1. Human Subject Research Protections: The Revised Common Rule
Office for Human Research Studies
Emily Eldh, CIP
January 2019

2. The (Forever Changing) Regulatory Landscape
Introductions
How did we get here?
Health and Human Services (HHS) Final Common Rule
21st Century Cures Act
What’s next?
Questions

3. Introductions – OHRS Senior Staff
Emily Eldh, CIP –
Director
Liz Bowie, JD, MPH, MSc –
Associate Director
Daniel Kronish, MD –
Associate Director of Medical Review
Casey Rich, CIP –
Research Review Manager: Activation, Meeting Management, Policy Documentation
Elizabeth Mutti –
Operations Manager: Intake, Online Communications, and OHRS Systems
Polly Goodman, CIP –
Senior Human Research Coordinator
Nicole Burbul –
Sean Murphy, CIP –

4. OHRS Organization Chart – January 2019
Emily Eldh, CIP - Director
Daniel Kronish, MD – Assoc. Dir. Medical Review
Elizabeth Buchbinder, MD – MD Reviewer
Eric Jacobsen, MD – MD Reviewer
Glenn Bubley, MD – MD Reviewer
Christina Ullrich, MD – MD Reviewer
Elizabeth Bowie, JD, MPH, MSc - Associate Director
Nicole Burbul, Senior HRC – Team B Lead
Preethi Fonseka, HRC III
Shannon Peabody, HRC III
Judelle Cummins, HRC II
Sara Ames, HRC I
Samantha Zina, HRC I
Melissa Syverin, HRC I
Sean Murphy, CIP Senior HRC
Open HRC I Position [TBD]
Polly Goodman, CIP Senior HRC – Team A Lead
Damien Christian, HRC IV
Elizabeth Tabbut, HRC II
Sephora Hollant, HRC II
Porsha Lark, MPH, MS, HRC I
Christina Desir, MPH HRC I
Aimee Gillespie, HRC I
Temp Employees
Lauren Perez, Temp BODFI
Casey Rich, CIP - Research Review Manager
Danielle Shaffer, HRC IV Act (to ODQ)
Katie Lane, HRC III Mtg Mgmt
Ashika Shah, HRC I Mtg Mgmt
Tafique Chowdhury, Temp Act
Samantha Muench, Temp Act
Elizabeth Mutti – Operations Manager
Peter O’Neil, OCC I (to ODQ)
Laura Gillis, OCC III (to ODQ)
Leslie Rawles, OCCI (to ODQ)
Marguerite Maclean – Admin Spec I – Front Desk / Mtg. Asst.
Catherine Singer, Admin Specialist I – Intake Float
Giuseppina Cucciniello, HRC I – Intake
Khari Linton, HRC I - Intake
Roseanna Wilder – Temp Event Intake
Xiaoyan Liang – Temp Intake
Terrell Williams – Temp Intake

5. How Did We Get Here?

6. How did we get here?
Health and Human Services (HHS) Common Rule &
Food and Drug Administration (FDA) regulations governing
Human Subjects Research detail:
What an Institutional Review Board (IRB) is charged with reviewing;
How an IRB should be organized; and
The Criteria for Approval of IRB reviewed research.
Note: HHS & FDA regulations are currently aligned (pre-1/21/2019).
Health Insurance Portability & Accountability Act (HIPAA)
The DFCI IRB also serves as the Privacy Board and determines whether waivers or alterations to the HIPAA Privacy Rule are appropriate in the context of human subjects research.

7. 41 Years Ago 38 Years Ago 22 Years Ago How did we get here? 1978
FDA Regulations - 21 CFR 50 & 56
1981
HHS Regulations - Common Rule 45 CFR 46
1996
Health Insurance Portability & Accountability Act (HIPAA)
We have had the same basic human subject regulations for the past 40 years. 22 years ago HIPAA was added.
41 Years Ago
38 Years Ago
22 Years Ago

8. 8 Years Ago 4 Years Ago 3 Years Ago How did we get here? 2011
Advanced Notice of Proposed Rule Making (ANPRM)
Comment Period on ANPRM
2015
Notice of Proposed Rule Making (NPRM)
Comment Period on NPRM
2016
NIH Single IRB Mandate (06/21/16)
21 Century Cures Act Signed (12/13/16)
In 2011 started the process of revising the human protection regulations (8 years ago now). The process starts with the ANPRM, then a NPRM. Additional changes impacting IRBs and human protection regulations are enacted – NIH and 21st Century Cures Act
8 Years Ago
4 Years Ago
3 Years Ago

