Policy/Position Statement
ASGCT Position Statement on Informed Consent
2010
Although there is universal consensus that informed consent is required from subjects (or their guardians) participating in clinical studies, ensuring that study subjects appropriately understand a clinical trial's risks, benefits, and objectives continues to present challenges. For studies of novel interventions, like those involving cell transplantation and gene transfer / therapy, the risks and benefits of study participation are often uncertain, thereby presenting challenges for informed consent. Of particular concern is the tendency for human subjects, who may be debilitated by illness, to underestimate risk, overestimate the likelihood of therapeutic benefit, and to misunderstand the way a trial's objectives might conflict with their own clinical goals.
The American Society of Gene and Cell Therapy (ASGCT) is dedicated to exacting standards of informed consent. Any communication with clinical trial participants by investigators conducting clinical trials should reflect a rigorous evaluation of the subject's understanding of potential risks and benefits of the study, and the informed consent process must be understandable and reciprocal. Even though national and international policies for protection of human research subjects establish informed consent standards,¹ ASGCT urges its members to be cognizant of distinctive consent challenges that are frequently encountered in cell transplantation and gene transfer / therapy studies. To this end, the ASGCT recommends the following guidelines:
1- Human subjects (or guardians) should be informed of the novelty and uncertainties about risk and potential therapeutic benefit surrounding studies. In initial studies of an agent, any reference to a potential therapeutic benefit should be avoided.
2- Many cell transplantation and gene transfer / therapy approaches involve interventions that are permanent and/or difficult to reverse. The possibility of irreversible or delayed adverse events, and the nature of long-term follow-up testing and procedures, should be explained as appropriate to subjects (or guardians).
3- Studies frequently involve procedures that are not intended for clinical management, and are instead designed to monitor the biological effects of interventions. Examples include biopsies to obtain pharmacodynamic information. Studies also involve design elements that are necessary for validity, but may interfere with the goals of subjects who enter studies. These include randomization in controlled clinical trials and the use of inflexible dosing regimens in phase 1 studies. The burdens and objectives of such study procedures should be clearly described to subjects (or their guardians).
4- The clinical study team should take measures to ensure adequate comprehension by subjects (or guardians) of the study. In particular, they should reserve time to discuss studies with prospective subjects, and endeavor to identify and dispel misunderstandings that might lead subjects (or guardians) to overestimate benefit, underestimate risk, or to not recognize the distinction between normal medical care and participation in the clinical study. In explaining risk and benefit, researchers should avoid vague and/or complicated language. For typical phase 1 studies, this should include explaining that studies are primarily designed to test safety, and that major therapeutic benefits are improbable.
5- Many studies involve commercial relationships, including study investigators holding intellectual property on interventions or having significant equity in study sponsors. Relevant disclosures of commercial interests, including financial interests of the study investigators and sponsorship, should be provided to study subjects (or guardians).
6- When clinical investigators have direct care relationships with trial subjects (as may be the case in studies involving chronic or rare diseases), consent discussions and solicitations should generally be performed by an individual not associated with the direct care of the subject. Investigators should also consider designating a disinterested party for handling some aspects of the consent process.
7- When studies involve levels of risk or burden that are significant or difficult to assess, complicated designs, highly expectant patient groups, or especially vulnerable subjects, research teams should consider evaluating the comprehension of subjects through discussion or use of a consent evaluation tool.
8- In preparing consent discussions and documents, investigators and sponsors should be attentive to their choice of language. The National Institutes of Health Office of Biotechnology has prepared a Guidance for Informed Consent.² This guidance was endorsed by the Recombinant DNA Advisory Committee. ASGCT strongly encourages members conducting clinical studies to adapt, as appropriate, language and practices outlined in this guidance with the assistance of their local Institutional Review Board (IRB).
ASGCT has compiled an additional list of resources for informed consent here.¹ In the U.S., these include 45 CFR 46. For applicable studies, these also include Appendix M of rDNA guidelines.
² Available at: http://oba.od.nih.gov/rdna/informed_consent_intro.html