REPORT: part one
CONDUCT THAT TAKES LIVES: WHY CRIMINAL PROSECUTION OF MEDICAL
RESEARCHERS WITH FINANCIAL CONFLICTS, WHO FABRICATE SAFETY DATA, HAS
BECOME AN ESSENTIAL COMPONENT OF REGAINING THE INTEGRITY OF DEVICE AND
DRUG RESEARCH IN THE UNITED STATES
James J. Neal, Copyright 2002
"Giant corporations are locked in a life and death struggle to
provide one of a kind instrumentation with which a given operation
"must" be done." Editor, Michael Baggish M.D., Journal of
the disinterested researcher. It is a phenomenon found in every
medical treatment using devices." "If you cant trust the studies,
what happens to the profession and what happens to patients." John
Wasson, M.D., Dartmouth, New York Times.
lost our way. Weve terribly, terribly lost our way. Science has
been lost in the rush for money." Steven Nissen, M.D., Cleveland
Clinic, New York Times.
punctured include bile ducts, bowel, small intestine, liver and
arteries and veins. Data shows high morbidity." Pennsylvania Medical
Society, comments on "hi tech" surgical devices.
Summary: In recent years, surgical instrument companies working
through surgeons with concealed equity interests in devices, have
created new procedures, to promote the sale of equipment. Corporations
have created demand for new surgical procedures "through massive
advertising campaigns to convince the public of [their] necessity."
Rutkow, IRA, The Socioeconomic Tyranny of Surgical Technology.
Archives of Surgery. Leading surgical researchers, with equity
interests have fabricated surgical research to demonstrate the safety
and efficacy of new procedures with device costs of $2,000-$5,000 per
operation. One sales rep described his companies philosophy as
"dollars per procedure." Although the device industry has generated
tens of billions of dollars in revenue using these tactics, serious
surgical morbidity from many new device dependent operations has
multiplied. Treating MDs and patients need law enforcements
assistance in deterring fabricated research data published by research
surgeons with concealed equity interests in expensive medical devices,
and new drugs. The question raised in this analysis is whether
fraudulent medical research is taking lives, and if so, how many.
represent a surgical device salesman "whistleblower" who has worked
for the two largest device companies in the United States. Another
client is a surgeon who supervises the use of new surgical technology.
Thousands of physicians have learned new surgical technology at the
center. A third client clinically tests new medical devices for many
instrument companies. A fourth client, a former Chief Medical Officer
at the Devices Division of the FDA has found over 1,000 misreported
device malfunctions. This report is about what law enforcement has
not done - but can do to deter deaths and
injuries from what Clients #1 and #2 refer to as "the medical mafia."
The third client, a prominent surgeon, after finding that a new
surgical device caused potentially fatal injuries in 3 of 18 patients
- was persuaded to avoid testifying about the injuries he observed, by
a company Chief Operating Officer. The device, which Client #3 told
the Chief Operating Officer was a "lethal weapon," has since injured
tens of thousands of patients, including an estimated 1,000-3,000
deaths. Doctor John Guerigian, an MD//biochemist who left the
FDA after over 20 years says, "Theyre killing people and no ones
going to jail." This document argues that some should. Fraudulent
device researchers with equity interests in products, who count on law
enforcements inaction - are doing serious harm with fabricated
studies backing some of the new long stemmed devices that are
COMFORTING MYTH ABOUT DEVICE AND DRUG RESEARCH
Dr. Richard Horton, the Editor of Lancet, one of the worlds
oldest and preeminent medical journals, published his conclusion that
the "notion" that drug and device research still serves medicine is a
"comforting but erroneous myth." The myth referred to by Horton
is about more than questionable research choices. It's about using a
portion of a 200 billion dollar plus annual revenue to pay some
"leading researchers" multimillions to purchase safety data that is
not valid. This permits a company to obtain FDA approvals, and promote
products based upon invalid data. There is a growing body of evidence
that misleading drug and device research in the burgeoning for profit
clinical medical research system is multiplying, is undeterred, is now
a threat to public safety that rivals firearms in magnitude, and
should be criminally prosecuted. If fabricated and otherwise
misleading research on new drugs and devices has contributed to over
100,000 deaths, as appears probable, prosecution of the most dangerous
offenders must be considered. Fabricating positive drug and device
research results can be extremely lucrative. Indeed, it can generate
billions of dollars in sales. Some fraud in commerce is self policing
through caveat emptor. However, the actual police are required when
fraudulent medical research "backs" a new drug or device - precluding
caveat emptor. Later in this document potential prosecutions of named
fraudulent researchers are detailed, but a background discussion of
systemic changes in for profit drug and device research since 1995 may
be helpful prior to discussing specific cases.
