Clinical Trials

UCI faculty and staff participate in numerous clinical trial projects to study investigational drugs or devices.  Such studies may be conducted under an industry-developed protocol or an investigator-developed protocol. These studies are most often conducted in conjunction with obtaining new drug (under Phase I, II, III, or IV) or device approval from the U.S. Food and Drug Administration (FDA), although they can be designed with the sole purpose of collecting and analyzing data about approved drugs or devices in order to contribute to medical knowledge about the treatment of a disease or medical condition.
Sponsored Projects Administration (SPA) is responsible for reviewing, negotiating and legally executing agreements from external funding sources. The resolution of many contractual issues requires coordination among the external funding source, Investigator and SP; the involvement of each party is essential to a successful contractual arrangement with mutually acceptable terms.

Confidential Disclosure Agreements

A company may want to send a protocol to the Principal Investigator (PI) so that he/she can decide whether to participate in the trial. The protocol may have confidential information that the company needs to safeguard. The mechanism to protect the confidential information is the execution of a Confidential Disclosure Agreement (CDA).  Please note that some sponsors do not require a CDA prior to releasing a protocol.

Once a sponsor or Contract Research Organization (CRO) has identified UCI as a potential site for a clinical trial, a CDA may be sent to the PI. In order to protect the University and the PI, all incoming CDA’s requiring University signature need to be reviewed, negotiated and executed by Sponsored Projects (SP).

CDAs are usually straightforward and require little negotiation; however, some CDAs can include requests that SP cannot honor. For example, as a State of California educational institution, the University cannot subject itself to the laws of other states.

To process the CDA:

  • Send the CDA to Garrett Larsen, Principal Contract Officer, at glarsen@uci.edu.
  • Include the name, address, telephone number and email address of the sponsor or CRO contact.
  • If needed, include a note with any concerns about the CDA.

Once the terms of the CDA have been negotiated, SP will execute the agreement and send the partially executed agreement to the sponsor or CRO for signature.

Once SP receives a fully executed CDA, the agreement will be processed and a copy will be sent to the PI for his/her files.

Master CDAs

UC Office of the President and UC Irvine have master CDAs in place with several sponsors. When dealing with the following entities, please inform them to use our master CDA:

Abbott
AbbVie
Amgen
Astellas
AstraZeneca
Beigene
Boehringer Ingelheim
Bristol-Myers Squibb Company
Chiltern
Covance
Eli Lilly
Frenova
Innovaderm
Iqvia
Merck
Novartis
Pharmaceutical Research Associates
Pharmacyclics
PPD
Sanofi US Services Inc

As of 7/14/2020

The Starting Point

The institutional review and endorsement of clinical trial protocols to for-profit sponsors also requires a submission of a proposal to Sponsored Projects.  When participation in an Industry Sponsored Clinical Trial appears likely, submit to Sponsored Projects in Kuali Research the documents listed below. These documents are required to begin contract negotiation.

  • In Kuali Research, the clinical trial questions under the "Questions" tab, within the "Compliance" panel must be answered
  • Form 700-U Financial Disclosure for Principal Investigator and/or Co-Principal Investigator (original to be forwarded to Office of Research) (no longer required after 9/25/17- for more information, click here)
  • Draft Budget
  • Clinical Trial Protocol
  • Draft Clinical Trial Agreement (CTA) or Draft Contract, if provided by sponsor

While the contract or CTA negotiation process proceeds, the PI and study team should proceed with other required startup activities, including developing and negotiating the budget.

Investigators should notify their assigned Principal Contract Officer as soon as possible when initiating a clinical trial supported by a for-profit sponsor. The review of the proposal and negotiation of the clinical trial agreement requires time and cannot be left to the last minute.

Sponsored Projects can begin to negotiate a clinical trial agreement prior to IRB approval. However, the clinical trial cannot commence until the IRB approves the protocol and Sponsored Projects has signed the clinical trial agreement.


Helpful Tools

Clinical Trial Decision Tree

The clinical trial decision tree is a visual aid designed to help assess whether industry-funded studies qualify as clinical trials under the UC definition.

Investigator-Initiated Trials (IITs) Toolkit

IITs require special consideration in the planning stages. UC Braid's IITs toolkit provides guidance on starting up an IIT to facilitate efficient contracting and move the trial forward as quickly as possible.

Negotiation of Clinical Trial Agreements

UCI 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.

Sponsored Projects (SP) is responsible for reviewing, negotiating and legally executing agreements from external funding sources. The resolution of many contractual issues requires coordination among the external funding source, Investigator and SP; the involvement of each party is essential to a successful contractual arrangement with mutually acceptable terms.

As a public, nonprofit educational institution, the University is bound by certain policies and regulations regarding what it can and cannot accept in a clinical trail contract. These policies are designed to protect the welfare of individuals participating as research subjects, foster the University's basic mission of teaching, research and public service, and minimize the various forms of liability associated with human research.

For-profit private sponsors, such as pharmaceutical companies, are motivated by different forces than the University. As a result, they sometimes do not understand the ideals and principles behind our policies. Consequently, additional time may be required for contract negotiations while SP works with the sponsor to arrive at a mutually acceptable agreement.

When negotiating clinical trial contracts, the University primarily focuses on securing acceptable contract clauses regarding high-risk issues such as subject injury, indemnification, confidentiality, ownership of data, patent rights and publication rights.

