By Margaret Munro CanWest News Service
VANCOUVER – The research promoters come courting Dr. Kam Shojania every few weeks. The busy rheumatologist was recently asked to enrol patients in a gene -therapy experiment sponsored by a U.S. biotech firm that entails injecting live, genetically engineered viruses in patients’ arthritic joints. Other companies came looking for volunteers to test new drugs that promise to arrest the crippling affects of rheumatoid arthritis.
Money is not a problem. The companies will pay $3,000, $4,000, $5,000 for every patient Shojania enrols – sometimes much more. One current ‘trial’ is paying $18,000 per patient. “It’s very labour intensive,” says Shojania, who heads clinical trials at an arthritis research centre in Vancouver.
The affable young doctor says he turns down about half the studies he is offered. But the research promoters keep coming round, pitching more trials because Shojania has ready access to something they cannot buy: human volunteers.
Pharmaceutical companies are not allowed to pay patients with disease to test or try their experimental medicines. (In the very early stages of drug development, companies can pay healthy volunteers to test promising compounds for toxicity.) But the companies are permitted to pay doctors to test new drugs and treatments on patients as part of clinical trials, which are a sideline for a growing number of Canadian doctors.
Physicians say there are perks – a steady flow of research money, expense-paid trips to investigator meetings, being on the leading edge – but they insist they are not getting involved in clinical trials to get rich.
The money is compensation for work done and the patients benefit most by getting early access to new medicines, says Shojania.
But some people, privy to the deals doctors are signing with research companies, say the fees paid to doctors for enrolling patients in trials are often generous, and sometimes excessive.
“The max I’ve ever seen is $2,000 for a single visit,” says Dr. Muhammad Mamdani, who sits on an Toronto ethics board that reviews clinical trials and has seen a few eye-popping numbers cross his desk.
So has Dr. Douglas Kinsella, retired assistant dean of medical bioethics at the University of Calgary, who now works as a consultant in Kingston, Ont. He knows of one psychiatry ‘trial’ that paid doctors close to $20,000 for every patient enrolled. “The fee was excessive, as they often are,” says Kinsella, who is particularly concerned with the growing number of doctors in community clinics running drug trials “like a business.”
“The docs basically sign the forms and collect the cheques. The research nurses do most of the work,” says Kinsella.
Dr. Paul Flynne, assistant registrar of the College of Physicians and Surgeons of Alberta, sees details of clinical ‘trial’ contracts signed by community-based doctors in Alberta. “Money is an issue I can assure you,” he says.
Physicians cannot charge provincial health plans for work done for trials and are paid instead by the sponsoring companies. The fees, when broken down in the budgets Flynne sees, are often double the rate paid by provincial plans for the same procedures. A patient consultation and check-up that would earn a doctor about $150 from the provincial health plan typically pays closer to $300 when done as part of a ‘trial’, he says.
The higher “private sector rate” often paid to doctors running trials is justifiable because provincial health plans are too low, as some fees have been frozen for years, says Dimitris Polygenis, an official with Phase 4 Health, a Toronto company that runs trials across the country.
Flynne says he may have a point. But Flynne stresses the need for a clear definition of what constitutes reasonable professional compensation for working on clinical trials and what should be considered outrageous.
“It is something that we need to come to grips with at a national level,” says Flynne.
Overhead fees are another grey area. Polygenis recalls a recent ‘trial’ run at several locations across Canada. It offered the same per patient payment to all participating doctors. But one physician, working at a private clinic, asked for an extra 25 per cent for unexplained “overhead.” He got the money, says Polygenis.
Simple trials, known as Phase 4s, involve new drugs approved by ‘Health’ ‘Canada’ and are widely seen as marketing tools. They usually entail the doctor giving a patient a new medication and asking him or her to fill out a questionnaire or two for the sponsoring company. Doctors are paid a fee for each patient they enrol – $10 to $300 for what often takes no more than 15 minutes, says Mamdani. But fees can be even higher, he says, citing the $2,000 payment for a single visit which his ethics board ruled excessive and didn’t allow.
Phase 3 trials involve drugs not yet approved for use by ‘Health’ ‘Canada’ and typically involve several return visits to the doctor’s office. They pay $2,000 to $5,000 per patient. But the fee can climb to $10,000 or more per patient for more complex, time-consuming trials like the current arthritis project in Vancouver.
“It’s paying $18,000 per patient, but everything is spoken for in the budget,” says Shojania. The patients involved have to undergo a drug infusion every six months – a procedure that involves three nurses and a supervising doctor, he says. Then there are monthly check-ups and tests over the course of the five-year study.
Shojania, one of B.C.’s busiest rheumatologists, sees close to 2,000 patients a year at clinics in Vancouver and nearby Richmond and White Rock. When standard therapies do not relieve a patient’s swollen, aching joints, Shojania says he might suggest they consider a clinical ‘trial’.
He says he is “picky” about the trials he joins. Some he has been asked to join were so badly designed he felt they were unethical. He will not name the companies involved but says those trials ended up in the reject pile.
Shojania says the profit margin on trials is typically 10 to 20 per cent – money that he and his colleagues put towards other research projects at the arthritis centre.
