Research Compliance

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Research Compliance

• Tommy Coggins

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Course Objectives

• You will become familiar with the Human Subjects
  Protection Program.
• You will become familiar with the Animal Care
  Program.
• You will understand conflicts of interest related
  to outside professional activities.
• You will become familiar with scientific
  misconduct policy.
• You will be introduced to export control
  regulation.
• You will learn about HIPAA Requirements.

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Public Trust

• The conduct of research is a privilege granted by
  society, not an inalienable right
• The granting of the privilege is based on the
  publics trust that research will be conducted
  responsibly
• Erosion of that trust can result in the publics
  withdrawal of the privilege
• Public trust is maintained through accountability

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Human Subjects in Research
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Human Subject Ethical and Regulatory Guidance

• National Research Act (1974)
• Belmont Commission
• Belmont Principles
• Respect for Persons
• Beneficence
• Justice
• Regulations
• 45 CFR Part 46 Common Rule DHHS
• 21 CFR Part 50, 56 - FDA

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Government Oversight

• Office of Human Research Protection (OHRP) -
  Health and Human Services
• Food and Drug Administration (FDA)

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Basic Regulatory Requirements

• Institutional assurance
• Review of research by an Institutional Review
  Board (IRB)
• Informed consent of subject

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Composition of the IRB

• Minimum of 5 members
• Diverse in gender and racial background
• Sufficiently qualified in experience and
  expertise
• One scientific member
• Non-scientific member
• Community member (non-affiliated)

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Definition - Research

• A systematic investigation, including research
  development, testing and evaluation, designed to
  develop or contribute to generalizable knowledge

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Definition - Human Subject

• Living individual about whom an investigator
  conducting research obtains 1) data through
  intervention or interaction with the individual
  or 2) identifiable private information

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USC IRB Review Process

• Faculty completes the HSA in USCERA
• Research Proposal/Protocol
• Abstract
• Consent Document
• Survey
• Advertisements/Recruitment Materials
• Complete the USC Human Subjects Training

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Levels of Review

• Exempt
• Expedited
• Full Committee Review

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Review Considerations (Required)

• Risks to subjects are minimized
• Risks are reasonable in relation to benefits
• Selection of subjects is fair and equitable
• Participation is voluntary with appropriate
  informed consent
• Appropriate monitoring of data to protect
  subjects
• Adequate provisions to protect privacy

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IRB Authorities

• Approve
• Require Modifications
• Disapprove

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Case Study

• Two weeks into the new semester, the professor
  in Marys course on family health gives the class
  a special assignment that was not on the course
  syllabus. Over the next week, everyone in the
  class is to talk with three classmates who are
  not in the course about the way their families
  deal with medical emergencies and chronic
  illness. Next week they should come to class
  prepared to report on their interviews. The
  Professor warns them, however, that in talking
  about their conversations they should not mention
  any names to protect the privacy of their
  classmates.
• The assignment makes Mary uneasy. In her basic
  psychology course last semester she learned about
  some of the rules pertaining to the use of human
  subjects in research. However, when she raises
  her concerns with her professor, he assures her
  that her informal conversations with classmates
  are not research and therefore not subject to
  regulation. Move-over, since she will not be
  mentioning any names, there are no privacy issues
  to worry about.
• Should Mary be content with these assurance and
  conduct the interviews?
• If she still has concerns, where should she turn
  for advice?
• Did the professor act properly in giving this
  assignment to the class?

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Case Study

• First-year dental students have cultivated oral
  bacteria from their own mouths as part of a
  microbiology laboratory class. Organisms
  recovered are identified to the species level as
  part of the laboratory exercise. At its
  conclusion, the instructor informs the class that
  he wants to use all of their cultures in his
  research project. He is doing epidemiological
  studies on the occurrence of antibiotic-resistant
  oral bacteria. The students comply and submit
  the culture dishes containing their bacterial
  isolates.
• Are the instructors actions appropriate?
• Is an IRB-approved protocol needed?
• Do the students need to give informed consent?

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Use of Animals in Research
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Legal Framework

• Public Law 89-544 - The Animal Welfare Act (1966
  amended 1970, 1976, 1985)
• Implementing Regulations 9 CFR Subpart A,
  Parts 1-4
• U. S. Department of Agriculture
• Public Law 99-158 - The Health Research Extension
  Act Animals in Research (1985)
• Implementing regulations PHS Policy on Humane
  Care and Use of Laboratory Animals
• Guide for the Care and Use of Laboratory Animals
• Office of Laboratory Animal Welfare (NIH)

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Regulatory Requirements

• USDA
• Animals mammals (exceptions)
• Registration
• IACUC
• 3 members
• Review program
• Inspect facilities
• Approve all activity using animals
• Authorized to suspend activity
• Annual inspection by agency

• PHS
• Animals vertebrates
• Assurance Condition of funding
• National Research Council Guide to Care and Use
• IACUC
• 5 members
• Others same as USDA
• Agency inspections are mainly for cause