Substantial lay media coverage of medical researchers financial
conflicts - including equity conflicts - in drug and device research
began in 2000 following the death of research subject Jesse Gelsinger
at the University of Pennsylvania. Gelsinger was a healthy young man
who, like many other research subjects, presumably takes a risk to
benefit science not to increase the value of a researchers
concealed equity interests in a device or a drug. The media learned
and reported that University of Pennsylvania researcher James Wilson,
M.D. was a major stockholder in the company sponsoring the research.
Dr. Wilsons share, when the company was sold was $13.5 million,
according to an April 22, 2002 cover story in Time magazine.
Shortly after Jesse Gelsingers death, there were similar revelations
at the "Hutch," a prominent research facility in Seattle. Reportedly,
80 of 82 studied patients died before researchers (including a Nobel
winners) equity conflicts were uncovered by the Seattle Times.
It appears likely that dozens of those patients would be alive today,
had they not been included in a study a researcher had a financial
interest in continuing - until it "succeeded." The Seattle Times
has suggested that many patients would never have joined the study if
they had known the facts re: financial conflicts and survival rates.
Following these public revelations, the scientific community began,
for the first time, to widely debate the effects of financial
conflicts on the integrity of research backing new drugs and devices.
interest of leading researchers in device and drugs they "study" have
become so substantial in the past five years, that treating physicians
across the country are beginning to question the integrity of research
on new drugs and devices. Treating physicians are asking whether new
therapies researchers advise them to employ are safe. (e.g. one recent
book, "Dispensing with the Truth": included a chapter titled
"Spin Doctors" which named the physicians who promoted a diet drug -
since recalled for causing heart valve damage.) Treating MDs are
becoming concerned about the data backing new therapies being provided
to them by researchers with equity interests in products:
a disease thats going to kill half of all people in America. How I
treat that disease ought not to be decided by whos lining someone
elses pocket." Steven Nissen, M.D., Cleveland Clinic, New York
Times, November 30, 1999.
2000, a first of its kind conference on financial conflicts and device
and drug research integrity attended by over 500 scientists was
convened by the Department of Health and Human Services (DHHS).
Participants agreed that existing safeguards fail to protect the
integrity of research on new medical devices and drugs.
"Existing safeguards are failing to protect scientific integrity,
participants agreed during a landmark government sponsored
conference last week
scientists increasingly hold a financial stake
in the outcome [of studies] said speakers from academia, government,
industry and advocacy groups
Conflicts of interests are very real,
very serious and a threat to our entire endeavor, said
Dr. Greg Koski, the newly named director of the Federal Office for
Human Research Protection. During the last five years, they may have
gotten out of control. Public trust has been
Some of the ethically dubious tactics include cash payments
to doctors as well as bias in the reporting of studies to favor the
projects funders." Cleveland Plain Dealer, August 28, 2000.
Boston Globes report on the DHHS conference added that "participants
described doctors eager to collect stock options, potentially
compromising the validity of studies." The Globe also
described Dr. Bodenheimers "whistleblowing" on research articles
favoring new treatments ghostwritten by company employees, but signed
by doctors "who had nothing to do with the study." Similarly,
Lancet published a 2001 editorial asking researchers to keep
their hands "firmly in their pockets," condemning "atrocious
venality" in research, and observing that researchers findings "can
be bought by the highest bidder."
first of its kind declaration, in September 2001, the editors of 13
medical journals (including JAMA, NEJM and LANCET) co-authored a joint
statement, highlighting their concerns about financial conflicts in
device and drug research. The Editors began the article with "the
publication of clinical research
is the ultimate basis for most
treatment decisions." The editors observed that, "We are
concerned about the current intellectual environment" citing
industrys use of clinical research "primarily for marketing."
The editors noted that published clinical research can "change
standards of care" resulting in "substantial financial gains
for the sponsor." The editors further observed that the results of
studies funded by device or drug companies "may be buried rather
than published if they are unfavorable to the sponsors product."
IN DEVICE AND DRUG RESEARCH IN THE PAST DECADE
past decade, systemic changes in clinical research on drugs and
devices have included:
identities of researchers. (In 1992, fewer than 1,000 "private"
physicians performed clinical drug research. Now, its closer to
locations of research. (In 1992, over 80% of clinical research was
conducted and monitored in academic centers. Now 65%-70% of clinical
research is in private offices or community hospitals.)
amount of money paid researchers by industry (up to $6,000 per
patient recruited for a study).
identity of individuals selecting researchers by industry. (In 1992,
20% of clinical research was placed by "for profit" contract
research organizations - now it is closer to 70%.)
