WASHINGTON _ The fialuridine (FIAU) clinical trial disaster thatkilled five people last year has already spawned three multi-milliondollar lawsuits. The unprecedented suits seek to apply legal principlesof medical malpractice and product liability to the conduct of anexperimental drug trial.Attorneys for the three FIAU victims who have filed suit argue thattheir clients signed inadequate informed consent documents. Inaddition, they argue that researchers were negligent because theyignored toxicities found in early preclinical and clinical tests of thedrug. But some experts argue that lawsuits such as these, if successful,could have a chilling affect on clinical research in the U.S. and couldincrease the costs of drug development.FIAU, a nucleoside analog that was being tested as a treatment forhepatitis B, showed early promise in combating the virus in Phase Iclinical trials in humans. As a result, in August 1992, Eli Lilly & Co.licensed the drug from Oclassen Pharmaceuticals Inc., a San Rafael,Calif., biotechnology firm, and began a Phase II trial run by researchersat the National Institutes of Health (NIH).That trial ended in tragedy when hepatitis B-infected patients, some ofwhom began the trial in good health and asymptomatic, began dying inJune 1993. FIAU exhibited a rare toxicity that ultimately proved fatalto five of the 15 Phase II patients and required that another twoundergo liver transplants.Scientists at Lilly, Oclassen and the NIH have argued that FIAU's toxiceffects could not have been foreseen and an independent panel ofexperts appointed by the NIH concurred. In contrast, the FDAconcluded that researchers missed early signals of toxicity, including atleast four deaths, and it sent "warning letters" to some FIAUinvestigators this summer. In an effort to reconcile the two agencies'versions of events and to clear the air, the Department of Health andHuman Services recently contracted with the Institute of Medicine tostudy the issue.Attorneys for the families of patients who died or were injured in FIAUclinical trials will be challenging the decisions of clinical investigators,decisions that have long been made under the cover of relativeobscurity and immunity that is typical of medical research."There's nothing unique about the notion that individuals, evenparticipants in an experiment, have a right to be fully informed of allrisks," said Matthew Myers, a Washington-based attorney whorepresents survivors of two FIAU victims in separate suits against EliLilly. "Normally, an informed consent form for an experimental drugtrial lists every possible risk. Here, that wasn't done."A Settlement Means No Legal PrecedentMyers said he could not rule out the possibility that a settlement withLilly might be reached before his clients' cases made it to court. Ifsettled out of court, the FIAU lawsuits will not establish a binding legalprecedent for future experimental drug trial litigation. However, theycould still have an impact."The practical affect of a settlement could be just as great as that of atrial," predicted Myers. "The very fact that a settlement was reachedwould cause other companies and institutions conducting clinicalresearch to think seriously about their obligations to research subjects."Another FIAU attorney said he hopes the lawsuits will impact theclinical research process. "I would hope that these lawsuits change theway clinical research is done so that it becomes less of an attempt bymanufacturers to dodge regulatory hoops," Los Angeles attorneyWilliam Downey told BioWorld. "Drug testing is now almostcompletely subsidized by drug companies. The tests are designed toprove efficacy, not to determine what the real effects of a drug are. Forexample, the animal studies (of FIAU) were grossly inadequate."Downey has been hired by Paul Melstrom, a California man whoclaims that his participation in an NIH-led Phase I trial of FIAU lefthim with a permanently debilitating peripheral neuropathy. Melstrom'ssuit lists Lilly, Oclassen and the U.S. government (namely, the NIHand five of its researchers) as defendants.But experts in clinical research lamented the entry of lawyers andlitigation into the territory of experimental drug research. "It is a totallyinappropriate extension of legal issues," said Richard Corlin, a SantaMonica, Calif., physician and vice speaker of the American MedicalAssociation's House of Delegates who served on the NIH panel thatreviewed the FIAU trials. "The purpose of a clinical trial is to discoverif 1) a drug is safe and, 2) if it's effective. This [FIAU] may be one ofthe most tragic occurrences of any clinical study ever done but itdemonstrates precisely why clinical studies are done in the first place."Corlin argued that the informed consent documents for the FIAU trials,which he said he has pored over at length, were more than adequate."You simply can't give patients in experimental drug trials the samereassurances as patients receiving FDA-approved drugs," he toldBioWorld. "If these legal tactics are successful, it will have the mostchilling effect imaginable on anyone doing clinical research in thiscountry."Corlin said he spoke personally with each of the 10 survivors of the ill-fated FIAU Phase II trial and concluded that the drug's toxicities werea "dreadful, unpredictable side effect." Lawyers are using the unjustpower of hindsight to make arguments about what should have beenknown by researchers before June 1993, he argued.Standards For Drugs Shouldn't Apply To Trials"If the same legal standards used to measure clinically proven drugs _drugs whose safety and efficacy are proven _ are applied to clinicaltrials anybody would be out of their mind to run a clinical trial using anexperimental drug," Corlin said. "It would virtually shut downbiomedical research."Peter Barton Hutt, a partner at the Washington law firm of Covington& Burling and a former chief counsel at the FDA told BioWorld thatthe FIAU lawsuits raise significant legal issues that could have afinancial impact. For example, he said that if informed consent doesnot protect companies from liability in experimental drug trials, thecost of obtaining insurance coverage for those trials could increase. (EliLilly engaged Covington & Burling to represent it in exchanges withthe FDA over the FIAU matter, although Barton Hutt was not directlyinvolved.)In addition, he said doctors who act as principal investigators in drugtrials may begin worrying about their own insurance coverage ifcompanies don't have policies adequate to cover potential disasters orif patients start suing them. He said the new concerns could drain whatis already a shrinking pool of clinicians willing to conduct clinicalresearch using experimental drugs. n
-- Lisa Piercey Washington Editor
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