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Accreditation - AAALAC

• Association for Assessment and Accreditation of
  Laboratory Animal Care (AAALAC)
• Private, non-government organization
• Voluntary Peer Review
• Regular site visits to the institution
• Gold Standard - uses USDA and PHS as the
  minimum standards

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USC IACUC Review Process

• Complete the Animal Use Protocol (AUP)
• http//uscm.med.sc.edu/ARF/forms.html
• Training Requirements
• Budget Considerations
• Species
• Numbers
• Per diem fees
• Side by Side Review

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IACUC Functions

• Semi-annual review of institutional animal care
  program
• Semi-annual review of animal facilities
• Report results of reviews to Institutional
  Official including noted deficiencies and
  recommendations
• Review, and if warranted, investigate concerns
  involving care and use of animals

• Review and approve, require changes, withhold
  approval of proposed research activities using
  animals
• Review and approve, require modification to
  changes in on-going activities
• Be authorized to suspend activities involving
  animals

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IACUC Review Criteria

• Procedures will avoid or minimize pain
• Appropriate sedation, analgesic, or anesthesia if
  more than minor pain
• Painless method of euthanasia if animals would
  experience chronic or severe pain
• Living conditions are appropriate and contribute
  to health and comfort
• Medical care available and provided by qualified
  veterinarian
• Personnel conducting procedures are appropriately
  trained and qualified

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Case Study

• You are a graduate student working on your Ph.D.
  Your advisor asks to meet with you to discuss
  your research project. Your advisor suggests a
  new series of experiments that will hopefully
  clear up a problem you have encountered. The new
  series of experiments involves surgical
  manipulations and you know that the IACUC
  protocol for the project did not contain any
  reference to surgery. You ask your advisor about
  submitting an amended protocol before starting
  these studies. Your advisor says that he does
  not wish to go through the trouble if the
  technique is not going to be useful. He suggests
  that first you try a few experiments, and if the
  procedure looks like it is going to work, you can
  submit an amended protocol at that time.
• What do you do?

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Conflict of Interest

• Federal Requirements and Institutional Policy

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What Is Conflict of Interest?

• 1 INTEREST/DUTY
• Research integrity
• Education
• Patient welfare

• 2 INTEREST
• Financial gain
• Recognition

JUDGEMENT
UNDUE INFLUENCE
ADVERSE OUTCOME
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Circumstances Creating Conflict

• Ownership and equity
• Outside management positions
• Paid consulting
• Honoraria
• Recruitment bonuses/incentives
• Finders fees

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Federal Policy Mandates

• Maintain an appropriate written and enforced
  policy
• Designate an institutional official
• Require disclosure of financial interests prior
  to submission of application for funding

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Federal Policy - Disclosure

• Required for all NSF and PHS funding applications
• Applies to those involved with the design,
  conduct, or reporting of research
• Related financial interests must be disclosed

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USC Policy Background

• Provides overall framework for unit policies
• Each unit having separate tenure and promotion
  criteria required to have a policy
• Review of unit policies by the USC Conflict of
  Interest Committee
• Last of 43 unit policies approved (July 1995)

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ACAF 1.50 Policy Requirements

• Faculty will seek prior administrative approval
  of outside professional activities, and will
  report these activities annually
• Definitions
• Faculty
• Financial Interest
• Immediate Family

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What Should Be Reported

• Compensated services
• Contract with any private sector entity
• Ownership or equity in a corporation
• Management or board position in a corporation
• Participation in a contract or proposal through
  an entity other than the USC
• Academic remuneration noted as fees or honoraria
• Unpaid consulting or pro bono service

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What Should Be Reported

• Activities not normally reported
• Seminars
• Textbooks
• Paintings
• Performances

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USC Reporting Requirements

• Type of activity
• Whether the activity is compensated
• Duration/time requirements
• Explanation of any potential conflict of interest
  or commitment
• Whether the activity involves the use of
  University facilities, resources, personnel
  (including students) or other commitment and
  whether appropriate procedures have been followed

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Reporting Procedure
Individual Faculty Member Local Unit Head
(Department Chair) Supervisory Unit Head
(Dean) Office of Research Compliance Vice
President for Research Conflict of Interest
Committee
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Supervisor Responsibilities

• Determination of conflict of interests or
  financial conflict
• Recommendations to prevent or reduce conflicts to
  a manageable level
• Required public disclosure
• Monitoring by independent reviewers
• Modification of research plan
• Disqualification from participation in research
• Divestiture of significant financial interests
• Severance of relationships that create conflicts

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Case Study

• Dr. Quick, an internationally renowned
  biomedical scientist, is an authority in her
  field. She serves on an NIH study section (10
  days per year), a state advisory panel (10 days
  per year), a federal advisory panel (10 days per
  year), an international advisory panel (10 days
  per year), and the board of a private foundation
  (5 days per year) and gives about one seminar a
  month a research universities across the country.
  
• What conflict-of-interest or conflict-of-effort
  considerations, if any, apply to this scenario?

