A counterweight to the influence of drug money on clinical trials?
Some more disheartening information is to be found in the Pioneer Press opinion piece by Carl Elliot, a U of M bioethicist. Once again a fairly obvious ethical lapse seems to have happened at the U in this case with fatal consequences.
These are the kind of events that make it absolutely essential that the University come forth with a conflict of interest policy that is exemplary. At this point doing a half-hearted job with the excuse that it is better than nothing is unacceptable. Somehow the current leadership at the U, both in Morrill Hall and Children's Rehab, still doesn't seem to get it.
The solution to AHC/med school problems may be on the horizon. The current dean will be gone, at the end of June, and the AHC head will follow in a year. Unfortunately, leadership change during the present financial challenges is less than optimal. But in the long run the change is both necessary and, hopefully, an improvement. Those of us who've been around for a while remember the disaster that was William Brody, Frank Cerra's predecessor. It took a very long time to find the current medical school dean. So, contrary to what you might hear from our glib administrators, change is not always good.
Carl Elliott teaches at the Center for Bioethics at the University of Minnesota. He's the author, most recently, of "Better than Well: American Medicine Meets the American Dream." His next book is "White Coat, Black Hat."
Five years ago this April, a handsome young man with an English degree and literary ambitions died while he was a participant in a research study at the University of Minnesota. His name was Dan Markingson. Whether Dan fully understood the research study he signed up for is disputed.
Also disputed is whether he had voluntarily agreed to take part. What is clear is that the study ended for him with what is known in the clinical trials industry as a "serious adverse event." He stabbed himself to death with a knife in the shower. He was 27 years old.
Dan grew up in St. Paul, but had moved to Los Angeles with hopes of becoming a screenwriter. In the summer of 2003, he began showing signs of mental illness. His thoughts became paranoid and delusional. He became convinced that he was part of a satanic cult, which was calling on him to murder his mother. Uninsured, with no access to medical care in Los Angeles, he was eventually persuaded to move back to St Paul.
A psychiatrist at the University of Minnesota believed that Dan's thinking had become so impaired that he was mentally incompetent to make his own medical decisions. The psychiatrist also thought Dan was potentially so dangerous that he ought to be involuntarily committed to a state mental institution. A judge agreed.
In Minnesota, however, a mentally ill patient who has been involuntarily committed has another option, called a "stay of commitment." The patient can avoid commitment by agreeing to comply with the treatment recommendations of his or her psychiatrist. In this case, however, Dan's psychiatrist recruited him into a drug study at the university, sponsored by a multinational pharmaceutical company and overseen by a Contract Research Organization — a specialized private company that manages clinical research.
The study was designed to test and compare three antipsychotic drugs on subjects who were experiencing their first psychotic episode. It was while Dan was in this study that he committed suicide.
New legislation being considered in Minnesota would aim to prevent the circumstances that surrounded Dan's death from happening again. Rep. Karla Bigham and Sen. Don Betzold have introduced a bill that would bar medical researchers from recruiting mentally ill patients who are under a court commitment order. The bill should be uncontroversial.
In fact, many studies of antipsychotic drugs already exclude anyone who is at risk of suicide or violence to others. (The study during which Dan Markingson died was supposed to exclude subjects "at serious suicidal risk" but did not mention violence.) Mentally ill patients who are dangerous to themselves or others do not belong in a drug study. They need to be given the best possible treatment, under extremely careful supervision, where they can be protected from their own actions.
Virtually any drug study will carry risks. Patients may be given drugs that do not work or that make them worse, or that have dangerous side effects. Sometimes patients are given a placebo. Even in studies where every drug under study has been approved by the FDA, patients may well get care that is inferior to what they would have gotten outside the study.
A study may place strict limits on the kinds of treatments the subjects are allowed to receive, for example. Because of the potential dangers of research, a cornerstone of research ethics is the voluntary and informed consent of the research subject. Yet how voluntary is a subject's consent when the other option is involuntary commitment?
The larger problem at issue here is the changing landscape of medical research. Over the past 25 years, clinical medical research has been transformed from an academic endeavor conducted largely in universities into a profit-driven, multinational industry. Most clinical research today is funded by the pharmaceutical industry, managed by Contract Research Organizations, approved by for-profit ethics boards, and supervised by physicians in private clinical trial sites. The financial stakes are enormous. Revenue from Contract Research Organizations alone exceeded $17 billion in 2007.
If universities want to compete for industry-funded studies today, they must compete on terms set by the world of private business. This means recruiting patients into studies as quickly as possible, in order to get drugs to market quickly while the patent clock ticks toward expiration. When the Office of the Inspector General of the Department of Health and Human Services investigated research practices in 2000, its report warned of the incentives given to university researchers to recruit patients into studies, such as departmental funding, equipment, authorship on journal articles and salaries for research staff. In addition, many university researchers have lucrative financial relationships with the companies sponsoring their research, such as paid consultancies and speaking arrangements.
Many universities propose to manage the conflicts of interest created by these financial relationships simply by disclosing them. But there is no evidence to suggest that disclosure alone will eliminate the pressure to recruit subjects. Disclosure merely gives the illusion that conflicts have been resolved while allowing researchers and universities to continue collecting industry money.
Any serious attempt to clean up industry-sponsored research must do at least two things. First, it must minimize the internal pressure faced by researchers to raise money for their departments. Second, it must eliminate the external financial incentives that lead researchers to recruit patients into studies instead of giving them proven treatment. Unless these conflicts of interests are eliminated, universities will continue to repeat the mistakes that preceded the death of Dan Markingson.