Clinical Trial Agreements
University of Kentucky faculty and staff participate in numerous clinical trial projects to study investigational drugs or devices. These studies are usually funded by pharmaceutical companies and are an important part of the process to assure the safety and efficacy of the drug or device, obtain Food and Drug Administration (FDA) approval and bring a product to market.
OSPA is responsible for reviewing, negotiating and legally accepting agreements from external funding sources. The resolution of many contractual issues requires coordination between the external funding source, Investigator and OSPA; the involvement of each party is essential to a successful contractual arrangement with mutually acceptable terms. Investigators should provide OSPA with a copy of the proposed agreement and a company contact person as early in the process as possible.
UK Research Foundation: Agreements should be made between the sponsoring company and The University of Kentucky Research Foundation (UKRF). UKRF is a non-profit, affiliated corporation of the University of Kentucky through which grants and contracts from external sponsors are received. Agreements from the sponsoring company must be reviewed by OSPA and signed by a UKRF official (see AR 7:3). Checks from the sponsoring company should be made payable to UKRF.
Although each document is reviewed on a case-by-case basis, there are a number of key issues which are common to most clinical trial agreements. These are summarized below.
It is often necessary for the sponsoring company to provide information of a proprietary nature to the Investigator and it is important to the company's business interests that the confidentiality of this information be protected. Written confidential information should be stamped as such and oral communication should be reduced to writing and stamped "confidential." Investigators and other University employees involved in the project may be required to sign a separate statement indicating they understand and will comply with the obligation to maintain confidentiality. Access to confidential information (including the protocol) must be strictly controlled and each Investigator should have a plan for assuring control.
Conflict of Interest
The University’s Conflict of Interest policy is applicable to all sponsored research. Investigators are required to complete a "Disclosure of Financial Interest Form" for each proposed study. Additional information on the University's Conflict of Interest policy is available on the Policies and Procedures page.
Facilities and Administrative Costs
Industry-funded Clinical Trials
Corresponding to the university’s new F&A (indirect) cost rate agreement effective July 1, 2017, F&A costs for industry-funded clinical trials will be assessed at the rate of 22.3% of total cash received. This is based on the actual calculated off-campus research rate of 28.7%. To estimate F&A costs when the direct costs are known, add 28.7% of the direct costs. The sum of the direct costs and F&A costs is the per-patient amount. For example, if $785 is needed to cover the direct costs of a clinical trial, 28.7% or $225 would be added for F&A, bringing the total to $1,010.
The definition of 'clinical trial' for the application of the industry-sponsored indirect rate is a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. These may also include prospective postmarket drug or device studies. Studies intended solely to refine measures and studies that involve secondary research with biological specimens or health information are not clinical trials.
Failure to meet these criteria may exclude an industry-sponsored study from eligibility for reduced F&A costs but should not be used to determine independent requirements for IRB approval, ClinicalTrials.gov registration or additional regulatory oversight.
Federally-funded and Flow-through-from-federal Clinical Trials
The budget for federally-funded or flow-through-from-federal clinical trials should be calculated at the university’s negotiated research rate of 53% Modified Total Direct Costs unless restricted by the sponsor. Federal agencies, including the National Institutes of Health, do not typically limit F&A on clinical trials. Correspondingly, the university’s F&A rate agreement does not include a separate rate for clinical trials funded by the federal government.
Clinical trials are usually funded on a per-patient basis with provisions for pro-rated payment for patients who do not complete the study. All costs necessary to conduct the study, including salaries, supplies and Facilities and Administrative costs, should be considered when determining the fixed per-patient amount. It is also desirable to obtain an initial, non-refundable payment for the administrative efforts of starting the project and recruiting subjects.
Governing and Enforcement
Generic Drug Enforcement Act
Many agreements include a clause which requires a certification that the Principal Investigator and others participating in the study are not debarred, and have never been debarred, under the Generic Drug Enforcement Act of 1992. The University must notify the company of any debarment or threat of debarment occurring during the term of the study. Investigators and others involved in the study may be required to sign such a certification.
Agreements must either be governed by the laws of the State of Kentucky or this provision must be absent from the agreement.
The Investigator must obtain approval of the study protocol and informed consent form from the University Institutional Review Board (IRB) before a subject may be enrolled in the study. A sponsoring company usually requires evidence of IRB approval before sending the study drug.
