By Elaine Schattner, M.D.
Independent journalist
An eclectic expert panel considered "Clinical Trials: Intersection of ethical, practical and financial" – a topic rife with undisclosed financial perks, conflicts of interest and potential benefits for participants, academic researchers, drug companies and patients.
The speakers included academic physicians Carl Elliott, M.D., Ph.D., and Jason Karlawish, M.D.; Robert (Bob) Helm, a former professional research subject; and John Fauber of the Milwaukee Journal Sentinel. Fauber, who has reported on problematic aspects of medical device research and FDA approval, organized and moderated the at-times intense discussion.
Elliott, a professor of bioethics and pediatrics at the University of Minnesota Medical School and author, offered the first segment: a harrowing tale of a dangerously psychotic young man who, under coercive circumstances and in the absence of clear-mindedness, signed on to a clinical trial (CAFE – comparison of atypicals in first episode of psychosis) in which he was prescribed Seroquel, a drug manufactured by pharmaceutical giant AstraZeneca. The patient's condition deteriorated and, ultimately, he killed himself.
As Elliott tells it, the psychiatrist who enrolled the patient on the study had significant monetary incentives to recruit subjects for this trial, to the tune of $15,000 per patient, besides consulting fees and other benefits. That doctor's department chair at the university also had lucrative dealings with AstraZeneca. Elliott outlined those financial relationships and told of the story's dénouement: the patient's mother, who'd tried desperately to get her mentally incapacitated son off the trial as his condition deteriorated, sued AstraZeneca after his death. The doctors and university were exonerated; she eventually settled upon being hit with countersuits. The FDA looked into the circumstances and found no fault.
Fauber, an award-winning AHCJ member, shared his take on research leading to the FDA's approval of BMP-2, a compound that's used in spinal fusion surgery. While examining transcripts of an FDA meeting, he noticed something odd: "I came across a comment by a panel member that nine of the doctors in the clinical trial had a financial stake in the trial, and their results were about twice as good as those who didn't have a financial interest in BMP-2."
Fauber found that more than a few doctors involved in the BMP-2 research had financial ties to Medtronic, which sells the product. Sales have reached around $800 million per year, and about 85 percent of that comes from the product's off-label use, he explained. The substance turns out to have significant side effects, as were highlighted in a recent New York Times article. Still, the physician investigators' receipt of large payments from Medtronic has not been mentioned in most medical journal articles supporting its use in surgery.
"Doctors who read about drugs or devices need to know who does the [research] work, and if there's a potential for bias," he emphasized. "Doctors need to know that, and patients need to know that too. This, also, raises questions on whether doctors who have such financial ties should even be allowed to do research on these products."
The third, riveting segment came from Helms, a former professional research subject, a.k.a. a human guinea pig. He's been through the mill, volitionally: he's taken blood-thinners, anti-viral drugs, anti-depressants and more by signing on to participate in clinical trials as a healthy control. Now that he's passed the "sweet" study age of 18 – 45, the period in which a healthy person can, in effect, make a living as a serial research subject, Helms has written about his experiences at GuineaPigZero.
What he told the audience was a mucky tale of a research protocol requiring swallowing pills and collection of stool samples for remnants, to see how well the drug dissolved internally. Paid study participants had to reside in an old hospital building with poor ventilation. After the trial's coordinators changed the study's timing so it interfered with participants' Christmas and New Year's plans, the paid research subjects demanded that they be better compensated for their work.
People would wonder why we weren't unionized, he said. "Human guinea pigs are not the employees of the hospital, or the drug company, or the doctor whom they volunteer for. They work under temporary contracts, he explained. "As things stand now, human guinea pigs are in the gray area between research volunteers and patients," he continued. "And it's much easier to stand up for your rights in that area than it would be as a temporary worker."
Finally, the crowd heard from the fast-talking and insightful Karlawish, a bioethicist, geriatrician, Alzheimer's researcher and professor of medicine at the University of Pennsylvania. After disclosing some potentially relevant interests, including his research at the Penn Memory Center and board participation at Senior Bridge, he went on to describe the evolving and increasingly business-oriented nature of academic medicine.
"We're witnessing the rise of 'academic capitalism,'" he said. "Pharmaceutical companies are shedding their drug discovery people and they're looking to the academy to fill it," he said.
The university has two valuable commodities: "They've got scientists – very smart, hard-working people, and specimens." These would include blood, other clinical samples and people with diseases, he explained.
In the last section of this session, Karlawish went on to consider the issue of biomarkers, and how doctors are using those, instead of clinical outcomes, to define diseases. "Biomarkers that will define Alzheimer's disease will generate a market for drugs," he said.
Finally, he introduced a term: theranostic. The neologism combines therapy and diagnosis; novel tests or markers would identify patients who, as defined, benefit from a particular therapy. The first international conference on theranostics will be held in June, he said.
The session ended, overtime, with some excellent questions. One that generated strong reactions was offered by Kelley Weiss from the California HealthCare Foundation Center for Health Reporting. She asked about health insurance coverage for volunteer medical research participants.
Helms fielded it first: "I'm very cynical on this." Usually the legal department of the sponsoring company takes on the problem. Their job is to make it go away.
"The public relations and legal department of the sponsoring company will do anything they think of," he said. "And it's sometimes ruthless and gets very ugly, to blame it on the guinea pig."
Elliott took over the mike and said that most institutions won't compensate research subjects for pain or injury. "To me this is one of the most outrageous things about our clinical trials systems. First we have this massive exploitation of the poor, and then if they happen to get injured in the trial, they get no help."
Dr. Elaine Schattner is an oncologist, hematologist, educator and journalist who writes about medicine .
