DOE Human Subjects Working Group Spring Workshop What New Policy/Guidance is Coming from OHRP? May 7, 2009 Julie Kaneshiro HHS Office for Human Research.

DOE Human Subjects Working DOE Human Subjects Working GroupGroup

Spring WorkshopSpring WorkshopWhat New Policy/Guidance is What New Policy/Guidance is

Coming from OHRP?Coming from OHRP?

May 7, 2009 May 7, 2009Julie KaneshiroJulie Kaneshiro

HHS Office for Human Research ProtectionsHHS Office for Human Research Protections

Phone: 240-453-8293 Phone: 240-453-8293

Email: Email: [email protected]

TopicsTopics

What’s been issued recently What’s coming soon What’s coming later

Recent Policies/GuidanceRecent Policies/Guidance

Guidance on the Genetic Information Nondiscrimination Act: Implications for Investigators and IRBs

Advanced notice of proposed rulemaking on IRB Accountability

IRB Registration Rule FAQs clarifying meaning of OHRP-registered IRB

and OHRP-approved FWA

Guidance on the Genetic Information Nondiscrimination Act

of 2008 (“GINA”) (Issued April 7, 2009)

What is GINA?What is GINA?

• A federal law that prohibits discrimination in health coverage (coverage provided by either health insurers or by employment-based health plans) and employment based on an individual’s genetic information

• The bill is intended to allow Americans to take advantage of the benefits of genetic testing without fear of losing their health insurance or their jobs

Important DefinitionsImportant Definitions

• An individual’s genetic tests (including genetic tests done as part of a research study)

• The genetic tests of the individual’s family members (dependents and up to and including 4th degree relative)

• Genetic tests of any fetus of an individual or family member who is pregnant, and genetic test of any embryo legally held by an individual or family member using assisted reproductive technology.

Genetic InformationGenetic Information means means information about:information about:

• The manifestation of a disease or disorder in family members of an individual (family history)

• Any request for, or receipt of, genetic services or participation in clinical research that includes genetic services (genetic testing, counseling, or education) by an individual or family member

(NOTE: Genetic information does not include information about the age or sex of an individual.)

Genetic InformationGenetic Information means means information about (cont):information about (cont):

• An analysis of human DNA, RNA, chromosomes, proteins, or metabolites that detect genotypes, mutations, or chromosomal changes

• Does not include tests such as CBCs, cholesterol tests, and liver-function tests that do not measure RNA, DNA, or chromosomal changes

• Does not include tests that analyze proteins or metabolites the results of which are directly related to a manifest disease, disorder, or pathological condition that could reasonably be detected by a health care professional with appropriate expertise and training in the field of medicine involved.

Definition of Definition of Genetic TestGenetic Test

What will GINA do?What will GINA do?

• Requesting, requiring, or purchasing genetic information of an individual or an individual’s family members, except in limited specified circumstances

• Using genetic information for decisions regarding coverage, rates, or preexisting conditions

Title I prohibit health insurers and Title I prohibit health insurers and health plan administrators from…health plan administrators from…

• Using genetic information in decisions regarding hiring, firing, promotion or any other terms of employment (e.g., benefits)

• Requesting, requiring, or purchasing genetic information of an individual or an individual’s family members, except in limited specified circumstances (e.g., when health or genetic services are offered by the employer as part of a wellness program)

• Disclosing genetic information concerning an employee, except in very limited circumstances.

• Retaliating against employees who file a complaint under GINA

Title II prohibit most employers from…Title II prohibit most employers from…

GINA’s limitations and GINA’s limitations and exceptionsexceptions

What GINA will not do:What GINA will not do:

• Health coverage provisions do not extend to life insurance, disability insurance, and long-term care insurance

• Does not mandate coverage for any particular test or treatment

• Employment provisions do not apply to employers with fewer than 15 employees

What GINA will not do (cont):What GINA will not do (cont):

• In the individual health insurance market, does not prohibit the health insurer from determining eligibility or premium rates for an individual based on the manifestation of a disease or disorder in that individual.

• In the group market (health coverage based on employment), the overall premium rate for an employer can be increased because of the manifestation of a disease or disorder of an individual enrolled in the plan, but the manifested disease or disorder of one individual cannot be used as genetic information about other group members to further increase the premium.

What GINA will not do (cont):What GINA will not do (cont):

• Does not prohibit health insurers or health plan administrators from obtaining and using genetic test results in making health insurance payment determinations.

