By Gary Evans

Wading into a thicket of ethical and legal issues, SACHRP is trying to clarify the concept of “re-consent” and when is it necessary.

In roughing out a draft at its July 30-31 meeting, the committee cited the following question presented to them by OHRP: “When new information requires revisions to the informed consent document for research that was approved under the pre-2018 Common Rule, is it necessary to transition a protocol and informed consent to the revised rule when the new information results in a change in the consent document?”

The committee’s answer: “SACHRP recommends that the provision of new information to research participants should not require a protocol to transition to the revised rule. When an informed consent document that was approved under the pre-2018 rules is revised, it should continue to be grandfathered under the pre-2018 rule.”

That seems clear enough, but other scenarios and contingencies soon clouded the discussion. For instance, does discovery of a new risk in an ongoing trial trigger the need to re-consent everyone? How would that scenario work in terms of transitioning it to any applicable provisions in the new Common Rule? SACHRP discussion diverged on this point, with some members noting certain consent forms are updated over minor changes and others warning not to err on the side of more paperwork.

“There’s no question about the ethics of giving people information,” said Stephen Rosenfeld, MD, MBA, chairman of SACHRP. “There’s a given that new information that might affect participation or willingness to continue needs to be shared. The question is really a mechanistic one: How you do that? Is it a rewrite of the consent form? Is it a consent addendum? Can you call people and record it in the study record?”

From a study participant’s perspective, signing forms and re-consenting is a burden that should not be pushed forward without significant cause, said Janet Freeman-Daily, MSc, ENG, a former clinical trial participant who serves as a patient advocate on the committee.

“I think there’s an ethical consideration for respect for persons,” she said. “If what is getting changed is not going to have any scientific impact, I don’t care. If it’s not going to affect my rights, I don’t care. In my clinical trial, first it was every two weeks, then four weeks, then eight weeks, I got to spend 20 minutes with my expert doctor. If I have to spend 10 minutes of that time signing documents that have no impact on me whatsoever, you’re not respecting my time. I think that I would like to see a positive step toward saying that if this is not going to impact this person’s perception of their rights or their risks in the trial, just give them a piece of paper and let them initial it and let that be the end of it.”

Speaking for the committee, Rosenfeld said most probably agreed on the point, but it could not be framed that forcefully in the draft document, which remains under development. “I think there’s pretty much universal agreement with that, but we did not frame it that positively because we wanted to sort of give people the choice for institutional policy and such, but that’s something we should consider — particularly from that perspective,” he said.

With some acknowledgement of these various potential entanglements, the document drafted by SACHRP gives IRBs options to address the issue on what will likely be a case-by-case basis.

‘As Flexible as Possible’

“Where we came down as the [SACHRP] subcommittees on this is that it should be as flexible as possible. That’s what the document reflects,” said David Forster, JD, co-chair of the SACHRP Subcommittee on Harmonization.

Forster gave an overview of the draft document, which underscored the bedrock principle of informed consent but also states that “re-consent” is a term more colloquial than clinical.

“The process of informed consent occurs when communication between a potential participant and a researcher results in the individual’s authorization or agreement to participate in a research study, or their refusal to participate,” the SACHRP draft document stated.

In some research studies, circumstances arise in which new information becomes available and needs to be shared with participants who have consented to the trial. “OHRP has asked the SACHRP subcommittees to comment on circumstances in which participants already enrolled in a study should be provided with relevant new information and have the opportunity to either withdraw from the research or to affirm and document their willingness to continue in the research,” the draft stated. “In the research community, this process is colloquially referred to as ‘re-consent.’”

Neither the Common Rule nor FDA regulations use the term re-consent or describe a process for providing new information to participants who already are enrolled in a research study. There is a provision about reporting “significant new findings,” the draft states. “However, providing new findings is not the same as asking an individual to review their consent to participate in research and confirm their willingness to continue participation.”

Potential Approaches

While IRB approaches for renewing informed consent over the course of a research study vary, there are a few commonly used pathways.

“Frequently, sponsors, clinical research organizations, and investigators submit a revised consent document with an accompanying recommendation of reconsent for all enrolled participants,” SACHRP stated. “However, data are lacking regarding what ultimately happens with that request. Do IRBs question whether reconsent is required or do they accept the request and approve the proposed process?”

Facing this conundrum, the committee cited the following possible approaches for providing new information to research participants:

  • Require researchers to repeat the informed consent process with the revised informed consent document(s), and document consent following the requirements;
  • Require that researchers present the new information using an addendum to the original informed consent document and either obtain documentation directly or describe the communication process in the participant’s research records;
  • Allow researchers to orally communicate the new information and document that communication.

“How additional information is communicated will depend on many factors, including the type of study, the complexity, and/or urgency of the new information and the research population,” the draft stated.

There also is information that does not have to be communicated to participants, such as changes to the inclusion criteria that have no effect on those already enrolled. With the revised Common Rule, OHRP reopened questions on a matter that has heretofore been handled by a wide variety of approaches.

“I have to say that from my IRB experience we talked about this, but it was never a problem in the context of individual protocols,” Rosenfeld said. “We could always calibrate the amount of information and ask for an addendum vs. an update to the consent form — there were lots of ways to do it. I don’t think it was perceived as a problem. That being said, there was no standard way. I’m sure every IRB did it differently. That’s the context. Once we started to dig [into this] there was more there.”

(Editor’s note: Video of the July 30-31 SACHRP meetings can be viewed online at: https://bit.ly/2kFFB7O.)