1. A Primer on Clinical Trials for the Research Administrator
David Lynch –
Executive Director of Office of Sponsored Research,
Northwestern University
Mike Ritz –
Research Compliance Officer,
University of Rochester
Tom Wilson –
Senior Research Administrator and Asst. Vice President
Rush University Medical Center

2. Contents of Chapter One “An Introduction to Clinical Research”
Definitions of Clinical Trial Terms
Phases of a Clinical Trial
Clinical Research Requirements
and Regulations
Clinical Trial Requirements and Regulations

3. Clinical Research Requirements and Regulations –
Protection of Human Subjects
FDA regulations
DHHS regulations
The Common Rule
While there are some differences, the basic
requirements of an institutional assurance approved
by DHHS, review of research by an IRB, the
informed consent of subjects, and education and
training are similar.

4. Clinical Research Requirements and Regulations -
Protection of Human Subjects
Human Subjects Protection Training
Individuals who will be involved in the design or
conduct of NIH-funded human subjects research
must fulfill the NIH education requirement.

5. Clinical Trial Requirements and Regulations -
Investigational New Drug (IND) Application
Current federal law requires that a drug be subject
of an approved marketing application before it is
transported or distributed across state lines. The
IND application is the means through which the
sponsor obtains the exemption.

6. Clinical Trial Requirements and Regulations -
Investigational Device Exemption (IDE)
Required prior to initiation of an investigational device study
Approval required from the Medicare Administrative Contractor and local carrier before Medicare can be billed for participants enrolled in a study.

7. Clinical Trial Requirements and Regulations -
Medicare Coverage for Clinical Trials
As stated in the National Coverage Determination, Medicare covers the routine costs of qualifying (as defined) clinical trials, as well as reasonable and necessary items and services used to diagnose and treat complications arising from participation in clinical trials.

8. Contents of Chapter Two “Preparing a Clinical Trial Budget”
Key Principles for Budgeting
Budgeting for Clinical Trials, other than Device Studies
Budgeting for Device Studies
Negotiation Tips
Appendix with Templates

9. Clinical Trials Other Than Device Studies
Prospective Reimbursement Analysis (PRA)
Identify all procedures, items and tests within a clinical trial and to whom they are billable
Two Steps
Is it a qualifying trial (as defined)?
If so, what costs can or cannot be charged to insurance?

10. Clinical Trials Other Than Device Studies
Text provides an example of a
template for documenting
the PRA.

11. Device Studies
Medicare reimbursement depends on the category the FDA assigns to the device
(Category A or Category B).
Costs associated with Category A devices are generally not covered by Medicare.
Device and routine costs associated with Category B devices might be reimbursable if approved by the Medicare Administrative Contractor.

12. All Studies – Participant Costs
Identify all encounters and tasks
Estimate costs of clinical procedures
Estimate cost of clinical team member time for tasks without billing codes

13. All Studies – Participant Costs
Text provides an example of
a template to budget
these costs.

14. All Studies – Non-Participant Costs
Text provides an example
of a template to budget
these costs.

15. All Studies – Non-Participant Costs
Ideal situation is for sponsor reimbursement to include (a) a per participant reimbursement reflective of only variable costs and (b) separately invoice-able provision for fixed costs.
If sponsor includes both fixed and variable costs in the per participant reimbursement, the recovery of fixed costs is then dependent on enrollment.
Text provides an example to demonstrate the financial risks associated with this scenario.

16. Indirect Cost Rate
Federal sponsor – use negotiated rate; remember there are costs excluded from the application of the rate
Non-federal sponsors – best practice is to have a documented policy (i.e. standard rate)

17. Inflation Considerations
Apply an inflation factor if the clinical study is anticipated to be active more than twelve months, considering
timing of expected enrollment; and
whether costs are concentrated to particular periods of the study
- Text provides examples of considerations

18. Negotiation Tips Consistent approach to budgeting and documentation
Consideration of deficits and surpluses
Timing of Payments

19. Contents of Chapter Three “Contracting with Industry”
Liability Issues
Confidentiality, Publication and Use of Data/Data Ownership
General Contract Terms
Intellectual Property
Appendix with Templates

20. Liability Issues Indemnification
One party’s obligation to take responsibility for the legal liability of another party
Insurance
Adequate amounts of insurance will be maintained by the sponsor throughout the study period and for some time afterwards.