Many, perhaps most, companies now prohibit researchers, by contract,
from publishing negative safety findings on a drug or device. (In at
least one case, a company threatened to sue a researcher if she
published adverse data - which showed liver toxicity of a new drug.)
increasing number of "leading researchers" - opinion makers for
entire clinical specialties hold equity interests (sometimes in the
tens of millions of dollars) in products they research and/or
promote to thousands of doctors at huge medical conferences chaired
by those same leading researchers.
is compensating leading drug and device researchers, directors of
large medical conferences (and perhaps some editors of medical
journals) with stock options, royalties, hundred thousand dollar plus
annual consulting fees, equity interests in drugs and devices, lavish
trips, and other benefits. Due to these sometimes immense financial
conflicts, the Director of Federal Human Research Protection opined in
August 2000 that "the entire endeavor" is now at risk. The argument
infra, is that law enforcements awareness and involvement is
essential to remove this risk.
FOR DOCTORS FOR DRUGS AND DEVICES
February 21, 2002 ABC News.com provided insight into one small town
doctors four month $10,000 interaction with industry.
"Disgusted by how the free gifts and trips add to the high price of
medicine, and moved by the plight of patients forced to skip needed
medication. Mueller agreed to provide Primetime with a rare
glimpse of the astounding number of drug company freebies he was
offered by various drug companies in a four month period. He was
presented with an estimated $10,000 worth, including an all expenses
paid trip to a resort in Florida, dinner cruises, hockey game
tickets, a ski trip for the family, Omaha steaks, a day at a spa and
free computer equipment. And the multi-billion dollar drug company
blitz extends throughout the profession, even at the yearly
gathering of one of the most prestigious medical groups, the
American College of Physicians. It was like a carnival: Doctors
could be seen taking free massages, free food, free portraits, free
Walkman players, free basketballs, and from one company pushing a
new antacid drug, free fire extinguishers
The new president of the
American College of Physicians, Dr. William Hall, says anything
beyond a pen or a mug could have an impact
But right now Halls
group receives $2 million a year from drug companies to have their
exhibition booths at the convention."
If a small
town doctor receives $10,000 in incentives in four months to influence
prescriptions, what do researchers who create the safety and efficacy
data used to promote new therapies receive? The Gelsinger case
unearthed a 13.5 million dollar equity interest. The New York Times
described other equity relationships between researchers and
industry. Dr. Spencer King, past president of the American College of
Cardiology was "a large shareholder in Novoste," whose "stock climbed
55%" on the day Novoste announced the results of Dr. Kings study of a
new device" (New York Times, November 30, 1999). The Times
further noted that:
Wholey of the Pittsburgh Vascular Institute was a featured speaker
of a prominent medical meeting. Dr. Wholey spoke enthusiastically
about using stents
But he cautioned there was a danger: shards of
debris from the procedure could lodge in the brain and cause a
stroke. The way to prevent that complication, he said, was to use a
high technology filter. What he did not disclose - in either his
lecture or in the meetings disclosure form - was that he was a
director of Angioguard, a Minnesota company preparing to market it.
Leon runs a conference attended by over 5,000 physicians, annually.
The Times wrote:
Thousands of heart specialists watched on closed circuit
The doctors heard the voice of Dr. Martin Leon, a
prominent cardiologist. "This is the paragon stent. Its a very nice
stent." Dr. Leon who conducted research on the experimental device
enthusiastically described its soft feel
the remarks seemed the
perfect endorsement by an objective scientist. What [Dr. Leon] did
not tell the assembled doctors
was that he was an investor in the
company that manufactured the stent. New York Times, November
the U.S. Attorney in Boston settled a Federal False Claims Act Case
("Qui Tam") against TAP Pharmaceuticals for nearly 900 million
dollars. One fraud? Kickbacks to MDs to prescribe Lupron, a drug,
which can cost a patient up to $1,000 per month. In an April 26, 2002
Chicago Tribune article, TAP Vice President Douglas Durand, who
blew the whistle on TAP kickbacks, blamed a "raucus cowboy culture" at
the company. Lupron has spawned a "Lupron victims" Internet group with
thousands of women members who say the drug has harmed them or their
babies. One of TAP Pharmaceuticals leading Lupron researchers -
Boston gynecologist Andrew J. Friedman, fabricated clinical research
to expand the off label market for this prostate cancer drug, to
include uterine fibroids (over 10,000,000 women have fibroids - far
more than men with prostate cancer - which Lupron was approved to
treat). Among other fabrications, it was noticed that "studied"
patients initials, listed on Friedmans data sheets matched the
initials of doctors at the hospital. In a second Friedman study, it
was found that patients were named after doctors applying for
fellowships at Harvard. Those "studied" patients, too, did not exist.
