ohrs submit" to "activation": where does the paperwork go

“OHRS Submit” to “Activation”:Where does the paperwork go and what are the common hold ups in review/activation?

Amanda Hammond, JDDeputy Director

Emily EldhAssistant Director for Clinical Research

Sara Harnish, JDAssistant Director for Non-Clinical Research

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Overview

• Background on OHRS

• Triage, review, approval and activation path for:

• New Protocols

• Amendments

• Continuing Reviews

• Pitfalls that slow the time to Approval and Activation

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OHRS

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OHRS Organization

Senior DirectorMichele

Russell-Einhorn, JD

Deputy DirectorAmanda Hammond, JD

IntakeAdministrators

MeetingCoordinators

Human Research

Coordinators

ActivationCoordinators

OnLineCommunications

Assist. Director for Clinical Trials

Emily Eldh

Assist. DirectorNon-Clinical Trials

Sara Harnish, JD

Operations SupervisorDarek Leslie

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OHRS Tracks and Processes…

399New

Protocols

~ 1,160 Adverse Events

~1,630 Continuing Reviews

~ 1,650 Other Events• deviations/violations • other DF/HCC reports

IND Safety Reports

~ 3,810 Amendments• general amendments • dose escalation changes • study team updates / add sites

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OHRS Tracks and Processes…

399New

Protocols

~ 1,160 Adverse Events

~1,630 Continuing Reviews

~ 1,650 Other Events• deviations/violations • other DF/HCC reports

IND Safety Reports

~ 3,810 Amendments• general amendments • dose escalation changes • study team updates / add sites

In 2008 OHRS Received

~ 8,650 Submissions (not including IND Safety Reports)

~ 26,500 Documents

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Coordinate Boards and Activation Agents

• At least 194 meetings each year

• 4 scientific review committees

• 6 institutional review boards

• Coordinate Routing for Activation at:

• BIDMC / BWH / CHB / DFCI / MGH

• Nursing / Pharmacy / Rad Safety / BioSafety /

QACT / Research Admin / CRL / CMCF / etc.

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Intake & Triage

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Intake and Triage:New Protocols

• When New Protocol Application is Complete:

• Route “preview” copies to:• Research Administration and Clinical Trials

Billing/Budget Offices at participating institutions

• Multicenter Coordinating Committee, if PI-initiated Multicenter study

• Tumor Imaging Metrics Core, if applicable

• Cell Manipulations Core Facility, if applicable

• Radiation Safety Officers at participating institutions

• Save electronic versions in OHRS Shared File

area

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• When New Protocol Application is Complete:

• Triage for P/SRC & IRB review:• SRC vs. PSRC• Expedited vs. Full P/SRC• IRB A/B vs. IRB D• Expedited vs. Full IRB

• Schedule for SRC/IRB meetings, as applicable

• Enter into ReX (which is the OHRS protocol database)

• Enter into new protocol tracking sheet

• Send notice to study primary contact and PI advising of

SRC/IRB review path and meeting dates, if applicable

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Intake and Triage:Sample Intake Checklist for New Protocols

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• Problem Spots

• Missing required documents

• Wrong application form was used

• Incomplete forms

• Inconsistent information provided on forms

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• New Project Applications:

• Clinical Trials

• Social/Behavioral Research

• Medical Record Reviews

• Use of Specimens

• Request for Exemption or Determination that

Research is Not Human Subject Research

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• Required documents

• Endorsement Form

• Front Sheet

• Application Form

• Staff Signature Pages

• Protocol

• Consent Form or

Request for Waiver

• Priority List

• Electronic Copy

• Also submit if applicable:

• Radiation Safety Screening

Form

• Subject/Pill Diary

• Questionnaires

• Recruitment Material

• Grant application

• Alert Page

• Investigator’s Brochure

• Lab Manual

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• Assigned to HRC Team Lead based on:

• Clinical Trial vs. Non-Clinical Trial

• Disease/Discipline Program

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HRC Team AssignmentsTeam A Team B Team C Team D Team E