21. Liability Issues Insurance Text contains “Risk Assessment and
Insurance Score Card”.

22. Liability Issues Subject Injury
Define who will be responsible for providing care to treat injuries and who will pay such costs

23. Confidentiality Generally requires the most negotiation
Openness in research and academic freedom versus secrecy and control of information
Define the term “Confidential Information” and the timeframe involved

24. Publication PI must have freedom to publish (written and unwritten).
Sponsor should never be given editorial rights, only the ability to review and comment.
Case study provided in text.

25. Use of Data / Data Ownership
Overarching principle is that the Principal Investigator may freely use the data generated by the study for future research and educational purposes.

26. General Contract Terms
The text provides and explains the terms and conditions often included in clinical trial agreements.
(Recitals, Period of Performance, Use of Name, Severability, Waiver, Notices, et cetera)

27. Intellectual Property (IP)
Maintain the institution’s right to use the IP that may be transferred to the sponsor (consistent with the institution’s research mission and non-profit status)

28. Contents of Chapter Four “Financial Oversight of a Clinical Trial”
Maintaining Participant-Level Information
Effort of Clinical Trial Team Members
Sponsor Reimbursement
Close Out
Appendix with Templates

29. Maintaining Participant-Level Information
Create a grid whereby each column corresponds to tasks conducted chronologically throughout the study for which the sponsor is to pay the cost
Each row is assigned to a participant enrolled in the study with respective dates the participant completes each procedure/visit.
Reconcile to the clinical study’s general ledger

30. Maintaining Participant-Level Information
Text provides an example of a grid

31. Effort of Clinical Trial Team Members
Allocate a reasonable percentage of each clinical trial team member’s effort directly to each clinical trial account
During each trial’s life, staff can account for time spent on trial activities to assist with reasonableness of allocations.
Reconcile to the clinical study’s general ledger

32. Sponsor Reimbursement
When payment is based on case report forms, ensure completeness of payments received.
When payment is based on milestones and associated invoice preparation
Maintain a list of invoices sent and payments received
Follow-through on unpaid amounts
Adopt standard payment terms

33. Close Out
Require a thorough review of final clinical study account balances
Identify reasons for deficits or residuals
Text provides an example of a policy regarding usage of clinical study residuals.

34. Contents of Chapter Five “Other Institutional Considerations”
Conflict of Interest
Billing Compliance
Unrelated Business Income
Centralized and External IRB Review
Clinical Research Administration Organization
Standard Operating Procedures
Appendix with List of Regulations Related to Clinical Research

35. Conflict of Interest
Public Health Service issued regulations to provide standards to manage, reduce or eliminate financial conflicts of interest.
Applies to IRB members, investigators, study coordinators, the institution, and others
Real or potential conflicts

36. Billing Compliance Adoption of Clinical Research Billing Policy
Education and training of employees
Mandatory billing plan/billing grid
Implement scheduling and registration controls
Implement clinical trial management system that verifies correct billing
Perform routine internal auditing

37. Unrelated Business Income
Academic medical centers may be required to pay taxes on business income that is unrelated to the entity’s tax-exempt purpose.
Avoid tax by establishing institutional policies interpreting its educational and research missions and strategic research operations

38. Unrelated Business Income
Conducting research is an exempt activity if “scientific research” is carried out in the “public interest”.
Best practice is a formal policy which requires, or encourages, publication of research results in a timely manner.

39. Organization Structure
No “right way” – it depends on the culture or tradition of the institution
Centralization
Advantages and disadvantages
Decentralization

40. Thank you!