A front page article in The Wall Street Journal provides a glimpse into the
nature of the true risks involved in participation in clinical trials. The
documented findings confirm our long-held view that current laws,
regulations, government or institutional oversight bodies fail utterly to
ensure the safety of human subjects.
"There is little definitive data on the number of injuries from clinical
trials, partly because there is no one government body that regulates all of
them."
Informed consent documents are crafted to provide liability protection to
corporations, universities, ethics review boards, and clinicians who conduct
the trials.
Patients are deliberately deceived by legal linguistic hyperbole:
"The prospect of compensation for injuries, of course, encourages volunteers
who might otherwise be reluctant. But the wording in these consent forms is
often confusing and vague. It can be unclear which research entity is
responsible for the cost of subsequent care, how much that entity will pay
and under what circumstances it is obligated to pay."
The WSJ reports that before Suzanne Davenport, aged 71, entered a clinical
trial testing a drug for Parkinson's disease, she could drive, cook and care
for herself.
Within months, she was wheelchair-bound and living in a nursing home.
Before entering the trial she signed a UCLA consent form (in 2004) stating:
"If you are injured as a direct result of research procedures, you will
receive treatment at no cost. The University of California does not provide
any other form of compensation for injury."
She then signed another consent document from the University of South
Florida, which employed the surgeon who would operate on her. The form
contained three "injury statements."
The first statement, from USF, said financial damages would be available to
her in the event of an injury "to the extent that negligent conduct of a
University employee caused your injuries," but such damages could be
"limited by law."
The second statement, from Tampa General Hospital, said the cost of
treatment for any injury "may be the responsibility of you or your insurance
company."
The third statement, from Berlex, said: "If because of your participation in
the study you require additional care that would not ordinarily be necessary
for your condition, this will be provided at no additional cost to you."
On Jan. 14, 2005, Ms. Davenport walked into Tampa General Hospital. When she
came out of the surgery, she was no longer the same person.
She could no longer stay upright in a chair and could not walk, her husband
says. She also needed a diaper and her mouth hung open.
The true nature of the potential risks of harm from experimental treatments
remain mostly concealed today--just as they had been concealed in 2000, when
18 -year old Jesse Gelsinger had unwittingly signed, what turned out to be
his death certificate, by volunteering for a fatally flawed gene therapy
(adenovirus) experiment.
Bioethicists with hidden financial ties to pharmaceutical companies-- then
as now--readily lend their rubber stamp of approval for whatever companies
do.
Contact: Vera Hassner Sharav
veracare@ahrp.org
212-595-8974
http://online.wsj.com/article/SB120173515260330205.html
THE WALL STREET JOURNAL
CLINICAL DECISION
When Drug Trials Go Wrong, Patients Have Little Recourse
By SARAH RUBENSTEIN
January 31, 2008; Page A1
COUPEVILLE, Wash. -- Before Suzanne Davenport entered a clinical trial
testing a drug for Parkinson's disease, she could drive, cook and care for
herself. Within months, she was wheelchair-bound and living in a nursing
home.
Ms. Davenport's family says the trial caused her precipitous decline. It is
suing the two drug makers that ran the trial and the university that
enrolled her in it for compensation to cover her mounting medical bills.
The case highlights one aspect of the legal and regulatory void surrounding
clinical trials. Federal law does not require researchers to compensate
participants harmed in such trials. It merely requires that their consent
forms spell out whether compensation will be available for research-related
injuries in trials that involve more than minimal risk.
The prospect of compensation for injuries, of course, encourages volunteers
who might otherwise be reluctant. But the wording in these consent forms is
often confusing and vague. It can be unclear which research entity is
responsible for the cost of subsequent care, how much that entity will pay
and under what circumstances it is obligated to pay. One big problem is that
it can be difficult to separate what was caused directly by a trial from the
natural progression of the participant's disease.
Companies "do not want to end up paying for all of somebody's care when that
care may simply be the product of the fact that that person had a grave
illness," says Haavi Morreim, a University of Tennessee bioethics professor
who has studied clinical-trials lawsuits.
The issue has come into heavier focus as drug companies, under increasing
financial pressure to bring drugs to market, have stepped up the pace of
clinical trials. World-wide, the number of industry trials rose to 59,000 in
2006 from 40,000 in 2000, according to an estimate from CenterWatch, a
clinical-trial listing service. The growth has come in part from a jump in
small early-stage trials meant to help drug companies weed out duds quickly.
Makers say it is also increasingly common to test a single drug multiple
times to see if it can treat different conditions.
There is little definitive data on the number of injuries from clinical
trials, partly because there is no one government body that regulates all of
them. But the issue is getting more attention following several widely
publicized lawsuits, including a suit over the 1999 death of Jesse
Gelsinger, an 18-year-old who participated in a gene-therapy trial at the
University of Pennsylvania.
Many lawyers had long been reluctant to pursue clinical-trial injury cases
because they worried the consent forms protected drug companies and
universities from liability, says Alan Milstein, the attorney for Mr.
