Obtaining Pre-Study

Approvals for Clinical Trials

K-30 Module 5 Navigating the Pre-Award Process

Helene Orescan, J.D.

Bishoy Anastasi, MBA, CCRP

David Geffen School of Medicine at UCLA

Industry Sponsored Clinical Trials

February 7, 2012 1

K30 Program

The Clinical Research Curriculum Award

(CRCA) is designed to attract talented

individuals to the challenges of clinical research

and to provide them with the critical skills that

are needed to translate basic discoveries into

clinical treatments.

Challenges, i.e. Regulatory-Approvals…

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Clinical Research and Clinical Trials

Human Research

Clinical Research

Clinical Trials

Investigator

Initiated

Protocol

Sponsor

Initiated

Protocol

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What is a “Clinical Trial”? September 2006

At UCLA a Clinical Trial is defined as:

The controlled, clinical testing in human subjects of

investigational new drugs, devices, treatments, or

diagnostics, or comparisons of approved drugs, devices,

treatments, or diagnostics, to assess their safety, efficacy,

benefits, costs, adverse reactions, and/or outcomes.

Such studies may be conducted under an industry-authored

protocol or an investigator-authored protocol.

Financial support for a clinical trial must be provided by a

for-profit entity.

www.research.ucla.edu/ocga/memos/CT_Definition_Memo.pdf

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What is Not Considered a Clinical Trial per UCLA Policy?

Retrospective chart review

Laboratory Research (i.e. bench and basic science studies)

Federally Funded Clinical Research

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Indirect Costs

Facilities & Administrative costs (F&A) also known as

overhead or Indirect Costs

Industry-sponsored Clinical Trials (both, sponsor-initiated &

investigator-initiated) – all costs subject to 26% Rate (with the

exception of mandatory IRB fees)

Other Clinical Research (not a “Clinical Trial”) conducted

on-campus – select costs subject to 54% Rate

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Sponsor-Initiated Clinical Trials

Industry Sponsor authors the protocol

Industry Sponsor holds the IND/IDE

Industry Sponsor funds the study

Industry Sponsor assumes most liability

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Investigator-Initiated Clinical Trials

Investigator authors the protocol

Investigator usually holds the IND/IDE

Industry sponsor funds the study

University generally assumes some liability

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Approvals Required to Conduct Clinical Trials

Institutional Review Board (IRB)

Contract/Grant

Sponsor Regulatory

Budget and Coverage Analysis

Conflict of Interest Review Committee (CIRC)*

Medical Radiation Safety*

Internal Scientific Peer Review Committee*

Reimbursement Review*

Value Analysis Committee (VAC)* *applicable to certain clinical trials – check with your contracts officer.

TIP: Avoid delays, submit applications/doc’s in parallel (IRB/contract/budget/etc.)

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IRB/Human Subjects Protection Approvals

UCLA Institutional Review

Board (IRB)

Functions under :

Federal Guidelines (CFR)

Federal-Wide Assurance (FWA)

UCLA policy and guidelines

UC policy and guidelines

Committees own decisions

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IRB and Related Approvals

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Web-IRB Tutorial:

https://webirb.research.ucla.edu

“Quick Reference Guides”

How you can help expedite the pre-award process

Simultaneous IRB & Contract submissions

Know your contacts At the IRB At the Sponsor At Industry Clinical Trials

Proactive completion of paperwork

Initial vs. Final

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Contracts & Grants Industry-Sponsored Clinical Trials – Clinical Trial

agreements (IIRP and sponsor-initiated) funded by industry (for-profit) sponsors

Office of Contract & Grant Administration

(OCGA)-Agreements related to Research (but not Clinical Trials), agreements with Gov’t or non-profit organizations e.g. NIH, foundations, etc.

Office of Intellectual Property & Industry Sponsored Research (OIP-ISR) –License agreements for University held patents, copyrights, etc., & research agreements funded by industry sponsors. 13

Clinical Trials Contracting

Clinical trial agreements/contracts contain many important legal terms & conditions

Authority to sign a contract is restricted to certain University officials

Principal Investigators are not authorized to

sign contracts that bind the University

Signing of a contract is contingent upon final IRB approval

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Industry Clinical Trials –

Our Role in Protecting You & the Institution

Contract negotiation and execution (mandatory for all clinical

trials before study initiation/enrollment)

Budget Coverage Analysis review and approval required prior

to contract execution

Assurance that financial terms in the Informed Consent Form,

Budget, and Contract are consistent.

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Available Resources and Services Industry Clinical Trials

Reviews, Negotiates and Executes Clinical Trial Agreements with industry (for-profit) sponsors.

Reviews Conflict of Interest Forms – submit to CIRC if required

Provides Clinical Research Administrators (CRAs) for

Support with Budget development and Coverage Analysis approval.

