By Mary R. Anderlik
Health Law & Policy Institute
Bioethicists involved in medical research are experiencing the best and worst of times. Medical research is hot. Presidential candidates are battling over who can give the biggest boost to the budget at the National Institutes of Health, and Medicare has officially extended coverage for participation in qualifying clinical trials. Reports of medical breakthroughs routinely feature commentary from bioethicists. Medical research is also under fire, with federal shutdowns of research programs at major medical centers and most recently, the filing of a lawsuit against investigators and a prominent bioethicist at the University of Pennsylvania.
In the fall of 1999, Jesse Gelsinger, an 18-year-old with a mild form of ornithine transcarbamylase deficiency or OTC, a rare metabolic disorder, died in the course of an experiment at the University’s Institute for Gene Therapy. It appears undisputed that the cause of death was multiple organ system failure triggered by the virus used to carry new genetic material into Gelsinger’s system. While deaths can occur in experiments without any wrongdoing on the part of researchers, the plaintiffs’ Complaint in Gelsinger v. Trustees of the University of Pennsylvania ("Complaint") alleges that this death was wrongful and that the wrongdoers include Arthur Caplan, director of the University’s Bioethics Department.
The experiment was what is known as a "Phase I trial," a first try on human beings. The chief goal of a Phase I trial is to obtain information on toxicity (harmful effects). In bioethics, there is a term for the belief research subjects often have that they personally will benefit from a Phase I trial. It is "therapeutic misconception." Sometimes the therapeutic misconception is the persistence of hope in the face of accurate information about the remoteness of any medical benefit. In other cases, the misconception is nurtured by inaccurate or incomplete information. The OTC case is interesting because Gelsinger clearly understood that there would be no benefit to him personally. The allegation is that he suffered from what I would label an "altruistic misconception," a belief that the primary and direct beneficiaries of his participation would be infants suffering from a fatal form of OTC when in fact the primary beneficiaries were the researchers themselves.
Matters become murky when researchers have a big stake in a particular trial because money or a major career advancement hinges on its progress. Major research universities often suffer from similar conflicts of interest. The Complaint in the Gelsinger case alleges, in essence, that the researchers employed a virus known to be more dangerous than other gene carriers or "vectors" because they held patents on that kind of virus and stood to gain financially. The Complaint also alleges that the researchers omitted information about risks from the informed consent process. According to the Complaint, Gelsinger believed that the risks of injection were "minimal" and the potential benefits were "enormous," whereas the risks of injection were significant and the potential benefits were both suspect and more likely to accrue to the researchers than to infants affected by OTC. Other allegations involve the researchers’ failure to adhere to eligibility criteria and other departures from good scientific and clinical practice.
So how comes Caplan to be named as a defendant? It is important to note at the outset that anybody can be sued. The filing of a lawsuit suggests little or nothing about the merits of a claim. Apart from purely strategic considerations, two factors appear to have caused the plaintiffs and their lawyers to pursue Caplan. First, the Complaint alleges that Caplan advised the researchers that parents of terminally ill children, initially viewed as the subject pool, were incapable of giving informed consent, and suggested it would be better, ethically, to use otherwise healthy adults with the mild form of OTC. Second, the Complaint relates that, following Gelsinger’s death, Caplan spoke bluntly about gene transfer experiments as safety studies with no direct medical benefits anticipated – and suggested that researchers were less than forthcoming about the nature of Phase I studies.
None of the lawsuits brought against bioethicists or ethics consultants appears to have produced a ruling on the merits. Claims have usually been some variant of negligence. Every first-year law student learns the elements of a claim for negligence: duty, breach of the applicable standard of care, loss or injury, and causation. The threshold question is whether Caplan had a legal duty to exercise care in his dealings with the researchers that extended to Gelsinger and his family. The Complaint is vague on the precise nature of Caplan’s role. In tort law, a bioethicist’s own understanding of his or her role in a particular instance (e.g., duty-free suggestion-maker) would not be determinative. Rather, the law uses concepts such as reasonableness and foreseeability, as well as considerations of public policy, to frame duties. If Caplan had a consulting relationship with the researchers and contributed to the design of a study using relatively healthy volunteers whose participation would likely be motivated by a misunderstanding of benefits coupled with an underappreciation of risks, and if he took no steps to ensure that potential subjects were adequately informed concerning benefits and risks, then liability would not be outlandish. (Somewhat oddly, Caplan is not named in the charge concerning lack of informed consent.) On the other hand, publishing on the ethics of research with terminally ill children, speaking on the subject to a colleague at a cocktail party or faculty picnic, and/or talking frankly to the media about Phase I trials should not land one in court.
To bring the discussion full circle, the current problems of medical research are related to its successes. As research activity has expanded, so has the burden of responsibility for bioethicists as well as clinical investigators. In the face of the complexities introduced by conflicts of interest and enrollment of vulnerable populations, bioethics is becoming a high-risk occupation. Bioethicists cannot call others to account and then cry foul whenever one of their own is subject to scrutiny. On the other hand, it would be a shame if lawsuits were to give rise to a defensive bioethics that substitutes caution for due care.