This monthly feature presents questions from clinical trial professionals answered by a variety of experts in the field. This month’s questions and answers come from the WCG Institute’s Ask the IRB Experts column and from the Secretary’s Advisory Committee on Human Research Protections (SACHRP) document, New Information Provided to Previously Enrolled Research Subjects.

Question: Is it mandatory to update the consent form during a yearly Investigator Brochure update when the safety updates were already shared with sites via Dear Investigator Letters, or can the updates wait until the next protocol amendment that requires a consent form update?

Answer: The answer to this question largely depends on what new information is contained within the Investigator’s Brochure update. When the new information is significant, such as new risk or safety information, then the start of the answer to this question is in 21 CFR 50.25(b)(5), which states that “significant new findings developed during the course of the research which may relate to the subject’s willingness to continue participation will be provided to the subject.”

The question is when and how. In its March 2020 recommendation on the topic, SACHRP notes that consent is an ongoing process and that “in some research studies, circumstances arise in which new information becomes available that needs to be shared with subjects as part of this ongoing consent process.”

As noted in the SACHRP recommendation, there is no regulatory requirement that states that the new information must be added to the consent form, and subjects thereafter re-consent to participation in the research. However, when the information is significant, it must be communicated to subjects, which can be done in several different ways. It may be by providing the information verbally to subjects and documenting the discussion in the research record or by use of a consent form addendum. However, modification to the existing consent form and re-consent of subjects is often a best practice.

A few key points to consider when determining when and how to provide significant new information to research subjects:

• Subjects should be provided significant new information as soon as possible;
• The significant new information will also need to be provided to new subjects that enroll in the research if the study is still open to enrollment; and
• It is appropriate to document, by a research record note or consent form (including addendum), that the subjects received the information and thereafter still agree to participation in the research.

Given these points, when there is significant new information that has been provided to investigators via a Dear Investigator Letter, the most prudent time to provide information to subjects is upon provision of the Dear Investigator Letter, rather than waiting until the time of updating the Investigator’s Brochure. If the consent form has not yet been updated by the time the Investigator’s Brochure has been updated, it would be appropriate to update the form at that time, rather than waiting until there is a protocol amendment necessitating further consent form updates. — Lindsay Abraham, regulatory lead for the IRB chairs at WCG WIRB

Question: When is it appropriate to just provide individuals with additional information but not necessarily obtain consent again?

Answer: In addition to the existing regulatory requirement related to significant new findings, there are other types of information that may impact subjects’ interest and ability to continue their participation, which must be shared from a practical standpoint. Examples of such information include the need to extend followup for an additional period of time or an increased frequency of visits to the research site for minimal-risk data collection activities.

How additional information is communicated to subjects will depend upon many factors, including the type of study, the complexity and/or urgency of the new information and the population. In some cases, a subject who continues to attend study visits and actively participate in a study after receiving additional information may signify continuing consent. In other situations, it is desirable to explicitly document a subject’s receipt of new information and their consent to continue their participation. IRBs, sponsors and investigators should balance the need for documentation with respect for the subjects and choose the least burdensome method of providing new information and/or obtaining and documenting re-consent consistent with the circumstances.

There is also information that does not need to be communicated to research subjects. Examples include changes to the inclusion criteria that have no impact on previously enrolled subjects (e.g., increase upper age limit from 60 to 70) or an increase in the overall number of subjects.

Due to the multiple factors that must be considered by the IRB, there will be variability with respect to the format for presenting information to current subjects. This can include: oral presentation of new information; a written addendum to the original informed consent document that describes the new information; an edited version of the consent document that clearly identifies any changes (e.g., redlining); and a revised consent document with changes incorporated. Irrespective of the written format, the investigator must employ an appropriate process for providing subjects with the new information and ascertaining their willingness to continue. Ongoing consent should be documented, either through documentation of the process in the subjects’ study records or by having subjects sign a written document. The requirements for documentation of initial consent and waivers of documentation may provide a useful framework for deciding when to formally document that subjects have received new information and gave consent for their ongoing participation. In certain low-risk cases, it may be acceptable not to ascertain the subjects’ willingness to continue participation. However, in such cases it is probably also acceptable not to provide the subjects with the new information. — Secretary’s Advisory Committee on Human Research Protections, New Information Provided to Previously Enrolled Research Subjects