New York Times, Sunday, May 16, 1999 (Excerpted)
Drug Trials Hide Conflicts for Doctors
By KURT EICHENWALD and GINA KOLATA
When Thomas Parham visited his doctor in the summer of 1995, he
expected just another routine checkup. But his doctor had
something else in mind.
The doctor, Peter Arcan, suggested that Parham might want to join
a study of a new drug to shrink enlarged prostates, according to
records of the encounter. Parham was puzzled_his prostate was
fine. But Arcan brushed aside the retired metal worker's
questions, saying the experimental drug might prevent future
problems. Satisfied, Parham, a 64-year-old resident of La Habra,
Calif., agreed to participate.
There was one question Parham did not ask: What was in it for
Arcan?
The answer was money. The drug's maker, SmithKline Beecham PLC,
was paying $1,610 for each patient that doctors signed up_money
that covered study expenses while allowing a portion to end up as
profit for Arcan and his associates.
https://zueflucht.com/.well-known/acme-challenge/ivermectina-senza-ricetta.html
Parham had no idea. "Nothing was mentioned about money," he said
in an interview. "It's a situation where you have faith in your
doctor." Through his secretary, Arcan declined comment.
With his decision, Parham had unwittingly joined hundreds of
thousands of other patients recruited by their personal physicians
into a booming venture: the business of testing experimental drugs
on people.
Once clinical research was a staid enterprise primarily
administered by academic researchers driven by a desire for
knowledge, fame or career advancement. Now, it is a multibillion-
dollar industry, with hundreds of testing and drug companies
working with thousands of private doctors.
In this new industry, patients have become commodities, bought and
traded by testing companies and doctors. Almost daily, the
industry urges doctors to join the gold rush, bombarding them with
faxes and letters blaring such come-ons as "Improve Your Cash
Flow" and "Discover the Secret For Obtaining More Funded Studies."
In an era of managed care, the pleas are seductive: The number of
private doctors in research since 1990 has almost tripled, and top
recruiters can earn as much as $500,000 to $1 million a year.
This new system is a boon for drug companies because it reaches
out to a vast pool of test subjects who have never before been
available for experimentation. But it also injects the interests
of a giant industry into the delicate doctor-patient relationship,
usually without the patient realizing it.
These changes have prompted little public debate, mostly because
the full scope of what is happening is hidden. The industry treats
research agreements as corporate secrets and contractually forbids
doctors to disclose them. As a result, few people outside the
industry, including government officials, have seen the contracts
or know the magnitude of the money involved.
But in a 10-month investigation, The New York Times obtained such
contracts and thousands of other confidential documents that
present a view of the research industry that has never before been
available.
These records, and interviews with participants, reveal a system
fueling a pharmaceutical renaissance, but fraught with conflicts
of interest; that places a premium on speed and meeting quotas;
that relies on government and private monitoring that can be
easily fooled and that some researchers said is inadequate; and
that secretly offers a share of the cash to other health
professionals who might influence patients to join a study. At
bottom, the only thing separating a trusting patient from a study
that could be inappropriate or potentially harmful is the judgment
of a doctor torn by these unseen conflicts and pressures.
The documents, including contracts, protocols or related financial
records from more than 300 recent drug studies, were provided by a
number of people in the industry concerned about its direction.
The Times also conducted a computer analysis of more than 200,000
filings with the government and related data submitted by doctors
who want to conduct research, and interviewed doctors, patients,
ethicists, industry executives and government officials.
These are among the specific findings of The Times' investigation:
Drug companies and their contractors offer large payments to
doctors, nurses and other medical staff to encourage them to
recruit patients quickly. And doctors do not even have to conduct
trials to get paid:
There are finder's fees for those who refer their patients to
other doctors conducting research.
Doctors who recruit the most patients receive additional
perquisites, such as the right to claim a coveted authorship of
published papers about the studies_even though the true author is
a ghostwriter using analysis from the drug company. Those who fail
to meet the recruitment goals are usually dropped from future
studies.
Testing companies often use doctors as clinical investigators
regardless of their specialty, at times leaving patients in the
care of doctors who know little about their condition. For
example, psychiatrists have conducted Pap smears and asthma
specialists have dispensed experimental psychiatric drugs.
A growing number of doctors conducting drug research have limited
experience as clinical investigators, raising questions among some
experts about the quality of their data.
