fellow reps “were the beautiful people,” including
former models, cheerleaders and athletes, usually without a
science or health care degree
• His meal allowance exceeded $60K/ year
• His job was “rewarding physicians with gifts and attention
for their allegiance to your product and company….”
• “The nature of this business is gift-giving.”
• “We were taught to minimize the side effects and how to
use conversational ploys to minimize it or change the
topic.”
• “Physicians can be influenced just like anyone else”
Are You Ready for Some Football?
Are You Ready for Some Football:
Cheerleaders as Drug Reps
• NY Times “Gimme an Rx! Cheerleaders Pep Up
Drug Sales”
– Former cheerleader Penny Otwell
Saul S. NY Times, November 28, 2005
Threats at Each Stage
• Pick important clinical problem that affects defined
populations
• Identify possible management options, and their possible
outcomes
• Systematic search for the best possible evidence
Suppression of research
•
•
•
•
Critical review of each study
Assess outcome probabilities (for each option)
Assess values (utilities) of possible outcomes
Combine probabilities and values to determine option with
most favorable benefit vs harm, or highest expected utility
Suppression of Research Examples
• 6% of faculty admitted delaying publication of
undesirable results[1]
• Anonymous cases of articles withdrawn because
results “ran counter to financial interests and strong
beliefs.”[2]
• Other older famous cases
– Betty Dong, UCSF, “thyroid storm”
– David Kern, Brown, flock lung
– Nancy Olivieri, U of Toronto, defirapone
1. Blumenthal D et al. JAMA 1997; 277: 1224. 2. Bodenheimer T.
NEJM 2000; 342: 1539.
Suppression of Research: Recent Examples
• Celebrex (celecoxib,Pfizer) – 12-month CLASS trial data showing no
benefits suppressed
• Vioxx (rofecoxib, Merck) – adverse cardiovascular event data from
VIGOR suppressed
• Ventak Prism ICD (Guidant) – data on failures due to short circuits
suppressed
• Famvir (famcyclovir, Novartis) – data possibly unfavorable to drug
suppressed
• Traysylol (aprotinin, Bayer) – observational study showing increased
adverse event rate suppressed
• Avandia (rosiglitazone, GlaxoSmithKline) – trials whose combined
data suggested increased cardiovascular risk suppressed
• SSRIs – 31% of pharma supported registered trials, mainly negative,
never published
Threats at Each Stage
• Pick important clinical problem that affects defined
populations
• Identify possible management options, and their possible
outcomes
• Systematic search for the best possible evidence
• Critical review of each study
– Manipulation of study design
• Assess outcome probabilities (for each option)
– Manipulation of study design
• Assess values (utilities) of possible outcomes values
• Combine probabilities and values to determine option with
most favorable benefit vs harm, or highest expected utility
Who Supports Clinical Research?
• Formerly, government agencies (e.g., NIH), foundations,
academic institutions
• Increasingly pharmaceutical, biotechnology, device and
other companies
– Approximate corporate total investment in biomedical research
rose from 32% in 1980 to 62% in 2000 (1)
• Commercial sponsors obviously have vested interests in
having studies provide results favorable to their products
– Stereotypically, fostered by marketing and finance people
• Commercial sponsors also have vested interests in
maintaining their reputations for honesty and the support
of good patient care, and honest, valid science
– Stereotypically, supported by scientific and medical people
1. Bekelman et al. JAMA 2003; 289: 454-465
Bias in Commercially Sponsored
Research?
• Multiple studies of how commercial sponsorship
relates to results favoring the sponsors’ products
• Two systematic reviews showed commercial
sponsorship predicted positive results
• Pooled odds ratios of sponsorship as predictor of
positive results:
– 3.60 (95% CI 2.63, 4.91)(1)
– 4.05 (2.98, 5.51)(2)