Following discovery of the fraud, Dr. Friedman was not prosecuted. He
left his division directorship at Womens and Brighams Hospital in
Boston to take a job full time with a pharmaceutical company. Why
would a pharmaceutical company hire a researcher whose medical license
was pulled, for fabricating safety data?
44,000-98,000 UNNECESSARY DEATHS PER YEAR FROM MEDICAL
the National Institutes of Medicine estimated unnecessary
deaths from medical interventions at 44,000-98,000 per year. At the
upper estimate the number of avoidable deaths from medical
interventions exceeds deaths from homicides, auto accidents, and air
crashes combined. How many of these deaths are due to dissemination of
unsafe devices or drugs via fabricated research? How many medical
research frauds are investigated by law enforcement? Although the
number of unnecessary deaths from unsafe drugs or
devices, promoted through misleading or fabricated research is
unknown, there is evidence that tens of thousands of deaths were
related to research which did not accurately predict the effects of a
drug or device in the general population.
Deadly Medicine, Thomas Moore makes the case that over 40,000
patients died unnecessarily, from one drug (i.e. double the annual
death toll from violent homicides). In reviewing Deadly Medicine,
the Cleveland Plain Dealer reported the "incestuous"
relationships between industry and "leading doctors" that made the
tragedy "possible and perhaps inevitable." Recently, in only a
ten month period, there were an unprecedented five drug recalls due to
deaths and injuries at frequencies apparently not predicted by the
research data provided the FDA by manufacturers. Business Week
reported that "its almost a grim routine now. After the FDA gives
the go ahead for a new drug, the product is yanked from the market
when some unforeseen problem occurs." In "Prescription for
Disaster," Thomas Moore makes the case that over 75,000 Americans
die from adverse drug reactions each year. A recent article in the
Journal of the American Medical Association estimated that 100,000
patients die from adverse drug reactions in a single year. Over 20
million Americans have taken a "recalled" drug since 1997. Total
spending on prescription drugs reached 155 billion in the U.S. in 2001
- double 1997 totals. In May 2000, the Washington Monthly
reported, "A new drug culture requires our attention. The pushers
in this culture wear lab coats and business suits and move their
product through HMOs and family doctors." Fabricated drug and
device research has not just the potential - but the likelihood of
eventually touching every American family, in some, perhaps thousands
of cases, fatally.
device research side, a disposable surgical instrument used in
approximately half of the four million laparoscopic procedures
performed in the U.S. each year is in the news. During a 2001 ABC
television interview, the researcher who tested the device called it a
"death machine." This researchers clinical testing, which yielded
three potentially fatal injuries in 18 patients, was concealed from
the FDA, by the manufacturer. An estimated 20-40 million of these
devices have been sold - and used during surgical procedures. In
November 2001, a former chief medical officer of the FDA devices
division estimated that this device has injured 40,000 surgical
patients in ten years (Smart Money, November 2001). It appears
that the device may have caused 1,000-3,000 deaths - many through
punctures of the aorta, iliac arteries or vena cava, which can fatally
wound a patient in the first five minutes of even a minor operation.
Thin women are disproportionately at risk of death from this device.
Statements by surgeons who researched and/or taught doctors to use
this device - by a field rep who sold it and by a former chief medical
officer at the FDA Devices Division, revealing the fraudulent
concealments behind this device are at p. 46 et. seq. This device,
which need not be used at all, has impaled every organ and major
vessel in the abdomen, according to reports filed with the FDA.
National Institute of Medicines estimate, in 2000, of 44,000-98,000
unnecessary annual deaths from medical interventions is
consistent with an earlier study of deaths in New York. In the largest
study of its kind, Public Health physicians from Harvard reviewed
medical records from 51 New York hospitals. Following that study, the
Harvard MDs estimated that 27,179 injuries, including 6,895 hospital
deaths in New York, in a single year, were avoidable. (NEJM,
1991; 324:370). Extrapolating this data, 101,356 avoidable hospital
deaths occur nationally each year. The Harvard investigators found
that half the hospital deaths they reviewed (51.5%) were avoidable.
