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Techiya Toaff, R.N., M.S.H.S. Director Regulatory Affairs NavonPharma Group January 2, 2018

C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

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Page 1: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

Techiya Toaff, R.N., M.S.H.S. Director – Regulatory Affairs NavonPharma Group

January 2, 2018

Page 2: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

Objectives Describe the evolution of the cIRB in the protection of human subjects

(HHS, OHRP , FDA).

Discuss the establishment of the cIRB – institutional relationship.

Define delegated and shared responsibilities of the local IRB and the cIRB.

Discuss mandatory agreements.

Page 3: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

What is a central IRB? A Single IRB of Record Overseeing all clinical trial sites participating in a multi-

center study.

Permits a single IRB to review human subject research activities for more than one site.

Commercial (nonaffiliated /independent). OR Institutional (site level).

Page 4: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

The USA Regulator –

Human Subjects

Page 5: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

Milestones in cIRB Regulation:

HHS

• 21 CFR 56.114 (“Cooperative Research”) (1979).

• Improve Rules Protecting Human Research Subjects (2015).

FDA

• FDA Guidance: Using a cIRB Review Process in Multicenter CT (March 2006).

OHRP

• Advance Notice of Proposed Rulemaking Fed. Reg. 74 (42) (March 5, 2009).

NIH

• Single IRB (sIRB) mandate (2018).

Page 6: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

IRB Registration

OHRP 2009:

IRB that reviews FDA-regulated studies (IND’s) must register in the federal registry to be in compliance with 21 CFR Part 56.106(a).

IRB registration is not a form of accreditation or certification by OHRP or FDA.

FDA may conduct an inspection of an IRB to verify compliance with regulatory requirements.

Page 7: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

Using a Centralized IRB Review Process in Multicenter

Clinical Trials (FDA Guidance for the Industry 2006)

Both parties must have written procedures in place to implement the centralized IRB review process (21 CFR 56.108, 56.114).

Institution:

Should develop policies for determining when/which studies conducted

in the site would be appropriate for centralized review & how a

centralized review would be conducted for such studies.

For example: How the site’s IRB determines that the central IRB is

qualified to review research conducted at the site.

Page 8: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

Using a Centralized IRB Review Process in

Multicenter Clinical Trials - FDA 2006 (Cont.)

Central IRB:

Must have written procedures describing how it implements its responsibilities under an agreement with a referring IRB.

For example: How the cIRB intends to communicate with relevant

sites, the site’s IRB(s) and investigators regarding its review.

Page 9: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

Centralized Review Process

Commercial or Institutional:

Centralized IRB review process involves an agreement under which

multiple study sites in a multi-center trial rely in whole or in part on the

review of an IRB other than the IRB affiliated with the research site.

A centralized process is to increase efficiency and decrease

duplicative efforts that do not contribute to meaningful human subject

protection.

Page 10: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

National Institutes of Health (NIH)

New IRB Review Policy

Effective January 25, 2018, the NIH will

mandate the use of single IRBs as a

contingency for funding of multi-center studies using the same protocol.

Page 11: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

FDA,OHRP & NIH Vision FDA Guidance (2006):

Consider the use of a single central IRB using centralized review could improve the efficacy of IRB review.

OHRP (2010):

“Fully agrees with FDA’s position on the benefits of relying on a single central IRB for multicenter research.”

NIH (2018):

Mandatory use of cIRB for federal funded multi-center studies.

Page 12: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

What is a central Independent IRB?

Independent IRB - a review board that is not owned or operated by the site.

Subject to the same US (CFR 21) and state regulatory requirements (e.g. liability, cost of participants, consenting minors) applicable to all IRBs.

Provides regulatory and ethical oversight for research conducted by one or more sites not otherwise affiliated.

Per specific agreement, it becomes the IRB of record for oversight of the research at all sites.

Page 13: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

What studies will the site send to cIRB? Industry-funded studies goes to cIRB; investigator-initiated research

stays with local IRB.

Research in certain therapeutic areas (e.g., oncology, neurology, etc.) goes to cIRB.

Late phase research goes to cIRB; early phase remains with local IRB.

Federally funded research goes to cIRB.

Page 14: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

Duties of the Reviewing IRB (IRB of Record) Conduct review of research according to all applicable regulations and laws

Suspend or terminate IRB approval.

Reviews unanticipated problems involving risks to participants or others.

Review incidents of serious or continuing non-compliance.

Notify the investigators and sites in writing of its decisions.

Make available relevant IRB meeting minutes to the relying site.

When appropriate, conduct on-site or remote post-approval monitoring or audits, unless delegated to the relying site.

Specify the contact person and provide contact information for the reviewing IRB.

Page 15: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

Roles of the Relying Site and Investigators Investigators: must comply with the determinations and requirements of the reviewing IRB . Site: responsible for ensuring compliance with the reviewing IRB

requirements. Prior to IRB review, provide the IRB with any local context issues (relevant to

the research protocol). Research may be further reviewed (scientific review) and approved or

disapproved by officials of the relying site, but they may not be approved by the site if it has not been approved by the reviewing IRB.

Page 16: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

Roles of the Relying Site and Investigators (Cont.)

The site and the investigators acknowledge and agree to cooperate and the IRB’s responsibly for initial and continuing review, record keeping and reporting.

All information requested by the IRB will be provided in a timely manner.

The relying site may conduct post-approval monitoring in addition to, or in

cooperation with, the reviewing IRB.

Specify the contact person and provide contact information for the relying site.

Page 17: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

IRB Reliance Agreements

A reliance agreement is also called an IRB Authorization

Agreement (IAA).

The agreement is for a single protocol or a portion of the site’s research.

Signed by two or more sites engaged in human subjects research.

Page 18: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

IRB Reliance Agreements (Cont.)

The signed agreement permits a single IRB to review human subject research activities for more than one site.

It can be a simple one-page agreement (OHRP’s template).

In many situations, however, it makes sense to develop more detailed agreements to establish expectations and process (CTTI - IRB authorization Agreement).

Page 19: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

IRB Reliance Agreements (Cont.)

Study-By-Study Agreement

This agreement establishes a reliance relationship between the cIRB and relying site for only a single study.

Master Agreement

Allows review by the cIRB of all research submitted by the relying site.

Page 20: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

Summary Relying on an external single IRB, whether it is for a single protocol or a

portion of the site’s research portfolio can be efficient and

cost-effective.

Research and regulatory environment is changing.

Single/cIRB review is becoming the new standard, however site has complete control over which studies are submitted to cIRB.

Page 21: C-Trials הכתובת לכל אנשי המקצוע בתחום ... - January 2, …Clinical Trials (FDA Guidance for the Industry 2006) Both parties must have written procedures in

Thank you for your attention