The People vs. Amgen
From: Pharmaceutical Executive
June 1, 2006
Clinical trial participants rarely sue pharma companies for
discontinuing an unsafe drug. Here’s what happened when two such
cases were brought to court.
By: Todd E. Betanzos
Successful Clinical Trials Management
"Most clinical trial lawsuits filed against pharma companies stem
from allegations that the investigational drug harmed participants.
But how often do you read headlines about clinical trial participants
protesting when a drug study is concluded because of safety concerns?
While patients often don’t want to continue a clinical trial after a
drug is pulled for safety, what are the implications for
pharmaceutical companies when they do? Such was the case in April
and June 2005. Two separate groups of people who had been subjects in
a Parkinson’s disease clinical trial sponsored by Amgen, sued the
pharma company in federal court for permanent injunctive relief and
monetary damages. But unlike traditional clinical trial lawsuits,
they weren’t asking for compensation or damages. (Suthers, et al. v.
Amgen and Abney, et al. v. Amgen). Instead, they wanted to force
Amgen to continue providing them with the product.
The Clinical Trial
The cases involved a Phase II clinical trial to study the effects of
a synthetic protein called glial cell line-derived neuroptic factor
(GDNF), to which Amgen owned the rights. The study was designed to
test whether GDNF would spur the growth of dopamine-producing cells
and alter the course of Parkinson’s disease (rather than simply
masking its symptoms like currently available therapies). It began in
2003 and involved 34 patients at eight sites—including the Kentucky
and New York sites where the plaintiffs participated. Prior to
undergoing surgery to implant a pump, a necessary step to supply GDNF
directly to the brain, each study subject signed an informed consent
document. The consent provided that the study participants could
elect to continue treatment for 24 months after the end of the study.
But it also stated that investigators could withdraw a subject from
the study if they found that the risk of continued participation
outweighed the benefits, or if the sponsor decided to discontinue the
study for a variety of scientific reasons. At the start of the
clinical trial, Amgen hoped to see a 25-percent increase in subjects’
scores relative to placebo after six months of treatment. By June
2004, however, the group using GDNF showed a bit more than a 10
percent increase, while the group using placebo had a 4.52 percent
increase. Seven of the 34 subjects showed dramatic improvement, but
four of those seven had received placebo. Since the results weren’t
up to Amgen’s expectations, the company terminated all clinical use
of GDNF in September 2004. It also cited two safety concerns: (1) the
results of a primate study in which four of 44 primates given GDNF
suffered cerebellar toxicity; and (2) the discovery that several
human subjects had developed neutralizing antibodies. Amgen also
cited lack of efficacy as a reason for discontinuing the study,
stating that any positive effects experienced by the study subjects
were from the placebo effect common in clinical trials for
Parkinson’s disease. Amgen consulted with FDA regarding the study’s
termination, and FDA agreed that the termination was reasonable in
light of the scientific evidence.
The Litigation
Upon filing suit in Kentucky and New York federal district courts,
both groups of plaintiffs asked the courts to issue preliminary
injunctions forcing Amgen to continue providing them with GDNF. They
argued that GDNF was beneficial to them, and Amgen had contracted to
supply them with the drug as long as it proved beneficial. They also
said that in undergoing the pump implantation surgery, they had acted
to their own detriment, relying on promises made by Amgen. Those
promises were enforceable pursuant to the law of promissory estoppel.
That doctrine provided that Amgen promised they would supply the drug
to the participants, and since they promised to, it would be unfair
not to follow through with their promise. Finally, by unreasonably
denying access to GDNF, Amgen was breaching a fiduciary duty it owed
them. After conducting hearings, both courts denied the requests.
In their claims for breach of contract and promissory estoppel, the
plaintiffs argued that the informed consent documents signed by study
subjects constituted a contract and a promise on Amgen’s part to
continue treatment indefinitely with the investigational drug. They
argued that, although the agreements were executed by the study
subjects and the investigators (rather than Amgen itself), the
investigators did so as Amgen’s agents. Finally, the plaintiffs
argued that Amgen was bound by the study investigators’ statements
that they would make decisions based on the patients’ best interests,
and that the subjects could continue to receive GDNF following the
conclusion of the study if it proved safe and effective. Both courts
disagreed. Noting that the investigators, and not Amgen, executed the
informed consent documents, the courts found that Amgen had not
entered into any contractual agreement with the participants. Citing
the express terms of Amgen’s clinical trial agreements with the
investigators—which provided that the investigators were independent
contractors, and which structured the study so that the investigators
would conduct it independent of Amgen—the courts also found no actual
authority on the part of the investigators to bind Amgen in any way.
Lastly, the courts found that Amgen had not said or done anything
which might have clothed the investigators in apparent authority to
act on its behalf.
In support of their breach-of-fiduciary duty claims, the plaintiffs
argued that Amgen, working through the study’s investigators,
breached its fiduciary duty to ameliorate their pain and treat their
illness with the best medicine available. However, the courts found
no evidence that Amgen agreed its sponsorship of the study was
undertaken primarily to benefit the participants. The courts further
emphasized that the study was intentionally structured to foster
independence and objectivity on the part of the investigators and
their research institutions, thereby insulating them from any
potential conflict of interest, which might arise from Amgen’s
involvement. For example, Amgen had not selected the subjects, met
the subjects or known the details of the subjects’ medical
conditions. Given these considerations and the rigid FDA regulations,
which govern the manner in which clinical trials are conducted, the
courts found no factual or legal basis to impose a fiduciary duty on
Amgen. Having lost in both Kentucky and New York, the plaintiffs
appealed each of the lower courts’ decisions. Although the New York
plaintiffs later withdrew their appeal, the Kentucky plaintiffs
continued. On March 29, 2006, the 6th US Circuit Court of Appeals in
Cincinnati, Ohio, found in favor of Amgen and upheld the Kentucky
federal court’s ruling.
The Implications
The courts’ rulings in Abney and Suthers represent important
victories for pharma companies. Current FDA regulations governing the
conduct of clinical drug trials mandate the respective
responsibilities of investigators, institutional review boards
(IRBs), and study sponsors. And, while compliance with regulations
may not always constitute an absolute defense to liability, it is an
important component of the defense, arising out of a clinical study.
Those same regulations mandate that the study investigators must
obtain the informed consent of each human subject to whom the drug
will be administered, and that they are responsible for protecting
the rights, safety, and welfare of subjects under their care. Had
the courts found a contract to exist between Amgen and the
participants, or had they found that Amgen owed them a fiduciary duty
despite the fact that research was conducted by independent
researchers, further litigation against the industry would have
resulted. Litigation would have continued, not only by participants
wanting to continue receiving investigational drugs after a trial’s
end, but by study participants hoping to take advantage of pharma
companies’ heightened obligations mandated by FDA’s regulations
governing clinical trials.
Todd Betanzos is senior associate at Sedgwick,
Detert, Moran & Arnold in Dallas. He can be
reached at [log in to unmask]
http://www.pharmexec.com/pharmexec/article/articleDetail.jsp?
id=333300&pageID=1
----------------------------------------------------------------------
To sign-off Parkinsn send a message to: mailto:[log in to unmask]
In the body of the message put: signoff parkinsn