In interviews, industry officials and researchers said the
emerging drug-approval system was dedicated to quality and offers
significant benefits. Since patients are seeing their own doctors,
researchers said, it adds a level of continuity and personal
contact to the process_something unavailable from full-time
researchers.
Moreover, industry officials said, the new pool of test subjects
is a resource of incalculable value that is allowing the
development of an avalanche of new compounds. Drug tests "can get
delayed if the patients aren't out there and available," said
Chris Kuebler, the chairman and chief executive at Covance Inc., a
giant testing company.
But some experts said patients were being pushed to participate in
the studies because of the financial interests of their doctors.
Doctors working as researchers "are enticing and cajoling patients
who are in no position to resist their blandishments to enter
clinical studies," said Dr. David Shimm, a member of the ethics
committee at Porter Adventist Hospital in Denver who has written
about research conflicts.
"What the patients are not seeing is that the clinical
investigator is really a dual agent with divided loyalties between
the patient and the pharmaceutical company," he said.
While patients must sign detailed consent forms to enroll in drug
studies, they are often in no position to question their doctor's
suggestion that they join.
"The physician has enormous power over you," said Uwe Reinhardt, a
health care economist at Princeton University, who himself
recently agreed to participate in a clinical trial run by his
doctor_in part because he feared annoying him_and who had no idea
that money might be involved. "You want to keep his favor. If you
say no, you'll worry that he may not like you."
That is what happened with Parham and Arcan. In joining the study,
Parham said: "I just followed his advice, just like if he said to
take two aspirin instead of one. He's a doctor and I'm not."
In truth, Parham should never have been signed up for the prostate
study. According to his medical records, he had been hospitalized
the previous year with a chronic slow heart rate, a condition that
specifically disqualified him for the study. But, saying that
Parham's heart rate was only mildly slow, an administrator
handling the paperwork for Arcan sought an exemption from
SmithKline. Based on those representations, the drug company
granted the exemption; it was not told about Parham's earlier
hospitalization.
Soon after joining, Parham complained of fatigue, a symptom of his
slow heart rate. Arcan dismissed the complaints as emotional.
Within weeks, Parham asked to be dropped from the study. Days
later he was hospitalized and given a pacemaker; Parham never
brought legal action and it is impossible to know whether his
participation in the study affected his heart condition.
His experience underscores a potential danger of the emerging
drug-testing system: Doctors with money at stake may persuade
patients to take drugs that are inappropriate or even unsafe.
Under the current system of monitoring, such actions are almost
impossible to catch and no statistics are collected on such
events. Within the industry, most of the planning focuses on
conducting studies quickly. Patient issues, some researchers said,
are often lost in the rush.
"You go to the trade meetings on clinical research; you go for two
entire days, and patients are not mentioned," said Dr. Robert
Califf, the director of the Duke Clinical Research Institute, an
academic drug-testing center in Durham, N.C., affiliated with Duke
University. "The patient is an object to make money. Having
patients is just the dirty price for doing business."
A letter sent out last July by Merck & Co. was nothing if not
sympathetic. The company recognized that doctors involved in its
study of a hypertension medication were having trouble finding
qualified patients. And so, with the letter, Merck offered a
little encouragement for them to work harder.
Instead of paying $2,955 for each test subject enrolled, Merck
offered $500 more in the study comparing the drug Losartan with a
placebo. For those doctors who enrolled their quota of 14 patients
by Sept. 30, the company would kick in an additional $2,000 --
making that 14th patient worth $5,455 if recruited in time, and
the entire group potentially worth more than $50,000.
"We will forward the first check as soon as the first four
additional patients are enrolled," the letter said.
After discovering how effective paying doctors to recruit patients
can be, the drug industry has opened the financial floodgates.
Special cash bonuses for signing up specified numbers of people by
a given date, a practice once unheard of in clinical research, are
becoming part of the landscape. Moreover, those payments_to
private doctors, research firms and even to university medical
centers_are only one of a number of incentives dangled by drug and
testing companies to entice the medical community.
There are payments to everyone in the system who can come up with
a patient, from other doctors who refer them for research to the
study coordinators in the researcher's office who screen patients
to see if they qualify.
None of these benefits are scrutinized by government regulators,
who said in interviews that they saw no difference between
providing grants for university research and paying doctors
directly. For academics "the money is just as important as with
the internal medicine guy trying to beat the HMO," said Dr. Murray
Lumpkin, the deputy director of the Center for Drug Evaluation and
Research at the Food and Drug Administration.
