After the Compliance Date: Revised Common Rule FAQs (Or: Why We Cancelled Our February Webinar)

As we mentioned in our September webinar on the revised Common Rule, OHRP published 3 guidance documents related to the burden reducing provisions on July 20, 2018. OHRP also recently provided instructions for posting ICFs to the Regulations.gov website (see #10 below).

FDA intends to harmonize to the extent practicable and consistent with other statutory provisions its regulations with the revised Common Rule, but we haven’t yet seen revised regulations for notice and comment. In October 2018, FDA published Impact of Certain Provisions of the Revised Common Rule on FDA-Regulated Clinical Investigations to address the impact of the revised Common Rule on FDA-regulated research. In that guidance, FDA clarified that key information and the new basic and additional elements required under the revised Common Rule may be included in consent forms for FDA-regulated research (they are not inconsistent but complementary to FDA requirements). FDA also provided clarification on the expedited review procedures (see #3 below) and reminded us that continuing review is still required for FDA-regulated research.

Under the revised Common Rule, IRBs are no longer required to determine that research on the expedited review list involves no more than minimal risk. It is now assumed that research on the list is minimal risk unless the IRB determines it is more than minimal risk and doesn’t qualify for expedited review (45 CR 46.110(b)(1)(i)). Because FDA has not revised its regulations, for FDA-regulated research the IRB must still determine that the research on the expedited review list involves no more than minimal risk to use the expedited review procedures.

Several of the new exemptions will cover research that also may fall within a category on the existing and as yet unchanged expedited review list. At Advarra, we will be using the exemptions if applicable and not the expedited categories. It is important for your institution to have a policy addressing which regulations you will apply when there is an overlap.

We’ve had several questions from IRBs about updating their electronic systems to implement the changes required by the revised Common Rule and track studies no longer requiring continuing review. Most electronic systems have their own unique features, and it is hard to offer general guidance. We know that some institutions have added a new regulatory tracker to indicate whether a study is subject to the old Common Rule, revised Common Rule, or FDA regulations (or a combination) and an additional tracker for studies subject to the revised Common Rule to indicate whether continuing review is required. We’ve found it helpful to have that information readily available to IRB staff and members to remind everyone of the regulatory framework for the review.

Some things to remember in terms of tracking: you may be reviewing research that is not federally funded, not FDA-regulated, federally funded, FDA regulated, and both FDA-regulated and federally funded. You’ll need to be able to identify which set(s) of regulations apply. For federally funded research, you’ll also need to track the dates of initial IRB approval to determine whether the old Common Rule or revised Common Rule applies, and whether the study has been transitioned to the revised Common Rule.

IRBs are still trying to get familiar with this new exemption category. This exemption applies only to adults who prospectively agree to the research and the information collected is limited to verbal or written responses, including data entry or audiovisual recordings. Remember: even though it applies to Subpart B, that only involves pregnant women not neonates since a foundational requirement for exemption 3 is that it applies only to adult subjects.

• A benign behavioral intervention is defined as an intervention that is brief in duration, harmless, painless, not physically invasive, not likely to have a significant adverse lasting impact on subjects and the investigator must have no reason to believe that the intervention will be offensive or embarrassing to subjects. In reviewing these submissions, IRBs should consider the study population, the topic, and other relevant factors.
• Deception is permitted only when subjects prospectively agree to participate in research in which they will be unaware of or misled regarding the nature or purposes of the research. Researchers should consider debriefing after the intervention.
• OHRP’s list of benign behavioral intervention examples includes having the subjects play an online game, having them solve puzzles under various noise conditions, or having them decide how to allocate a nominal amount of received cash between themselves and someone else.
• Physical interventions that are physically invasive or those that could be harmful or painful would not meet the exemption. Even low risk physical procedures like wearing sensors/data collection devices (e.g., trackable devices, Fitbit, blood pressure monitoring), blood draws, or the collection of bodily fluids by introduction of a tool into the body (e.g., buccal swab) would not meet this exemption.
• To qualify for this exemption, one of the following criteria must be met:
  • The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects;
  • Any disclosure of the human subjects’ responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, educational advancement, or reputation; or
  • The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by 45 CFR 46.111(a)(7).
• For additional information, here is a link to the Secretary’s Advisory Committee of Human Research Protections (SACHRP) recommendations for benign behavioral interventions. Note these are recommendations only.

For research subject to the revised Common Rule, there is a new additional criterion in order to grant a waiver of consent for studies using identifiable private information or identifiable biospecimens. For these studies, the IRB must determine that the research could not practicably be carried out without using the information or biospecimens in an identifiable format. FDA has not adopted this additional criterion, so for FDA-regulated research, it is not applicable.

Remember, if research is exempt there is no need for a waiver of consent, but there might be a need for limited IRB review.

• For Exemption 4 (secondary research use of identifiable private information or identifiable biospecimens), a full or partial HIPAA waiver may still be required.

Some investigative sites have inquired about how the revised Common Rule impacts their site and what they need to know about it. Many of the revisions to the Common Rule directly impact the IRBs and required changes to their regulatory review framework and processes. As an investigative site, it will be important to know the funding source for the research because federally funded research will require additional information in the consent form. You may also find that some federally funded studies no longer require continuing review (and the IRB will advise you whether continuing review is or is not required). In addition, there are several new or revised exemptions that may apply to your research, including benign behavioral interventions and storage, maintenance and use of identifiable private information and identifiable biospecimens obtained with broad consent.

Remember that for clinical trials conducted or supported by a Common Rule department or agency, 1 IRB-approved version of an ICF that has been used to enroll participants must be posted on a public federal website designated for posting such documents. It must be posted after recruitment closes, and no later than 60 days after the last study visit. Federal departments or agencies may permit or require redactions as appropriate. For multisite trials, it will be important to identify who is responsible for posting the ICF and ensuring they are advised of the last study visit.

• There are 2 publicly available federal websites that will satisfy the consent form posting requirement under the revised Common Rule: ClinicalTrials.gov and a docket folder on Regulations.gov (Docket ID: HHS-OPHS-2018-0021) OHRP has also launched a webpage with instructions on posting consent forms on Regulations.gov.