1. Revisions to the Common Rule
Jerry Menikoff
Office for Human Research Protections

2. Disclaimer
The opinions expressed are those of the presenter and do not necessarily reflect the policy of the U.S. Department of Health and Human Services.

6. To be covered: Brief background on the revised rule
Major proposals not adopted
Summary of some key changes:
Single IRB review
Definition of “research” carve-outs
Continuing review
Expedited review
Expanding exemptions
Informed consent

7. Why Revise the Common Rule?
Better protect research subjects, where appropriate
Reduce inappropriate administrative burdens

8. Brief Overview of Rulemaking Process
ANPRM NPRM Final Rule
July 2011
September 2015
January 19, 2017
Public Comment
Public Comment

9. Implementation Dates
General implementation date currently July 19, 2018
Notice of Proposed Rulemaking released asking for public input on possible additional 6-month delay
Additional protections for subjects can comply with now

10. Major Proposals Not Adopted
Extension of Common Rule to cover research using non-identified biospecimens, which would almost always require consent
Extension of Common Rule to clinical trials that are not federally funded
Rather than creating required, standard privacy protections as proposed in the NPRM, the final rule commits the Secretary of HHS to develop guidance for IRBs on assessing the adequacy of privacy and confidentiality protections. Will be done in consultation with the other Common Rule agencies and OMB.

11. Requirement for Single IRB Review
Applicability
U.S. institutions engaged in cooperative research for the portion of the research conducted in the U.S.
Does not apply:
When more than single IRB review is required by law (including tribal law)
Whenever any Federal department or agency supporting or conducting the research determines and documents that the use of a single IRB is not appropriate for the particular context – flexibilities allowed
§_.114(b)
Does not apply to foreign institutions or to research conducted outside of the U.S. by U.S. institutions.
The lead reviewing IRB is selected by the Federal department or agency supporting or conducting the research, or the lead institution, subject to the acceptance of the Federal department or agency.
Reminder: The new single IRB requirement applies to research approved by an IRB on or after January 20, 2020
We recognize that it may take institutions more time to develop the systems and policies needed to comply with this new requirement, so institutions have 2 additional years to comply with this requirement compared to the other provisions
A U.S. institution conducting research initially approved by an IRB before January 20, 2020, will not be required to comply with the new single IRB requirement.

12. Definition of Research: Activities Deemed Not To Be Research
Scholarly and journalistic activities
Focus on the specific individual about whom information is collected
Excludes certain activities, not entire academic fields
Government functions with separately mandated protections
Public health surveillance activities
Collection of information for criminal justice purposes
Operational activities for national security purposes
§_.102(l)
Scholarly and journalistic activities include, but are not limited to, oral history, journalism, biography, literary criticism, legal research, and historical scholarship. (These are only examples of scholarly and journalistic activities.)
It is not the particular field that removes the activity from the definition, but rather the particular activity’s focus on specific individuals

13. Eliminating Certain Continuing IRB Reviews
In general, no continuing review required for:
Research approved by expedited review
Research that has completed interventions and only involves:
Analyzing data, including analyzing identifiable private information or identifiable biospecimens
Accessing follow-up clinical data from clinical care procedures
IRB can override this default and require continuing review, but this must be documented
§_.109(f) and §_.115(a)(3)

14. Updating and Simplifying Expedited Review
List will be reviewed every 8 years and updated if necessary
Presumption that activities listed are minimal risk
Unless expedited reviewer determines otherwise
§_.110, §_.109(f) and §_.115(a)(8)
Mention that we are in the process of reviewing the expedited list, and have asked SACHRP’s Subcommittee on Subpart A to develop recommendations for consideration by SACHRP, and ultimately, HHS and OHRP.

15. Summary of Changes to Exemptions
Revised Common Rule
Pre-2018 Rule (Current)
Exemption 1
Exemption 2
Exemption 3
Exemption 4
Exemption 5
Exemption 6
Restrictions added Expanded Removed and replaced with a new exemption 3 Expanded old and added new Expanded with changes No change *New Exemption 7 *New Exemption 8 *New - limited IRB review
This will just be a high-level discussion of the key changes to the exemption categories in the revised rule.
One general difference from the pre-2018 rule is that some of the current exemptions have been expanded, and new exemptions have been added that allow investigators to retain identifiable information that might be sensitive, provided that specified privacy and confidentiality protections are satisfied.
The changes are also intended to exempt more low risk social and behavioral research

16. Expanding Exempt Research: Exemption 2
Educational tests, surveys, interviews, and observations of public behavior exemption when
Information recorded cannot be readily linked back to subjects, or
Any information disclosure would not place subjects at risk of harm, or
Identifiable information recorded with limited IRB review for privacy and confidentiality protection under §_.111(a)(7)
§_.104(d)(2)

