Legal land mine: Informed consent goes on trial
Case is a cautionary tale
By J. Mark Waxman, JD
General counsel
CareGroup Healthcare System
Boston
A recent decision by the Ninth Circuit Court of Appeals (Goodman v. United States, Slip Op. No. 0135240, Aug. 2, 2002) provides an interesting view of informed consent requirements as they relate to information known to physicians at the inception and over the course of a clinical trial. Informed consent is, of course, the essential element of participation in a clinical trial. In general, informed consent requirements mandate that each subject receive at least the following:
• an explanation of the purposes of the research, the duration of the subject’s participation, the procedures to be followed, and an identification of any procedures which are experimental;
• a description of any reasonably foreseeable risks as discomforts to the subject;
• the reasonably expected benefits of the research;
• a disclosure of appropriate alternatives that may be advantageous;
• a statement that participation is voluntary and that the subject may discontinue participation at any time without penalties or loss of any benefits;
• other mandated disclosures (45 CFR §46.116).
Foreseeable risks unpredictable
Recent case law reviewing such requirements, in particular the Grimes v. Kennedy Krieger, previously discussed in the July 2002 issue of IRB Advisor, indicate that these requirements remain fluid during the course of a trial. For example, if facts become known during a trial that may influence participation by a subject, the subject must be told. As the court in that case interpreted it, a consent is a bilateral contract that requires "full, detailed, prompt, and continuous warnings as to all the potential risks and hazards inherent in the research or that arise during the research."
The Goodman case involved a National Cancer Institute study conceived by a National Institutes of Health physician. The goal of the clinical trial was to study the effects of isolating the liver through a major surgical procedure [isolated liver perfusion (ILP)] and then administering increasing doses of Melphalan infused with an experimental cancer-fighting agent. The trial had received IRB approval, as did the particular consent form employed.
As part of the enrollment process, the patient discussed the ILP procedure with the involved physicians and received an explanation of the consent form. During follow-up examinations, the treating physician noted that the patient "understands quite well, I think, that it may have only a small chance of helping her since she has a rapidly growing disease."
The day before the operative procedure itself, a physician involved with the study discussed the procedure again and the experiences of three other patients who had undergone the procedure at the same dosage levels. A second consent form was executed, which included a discussion of a variety of potential results, and the statements that: 1) the results of the side effects in the liver were not completely known; and 2) the operative procedure itself could cause clotting or blockage of blood vessels to and from the liver.
Following the surgical procedure, the patient died. It was determined that the dosage of Melphalan caused liver toxicity and a syndrome whereby the small blood vessels in the liver became blocked (known as VOD), ultimately leading to the death. None of the prior patients had suffered from VOD. Nevertheless, the plaintiff (the patient’s husband) asserted that the physicians had failed to inform his wife of the foreseeable risks of the ILP surgery and obtain a specific supplemental consent indicating that earlier ILP patients had suffered complications from the surgery.
In this case, the court unanimously found in favor of the physicians. The decision was based upon the application of the scope of the duty to warn and explain, as the critical part of the consent process, to the facts before it. The duty to warn required a disclosure of "the nature of the ailment, the nature of the proposed treatment, the probability of success of the contemplated therapy and its alternatives, and the risk of unfortunate consequences associated with such treatment." (Sard v. Hardy, 379 A. 2d 1014, 1020, [Md. 1977]).
Based upon the facts before it, the court found that the doctors involved not only did not know, but could not reasonably have been aware that the particular complication involved would occur at the dosage level actually administered. Further, the court appears to have found, in rather broad terms, "there is no legal requirement that the consent form developed for [The ILP] study must be amended as each group of patients proceeds through the study."
The court further determined that "to hold that the signed consent form was inadequate would require the NIH to update its already detailed consent form every time a patient experiences any sort of complication from an experimental procedure. . . . The consent form and procedures were medically reasonable and adequate." (Emphasis added.) Of great interest is that in reaching this conclusion, the court failed to cite any statutory, regulatory, or case law authority.
Report identified risks
While the court’s ultimate determination may well have been correct, this latter portion of the court’s holding bears scrutiny. The notion that knowledge of complications learned during the course of a trial, if it could affect the informed nature of consent, need not be reincorporated into the consent process, would not be consistent with a common sense understanding of the applicable law and would present an inappropriate view of the legitimate requirements of an informed consent process.
IRBs and investigators faced with actual evidence of complications occurring during a trial, stemming in any way from the experimental processes themselves, would undoubtedly want, and would likely feel a mandate, to bring these matters to the attention of their subjects. It cannot be said that ongoing consent to participate is truly informed when material information learned from the inception is not presented to trial subjects.
Indeed, there is federal law on the subject — 45 CFR §46.116(d)(4) — that directly requires the provision of additional pertinent information after participation. As a result, it is likely that this portion of the court’s opinion is to be read in the context of its overall factual and legal conclusion that, whatever the consent forms actually said, the effect of the entire informed consent process was, in fact, that the subject "was fairly warned of the risks of the experimental ILP procedure that preceded her tragic death."
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