1. Bekelman JE et al. JAMA 2003; 289: 454-465. 2. Lexchin J et al.
BMJ 2003; 326: 1167-
Tactics to Increase Likelihood of Favorable Results
• Study Population
– Select a study population unlikely to have adverse
outcomes, but unrepresentative of patients who might use
the treatment
– Keep the trial too small to detect adverse effects of
treatment
• Alternative Treatment
– Compare the treatment to one known to be inferior
– Use a dosage of the comparison treatment that is too low
(so it won't work), or too high (so it will have side
effects)
Smith R. PLoS Medicine 2005; 2: 364. Brophy JM. JAMA 2005:
294: 2633
Tactics to Increase Likelihood of Favorable Results II
• Measurement
– Use multiple endpoints in the trial, but pick the one that shows a favorable result
– Use composite endpoints related to possible benefits to increase the likelihood of
finding a statistically significant effect
– Use individual endpoints related to possible harms to decrease the likelihood of
finding a statistically significant effect
– Use intermediate outcomes (e.g., laboratory tests) rather than clinical outcomes
• Analysis
– Do multi-center trials, but use only results from the centers with favorable
outcomes for the product
– Do multiple sub-group analysis, but only publish those with favorable results
– Do “on-treatment” rather than intention-to-treat analysis of adverse events, thus
omitting events that occur after treatment stops
Smith R. PLoS Medicine 2005; 2: 364. Brophy JM. JAMA 2005:
294: 2633. Psaty BM et al. JAMA 2008; 299:1813.
Mechanisms to Facilitate Influence of
Vested Interests
• Research by contract research organizations (CROs)
may lack safeguards against bias
– CROs perform increasing proportion (28% of drug trials
in 1993, 64% in 2003) of commercially sponsored
clinical research (1)
– CROs report directly to sponsors, advertise speed and
responsiveness to clients
– CROs supervised by for-profit “institutional review
boards” who also report directly to sponsors
Schuchman M. NEJM 2007; 357: 1365.
Mechanisms to Facilitate Control of
Research by Sponsors
• Much clinical research still done in academic
settings
• Medical schools/ academic medical centers
increasingly focused on funding rather than what
they have to do to get it
– Goldman: “Bottom line, you should strive to be a
‘taxpayer.’” (1)
• Medical school faculty investigators often have
individual conflicts of interest
Goldman L et al. SGIM Forum, April, 2007.
The Contractual Basis of Sponsors’ Influence on
Research Done in Academia: the Mello Study
• Surveyed 107/122 medical school research
administrators
• Asked about acceptability of a variety of research
contract provisions, especially about control of the
sponsor (external funding organization, including
industry, pharma, device manufacturing, biotech etc)
over aspects of the research
Mello Study: Proportion of Research Administrators
Finding Contract Provisions Acceptable
Contract confidential
Investigators cannot discuss while ongoing
Sponsor writes up results
Sponsor may do statistical analysis
Sponsor can alter study design
Investigators cannot alter study design
Sponsor will own the data
0
10
20
30
40
50
60
70
80
90
Threats at Each Stage
• Pick important clinical problem that affects defined
populations
• Identify possible management options, and their possible
outcomes
• Systematic search for the best possible evidence
• Critical review of each study
Manipulation of study reporting
• Assess outcome probabilities (for each option)
Manipulation of study reporting
• Assess values (utilities) of possible outcomes values
• Combine probabilities and values to determine option with
most favorable benefit vs harm, or highest expected utility
Manipulation of Research Reporting: Ghost
Writing of Reviews and Editorials
• Reports going back to 1993 that pharmaceutical
companies may pay for medical education
companies to ghost write review articles which favor
their products, or disfavor competitors, then lure
academics to be front authors (also called guest
authors)
Anon. Lancet 1993;342: 1498.
AstraZeneca RxComm Ximelagatran Case
• Adriane Fugh-Berman approached by RxComm to author a review of
herb-warfarin interactions, sponsored by AstraZeneca
• RxComm sent her complete draft of article, with title page stating Dr.
Fugh-Berman was author
• RxComm said “whilst there is no promotion of any drug within this
paper, AstraZeneca is keen to set the scene for new anticoagulants that
are not subject to the numerous limitations of warfarin”
• A new oral anticoagulant, ximelagatran, made by AstraZeneca, had
been licensed in France, and a US New Drug Application was pending
• Fugh-Berman refused to “author” the article
• The same article, somewhat revised, with a new “author,” was
submitted to the Journal of General Internal Medicine, and sent to
Fugh-Berman for review, who then blew the whistle
Fugh-Berman A. J Gen Intern Med 2005; 20: 546.
