ARTICLE: The People vs. Amgen

["ljherman1@xxxxxxxx" <ljherman1@xxxxxxxx>]

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 todd.betanzos@xxxxxxxx 
                                 
http://www.pharmexec.com/pharmexec/article/articleDetail.jsp?
id=333300&pageID=1

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