9. < 2 Years Ago <1 Year Ago Now How did we get here? 2017
Final Rule Announced in the Federal Register (1/19/17)
60 Day Congressional Hold by the New Administration
2018
Final Rule Effective (1/19/18)
Interim Final Rule = Delay (1/22/18)
NPRM Delay + 3 “Burden Reducing Provisions” (4/20/18)
Final Rule Delay (6/19/18)
Final Rule Effective and Compliance (1/21/19)
Final Rule – sIRB Requirement (1/20/20)
Revised final rule announced in January 2017 days before the new administration takes office. Hold, delay, delay + burden reducing provisions, Final Revised Final Rule Date – January 2019! With single IRB following in 2020.
< 2 Years Ago
<1 Year Ago
Now

10. What didn’t happen?
Revised Final Rule - Notable Deviations from the NPRM:
Regulations do not cover clinical trials that are not federally funded.
Biospecimens – What did not Happen?
No Broad Consent Requirement (Optional “Regulatory Broad Consent” added).
The definition of “human subject” was not expanded to include deidentified biospecimens or the requirements to obtain informed consent from the originating human source for the retention and future use of such specimens.
Eliminated proposed standardized privacy safeguards for identifiable private information and identifiable biospecimens.
The restrictive proposed criteria for obtaining a waiver of consent requirements relating to research with identifiable biospecimens were not adopted.
Informed Consent Presentation Requirements more flexible than originally proposed.
Exempt / NHSR Determinations will NOT be made by investigators - No Decision Tool
- OHRP received more that 2,100 public comments in response to the NPRM.
Biospecimens, bullet 1: New elements of consent, including a statement regarding research involving the collection of identifiable private information; and new elements for broad consent to the storage, maintenance, and secondary research use of all biospecimens (regardless of identifiability) or identifiable private information.
Broad consent is now permissible but not required for the secondary use of specimens
Criteria for obtaining a waiver of informed consent remain unchanged
Efforts to improve the IC process remain; including the requirement to post IRB-approved consent forms for clinical trials on a publicly available website.
Not discussed is the elimination of “excluded” activities and the expansion of Exempt categories. OHRP relies on definition of research with the Preamble identifying specific activities as not human subject research (e.g., journalistic activities, oral histories)
Broad Consent – not required and now only applicable to identifiable private information or identifiable specimens; However, FR prohibits IRBs from issuing a waiver of IC if a subject is approached but declines to provide broad consent.

11. Final Revised Common Rule
What is changing?
Definitions (Scope)
IRB Operations
Informed Consent Content
New Guidelines for Exemptions
Other
Major Changes for Investigators are noted with an asterisk.
Changes to IRB operations, the informed consent process, the type of research governed by DHHS regulations and additional guidelines for Exempt review

12. Final Revised Common Rule: Definitions
Definitions / Scope
Details
DF/HCC Impact
Definition of what is NOT Research
Defines what is NOT research to “resolve long-standing debate and uncertainty”
Scholarly and Journalistic activities
Public health surveillance
Criminal justice activities
Authorized operations in support of national security
Update Policies and Procedures
Minimal Impact
Definition of Human Subject
Includes “information or biospecimens” obtained through intervention and interaction OR “identifiable private information or identifiable biospecimens”
“Information” or “biospecimens” replaces “data”. “Data” implied information and biospecimens.
Definition of Clinical Trial
Clinical trials are now specifically defined; consent forms for these trials will now need to be posted on a federal website upon study completion
Posting of consents to federal website will be a Moderate Impact*

13. Final Revised Common Rule: IRB Operations
Details
DF/HCC Impact
Administrative
Reliance arrangement with non-institutional IRB must be documented
Institutions are no longer required to provide a current list of IRB committee members and their qualifications – IRBs should maintain their own list.
Institutions are no longer required to designate one or more IRBs on its FWA
OHRS Documents reliance agreement arrangements (no change)
OHRS maintains the DFCI IRBs membership rosters
OHRS will no longer designate an IRB on our FWA
“Checking the Box” Removed
Option for FWA holders to check the box has been eliminated. The Common Rule now only applies to federally funded research.
DFCI and DF/HCC clinical sites had unchecked the box on our FWAs
DFCI and DF/HCC clinical sites Apply the Common Rule to all Research regardless of funding with limited exceptions (e.g. 2 year continuing reviews)

