Compliance with FDA regulations is only the first step in minimizing the risk associated with the informed consent process. This article provides an overview of requirements and several best practices for the sponsors of clinical trials.
In 1999, Jesse Gelsinger agreed to participate in a gene therapy trial at the University of Pennsylvania. Jesse suffered from a genetic condition that made him unable to metabolize certain substances, forcing him to maintain a strict diet and medication schedule. As part of the trial, Jesse was injected with a virus that contained human gene fragments. The virus was supposed to insert the gene fragments into Jesse’s liver cells and return them to normal genetic function. However, the injection caused a massive immune response that led to multiple organ failure. Four days after his first injection, Jesse died.
Jesse’s parents sued the University and, in the course of the litigation, learned that four previous volunteers had experienced toxic side effects from the virus. They also learned that two monkeys died during the study’s animal safety tests and that the dose of virus Jesse received was larger than that of previous patients. Jesse’s parents argued that even though Jesse signed a form in which he consented to participate in the trial, he did not give informed consent as required by law because he did not adequately understand the nature of the risks involved.
Informed Consent and the Duty to Warn
Deficiencies in informed consents are frequently alleged in lawsuits that involve clinical trial participants. Informed consent causes of action are often directed towards drug and device manufacturers in their roles as clinical trial sponsors. In products liability lawsuits that do not involve clinical trials, manufacturers can sometimes satisfy their legal duty to warn the patient of product risks by warning the learned intermediaries—the healthcare professionals who administer care to the patient. However, the experimental nature of clinical trials requires that such warnings be given directly to the patient through the informed consent process. If adequate informed consent is not obtained, the sponsor could be responsible for potentially large liabilities should something go wrong during the trial.
Informed Consent Requirements
There are international, federal, and state laws that govern the process by which a patient consents to participate in a clinical trial. International requirements regarding the informed consent process are found in paragraph 22 of the Declaration of Helsinki which states:
In any research on human beings, each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail. The subject should be informed of the right to abstain from participation in the study or to withdraw consent to participate at any time without reprisal. After ensuring that the subject has understood the information, the physician should then obtain the subject’s freely-given informed consent, preferably in writing. If the consent cannot be obtained in writing, the non-written consent must be formally documented and witnessed.
FDA regulations provide more detailed guidance regarding informed consents (45 CFR 116—117; 45 CFR 46 Subpart D). They require investigators to obtain consent only under circumstances that provide the prospective subject with a sufficient opportunity to consider whether or not to participate. Such circumstances must also minimize the possibility of coercion or undue influence. Informed consent documents must be approved by an institutional review board (IRB) and must contain the following:
FDA regulations do not preempt any other laws which require additional information to be disclosed for the informed consent to be legally effective. Indeed, in court, the informed consent process is often judged against best practices of the industry. So while compliance with FDA regulations is crucial, regulatory compliance alone is not enough to protect the sponsor from liability. Most states also have common law requirements concerning the informed consent process.
For example, in Massachusetts, it is not required that remotely possible risks be disclosed; however, physicians are required to disclose all significant medical information that they possess (or should possess) that allows the patient to make an intelligent decision about whether to undergo a proposed procedure (Harnish v. Children’s Hospital Medical Center, 439 N.E. 2d 240). If this standard had been applied to the Gelsinger case discussed previously, the Gelsingers would likely have succeeded had their case gone to trial. They would have argued that the University failed to obtain informed consent because it failed to disclose the toxic effects observed in previous subjects, the deaths of the monkeys during the animal safety study, and the increased dosage—all material facts that arguably may have changed Jesse’s mind about participating in the trial.
Informed Consent Best Practices
Lawsuits involving clinical trial subjects often involve scrutinizing the adequacy of the informed consent. There are a number of risk management practices a sponsor can implement in order to ensure that clinical trial participants are participating voluntarily and with full knowledge of the risks associated with the trial. The following suggestions are by no means an exhaustive list, but are intended to provide some general guidelines for sponsors who are interested in increasing the effectiveness and minimizing the risk of their informed consents
The choice to participate in a clinical trial cannot be adequately exercised without information regarding the purpose of the trial and its potential risks and benefits. Following the aforementioned suggestions in addition to complying with FDA regulations can help a clinical sponsor reduce the risk of liability and ensure that the informed consent process is the best that it can be.
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