Obtaining Pre-Study Approvals for Clinical Trials K-30 Module 5 Navigating the Pre-Award Process

Transcription

1 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,

2 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 2

3 Clinical Research and Clinical Trials Human Research Clinical Research Clinical Trials Investigator Initiated Protocol Sponsor Initiated Protocol 3

4 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. 4

5 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 5

6 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 6

7 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 7

8 Investigator-Initiated Clinical Trials Investigator authors the protocol Investigator usually holds the IND/IDE Industry sponsor funds the study University generally assumes some liability 8

9 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.) 9

10 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 10

11 IRB and Related Approvals Web-IRB Tutorial: Quick Reference Guides 11

12 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 12

13 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

14 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 14

15 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. 15

16 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. 16

17 Industry Clinical Trials Current Assignment Directory OCT_Contracting_Directory.pdf 17

18 Minimum Documents REQUIRED to Initiate Contract Review Current Protocol Draft Clinical Trial Agreement Draft Goldenrod (only PI signature is required) Financial Disclosures 18

19 Financial Disclosure Process & CIRC Form State or Federal Requirement 700U State of California Form 700U Addendum Institutional Form Who Discloses Principal Investigator PI & Key Personnel What to Disclose $500+ $10,000+ Positive Disclosure Supplement CIRC Review CIRC must review and approve disclosures prior to contract sign-off. 19

20 700-U 700-U Addendum 20

21 Financial Disclosure Instructions 21

22 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. 22

23 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) 23

24 2012 CIRC Meeting Deadlines 24

25 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. 25

26 Here are some tips to help you navigate the pre-award clinical trial process. 26

27 Simultaneous Submission Process Clinical Trial Sponsor PI (Principal Investigator) Contracts Submission -Min. Documents, incl. Financial Disclosure Forms to CO Budget Development Industry Contracts CRA Review IRB Submission CIRC Review & Approval CO Negotiates CTA Negotiate Budget w/ Sponsor Budget Finalized Scientific Review ISPRC, MSRC, CTRC Final Docs To CO CTA Fully Executed IRB & Other Approvals To ORDM/EFM for Fund Number 27

28 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 28

29 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 29

30 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 30

31 Clinical Trial Budgets 31

32 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 32

33 Can the Budget pull the weight? 33

34 Budgeting: Key Budget Elements 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. 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. 34

35 Cost Per Patient Budget 35

36 Invoiceable Items 36

37 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. 37

38 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. 38

39 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) 39

40 Clinical Research Administrator s (CRAs) Role Provide support to investigators during the preaward 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 40

41 Other Approvals Radiology Reduced Research Rates 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 UCLA CTRC (formerly GCRC) 41

42 CTSI CTRC website 42

43 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 43

44 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) 44

45 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 45

46 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 46

47 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 47

48 Additional Resources Industry Contracts Website: For Patient/Community For Faculty/Staff Contact us 48

49 ClinicalTrials.ucla.edu 49

50 Clinical Trials Website Log-In: User name: Password: Please note: Site access is limited to on-campus IT connections. 50

51 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 9 th, :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. 51

52 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.) 52

53 Industry Clinical Trials Contact Info Helene Orescan, J.D. Director DGSOM Dean s Office, Industry Clinical Trials Horescan@mednet.ucla.edu Bishoy Anastasi, MPH, MBA, CCRP CRA Supervisor DGSOM Dean s Office, Industry Clinical Trials Banastasi@mednet.ucla.edu