““Research Exception” Under Title I Research Exception” Under Title I • Allows health insurers and group plans engaged in

research to request (but not require) that an individual undergo a genetic test, if the following conditions are met: Request made pursuant to research that complies with

45 CFR 46, or equivalent regs., and any applicable state or local laws for protection of human subjects

Clear indication that participation is voluntary and that non-compliance will have no effect on enrollment status or premium or contribution amounts

Genetic information collected as part of the research may not be used for underwriting purposes

The health insurer or group health plan notifies the Federal government in writing of the research being conducted pursuant to the exception

The issuer complies with other conditions as the Secretary may by regulation require

““Research Exception” Under Title II Research Exception” Under Title II • Allows employers to disclose genetic

information about an employee to an occupational or other health researcher if the research is conducted in compliance with 45 CFR part 46

Implementation of GINAImplementation of GINA

Effective DatesEffective Dates• Health coverage provisions (Title I) related

to individual health insurers will take effect May 22, 2009

• Health coverage provisions (Title I) related to group health plans will take effect between May 22, 2009 and May 21, 2010

• Employer provisions (Title II) will take effect November 21, 2009

GINA RulemakingGINA Rulemaking

• Department of Labor issued an RFI notice in Federal Register soliciting comments in October 2008 regarding title I provisions

• EEOC issued an NPRM on March 2, 2009 proposing regulations implementing Title II provisions (29 CFR part 1635); 60-day comment period

OHRP’s OHRP’s Guidance on the Genetic Guidance on the Genetic Information Nondiscrimination Act: Information Nondiscrimination Act:

Implications for Investigators and Implications for Investigators and Institutional Review BoardsInstitutional Review Boards

GINA and the Criteria for IRB GINA and the Criteria for IRB Approval of ResearchApproval of Research

• Risks to subjects are minimized (45 CFR 46.111(a)(1))

• Risks to subjects are reasonable in relation to anticipated benefits, if any, to the subjects and importance of knowledge that may reasonably be expected to result (45 CFR 46.111(a)(2))

• When appropriate, adequate provisions to protect privacy of subjects and confidentiality of data (45 CFR 46.111(a)(7))

GINA and the Requirements for GINA and the Requirements for Informed ConsentInformed Consent

• A description of any reasonably foreseeable risks or discomforts to the subjects (45 CFR 46.116(a)(2))

• A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained (45 CFR 46.116(a)(5))

OHRP Guidance on GINA: OHRP Guidance on GINA: Implications for Investigators Implications for Investigators

and IRBs: and IRBs: http://www.hhs.gov/ohrp/humansubjects/guidance/gina.pdf

Advanced Notice of Advanced Notice of Proposed Rulemaking on Proposed Rulemaking on

IRB AccountabilityIRB Accountability(Issued March 5, 2009)(Issued March 5, 2009)

Meetings on Alternative IRB ModelsMeetings on Alternative IRB Models

Secretary’s Advisory Committee on Human Research Protections recommendation:

OHRP, NIH, and FDA should consider holding a workshop focused on central IRB review mechanisms and that SACHRP use the workshop experience and other processes as a means of gathering information and moving forward toward future committee action (Fall, 2004).

Meetings on Alternative IRB ModelsMeetings on Alternative IRB Models

OHRP co-sponsored meetings on alternative IRB models in November 2005 and November 2006

Other sponsors were NIH, the Association of American Medical Colleges, and the American Society of Clinical Oncology

Meetings on Alternative IRB Meetings on Alternative IRB ModelsModels

A key conclusion: A key conclusion:

Despite existing regulatory flexibilities Despite existing regulatory flexibilities some institutions remain reluctant to some institutions remain reluctant to designate external IRBs and rely on designate external IRBs and rely on cooperative review arrangements.cooperative review arrangements.

Meetings on Alternative IRB ModelsMeetings on Alternative IRB Models

A key factor:

OHRP currently holds institution engaged in human subjects research study accountable for noncompliance on the part of the external IRB designated on FWA to review the research.

OHRP Proposal to Hold IRBs OHRP Proposal to Hold IRBs AccountableAccountable

Should OHRP revise 45 CFR part 46 to enable HHS to hold IRBs and IRB organizations (IORGs) directly accountable for compliance?

An Advanced Notice of Proposed Rulemaking published March 5, 2009

Proposal to Hold IRBs AccountableProposal to Hold IRBs Accountable

Issues to consider:1. FDA’s IRB regulations explicitly include

compliance provisions (21 CFR part 56)

2. Is there sufficient need for HHS to pursue a regulatory change to 45 CFR part 46 to hold IRBs directly accountable?

Proposal to Hold IRBs AccountableProposal to Hold IRBs Accountable

3. Would such a regulatory change have the unintended effect of making IORGs less willing to have their IRB designated on other institutions’ FWAs?

4. How should the IRB authorization agreement be used to inform OHRP’s compliance oversight evaluations?

Proposal to Hold IRBs AccountableProposal to Hold IRBs Accountable

5. How should OHRP categorize the responsibilities of the IRB/IORG and FWA holding institution?

Regulatory requirements seem to fall into three categories of responsibilities.

Proposal to Hold IRBs AccountableProposal to Hold IRBs Accountable

Categories of regulatory responsibilities:1. Responsibilities unique to IRBs/IORGs;

2. Responsibilities unique to institution engaged in human subjects research;

3. Responsibilities that may be fulfilled by either IRBs/IORGs or institutions engaged in human subjects research.

Is there a category of responsibilities that are inherently shared by the IRBs/IORGs and engaged institutions?

