Clinical Trials Submitted Successfully – Session #12 Heritage Gallery Presenters:

1. Clinical Trials Submitted Successfully – Session #12 Heritage Gallery Presenters: Laura Williams – Sponsored Projects Administration Debra Dykhuis – Office of Clinical Research Bridget Foss – Sponsored Projects Administration

2. Clinical Trials Trivia Time • According to clinicaltrials.gov, there are approximately how many open clinical studies underway in the state of Minnesota? 1,231

3. Order of Presentation Laura Williams – Feasibility Considerations in Clinical Trials Debra Dykhuis – Budgetary Considerations in Clinical Trials Bridget Foss - SPA Submission Processes and Shortcuts

4. Feasibility Considerations in Clinical Trials

5. Protocol Review Considerations Ethical Considerations Business Considerations Scientific Review Institutional Review Regents Policies Certainly not to be ignored, but not covered today: FDA GCP ICH Investigator-sponsored clinical trials What We’ll Cover Today

6. Protocol Review Considerations

7. Feasibility • Population • Staff • Space • Technical capability

8. Profitability • Cost per subject • Complexity of protocol • Duration of study • Survivability

9. Scientific Merit • Adequate study design • Main hypothesis • Blinding, randomization • Biostatistical methodology • Endpoints • Publishability

10. Ethical Considerations • Target population • Safety • Severity of disease • Availability of alternative treatments • Side effects • Peds / Elderly • Underserved populations

11. Business Considerations • Frequency and complexity of monitoring visits • Closeout visits • Funder resources and assistance during the trial • Working with the PI • Cost sharing • Multi-departmental

12. Business Considerations • CRO involvement • Past dealings with sponsor • History of timely payments (or not!) • SIV Process

13. Business Considerations – The Clinical Trial Agreement • Publications • University’s policies and continuing tax status are dependent on fulfilling our threefold mission: • Research and Discovery • Teaching and Learning • Outreach and Public Service • Intellectual Property • Terms must also be respondent to the University research mission • Principles of exercising academic freedom • Indemnification and Subject Injury • Payments • Important to understand these are negotiable • SPA will defer to the coordinator/PI

14. Scientific Review • To be performed by independent, peer reviewers – no one from the research team • One of three methods must be utilized • Full peer review by grant committee of NIH, NSF or a foundation – excludes industry sponsored clinical trials; or • U of M scientific review committees; or • CPRC provides initial evaluation and review of all University of Minnesota clinical cancer research protocols, and monitors and renews the protocols annually. Those with low success may be terminated.

15. Scientific Review • General Clinical Research Center (GCRC) Scientific Advisory Committee – only if GCRC center is utilized • Protocol Review and Data Use (PRDU) - protocols involving solid organ transplant • Interdisciplinary Site Specific Committee – translational • Others – Surgery, OB/Gyn • Any appropriately constituted departmental or collegiate – at least two reviewers reach consensus on science, documentation of the review process filed with the college-level associate dean • Required prior to IRB submission

16. Regents Policies • Openness in Research - Subd. 1 • The University shall not accept support from any source for research under a contract or grant that prohibits the disclosure of the research relationship, the nature of the research….. • IP Sharing • Commercialization activities are encouraged per Policy • Can not inhibit open research • Research should result in generation and dissemination of new knowledge • Ethics • Just the appearance of impropriety is to be avoided

17. Institutional Research Review and Committees • IRB – Human subjects • COI – Financial or other types of potential conflicts of interest • HIPAA • ICD • IBC - recombinant DNA, infectious agents or biologically derived toxins • AURPAC - ionizing radiation

18. Reference Resource • http://cflegacy.research.umn.edu/irb/about/ • http://cflegacy.research.umn.edu/subjects/ • http://cflegacy.research.umn.edu/irb/ScientificReview/index.cfm • www.umn.edu/regents/polindex.html • http://www.ospa.umn.edu/index.html Questions: Laura Williams, Principal Grant and Contract Administrator willi478@umn.edu

19. Clinical Trials Submitted Successfully Estimating Personnel Time and Optimizing Payment Terns Debra Dykhuis 02.17.2009

20. The crystal ball approach to estimating personnel time…… • “…there are many ways of losing money. Women are the most fun. Gambling is the fastest. Research is the most certain.” Lord Hives, Former Chairman of Rolls Royce

21. What is at stake? • Quality of the data • Speed of accrual • Attention to compliance • Prospects of getting future research funding • Staff burnout/turnover • Jobs

22. What can be done? • Have a clear clinical trial plan • Abandon the notion that guessing is the best we can do • Abandon the notion that the sponsor, agency, or center knows what it will cost to do the trial (and has our best interests at heart) • Create a column for every time point data will be collected • Create a row for every person who will have a job to do

23. What can be done? • Consider what each person will be required to do for each visit and write it down • Attach an estimate of time to do each part of the work • Ask the person who will be doing it what they think of the estimate • Adjust as needed and enter the number of hours required for each protocol time point or visit

24. What can be done? • Be sure to consider time staff will spend at research meetings, on subject recruitment, the time to prepare for research subject visits and the follow-up that might be needed, event reporting, managing interactions with monitors, and data queries • For industry trials, include time for start-up and close out, regulatory documents, amendment processing, etc.