Their conclusion was "there is a substantial amount of injury to
patients from medical management."
"REVOLUTION" TO REMOTELY PERFORMED ABDOMINAL SURGERY
general surgerys deans, Professor Cushieri of Scotland has called the
"revolution" in a new abdominal surgical techniques and devices "the
greatest unaudited free for all in the history of medicine." Columbus,
Ohio Chief of Surgery, Francis Barnes wrote to an Editor that "the
biggest problem with these new [surgical] techniques is that there are
gurus putting on very expensive seminars selling their procedures
almost as though they were some type of tele-evangalist." Some of
these "gurus" have concealed equity interests in devices. Lahey Clinic
Surgeon John Braasch summarized the factors driving the revolution in
Promotion by the medical-device industry.
Efforts by surgeons to expand market share.
Hospitals desiring their operating rooms to be "full."
noted that other beneficiaries of the revolution are
"anesthesiologists who benefit from longer operating times" and
"lawyers whose personal injury suits are numerous."
CONCERNS PALE BY COMPARISON
Hospital Risk Manager in the 1980s, my primary concerns were a
limited number of dangerous individual practitioners and flawed
hospital systems that unnecessarily increased risk. There were no
concerns that entire standards of practice re: procedures and drugs
were based on fraudulent research. That risk materialized in the 90s,
due to "leading researchers" equity interests in devices and drugs.
WEALTH IN RETURN FOR RESEARCHERS POSITIVE FINDINGS
November, 1999, the New York Times revealed multimillion dollar
equity interests of leading cardiology researchers in devices they
studied then promoted at huge medical conferences they directed -
without disclosing their equity interests. These $2,500-$5,000 devices
have been implanted in over a million patients. They reportedly cost
less than $50 to manufacture. In reporting on the tangle of financial
conflicts between "leading researchers" and the device industry, The
can earn vast wealth so long as their results are
positive. New York Times, November 30, 1999.
November 2001, Smart Money, reported that "manufacturers vie
furiously for leading doctors to endorse their wares. You wanted a big
doctor to endorse your trocar, said [a salesman]. It was like getting
Michael Jordan to say your basketball shoes were better." (This
device is described at p. 46 et. seq.) Similarly, in July 2001, a
California newspaper reported:
Dr.Morris Wortman, says that often unknowing surgeons are sold
products at industry sponsored workshops, where prominent surgeons
push products made by the company paying them to speak. "It makes
for great video, you can show your patients how good it looks.
Everyones happy. Except for one problem - its all based on lies.
Those people who flip the slides at the podium have unregulated
power." San Jose Metro News, July 5, 2001.
Michael Baggish, the editor of the Journal of Surgery, has written of
surgeons who do the "bidding" of device companies and the replacement
of "time proven techniques" with the "latest trendy operation,"
requiring the use of expensive disposable devices. In commenting on
one new surgical technology that can add up to $5,000 to the cost of
an operation, the New York Department of Health found was causing a 35
fold increase in serious injury including injuries "rarely or never
reported before," Dr. Harvey Bernard, a New York Health Department
spokesman cautioned surgeons attending a convention on the new
technology that "we have to be reasonably sure that its not
related to one of medicines black beasts - ignorance, arrogance,
intellectual dishonesty and greed."
On May 15,
2002, the New York Times reported that one drug/device
companys internal memo "listed doctors the company considered to
be movers and shakers at prestigious medical schools." The
Times indicated that a lawsuit in Boston accuses this company of
"paying dozens of doctors to speak to their peers, some garnering
tens of thousands of dollars per year" to push product. The
Times reported that marketing firms were hired to write medical
journal articles, at $12,000 per "scientific" article, then find
doctors to sign their names as authors at $1,000 per signature.
New York Post article exposed industry benefits provided to
"prominent" state psychiatric researchers. Doctor Adil Shamoo, a
bioethicist, commenting on the immense sums paid to "leading
researchers" told the Post:
gold rush of the 21st century. Youre talking tens if not
thousands of millions in profits (March 1, 1999).
did the Post find "a dozen key state researchers who
profited from drug firms," it also found that the state
psychiatric institute "did non therapeutic research on children
with fenfluramine, which was subsequently yanked off the market."
The Post reported that New York hadnt imposed strict financial
conflict rules on state psychiatrists because they are "fearful it
could alienate the drug firms" (March 1, 1999).