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Case Study

• Dr. Cox at Research University is a renowned
  clinical pharmacologist. He has a large,
  productive research program in experimental
  therapeutics, sponsored by federal grants and
  industrial contracts. His reputation is such
  that his participation in a conference attracts
  news media attention and a large attendance. Big
  Company engages Dr. Cox for a series of lectures
  at conferences designed to promote Big Companys
  new therapeutic agent. Dr. Cox is paid a
  speakers fee of 25,000 and all expenses for
  each presentation. Dr. Cox is free to select his
  topic and the contents of his presentation. Dr.
  Cox makes five to six appearances per year at the
  Big Companys conferences.
• Comment on potential conflicts associated with
  the lecture series.

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Scientific Misconduct
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Federal Scientific Misconduct Policy (42 CFR
Part 93)

• Means Fabrication, falsification, or plagiarism
  in proposing, performing, or reviewing research,
  or in reporting research results.
• Fabrication is making up data
• Falsification is manipulating, changing, or
  omitting data or results
• Plagiarism is taking another persons ideas
  without giving appropriate credit
• It does not include honest error or honest
  differences in interpretations or judgments of
  data

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USC Policy

• Same as federal policy with following additions
• Material failure to comply with requirements for
  protection of researchers, human subjects or the
  public, or for ensuring the welfare of laboratory
  animals
• Failure to meet other material professional
  standards or legal requirements governing
  research
• Procedure
• Allegation
• Inquiry
• Investigation
• Final Action including sanctions

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Case Study

• Dr. José M. is beginning his fifth year as an
  independent researcher. His work is going well.
  He has published a number of important articles
  and secured a large grant for future work. Based
  on this progress, he expects his pending
  promotion review to proceed without problems.
• Late one afternoon a graduate student hands José
  two papers written by a senior colleague in his
  department. She has circled graphs in each of
  the papers that are clearly the same but reported
  as representing two different experiments. After
  checking the graphs carefully and reviewing the
  supporting data, José agrees that something is
  wrong. The senior colleague, who will almost
  certainly be a member of his promotion review,
  has either made a careless mistake or falsified
  information in a publication.
• What should he do?

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Export Control
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Export Control Regulations

• U.S. export control laws and regulations are
  intended to serve various objectives and
  interests
• Restrict the export of goods and technologies
  that could contribute to the military or economic
  potential of U.S. adversaries dual use
  technologies
• Prevent the proliferation of nuclear, chemical
  and biological weapons
• Prevent terrorism and other illicit activities
  (e.g. drug trafficking)
• Increased focus on enforcement since 9/11/2001

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What is an Export?

• Sending to anyone or taking a defense article or
  controlled technical information out of the U.S.
• Sending to anyone or taking an export controlled
  item, material, or technical information out of
  the U.S.
• Transferring export controlled information in the
  U.S. to a foreign person or entity from a country
  for which a control exists (deemed export)
• Performing defense services for the benefit of a
  foreign person or entity, in the U.S. or abroad
  from a country for which a control exists

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Federal Responsible Agencies

• State Department
• Inherently military technologies--International
  Traffic in Arms Regulations (ITAR)
• Commerce Department
• Dual-Use technologies (primary civil use) --
  Export Administration Regulations (EAR)
• Treasury Department, Office of Foreign Assets
  Control (OFAC)
• Prohibits transactions with countries subject to
  boycotts, trade sanctions, embargoes

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Licensing and Exclusions

• An export license may be required before a
  controlled item or material may be exported
• Most university research and teaching qualifies
  for regulatory exclusions or license exemptions
• If a license is required and denied, export or
  deemed export is prohibited

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Education Exclusion

• No license is required to share with foreign
  nationals information concerning general
  scientific, mathematical or engineering
  principles commonly taught in universities or
  information in the public domain
• Students using controlled equipment to conduct
  research should be registered for a research
  credit class

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Fundamental Research Exclusion

• Fundamental research exclusion applies to
  information when the research is
• Basic or applied
• Performed at a U.S. institution of higher
  learning
• Ordinarily published and shared broadly in the
  scientific community
• No restrictions on access or dissemination

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Fundamental Research Exclusion

• Is destroyed if the University accepts any
  contract clause that
• Forbids the participation of foreign nationals
• Gives the sponsor a right to approve publications
  resulting from the research or
• Otherwise operates to restrict participation in
  research and/or access to and disclosure of
  research results

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University Strategy

• Protect fundamental research exclusion by
  eliminating contractual clauses that destroy our
  ability to claim the exclusion

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Implications of Export Laws

• No effect on vast majority of university research
• But potential impact on
• Ability of foreign students to participate in
  research involving a controlled technology
  (mostly under ITAR)
• Ability to provide services (including training
  in the use of controlled equipment) to foreign
  nationals (ITAR, EAR, OFAC)
• Ability to send controlled equipment to foreign
  countries (ITAR, EAR, and OFAC)

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Conclusion

• You are familiar with USC Human Subjects
  Protection Program.
• You are familiar with USC Animal Care Program.
• You understand conflicts of interest related to
  outside professional activities.
• You are familiar with scientific misconduct
  policy.
• You have been introduced to export control
  regulation
• You have learned about HIPAA Requirements.