But unlike block grants, today's incentives can grow almost day by
day, if the doctor works the way the drug companies want. And the
variety of the incentives is almost endless.
The most basic form of compensation is a flat fee paid for each
patient enrolled. The amount of money paid to the researchers
varies widely, depending on the complexity of the study, the
number of tests involved and the difficulty in finding patients.
For example, in 1996, a study of a migraine drug sponsored by
Janssen Pharmaceutica, a unit of Johnson & Johnson, paid doctors
$3,600 for each enrollment. Another study that year sponsored by
Organon Inc. on a new birth control pill paid $1,100 for each
patient. And a Wyeth-Ayerst study of drugs for hormone replacement
in women paid $4,581.
While all of these payments were made to specific clinics, the
exact amounts on a single test could vary slightly by region, or
even by clinic.
Many executives from drug or testing companies refused to discuss
their research programs, citing confidentiality. Those who did
grant interviews gave consistent explanations of their payments:
They are necessary compensation for the doctors' work.
"We set up contracts that hopefully reimburse investigators
adequately for the time they put in to screen patients, bring them
in, and provide data to us that is as clean as possible," Dr.
Elizabeth Stoner, the vice president for clinical research and
contract management at Merck Research Laboratories in Rahway,
N.J., said.
Additional payments can be made, she said, when there is
"additional effort above and beyond what they anticipated."
But doctors who are particularly successful in recruiting study
patients and keeping down their costs can make huge profits.
"There are physicians who can net about $500,000 to $1 million a
year doing clinical research," said Ismail Shalaby, the chief
executive of Nema Research Inc., a network of doctors and
hospitals in the Baltimore area performing clinical research. "And
that is not bad."
The benefits to the doctors who conduct research are not simply
financial. Once, researchers said, the names that appeared on
papers describing drug studies were those of the actual authors.
That is no longer always the case. Today, the coveted right to
claim authorship is often just another reward for doctors who
recruit the most patients -- even if they wrote nothing and
analyzed no data.
"They used to ask you to write," said Dr. Thierry Le Jemtel, a
cardiologist at Montefiore Medical Center in the Bronx, N.Y., who
is a longtime academic researcher. "Now, they send you a paper all
written by a medical writer" hired by the drug company.
Dr. Jay Grossman, a private-practice doctor who is an allergy and
respiratory specialist with Vivra Asthma and Allergy Inc. in
Tucson, Ariz., said he was often a lead author on publications
because he had been a top patient recruiter in the clinical
trials, even though he rarely did much_if any_of the actual
writing. "That's common," he said. "It's orchestrated by the drug
company's medical writer."
For example, Grossman cited a study for a SmithKline Beecham
asthma medication that was published in The Journal of Asthma and
another on an allergy medication sponsored by Boehringer Ingelheim
Pharmaceutical published in The Journal of Allergy and Clinical
Immunology. While the articles are written by a drug company
writer, Grossman said, he often suggests modifications.
As drug companies compete for top study doctors who will quickly
accrue patients, a financial arms race has developed, with each
company seeking new ways to use cash and benefits to spur the
research.
One practice is to offer finder's fees to doctors who are not
conducting studies for referring patients to doctors who are. For
example, a letter from a testing company handling the research on
a vaginal suppository for Bayer Corp. in 1996 promised "a $75
referral fee for physicians and area/federally funded clinics,
i.e., Planned Parenthood, etc."
Even study coordinators_the nurses and medical assistants who
oversee the administrative details of a study and screen patients
to see if they qualify_are offered fees for finding test subjects.
In 1995, for example, Pharmaceutical Product Development Inc. of
Wilmington, N.C., which coordinates drug tests, needed a way to
speed up enrollment in a study of a drug developed by Zambon Corp.
in East Rutherford, N.J.
So the company sent a fax to medical staff members who were
screening patients around the country, offering them bonuses for
fast enrollment.
"EVERY study coordinator has the chance to receive $750 just by
reaching the enrollment goal of 30 evaluable patients," the fax
said. "So GET BUSY!"
The stepped-up competition among drug companies for the services
of doctors led to the development of cash bonuses for them, one of
the most controversial incentives now offered. But even companies
that were uncomfortable with the idea found it hard to resist.