AstraZeneca RxComm Ximelagatran Case:
Editorial Comments
• “Publishing biased literature is not simply ‘getting the message out’
for the pharmaceutical client of the medical education company.”
• “It injects bias and untruth into the scientific dialogue in order to
enhance corporate profits.”
• “How much is sullying the medical literature worth in market share?”
• “What are the long-terms effects on scientific discourse and the bond
of trust among the scientific and clinical communities, pharmaceutical
manufacturers, and the public?”
• “What is the ultimate effect on market share if that trust is breached?”
Tierney WM et al. J Gen Intern Med 2005; 20: 550.
Ross et al Study of Rofecoxib Publications
• Based on documents from Vioxx litigation
• Searched for documents related to authorship (of
clinical trials or review articles)
• Using grounded theory, reviewed for broad themes
by one investigator
• Then negotiated consensus of all investigators
• Searched for relevant published articles
Ross JS et al. JAMA 2008; 299: 1800-1812.
Ross et al: Rofecoxib Clinical Trials
• For 20 trials, Merck author prepared first draft
• For 16/20 articles reporting these trials, first author
of published version was academic external to
Merck
• For these 16, all had two or more academic
affiliated authors, mostly as first-third listed
authors
• 22/24 clinical trials disclosed Merck sponsorship
of research
Ross et al: Rofecoxib Clinical Trial 78
Example
• Draft version had “external author?” as first author,
all other nine authors from Merck
• Published version had three academics as first three
authors
• Only one of these three listed as being in Trial 78
study group prior to publication of paper
Ross et al: Review Papers
• Merck contracted with medical education and
communication companies (MECCs) to write
review papers, and handle publication process
• Then external academics identified to pose as
authors
• 50/72 published review articles each had only one
author who was an academic external to Merck
• 36/72 review articles disclosed Merck financial
support of paper or of author
Ross et al: Conclusions
• “Merck used a systematic strategy to facilitate the publication of
guest authored and ghost written medical literature.”
• “Articles related to rofecoxib were frequently authored by Merck
employees but attributed first authorship to external, academically
affiliated investigators who did always disclose financial support
from Merck, although financial support of the study was nearly
always provided.”
• “Similarly, review articles related to rofecoxib were frequently
prepared by unacknowledged authors employed by medical
publishing companies and attributed authorship to investigators
who often did not disclose financial support from Merck.”
Flanagin Survey: Ghost Writing in Major
Journals
30
25
20
Total
Research
Review
Editorial
% of Articles
15
Ghostwritten
10
5
0
Am J
Card
Am J Am J Ann Int JAMA NEJM
Med Ob Gyn Med
Misuses of EBM – Montori and Guyatt
• “An analogy can be made between EBM and nuclear
fission: it can be very powerful when used appropriately and
dangerous when used inappropriately. The term evidencebased precedes many recommendations, guidelines, and
algorithms that are not transparently linked to the
underlying evidence base and do not represent the
results of a systematic and critical appraisal of that
evidence. It sometimes appears as if using the term obviates
the need to describe the quality of underlying evidence, the
magnitude of effects, or the applicability of any of the
results in the context, values, and preferences of the
patients.”
Montoria VM, Guyatt GH. JAMA 2008; 300: 1814-1816.
Misuses of EBM – Montori and Guyatt II
• “This is particularly problematic because the EBM era has
coincided with a dramatic increase in the for-profit funding
of research. Researchers funded by industry interpret
their results differently and in favor of the industry
product relative to not-for-profit funding. Problems
associated with industry funding include use of
inappropriate control interventions, surrogate outcomes,
publication and reporting bias, and misleading descriptions
and presentations of research findings—all forms of
corrupting the evidence base. Unsophisticated users of
the medical literature, assuming that medical editors, peer
reviewers, and topic experts have now become familiar with
the tenets of EBM, may trust these corrupted research
reports and advocate for their application in practice.”