17. Expanding Exempt Research: New Exemption 3
New exemption for research involving benign behavioral interventions with adults who prospectively agree when information collection is limited to verbal or written responses (including data entry) or audiovisual recording

18. Expanding Exempt Research: Exemption 4
Secondary research use of identifiable private information or identifiable biospecimens (materials no longer need to be “existing”) if:
Identifiable private information or identifiable biospecimens are publically available, OR
Information, which may include information about biospecimens, is recorded by the investigator in such a manner that the identity of the human subjects cannot be readily ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects or re-identify subjects, OR
New provisions under exemption 4 – only apply to studies that only involve secondary research. They do not apply to studies that involve research interventions or interactions with subjects.
This exemption now covers research involving identifiable private information and identifiable biospecimens that are not existing at the time the research is proposed for exemption
First 2 provisions of the new Exemption 4 are essentially an expansion of current exemption 4. Includes other relatively minor changes that essentially clarify the how such information may be recorded by investigators

19. Expanding Exempt Research: Exemption 4, cont’d
Secondary research use of identifiable private information or identifiable biospecimens for which consent is not required, if:
Investigator’s use is regulated under HIPAA as “health care operations,” “research,” or “public health” OR
Research is conducted by, or on behalf of, a Federal agency using data collected or generated by the government for non-research purposes, and the information is protected by federal privacy standards
§_.104(d)(4)
The HIPAA-related exemption is limited to studies where the recipient investigator’s use of the identifiable private information or identifiable biospecimens is protected under the HIPAA rules. It does not apply if only the entity disclosing the information or biospecimens is subject to the HIPAA rules, and not the recipient investigator.
The fourth provision under Exemption 4 has limited applicability to Federal reserachers and those researchers conducting studies on behalf of the Federal government, such as contractors.

20. Expanding Exempt Research New Exemptions 7 and 8: Require Broad Consent
Exemption 7: Storage or maintenance of identifiable private information or identifiable biospecimens for secondary research
Exemption 8: Secondary research using identifiable private information or identifiable biospecimens
§_.104(d)(7) and (8)

21. Some of Changes to Informed Consent
Posting Consent Forms for Clinical Trials
Broad Consent
General Improvements to Informed Consent
Only addressing 4 key changes related to consent, but there are other important changes that generally create more flexibility in the rule, such as the change to the definition of LAR, changes to the documentation of consent, and facilitating screening and recruitment of subjects.

22. Posting of Consent Forms for Clinical Trials
For clinical trials supported by federal funding, one IRB-approved consent form used to enroll participants must be posted on publicly available Federal website to be designated §_.116(h)
Goals are to increase transparency, increase trust, and ultimately improve the quality of informed consent – forward looking.
If the federal department or agency supporting or conducting the clinical trial determines that certain information should not be made publicly available, they can permit or require reductions.
In some rare cases the federal department or agency may determine that the existence of a particular clinical trial should not be made public, in which case no posting of such a trial would be required.

23. Allowing the Use of Broad Consent for Secondary Research
Optional: An alternative to traditional informed consent or waiver of informed consent: open-ended consent to non-specified future research
Applicable to:
The storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens
Collected for either a different research study, or for non-research purposes
Plays a very different role than as was proposed in the NPRM when consent would almost always have been required for the use of biospecimens – including non-identified biospecimens.
In response to public comment, now functions as offering a new flexibility or alternative to:
Obtaining study-specific consent OR
Seeking a wavier of consent
And can be used to meet 2 new Exemptions (Exemptions 7 and 8).
Broad consent includes elements of consent from the “basic” and “additional” elements of consent, and some that are unique to broad consent.
Goal to be meaningful, informed consent even though specific research studies do not need to be described. Must provide a general description of the types of research that may be conducted—providing sufficient information to allow a reasonable person to expect that the broad consent would permit the types of research conducted.
When information about specific research is not to be provided, the broad consent must inform subjects that they might have chosen not to consent to some of those specific research studies.
At the same time, the broad consent requirements in the revised rule are simplified and less restrictive than proposed in the NPRM (e.g., does not include limitations on the biospecimens or information that the broad consent can cover, such as the NPRM proposal to limit this to those biospecimens and inforamtion to be collected up to 10 years after broad consent was obtained.)

24. General Consent Changes
Goal: consent form as decision aid, not just risk disclosures (compare to drug ads on TV – many risks, nothing about alternatives)
Form should be written in way to help person make a good decision
This is an outline for the major areas of your presentation -- what you’re going to talk about. You should not include the title, introduction or conclusion in your outline. Just highlight the major areas of your talk.