Selvin OheneBen ClopperGene Kane

Katharine Cantelli

Sasha BarajasNicole BrooksJohn Reardon

Kim WilliamsBrian Durie

Ashley Faber

Sara HarnishHoon ChungAshley Yull

Lori HennellyRaina Rothschild

Gastrointestinal Malignancies

Leukemia (Malignant

Hematology) Breast Social/Behavioral Neuro-Onc

Kidney (Other non-Prostate

GU)Sarcoma Gyn Tissue Collection Head & Neck

Prostate (GU)Lymphoma &

MyelomaPhase 1

Medical Record Review

Cancer Imaging(non-disease specific)

Cutaneous Onc & Melanoma

Radiation Onc(non-disease specific)

Lung (Thoracic)

Other non-clinical Benign Hematology

Pedi-Onc Transplant

CHB IRB Only Protocols

Cancer Immunology (vaccine/gene

transfer & therapy)

HIV/AIDS related

Other "Not Cancer" related

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Intake and Triage:Amendments

• Download from OHRS Submit by saving to OHRS Shared File

• Print all associated documents

• Problem Spots

• Make sure all supporting documents are submitted

• If you reference adding study team members in

your “general amendment form,” please post your

study team update form with the general

amendment

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• Considerations for triaging for SRC/IRB Review:• Nature of changes, e.g.

scientific, etc.

• Minor vs. Major changes

• Expedited vs. Full Review

• Activation Agents• Sign-off required vs.

Notification

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• Once triaged:

• Schedule in ReX

• Enter into Tracking Sheet

• Send notice of review path and meeting dates to

primary contact and PI• Except for dose escalation/cohort changes, study team

updates and add sites

• Route to assigned HRC

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Intake and Triage:Continuing Reviews

• Download from OHRS Submit by saving to OHRS Shared File

• Print all associated documents

• Problem Spots

• Make sure all supporting documents are submitted

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Intake and Triage:Continuing Review

• Pull relevant history for IRB review from ReX, OncPro & QACT:

• Protocol Summary

Report

• Deviation Report

• Current version of

Consent

• Prior minutes

• Accrual data from QACT

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Intake and Triage:Continuing Review

• Expedited vs. Full Board Review

• Eligible for expedited IRB review if meet

categories set out in OHRP/FDA List:• Minimal Risk and was originally determined to meet

criteria in one of Categories 1 – 7, or

• Greater than Minimal Risk but:• Research is permanently closed to enrollment and all

subjects have completed all research-related interventions and active for long-term follow-up only, OR

• No subjects have been enrolled locally and no additional risk identified anywhere, OR

• Research is active for data analysis only

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Intake and TriageCRs• Typically expedited if check:

• Box 1 *• Box 2 *• Box 5 **• Box 6• Box 7

• Typically full board if check:• Box 3• Box 4

* Note: may require full board review if additional risks identified at other sites

** Note: may require full board review if not permanently closed to enrollment

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OHRS Pre-Reviews & Board Reviews

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HRC Pre-Review & Board ReviewsNew Protocols

• OHRS Pre-Review

• Consistency among forms

• Identify missing information

• Focus on consent form

• Goal is to lessen conditions for IRB approval

• Anticipating IRB conditions based on discussions

at previous IRB meetings

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• OHRS consent form comments:

• Suggestions and not required

• Based on comments made by IRB at meetings

• OHRS comments are forwarded to IRB for

consideration

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• Problem spots• Poorly formatted informed consent documents

• Language is too technical

• Consents are not consistent with protocol

• Potentially exculpatory language included

• Consent Template is being updated• Standard language for procedures

• Reflect recent IRB preferences

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• IRB meeting date is tentatively scheduled 4 weeks from SRC review date• OHRS tries to get SRC minutes ASAP

• Provide three meeting dates with submission due dates

• Meeting Preparation – at least 1.5 weeks before meeting• Organize all protocol paperwork