Proposal to Hold IRBs AccountableProposal to Hold IRBs Accountable

1. Responsibilities that may be unique to IRBs/IORGs; a few examples: Provisions regarding IRB membership (45

CFR 46.107) Provision that identifies criteria for IRB

approval of research (45 CFR 46.111) Provision that permits IRB to alter or waive

informed consent (45 CFR 46.116(c) and (d))

Proposal to Hold IRBs AccountableProposal to Hold IRBs Accountable

2. Responsibilities that may be unique to engaged institutions; a few examples:

Requirement that investigator obtain IRB review and approval before beginning non-exempt human subjects research (45 CFR 46.109(a))

Requirement that no investigator conduct non-exempt human subjects research without obtaining and documenting subjects’ informed consent unless an IRB has waived these requirements (45 CFR 46.116 and 46.117).

Proposal to Hold IRBs AccountableProposal to Hold IRBs Accountable

3. Responsibilities that may be fulfilled by IRB/IORG or engaged institutions; a few examples:

Determining applicability of 45 CFR part 46 (e.g. exemptions) (45 CFR 46.101(b))

Developing written IRB procedures which IRB will follow (45 CFR 46.103(b)(4))

Fulfilling documentation and recordkeeping requirements associated with IRB activities (45 CFR 46.115)

ANPRM on IRB Accountability: ANPRM on IRB Accountability:

http://edocket.access.gpo.gov/2009/pdf/E9-4628.pdf

*Comments due June 3, 2009 *Comments due June 3, 2009

IRB Registration RuleIRB Registration Rule (Issued January 15, 2009) (Issued January 15, 2009)

IRB Registration RuleIRB Registration Rule

OHRP added a new subpart E requiring IRB registration for:IRBs reviewing HHS-conducted or supported

human subjects research; and Designated on a Federal wide Assurance

FDA simultaneously issued IRB registration rule

Both rules become effective July 14, 2009

IRB Registration RuleIRB Registration Rule

First time registration required within 60 days of effective date (9/14/09)

Already registered IRBs as of 9/14/09 must re-register within 3-year expiration date or within 90 days of any changes regarding: the contact person who provided the IRB

registration information; or the IRB chairperson

IRB Registration RulesIRB Registration RulesOHRP: OHRP:

http://edocket.access.gpo/gov/2009/E9-588.htm

FDA: FDA: http://edocket.access.gpo/gov/2009/E9-682.htm

FAQs on Meaning ofFAQs on Meaning of OHRP-Registered IRB OHRP-Registered IRB and OHRP-Approved and OHRP-Approved

FWAFWA(Issued May 6, 2009)(Issued May 6, 2009)

FAQs on IRB Registration/FWAFAQs on IRB Registration/FWA

Clarify that IRB registration does not mean that an IRB is in full compliance with the HHS human subject protection regulations.

Clarify that OHRP-approved FWA does not mean that an institution is in full compliance with the HHS human subject protection regulations.

FAQs: FAQs: IRB Registration (see Question #14): IRB Registration (see Question #14): http://www.hhs.gov/ohrp/IRBfaq.htmlFWA approval: (see Question #25): FWA approval: (see Question #25): http://www.hhs.gov/ohrp/FWAfaq.html

Policy/Guidance Coming Soon…Policy/Guidance Coming Soon… Guidance on discontinuation of participation in human

subjects research (draft issued for public comment December, 2008)

Draft guidance on continuing review (will address several SACHRP recommendations)

Revised guidance on stem cell research (will update references to NIH’s guidelines for human stem cell research)

Notice to modify expedited review category 5 and/or 7 (notice issued for public comment October, 2007)

FAQs on IRBs (expected to send to Common Rule agencies for comment before issuance)

Guidance to clarify investigator is not prohibited from making exemption determinations.

Policy/Guidance Coming Soon (Maybe)Policy/Guidance Coming Soon (Maybe)

Several possible modifications to the FWA—seeking comments from Common Rule Departments/Agencies:Eliminate “check-box”Eliminate requirement that all IRBs being relied upon

by institution be designated on its FWA (e.g. internal IRBs only, or if none internal only the external IRB that reviews the most human subjects research)

Eliminate references to international standards on FWA for international institutions

Require electronic submission of FWAEliminate collection of HHS Institutional Profile File

code and Federal Entity Identification number

Policy/Guidance Coming Later…Policy/Guidance Coming Later…

Guidance on human biological specimens, repositories and databanks (SACHRP is addressing a subset of these issues)

Guidance on research involving children (taking into account SACHRP’s and IOM’s recommendations)

Possible NPRM to eliminate requirement for reporting IRB membership rosters to OHRP (responsive to a SACHRP recommendation)

DISCUSSIONDISCUSSION