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."