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http://clinicaltrials.ucla.edu/workfiles/ OCT_Contracting_Directory.pdf

Industry Clinical Trials – Current Assignment Directory

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Minimum Documents REQUIRED to Initiate Contract Review

Current Protocol

Draft Clinical Trial Agreement

Draft Goldenrod (only PI signature is required)

Financial Disclosures

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Financial Disclosure Process & CIRC

700U

State of

California Form

Principal

Investigator

Form

State or Federal Requirement

Who Discloses

What to Disclose

Positive Disclosure Supplement CIRC Review

$500+

700U

Addendum

Institutional

Form

PI & Key

Personnel

$10,000+

CIRC must review and approve disclosures prior to contract sign-off. 19

700-U 700-U Addendum

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Financial Disclosure Instructions

http://rpc.research.ucla.edu/RPC/Pages/COIForms.aspx

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Why do we need financial

disclosure forms?

It’s the law!

Institution must manage financial interests.

Positive disclosure(s) may affect Informed Consent Form

language.

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Financial Disclosure Process & CIRC

Important Facts:

Disclosures are effective for a 12-month period (700U = report 12 months prior, 700U Addendum = report 12 months prior & future)

CIRC Meeting & Submission Deadlines Industry Contracts office must receive disclosure

documents at least three (3) business days before CIRC case submission deadline

Missed deadline can cause a significant delay (30 days minimum)

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2012 CIRC Meeting Deadlines

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Financial Disclosure Process & CIRC

Important Facts to Note:

If a Clinical Research Organization (CRO) is executing

the contract, disclosure forms need to be completed for

both the study Sponsor and CRO.

Contract Amendments that add funding or change the

Principal Investigator, also require completion of new

700U/700U-Addendum forms.

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Here are some tips to help you navigate the pre-award clinical trial process.

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Clinical Trial Sponsor

PI (Principal Investigator)

Negotiate Budget w/

Sponsor

Contracts Submission

-Min. Documents, incl.

Financial Disclosure

Forms to CO

Budget

Development IRB Submission

CO

Negotiates

CTA Budget Finalized

Scientific Review ISPRC, MSRC, CTRC

IRB & Other

Approvals

Simultaneous Submission Process

CTA Fully Executed

CIRC Review

& Approval

To CO

To ORDM/EFM for Fund Number

Final Docs

Industry Contracts CRA

Review

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What’s Involved?

Confidentiality Disclosure Agreement (CDA) Negotiated

(Industry Contracts – Bill Wu)

Feasibility Questionnaire & thorough Protocol Review

Initial “Go”/ “No-Go” Decision

Budget Development and Negotiation

Regulatory Submission and Approvals

Clinical Trial Agreement (CTA) Negotiation

Coverage Analysis and Approval

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Phase 1 - “Go”/“No-Go”

Adequate Subject Population to conduct Study?

Adequate Resources to conduct Study? Personnel(PI and staff time)

Physical Space

Other ancillary support

Pharmacy

Radiology

CTRC

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Phase 2 – Regulatory Approvals at UCLA IRB Submission & Approval

Financial Disclosures

Contract Review & Negotiation

Budget Negotiation & Coverage Analysis

Other Institutional Approvals (if applicable)

RAD safety, VAC, Reimbursement Review

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Clinical Trial Budgets

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To Develop A Budget That Covers All Costs:

Understand the Protocol

Differentiate between routine care and research procedures

& services

Analyze Costs Personnel Hidden Costs Administrative Patient care Indirect Costs

Develop appropriate payment criteria

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Can the Budget pull the weight?

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Budgeting: Key Budget Elements

Invoiceable Items Non-refundable Start-Up Costs

IRB Prep and IRB Review Fees Setup Fees for Rx, RAD, CTRC, etc.) Ongoing drug dispensing costs

Additional Procedural Costs

Unscheduled visit, additional labs/tests, blood/tissue samples, biopsy, etc.

Study Admin & Maintenance fees SAEs

Annual Renewal Fees (IRB, Rx, etc.)

Protocol Amendment fees

Record Retention

Additional Supplies

Shipping Fees

Misc.

Screen Failures, Re-consent, etc.

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Cost Per Patient (CPP) Budget

All protocol required procedures and services identified (budget should mirror protocol visit schedule).

Procedural costs (reduced research rates available online for outpt services)

PI Effort – compensation for time/effort managing study.

Research Staff Effort – study coord, nurse, and/or data manager.

Overhead/Indirect Costs

Screening and randomization costs.

Cost Per Patient Budget

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Invoiceable Items

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Budgeting: A Process

Determination of the true cost to perform clinical trial at UCLA.

Careful consideration of routine care versus research-induced costs.

Necessary pre-approval/pre-authorizations for devices/certain standard of care charges.

Budget approval by someone with fiduciary responsibility or as required by department.

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Coverage Analysis (CA)

Budget Coverage Analysis is conducted on all “qualifying trials”.

CA documents the process of identifying the procedural costs which may be billed to insurance as routine care, vs. research costs, which will be paid for by the sponsor, for procedures/services performed as a result of a subject’s participation in a clinical trial.

Routine Care = Billable to Insurance

Research Procedure/Service = Must be provided for by Sponsor.

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Coverage Analysis – What is a Qualifying Trial?

