SACHRP Task Force Report: Prioritization of SACHRP Recommendations

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SACHRP Task Force ReportPrioritization of
SACHRP Recommendations

• Barbara E. Bierer, MD
• SACHRP
• March 3-4, 2009

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Outline

• Review of SACHRP Charter Purpose and Function
• Charge to Task Force
• SACHRP Task Force Process
• Brief review and Synthesis of Recommendations
• Next steps
• Questions and discussion

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SACHRP Charter Purpose

• Purpose
• The Secretary is responsible for regulatory
  oversight of the system for the protection of
  human subjects in biomedical and behavioral
  research supported or conducted by the Department
  of Health and Human Services. The Secretarys
  Advisory Committee on Human Research Protections
  shall provide expert advice and recommendations
  to the Secretary and the Assistant Secretary for
  Health (ASH) on issues and topics pertaining to
  or associated with the protections of human
  research subjects. The Committee will work to
  advise the Secretary as to how to improve the
  quality of the system of human research
  protection programs, including the
  responsibilities of investigators, institutional
  review boards, administrators, and institutional
  officials, and the role of the Office of Human
  Research Protections and other offices within the
  Department of Health and Human Services.
• Formerly known as NHRPAC, Initial
  Charter October 1, 2002
• Last Renewed October, 2008

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SACHRP Charter

• Function
• The Committee shall advise, consult with, and
  make recommendations on matters pertaining to the
  continuance and improvement of functions within
  the authority of the Department of Health and
  Human Services (HHS) directed toward protections
  for human subjects in research. Specifically,
  examples include but are not limited to advice
  relating to the responsible conduct of research
  involving human subjects with particular emphasis
  on
• Special populations, such as neonates and
  children, prisoners, and the decisionally
  impaired
• Pregnant women, embryos, and fetuses
• Individuals and populations in international
  studies
• Populations in which there are individually
  identifiable samples, data, or information and
• Investigator conflicts of interest.
• Formerly known as NHRPAC, Initial
  Charter October 1, 2002
• Last Renewed October, 2008

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SACHRP Charter

• Function
• In addition, the Committee shall be responsible
  for reviewing selected ongoing work and planned
  activities of the Office of Human Research
  Protections (OHRP) and other offices/agencies
  within HHS responsible for human subjects
  protection. These evaluations may include but are
  not limited to a review of assurance systems, the
  application of minimal research risk standards,
  the granting of waivers, education programs
  sponsored by OHRP, and the ongoing monitoring and
  oversight of institutional review boards (IRBs)
  and the institutions that sponsor research.
• Formerly known as NHRPAC, Initial
  Charter October 1, 2002
• Last Renewed October, 2008

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SACHRP Principles

1. Help the research community maintain the highest
   possible standard of human subject protection
   while advancing knowledge for the benefit of
   society
2. Improve the effectiveness, quality, and
   efficiency of the informed consent and the
   protocol review and monitoring process
3. Reduce regulatory burden that does not contribute
   meaningfully to human subject protection
4. Uphold public trust in the integrity of research
   conduct

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147 recommendations, grouped into topic areas,
were reviewed at SACHRP on October 27, 2009

• Research involving children and subpart D of 45
  CFR part 46 (38)
• Accreditation of human research protection
  programs (HRPPs) (5)
• Adverse event reporting (1)
• Research involving pregnant women and subpart B
  of 45 CFR part 46 (1)
• HIPAA Privacy Rule (9)
• Research involving prisoners and subpart C of 45
  CFR part 46 (9)
• OHRP/NIH/FDA workshop on central IRB review
  mechanisms (1)
• Subpart A of 45 CFR part 46 (79)
• Tribal authority over research involving American
  Indian or Alaska Native populations (1)
• Research in disaster settings (2)
• Review of the human subjects protection system
  (1)
• Total number of recommendations 147

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Task Force

• The SACHRP Task Force was endorsed at the October
  27-28, 2008 meeting of SACHRP following a
  recommendation by Dr. Myron Genel
• SACHRP will establish an ad hoc committee to
  review and prioritize pending SACHRP
  recommendations to the Department of HHS, with a
  report to be presented to SACHRP at its next
  meeting (March 3-4).
• Letters of Recommendations to the Secretary
  http//www.hhs.gov/ohrp/sachrp/commsec.html

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Task Force Process
Membership

