IMPLEMENTING THE FDA GUIDANCE ON KEY INFORMATION IN INFORMED CONSENT

The new FDA draft guidance, Key Information and Facilitating Understanding in Informed Consent, (March 2024) provides some food for thought regarding the informed consent process and how we should organize our informed consents to best inform potential study participants about the studies we are conducting. I’ve recently read Patient H.M. (Luke Dittrich, 2016), about a patient with severe epilepsy who was treated with a lobotomy in an effort to reduce the seizures. While seizures remained severe, the procedure resulted in eliminating the patient’s ability to establish short-term memory and erased or jumbled most of the patient’s long-term memory. While it was noted that this particular patient did consent to the procedure, the book also chronicles stories of asylum patients with mental disorders who were given lobotomies without their or their legal representative’s prior consent. I am always both amazed and horrified when reminded that these types of research methods occurred in my lifetime. The processes we currently follow in generating informed consent forms (ICFs) for use in today’s clinical studies were not always standard procedure. Remembering this and understanding the importance of having each trial subject freely give consent, after being fully informed of the trial’s objectives, risks and benefits, is an interesting, important and relevant topic for consideration as we design and execute clinical studies.

The ICFs, which we develop to educate potential study participants on the procedures, risks and benefits of the clinical studies we are conducting, are routinely developed following the principals outlined in the Declaration of Helsinki and the elements of informed consent outlined in 21CFR Part 50. As a majority of clinical studies also now collect biological, including genetic, samples and many are stored for future use, information from the Common Rule and data privacy provisions are routinely included in ICFs. Those of us who work on NIH studies may already be familiar with the Key Information section but this section may be new to those of us involved in industry-sponsored studies only.

Over the years, FDA has issued a number of guidances on informed consent, focusing on the elements of informed consent, [i] guidance for IRBs, Investigators and Sponsors, [ii]  the prohibition of the use of exculpatory language, [iii] exceptions for emergency use, [iv]and the use of electronic informed consent documents.[v]

With this in mind one might ask, why do we need an additional guidance?

While the rationale is that this guidance has been issued to harmonize with the Common Rule’s requirement for a Key Information section, it also provides some useful suggestions on how to make our informed consent documents more user friendly.

Requirement for a Key Information Section of the ICF

Both the Common Rule (46.116(a)(5)(i)) and the new guidance state that consent should “begin with a concise and focused presentation of the key information that is most likely to assist a prospective subject or legally authorized representative in understanding the reasons why one might or might not want to participate in the research.” This has come to be called the Key Information section.

FDA recommends that the Key Information section of the consent form begin with an introductory statement to frame the key information included in the consent form and to guide prospective subjects when reading the entire document. The key information section does not need to include all elements of informed consent.

The guidance recommends providing, on the first page, if possible, information about the most common and serious risks and discomforts the participant may experience during the trial. All risk information does not need to be included in the Key Information section; a cross-reference (or hyperlink for electronic documents) that provides the location of additional information within the consent can be noted. Similarly, a brief description of potential benefits to the participant or to others with the same medical condition should be included in the Key Information.

Other topics that may be appropriate for the Key Information section may include the statement that the participant may decline to enroll or may exit the trial without jeopardy to continued treatment for their disease, the types of treatment the participant may get in the trial, what alternatives are available if the participant does not enter the trial, what costs the participant may incur and whether these will be compensated, how long participation may be, and what major procedures may occur. The elements of informed consent that are addressed in the Key Information section do not need to be repeated in other parts of the ICF but there is no prohibition of doing this if it makes the ICF more informative. The content of the Key Information section should be customized for the specific trial and participant population.

The Key Information section may also be presented using other media, such as illustrations, video, and electronic tablets, if this helps to meet the goals of improving clarity and increasing prospective participants’ understanding of the information. For example, illustrations may be useful if the population consists of young children or persons for whom written language may be a barrier to understanding.

While the development of a Key Information section of the ICF is an additional burden on the Sponsor, in today’s world, in which we are conducting increasingly more complex studies, including the collection of multiple biological samples, and at the same time are trying to include a more diverse patient population, the Key Information section may prove to be useful for all parties. By using the FDA-suggested structure, with boxes delineating information by topic, the participant may find it easier to digest the information and obtain additional knowledge of the disease being studied. In this way, the Key Information can help facilitate more meaningful discussions between Investigators and potential participants.

While it may take us a bit of time to get used to these enhancements to the ICF, it should make the documents more user-friendly to potential study participants and easier to navigate. Hopefully, this will also result in a better dialog between Investigators and potential participants, resulting in the appropriate individuals agreeing to participate in research studies. If we are really lucky, it may also help us in our quest to enroll a more diverse population in clinical trials.