In order to be covered, the service must be part of a trial that meets all of the following criteria to be considered a “qualifying trial”:

Evaluates a Medicare benefit – an item or service that falls within a Medicare Benefit category and is not statutorily excluded from coverage (e.g. cosmetic surgery, hearing aids); and

Has therapeutic intent – conversely not designed exclusively to test toxicity or disease pathology; and

Enrolls diagnosed beneficiaries – trials must enroll patients with diagnosed disease rather than healthy volunteers (but may also enroll a healthy control group); and

Has desirable characteristics:

Trials funded by NIH, CDC, AHRQ, CMS, DOD and VA; or

Trials supported by centers or cooperative groups funded by NIH, CDC, AHRQ, CMS, DOD and VA; or

Trials conducted under an IND reviewed by the FDA; or

IND exempt under 21 CFR 312.2(b)(1)

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Clinical Research Administrator’s (CRAs) Role

Provide support to investigators during the pre-award process and beyond:

Budget Review

Coverage Analysis and Approval

Billing compliance guidance

Resource for Pre-Study requirements

Current CRAs:

Bishoy Anastasi, MPH, MBA, CCRP

Silvia Estrada, MPA, CCRC

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Other Approvals

Radiology – Reduced Research Rates

https://research.radiology.ucla.edu

Use “Contact Us” link to register for a username/password

Outpatient/Inpatient Laboratories

Contact Nerissa Juse, Njuse@mednet.ucla.edu

Investigational Pharmacy

Contact Bill Hirokawa or Christina Shin, x 7-8522

UCLA CTRC (formerly GCRC)

https://www.ctrc.medsch.ucla.edu

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CTSI – CTRC website

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Other Institutional Approvals

Some examples:

Conflict of Interest Review Committee (CIRC)

Reviews positive disclosures of financial interest (and makes recommendations regarding award acceptance

Environment, Health & Safety (EH&S)

Medical Radiation Safety Committee

Research use of isotopes or radiation machines in humans

Institutional Biosafety Committee

Research use of infectious substances

Research use of recombinant DNA

Internal Scientific Peer Review Committee (ISPRC)

Cancer and cancer prevention studies

Billing/Reimbursement Review

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Sponsor Regulatory Documents

CV(s)

Current Medical License(s)

FDA Form 1572

Lab Normals and CLIA certificates

Delegation of Authority Logs

IRB/ICF Approvals

Financial Disclosure Forms (FDFs) for Sponsor

(independent of Institutional FDFs)

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Final Documents REQUIRED for Contract Execution

Final Protocol

Final Budget

Coverage Analysis

Final Goldenrod

Financial Disclosure Forms (and online supplement, if applicable)

CIRC Approval (if applicable)

IRB Approval, including approved ICF

PI Exception Letter (if applicable)

Other documents specific to your department

DOM: Investigator Responsibilities, Other Support Summary

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Top Reasons for Delays in Contract Execution: Incomplete and/or Missing Forms

Financial Disclosure Forms (700U/700U Addendum)

Online Supplement (for positive disclosure)

Goldenrod (missing signatures or e-sign (wet-ink signatures required))

P.I. Exception Letter (must be signed by department chair and Dr. Rome (Associate Dean of Research))

Budget

Draft vs. Final Budget

Investigator Approval

Coverage Analysis Approval

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After IRB approval and contract execution…

Running the study

Subject recruitment and screening

Study visits

Data management

Regulatory compliance

Adverse event reporting

Maintaining IRB approval

Protocol Amendments

Financial management

Account set-up and receipt of initial funds

Expenditure transactions

Sponsor invoicing and accounts receivables management

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Additional Resources

Industry Contracts Website:

http://clinicaltrials.ucla.edu

For Patient/Community

For Faculty/Staff

Contact us

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ClinicalTrials.ucla.edu

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Clinical Trials Website Log-In:

User name:

Password:

Please note: Site access is limited to on-campus IT connections.

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Industry Clinical Trials Training Opportunities

Current Workshops offered through Campus Human Resources (lms.ucla.edu)

Clinical Trial Budgets 101 – Intro to development & negotiation.

Thursday, February 9th, 2012. 10 – 11:30am

Upcoming Workshops:

Clinical Trial Budgets 201 – Performing Coverage Analysis

Clinical Trial Budgets 301 – Advanced development & negotiation. Focus: Investigator-Initiated budgets.

Focused training can be developed upon group/department request.

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Industry Clinical Trial Services

Available Upon Request

Budget Development & Negotiation*

Pre-Study Support

Advice & Consultation (including protocol feasibility assessment – no charge)

(*Fee-based services that can be written into budgets and passed through to the sponsor.)

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Industry Clinical Trials – Contact Info

Helene Orescan, J.D. Director DGSOM Dean’s Office, Industry Clinical Trials Horescan@mednet.ucla.edu 310-794-0137 Bishoy Anastasi, MPH, MBA, CCRP CRA Supervisor DGSOM Dean’s Office, Industry Clinical Trials Banastasi@mednet.ucla.edu 310-794-0545

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