Earlier this summer, the Food and Drug Administration (FDA) issued a draft 42-page "Informed Consent Information Sheet" that provides guidance for institutional review boards (IRBs), clinical investigators, and clinical trial sponsors on complying with the Agency’s informed consent regulations. Once finalized, the draft guidance will supersede FDA’s previous Information Sheet on this topic, "A Guide to Informed Consent," which was last updated over 15 years ago, in 1998. The guidance, which is a compilation of FDA’s regulations and past guidances on informed consent, also reflects the Agency’s coordinated efforts with the Department of Health and Human Services (HHS) to facilitate consistency across informed consent requirements and policies among federal government agencies.

Broadly, the new guidance indicates FDA policy shifting towards enhanced informed consent processes. More narrowly, the draft guidance explains the various and often caveated elements of informed consent (including providing patients with a description of the trial, its risks, benefits, alternative treatments, confidentiality and compensation in the event of injury), depicts the detailed responsibilities of IRBs, clinical investigators and sponsors of clinical trials (including compliance with the process, elements and documentation of informed consent), and provides examples of recommended language to assist industry parties in complying with FDA’s informed consent regulations. FDA accomplishes this task by clarifying some aspects of existing guidance and creating additional guidance in new areas.

The following provides an overview of some of the draft guidance’s notable new and revised provisions.

  • Risks and discomforts: In a new policy, FDA states that “all possible risks do not need to be described in detail in the informed consent form, especially if it could be overwhelming for subjects to read.” Instead, FDA states that only risks that are more likely to occur and those that are serious should be included. This is a change from the 1998 information sheet in which FDA stated that “[a]ny procedures relating solely to research…should be explained to the subjects.”
  • Alternative procedures: Like FDA’s new stance on risks and discomforts, the Agency does not require that all alternative treatments be explained. Unlike the 1998 information sheet, which stated that “subjects should be aware of the full range of options available to them,” now the Agency states that “it may be appropriate to refer the subject to a healthcare professional who can more fully discuss the alternatives.” Although FDA clarifies that such a referral should be completed before the subject signs and dates the informed consent form, the question remains as to how an investigator should document the referral.
  • Off-label use disclosure: FDA clarifies in the guidance that disclosures of alternative treatment, as required under 21 C.F.R. 50.25(a)(4), must include a description of medically recognized standards of care, which may include off-label uses of approved products. FDA’ position on the disclosure of off-label uses is likely to create a new burden for investigators and sponsors to determine when an off-label use of a product has become a “standard of care.”
  • Impaired consent capacity: The guidance introduces a new section on obtaining informed consent of patients with impaired consent capacity, ranging from minor or temporary impairments to complete or permanent impairments. In these cases, FDA suggests that clinical trial enrollment forms may require modification, and that investigators should consider if including patients with impaired consent capacity is “ethically appropriate and scientifically necessary.”
  • Alternative methods of obtaining informed consent: In this new section, FDA recognizes that new technologies (e.g., fax or email) may be used as part of the consent process and may serve as an alternative to the traditional paper consent form. FDA encourages those interested in pursuing alternative methods of obtaining informed consent to contact the Agency and provide comments on these alternative methods.
  • Reviewing patient records: The guidance indicates that sponsors and investigators may seek to review patient medical records for a variety of reasons related to a clinical investigation, such as to determine if a patient is eligible for a clinical trial or to retrospectively review the records of a previously enrolled patient. Whether consent or “reconsent” of the patient is necessary is determined on a case-by-case basis. Apart from a potential need for consent, sponsors and investigators must also consider the need to comply with federal and state privacy laws, such as HIPAA.
  • Multiple trial participants: FDA “strongly discourages” the practice of individual patients participating in multiple and simultaneous clinical trials or enrolling in a single clinical investigation multiple times. The Agency’s rationale is partly due to medical safety reasons for the patient, and also due to the high likelihood of trial subjects not fully understanding all the risks, proposed benefits and demands of multiple trial protocols, thereby delegitimizing informed consent.
  • Affirmative right to compensation for injury: Expanding FDA regulation that requires informed consent documents to include a “statement that compensation or medical treatment are or are not available if unanticipated injuries occur and of what they consist,” the draft guidance encourages sponsors to include in informed consent forms an affirmative statement that subjects are “not precluded from seeking to collect compensation for injury related to malpractice, fault or blame on the part of those involved in the research.”

In addition to the above new and expanded sections, the guidance also offers additional insight into topics such as “assent” to research by children, informed consent of non-English-speaking clinical trial participates, and when to disclose to subjects when an investigator conflict of interest exists or when a study has been suspended or terminated.

The new guidance raises many questions and considerations for clinical trial sponsors, investigators and IRBs and provides an important opportunity for these industry parties to provide comments to FDA. Comments on the draft guidance are due to FDA by September 15, 2014 and can be submitted here.