Responsible Conduct of Research Taking Steps to Protect Research Subjects

1
Responsible Conduct of Research Taking Steps to
Protect Research Subjects

• Sreekant Murthy, Ph.D.
• Vice Provost for Research Compliance
• Drexel University

2
Regulatory Research Environment

• The last few years have witnessed increased
  public and governmental scrutiny of research
  involving research subjects resulting in a move
  towards significant enhancement in regulatory and
  ethical standards to ensure that researchers,
  sponsors and funding agencies operate in
  accordance with all applicable regulations
• Therefore, in this enterprise, researchers,
  institutions and funding agencies bear the heavy
  responsibility to keep research subjects out of
  harms way.
• An important consideration in this environment
  is
• Grasp of regulatory issues
• Compliance by researchers and others involved in
  this enterprise
• Gain public acceptance and confidence

3
Consequences

• Fundamentally unethical
• Reputational damage to
• Research Focus and advancing research
• Researcher and his/her institution financial
  hardship (loss of funding, etc.)
• Whistleblowing
• Litigation
• Regulatory sanctions
• All of the above force us to reexamine concepts
  of
• - Personal responsibility
• - Ethical or legal culpability

4
Office of Research ComplianceObjective

• Objective is to provide assistance and guidance
  to investigators to ensure ethical conduct and
  compliance in performance of research in the
  following areas
• Human subjects protection
• Animal care and use
• Use of hazarodus agents, radioactive materials or
  recombinant DNA material
• Responsible conduct of research (Ethics and
  Integrity)
• Conflict of Interest

5
Requirements

• All studies that receive federal funds must be
  reviewed and approved by an independent review
  board (IRB, IACUC, UBSC or RSC) to ensure
  research subjects are safeguarded before the
  research can begin.
• Drexel University will follow the same rules for
  internal, non-federally funded research

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What is an IRB?

• It is an administrative body/board, which has
  the authority to approve, modify or disapprove
  research involving human subjects.
• IRBs are federally mandated to ensure that human
  subject research is conducted in accordance with
  federal regulations and rights of subjects are
  protected in accordance with federal regulations.
  
• Federal regulations require that all research
  involving human subjects or analysis of data
  gathered from human subjects including data
  mining, surveys, clinical records and charts,
  regardless of funding source/status be reviewed
  by the IRB PRIOR to the implementation of any
  research activity.

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What is an Assurance?

• This is a formal mechanism by which the
  institution has assured the HHS that the rights
  of human research subjects are protected
• This is guided by Common Law (45 CFR 46) and by
  three basic ethical principles as described in
  the Belmont Report
• Respect for persons incorporates at least two
  ethical convictions first, that individuals
  should be treated as autonomous agents, and
  second, that persons with diminished autonomy are
  entitled to protection.
• Beneficence - Persons are treated in an ethical
  manner. Two general rules have been formulated as
  complementary expressions of beneficent actions
  in this sense (1) do not harm and (2) maximize
  possible benefits and minimize possible harms.
• Justice - Who ought to receive the benefits of
  research and bear its burdens? This is a question
  of justice, in the sense of fairness in
  distribution or what is deserved.

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Drexel University and DrexelMed IRBs

• Under the FWA, the institution operates three
  IRBs.
• IRB 1 Review of protocols involving
  biomedical interventions involving adult
  subjects
• IRB 3 Review of research protocols involving
  social and behavioral sciences
• IRB 4 - Review of protocols involving minors
  and children

Guidelines and procedures to apply for IRB
approval and conduct of human subject research is
posted on the website www.research.drexel.edu
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Meeting Dates

• IRB 1 meets every first and third Wednesday of
  each month at center city campus
• IRB 3 meets every third Thursday of each month
  at Drexel University West Philadelphia Campus
• IRB4 meets every third Wednesday of each month
  at St. Christophers Hospital for Children.
• Meeting dates and deadlines for submission for
  full board meetings are posted on the Office of
  Research Website www. research.drexel.edu.
• There are NO deadlines for Exempt and Expedited
  review applications.

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What Constitutes Human Subject Research?

• DHHS regulations define research as a systematic
  investigation, including research development,
  testing and evaluation, designed to develop or
  contribute to generalizable knowledge.
• Examples of systematic investigations include
• surveys and questionnaires
• interviews and focus groups
• analyses of existing data or biological specimens
  
• epidemiological studies
• evaluations of social or educational programs
• cognitive and perceptual experiments
• medical chart review studies or data mining

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Human Subjects ResearchLevels of Review

• Study may fall within the guidelines at following
  levels of review
• Exempt from IRB review? (existing data,
  anonymous,)
• Expedited review (minimal risk)
• More than minimal risk requiring rigorous review
  of risks and benefits by convened IRB

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Does my Research Require IRB Review? Who will
make that determination?

