Easing the Burden on the Clinical Site Kathy Kioussopoulos, RN Director, Interventional Cardiology Clinical Research University of Colorado Health Sciences Center March 24, 2007

Challenges for the Clinical Site A majority of clinical trial budgets are paid on a “per patient” fixed fee Very difficult to predict patient enrollment The site must maintain study personnel in order to staff the study Payments only happen after enrollment and monitoring Sites end up supporting the start-up costs for the study

How involved are you in the budget process for the trials done at your site? Very involved Somewhat involved Not at all involved Does not apply

How involved are you in the budget process for the trials done at your site? Very involved Somewhat involved Not at all involved Does not apply

Sample Device Study Early Phase Pivotal Device Trial Projected enrollment of 20 patients Average per-patient payment to site: $12,800 Required study visits: one outpatient hospital visit with device implant Pre-implant clinic visit One follow-up clinic visit at one year

Sample Device Budget Direct Costs $ Amount Personnel Salaries and Wages $31,377 Benefits $9,099 Hospital Patient Care Cost $205,000 IRB Review $1,800 Other Expenses Total Direct Costs $247,276 Institutional Overhead (indirect costs) $10,523 Total Direct/Indirect Costs $257,799

Sample Phase II Outpatient Drug Trial Per patient amount: $4,964 Projected enrollment of 20 patients Required visits include 10 clinical visits (including 2 phone contacts)

Sample Drug Trial Budget (Phase II Outpatient Study) Direct Costs $ Amount Personnel Salaries and Wages $18,260 Benefits $5,296 Hospital Patient Care Cost ($3,390/pt) $67,800 IRB Review $1,800 Other Expenses Total Direct Costs $93,156 Institutional Overhead (indirect costs) $6,125 Total Direct/Indirect Costs $99,280

How much coordinator time does this buy? Device Study $40,476 (annual salary and benefits) = 913 hours for 20 patients, or 46 hours per patient Phase II Drug Study $23,556 (annual salary and benefits) = 531 hours for 20 patients, or 27 hours per patient

Clinical Workday Assumptions Study Visits (average 1 hour/visit) Non-Study and Screening Clinic Visits No-Show Clinic Appointment

Which of the following causes you the most frustration? Monitor/CRA turnover CRF/eCRF completion Protocol amendments SAE reporting Trial-specific conference calls Other

Which of the following causes you the most frustration? Monitor/CRA turnover CRF/eCRF completion Protocol amendments SAE reporting Trial-specific conference calls Other

Administration and Support Study Coordinator Tasks Daily Tasks CRF completion—2 hours /day Phone, fax, and/or e-mail—1 hour/day

Weekly Tasks Sponsor’s CRA monitoring visits Patient recruitment /chart review Lab shipments for study supplies Protocol review and staff meetings Data corrections/data queries Regulatory documents/IRB correspondence Collect and process AEs Read and implement protocol amendments Read and comment on new protocols Administer and explain informed consents

Monthly Tasks Site qualification visits Site initiation visits Site closeout visits In-services for hospital staff Filing of documents Ordering study supplies

Other Challenges

Regulatory Challenges for the Clinical Site Local IRB (annual training requirements for staff) Local Hospital Review committee—Veterans Administration Hospital versus University Hospital (annual compliance training requirements for staff) FDA-NIH regulatory compliance (how does site stay current?)

Study Management How do you maximize staff productivity and site viability?

Which of the following resources could be most helpful to you in resolving your challenges? Tools and Templates (i.e. budget, AE/SAE reporting guidelines, SOP, etc.) Training (Keys to building a successful research site, GCP, etc.) Ongoing discussion forums (online, sc symposia, etc.) All of the above Other

Which of the following resources could be most helpful to you in resolving your challenges? Tools and Templates (i.e. budget, AE/SAE reporting guidelines, SOP, etc.) Training (Keys to building a successful research site, GCP, etc.) Ongoing discussion forums (online, sc symposia, etc.) All of the above Other

Creating, Implementing, and Sharing Best Practices for Clinical Trials Networks Implement programs and tools to build site capability for the recruitment, retention, and performance of clinical research sites Professional development at the site Standardized tools to accelerate trial timelines Tracking and benchmarking of site metrics to improve performance and accountability

Building and Expanding Site Capability Certification/training in protection of human subjects Comprehensive program on good clinical research practices Evidence-based medicine educational series Practice of conducting trials Yearly symposia and network e-newsletters Access to DCRI research conferences Clinical research writing education series

Background: Clinical Research Problems & Gaps Site Capability Fundamentals of clinical research Human subjects protection training Good clinical research practice Site Work “Tools” Budgets Contracts Recruitment/timelines Productivity metrics

Building Site Capability and Performance Dynamic Web page constructed with Study Coordinator Advisory Committee, delivering high-quality education tools for sites to access GCP Lessons from a Horse Named Jim Human Research Subject Protection Keys to Building a Successful Research Site Templates: SOPs, Source Documents E-newsletters DCRI Research Conference Evidence-Based-Medicine Educational Series Writing Series (abstracts, protocols, substudies, manuscripts)

Study Coordinator Advisory Committee Purpose To provide expert advice, feedback, and guidance to the CTNBP management team on the implementation of program deliverables as they pertain to clinical research (site) networks

Responsibilities Develop strategies for ensuring successful collaboration between intradisciplinary network team members. Provide guidance on the planning, development, and delivery of educational materials and programs for use by the networks.

Responsibilities Act as site advocates to encourage abstract and journal publications specific to CTNBP networks. Recommend strategies to improve the overall conduct of clinical research trials by network sites.

Study Coordinator Advisory Committee Black Hill CRC St. Mary’s Medical Genesis Health Care Penn State Hershey Medical Univ. of Colorado Duke Methodist Hospital The Heart Center Study Coordinator Advisory Committee

Sample Study Budget https://www.ctnbestpractices.org/sites/studyops/studystartup/budgettemplate/

“Study Coordinators Hidden Costs” –Budget Considerations Patient Screening Costs – a. Talking to patients and families b. Mailing consents and materials c. Follow up on phone call and mailed consents (time!) d. Screen Failures and randomization failures (partial payment) Serious Adverse Event Follow up a. Getting medical records and data b. Follow up with patient and extra follow up c. Time reporting requirements dictate fast turn around(prioritization) Sponsor Audits/FDA Audits a. On site visits b. Lengthy monitor visits

“Study Coordinators Hidden Costs” –Budget Considerations Misc Supplies a. Dry ice b. Copies, faxes, mailing (some places may be able to use their overhead for this) c. Internet connectivity – e.g.; some studies want a dedicated line for their equipment. Queries! a. Some studies can generate 100’s of these and they dictate a turn around time that can be difficult to manage b. Query resolution can impact your reimbursement c. Does the PI have to sign off on the query? Can affect your turn around time…. d. Getting queries months after a study has closed or finished!

Recommended Strategies Negotiate an up front payment ( ask for all start up costs up front and include two patient payments in advance.) Review the CRF in advance (see if time provided and payment matches what would actually take) Review protocol carefully to determine what is standard of care for your site (ex: labs, ecg’s, clinic appointments) and make sure these items are included as a line item in your protocol. Don’t let more than one monitor come at a time, you should dictate how much of your coordinator time they get, not them. Pre-specify prior to the visit that you will give them a set amount of time during the visit. Negotiate a line item budget for the screen failures and non randomized patients