Negotiation of Clinical Trial Agreements
Sponsored Programs Administration (SPA) is responsible for reviewing, negotiating, and executing agreements, including clinical trial agreements (CTAs), from external funding sources (e.g., pharmaceutical companies). As a public, nonprofit educational institution, the University is bound by certain policies and regulations regarding what it can and cannot accept in a CTA. These policies are designed to protect the welfare of individuals participating as a research subject; foster the University's basic mission of teaching, research, and public service; and minimize the various forms of liability associated with human research.
Principal Investigators (PIs) are encouraged to discuss all aspects of the clinical trial with SPA prior to the start of negotiations. For instance, apprising SPA of the PI's involvement in the protocol development and/or study design raises intellectual property implications that may result in the negotiation of different or additional contractual terms.
The contractual language proposed by the University during contract negotiations is predicated upon the following:
- That the clinical investigation is conducted under a protocol that is a FDA Phase I, II, II, or IV drug study or a FDA regulated medical device study;
- That the sponsor provides its proprietary product (e.g., drug and/or device) to the University for the purpose of conducting the sponsor-initiated or investigator-initiated clinical trial;
- That the sponsor provides its study protocol to the University, if it is a sponsor-initiated clinical trial
- That the PI is the author of the study protocol, if it is an investigator-initiated clinical trial; and
- That the sponsor will fully fund the cost of the study (i.e., no work will be supported in whole or in part with other funds),
When negotiating CTAs, the University's primary focus is on securing acceptable contract clauses regarding high-risk issues (e.g., indemnification, confidentiality, publication rights, data ownership, patent rights, and subject injury).
Although each agreement is reviewed on a case-by-case basis, there are a number of key contractual provisions that are common to most CTAs. Some of those provisions and the accompanying explanation as to the University's handling thereof are as follows:
PARTIES TO THE AGREEMENT
CTAs should only be made by and between the study sponsor and The Regents of the University of California, on behalf of its Riverside campus. The PI, although an employee of UCR, does not have the delegated legal authority to enter into CTAs on behalf of The Regents and, therefore, may not be a named party to the agreement. That said, an acknowledgement block may be included at the end of the CTA whereby the PI may acknowledge that s/he has read the terms of the CTA and understands his/her obligations to comply therewith.
Note: Since UCR does not own a medical facility conducive to conducting clinical trials, UCR will need to contract with another entity for the use of their clinical facility and/or clinical support services. While such contractual arrangement will typically be handled in a separate agreement (e.g., subcontract) between The Regents and that other entity, there could be instances where a study sponsor, instead, may require such other party to be a named party to the CTA.
CTA typically contain a payment schedule which includes a per subject fixed-price. Such schedules usually provide for periodic payments at regular intervals or payments upon the completion of milestones (e.g., enrollment of a certain percentage of subjects, submission of a certain number of case report forms, etc.).
The University cannot underwrite expenses for the sponsor; therefore, the University requires a minimum advance payment, typically between of 10-20% of the total anticipated cost, upon execution of the agreement. When a project involves significant start-up costs, the University may require a larger initial payment.
When conducting a sponsor-initiated clinical trial whereby the sponsor is the author of the protocol, the University is following the sponsor's instructions. As a public, non-profit educational institution, UCR cannot bear the financial responsibility for any injury (including damages) resulting from the performance of such a clinical trial. Consequently, UCR requires the sponsor to maintain a policy or program of insurance sufficient to support its indemnification obligation. The sponsor's obligation to assume all financial responsibility, however, does not apply to injury that is: (i) caused by UCR's failure to adhere to the protocol; (ii) failure to comply with FDA or other governmental requirements; or (iii) caused by the negligence of a faculty member or the University.
UCR must maintain an open academic environment to fulfill its mission, and meet its fiduciary responsibilities, as a public educational institution. Clinical trials involving the use of a sponsor's confidential information should be limited to that information necessary for the performance of the clinical trial, and clearly identified by the sponsor as confidential.
Raw source data or documentation generated by the University during the conduct of a clinical study cannot be considered to be owned by the sponsor, nor can it be considered or treated as confidential information.
In addition, any agreements entered into by the University are subject to public disclosure under the State of California Public Records Act.
Timely publication and dissemination of research/study results are important principles behind the academic freedom afforded to each UCR faculty member. The publication provision, however, may provide a sponsor with a pre-publication review and comment period during which the sponsor may request the removal of its confidential information from the proposed publication. Additionally, the sponsor may promptly make arrangements for the protection of its intellectual property prior to publication. UCR is also willing to delay dissemination of study results for a reasonable period of time to accommodate multi-site studies. However, the resulting agreement cannot restrict UCR faculty from freely publishing UCR's research/study results.
Sponsors of UCR research are usually granted patent rights in accordance with University policies. However, UCR may grant greater rights to sponsors of sponsor-initiated clinical trials that meet all of the following criteria:
- The clinical investigation is an FDA Phase I, II, III or IV drug study or an FDA regulated medical device study.
- The sponsor provides its proprietary product and study protocol to the University for the clinical investigation.
- The cost of the clinical investigation, conducted according to the sponsor's protocol, is fully funded by the sponsor and is not supported, in whole or in part, with any other funds, including Federal funds, gift funds or foundation funds.
- There are no known third-party rights to intellectual property of The Regents that would be compromised by granting rights to the clinical trial sponsor.
- All University requirements regarding the administration of agreements with private sponsors for drug and device testing using human subjects have been satisfied.
If all of the above criteria are met, UCR may grant to the sponsor a certain range of rights to inventions made in the direct performance of the clinical trial protocol; provided, however, that with regard to Phase III or IV trials, there must have been little or no investigator involvement in the conception or development of the protocol. Notwithstanding the foregoing, UCR reviews patent terms on a case-by-case basis and prefers to do so with a thorough understanding of the work contemplated.
As a matter of UC policy, in the event a study subject is injured resulting directly from the administration of study drug or the study procedures carried out in accordance with a sponsor-designed protocol, UCR will provide reasonably necessary medical treatment. UC policy specifically prohibits billing the study subject or a third-party for the costs of treating such injuries. Therefore, UCR requires reimbursement for the cost of such treatment from the sponsor. Human subject welfare is a primary concern for the UCR and exceptions to these terms cannot be accommodated.
To support its indemnification obligations, the sponsor must maintain a sufficient level of insurance.
The University of California is self-insured and, during the term of the agreement, will maintain in force adequate insurance to cover its indemnification obligations.
The University of California is a constitutional corporation of the State of California and contracts accepted by the University are to be interpreted under California Law. UCR will also consider contractual silence regarding this issue.
Each of the parties to the CTA must have the ability to terminate, upon the giving of reasonable notice. In the event of early termination, UCR will seek reimbursement from the sponsor for all costs and uncancellable obligations incurred up to the date of termination. In addition, untimely withdrawal from the protocol could jeopardize the welfare of human subjects; therefore, the UCR shall request that the sponsor cooperate with UCR to safely withdraw subjects from the protocol.
USE OF NAME
California Education Code Section 92000 provides that the use of the name "University of California" is the property of the State of California and that the sponsor's use of such name, campus, or logo must also comply with such section. Accordingly, the sponsor is prohibited from using UCR's name in connection with any advertisement, press release, or other form of business promotion or publicly, or to suggest that it endorses a product or service. A sponsor may, however, use UCR's name to fulfill its obligations as required by law, or by otherwise requesting prior written approval from UCR.