• OHRP has recommended that investigators not be
  given the authority to make an independent
  determination that research does not involve
  human subjects
• Therefore, all investigators irrespective of
  whether their study involves human subjects or
  not, must submit their application to the Office
  of Research Compliance for determination to be
  made whether the proposed study is research and
  whether it involves humans subjects
• The individuals who are authorized to make this
  decision at Drexel University and Drexel
  University College of Medicine are
• Vice Provost for Research Compliance
• IRB Chairs or Chairs designees

13
When is Some Research NOT considered human
subject research?

• The investigator cannot readily ascertain the
  identity of the individuals to whom the coded
  information pertain. For example
• The key to decipher code is destroyed before the
  research begins
• The investigator and the holder of the key enter
  into an agreement prohibiting the release of key
  to the investigators under any circumstances
• There are legal or IRB written policies for a
  repository that prohibit the release of the key
• Oral history interviewing projects in general do
  not involve the type of research defined by HHS
  regulations and are therefore excluded from
  Institutional Review Board oversight.
• Certain Focus Groups

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The Process

• Who can Assist you?
• Office of Research Compliance
• www.research.drexel.edu
• Phone [phone]
• Address
• 2105 New College Building (2nd Floor)
• 245 N 15th Street
• Philadelphia, Pa 19102

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Mandatory Training

• Every investigator and staff directly involved in
  the proposed research activity must complete the
  following training modules before a research
  protocol is approved
• Human Subject Research Training and Certification
• HIPAA and Medical Research
• HIPAA Electronic Security (SCHC Training
  accepted)
• Shipping Hazardous samples
• Proxy Consenting
• Web site for obtaining certification
• www.research.drexel.edu

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Dealing with the IRB

• Pre-submission questions
• Set up an appointment with ORC
• Attend monthly lunch and learn workshops
• Request for departmental meeting
• Ask questions
• Obtain information on how to complete forms
• Obtain information on levels of review
• Review status and follow up assistance

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What does an IRB expect of an application?

• Consideration of how the substantive issues
  methods fit with ethical guidelines IRB
  requirements
• Clarity in statement of problem, Research
  Questions Methods of data collection
• Consistency in content of all documents
• Completeness of all materials

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How Long Does the Approval Take?

• IT DEPENDS upon the level of review and the
  investigators responses to IRB conditions.
• Exempt and Expedited reviews generally take less
  time than full board reviews.
• In general, the turn around time generally rapid
  if investigators respond to IRB/ORC questions.
• Need assistance in responding to questions or
  clarifications on questions, contact ORC so the
  office can help you resolve those questions

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What happens after initial Approval?

• How can I change the protocol after it is
  approved?
• Researcher submits for review modifications or
  amendments (if any and however trivial they
  are)
• Every project is approved for the duration of one
  year. Yearly (at least) continuing reviews and
  approval is required for the continuation of the
  research
• Protocol Expiration
• If continuing reviews are not done, the project
  expires on the expiration date, no new subjects
  should be enrolled into the study.
• Expired protocols for reactivation requires brand
  new review.

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What are Your Responsibilities?

• IRB, after careful review of disclosed
  risks/benefits, conflict and confidentiality
  approves protocols.
• Protocols must be implemented as approved.
• DO NOT RECRUIT SUBJECTS/CONDUCT SURVEYS OR CHART
  REVIEWS MORE THAN THE NUMBER APPROVED BY THE IRB
• If changes are required (however minor they are,
  including increasing the sample size), they must
  be approved by the IRB prior to implementing such
  changes.
• Report protocol deviations when they occur
• Report adverse events to the sponsor and the IRB
  when they occur.
• Serious adverse events MUST be immediately
  reported to the sponsor and IRB

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Reports, Records and Continuing Reviews

• Final reports
• Adverse event reporting
• Reporting non-compliance and suspensions to
  regulatory authorities, IO and funding agencies
• Accurate record keeping is critical
• Continuing reviews done as often as necessary,
  but not less than one year

22
Animal Care and Use Education and Research

• IACUC to review and approve all protocols that
  use animals
• Complete certification to work with animals
  (www.research.drexel.edu)
• Obtain an occupational safety certification
  (physicians certification)
• Develop plans to
• Refinement
• Reduction
• Replacement
• Rationale for animal use
• Study objectives
• Description of Experimental design and procedures
  used and procedures to alleviate pain and
  distress to animals
• Surgery or Multiple surgeries (if any)

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Non-complianceConsequences

• Serious Noncompliance
• Human subject research being carried out without
  IRB review and approval by institutions IRB.
  Serious noncompliance also includes substantive
  modifications to IRB-approved research without
  IRB approval.
• Continuous Noncompliance
• This involves a principal investigator making
  the same mistake several times repeatedly,
  particularly after an IRB has informed him or her
  and his/her team member(s) of the problem.
  Continuous noncompliance also includes if the
  principal investigator has multiple problems with
  noncompliance over a long period of time or has a
  problem with multiple projects.
• Suspension or Termination
• The IRB and the Signatory Official and the
  Humans Subject Protection Administrator have the
  authority to suspend or terminate approval of
  human subject research that is not being
  conducted in accordance with the IRBs
  requirements

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What is the bottom line?

• When in doubt, ask questions seek help
• Remember consideration, clarity, consistency,
  completeness
• On-going process keep dialogue open
• All committees use reasonable person standard
  to ensure high standards of ethical research
• These committees help facilitate responsible of
  conduct of research