Gelsinger's family. The Gelsinger case, which settled for an undisclosed
sum, helped raised public awareness of safety issues with trials. The
lawsuits also showed that it was possible to find flaws in the
informed-consent process and sufficient maneuvering room in the wording to
be successful. Mr. Milstein says he has filed 13 cases involving
clinical-trial injuries since then, with 11 involving full or partial
settlements.
A Gradual Decline
Suzanne Davenport, a 71-year-old retired kindergarten teacher, was diagnosed
with Parkinson's in 1989 after her husband noticed she was inadvertently
knocking her hand against posts as they walked their dog.
Her decline was very gradual, her family says. For years, she continued to
quilt, an activity that required the sorts of fine motor skills that
Parkinson's can ravage. But by 2003, the disease had advanced. Among other
things, Ms. Davenport had to keep redoing her stitches to get them right,
says her husband, Jim Davenport. She gave up the hobby.
In early 2004, neurologists at the University of California, Los Angeles,
where Ms. Davenport was receiving some of her care, discussed with her the
idea of participating in a clinical trial. It involved surgically implanting
an experimental drug called Spheramine into the brains of Parkinson's
patients with the aim of improving their motor skills.
The drug was in mid-stage development. An early-stage study in 2000
involving six trial participants with Parkinson's found that it was "well
tolerated without serious adverse events related to the treatment," and
patients' motor symptoms improved, according to a 2005 article in the
Archives of Neurology.
Spheramine was originally developed by Titan Pharmaceuticals Inc. of South
San Francisco, Calif. Titan entered into a partnership to develop the drug
with another company, Berlex Inc., which was the U.S. arm of the German drug
maker Schering AG. Berlex sponsored the trial and UCLA enrolled patients and
evaluated them before and after receiving the treatment.
On June 10, 2004, Ms. Davenport signed a UCLA consent form stating: "If you
are injured as a direct result of research procedures, you will receive
treatment at no cost. The University of California does not provide any
other form of compensation for injury."
Decoding 'Injury Statements'
Consent forms and compensation plans vary by institution. There have been
sporadic calls to standardize these programs, but none have been widely
adopted. The Institute of Medicine, a nonprofit group that advises the
government on health policy, recommended in 2002 the creation of a "no
fault" compensation system for injured subjects. The goal was to help trial
participants resolve their claims quickly, without having to resort to
lawsuits.
Throughout the second half of 2004, Ms. Davenport went through periodic
pre-operative tests at UCLA. Shortly before the scheduled operation, the
venue for the procedure was switched from Stanford University's medical
center to Tampa General Hospital in Florida.
Ms. Davenport signed another consent document, this one from the University
of South Florida, which employed the surgeon who would operate on her. The
form contained three "injury statements."
The first statement, from USF, said financial damages would be available to
her in the event of an injury "to the extent that negligent conduct of a
University employee caused your injuries," but such damages could be
"limited by law." The second statement, from Tampa General Hospital, said
the cost of treatment for any injury "may be the responsibility of you or
your insurance company." The third statement, from Berlex, said: "If because
of your participation in the study you require additional care that would
not ordinarily be necessary for your condition, this will be provided at no
additional cost to you."
On Jan. 14, 2005, Ms. Davenport walked into Tampa General Hospital. When she
came out of the surgery, she was no longer the same person.
She could no longer stay upright in a chair and could not walk, her husband
says. She also needed a diaper and her mouth hung open. On the flight home,
Mr. Davenport says he spent about four hours propping his wife's upper body
against the back of her seat so she wouldn't fall forward. In the following
weeks, Ms. Davenport hallucinated frequently and her cognitive skills had
diminished considerably, says her daughter, Julie Languille.
By September 2005, eight months after the surgery, Ms. Davenport required
constant monitoring. The family decided to put her in a nursing home outside
Seattle, near Ms. Languille's home. There, Ms. Davenport lost her balance
and fell a few times. The nurses put her in lap restraints to keep her from
getting out of her wheelchair.
Ms. Davenport's neurologist, John Roberts of Virginia Mason Medical Center
in Seattle, says he believes Spheramine caused her sudden decline. Dr.
Roberts was not involved in the trial, but learned from a UCLA neurologist
in early 2006 that Ms. Davenport was among the patients who had received the
drug. As is the case in many clinical trials, some patients who were part of
a control group had not received the drug.
Dr. Roberts, who had been treating Ms. Davenport for almost a year before
she entered the trial, says before the trial, she was able to walk and
conduct basic living activities independently. Based on her age and her
overall health, he estimates she could have gone another 10 years before
needing to move into a nursing home had she not taken part in the trial.
Ms. Languille says Medicaid, the government health-insurance program for the
poor, has paid for most of Ms. Davenport's care since the surgery, more than
$100,000 to date. Mr. Davenport, a retired aerospace engineer, is required
to contribute $700 a month. So far, the family says it has spent more than
$28,000 on her care.
In March 2006, Ms. Languille decided to seek compensation. She started with
Jeff Bronstein, the neurologist who was the lead investigator at UCLA. Based
on conversations with clinicians at other trial sites where patients
received Spheramine, Dr. Bronstein says Ms. Davenport's condition after the
trial was unusual. He says it was also not typical of Parkinson's patients,
which indicated to him that the drug was likely a contributing factor.
