Reality vs Urban Myth: The Truth About Regulations

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Reality vs Urban Myth The Truth About
Regulations

• Marisue Cody, PhD
• Deputy Director, PRIDE

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Objectives

• Understand the variety of regulations and other
  requirements under which the HRPP operates
• Analyze complex problems when more than one set
  of requirements apply

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Authority Responsibilities

• United States Code (U.S.C.)
• Code of Federal Regulations (CFR)
• Directives
• Handbooks
• Manuals
• Memorandums
• Professional standards

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U.S. Codes (law)

• 5 Government organization employees
• 21 Food and drugs
• 38 Veterans benefits
• 41 Public contracts
• 42 Public health welfare

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Code of Federal Regulations

• 5 Administrative personnel
• 21 Food drugs
• 38 Pensions, bonuses, Veterans relief
• 41 Public contracts property management
• 45 Public welfare
• 48 Federal acquisition regulations system

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VA Policy Requirements

• Brochures - Informational material mass-produced
  for patients and staff
• Directives - establish mandatory VHA policies
• Handbooks - prescribe mandatory VHA procedures
  and/ or operational requirements
• Manuals - also prescribe mandatory VHA procedures
  or operational requirements (older documents not
  yet replaced by Handbooks)
• Memorandums - establish mandatory VHA policies
  which apply within VHA Central Office
• Information Letters - release nondirective
  information of one-time interest or short
  duration i.e., applications for training
  opportunities, describing new programs,
  announcing meetings, reminders etc.
• Notices - provide significant information of
  interest VHA-wide
• Program Guides - contain non-mandatory and
  non-directive procedures for development of a
  program
• VHA Record Control Schedule (RCS 10-1) - provides
  disposal authorities for VHA general and
  administrative records and program records.

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VA-wide policies

• Information security
• Directive 6500
• Handbook 6500

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VHA Temporary Directives

• 2008-014 - AUDITING OF VHA HUMAN SUBJECTS
  RESEARCH TO DETERMINE COMPLIANCE WITH APPLICABLE
  LAWS, REGULATIONS, AND POLICIES
• 2007-044 - USE OF A COOPERATIVE RESEARCH AND
  DEVELOPMENT AGREEMENT (CRADA)
• 2007-040 - APPOINTMENT OF FACILITY INFORMATION
  SECURITY OFFICER (ISO) AND PRIVACY OFFICER TO THE
  INSTITUTIONAL REVIEW BOARD (IRB) OR THE RESEARCH
  AND DEVELOPMENT (RD) COMMITTEE

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VHA Directives

• 1058 - RESPONSIBILITIES OF THE OFFICE OF RESEARCH
  OVERSIGHT
• 1200 - VETERANS HEALTH ADMINISTRATION RESEARCH
  AND DEVELOPMENT
• 1201 - OVERVIEW OF VHA RESEARCH PROGRAMS
• 1605 - VHA PRIVACY PROGRAM

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VHA Handbooks - ORO

• 1058.03 - ASSURANCE OF PROTECTION FOR HUMAN
  SUBJECTS IN RESEARCH
• 1058.04 - DEBARMENTS AND SUSPENSIONS BASED ON
  RESEARCH IMPROPRIETY IN VA RESEARCH
• 1058.1 - REPORTING ADVERSE EVENTS IN RESEARCH TO
  THE OFFICE OF RESEARCH OVERSIGHT
• 1058.2 - RESEARCH MISCONDUCT

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VHA Handbooks - ORD

• 1200.05 - REQUIREMENTS FOR THE PROTECTION OF
  HUMAN SUBJECTS IN RESEARCH
• 1200.06 - CONTROL OF HAZARDOUS AGENTS IN VA
  RESEARCH LABORATORIES
• 1200.1 - THE RESEARCH AND DEVELOPMENT (RD)
  COMMITTEE HANDBOOK
• 1200.18 - INTELLECTUAL PROPERTY

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VHA Handbooks - Privacy

• 1605.1 - PRIVACY AND RELEASE OF INFORMATION
• 1605.2 - MINIMUM NECESSARY STANDARD FOR PROTECTED
  HEALTH INFORMATION

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VHA Handbooks others.

