If with Federal Funding Add Shaded Boxes

LOMA LINDA UNIVERSITY SHARED SERVICES

RESEARCH AFFAIRS

UNANTICIPATED PROBLEMS

Supplement

Version E (r1)

J.R. Krausz, et al. © Loma Linda University 2011 A & B without DMC  Unanticipated Problems IRB itself Performs AE Oversight

(if With Federal Funding – add shaded boxes)

WHAT KIND BY Whom TO Whom WHEN (AE or ADR) 1 SERIOUS RELATED that are Within 5 working days UNEXPECTED of investigator awareness (OHRP guidance: and Dated 01-15-07 that suggest the study risks are V.(2) ) greater than previously recognized

Investigator * IRB 5 NOT SERIOUS Within 10 working days RELATED of investigator awareness that are (OHRP guidance: UNEXPECTED Dated 01-15-07 V.(2) ) and that suggest the study risks are greater than previously recognized

Within 10 working days Institutional of notice to IRB IRB Official 1, 5 (not regulatory- this RELATED allows time for I/O to consider before reporting to OHRP) that are UNEXPECTED OHRP and Institutional and that suggest the study risks are Within one month of Official Funding greater than previously recognized notice to IRB Agency (OHRP Guidance) C. with DMC –Unanticipated Problems Study with LLU-Appointed DSMB (if With Federal Funding – add shaded boxes)

WHAT KIND BY Whom TO Whom WHEN (AE or ADR) 1, 5 RELATED and DMC UNEXPECTED and that suggest the study Within 5 working days risks are greater than of investigator awareness previously recognized Investigator 1 OHRP guidance: SERIOUS Dated 01-15-07 RELATED §V.(2) and UNEXPECTED and IRB that suggest the study risks are greater than previously recognized

Within 5 working days DMC of DMC awareness institutional requirement (1) 1, 5 RELATED and Within 10 working days Institutional IRB UNEXPECTED institutionally required report timing; Official allows time for I/O to consider before and reporting to OHRP that suggest the study risks are greater than previously recognized Institutional OHRP Within one month of notice to and Official IRB Funding Agency (OHRP Guidance dated 01-15-07)

NOTE: This matrix is for studies that are not within FDA regulations for an IND (Investigational New Drug) or an IDE (Investigational Device Exemption).

D & E  Unanticipated Problems AE Oversight provided by non-LLU entity (NON-FDA Study) (if With Federal Funding – add shaded boxes)

WHAT KIND BY Whom TO Whom WHEN (AE or ADR)

As Required by As Required by protocol, protocol, Sponsor grant, or contract grant, or contract

1 SERIOUS RELATED Within 5 working days that are of investigator awareness OHRP guidance: UNEXPECTED Dated 01-15-07 Investigator and § V.(2) that suggest the study risks are greater than previously recognized IRB 5 NOT SERIOUS RELATED Within 10 working days that are of investigator awareness OHRP guidance: UNEXPECTED Dated 01-15-07 and § V.(2) that suggest the study risks are greater than previously recognized

Within 10 working days Institutional 1, 5 IRB of notice to IRB Official RELATED (allows time for I/O to consider and before reporting to OHRP) UNEXPECTED OHRP that suggest study risks Institutional and are greater than previously Within one month of Official Funding Agency * notice to IRB recognized (OHRP Guidance)

* On a multi-center study, although AE’s are reported to an external oversight body such as COG, regulations still place responsibility on LLU to assure reporting to OHRP of Unanticipated Problems that occur at our site.. When LLU PI is a Sponsor-Investigator

G & K – Drug or Device Trial: FDA-ICH with LLU Appointed DMC Unanticipated Problems (that are not AE’s) (if With Federal Funding – add shaded boxes)

WHAT KIND WHEN BY Whom TO Whom (AE or ADR) 1 DMC SERIOUS RELATED Within 5 working days* and of investigator awareness UNEXPECTED (not regulatory ) that suggest study risks are greater than previously Sponsor- recognized Investigator 5 IRB NOT SERIOUS Within 10 days RELATED of investigator awareness and (OHRP guidance: UNEXPECTED Dated 01-15-07 that suggest study risks are § V.(2) ) greater than previously recognized Within 5 working days* DMC IRB of DMC receipt (not regulatory) Within 10 working days Institutional 1, 5 of IRB receipt IRB (not regulatory) Official RELATED and (21 CFR 56.108 “prompt”)** UNEXPECTED that suggest study risks FDA are greater than Within one month of Institutional previously recognized notice to IRB (OHRP Guidance) Official OHRP and Funding (21 CFR 56.108 “prompt”) Agency

* 1 week investigator to DSMB + 1 week DSMB to IRB = 2 weeks, which meets 2 week OHRP guidance for reporting of non- AE UP’s to IRB; + 10 days IRB to I/0 = 24 days, leaving 7 more to report to OHRP within recommended one month. This does not comply strictly with OHRP guidance for investigator to notify IRB about a serious UP within 5 days, but neither does the guidance mention prior reporting to an internal DMC.

** Extract from 21 CFR 56.108: In order to fulfill the requirements of these regulations, each IRB shall: “b) Follow written procedures for ensuring prompt reporting to the IRB, appropriate institutional officials, and the Food and Drug Administration of: (1) Any unanticipated problems involving risks to human subjects or others;

H, I, L, M -  Unanticipated Problems Device or Drug Trial: FDA-ICH , AE Oversight provided by non-LLU entity

(if With Federal Funding – add shaded boxes)

WHAT KIND WHEN BY Whom TO Whom (AE or ADR)

As required, by protocol, As required, by Sponsor grant, or contract protocol, grant, or contract 1 SERIOUS RELATED Within 5 working days and of investigator awareness (OHRP guidance: UNEXPECTED Dated 01-15-07 and § V.(2) ) Investigator that suggest study risks are greater than previously recognized IRB 1, 5 RELATED Within 10 working and days UNEXPECTED of investigator awareness and (OHRP guidance: that suggest study risks are Dated 01-15-07 greater than previously V.(2) ) recognized

Within 10 days from Institutional IRB IRB receipt Official 1, 5 (not regulatory)(1) RELATED and FDA(2) UNEXPECTED and Institutional Within one month of that suggest study risks are notice to IRB Official greater than previously OHRP and (OHRP Guidance) Funding recognized Agency

(1) Sets-up correct report timing to IRB, I/O, FDA, and Funding Agency, per Guidance

(2) Reporting of (non-AE) unanticipated problems to the FDA, is specified in 21 CFR 56.108.