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The plaintiffs argued that Amgen breached its fiduciary duty to ameliorate their pain and treat their illness with the best medicine available.
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 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.
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 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 firstname.lastname@example.org