Distortion of the Evidence Base: Summary
• The clinical evidence base is likely severely
distorted due to a variety of deceptive practices
driven by leadership of pharmaceutical,
biotechnology and device companies focused on
marketing and short-term profits, with considerable
cooperation from academic medical leadership
focused on “external funding”
Examples: Effects of Bad
Leadership
• Distortion of the clinical evidence-base
• Pay for what sort of performance?
Problems with P4P
• Pay for performance based on guidelines
which in turn were based on distorted
evidence base
Example: Guidelines for Management of
Depression in Primary Care
• Agency for Health Care Policy and
Research (AHCPR) – 1993
• US Preventive Services Task Force – 1996
• US Preventive Services Task Force – 2002
• Ambulatory Care Quality Alliance Recommended Starter Set
AHCPR 1993 Guidelines:
Pharmacologic Treatment
• “Guideline: Medications have been shown to be effective in
all forms of major depressive disorder. Barring
contraindications to these agents, antidepressant
medications are first-line treatment for major depressive
disorder when:
– The depression is moderate to severe.
– There are psychotic, melancholic, or atypical (overeating,
oversleeping, weight gain) symptom features
– The patients requests medication
– Psychotherapy by a trained, competent psychotherapist is not
available
– The patient has shown a prior positive response to medication
– Maintenance treatment is planned”
AHCPR 1993 Guidelines:
Pharmacologic Treatment
• “Guideline: No one antidepressant is clearly more effective than
another”
• “If the patient is a candidate for maintenance therapy, the long-term
side effects are key considerations in maximizing adherence, and they
should be minimal. The newer antidepressants (e.g., bupropion,
fluoxetine, paroxetine, sertraline, trazadone) are associated with
fewer long-term side effects, such as weight gain, than are older
tricylic medications.”
• “First- and second-line choices:
–
–
–
–
–
–
Secondary amine tricyclics (e.g., nortriptyline, desipramine).
Bupropion
Fluoxetine
Paroxetine
Sertraline
Trazadone”
USPSTF 2002 Guideline
• “The U.S. Preventive Services Task Force (USPSTF)
recommends screening adults for depression in clinical
practices that have systems in place to assure accurate
diagnosis, effective treatment, and follow-up. This is a
grade B recommendation.” Based on:
– “Ten trials measured the effect of screening and feedback on
depression outcomes from 1 month to 2 years after the
intervention. Five of these 10 studies reported significant
improvements in the clinical outcomes of depressed patients, and
3 others reported improvements that did not reach statistical
significance.”
Recommended Starter Set:
The Ambulatory Care Quality Alliance
• Two measures of quality for “antidepressant
medication management:
– Acute Phase: Percentage of adults who were diagnosed
with a new episode of depression and treated with an
antidepressant medication and remained on an
antidepressant drug during the entire 84-day (12week) Acute Treatment Phase.
– Continuation Phase: Percentage of adults who were
diagnosed with a new episode of depression and treated
with an antidepressant medication and remained on
an antidepressant drug for at least 180 days (6
months).”
The Guidelines
• In plain language: Primary care physicians
should look out for depression, and treat
nearly all depressed patients, preferably
with new, usually SSRI anti-depressants
Do Physicians Follow the Guidelines?
• No
• Primary care physicians don’t adequately diagnose
depression
• Primary care physicians don’t adequately treat
depression, and particularly don’t use new, mainly
SSRI anti-depressants often enough
– And as a primary care physician, but one who did not
have a special interest in depression, I felt worse and
worse about my inadequacies in this area
Update: Benefits of Pharmacologic
Treatment
• Underlying guidelines were meta-analyses and
systematic reviews of controlled trials of antidepressant medications
– These suggested that newer pharmacologic treatments for
depression were very safe and effective
• What if these really did not include all the relevant
evidence from all relevant trials?
Was Evidence About Efficacy of Paxil
Suppressed? – CMAJ Report
• CMAJ reported in 2004 that internal
GlaxoSmithKline (GSK) document showed how
company suppressed findings of Study 329 of
paroxetine (Paxil) in adolescents:
– Efficacy results “insufficiently robust” to support
indication for adolescent depression in the UK
– While “a full manuscript … will be progressed,”
– However, “It would be commercially unacceptable to
include a statement that efficacy had not been
demonstrated, as this would undermine the profile of
Paxil.”
