Firms Aim to Educate Patients on Test Risks
By Julie Bell
July 17, 2005
Tamir Orbach had just learned that he had a potentially fatal bone marrow disease when he had to grapple with an extraordinarily difficult choice.
Should he have the standard treatment: a bone-marrow transplant with high-dose chemotherapy and radiation that could cause life-threatening complications itself? Or should he choose a transplant and an experimental, lower-dose treatment that might be easier on his body but was unproved?
"I was terrified," said Orbach, 31, of Gaithersburg, Md., who was told last year that he had an aggressive case of a rare bone-marrow disease known as PNH. "Up until then, I thought I was invincible."
Like Orbach, patients and their families often are overwrought from bad health news when they are asked to consider participating in a clinical trial. Weighing the potential risks and benefits is even more difficult when in an emotional fog.
But recently, a small, yet growing number of clinical research programs have been making efforts to better educate patients and the public about the risks and benefits of participating in trials - the human tests of drugs and medical devices for which millions of people volunteer annually.
People who run clinical trials acknowledge that the motivations for patient and public education go beyond wanting to do the right thing. They are also a response to fear of lawsuits, pressure from insurers, the desire to appear competitive to drug companies in search of clinical trial sites, and concern over a dip in public trust in the wake of research deaths.
"Anybody who's in the field understands that there has been some erosion of public trust as a result of some of the problems that have occurred," said Susan Buskirk, executive director of the University of Maryland School of Medicine human research protections program.
Aurora Health Care in Milwaukee recently conducted a forum to explain clinical trials to the public. A National Institutes of Health grant pays for a clinical trials educator at a nonprofit organization that helps bone-marrow disease patients such as Orbach. And organizations such as Dallas-based Baylor Research Institute, which oversees clinical trials in at least 13 institutions, and the University of Maryland medical school have developed brochures and are planning improved Web sites to help potential enrollees examine their options.
The Johns Hopkins University is deciding how to expand education, as well.
An increasing number of academic medical centers and private clinical trials oversight boards are even seeking accreditation. They hope that will increase both their efficiency and the public's trust - helping attract more trials and patients for them. The two organizations that offer such accreditation - the Partnership for Human Research Protection and the Association for the Accreditation of Human Research Protection Programs - require efforts to educate those who might enroll.
The U.S. Food and Drug Administration requires clinical trials - a series of tests in humans - to show the safety and effectiveness of drugs and medical devices before they are marketed. Without them, medical advances would grind to a halt.
But trials are also big business that can lead to conflicts of interest. Drug company sponsors pay institutions to serve as host for them; the scientific breakthroughs that result can bring fame - and potentially fortune - for the physician researchers who oversee them; and medical centers compete hard for trials to be at the center of cutting-edge medicine and the money that comes with that.
Alan C. Milstein, a Philadelphia-area attorney who has made a name representing clients harmed in research experiments, said accreditation will do little to improve safety, no matter how many questions research subjects learn to ask.
"There's so much research going on. The money is so big, that I don't believe this is a measure that solves the problems that exist in the system," Milstein said about accreditation.
Worldwide, about 50,000 trials were under way in 2003, about 35,000 of them in the United States, according to CenterWatch, a Boston-based unit of the Thomson Corp. It estimates U.S. trials have as many as 3.5 million enrollees.
Despite the large numbers, the U.S. scientific community has trouble recruiting patients for them. About 80 percent, CenterWatch says, are delayed at least one month partly because they can't find research subjects fast enough to fill them.
The theory behind increased outreach is in part that patients who are knowledgeable about trials will be more confident in their ability to weigh risks and benefits.
Patient education is also in order, advocates say, because the clinical trials enterprise is overseen by a fragmented and understaffed federal oversight system.
The 38-person Office of Human Research Protection has jurisdiction over trials conducted or funded by the Health and Human Services Department. The FDA - with 276 U.S. clinical investigators in 2002, the most recent figure available - has oversight of any trial that spawns data submitted to put a drug or device on the market.
In practice, trials largely are overseen by local ethics panels called Institutional Review Boards. The boards, which can be associated with an institution or be independent, are charged with ensuring human research subjects are protected and that the risks of a scientific experiment on them are appropriate and in balance with the potential benefits for society as a whole.
But with federal oversight stretched thin, their performance isn't regularly reviewed by any outside authority. That became clear following the deaths of research volunteers Jesse Gelsinger at the University of Pennsylvania in 1999 and Ellen Roche at Johns Hopkins University in 2001.
Gelsinger died in an experiment at Penn's gene therapy institute, whose director co-founded a company that hoped to market the discoveries. Roche, a Hopkins lab technician, died after inhaling a chemical in a study of healthy lung function. Previous studies had shown the chemical caused fatal reactions, but researchers had failed to find them.
"Obviously, we had a terrible tragedy here," said Dr. Michael J. Klag, the Hopkins physician and administrator who took the position of vice dean for clinical research to help change medical school practices in the wake of Roche's death.
The school went from two IRBs to five internal ones, while contracting with a sixth, and has gone from spending very little on human research oversight to a budget of about $5 million a year. Now, he said, the university is pursuing accreditation to ensure it is regularly reviewed - and looking at expanding its patient education efforts.
Although accreditation is voluntary and only 28 organizations so far have gotten it, insurers might begin requiring it. The Chubb Group of Insurance Cos., which covers life science companies, has begun to ask whether the sites organizations use for clinical trials are accredited.
The two accreditation organizations say they can help fill in the gaps in federal research oversight, including by requiring the kinds of outreach to patients that traditionally haven't been required by anyone.
The Partnership for Human Research Protection has begun its own national education program, largely consisting of a brochure that explains trials and gives patients questions to ask the physicians overseeing their trial.
Among the questions patients are encouraged to ask: "Who stands to benefit financially from the results of this study?" and "Is it possible I will receive a placebo?"
Orbach, whose doctor says he was cured of PNH by the treatment he got in a National Institutes of Health clinical trial, used the Internet to find out about clinical trials and his disease. But he says he supports patient-education efforts such as the partnership's.
"I had myself, my parents, my friends, ask (questions)," he said. But there were plenty he didn't know to ask, including questions about financial conflicts. "It wouldn't have occurred to me," he said, "and I think those are important questions."
Paul Gelsinger, Jesse's father, also supports such efforts. In a conference call with reporters last month, he urged potential clinical trials volunteers to ask questions, saying "I didn't know about the serious dangers Jesse faced until after he died."