Experience and innovation in ethical review.®
An Update and Overview of the
US Common Rule Regulations
David Borasky, MPH, CIP
Copernicus Group IRB
CAREB – 30 APRIL 2015
Objectives for this session
In this session, we will….

Review the current US regulatory framework

Key requirements for REBs reviewing
research subject to us regs

Potential changes to the US regulations and
national policy
US National Research Act
July, 1974
• National Commission for the Protection of
Human Subjects of Biomedical and Behavioral
Research (1974-1978)
Public Law 93-348
Charge to the National Commission
 Identify the basic ethical principles which
should underlie the conduct of biomedical and
behavioral research involving human subjects
 Develop guidelines to assure that such
research is conducted in accordance with those
principles
National Research Act, 1974 (PL 93-348)
Belmont Report (1979)

Moral framework for US regulations

Three fundamental principles:



Respect for persons
Beneficence
Justice
5
US Federal Regulations & Policy


45 CFR 46 - Basic DHHS Policy for Protection of
Human Research Subjects - Subpart A
 January 13, 1981
“The Common Rule” - Federal Policy for the
Protection of Human Subjects


June 18, 1991
Core regulations adopted by most US Departments /
Agencies that support or conduct research
6
Dept of Education
US Federal Regulations & Policy
Additional Protections Included in 45 CFR 46:

Subpart B - Additional protections for research involving
pregnant women and fetuses

Subpart C - Additional protections for research involving
prisoners

Subpart D - Additional protections for research involving
children
8
Additional Federal Laws


Dept of Education

Dept of Defense

34 CFR 97 Subpart D

10 USC 980

34 CFR 98

DoDD 3216.2

34 CFR 99

DoDD 6000.8

34 CFR 350.4(c)

DoDD 6002.2
34 CFR 356.3(c)

AFI 40-402


AFI 40-403

AR 70-25

AR 40-38

SECNAVINST 3900.39B

NMRDINST 3900.2

BUMEDINST 6000.12

NSHSBETHINST 6000.41A

USUHS Instruction 3201
Dept of Justice



28 CFR 512 Subpart B
Dept of Energy

Order 443.1

Order 481.1A

10 CFR Part 850
VA

38 CFR 17.85

Dept of Homeland
Security

Subparts
US Food and Drug Administration (FDA)
Govern US research involving drugs, devices,
biologics

21 CFRF 50 – Informed consent

21 CFR 56 – Requirements for IRBs

FDA and Common Rule mostly aligned

Studies can be subject to both Common Rule and
FDA!
10
Key Elements of Regulatory
Protections Under Common Rule
• All human subjects research must have prior REB
approval
• Informed consent unless waived
• An “Assurance” to uphold ethical and regulatory
requirements  FWA Mechanism
LOOPHOLES
• Non-federally-funded research, not
involving FDA-regulated items, in an
institution not holding a FWA
• Classified (US government) research
Applicability of
Regulations
Federally Funded
DHHS (FWA)
FDA
17 Departments
& Agencies
45 CFR 46
Subpart A

Common Rule
Subpart B
Subpart C
Subpart D
• Other research covered by FWA
Dan Nelson
The Federalwide Assurance
•
Common Rule requires written “assurance of
compliance”
•
•
•
HHS/OHRP uses FWA mechanism
Other departments accept FWA or have similar
mechanism
FWA is promise to follow applicable U.S.
regulations
•
Required of all engaged sites in HHS-funded
research
REB written procedures
OHRP / FDA required written procedures:
1.
The procedures which the REB will follow for
conducting its initial review of research;
Use of primary reviewers
 Approvals with contingencies

2.
The procedures which the REB will follow for
conducting its continuing review of research

Meaningful, substantive
REB written procedures
3.
The procedures which the REB will follow for
reporting its findings and actions to investigators and
the institution

4.
which institutional offices / officials are notified of REB
findings and actions and how notification to each is
accomplished;
The procedures which the REB will follow for
determining which projects require review more often
than annually
Level of risk
 Population being studied
 Previous PI compliance issues

REB written procedures
5.
The procedures which the REB will follow for
determining which projects need verification from
sources other than the investigators that no material
changes have occurred since previous REB review
Randomly selected projects;
 Complex projects involving unusual levels or types of risk to
subjects
 Investigators with past compliance issues

REB written procedures
6.
The procedures which the REB will follow for ensuring
prompt reporting to the REB of proposed changes in a
research activity, and for ensuring that such changes in
approved research, during the period for which REB
approval has already been given, may not be initiated
without REB review and approval except when
necessary to eliminate apparent immediate hazards to
the subject
Training programs and materials for investigators,
 Specific directives included in approval letters to investigators
 Random audits of research records

REB written procedures
7.
The procedures for ensuring prompt reporting to the
IRB, appropriate institutional officials, any
Department or Agency head, and OHRP of:
Any unanticipated problems involving risks to subjects or
others;
○ Any serious or continuing noncompliance with 45 CFR Part
46 or the requirements or determinations of the IRB; and
○ Any suspension or termination of IRB approval.
○
REB written procedures
• Guidance available at:
http://www.hhs.gov/ohrp/policy/irbgd107.html
• Many institutions post their institutional policies
online – do not be afraid to borrow!
New Era of Change?
• Common Rule regulations largely
unchanged since 1991
• Regulations could not anticipate 21st
century research realities
• Changes proposed on multiple fronts
HHS/OHRP - Potential Notice of
Proposed Rule Making (NPRM)
• Advanced NPRM published in 2011
• Multiple proposed changes
• Single IRB
• All specimens = identifiable
• Revisions to exempt and expedited
• Numerous comments from regulated
community
NPRM Concerns
• 4 years since ANPRM
• Lack of transparency
• Disagreement among Common Rule
agencies  end of Common Rule?
• Further separation from FDA regs?
NIH Single REB Policy
• Would require single REB for all multi-site
research studies (US domestic only)
• Only NIH-funded research
• Many institutional REBs not equipped to
serve as central REB
• Concerns about REB policy being dictated
outside of the regulatory structure
Newborn Dried Bloodspot Law
• New law signed in December 2014
• Affects HHS-funded research using residual
newborn dried bloodspots
• Bloodspots = human subject, even when
otherwise considered de-identified
• REB may not waive informed consent for
research user
21st Century Cures Initiative
• Proposed healthcare legislation
• Would expand regulatory oversight /
eliminate loopholes
• Not yet clear which current regulations
would be expanded, or if replaced with new
Other issues related to REBs
• Big Data
• Who controls the data
• Consent issues
• Research involving social media
• Facebook Study
• Return of Results
• General
• Individual
Questions, Comments and Discussion