General

1
OHRP Doing it right
together! OFFICE FOR HUMAN RESEARCH PROTECTIONS,
DHHS (http//ohrp.osophs.dhhs.gov/) SBIR/STTR
HUMAN SUBJECT REQUIREMENTS (http//ohrp.osophs.dhh
s.gov/educmat.htm) Clifford C. Scharke, D.M.D.,
M.P.H. Last Revised May 20, 2002
2
Introduction and Overview

• Why - Concepts
• When - Applicability
• What - Process
• How - Resources
• Who - Human Assistance
• Wow - Things That Can Go Wrong

3
Concepts

• Volunteers - Human Subjects
• Permission - Informed Consent
• Oversight - Institutional Review Boards
• Documentation - Assurance and Records
• Self-Interest - Whats it to you?

4
Volunteers - Human Subjects

• Other people and their private information dont
  belong to the PI
• The sheer value of the research does not
  automatically trump rights of people
• Ask before you take unless IRB approves
• Definition of a human subject

5
Definition of a Human Subject

• Human subject means a living individual about
  whom an investigator (whether professional or
  student) conducting research obtains
• data through intervention or interaction with
  the individual, or
• identifiable private information

6
Permission - Informed Consent

• From the Nuremberg Code on, the right to say no
  is the first right of a subject
• Permission of a duly informed volunteer is
  required unless the IRB says otherwise
• Volunteers who are not of legal age for the
  intended procedure must also grant permission (if
  theyre able to do so)
• Definitions of consent and assent

7
Definitions of Consent and Assent

• Consent - legally effective agreement of the
  subject or the subject's legally authorized
  representative based on information that is given
  to the subject or the representative in language
  that is understandable
• Assent - childs affirmative agreement to
  participate in research
• Permission - agreement of parent(s) or guardian
  to the participation of their child or ward in
  research

8
Oversight - Institutional Review Boards

• An objective review panel under 45 CFR 46
• (http//ohrp.osophs.dhhs.gov/humansubjects/guidan
  ce/45cfr46.htm46.102)
• Competent for review of science ethics
• Adequate in number and composition
• Voting members are free of conflict
• Suitably composed for involved human subjects
• Sufficient knowledge of local context
• (http//ohrp.osophs.dhhs.gov/humansubjects/guidan
  ce/local.htm)

9
Documentation - Assurance and Records

• Prior written promise to meet minimum Federal
  standards to protect subjects
• IRB minutes in required detail
• Ongoing IRB certification and enduring records of
  all required reportable events
• If it isnt documented, it didnt happen
• Definitions of Assurance and Records

10
Documentation - Assurance and Records

• Assurance - a legally binding written document
  that commits a public or private entity to
  compliance with applicable Federal minimum
  standards for the protection of human subjects
  prior to engagement in Department or Agency
  conducted or supported research (i.e., prior
  binding promise to follow applicable rules) and
  includes citation of ethical principles,
  designated IRB, list of IRB members, IRB
  procedures, and institutional and investigator
  responsibilities

11
Documentation - Assurance and Records

• Records - An institution, or when appropriate an
  IRB, shall prepare and maintain
• Copies of all research proposals reviewed, any
  scientific evaluations, approved sample consent
  documents, progress reports submitted by
  investigators, and reports of injuries to
  subjects
• Minutes of IRB meetings which shall be in
  sufficient detail to show attendance actions
  taken the vote on these actions the basis for
  requiring changes in or disapproving research
  and a written summary of the discussion of
  controverted issues and their resolution

12
Documentation - Assurance and Records

• Records - An institution, or when appropriate an
  IRB, shall prepare and maintain
• Records of continuing review activities
• Copies of all correspondence between the IRB and
  the investigators
• A list of IRB members in the same detail as
  described in 46.103(b)(3)
• Written procedures for the IRB in the same detail
  as described in 46.103(b)(4) and 46.103(b)(5).

13
Self-Interest - Whats it to you?

• Defensible research must be ethical research
• Rules that protect subjects protect the PI
• PI integrity is measured by compliance
• The reputation of the PIs institution is at
  stake
• Future funding can be jeopardized
• Funding authority credibility can be questioned
• As goes the publics trust, so goes research

14
Applicability

• Research - a systematic investigation, including
  research development, testing and evaluation,
  designed to develop or contribute to
  generalizable knowledge (regardlesss of what it
  might be called) (http//ohrp.osophs.dhhs.gov/huma
  nsubjects/guidance/45cfr46.htm46.102)
• 45 CFR 46 applies if Human Subjects DHHS
  Research - Exemptions (http//ohrp.osophs.dhhs.gov
  /humansubjects/guidance/decisioncharts.htm)
• Awardees of DHHS-supported human subject research
  and all entities that interact with, intervene
  upon, or have potential access to private
  identifiable information of living persons are
  engaged and are required to possess an applicable
  Assurance prior to human subjects
  (http//ohrp.osophs.dhhs.gov/humansubjects/assuran
  ce/engage.htm)

15
Process

• Preparation - its never too early to consult
  with the population, institutions, and IRB
  Chair(s) when planning the research design
• Pre-application - Assurance and IRB approvals are
  not required (needed prior to any award)
• PHS 398 Application complete instructions
• (http//grants.nih.gov/grants/funding/phs398/phs3
  98.html)

