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, which 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 unproven?
"I was terrified," said Orbach, 31, of Gaithersburg, who was told last year that he had an aggressive case of a rare bone-marrow disease known as PNH.
Like Orbach, patients and their families are often overwrought 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.
Those 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," said Susan Buskirk, executive director of the University of Maryland School of Medicine human research protections program.
Aurora Health Care in Milwaukee recently held a forum to explain clinical trials to the public. A National Institutes of Health grant pays for a clinical trials educator at a nonprofit that helps bone-marrow disease patients. 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 seeking accreditation. They hope that will increase both their efficiency and the public's trust - helping them attract more trials and patients. 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 that serve as hosts for trials; scientific breakthroughs can bring fame and fortune to physician researchers; and medical centers compete for trials to be at the forefront of cutting-edge medicine and the money that comes with it.
Alan C. Milstein, a Philadelphia-area attorney who represents clients harmed in research experiments, said accreditation will do little to improve safety, no matter how many questions the 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," Milstein said.
Worldwide, about 50,000 clinical trials were under way in 2003, with 35,000 in the United States, according to CenterWatch, a Boston-based unit of the Thomson Corp. Up to 3.5 million people are enrolled in current U.S. trials, the group estimates.
Despite the large numbers, U.S. researchers have trouble recruiting patients for clinical trials. About 80 percent of trials are delayed at least a month partly because researchers can't find subjects fast enough, CenterWatch says.
The theory behind increased outreach is in part that patients who are knowledgeable about trials will be better able to weigh risks and benefits.
Patient education is also in order, advocates say, because clinical trials are 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 (IRBs). The panels, which can be associated with an institution or be independent, are charged with ensuring that human subjects are protected and that the risks of an experiment 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 after the deaths of research volunteers Jesse Gelsinger at the University of Pennsylvania in 1999 and Ellen Roche at Hopkins 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 that the chemical could cause fatal reactions.
Filling the gaps
"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 reform 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 less than $1 million a year on human research oversight to a budget of about $5 million. Klag said the university is pursuing accreditation to ensure that it is regularly reviewed - and looking at expanding its patient education efforts.
Though accreditation is voluntary and only 28 organizations have received it so far, there is evidence that insurers may begin to require it. The Chubb Group of Insurance Cos., which covers life science companies, has begun to ask whether the sites they use for clinical trials are accredited.
"My interest is safety," said Jill Wadlund, a Chub vice president.
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.
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 them.
Among the questions that patients are encouraged to ask: "Who stands to benefit financially?" and "Is it possible I will receive a placebo?"
Orbach, whose doctor says he was cured by the treatment he got in a National Institutes of Health clinical trial, used the Internet to find out about clinical trials and PNH. 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 conflicts of interest. "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, he urged potential volunteers to ask questions about clinical trials, saying: "I didn't know about the serious dangers Jesse faced until after he died."
Planning to enroll in a trial?
Questions to ask your doctor or the researcher before enrolling in a clinical trial:
Why is this experiment being conducted?
Who is doing the study?
Will I be able to continue to see my own doctor?
Is there any cost to me or will I be paid to participate in this study?
Does anyone receive money for my enrollment in the study?
How long will the study last?
What tests or treatments will be used in the study?
What other options do I have if I decide not to take part?
Might I receive a placebo?
What could happen to me if I take part in the study? Have there been any ill effects reported? How serious?
Could my condition get worse during the study? What will happen if it does? If my condition worsens, will I be notified?
Can I stop participating in the study if I change my mind?
Could there be any danger to me if I stop participating?
Who pays for my care if I'm injured during the study?
What will happen to me at the end of the study? Will I be told the results?
Whom do I contact for information about the study? Do you have patient advocates, independent of your institution, I can talk to?
Who stands to benefit financially from the results of the study? Does the researcher have a potential conflict of interest? If so, how is it being managed?
Is the research program or institutional review board accredited?
Source: Partnership for Human Research Protection