Human Research Protection Program 101

March 19, 2007Cincinnati, OH

The Common Rule and VHA 1200.5: One and the Same?

Presented by: Marisue Cody

Presented by: Marisue Cody

Objectives

Evaluate applicability of the Common Rule

Define the scope of regulations described in VHA 1200.5

Describe the areas of overlap between the Common Rule and VHA 1200.5

17 Federal Agencies that Signed the Common Rule: Dept of Agriculture Dept of Energy Dept of Commerce Dept of Justice Dept of Defense Dept of Education Dept of Transportation Dept of HHS HUD National Science Foundation

NASA AID Social Security Administration CIA Consumer Product Safety EPA Dept of Veterans Affairs

Code of Federal Regulations 38 CFR 16 refers to the VA

21 CFR 56 (IRB) and 50 (informed consent) refers to the FDA

45 CFR 46 refers to DHHS

Subparts B: Additional Protections for Pregnant Women,

Human Fetuses and Neonates involved in Research

C: Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects

D: Additional Protections for Children Involved as Subjects in Research

What are the Common Rule and VHA 1200.5?

Common Rule

Federal Policy for the Protection of Human Subjects

• Originally issued in 1974 as Part 46 of Title 45 of the Code of Federal Regulations (Subpart A) by DHEW

• Adopted in 1991 by 17 agencies

• VA: Part 16 of Title 38 of the Code of Federal Regulations

What is VHA Handbook 1200.5?

Handbook describing procedures for the protection of human subjects

VHA 1200.5 issued July 15, 2003

Handbook vs. Federal Regulations

Same regulatory weight (not optional)

Applicability

Common Rule and VHA 1200.5

Common Rule Establish IRBs Ensure Informed Consent of Subjects

VHA Handbook 1200.5 Medical Center Responsibilities IRB Composition & Responsibilities Investigator Responsibilities Investigational Drugs & Devices in VA

IRB Composition & Responsibilities

IRB Membership (.107) At least 5 members with varying backgrounds

Gender balance, more than one profession

At least 1 scientist, at least 1 non-scientist

At least 1 member not affiliated

May not participate if has a COI

Invite consultant if require expertise

IRB Composition– VHA 1200.5Licensed Physician for FDA regulated products

ACOS/AO/RCO MAY serve as non-voting members

Members of a VA IRB Appointed by the Medical Center Director Initial appointment 3-years

Chair of a VA IRB Initial appointment 1-year

Affiliate IRB (Paragraph 5) Two VA IRB voting members One VA IRB voting member must have scientific expertise

IRB Functions & Operations Follow written procedures

Review must take place at a convened meeting with a majority present, including a non-scientist. Approval must be by the majority present.

VHA 1200.5 Written procedures for operation (turn to page 13-14)

More detail, plus some extras: Reporting to the R&D Committee Projects needing verification from sources other than the

investigator Reporting requirements Conducting audits Education requirements Reporting to Privacy Officer Reporting to VHA Information Security Officer

IRB Review of Research (.109) Authority to: Approve, require modifications to seek approval, or

disapprove Require that information given to subjects is in compliance

with .116 Shall require documentation of informed consent or waive

documentation Notify investigators in writing of its decision Conduct continuing review and have authority to observe consent

process and research

Additional VHA 1200.5 requirements

Prior to initiation

Research reviewed and approved by IRB AND R&D

If approval is contingent on substantive modifications, subsequent review must be by the convened IRB

If approval is contingent on specific minor conditions, the IRB chair or designee may approve it on behalf of the IRB

Continuing Review in VHA 1200.5

Requires submission of a written progress report that includes:

Brief summary Number of subjects entered and withdrawn Gender and minority status Number of subjects – vulnerable populations Copy of proposal and all approved amendedments Copy of current consent document for the IRB to review

Continuing Review

Written Progress Report (cont.)

Copy of current HIPAA Authorization document Information that may impact on risk benefit ratio Research findings to date Summary of DSMB or DMC meetings Assurance that all SAEs and UAEs have been reported New scientific findings in the literature, or other relevant

findings

Lapse of approval Automatically suspended

Local research office to notify the PI

IRB in consultation with COS may allow continuation of research interventions if it is in the best interest of individual subjects

Inform other agencies as appropriate

Re-approval must occur prior to re-initiation

Expedited Review (.110) List of categories is published in the Federal Register (on

OHRP website & is the same as Appendix B)

Must be no more than minimal risk, OR minor change in already approved protocol

Carried out by IRB Chair or designee, cannot disapprove the research

Have a process to inform the IRB members

May be restricted by agency head

VHA 1200.5 No differences except the labeling of the expedited

categories

Criteria for IRB Approval (.111)

1. Risks to subjects are minimized2. Risks are reasonable in relation to benefits3. Selection of subjects is equitable4. Informed consent will be sought prospectively5. Informed consent is appropriately documented6. Research plan makes adequate provisions for safety monitoring7. There are adequate provisions to protect privacy and

confidentiality8. Protection of Vulnerable Subjects9. Conflict of Interest10. Ensure Investigator educational requirements and certifications