2001, writing for his Fort Worth area medical society, Doctor Timothy
Gorski warned of researchers "million dollar deals with
pharmaceutical and surgical instrument companies." Also in 2001,
USA Today reported on Dr. James Rowseys use of an
investigational medical device he had an equity interest in. Rowsey
projected $112 million in sales in five years, if the FDA approved the
device. In pursuit of approval, Rowsey "performed unaopproved
research on more than 60 people, including children." Nine year
old Joanne Cassidy and 85 year old Harry Rodgers have sued, one
claiming decreased vision, the other alleging legal blindness. USA
Today noted that the University which also had an equity
interest in the device, "did not monitor his work." USA
Today quoted one patients counsel: "I call it Nasdaq medicine.
It is not scientists racing for a cure. It is scientists racing each
other for the money." Rowsey told USA Today that he didnt
inform patients of his financial interests because they were
professor Cary Gross, citing vast differences in reported results,
depending on who sponsors and funds drug research, observed in the
Journal of Philosophy, Science and Law that the "foundations of
medical research in the United States have been shaken." A recent
study at Northwestern found that negative results on new therapies
were reported 5% of the time when industry paid for the study v. 38%
when the research was not industry funded. On April 22, 2002, Time
magazine reported "96% of researchers who were supportive of [a
controversial therapy] had ties to companies that manufactured it, and
only 37% of these critical of the drug had such ties." Dr. Jermone
Kassirer asked, in an American Journal of Law and Medicine
article on research, "How large is the hidden epidemic of financial
conflict of interest and what impact does it have on the practice of
FINANCIAL CONFLICTS - AND THE INTEGRITY OF DRUG AND DEVICE RESEARCH
ARE OUT OF CONTROL
medical reporter has described the assumption which
permitted drug and device researchers multimillion dollar equity
conflicts which would be unacceptable in any other profession.
Researchers can own stock in companies whose products they test.
They can accept consulting fees and attend conferences in warm
tropical locales at the companys expense. They can be officers in
the companies. Scientists have been untouched by conflict of
interest rules because of the widespread assumption
that they were devoted intellectually driven people who dont care
assumption that medical researchers are more trustworthy than anyone
else is belied by surveys of medical school students - including one
showing that 88% of medical school students cheat, and a recent survey
of students in Toronto. 62 of 102 students observed their instructors
engage in unethical (not poor) practices. The failure to prohibit
ownership interests by researchers in drugs and devices they study is
based on a false assumption. Because truth telling is
related to accountability, an argument could be made that researchers
with financial conflicts are less apt to be truthful than those whose
business is conducted in the open.
CONTRACT RESEARCH ORGANIZATIONS (CROS)
Research Organizations (CROs) contract with drug and device companies
to perform clinical research, and place the research through networks
of physicians in private offices, community hospitals and other
locations. Approximately 65-70% of clinical research in the U.S. is
now conducted by for profit contract research organizations ( v. 21%
in 1991). USA Today reported that "Marcia Angell, former
editor of the New England Journal of Medicine fears that some CROs,
dependent on a particular company for survival, might bury study
1992 and 1998, the number of private practice physicians involved in
recruiting research subjects increased from 988 to 5,380 according to
a report by HHSs inspector general. The total may exceed 10,000 by
now. (Ads by the Pharmaceutical Manufacturers Association indicate
they work with 50,000 "researchers.") The Boston Globe has
described this evolution:
experiments were conducted openly in academic settings, but now most
are done under the cloak of secrecy [in thousands of private offices
and community hospitals]."
now over 1,200 CROs. The largest, Quantiles Transactional Corporation,
broke the one billion dollar revenue mark in 1998, an increase of 39%
in one year with an increase in net income of 50%.
POSITIVE DEVICE AND DRUG RESULTS ONLY
medical writer described the negative reinforcement tactics used by
industry to thwart adverse safety data by researchers not yet on the
drug or device "team."
John W. Norton supplemented his salary by giving talks sponsored by
drug companies. But the sweet arrangement ended when Norton
published a brief article discussing sexual dysfunction triggered by
the drugs whose makers were paying his honoraria. Nortons career as
a pharmaceutical educator came to a sudden end."
an article by Dr. Thomas Bodenheimer in the New England Journal of
Medicine reports interviews with six researchers who maintain that
a company halted publication of or altered their studies. In some
cases, researchers were informed that their work would not be funded
again, after they reported adverse reactions, to the studied drug.
Bodenheimer quotes one researcher, "Companies play hardball. Its
tricky for those who need more money for studies."
14, 2002 Lancet editorial did not mince words about the lethal
effects of suppressing adverse safety findings.
by drug companies to suppress, spin, and obfuscate findings that do
not suit their commercial purposes were first revealed to their
full, lethal extent during the thalidomide tragedy
tactics of big
pharma have changed little."
magazines April 22, 2002 cover story on clinical research addressed
the concealment of adverse study results.
time Cherlynn Mathias was ready to blow the whistle on Doctor
Michael McGee two years ago, it had been clear for quite a while
that something fishy was going on
We have the best vaccine out
there, she remembers him saying
[However] more than a third
developed severe side effects, including uncontrollable nausea,
fevers, rashes, swelling and terrible headaches
worst of all [McGee]
kept most of the data on adverse side effects secret."
February 21, 2002, Dr. Arnold Relman, Professor Emeritus of Social
Medicine at the Harvard Medical School, former Editor-in-Chief of the
New England Journal of Medicine, and one of the leading critics
of financial conflicts in research, spoke to the Canadian Senate about
the effects of the commercialization that yields a research system
where companies prohibit publishing of an investigators adverse
safety results, by contract.
about the only parts of U.S. society happy with our current
market-driven health care system are the owners and investors
in the for-profit industries now living off the system
health care system in the industrialized world is as heavily
commercialized as ours, and none is as expensive, inefficient, and
inequitable - or as unpopular."
recalled for lethal effects, liver toxicity, heart valve damage, etc.
in recent years were not essential therapies. They were for pain,
heartburn, weight loss and diabetes - conditions with safe and
effective therapies, already on the market. These drugs were
aggressively promoted as "breakthrough" therapies but were not. They
were however, more lethal than predecessor drugs. (e.g. the April 22,
2002, Time cover story on clinical research refers to "pharmaceutical
companies looking for a share of the blockbuster drug market pump[ing]
out copycat medicines that no one really needs.") A new drug -
backed by misleading safety data and accompanied by aggressive direct
to consumer advertising plus incentives (including kickbacks) to MDs,
sells in the U.S. - even if its deadly enough to be
recalled. In a year or two, a heavily promoted new drug can yield
several billion dollars in sales (in Europe consumers are more
skeptical of "new").
by critical researchers that their work is altered, buried, or
distorted by the device and drug industry - or that they are
terminated as investigators - are ironic. The industrys image is
built on the benefits of research - presumably conducted to obtain
valid data on what helps and what hurts.
Pharmaceutical Manufacturers Association
built an image campaign
around a single word: research
The [research] message
was so powerful that the Pharmaceutical Manufacturers Association
inserted the word research into its name, creating a new, if
grammatically awkward, monitor - the Pharmaceutical Research and
Manufacturers of America." New York Times, October 5, 2000
physicians concerns about data distortion by what Lancet calls
"big pharma," there is at least some FDA oversight of drug research.
The FDA does audit over 5% of drug studies at clinical testing sites.
However, virtually no device research is audited by the FDA at
clinical testing sites. (i.e. no one looks at patient records
to see if they match what the researcher reports in the scientific
literature about the effects of using the device.)
current regulatory framework typically provides device investigators
complete freedom from FDA investigation, oversight, and regulation.
This is so because a loophole in the FDAs "510-K" approval process
grants approval to market a new device prior to
presentation of either working models or clinical research data (v.
new drugs where data is always required by the FDA). Approximately 97%
of medical devices applications are approved through the 510K process.
Even the 3% that are approved via a more stringent process, are only
sporadically audited. Using the 510-K process, a company typically
first obtains approval to market a device based on drawings, then
conducts its first clinical study, for promotional purposes, after the
FDA grants approval to market the device. (The device can be approved
before it exists.) By using "strategy," the company can completely
avoid FDA oversight of its initial clinical study of the device.
Devices are then marketed using "post approval" clinical studies. The
FDA does not audit these studies. (It appears that few - perhaps no
new medical devices are marketed without a clinical "study" by a
"leading researcher" to present to prospective purchasers showing
advantages and/or superiority.) Further, the Hospitals Institutional
Review Board - which is supposed to monitor research - typically does
not monitor a post FDA approval surgical device study either (even
when the study is the first clinical study ever conducted on
the device). As such, the regulatory system permits fabricated device
studies for promotional purposes, with virtually no risk of detection
- or correction. These studies are device companies primary marketing
tools. Deterrence of fraud in promotional device studies is more
sorely needed than in drugs because fabricated device studies are
virtually immune from audit in the current system.
The FDA is
generally relegated to trusting data it is provided. It is also
overwhelmed, and needs the assistance of Federal prosecutors in
finding and deterring device research fraud. As the Washington Monthly
should be the first line of defense against companies pushing
dangerous product. But asking the FDA to rein in the industry is a
bit like sending someone out to catch Niagara Falls in a bucket. The
FDAs annual budget for approving, labeling, and monitoring drugs is
roughly 290 million. Compare those numbers to the $11 billion
promotional budget the drug industry gives itself." (May 2000).
FDA needs prosecutors help ferreting out device data fraud is
demonstrated by the fact that while 72 FDA employees track the post
market safety of thousands of drugs and devices that some believe take
100,000 lives per year, over 10,000 inspectors examine airplanes
which, in aggregate, cause a five year average of fewer than 700
deaths per year. (Seven airplane inspectors per death. One FDA post
market inspector per 1,000+ deaths.) In addition, as the LA Times
reported in a Pulitzer prize winning story in 2000, the FDA is
increasingly dependent on industry funding to do its job. This creates
obvious oversight problems. The FDA needs federal prosecutors help
(and independence) in finding and prosecuting device data fraud. (e.g.
the device described at p. 46 et. seq. has injured an estimated 40,000
patients in a decade including an estimated 1,000-3,000 deaths. Its an
optional device. Two companies sell it. One definitely
concealed adverse data and the other allegedly used fabricated safety
data to market the device.)
FOR ACTION BY LAW ENFORCEMENT
of the literature since 1995 on drug and device research integrity,
financial conflicts, product recalls, and patient deaths from drugs
and devices demonstrates that NIHs Greg Koski was justified in
concluding that "during the last five years [conflicts] may have
gotten out of control" - placing the entire research endeavor at
risk. When the editor of Lancet concludes that the "notion"
that drug and device research still serves medicine is an "erroneous
myth," an unprecedented number of drugs are recalled in ten months
because research data on safety did not predict what happened
in the general population, a single drug causes an estimated 40,000
deaths and an estimated 40,000 more patients are injured/killed from a
single elective surgical device, safety data reported by conflicted
researchers can legitimately be termed a pressing public health issue.
As Dr. Wortman recently told a California newspaper, influential
device researchers - who often have concealed equity interests in
devices they promote - have "unregulated power." And its a power that
can lead to injury or death nationwide without accountability or
correction, when unaudited safety data is fabricated to promote sales.
This battle is between treating MDs trying to help patients based on
real evidence and "leading researchers" who have sold out. How many is
unknown, but it appears to be more than suspected. (In the early 90s,
Congressman Dingells hearings on research integrity were met with
doctors claims - but no evidence - that medical research fraud was "vanishingly
PROMOTION BY RESEARCHERS IS MORE VALUABLE TO INDUSTRY THAN INVENTION
York Times investigative report provided rare insight into the
value to device companies of prominent researchers. Device researchers
who also chaired large cardiology conferences were allocated five
times the equity interests by the device company, as were allocated to
the inventor of the device. When the Times
provided these facts to Doctor John Wasson, a professor of medicine at
Dartmouth, he said, "the conflicts are just overwhelming. If you
cant trust the opinion leaders, and worse, the studies themselves,
what happens to the profession and what happens to patients." (Times,
November 30, 1999) [emphasis supplied] Even the tobacco
companies can purchase what they need - signatures of leading
companies secretly paid 13 scientists a total of $156,000 to write a
few letters to influential medical journals. One biostatistician
received $10,000 for writing a single, eight paragraph letter that
was published in the Journal of the American Medical Association.
A cancer researcher received $20,137 for writing four letters and an
opinion piece to [the British medical journal] the Lancet,
the Journal of the National Cancer Institute, and the Wall
Street Journal. The scientists didnt even have to write the
letters themselves. Two tobacco industry law firms were available to
dot he actual drafting and editing." (Metro Times Detroit,
February 6, 2001)
tax system would fail without audits and prosecutions of the largest
cheats. There is so much evidence and concern that a substantial
portion of drug and device research has lost integrity, with no
effective mechanism to reverse the trend, that the most rapid and
perhaps the only effective method of deterring fabricated or
misleading research to promote product, may be prosecution of those
researchers who combine large financial conflicts with large research
frauds. Recently obtained evidence indicates that the most substantial
frauds in clinical device research and promotion may be three research
surgeons (brothers) who have generated published data on over 30 new
surgical devices and/or procedures which promote over $10 billion
dollars in sales - obtaining personal revenues of up to $500 million
in the process.
CASE OF FRAUD