25. Specific consent changes in regulations
The revised Common Rule explicitly establishes a new standard: to provide the information needed to make an informed decision about whether to participate
§__.116(a)(4)
Explain new standard of highlighting helping a person make a decision between several options

26. Specific changes in consent regulations
Reasonable person standard used to determine more specifically what information to include
Long used for clinical informed consent
Considered most consistent with ethical principles
§__.116(a)(4)
Traditional disclosure standard for clinical care (a matter of state tort law) deferred to expertise of physicians (“professional standard”). But more modern view is that professional expertise is not needed to determine which risks a patient should be told about: instead, determine disclosures based on “reasonable person” standard. This is viewed as a standard with greater justification in ethics.

27. Specific changes in consent regulations
Information presented in sufficient detail, and organized and presented in a way that facilitates subject’s understanding of reasons why one might or might not want to participate
Not merely a list of isolated facts
§__.116(a)(5)(ii)
Information should be presented in sufficient detail.
For example, common practice to just say someone may or may not benefit from being in a study.
Often, more can be said – and if so, it should be (e.g., very unlikely that being in this study will cure your cancer).
Information should be presented in a way that is designed to help someone make an appropriate decision.
Another example: Instead of listing the side effects of each chemotherapy agent separately, one option could be to describe the side effects of the
combination of treatments for each arm. And to specifically address and highlight the DIFFERENCES between the side effects of the two arms,
instead of requiring the subject to puzzle it out from the separate lists.

28. Sufficient detail
Consent forms commonly criticized for often failing to provide specific information about the research study
E.g., benefits discussion that merely says “you may or may not benefit”
Instead, give some specific information about type of benefit (cure disease, remediate symptoms) and likelihood
This is an outline for the major areas of your presentation -- what you’re going to talk about. You should not include the title, introduction or conclusion in your outline. Just highlight the major areas of your talk.

29. Facilitates understanding - not merely lists
Note common practice of consent forms having separate benefits, risks, alternative sections – isolated pieces of information, without explanation putting it together
Goal of new rules is to include that explanation, make it easier to understand
This is an outline for the major areas of your presentation -- what you’re going to talk about. You should not include the title, introduction or conclusion in your outline. Just highlight the major areas of your talk.

30. Specific changes in consent regulations
There is a new requirement that certain key information must be provided first
§__.116(a)(5)(i)

31. Why Participate – or Not
That key information must be about why one might or might not want to participate. It would often include (though not limited to) information about purposes, risks, benefits and alternatives.
§__.116(a)(5)(i)
How does standard of “why one might or might not want to participate” differ from current (“pre-2018”) regulations? Ask, how often do current consent forms point out why someone might not want to participate (apart from listing risks). Virtually never – consistent with the impression that consent forms are merely making sure the right disclosures are made (the legal requirements met), without genuinely engaging the prospective subject about whether participation is or is not in their best interests.

32. Concise and Focused
That key information must be provided in a concise and focused presentation
§__.116(a)(5)(i)
Introduce notion of “initial part of consent form/process”
What does concise and focused mean?
What may be considered ‘key information?’ Operationally, what does it mean by presenting the key information first, how does this work, how might this impact on the section that presents the key elements, and how is this supposed to help with keeping informed consent form at a reasonable length?

33. Ex: Radiation for Breast Cancer
Should radiation be used for treating breast cancer with 1 to 3 positive nodes?
Women being treated with radiation and chemo – question is whether to add radiation
Study randomized women to radiation or not
Consent form’s entire discussion of why the study was being done: “to find out whether [radiation] treatment after chemotherapy will reduce the risk of breast cancer recurrence and thus help patients to live longer.”

34. Ex: Radiation for Breast Cancer
In “A Debate on Radiation in Breast Cancer” ( in the NY Times, Feb 24, 2004, Laurie Tarkan:
Discusses decision-making in the clinical context
Already know that for women with 4+ positive nodes, adding radiation increased survival

35. Ex: Radiation for Breast Cancer
Benefits from adding radiation appeared to become less clear as cancer became more localized
“There is no question that if given radiation, these women would further reduce the rate of recurrence by two-thirds, bringing it down to 3 to 5 percent.”
“But whether that translates into a survival benefit – and how much of one – is not known.”

36. Ex: Radiation for Breast Cancer
Should the consent form perhaps:
Include more of this specific information?
Would a reasonable woman in this circumstance want to know that adding radiation would reduce the likelihood of the cancer recurring by two-thirds (even though unknown whether it extends survival)?

37. Ex: Radiation for Breast Cancer
Should the consent form perhaps:
Explain how a woman could use the additional information to make a decision to enroll or not to enroll, based on her values
For example, it could point out that a woman who wanted to minimize the chance of the cancer coming back, even at the risk of radiation side effects, and even if it isn’t clear that it increases her survival, should probably not enroll, but instead choose radiation

38. Ex: Radiation for Breast Cancer
Should the consent form perhaps:
Also discuss views of a woman who is very concerned about side effects of radiation (such as lymphedema, reduced ability to have breast reconstruction), and who might want to especially avoid that treatment in the absence of clear evidence that it will likely extend her life