OHRPOPRR http:grants'nih'govoprroprr'htm

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OHRP/OPRR(http//grants.nih.gov/oprr/oprr.htm)

• OFFICE FOR HUMAN RESEARCH PROTECTIONS, DHHS
• formerly
• OFFICE FOR PROTECTION FROM RESEARCH RISKS, NIH
• SBIR/STTR HUMAN SUBJECT REQUIREMENTS
• (http//grants.nih.gov/grants/oprr/humansubjects/a
  ssurance/sbirsttr/requirements.htm)
• Clifford C. Scharke, D.M.D., M.P.H.
• July 11, 2000

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Introduction and Overview

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

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Concepts

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

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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

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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

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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

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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

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Oversight - Institutional Review Boards

• A local and objective review panel
• Voting members are free of conflict
• Suitably composed for subject context
• Competent for review of science ethics
• Adequate in number and composition
• Definitions of IRB and Local Review

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Oversight - Institutional Review Boards

• IRB - an Institutional Review Board established
  in accord with and for the purposes expressed in
  45 CFR 46 (http//grants.nih.gov/grants/oprr/human
  subjects/45cfr46.htm46.102)
• Local Review - an IRB that possesses sufficient
  knowledge of the local research context (see
  guidance found at http//grants.nih.gov/grants/opr
  r/humansubjects/guidance/local.htm)

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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

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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

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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

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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).

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Self-Interest - Whats it to you?

• Valid research is 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

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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//grants.nih.gov/grants/opr
  r/humansubjects/45cfr46.htm46.102)
• Human subject DHHS research - Exemptions
  (http//grants.nih.gov/grants/oprr/humansubjects/g
  uidance/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//grants.nih.gov/grants/oprr/humansubjects/a
  ssurance/engage.htm)

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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)

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Process

• SBIR/STTR Application entries - dont miss
• Face Page/Item 4 - leave IRB date blank and do
  not enter Assurance number for the institution
  with the designated IRB (enter None) if
  applicant possesses a Multiple Project Assurance,
  then enter either an IRB date or Pending and
  applicable MPA number (http//grants.nih.gov/grant
  s/funding/sbirsttr1/11instructions.htm11b)
• Research Plan/Item G - respond to all numbered
  items or, if exemption claimed, explain (see
  below) (http//grants.nih.gov/grants/funding/sbirs
  ttr1/11instructions.htm11b)
• Human Subjects - exemptions and investigators
  role (http//grants.nih.gov/grants/funding/sbirstt
  r1/11instructions.htm11j)

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Process

• Pre-award assurance to comply with 45 CFR 46
• Applicant will be notified in writing of award
• Award held until Assurances confirmed for
• Awardee
• All sites engaged in human subject research
• Funding authority notifies OHRP/OPRR
• OHRP/OPRR seeks Assurances through PI
• Awardee/PI need not contact OHRP/OPRR

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Resources

• Sneak Preview - OHRP/OPRRs request review in
  detail to be ready and then wait
  (http//grants.nih.gov/grants/oprr/humansubjects/a
  ssurance/spainfo.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//grants.nih.gov/grants/oprr/library_human.h
  tmASS)
• Seek out an independent IRB that is local
  (http//grants.nih.gov/grants/oprr/humansubjects/g
  uidance/local.htm)

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Resources

• OHRP/OPRR Website (http//grants.nih.gov/grants/op
  rr/oprr.htm) - seek, find, and fill needs
• Belmont Report (ethical principles)
• IRB Guidebook (topics of interest to PIs)
• Training Video-tapes and Workshops
• Links to other Websites
• Commercial Institutional Review Boards
  (http//www.himanet.com/irb.htm) - not endorsed
  by OHRP/OPRR URL provided as a courtesy not all
  listed IRBs necessarily conform to OHRP/OPRR
  local IRB and conflict-free requirements
  (http//grants.nih.gov/grants/oprr/humansubjects/g
  uidance/local.htm)

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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/OPRR Staff
• (http//grants.nih.gov/grants/oprr/ab-staff.htmT
  able1)
• General SBIR/STTR questions - Helen Gordon
• Assurance negotiation - Assurance Coordinators
  (ACs) (http//grants.nih.gov/grants/oprr/ab-staff.
  htmTable2)
• Note Click on geographic location of awardee
  for correct AC

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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 by funding
  authority or erroneous lack until its too late
• PI falls victim to miscellaneous investigator
  shortcomings (e.g., special protections, protocol
  revisions, adverse events, and progress reports)
  (http//grants.nih.gov/grants/oprr/findings.pdf)

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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!