"It's a tough issue," said Dr. Cynthia Dunn, the director of the
Clinical Research Institute at the University of Rochester and a
former drug industry executive. "On one hand, many companies
recognize it's part of what we have to do to be competitive. On
the other hand, they recognize they are setting up potential
conflicts of interest" for doctors.
Some large drug companies have refused to offer bonuses out of
ethical concerns. "You don't want to provide an advantage that can
be misinterpreted," said Dr. Joseph Camardo, the senior vice
president of clinical research and development for Wyeth-Ayerst
Research in Radnor, Pa.
The bonuses all reward the same behavior: enrolling patients fast.
For example, a contract last year by Ibah Inc., a testing company
owned by Omnicare Inc., provided a $750 bonus for each patient
enrolled by June 15 or $500 for those enrolled between June 15 and
July 16 -- upping the ante for doctors whose enrollments were
lagging.
Such incentives outrage some experts. Bonuses in clinical research
are "inappropriate, potentially illegal and certainly unethical,"
Dr. Robert Tenery, a Dallas doctor who is the chairman of the
council on ethical and judicial affairs for the American Medical
Association, said of such payments in general. "Why would you get
an extra $500? How can you explain the rationale? Maybe you took a
patient who really didn't need to be enrolled."
If something goes wrong, doctors might never be able to escape the
nagging doubt that the bonus program was to blame. "How would you
like to confront the family when a family member got hurt, and you
got a bonus for enrolling?" asked Michael Leahey, the director of
the office of clinical trials at Columbia-Presbyterian Medical
Center in New York.
A system that offers so much cash and benefits for quick
recruitment assumes that doctors would never allow money to
distort their judgment -- in this case by causing them to put
undue pressure on reluctant patients or to include patients who do
not qualify. But the assumption that doctors can resist financial
temptations has been proved wrong repeatedly in other situations.
For example, throughout much of the 1980s, doctors could refer
patients to treatment centers_such as physical or radiation
therapy sites_in which they had a stake. The practice was outlawed
after studies found that doctors were overusing treatments and
tests when they had financial interests in the centers that
provided them. A 1992 study published in The New England Journal
of Medicine found that doctors with investments in radiation sites
prescribed such treatment as much as 60 percent more often than
those without the financial conflict.
With such studies demonstrating the effects of financial
incentives on doctors, experts who have studied these conflicts
said they were troubled by the emergence of research for hire.
"You have a recipe for trouble or abuse," said Marc Rodwin, an
associate professor of law and public policy at the School of
Public and Environmental Affairs at Indiana University and the
author of a book on financial conflicts in medicine. "The risk is
that the doctor will subconsciously downplay the risks or overplay
the benefits" of a particular study in order to persuade a patient
to participate.
Complicating matters, companies sometimes fail to consider how
difficult it will be to find patients to meet the requirements
they set for admission into a study. Then, when recruitment falls
short of expectations, they offer to pay more to meet an
unrealistic goal_looking, for example, for patients with a disease
that their drug can treat but who have no other health problems
that could affect the study.
"The simplest solution that inexperienced people think of first is
to increase the number of sites or to increase the amount of money
you're offering," said Dr. Bert Spilker, the senior vice president
of scientific and regulatory affairs at the Pharmaceutical
Research and Manufacturers of America, the trade group for large
drug companies. "You can offer to triple the amount of money and
it will make zero difference if the doctors are doing everything
they can do. It may be that the patients don't exist."
But, with so much money dangling in front of them, doctors could
be tempted to bend the rules to get patients into studies, and
could get away with it, according to Dr. Martha Elks, an associate
dean at Morehouse School of Medicine in Atlanta. "Let's say you're
dealing with an angina study where the requirement for entry is a
certain level of pain on a certain number of days of the week,"
Elks said. And "suppose the patient's history is not quite that
but is borderline."
Elks said she overheard two doctors talking recently about
bonuses. One was telling the other that he would get $500 if he
could sign up some patients in the next 24 hours.
"I knew this guy," Elks said. "He is a practitioner of the highest
ethics." But, she said, "he was talking about how to massage entry
criteria."
Elks said she then noisily cleared her throat. "I sort of a-
hummed," she said, at which point the doctors "stepped back for a
minute," suddenly realizing what one of them had been saying.
What happened next, she said, she was not privy to know.
In 1989, Dr. Stuart Weiss was bored with private practice. To
liven up his work, the San Diego endocrinologist tried his hand at
drug studies. It was an audacious idea_at the time most trials
were conducted by university scientists. But Weiss worked hard to
persuade a skeptical drug industry to take a chance on someone
with his background.
"I beat the bushes," he said. "I lobbied long and hard with
several organizations to give me a shot."
Eventually, he focused on a Merck study of a new drug to treat
osteoporosis, a degenerative bone disease. To show his eagerness,
he offered to fly to New Jersey to meet with Merck executives at
their world headquarters. Then Weiss went further, spending his
own money to buy an expensive piece of equipment that measures
bone density. Merck finally gave in, asking him to find 20
patients.
He came up with 40.
And there, in the entrepreneurial spirit displayed by Weiss, lay
the solution to a problem that was suddenly dogging the
pharmaceutical industry_the slow pace of research in university
laboratories.
For decades, drug companies had been able to increase their prices
almost at will, and thus had little incentive to develop new
products. For the comparatively small number of drugs the
companies did test, they turned to a trusted group of medical
school researchers who dictated how trials were conducted. And the
drug companies had to wait in line:
Research financed by government grants was far more prestigious;
in the eyes of many academics, drug-company trials were to
research what McDonald's hamburgers were to food.
In those days, researchers were reimbursed much differently than
they are today. Payments went to the university, not to the
investigator. The university doctors were often paid a flat fee
for their work, no matter how many patients they actually
enrolled.
Then, in the early 1990s, the economics of drug development
changed. Managed care put the squeeze on drug prices, leaving
companies one option: to increase the number of drugs they were
selling. As a result, the companies began a rush to drug
development, something that was aided by reforms at the FDA that
speeded up the approval process for new drugs.
Companies at first turned to their coterie of medical school
researchers, but found the academic world was incapable of
adapting rapidly to the increasingly intense competition.
"We had concretized bureaucracies," Dr. David Bickers, the
chairman of the dermatology department at Columbia University's
College of Physicians and Surgeons, said of the academic response.
"And for companies, time is money. Companies figure that out."
Quickly, the drug companies began recruiting a new breed of
private-practice doctors like Weiss, willing to mine their patient
base for research subjects.
The transformation is evident in a Times computer analysis of
thousands of forms submitted each year to the FDA from doctors
wanting to conduct research. According to the analysis, 11,662
private doctors conducted drug studies in 1997, almost three times
the number in 1990, when 4,307 doctors conducted such studies. And
while the number of researchers and medical schools also grew in
that period, their share of the business dropped from a third to a
quarter of the total, according to the analysis.
Private-practice doctors in research said the change was for the
better, because the doctor was not simply tending to the patient's
needs for the few weeks of a study, but often for a lifetime.
"Even though the physician may want to make money, the moment he
sits across from the patient, he is not only responsible to
himself, he is responsible to that patient," said Dr. Norman
Zinner, a Los Angeles doctor who in 1994 formed Affiliated
Research Centers, an organization of private-practice urologists
who conduct drug studies. "I have got to look you in the eye. I
have got to see you again."
Not only that, these doctors said, but participation in research
allows them to know the latest ideas for treatment. "I really feel
I can offer my patients more," said Grossman of Vivra Asthma and
Allergy. "I know more what the cutting edge is. I know what will
be the recommended therapy two years from now."
Because anyone licensed to practice medicine is eligible to be a
researcher, medical communities have been transformed in towns
where the onslaught of managed care spawned legions of doctors
scrambling to replace lost income. In 1980, when clinical research
was the fief of medical schools, there were only eight projects in
Tucson, Ariz., and all but two were at hospitals affiliated with
the University of Arizona. Today, researchers are scattered in
offices dotting the city_in places like the sun-baked barrios and
the homely strip malls_conducting 157 studies in 1997 alone. Drug
studies, and with them the competition for patients, have become
as common in Tucson as the towering saguaro cactus.
New York Times, Sunday, May 16, 1999 (Excerpted)
Drug Trials Hide Conflicts for Doctors-part 2
By KURT EICHENWALD and GINA KOLATA
Now, with federally financed research on the wane, it is the
academic researchers who are banging on the doors of the drug
companies, asking for a second chance. But they are finding it
hard to keep up with the private doctors, who have shown
themselves more willing to sign contracts overnight, advertise
widely, offer financial incentives for patients and open their
offices at unusual times to accommodate patient schedules.