He says trials that pay high fees usually have strict enrolment criteria that make it difficult to find suitable patients. And the companies co-ordinating the trials are sticklers for detail. “They make us work for the money,” he says.
Shojania recalls how it took months to get a waiver for a nun enrolled in a ‘trial’ that required women to undergo a pregnancy test and take birth control pills. Another company complained “because they couldn’t read my signature,” he says.
Family practice clinics are also key to the growing network of clinical ‘trial’ “sites” across Canada. They typically have nurses organizing trials and feeding blood samples, forms and data to the sponsoring research company.
Nurse Bea Carlson co-ordinates trials at a busy family practice in Coquitlam, B.C., which includes several doctors including her husband Dr. Brian Carlson. It is one of 220 clinics around the world, including one in Conception Bay, Nfld., and two in Thunder Bay, Ont., which recently posted recruiting ads on the Internet looking for 600 people to test a new diabetes treatment.
Carlson would not name the company paying for the ‘trial’, or disclose the fee paid to enrol patients, citing confidentiality. “It’s for the protection of the patient,” she said.
The story is much the same at Vancouver Hospital, where Dr. Bernie Bressler oversees clinical research which in brings millions of dollars each year.
Payment for trials is typically paid on a per-patient basis, he said, but amounts vary greatly depending on the complexity of the ‘trial’. The fees paid are confidential, he says.
Many observers say it is hard to know if the interests of the patients are paramount. They say doctors and universities should be open and tell patients how much they are paid to enrol them in a study, be it $100 or $10,000. “I don’t see why it should be hidden,” says Flynne.
Ethicist Michael McDonald at the University of British Columbia is even more emphatic. “Doctors should be absolutely clear how much they are being paid,” he says.
CLINICAL ‘TRIAL’ PROBED:
The U.S. Department of Health and Human Services last year launched a probe into a clinical ‘trial’ conducted by Canadian drug company, Biovail Corp, based in Mississauga, Ont.
U.S. investigators are looking into a Biovail project called PLACE, which stands for Proving LA Through Clinical Experience. Biovail offered doctors as much as $1,000 US if 11 of their patients tried Biovail’s new heart medication, Cardizam LA. Office managers were paid $150 for helping the doctors with the prescription program. While the investigation is said to revolve around whether the payments violate U.S. anti-kickback laws, Biovail spokesman Ken Howling said last fall the doctors were participating in clinical research and that it was “standard practice to compensate doctors for clinical research.”
‘Health’ ‘Canada’ has no comment on whether Biovail has been operating similar trials in Canada, saying the department does not regulate so-called Phase 4 trials, which involve drugs that have been approved for use. “It is not within our jurisdiction to investigate,” says spokeswoman Krista Apse. “This is a practice of medicine issue,” she said, and falls under provincial jurisdiction.
SLOPPY PRACTICES PLAGUE DRUG TRIALS:
When ‘Health’ ‘Canada’ inspectors took a close look at a small number of clinical trials underway across the country, it made some disturbing findings. They uncovered deficiencies in almost all the trials, ranging from sloppy bookkeeping to unqualified staff.
In one instance, the inspectors found that a woman helping to run a ‘trial’ had no apparent training for the job. But that did not stop her from assisting with heart scans or signing off on key study tasks.
“There was no documented evidence that the office administrator to the qualified investigators was trained in any aspects of the study,” says a recent ‘Health’ ‘Canada’ report. “However her name appeared on the site staff signature sheet with a Key Delegated Study Task, E she also indicated that she assisted in performing ECG procedures on study subjects.”
The report details findings of voluntary inspections done on 18 trials across Canada in 2002. The inspectors made 108 observations, with deficiencies in staff training and “inappropriate delegation of responsibilities” noted nine times.
But the most prevalent deficiency – noted in the inspectors’ logs 41 times – was with record keeping and paperwork: A “severe headache” noted by a doctor was transformed into a “moderate” headache on an adverse event report. Patient records and signed consent forms went missing. Consent forms failed to lay out the risks patients were taking by joining the experiment or drug ‘trial’.
The report also notes how one patient was enrolled in a ‘trial’ before undergoing the necessary medical examinations.
In another case an experimental drug – which needed to be kept between 15 to 30 C – was shipped in the dead of winter. “The shipping of these drugs occurred during the months of November and February E when tablets and capsules must be protected from cold temperatures and humidity,” the report notes.
‘Health’ ‘Canada’ will not identify the drugs tested or the location of the trials.
“It could be anywhere in the country,” says ‘Health’ ‘Canada’ spokesman Krista Apse, when asked for more information on the untrained office administrator assigned key study tasks. “At what point do I draw the line, if I say Ontario, you’ll ask the town,” said Apse, stressing the need to protect the confidentiality of the companies, doctors and patients involved.
The inspections were done as part a year-long “confidence-building phase” initiated by ‘Health’ ‘Canada’ so companies and investigators could better understand what is required to be in compliance with federal rules for clinical trials that came into force in January 2002.
The department said in early 2002 that it planned to inspect 80 trials a year out of the approximately 4,000 on-going clinical trials in Canada. In the end Apse says about 25 inspections took place between Nov. 2002 and Dec. 2003. The findings are to be released later this spring.