Kondro W. Can Med Assoc J 2004; 170: 783.
Was Evidence About Efficacy of Paxil
Suppressed? – Spitzer Suit Against GSK
• In 2004, Eliot Spitzer, then NY state attorney
general, sued GSK for suppressing data
unfavorable to Paxil
• GSK settled within 3 months, agreed to put
summaries of data from all its drug trials, including
unpublished ones, on a public web-site
Benefits of Pharmacologic Treatment: Including the
Suppressed Studies in the Meta-Analysis
• Turner et al. Selective publication of antidepressant
trials and its influence on apparent efficacy. N Engl
J Med 2008; 358:252-260.
• Kirsch I, Moore TJ. The emperor’s new drugs: an
analysis of antidepressant medication data submitted
to the US Food and Drug Administration.
Prevention Treatment 2002; 5:
Turner et al MetaAnalysis: Publication
According to Direction
of Results
Turner et al Meta-Analysis: Apparent
Effect Size, Published vs All Studies
• Overall mean weighted effect size:
– FDA analysis of all studies = 0.31
– Published studies = 0.41
Small = 0.2, Medium = 0.5
Turner et al
Meta-Analyis:
Apparent Effect
Size for
Different Drugs
Turner et al Meta-Analysis: Conclusions
• “We found a bias toward the publication of positive
results. Not only were positive results more likely to be
published, but studies that were not positive, in our
opinion, were often published in a way that conveyed a
positive outcome.”
• “We found that the efficacy of this drug class is less than
would be gleaned from an examination of the published
literature alone. According to the published literature, the
results of nearly all of the trials of antidepressants were
positive. In contrast, FDA analysis of the trial data showed
that roughly half of the trials had positive results.”
Kirsch and Moore Meta-Analysis: HRSD
Score Results
Drug
Fluoxetine
Improvement
post Drug
8.30
Improvement
post Placebo
7.34
Paroxetine
9.88
6.67
Sertraline
9.96
7.93
Venlafaxine
11.54
8.38
Nefzodone
10.71
8.87
Citalopram
9.69
7.71
Clinically important
difference per NICE = 3
Kirsch and Moore Meta-Analysis:
Conclusions
• When combining all, not just published,
trials’ results
– Effect size of SSRIs for acute treatment of
moderate-severe depression is barely clinically
significant
Was Evidence About Efficacy of
SSRIs Manipulated?
• Turner et al meta-analysis review of
equivocal studies’ methods
• Study 329 example
Turner et al: Methodologic Problems of Questionable
or Negative Studies Published as Positive
• Of 11 studies:
– 2 did not clearly report FDA primary outcome
variable results
– 4 reported a principal outcome variable which had not
been reported to FDA
– 2 presented data from only one site of multi-site study
– 4 reported data of “efficacy subset” of intention to treat
analysis
– 6 changed method of handling drop outs
Design of Study 329
• Proposed by Dr Martin Keller, Chair of
Psychiatry at Brown University
• RCT of paroxetine (Paxil, Seroxat) vs TCA or
placebo in adolescent major depression
• Funded by SmithKline Beecham (later GSK)
• Primary outcome measures: change in total
HAM-D, proportion with HAM-D < 8 or reduced
by > 50%
• Six secondary outcome measures
Keller MB et al. J Am Acad Child Adolesce Psychiatr 2001; 40: 762
Manipulation of Study 329: Efficacy
• Jureidini et al reviewed internal papers, emails, memos disclosed in
litigation
• Initial analysis showed no advantage of paroxetine on two primary or
six secondary measures
• Authors post-hoc assessed drugs with 19 other measures, found four
on which paroxetine showed an advantage
• Authors replaced four original outcome measures with four post-hoc
measures
–
–
–
–
HAM-D < 8
HAM-D depressed mood item
K-SADS-L depressed mood item
CGI 1 or 2
• One original primary outcome measure (change in HAM-D) not
reported
Was Evidence About Harms Suppressed? –
Systematic Data
• Fergusson et al meta-analysis of published
studies
• Khan et al re-analysis of data submitted to
FDA
Fergusson et al Meta-Analysis: Methods
• All published randomized controlled trials of SSRIs,
regardless of condition or age of patients
• Trials found by Medline and Cochrane
Collaboration searches
• Crossover trials excluded
• Primary outcome considered was suicide attempts
• Found 702 trials: 411 vs placebo, 220 vs TCA, 159
vs other treatments
Fergusson D et al. Br Med J 2005; 330: 396.