16
Process

• SBIR/STTR Application Instructions - dont miss
• I.C.1 Face Page - Item 4 - Human Subjects
• No Human Subjects
• Human Subjects Involved
• Exemptions from Regulations
• Human Subject Assurance Number
• NIH-Defined Phase III Clinical Trial
• I.C.1 Face Page - Item 15 - Organization
  Certification
• Human Subjects
• Transplantation of Human Fetal Tissue
• NIH Women and Minority Inclusion Policy
• NIH Inclusion of Children Policy
• Use of Embryonic Stem Cells
• I.C.8 Research Plan 8.e - Human Subjects
  Research
• Note These are policies to which questions are
  best addressed to NIH

17
Process

• SBIR/STTR Application Highlights - dont miss
• I.C.1. Item 4 - Face Page enter yes or no
  for human subjects and exemptions if yes for
  both, then enter E1-6 (http//grants1.nih.gov/gran
  ts/funding/phs398/section_1.htmle_humansubs)
  -see footnote to 46.101(b) for limitations to
  exemptions
• I.C.1. Item 4 - Face Page - do not enter
  Assurance number for the institution with the
  designated IRB (enter None) if applicant
  possesses a Multiple Project Assurance (MPA) or
  Federalwide Assurance (FWA), then enter number -
  check OHRP Website if not sure
• (select link to MPA or FWA from
  http//ohrp.osophs.dhhs.gov/irbasur.htm)

18
Process

• SBIR/STTR Application entries - dont miss
• Research Plan/Item 8e Human Subjects Research
  
• Follow PHS 398 instructions carefully to avoid
  your application from being designated
  incomplete
• Human Subject/Exemption/Clinical/Clinical Trial
  Status
• Exemption Categories 1 through 6 (select as
  applicable)
• Risks/Protections/Benefits/Importance
• Certificates of Confidentiality
  (http//grants.nih.gov/grants/policy/coc/index.htm
  and
• http//ohrp.osophs.dhhs.gov/humansubjects/guidanc
  e/cert-con.htm)
• Collaborating Sites
• Engagement of sites in human subject research
  (http//ohrp.osophs.dhhs.gov/humansubjects/assuran
  ce/engage.htm)
• Note Scenarios are given in the instructions to
  assist.

19
Process

• Assurance to Comply with 45 CFR 46 Before Award
• Applicant will be notified by NIH in writing of
  award
• Award conditioned on Assurances to OHRP from
• Awardee
• All sites engaged in human subject research
• Funding authority identifies the need for and
  seeks Assurances through the awardee for all
  engaged sites
• Each site without a Federal-wide Assurance files
  an FWA, designates a registered IRB sends to
  OHRP (see instructions at http//ohrp.osophs.dhhs
  .gov/irbasur.htm)
• OHRP advice required for options other than FWA
• Awardee/PI may but need not contact OHRP

20
Specific Resources

• OHRP Web-based FWA Filing and IRB Registration
  review in detail and act when timely
  (http//ohrp.osophs.dhhs.gov/irbasur.htm)
• Options to finding an IRB to designate
• Establish your own (potential conflicts)
• Rely on suitable IRB of a collaborating site
• Locate willing MPA institution near subjects
  (http//ohrp.cit.nih.gov/search/asearch.asp)
• Identify suitable independent IRB (see next
  slide)
• Designated IRB must perform local review
  (http//ohrp.osophs.dhhs.gov/humansubjects/guidanc
  e/local.htm)

21
General Resources

• OHRP Website
• (http//ohrp.osophs.dhhs.gov/index.htm) - seek,
  find, and fill needs
• Belmont Report (ethical principles)
• IRB Guidebook and Investigator 101 CD
• Training Videotapes and Workshops
• Common Findings in Noncompliance
• Links to Other Websites
• Independent Institutional Review Boards (for a
  listing see http//www.advamed.org/solutions/revie
  wboards.shtml) -
• Note URL not endorsed by OHRP - provided solely
  as a courtesy not all listed IRBs necessarily
  conform to OHRP local IRB and conflict-free
  requirements (see previous slide)

22
Human Assistance

• IRB Chair
• Pre-protocol planning to enhance and prevent
  problems
• Arrange for investigator training to preserve
  integrity
• Advice on exemptions and expedited review
• Expertise on human subject issues
• Referral to other sources of expertise
• OHRP Assurance Staff
• (http//ohrp.osophs.dhhs.gov/dpa-staff.htmTable1
  )
• General SBIR/STTR questions - Assurance
  Coordinators
• IRB Registration questions - Helen Gordon
• Federalwide Assurance negotiations - Assurance
  Coordinators (http//ohrp.osophs.dhhs.gov/dpa-st
  aff.htmTable2)
• Note Click on geographic location of awardee
  for correct AC

23
Things That Can Go Wrong

• Doesnt see PI and subject interests are same
• Investigator waits too long for IRB input
• Underestimates the value added by the IRB to the
  integrity of the process and reputation of all
• PIs unaware of accrual restrictions or is not
  informed by funding authority until its too late
• PI falls victim to miscellaneous investigator
  shortcomings (e.g., special protections, protocol
  revisions, adverse events, and progress reports)
  (http//ohrp.osophs.dhhs.gov/references/findings.p
  df)

24
Conclusions

• Volunteers grant permission with IRB oversight
  that is assured in advance
• Prepare early for human subject issues
• Know when and from where to get help
• Prepare your application with confidence
• Let the system work for you know when it isnt
  confirm with funding authority
• Whats good for subjects is good for you!