• Identify and confirm reviewers

• Packets need to be printed, collated and posted electronically

• Packets delivered/distributed at least 1 week prior to meeting

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• Problem spots

• Responses that include changes beyond the

scope of SRC or IRB conditions• Requires submission of an Amendment

• Late “Add Site” Amendments• May cause delay in activation and need for subsequent

amendment if activation agents require changes to IRB approved documents

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HRC Pre-Review & Board ReviewsAmendments

• Dose Escalations/Cohort Change – High Priority

• If consistent with protocol, then routed for

expedited IRB review

• If changes the protocol, then may require full

board review

• Opening next study Phase – High Priority

• Scheduled for earliest full board – typically

Tuesday IRB

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• Regular Amendment affecting Safety – High Priority

• Scheduled for earliest full board meeting

• Protocol status may be updated prior to meeting

• CTEP Amendments – Priority

• Must be reviewed with 90 days

• IDB Updates

• Routed for expedited review

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• Regular Amendments

• Minor changes may be eligible for expedited review

• Major changes may require SRC review

• Change from single center study to multicenter study

requires MCC review prior to IRB review

• Study Team Updates


• Add Sites


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• Problem Spots

• Justification does not provide enough information

• Supporting documentation is not included

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HRC Pre-Review & Board ReviewsContinuing Review

• Expedited Continuing Reviews

• If medical review required, routed to medical

reviewer room

• Given volume of submissions, currently reviewed

in order of expiration date

• Full Board Continuing Reviews

• Attempting to schedule for review in real time (i.e.,

as close to submission date as possible)

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HRC Pre-Review & Board ReviewsContinuing Reviews

• Problem Spots

• Continuing review submitted close to expiration

date

• Form is not complete or includes inconsistent

information

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HRC Pre-Review & Board ReviewConditions and Approvals

• Once responses to conditions are submitted:

• HRC reviews to confirm responses are complete and

address committee concerns

• Verification Record is created and routed to an IRB member

for review and approval

• Approval memo is generated

• ReX is updated

• Tracking Sheet, if applicable, is updated

• Material is forwarded to the OnLine Team and Activation

Coordinators

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HRC Pre-Review & Board ReviewRouting Verification Records

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Activation

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Activations

• Activation packets are routed within 1 day of distribution of approval memo

• OHRS sends follow up reminders to activation agents at least once every 2 weeks

• Advise activation agents of high priority circumstances

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Activations

• Absent justification and approval by the OHRS Senior Director/Deputy Director, studies must first be activated at the lead site before being activated at any other participating site.

• Before activating at a participating site, the lead site Pharmacy must sign off or you must check with the lead site Pharmacy to make sure that it is ok for other participating sites to be active (if it is high priority and needs to be activated ASAP).

• DFCI Research Admin sign off is always needed (industry sponsored trials only) unless at BIDMC only.

• If BWH is being added as a site (amendment) or if they are the only participating site, you must obtain DFCI Pharmacy, Nursing and Research Admin (industry sponsored trials only).

• Pediatric vs. Adult sign off for pharmacy & nursing depends on which clinics are being utilized.

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Activations

• Problem Spots

• Activation agents may require changes - “post approval/pre-

activation” amendment process

• In-services not complete

• Waiting for drug

• COE / doctor’s orders sheets

• Funding issues

• Amendment may be ready for activation at one site but not

another – can only post one version to OncPro

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Additional Considerations

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Additional Considerations

• Working on notification to study teams of new protocol assignment to HRC

• Working on updating informed consent template

• Please remember to use most current versions of forms available at website

• If you have a complicated submission, please feel free to call OHRS for guidance

• Let us know when changes are good and we are on the right track

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OHRS Contacts

• OHRS website:

• www.dfci.harvard.edu/ohrs

• OHRS front desk:

• (617) 632-3029

ohrs submit" to "activation": where does the paperwork go

Documents

intake triage

ohrs triage

new protocols amendments

nonclinical research

new protocol application

study team update form

study team members

ohrs tracks