• Elizabeth Bankert
• Barbara Bierer
• Jeff Bodkin
• Myron Genel
• Stephen Shodeke
• David Strauss
• With participation and support from
• Julia Gorey
• Jerry Menikoff
• Ivor Pritchard

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Task Force Process

• Process
• 2 conference calls
• Receipt and review of OHRP input
• Review with Subcommittees
• SAS
• SIIIDR
• Prioritization sent to SACHRP members, past
  chairs, past subcommittee chairs for input
• Input collated and recommendations re-ordered
• Summary and presentation to SACHRP March 3-4,
  2009

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SACHRP Criteria for Prioritization

• Enhance protection of human subjects
• Reduce regulatory burdens that do not contribute
  to the protection of human subjects
• Clarify confusing or apparently inconsistent
  regulatory language
• Importance
• vs
• Ease of Execution (Low-hanging fruit)
• Individuals were encouraged to apply their own
  criteria and were not asked to explain ranking

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Recommendations requiring prioritization as
requested by OHRP

• Topics for OHRP regulatory action/policy or
  guidance development requiring substantial
  investment by OHRP (n recommendations)
• A. Children (38)
• B. Prisoners (9)
• C. Research Involving Pregnant Women (1)
• D. Continuing Review (14)
• E. Expedited Review (6)
• F. Training and Education (4)
• G. Waiver of Informed Consent (6)
• H. Minimal Risk (6)
• I. Waiver of Documentation of Informed Consent
  (5)
• J. Exemptions (27)
• K. Roles of Institutional Officials (5)
• L. Submission of Membership Rosters (5)

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Recommendations requiring prioritization as
requested by OHRP

• Topics for OHRP regulatory action/policy or
  guidance development requiring substantial
  investment by OHRP (n recommendations)
• A. Children (38) (A-C Enhance protections of
  human subjects)
• B. Prisoners (9)
• C. Research Involving Pregnant Women (1)
• D. Continuing Review (14)
• E. Expedited Review (6)
• F. Training and Education (4)
• G. Waiver of Informed Consent (6)
• H. Minimal Risk (6)
• I. Waiver of Documentation of Informed Consent
  (5)
• J. Exemptions (27)
• K. Roles of Institutional Officials (5)
• L. Submission of Membership Rosters (5)

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Recommendations requiring prioritization as
requested by OHRP

• Topics for OHRP regulatory action/policy or
  guidance development requiring substantial
  investment by OHRP (n recommendations)
• A. Children (38) (A-C Enhance protections of
  human subjects)
• B. Prisoners (9)
• C. Research Involving Pregnant Women (1)
• D. Continuing Review (14) (D-L Reduce regulatory
  burdens, Clarify confusing or apparently
  inconsistent regulatory language
• E. Expedited Review (6)
• F. Training and Education (4)
• G. Waiver of Informed Consent (6)
• H. Minimal Risk (6)
• I. Waiver of Documentation of Informed Consent
  (5)
• J. Exemptions (27)
• K. Roles of Institutional Officials (5)
• L. Submission of Membership Rosters (5)

Importance vs Ease of Execution (Low-hanging
fruit)
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Recommendations requiring prioritization as
requested by OHRP

• Topics for OHRP regulatory action/policy or
  guidance development requiring substantial
  investment by OHRP (n recommendations)
• A. Children (38)
• B. Prisoners (9)
• C. Research Involving Pregnant Women (1)
• D. Continuing Review (14)
• E. Expedited Review (6)
• F. Training and Education (4)
• G. Waiver of Informed Consent (6) (G-L Secretary
  acknowedgement pending)
• H. Minimal Risk (6)
• I. Waiver of Documentation of Informed Consent
  (5)
• J. Exemptions (27)
• K. Roles of Institutional Officials (5)
• L. Submission of Membership Rosters (5)

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Recommendations suggested to be moot and not
recommended for further action by OHRP

• Recommendation topics where prioritization for
  regulatory action/policy guidance development is
  Moot
• A. Adverse Event Reporting (1)
• B. Central/Alternative IRB mechanisms (1)
• C. HIPAA Privacy Rule (9)
• D. Accreditation of HRPPS (5)
• E. Tribal Authority over Research Involving
  American Indian or
• Alaska Native Populations (1)
• F. Demonstration Projects related to system-level
  changes in the Human Subjects Protection
  System (1)

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Recommendations suggested to be moot and not
recommended for further action by OHRP