Dr. Bronstein referred Ms. Languille to an official at Titan who was his
main contact for the trial. He says he thought the companies were
responsible for compensation. "I thought it was going to be the best way to
help the family, and the fastest way," he says.
A contract between Berlex and the Regents of the University of California,
obtained by The Wall Street Journal through a public-records request, says
Berlex would reimburse the university for "reasonable" costs for treatment
needed as a result of the trial, assuming the study was conducted according
to its rules and the university wasn't negligent.
Ms. Languille spoke with Dmitri Lissin, a clinical-development director at
Titan. He asked her to send him the nursing-home bills so he could submit
them for payment. In a subsequent letter, Dr. Lissin wrote that Titan had
initiated a legal review of her mother's case. Ms. Davenport's decline "can
possibly be attributed to the natural course [of her disease] or
experimental treatment, or both," he wrote.
In an interview, Dr. Lissin, who no longer works for Titan, said
responsibility ultimately rested with Berlex, and he was helping them to
review the case.
Titan declined to comment on its role in Ms. Davenport's case but said in
written a statement that all trials of Spheramine have been monitored for
patient safety. It added that it is "committed to the...continued
development of Spheramine as a potential new treatment option for patients
suffering with Parkinson's disease."
Ms. Languille says she was next contacted by Berlex. In an email, Walter
Hong, a Berlex medical-development director who was following up on her
case, asked whether Ms. Davenport received any state aid, whether she would
qualify for Medicaid, and whether the family had "a plan in place for
spending down" its income and savings. The company says it was trying to
determine whether any settlement would damage Ms. Davenport's eligibility
for insurance from the government or another provider.
She was contacted next by a Berlex attorney, Eric Threadgold. She says he
told her over the phone that if the company were to pay, it would prefer to
do so in one lump sum rather than in monthly payments as bills arose. He
also said since Ms. Davenport would have required nursing-home care at some
point anyway, Berlex would only be accountable for the extra care required
as a direct result of the trial. He asked for an estimate of those costs.
Mr. Threadgold would not comment on the case.
Ms. Languille wanted to move her mother back home and hire live-in aids to
help take care of her. She calculated the cost over 20 years, including
equipping the house and providing 24-hour nursing care. Her calculation,
which also included reimbursement for prior costs, came to $3,429,248.
According to court documents, Mr. Threadgold wrote in an email to Ms.
Languille a month later that the company was willing to try to resolve her
mother's situation in a "mutually acceptable manner." He cited "Medicare,
tax and projected nursing-home expenses" as some issues that needed to be
addressed.
Fearing that the company was dragging its feet, Ms. Languille hired a
lawyer, Stephen Pappas. Mr. Pappas took over conversations with Berlex in
the fall of 2006.
In 2007, the family decided to sue Titan, Berlex and the regents of the
University of California, seeking more than $5 million for damages, medical
expenses and attorney's fees. Mr. Pappas says he sued the California regents
rather than Tampa General Hospital or the University of South Florida in
part because the UCLA consent form offered the broadest description of
compensation for medical care.
The University of California declined to comment on the substance of Ms.
Davenport's case because of the pending litigation. A spokeswoman for the
university said in a written statement that the university "takes these
matters very seriously" and that the parties "are working to determine a
satisfactory resolution."
[Testing, Testing]
<file:///C:/DOCUME~1/Vera/LOCALS~1/Temp/msohtml1/01/clip_image003.gif>
In a response to the Davenports' complaint filed in Alameda County Superior
Court in California, the regents said, among other things, that the
university had fulfilled its informed-consent obligation to Ms. Davenport.
It added that the university wasn't liable for an alleged "defectively
manufactured medical product."
Since testing of Spheramine began, Schering AG was acquired by Bayer AG, and
Berlex was renamed Bayer HealthCare Pharmaceuticals Inc. A spokeswoman for
Bayer said in a written statement that the company "has undertaken efforts
to try to agree on some type of compensation for Ms. Davenport's care" even
though "it has not been established" that her "current symptoms" were
related to the trial. She also said, "We sympathize with Ms. Davenport and
her family, and remain committed to resolving this matter as soon as
possible," adding that the parties are close to a legal settlement.
'Great Promise'
Bayer says Ms. Davenport was one of 71 patients enrolled in this stage of
the drug trial. It says the study is being monitored by an independent board
which has not reported a safety concern. Because the research is ongoing,
Bayer says results from the trial are not yet available, but says "early
research has shown great promise." It expects late-stage testing of
Spheramine will begin in the second half of 2009.
During a visit to her nursing home this past fall, Ms. Davenport rambled
mostly incoherently. At one point, she said she had been in the nursing home
"almost three years," prompting Ms. Languille to correct her. She had been
there two years, Ms. Languille reminded her. "But I bet it feels like
three," she added.
"Yes, it does," her mother responded.
Write to Sarah Rubenstein at sarah.rubenstein@wsj.com
<mailto:sarah.rubenstein@wsj.com>