14. Final Revised Common Rule: IRB Operations
Details
DF/HCC Impact
Single IRBs for multisite research (effective: 2020)*
Single IRBs generally required, some flexibility in determining/documenting when not appropriate
NIH sIRB Rule for Multi-Center Research already effective (1/25/18)
Updated Policies and Procedures
Continuing Review*
Eliminate Continuing Review for studies where study interventions have ended (e.g. clinical trials in long term follow up or data analysis - unless FDA Regulated)
When continuing review is not required, OHRS will communicate with the PI and study teams annually (or biennial) their ongoing responsibilities and obligations for continued IRB approval of the research.
Ongoing Responsibilities and Obligations include (but are not limited to): 1. Following the Research as approved by the IRB, 2. Submitting any changes to the research for IRB approval before implementation, 3. Reporting any deviations from the IRB approved research to OHRS, 4. Reporting to CT.gov when required, 5. Notifying OHRS when the research has ended.

15. Final Revised Common Rule: Informed Consent
Informed Consent (IC)
Details
DF/HCC Impact
New language / clarity*
New emphasis on the subject’s comprehension. The intent of the changes is:
To facilitate the subject’s understanding of the proposed research
AND
Ensure that the subject understands how their data and Biospecimens may be used
New Consent Form Introduction requires:
A concise and focused presentation of key information “that a reasonable person” would want to have in order to make an informed decision about whether to participate, and an opportunity to discuss that information.
Major Impact for Study Teams
Consent Form Template revised and Required for all research as of December 1, 2018
NEW Studies reviewed on/after January 21, 2019 may have to add new elements to the consent for IRB approval.
The DF/HCC Consent Form Template is available on the OHRS website here:
FDA Guidance – The new consent form requirements ARE NOT INCONSISTENT with FDA’s current policies and guidance’s.

16. Final Revised Common Rule: Informed Consent
Informed Consent (IC)
Details
DF/HCC Impact
New language / clarity*
Continued
The Concise Summary is defined as:
Summary of information that is most crucial to making a decision whether or not to participate. [Note: Type of Information is not defined in the rule, it will depend on the study.]
Information presented first, rather than being dispersed in the document. [Estimate ~ 2 pages maximum]
Is an opportunity for the consenting investigator to consider or seek input on the Key pros and cons that a prospective participant would need to weigh in making a decision.
Major Impact for Study Teams
Consent Form Template revised and Required for all research as of December 1, 2018
NEW Studies reviewed on/after January 21, 2019 may have to add new elements to the consent for IRB approval.
The DF/HCC Consent Form Template is available on the OHRS website here:
FDA Guidance – The new consent form requirements ARE NOT INCONSISTENT with FDA’s current policies and guidance’s.

17. Final Revised Common Rule: Informed Consent
Informed Consent (IC)
Details
DF/HCC Impact
Basic and additional elements of IC*
New required element of consent:
Statement on whether the identifiers might be removed and information or biospecimens could be used for future research without additional informed consent
New additional elements added to be used when appropriate:
Biospecimens may be used for Commercial profit (and whether to subject will share in that profit)
Return of clinically relevant results (or not)
Research will involve whole genome sequencing of Biospecimens
Major Impact for Study Teams
Consent Form Template revised and Required for all research as of December 1, 2018
NEW Studies reviewed on/after January 21, 2019 may have to add new elements to the consent for IRB approval.
The DF/HCC Consent Form Template is available on the OHRS website here:
FDA Guidance – The new consent form requirements ARE NOT INCONSISTENT with FDA’s current policies and guidance’s.

18. Final Revised Common Rule: Informed Consent
Informed Consent (IC)
Details
DF/HCC Impact
Broad consent
Option for storage maintenance, and secondary research use of identifiable private information/biospecimens
Use permits use of new Exempt Categories 7 and 8
DFCI IRB and other clinical DF/HCC sites will not implement “Regulatory Broad Consent”
DFCI IRB and other clinical DF/HCC sites will not use new Exemptions 7 or 8
Electronic consent
Electronic consent is ok; must provide subjects with a copy ( / hard copy)
Study teams must have a plan to provide subjects with a copy of the signed electronic consent form.

