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.
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.
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."
Copyright 1999 The New York Times Company