The drug or device being tested in the clinical trial is normally owned by the sponsoring company and already covered by patent protection. Although each situation must be reviewed on its own merit, it is the University's general policy that title to inventions arising from projects conducted by faculty, staff or students will be owned by the University. Clinical studies usually afford the sponsoring company the right of first refusal to obtain an exclusive, worldwide, royalty-bearing license to discoveries arising from the conduct of the study.
indemnification and insurance
The sponsoring company, and the actual owner of the study drug or device if an intermediary is involved, must agree to indemnify and hold harmless the University, UKRF, Investigators, trustees, officers, agents and employees from any and all liabilities, claims, actions or suits for personal injury or death arising from the administration of the study drug. The complete indemnification statement will have certain limits and conditions designed to protect both parties.
To support the above indemnification the sponsoring company must maintain a sufficient level of insurance.
publications records data
Agreements must allow the Investigator the freedom to publish study results. However, the company may have the right of prior review to identify proprietary information.
Records and Data
The University must retain possession of original data and any medical records generated by the study. The sponsoring company usually provides forms on which to record relevant subject information; the originals of these forms may be forwarded to the company with a copy retained by the University.
Reimbursement of Subject Injury Costs
The agreement shall include a provision that the sponsoring company will reimburse the cost of reasonable and necessary medical expenses incurred by a study subject as a result of participation in the trial, provided such expenses are in no way attributable to negligence on the part of the University.
To obtain a University account number for the project the following documentation is required: a fully routed electronic Internal Approval Form (IAF) and Fixed-Price Agreement Budget Form (pdf, 1pg), a Financial Conflict of Interest Disclosure, a copy of the study protocol, a signed written agreement between the sponsoring company and UKRF, and Institutional Review Board (IRB) approval. The account budget will be established for a period of two years and based on actual cash from the sponsoring company and increased each time payment is received.
A standard extension may be requested when the account is set to close, but the study is ongoing. It is appropriate when the study is still IRB-approved, and the contract term has not ended. If IRB approval has ended with no expectation of continued approval, a standard extension is not an appropriate option.
To request a standard extension, please send to the OSPA Research Administrator (RA): 1) IRB approval letter showing the study is currently approved, and 2) a completed Prior Approval Request for Revision/Action on Sponsored Project Account (pdf, 1pg) form or an email including a justification for the extension. The account will be extended for a period of one year and can continue to be extended for additional one-year periods if work is continuing and the above conditions are met.
The RA will check conflict of interest (“COI”) disclosures for all personnel listed on the IAF before extending.
This option may be requested when the IRB approval has ended but there is still work left to be done and it does not involve contact with human subjects. Each of the following must be true for the No-IRB Extension to be approved:
The OSPA RA has received a signed and fully-completed No-IRB Extension Memo;
The PI/department’s planned activity consists of more than just waiting on payment (i.e., activity that should result in charges to the account such as data entry or coordination with the sponsor on closeout activities);
The study is not federally funded; and
An extension would not contradict any term in the clinical trial agreement, contract, award or guidelines.
To request a no-IRB extension, please send the following information to the OSPA RA: 1) a signed No-IRB Extension Memo, and 2) a completed Prior Approval Request for Revision/Action on Sponsored Project Account (pdf, 1pg) form or an email including a justification for the extension. The account will be extended for a period of six months with an additional extension possible if approved by the OSPA Executive Director.
Final Financial Report (FFR) Extension
If the study is completed and no additional charges will be placed on the account, but payment is expected, the account will be closed by the Research Financial Services (RFS) Financial Administrator (FA) who will extend the date of the Final Fiscal Report (FFR). The account will be placed in closed status, but it will not be financially closed out until after the expected payment is received; however, the total extension period cannot exceed 18 months from the study’s original end date. New charges will not be able to be posted to the account, as it is in closed status.
To request extension of the FFR, please notify the OSPA RA and RFS FA that Study is completed but payment is expected. Include the amount of the payment and its anticipated receipt date in the email.
Internal Approval Form
A University Internal Approval Form (IAF) must be completed, signed and provided to OSPA for each clinical study. In addition, a Fixed-Price Agreement Budget Form (pdf, 1pg) with Column A completed should be attached to the IAF. A Financial Conflict of Interest Disclosure form is also required.
At the conclusion of any fixed-price agreement there may be a cash balance remaining. If expenditures incurred to conduct the study are reasonable in relation to the projected cost and when all costs (direct and Facilities and Administrative Costs) have been properly charged and documented, the cash balance will be made available to the Investigator.
A note regarding other types of agreements: Projects which do not involve human clinical activity are subject to different Facilities and Administrative Cost rates than those noted above. They may also have different administrative requirements such as approval by the Institutional Animal Care and Use Committee (IACUC) if animal subjects are used.
For more information please contact the Office of Sponsored Projects Administration (OSPA) at 257-9420. OSPA has a model agreement available on this page which may be given to a prospective sponsor as an example to be used in whole or in part.