Reality vs Urban Myth: The Truth About Regulations

Marisue Cody, PhD

Deputy Director, PRIDE

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

Authority & Responsibilities

• United States Code (U.S.C.)

• Code of Federal Regulations (CFR)

• Directives

• Handbooks

• Manuals

• Memorandums

• Professional standards

U.S. Codes (law)

• 5 – Government organization & employees

• 21 – Food and drugs

• 38 – Veteran’s benefits

• 41 – Public contracts

• 42 – Public health & welfare

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

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.

VA-wide policies

• Information security

• Directive 6500

• Handbook 6500

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 (R&D) COMMITTEE

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

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

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 (R&D) COMMITTEE HANDBOOK

• 1200.18 - INTELLECTUAL PROPERTY

VHA Handbooks - Privacy

• 1605.1 - PRIVACY AND RELEASE OF INFORMATION

• 1605.2 - MINIMUM NECESSARY STANDARD FOR PROTECTED HEALTH INFORMATION

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

Examples

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?

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

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?

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

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:

• <Name of witness>, who is not associated with the study, has read the informed consent document to me and was present when <name of investigator> presented the study to me.  (subject would sign)

• Witness to Informed Consent Process –  I have read the informed consent document to <name of subject> 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?

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

Administration of drugs legally marketed by a foreign country• A patient suffers from Hansen’s 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?

Studies involving drugs

• 21 CFR 11, 50, 54, 56, 312

• Good Clinical Practice

• VHA Handbook 1200.05

• VHA Handbook 1108.04