Review by institution (.112) Research approved by an IRB may be subject to further

review by official of the institution

Those officials MAY NOT approve the research if it is not approved by the IRB

Suspension or termination of IRB approval (.113) IRB has authority to suspend or terminate a project not

being conducted in accordance with its requirements or is associated with unexpected harms to subjects

Must be reported

Cooperative research (.114) With approval of the department or agency head, an

institution participating in a cooperative project may enter into a joint review arrangement, rely upon the review of another qualified IRB, or make similar arrangements for avoiding duplication

IRB records (.115) Proposals reviewed, scientific evaluations (if any), sample

consent documents, progress reports, reports of injuries Minutes of IRB meetings Continuing review activities Correspondence List of IRB members Written procedures Statements of significant new findings Shall be retained for at least 3 years

Extras in IRB records (1200.5) Minutes must include

Minutes available in 3 weeks Additional safeguards to protect vulnerable subjects Determination of level of risk

Correspondence with R&D Committee

Retain records for 5 years Records are the property of the VA Non-redacted minutes of affiliate IRB

Informed Consent

General requirements for informed consent (.116) Basic elements

Study involves research Description of risks Description of benefits Disclosure of alternative procedures Extent of confidentiality If more than minimal risk, compensation for injury Whom to ask questions of Statement that it is voluntary

General requirements for informed consent (.116) Additional elements

Unforeseeable risks Anticipated circumstances where participation may be

terminated Additional costs Consequences of withdrawal Significant new findings Approximate number of subjects

General requirements for informed consent (.116) Alteration or waiver (c)

The research is conducted by or subject to the approval of state or local government officials and is designed to study, evaluate or otherwise examine a public benefit program, AND

It could not practicably be carried out without the waiver or alteration

General requirements for informed consent (.116) Alteration or waiver (d)

1. Involves no more than minimal risk2. Will not adversely affect the rights and welfare of subjects3. Could not be practicably carried out without the waiver, AND4. Whenever appropriate the subjects will be provided pertinent

information

Documentation of informed consent (.117)

Written consent Approved by the IRB Signed by the subject or LAR Copy given to person signing the form

Must be read to the subject or LAR, who is given adequate opportunity to read it before it is signed, or given a short form

Documentation of informed consent (.117)

Waiver of requirements (c)

Only record linking the subject with the research and breach of confidentiality would be harmful, OR

Research presents no more than minimal risks and involves no procedures for which written consent is normally required outside of the research context

VHA 1200.5 Appendix C 10-1086 must be used

• Signed, dated by:Subject or LARWitness (to signature only)Person obtaining consent

Progress note• Consent• Entry• Termination

Flag medical record Filed in Case History

Subparts B-D

Subpart B-Additional Protections for Pregnant Women, Human Fetuses and Neonates

Definitions

Duties of the IRB

Risks and benefits

Consent

VHA Handbook 1200.5 Appendix D

Paragraph 4 Forbids research with a fetus, in-utero or ex-utero

(including human fetal tissue) Forbids research related to in vitro fertilization Allows participation of pregnant women, rules are

consistent with Sub-part B section 204

Subpart C-Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects

Definitions

Duties of the IRB

Permitted Research

VHA Handbook 1200.5 Appendix D

Paragraph 5 Requires a waiver from the CRADO If waiver is granted, must follow Subpart C

regulations

Subpart D-Additional Protections for Children Involved as Subjects in Research

Definitions

Duties of the IRB

Risks of Research

Requirements for permission by parents or guardians and for assent by children

VHA Handbook 1200.5 Appendix D

Paragraph 7 Requires a waiver from the CRADO VHA Directive 2001-028

• Guidance for waiver process• Requires IRB to have specific policies and

procedures regarding children in research• IRB must have expertise

If waiver is granted, must follow Subpart D regulations

Research Involving Human Subjects with Surrogate Consent Common Rule

Section 117 – “subject’s legally authorized representative”

VHA Handbook 1200.5 Paragraph 11 Appendix D Paragraph 6

Paragraph 11a. Under appropriate conditions

(1) Research problem must be unique(2) Priority of who can sign consent(3) How determination is made regarding capacity

(turn to page 21)

b. IRB must find that the research meets the conditions in Appendix D

Appendix D, Paragraph 6c. Conditions for approval

(1) Only persons with impaired decision making capacity are suitable as research subjects

(2) Research entails no significant risks; or if possibility of harm, there must be at least a greater probability of direct benefit

(3) Procedures assure participant’s representatives are well informed about their roles and obligations

Investigational Drugs & Devices

Investigational Drugs

VHA Handbook 1108.04

VA differs from FDA on how it defines investigational drugs

Yields to FDA on investigational drug regulatory jurisdiction when there is conflict

Investigational Devices

Conducted according to FDA regulations at 21 CFR Part 812

Significant risks (SR) vs. Nonsignificant risk (NSR)

Receipt, control, custody and dispensing

Investigator Responsibilities

Investigator’s Responsibilities

There is NOTHING regarding investigators in the Common Rule

VHA 1200.5 Paragraph 10 Training and credentialing Research plan Consent process Reporting of SAEs and/or AEs Amendments IRB Review Record retention HIPAA