• Recommendation topics where prioritization for
  regulatory action/policy guidance development is
  Moot
• A. Adverse Event Reporting (1)
• Guidance finalized by OHRP FDA final guidance
  issued January, 2009
• B. Central/Alternative IRB mechanisms (1)
• Workshops held and report generated
• C. HIPAA Privacy Rule (9)
• Office for Civil Rights has responsibility for
  HIPAA privacy rule
• D. Accreditation of HRPPS (5)
• No recommendation suggested no guidance required
• E. Tribal Authority over Research Involving
  American Indian or Alaska Native Populations (1)
• Referred to Secretary for action
• F. Demonstration Projects related to system-level
  changes in the Human Subjects Protection System
  (1)
• No regulatory action/policy guidance development
  needed

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Recommendations suggested to be moot and not
recommended for further action by OHRP

• Recommendation topics where prioritization for
  regulatory action/policy guidance development is
  Moot
• A. Adverse Event Reporting (1)
• Guidance finalized by OHRP FDA final guidance
  issued January, 2009
• B. Central/Alternative IRB mechanisms (1)
• Workshops held and report generated
• C. HIPAA Privacy Rule (9)
• Office for Civil Rights has responsibility for
  HIPAA privacy rule
• D. Accreditation of HRPPS (5)
• No recommendation suggested no guidance required
• E. Tribal Authority over Research Involving
  American Indian or Alaska Native Populations (1)
• Referred to Secretary for action
• F. Demonstration Projects related to system-level
  changes in the Human Subjects Protection System
  (1)
• No regulatory action/policy guidance development
  needed

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SACHRP PRIORITIES

• Recommendation Topics for OHRP regulatory
  action/policy
• guidance development requiring substantial
  investment by OHRP
• Children (38) A
• Expedited Review (5) E1,2,4 are guidance, E3
  regulatory, E5 started
• Waiver of Informed Consent and
• Documentation of IC (11) G and I combined
• Continuing Review (14) D1, D3-14 guidance, D2
  regulatory,
• Membership Roster (2) L
• Minimal risk (6) H (6-8 Similarly Ranked)
• Exemptions (27) J
• Institutional Officials (5) K
• Training and Education (4) F FR notice posted,
  process started
• Prisoners (9) B
• Research involving Pregnant Women and Subpart B
  (1)

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Recommendations 1. Children

• 1. Children (38)
• ??46.407 Majority of (6) recommendations
  implemented via OHRPs May 26, 2005 guidance on
  the 407 review process and OHRPs and FDAs
  implementation of a joint review process for
  research regulated by both agencies.
• FDA issued guidance on its process under 21 CFR
  50.54.
• Algorithm for analysis under subpart D (part of
  recommendation I) still under consideration by
  OHRP.
• Recommendation regarding a SACHRP subcommittee
  assessing aspects of 407 process implementation
  and making annual reports (part of recommendation
  VI) not implemented.

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Recommendations 1. Children

• 1. Children (38)
• ? 46.404 research not involving greater than
  minimal risk (7)
• ? 46.405 research involving greater than minimal
  risk but presenting the prospect of direct
  benefit to individual subjects (5)
• ? 46.406 research involving greater than minimal
  risk and no prospect of direct benefit, but
  likely to yield generalizable knowledge about the
  subjects disorder or condition (4)
• ? 46.402 child assent (3)
• ? 46.408c parental permission and its waiver for
  research designed for conditions for which
  parental or guardian permission is not a
  reasonable requirement to protect subjects (3)
• ? 46.409 research involving children who are
  wards (6)
• ? 46.116(d) vis-a-vis waiver of parental
  permission (4)

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Recommendations2. Expedited Review

• 2. Expedited Review (6)
• 3 calling for revised OHRP and FDA guidance on
  expedited review
• solely clerical or administrative by qualified
  IRB staff
• IRBs may give qualified staff authority for
  clerical/administrative
• IRBs may develop stipulation mechanisms for
  verifying required change
• 1 calling for revision of the regulations by
  changing Expedited review to Delegated review
  (Harmonization with FDA encouraged)
• 1 calling for specific revisions to expedited
  category 7 regarding behavioral research, and
• 1 calling for OHRP review of the expedited
  categories every 5 years, harmonizing list of
  categories with FDA

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Recommendations3. Waiver of, and Waiver of
Documentation of, Informed Consent