19. Final Revised Common Rule: Exemptions
Details
DF/HCC Impact
Additional Exemptions for low-risk studies*
New exemptions added; including exemptions for secondary research on identifiable private information and identifiable biospecimens under various circumstances; various regulatory requirements such as “limited IRB review” and broad consent may apply
Category 1 - Normal Education Setting (Restricted)
Category 2 - Educational Tests, Surveys, Interviews, Public Observation (Expanded)
Category 3 - Benign Behavioral Intervention (Adults Only - New)
Category 4 - Secondary Research of Identifiable Information or Specimens Collected for Other Purpose for which Consent Not Required (Expanded)
DFCI IRB and other clinical DF/HCC sites will not use new Exemptions 7 or 8
When “Limited IRB Review” is required, OHRS will conduct this review as if it was an expedited IRB review
Category 4 is the most commonly used Exemption by DF/HCC Investigators

20. Final Revised Common Rule: Other Considerations
Details
DF/HCC Impact
Transition Provisions
Studies reviewed under the old rule may transition to the new rule but must comply with all aspects of the new rule (e.g. Consent Form content)
OHRS will not transition studies to the new rule for at least 6 months
Studies will only transition if the benefit is greater than the new requirements under the revised rule
Grant Review
Removal of the requirement for Institutional Review Boards (IRBs) to review grant applications and contract proposals related to research.
The IRB will not need to review grants unless required by the funding agency or institution.
NEW: NIH – no review needed! IRB must continue to review and approve all NIH supported non-exempt Human Subject Research (no change).

21. Other Requirements: 21st Century Cures Act
Aims to minimize administrative burden on researchers
Highlights include:
HHS Secretary to Harmonize FDA regulations and the revised Common Rule (Note: They will not be aligned when the Final Rule is implemented)
Requires Drug Manufacturers to publicly post their expanded access policies and provide points of contacts for requests.
Removes Local IRB oversight requirement for device (IDE) studies
Requires NIH to ensure that centers and institutes collaborate on projects collecting similar data
Requests Guidance from HHS on HIPAA Privacy Rule and future uses of specimens and data
Consent alteration or waivers for minimal risk FDA-governed research

22. What’s needed to prepare and implement?

23. What’s next? Keeping Track
Absent OHRP Guidance, Await SACHRP Guidance
Work with DF/HCC Consortium Institutions
Harvard Catalyst Regulatory Committee
NCCN IRB Directors Forum
PRIM&R Educational Sessions and Conferences

24. What’s needed to prepare and implement?
1. Update and Require use of Revised Consent Form Template (done)
2. Revise and Finalize DFCI IRB Policies and Procedures and Guidance Documents (ongoing)
3. Update Systems and IRB Documentation including Forms to accommodate Rule Change (ongoing)
4. Train Research Community (ongoing):
Revised Consent Form Training: November 9th and 28th 2018
IRB Member Consent Form Training: December 10th – December 20th 2018
OHRS Staff Rule Change Training: December 19th 2018
IRB Chair Rule Change Training: December 20th 2018
Rule Change Training: January 4h and 10th 2019

25. What’s still needed to prepare and implement?
Guidance from OHRP
Read the text of the revised Common Rule Read about the revised Common Rule Revised Common Rule Q&As
Activities Deemed Not to be Research: Public Health Surveillance, 2018 Requirements
Scholarly and Journalistic Activities Deemed Not to be Research: 2018 Requirements
When Continuing Review Is Not Required During the 6-Month Delay Period
Elimination of Institutional Review Board (IRB) Review of Research Applications and Proposals: 2018 Requirements
Guidance from SACHRP
Guidance from FDA
Impact of Certain Provisions of the Revised Common Rule on FDA-Regulated Clinical Investigations (10/2018)
Guidance from NIH
NIH Implementation of the Burden-Reducing Provisions of the 2018 Common Rule:
NIH Implementation of the Final Rule on the Federal Policy for the Protection of Human Subjects (Common Rule):

26. Additional Recommended Training on the Revised Common Rule:
The CITI program has a new optional training module on the Common Rule changes. 
Please keep in mind CITI will not describe specific plans for implementing this new rule at DF/HCC.  Additional information on implementation plans will be communicated separately.
CITI program: 
These are groups that oversee research activities conducted at DF/HCC institutions and require specific information about the research related to regulatory determinations.

27. More Info to Come!
2019 Common Rule Webpage: OHRS has created a new page on the OHRS website where updates concerning the revised common rule will be placed.

28. Thank you! OHRS Common Rule Website:
Office for Human Research Studies (OHRS)
Dana-Farber Cancer Institute
450 Brookline Avenue, OS229 Boston, MA Phone: Fax: