Columbia University IRB

IRB 101

September 21, 2005

George Gasparis, Executive Director, CU IRB

Asst. V.P. and Sr. Asst. Dean for Research Ethics

September 21, 2005 Page 2

Objectives

This session will provide information on:

• Submission of modifications/amendments to the IRB

• IRB review of modifications

• Submission of unanticipated problems involving risks/adverse events to the IRB

• IRB review of adverse events – IRB oversight monitoring of risks

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All Human Research at Columbia University

Governed by Ethical Principles and the Requirements of HHS and FDA Regulations and

NY State Law

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Declaration of Helsinki, 1964

-Provides ethical principles for human research

with emphasis on clinical research

-Developed by the World Medical Assembly

-Has undergone 8 revisions; the most recent in October 2000 with clarification posted in 2002

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Declaration of Helsinki, 2002

-Article 16: Physicians should abstain from…research…unless

they are confident that the risks…have been adequately assessed

and… satisfactorily managed.

Physicians should cease any investigation if the risks are found to

outweigh potential benefits or if there is conclusive proof of

positive and beneficial results.

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Declaration of Helsinki, 2002

-Article 13: The researcher has the obligation to provide

monitoring information to the committee, for review, information

regarding funding, sponsors, institutional affiliations, other

potential conflicts of interest and incentives for subjects.

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DEPARTMENT OFDEPARTMENT OFHEALTH & HUMAN HEALTH & HUMAN

SERVICESSERVICES

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Federal Regulations for the Protection of Subjects from Research Risks

45 CFR Part 46

1981

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45 CFR 46.103(b)(4)

Written procedures which the IRB will follow:

(iii) for ensuring prompt reporting to the IRB of proposed changes in a research

activity, and for ensuring that such changes in approved research, during the

period for which IRB approval has already been given, may not be initiated without

IRB review and approval except when necessary to eliminate apparent immediate

hazards to the subject.

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CUMC IRB Approval Letter

“Any proposed changes in the protocol must be immediately submitted to

the IRB for review and approval prior to implementation, unless such a

change is necessary to avoid immediate harm to the participants.

Additionally, any serious and unexpected adverse events or other

problems that involve risks to subjects must be reported to the IRB in

accordance with the CUMC IRB AE Reporting Policy, dated April 13, 2004.

All submissions for modifications and adverse events must be submitted

through RASCAL.”

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45 CFR 46.109(a)

An IRB shall review and have authority to approve,

require modifications in (to secure approval) or

disapprove all research activities covered by this policy.

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As a result modifications may arise from:

1) A request from the IRB as a stipulation for approval.

-these are handled in RASCAL within the submission of the new protocol or continuing review as “returns” to the investigator, if done prior approval.

IRB does not call these “modifications”, unless they occur after approval.

______________________

2) A request from the sponsor or “lead Principal Investigator (PI)” when collaborating with other sites.

3) At the discretion of the Columbia PI (e.g., modifying the research procedures, change in research personnel; change in funding source).

-items 2 and 3 are handled in RASCAL as a new submission, called a “modification”.

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IRB Review of Modifications/AEs

1) Expedited Review – “minor changes in previously approved research during the period (of one year or less) for which approval is authorized” OR adverse events that are not believed serious, unanticipated, and related to the study intervention.

OR

2) Full Committee Review – all other modifications or serious and unanticipated adverse events

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Considerations for Modifications

1) Change in Funding Source:

-attach complete grant or contract application;

-summarize changes in research as a result of grant;

-if multicenter and Columbia is the prime awardee:

-summarize what each site will do.

2) Changes in Research Personnel:

-change in research staff should not only be summarized in the

modification, BUT ALSO added in the Personnel Section;

ensure that each new “key personnel” member has completed

GCP and HIPAA training.

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Considerations for Modifications3) If the modification affects the information in the informed

consent document OR the subject should be notified of new

information that may affect their decision to participate,

ensure that the consent form is appropriate revised;

mention in the Modification Summary that the consent has

been revised accordingly.

4) If consent forms are revised and the submission includes

both a RASCAL generated consent form and one attached in

RASCAL, explain how the forms are different. If not

different, archive the one that is attached in RASCAL, so

that the RASCAL generated consent will be the final

approved form(s).

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Considerations for Modifications

3) Ensure that Outdated Attached Documents are Archived in

RASCAL

4) Ensure that Attached Documents are clearly and consistently

labeled (e.g., “ICF 04022004” for the form attached in 2004 and

“Adult consent form 04012005” for the one attached in 2005).

-This will eliminate the need for the IRB and research staff

to open all/several attachments to identify whether a document

was previously attached and not revised, previously attached

and revised or a new document will increase efficiency and

turnaround time.

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Considerations for Modifications

5) If the Version Date of the protocol is included in the title or

in the Protocol Version Field, ensure to update the

information when a modification includes a revised protocol.

6) Ensure that the Modification Summary and the Attached

Documents are consistent.

- (e.g., Modification Summary states “Spanish

consent

forms” but the attachments include the Spanish consent

forms and a DSMB report)

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Considerations for Adverse Event Reports

Adverse Events and Unanticipated Problems

involving risks to Subjects

should be submitted either Promptly or

at Continuing Review

in accordance with the

Columbia Adverse Event Reporting Policy (April 13, 2004)

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Considerations for Adverse Event Reports

If the events meet the criteria for prompt reporting, submit the

Information using the Adverse Event Report module in RASCAL.

All other events should be summarized in a separate report and

attached in the submission for Continuing Review