25. What do we know? • Reviewed time data for 20 clinical trials completed 2005-2007 • Areas of cancer, solid organ transplant, critical care, rare diseases • Average time per study visit for a research coordinator – 11 hours • Average start-up time – 45 hours for regulatory processes; 24 hours for clinical research coordinator

26. Applying what we know • Approximately 35% of an employee’s appointment time is consumed by vacation/sick leave, breaks, and other work that may not be directly related to a clinical trial • Consider this when writing budgets that require budgeting by FTEs • Example: a .5 research coordinator on a solid organ transplant study will be able to manage about 61 visits per year (at 11 hrs/visit)

27. Optimizing contract payment terms in agreements with industry • Start date: terms should allow payment for work as soon as it starts • End date: should be “until all study work completed” • Start-up and close-out costs: should be non-refundable, unrelated to subject enrollment, payable on contract execution • Final payment: not more than 10% withheld • Payment frequency: no less than quarterly for work performed • Items payable on invoice: limit these to items that will truly be sporadic or unpredictable (not as a way of making reimbursement conditional)

28. Resources • Good Clinical Practice Protocol Template • Clinical Trial Budget Template

29. Clinical Trials Submitted Successfully SPA Processes Bridget Foss 02.17.2009

30. Expedited Process for Industry Funded Clinical Trials This process allows SPA to negotiate the Agreement while the department is completing budget negotiations. Expedited PRF Package Includes: • Draft PRF signed by Principal Investigator • Draft Budget • Draft Protocol • Agreement (if available) * It is essential that a sponsor contact is included on the PRF for this process to be effective.

31. Standard (“Final”) PRF Package Proposals, non-industry funded trials, and industry funded trials after budget negotiation require the following: • Fully Routed PRF • Final Protocol • Negotiated Budget • TASCS Billing Grid

32. Is the trial investigator sponsored? Is the project an animal clinical trial or pre-clinical research? What is the appropriate F&A rate for this particular project? Industry Funded Clinical Trial: 26% TDC Non-Industry Funded Clinical Trial: 51% MTDC Pre-Clinical Research: 51% MTDC Questions to Consider During PRF Prep

33. Compliance Checks Compliance requirements for Investigators: • Approved REPA • Completed RCR training (or approved extension) SPA also checks the RSPP database for human subjects, animal subjects and/or IBC approvals. Please note that the title used on the PRF needs to match the protocol title approved by RSPP.

34. Advance Account • If costs are incurred prior to execution of the agreement, an advance account should be requested. • SPA attempts to insert language allowing pre-award costs; however, all pre-award costs are incurred at the department’s risk. • Departments often request advance account in order to complete Fairview submissions.

35. Agreement Negotiation • SPA reviews and negotiates the contract language for conformity with University policy, and works in consultation with the Office of General Counsel, the Office of Technology Commercialization, and the Principal Investigator. • Problem clauses may include publication, confidentiality, intellectual property, and indemnification. Negotiations take time!

36. Agreement Execution • If expedited process is used, SPA will not execute the agreement until it receives the final PRF package. • Compliance issues need to be resolved prior to execution and award set up. • Agreements are sent to the investigators for final review and or approval prior to University execution.

37. Award Set Up for Industry Funded Clinical Trials • Fixed price industry funded clinical trials are set up in accordance with the University procedure “Handling Industry Sponsored Clinical Trial Research Agreements.” • Accounts are initially set up for $0. Dollars are set up on the Project by Sponsored Financial Reporting as funds are received. It is the department’s responsibility to re-budget dollars into the appropriate accounts based on the budget.

38. Award Set Up for Non-Industry Funded Clinical Trials • Cost reimbursable awards and non-industry funded trials are set up based on the department provided and sponsor approved budget for the current period. Account set up, regardless of funding source, is subject to the terms and conditions of the agreement governing the project. Each project is handled on a case by case basis.

39. References • B&I Expedited Procedure: http://www.ospa.umn.edu/policiesandprocedures/B&Iclinicaltrials.html • F&A Rates: http://www.ospa.umn.edu/forms/rates/F&A.html • Advance Account Policy: http://www.fpd.finop.umn.edu/groups/ppd/documents/policy/Preaward_Policy.cfm • Openness in Research policy: http://www1.umn.edu/regents/policies/academic/Openness_in_Research.pdf • Handling Industry-Sponsored Clinical Trial Research Agreements: http://www.fpd.finop.umn.edu/groups/ppd/documents/procedure/clinical_trials_proc1.cfm