• 3. Waiver of, and Waiver of Documentation of,
  Informed Consent (11)
• 6 recommendations regarding the interpretation of
  the provisions under ? 46.116(d) for waiver of
  the requirements for obtaining informed consent.
• 5 recommendations regarding waiver under ?
  46.117(c) of the requirements for documenting
  informed consent

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Recommendations4. Continuing Review

• 4. Continuing Review (14)
• Revision of OHRPs guidance regarding continuing
  review (13)
• Duration and stipulations of CR required after
  data collection (1)
• Simplified criteria and content of CR depending
  on study risk (1)
• (similar action called for by FDA)
• Expedited review for no additional risks,
  interventions, or activities at any sites and
  expanded examples of expedited review (2)
• Responsibility for literature review by
  investigator, not IRB (1)
• No requirement for ongoing review of exempt
  protocols (1)
• Guidance on substance and timing of CR (4)
• Continued participation of already enrolled
  subjects if lapse in IRB CR
• Clarity of protocol summary (1)
• Qualified IRB staff may accomplish review of
  protocol (1)
• Advance Notice of Proposed Rulemaking
  46.109(e)proposal to allow continuing review to
  occur less frequently than once per year, but not
  less than every 2 years (1)

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Recommendations5. Membership rosters

• 5. Submission of Membership Rosters (5)
• On January, 2009, OHRP (and FDA) published
  Subpart E largely defining requirement for
  electronic and, if necessary, written
  registration of IRBs.
• Relevant to Assurance stipulation discussed at
  this meeting

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Recommendations6 Minimal Risk and 7. Exemptions

• 6. Minimal Risk (6)
• 6 recommendations regarding the interpretation of
  the definition of minimal risk at ? 46.102(i)
• 7. Exemptions (27)
• 27 recommendations regarding the exemptions.

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Recommendations8. IOs and 9. Training and
Education

• 8. Roles of Institutional Officials (5)
• 5 recommendations regarding roles of
  institutional officials in protecting human
  subjects.
• 9. Training and Education (4)
• 4 recommendations calling for new regulations
  requiring initial and continuing training
• IRB members (1)
• IRB staff (1)
• Institutional Officials and Human Protection
  Administrator (1)
• Investigators and research team (1)
• OHRP published a Federal Register notice seeking
  information and comment

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RecommendationsPrisoners

• Prisoners (9)
• 1 recommendation calling for extensive revision
  of subpart C.
• 8 recommendations regarding interpretation of
  current provisions of subpart C.?(July 28, 2005)
• (One recommendation, that a prisoner
  representative should be a reviewer when research
  involving prisoners is reviewed by an IRB under
  an expedited review procedure, has been
  incorporated into OHRP FAQs.
• All other recommendations would require
  development of new guidance or revision of
  subpart C regulations and are under consideration
  by OHRP, along with many other recommendations
  made by the IOM.

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RecommendationsResearch involving Pregnant Women

• Research Involving Pregnant Women and Subpart B
  (1)
• Recommendation OHRP should develop guidance on
  subpart B regarding how to interpret Biomedical
  knowledge in broadest possible sense, and the
  requirement that data cannot be collected by any
  means other than by enrolling pregnant women. The
  guidance should stress the appropriate use of the
  exemption clause.

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SACHRP PRIORITIES

• Recommendation Topics for OHRP regulatory
  action/policy
• guidance development requiring substantial
  investment by OHRP
• Children (38) A
• Expedited Review (5) E1,2,4 are guidance, E3
  regulatory, E5 started
• Waiver of Informed Consent and
• Documentation of IC (11) G and I combined
• Continuing Review (14) D1, D3-14 guidance, D2
  regulatory
• Membership Roster (2) L
• Minimal risk (6) H (6-8 Similarly ranked)
• Exemptions (27) J
• Institutional Officials (5) K
• Training and Education (4) F FR notice posted,
  process started
• Prisoners (9) B
• Research involving Pregnant Women and Subpart B
  (1)

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Refinement Subpart A
E 1,2,4 Exp. Rev guidance 3
GI Waiver of IC and doc 6
D-2 Cont. Rev. guidance 8
L Membership Roster 11
J Exemptions 12
E5 Exp. Rev, process started 12
H Minimal Risk 12
K I.O.s 14
F Training 16
D2 Cont. (2 yrs) 17
E3 Exp. Rev term change 21
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Comments and Discussion