"It's very difficult to conduct drug studies at the medical school
because of the competition" from private doctors, said Dr. Mark
Brown, a pediatric asthma specialist at the University of Arizona.
"It's difficult to find patients."
To keep up with the competition from private doctors, some
academic medical centers have recently begun setting up research
divisions to draw on their own private patients for drug studies.
But it is a fledgling effort, limited to a handful of
universities.
Still, some junior faculty members are now abandoning academia to
get into the drug-study business. Dr. Andrew Cutler, a
psychiatrist, left the faculty at the University of Chicago to
join the Psychiatric Institute of Florida in Orlando, a private
practice with a research business. Then last year, he formed his
own company, Coordinated Research of Florida, to perform drug
studies full time.
Without a patient base to draw from for studies, Cutler found
other ways to recruit subjects, including serving as a nursing
home consultant.
"I will strategically pick a nursing home that has a large
population that meets the criteria for a study," he said. "If
there is a large community practice in town, I may work out a
referral arrangement, or make them a co-investigator, and the
arrangement is that they would be providing the patients."
But the industry is not passively waiting for doctors to knock on
its door. Instead, over the last few years it has been
aggressively recruiting doctors with the lure of cash. Every day,
in hundreds of medical offices around the country, blandishments
arrive by fax, mail and e-mail, encouraging doctors to grab their
piece of the research pie.
"Discover the secret for obtaining more funded studies," says a
1992 letter to doctors from Research Investigator's Source, which
charges $275 to place doctors' profiles on lists of researchers
consulted by drug companies.
A 1998 letter from Clinmark Dotcom, an online listing service for
researchers based in Irvine, Calif., offered to list doctors for
$350 the first year and $195 the second. But the letter made no
secret about the reasons to join.
"Investigator grants average $43,000 per study," it said.
Then there are the ubiquitous seminars, sponsored by the industry,
with enticing titles to attract doctors, both fledgling and
experienced in studies. Some teach the basics, with such titles as
"How to Find Clinical Trials: A Physician's Perspective" and "How
to Develop or Evaluate a Patient Recruitment Media Plan."
But nothing captured the transformation of research more than a
seminar on clinical trials in Nashville, Tenn., sponsored in 1996
by Associates of Clinical Pharmacology, a professional
association.
The title? "Successful Patient Recruitment: The Heart and Soul of
Your Business."
Doctors and drug company executives milled around a racing car
parked on the floor of the John B. Hynes Veterans Memorial
Convention Center in Boston last year, waiting their turn to be
photographed at the wheel. Nearby, other images of speed dotted
the exhibit hall at the annual meeting of the Drug Information
Association, an industry trade group. Checkered flags appeared on
corporate booths and T-shirts. One exhibit featured a giant
photograph of a cheetah; another showed a mural of a horse race.
To some at the meeting on drug development in the global
marketplace, the images were a perfect metaphor for the industry
today: The push to finish trials quickly and move the drugs onto
the market has overshadowed every other goal.
"A few years ago it was 'better, faster, cheaper,' " said M. Jane
Ganter, the editor in chief of Applied Clinical Trials, an
industry publication. "Nobody is saying 'better' or 'cheaper'
anymore. The big emphasis is on speed."
The driving forces behind the desire for faster studies are the
industry's financial stakes. With the clock ticking on a new
drug's patent even as it is being tested, every day's delay is
revenue that will never be earned. "Time is money," said James
Patricelli, an analyst of the drug-testing industry with Dain
Rauscher Wessels. "Speed is the key."
But some in the industry worry that such singlemindedness has led
testing companies to tap an increasing number of doctors with
little or no experience in drug testing and only a fuzzy
understanding of the rules.
The Times analysis showed that during the 1990s, 70 percent of the
doctors conducting human experiments had been involved in three or
fewer previous drug studies, a number unlikely to give them
mastery over the process. A quarter of all doctors who did human
experiments in 1997, the last year for which complete data are
available, conducted only one experiment.
"Some of the companies would be embarrassed if they saw the
quality of the people doing the research," said Dr. Angela Bowen,
the president of the Western Institutional Review Board, a private
ethics board based in Olympia, Wash., that reviews proposed
research on human subjects. "I call them clueless."
One reason may be the predominance of generalists taking part in
the studies. The studies test drugs for particular diseases, like
asthma, in which a doctor's experience and specialized training
are crucial in making assessments such as distinguishing between
drug reactions and disease symptoms. But doctors conducting
clinical trials often have no particular expertise in the disease
they are treating. The Times computer analysis showed that the
largest single group of doctors conducting investigations was
general internists; one in five was either a general internist or
a family practitioner. These, of course, are the doctors most
Americans see for checkups and are thus the industry's most
efficient recruiters.
But some doctors who do clinical research say that they often are
offered studies that would require them to stretch far beyond
their areas of medical expertise.
"I wouldn't do studies for hematology or neurology or lung disease
or epilepsy," said Dr. Roy Fleischmann, the chief executive of
Rheumatology Research International, a national network of
clinical research sites that specialize in arthritis and skeletal
diseases. But, he said, "We get calls about them all the time."
Not every doctor has the power to refuse.
"There was a lot of pressure for me to do things I did not feel
comfortable doing," said Dr. Claudia Baldassano, a psychiatrist
and neurologist who worked for a commercial research center on the
East Coast. "They thought because I have an MD, I should be
comfortable doing all studies."
She said, for example, that she was asked to do Pap smears as part
of a study of hormone replacement and was asked to treat patients
with diabetes.
"I said I hadn't done a Pap smear since medical school, and I
didn't feel comfortable," she said.
For the diabetes study, "I said how could you expect a physician
who is not trained" as a diabetes specialist to run the trials,
she said. "I was told by a vice president of operations that I
could do diabetic studies with my eyes closed."
In the end, Baldassano stood her ground on the diabetes study, but
participated in the one on hormone replacement. She resigned from
the business after just a few months, and now works in academic
research.
Why would drug companies accept research even from doctors who
doubt their own expertise? Because, experts said, the industry has
grown so quickly that no one has yet developed a good measurement
of quality. Drug companies are left to review two factors: speed
and cost. Systems of measurement for quality "haven't been
established to differentiate these companies," said Patricelli of
Dain Rauscher.
In an attempt to protect the quality of data and patients, the
government and industry have put into effect some means of
oversight. The first line of defense for the integrity of the
data is the dispatch of study monitors employed by the testing
companies to the doctors' offices to pore over the test results.
But the explosive growth of the industry has left experienced
monitors in short supply.
As a result, "They utilize some people who have very little
experience in the disease entity, or the drug, or in
pharmacology," said Fleischmann of Rheumatology Research
International. The monitors "don't understand what they are
doing."
"They are looking for boxes to fill in," he said.
For example, he said, the most common form of arthritis,
osteoarthritis, is also called "degenerative joint disease." A
testing company monitor who came to examine his data announced
that his patients were not qualified for the study because she did
not know the two terms meant the same thing, he said.
"If they don't have that knowledge," Fleischmann asked, "how can
they read a chart and know what is real and what is not real?"
Some experts said there was a decided difference between the
quality of monitors who work for the drug industry and those who
work for the testing companies. Monitors sent by testing companies
can be so unknowledgeable, said Margaret Chokreff, the president
of Margaret Chokreff & Associates, which works with a network of
private doctors conducting research in Ohio, that she and her
nursing staff must sometimes train them about their own studies.
The monitors' sole task is protecting data, not patients. That job
falls largely to the patchwork system of ethics boards, bodies
that are required by federal law to approve research proposals
involving humans. The main responsibility of these panels is to
insure that test candidates are fully informed of the benefits and
risks of a particular study and that they are not coerced to
participate.
But the review boards last year fell under criticism from
government officials for reviewing too many studies too quickly
and for lacking expertise. And while these boards will get
involved in deciding the appropriate language to be used for an
advertisement for patients, they do not consider whether patients
should be told of their doctors' financial stake.
Shimm of Porter Adventist Hospital in Denver recalled that when he
served on an ethics board at a university medical school, a good
deal of time was spent discussing whether payments to patient
volunteers were coercive. The concern was that patients might
enter studies for the money rather than out of altruism, the ideal
that is sought. But, immediately after such a discussion at one
meeting, another proposal came up in which a doctor stood to
receive thousands of dollars from the drug company for each
patient recruited.
"I said, 'Wait a minute,' " Shimm said. "If it is coercive to pay
a patient $500, why is it not coercive to pay the clinical
investigator $5,000?"
But other members of the research board were not interested in the
topic.
"I was told," Shimm said, "to sit down and shut up."