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Clinical Trials Submitted Successfully – Session #12Clinical Trials Submitted Successfully – Session #12

Heritage GalleryHeritage Gallery

Presenters: Presenters:

Laura Williams – Sponsored Projects AdministrationLaura Williams – Sponsored Projects Administration

Debra Dykhuis – Office of Clinical ResearchDebra Dykhuis – Office of Clinical Research

Bridget Foss – Sponsored Projects AdministrationBridget Foss – Sponsored Projects Administration

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According to clinicaltrials.gov, there are approximately how many open clinical studies underway

in the state of Minnesota?

Clinical Trials Trivia Time

1,231

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Order of Presentation

Laura Williams – Feasibility Considerations Laura Williams – Feasibility Considerations in Clinical Trialsin Clinical Trials

Debra Dykhuis – Budgetary Considerations Debra Dykhuis – Budgetary Considerations in Clinical Trialsin Clinical Trials

Bridget Foss - SPA Submission Processes and ShortcutsBridget Foss - SPA Submission Processes and Shortcuts

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Feasibility Considerations in Clinical TrialsFeasibility Considerations in Clinical Trials

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What We’ll Cover Today Protocol Review

Considerations Ethical Considerations Business Considerations Scientific Review Institutional Review Regents Policies

Certainly not to be ignored, but not covered today:FDAGCPICHInvestigator-sponsored clinical trials

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Protocol Review Considerations

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◦ Population

◦ Staff

◦ Space

◦ Technical capability

Feasibility

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Profitability

◦ Cost per subject

◦ Complexity of protocol

◦ Duration of study

◦ Survivability

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Scientific Merit

◦ Adequate study design

◦ Main hypothesis

◦ Blinding, randomization

◦ Biostatistical methodology

◦ Endpoints

◦ Publishability

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Ethical Considerations

Target population Safety Severity of disease Availability of alternative treatments Side effects Peds / Elderly Underserved populations

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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

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Business Considerations

CRO involvement Past dealings with sponsor History of timely payments (or not!) SIV Process

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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

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Scientific Review

To be performed by independent, peer reviewers – no one from the research team

One of three methods must be utilized

1. Full peer review by grant committee of NIH, NSF or a foundation – excludes industry sponsored clinical trials; or

2. U of M scientific review committees;

or

3. 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.

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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

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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

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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

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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

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Estimating Personnel Time and Optimizing Payment TernsDebra Dykhuis

02.17.2009

Clinical Trials Submitted Successfully

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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

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What is at stake?

Quality of the data Speed of accrual Attention to compliance Prospects of getting future research funding Staff burnout/turnover Jobs

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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

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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

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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.

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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

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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)

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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)

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Resources

Good Clinical Practice Protocol Template

Clinical Trial Budget Template

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SPA ProcessesBridget Foss02.17.2009

Clinical Trials Submitted Successfully

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This process allows SPA to negotiate theAgreement 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.

Expedited Process for Industry Funded Clinical

Trials

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Proposals, non-industry funded trials, andindustry funded trials after budgetnegotiation require the following:

Fully Routed PRF Final Protocol Negotiated Budget TASCS Billing Grid

Standard (“Final”) PRF Package

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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% TDCNon-Industry Funded Clinical Trial: 51% MTDC

Pre-Clinical Research: 51% MTDC

Questions to Consider Questions to Consider During PRF PrepDuring PRF Prep

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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.

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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.

Advance Account

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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!

Agreement Negotiation

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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.

Agreement Execution

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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.

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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.

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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

References

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