Fergusson et al Meta-Analysis: Results
• OR for suicide attempts (95% CI)
– SSRI vs Placebo = 2.28 (1.14, 4.55)
– SSRI vs TCA = 0.88 (0.54, 1.42)
– SSRI vs other = 1.94 (1.06, 3.57)
• But, SSRIs are meant to treat depression, and
suicidal ideation, attempts and completion are
generally thought to be consequences of suicide
• So, all things being equal, one would expect
treatment of depression should lessen suicide
attempt rates, if not statistically significantly
Manipulation of Study 329: Adverse
Effects
• “Subsequently SKB senior scientist McCafferty composed a
paragraph on SAEs (severe adverse events) that appeared for the first
time in the draft of July, 1999. It disclosed that 11 patients on
paroexetine, compared to two on placebo, had SAEs, but did not
mention that statistical significance….” (which was p=0.01)
• “Subsequently McCafferty’s disclosures of overdose and mania were
edited out, and SAEs on paroxetine were attributed to other causes.”
• Paper concluded, “Paroxetine is generally well tolerated in this
adolescent population, and most adverse effects were not serious.”
• Promotion of Paxil using Study 329 by GSK: “Paxil demonstrates
REMARKABLE efficacy and safety in the treatment of adolescent
depression.”
How Reliable Was the Evidence on Which
the Guidelines Were Based?
• Studies which showed low or no efficacy were
suppressed, or reported as if they were positive
• Studies had flaws in design, data collection, or
analysis seemingly intended to maximize apparent
efficacy and minimize apparent harms
• SSRIs are not as efficacious for depression in adult
patients as they seemed
• SSRIs may have higher risk of adverse effects for
such patients than was previously appreciated
Guidelines Based on Pseudo-Evidence
• Guidelines for treatment of depression seem more
based on Pseudo-Evidence than Evidence
– “Pseudo-Evidence” – falsehood disseminated as truth
• It is likely that most guidelines are similarly based
on a distorted clinical evidence base,
– Hence may cause perverse incentives if used as the basis
for P4P
Other Problems with P4P
• As advocated by payers, may be based more on
“efficiency,” i.e., cost control than quality
• May be based on guidelines influenced by vested interests,
so which push products or services supplied by those
interests
• Based on most easily measured factors, may be an incentive
to decrease quality in unmeasured spheres
• Guidelines written for simple patients do not apply to
complex patients, may be incentive to avoid sicker patients
• Outcome measures may not be controlled for severity and
complexity, again may be incentives to avoid sicker patients
Outline
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•
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•
•
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•
•
Why are we miserable? – qualitative study
Case-study: AHERF
Conceptual model of health care dysfunction
Historical background
Conflicts of interest
Bad leadership
Case studies
What can be done?
A Start Toward Solutions
• Put core values first
• Empower patients and health care professionals
• Re-organize, regulate, sometimes disband large
organizations
• Make governance representative, transparent, accountable,
bound by ethical rules
• Licensing of health care organizational leaders
• Full and detailed disclosure of conflicts, ?ban conflicts
affecting physicians and health care leaders?
• Ban those with vested interests in particular results from
running clinical research
AMA, 1980
• In the practice of medicine, a physician
should limit the source of his professional
income to medical services actually
rendered by him, or under his supervision to
his patients
• The practice of medicine should not be
commercialized, not treated as a commodity
in trade
Possible Solutions: Lancet on Transparency
International’s Global Corruption Report
• Any cure should start with maximum
transparency.
• Codes of conduct need to be adopted by health
workers and private sector companies.
• Any transgressions have to be rigorously
prosecuted.
• Whistleblowers from all sectors should be
protected.
Anonymous. Lancet 2006; 367: 447.
Better Understanding: A Plug
• Health Care Renewal Blog:
http://hcrenewal.blogspot.com/
• Foundation for Integrity and Responsibility
in Medicine: http://www.firmfound.org/