• 1004.1 - VHA INFORMED CONSENT FOR CLINICAL
  TREATMENTS AND PROCEDURES
• 1050.1 - VHA NATIONAL PATIENT SAFETY IMPROVEMENT
  HANDBOOK
• 1108.04 - INVESTIGATIONAL DRUGS AND SUPPLIES
• 1907.01 - HEALTH INFORMATION MANAGEMENT AND
  HEALTH RECORDS

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Examples
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Conflict of Interest Case

• An investigator asks you whether he needs to
  disclose that Lilly has invited him to speak at a
  seminar they are conducting. The honorarium is
  under the 10,000 limit. He will be speaking
  about the outcomes of the clinical trial he has
  been a lead investigator on.
• What would you do?

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Conflict of Interest

• 18 USC 11.208 Bribery, graft, and conflicts of
  interest
• 5 CFR 2635 Standards of ethical conduct for
  employees of the executive branch
• 48 CFR 9.500-9.508 Federal acquisition
  regulation (institutional COI)
• Memorandum Sept 23, 2005 Financial conflicts of
  interest
• VHA Handbook 1200.13 Financial conflicts of
  interest in research (rescinded). Also mentioned
  in 1200.05 and 1200.1

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Failure to report SAEs

• A recent OIG report cited a PI and the facility
  for failure to report SAEs as required by VA
  policy. The study in question was a longitudinal,
  observational study of veterans with prostate
  cancer. There were 105 deaths that were not
  disclosed AND it was unlikely that study
  participation contributed in any way to their
  deaths.
• Why is this a problem?

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Unanticipated Problems and Adverse Events

• 38 CFR 16.103(b)(5)
• 21 CFR 56.108(b)(1) 21 CFR 312.32 21 CFR
  812.150(a)(1) 21 CFR 812.3(s)
• VHA Handbook 1200.05
• VHA Handbook 1058.1
• VHA Handbook 1050.1
• OHRP Guidance on reviewing and reporting
  unanticipated problems involving risks to
  subjects or others and adverse events, Jan 15,
  2007
• Memorandum, Reporting UPRs and AEs to IRBs, Dec
  6, 2006

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How do you consent a blind person?

• We have an investigator who wishes to consent a
  legally blind participant for a study and they
  did not present this possibility to the IRB when
  the study was originally approved.  Questions
• Can they have a witness to the process (not
  associated with the study) who also reads the
  informed consent document orally to the subject
  before it is presented to them by the
  investigator?
• Do they need statements added to the usual
  statements similar to the following
• ltName of witnessgt, who is not associated with the
  study, has read the informed consent document to
  me and was present when ltname of investigatorgt
  presented the study to me.  (subject would sign)
• Witness to Informed Consent Process  I have
  read the informed consent document to ltname of
  subjectgt and was present for the oral
  presentation by the investigator. 
• If they do this, do they need to have IRB
  approval for this change in the normal process
  before consenting the subject?  If so, can it be
  expedited?

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Informed Consent

• 38 CFR 16.116 .117 45 CFR 16.116 .117 21
  CFR 50.20-27
• 38 CFR 17.32
• VHA Handbook 1200.05
• VHA Handbook 1004.1
• VHA Handbook 1907.01
• VHA Handbook 1605.1
• OHRP guidance
• State laws

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Administration of drugs legally marketed by a
foreign country

• A patient suffers from Hansens disease
  (leprosy). He is unable to tolerate any of the
  U.S. legally marketed drugs for the treatment of
  his disease because of life-threatening side
  effects. His disease has progressed to where he
  is suffering from paralysis of fingers and toes.
• The patient has been taking a drug marketed in
  Europe for 13 months which has slowed the
  progression of his paralysis. The drug is not
  marketed in the United States.
• The patient has been admitted to the VAMC with
  pneumonia. Both he and his wife beg his
  admitting physician to allow him to continue
  taking the only drug that has been effective for
  the treatment of his illness. The drug has been
  brought to the VAMC by the patient.
• Question Can this drug be given to the patient?

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Studies involving drugs

• 21 CFR 11, 50, 54, 56, 312
• Good Clinical Practice
• VHA Handbook 1200.05
• VHA Handbook 1108.04

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QUESTIONS