The University's standard clinical trial agreement and the clauses proposed by the University during contract negotiations are based on the following assumptions:

  • 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 and study protocol to the University for the purpose of conducting a clinical trial; and
  • That the sponsor will fully fund the cost of the trial (i.e., no work will be supported in whole or in part with other funds, including Federal funds).

Principal Investigators should discuss all aspects of the clinical trial with their Contracts Officer prior to the start of negotiations.  The involvement of UCI faculty in protocol development and/or study design creates additional issues that both parties must fully address. As a result, different or additional contract terms must be negotiated.

Investigators should provide SP with a copy of the draft clinical trial agreement (CTA), protocol, and a company contact person as early in the process as possible.  If a Master Agreement between the Sponsor and the University of California exists already, the negotiation process will typically be expedited.  IRB approval is not required in order to submit the proposal to SP and begin contract negotiations.

Although each document is reviewed on a case-by-case basis, there are a number of key issues that are common to most clinical trial agreements. These following items will be negotiated by SP with the sponsor:

AGREEMENT PARTIES

All Clinical Trial Agreements should be only between The Regents of the University of California and the Sponsor. The Investigator is an employee of the institution and should not be a named party to the Agreement.

FINANCIAL ARRANGEMENTS

Generally, the University negotiates a firm fixed-price per subject contract with a payment schedule. 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 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.

As a public-supported institution, UCI must recover the full cost of research conducted for outside sponsors, including all associated operating costs (overhead). To do otherwise would result in subsidizing for-profit research with public funds. Overhead costs are facilities and administrative (F&A) costs incurred in support of the University's research infrastructure. The University pools its overhead costs for ease of accounting because it is difficult to assign these costs with a relative degree of accuracy to a specific project or program. The federal government's Office of Management and Budget establishes the standards for calculating the indirect cost rate and UCI negotiates its rates with the United States Department of Health and Human Services audit agency on a periodic basis. The University derives its overhead rate for clinical studies from applicable components of the federally approved rate.

Our facilities and administrative (indirect) costs web page contains more information about F&A costs and current applicable F&A rates.

INDEMNIFICATION

When conducting a sponsor-designed clinical trial protocol, the University is following the sponsor's instructions. As a public, non-profit educational institution, UCI cannot bear the financial responsibility for any injury or damages resulting from the performance of the clinical trial. Consequently, UCI requests that the sponsor maintain a policy or program of insurance sufficient to support this obligation. The sponsor’s obligation to assume all financial responsibility does not apply to injury or damage to the extent caused by: 1) UCI's failure to adhere to the protocol; 2) UCI's failure to comply with FDA or other governmental requirements; or 3) the negligence of a faculty member or the University.

CONFIDENTIALITY

UCI must maintain an open academic environment to fulfill its mission and meet its fiduciary responsibilities as a public educational institution. Clinical studies involving the use of a sponsor’s confidential information will be accepted if: (1) the extent of confidential information shared with the University is limited; (2) the information is clearly identified by the sponsor as confidential: and (3) the sponsor agrees that the University will not be financially liable for disclosure. The University cannot accept projects requiring overly-broad access and use restrictions or elaborate data protection procedures.

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.

PUBLICATION

Timely publication and dissemination of research/study results are important principles behind the academic freedom afforded to each UCI faculty member. However, the sponsor may want to comment on the content of such publications, make arrangements for the protection of intellectual property, or ensure that sponsor confidential information is not improperly disseminated in such publications. These are legitimate business concerns and UCI is willing to work with sponsors to address these concerns. However, the resulting agreement cannot restrict UCI faculty from freely publishing research/study results.

UCI negotiates CTAs that address the needs of both parties by providing the sponsor with a pre-publication review and comment period. The sponsor may also request that their confidential information be removed from the proposed publication. UCI is also willing to delay dissemination of study results for a reasonable period of time to accommodate multi-site studies.

INTELLECTUAL PROPERTY

Sponsors of University research are usually granted patent rights in accordance with University policies. However, the University may grant greater rights to sponsors of studies 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 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, the University may grant to the sponsor a certain range of rights to inventions made in the direct performance of the clinical trial protocol. The terms contained in the standard clinical trial agreement are used for Phase III or IV trials meeting the above criteria and involving little or no investigator involvement in the conception or development of the protocol. However, the University reviews patent terms on a case-by-case basis and prefers to do so with a thorough understanding of the work contemplated.

SUBJECT INJURY

As a matter of University policy, in the case of subject injury resulting directly from study drug administration or study procedures carried out in accordance with the sponsor-designed protocol, the University will provide reasonably necessary medical treatment. University policy specifically prohibits billing the subject or a third-party for the costs of treating such injuries. Therefore, the University requires reimbursement for the cost of such treatment from the sponsor. Human subject welfare is a primary concern for the University and exceptions to these terms cannot be accommodated.

INSURANCE

To support the above 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 adequate insurance to cover its indemnification obligations.

GOVERNING LAW

The University of California is a constitutional corporation of the State of California and contracts accepted by the University also will be interpreted under California law. The University will also consider contractual silence regarding this issue, but cannot negotiate any other terms.

TERMINATION

Generally, either party must have the ability to cancel the agreement by giving reasonable notice. In the event of premature termination, the University will seek reimbursement from the sponsor for all costs and uncancellable obligations incurred up to the termination date. In addition, untimely withdrawal from the protocol could jeopardize the welfare of human subjects. Therefore, the University requests that the sponsor cooperate with the University to safely withdraw subjects from the protocol should thirty days notice not be sufficient.

USE OF NAME

California Education Code Section 92000 prohibits the use of the University’s name to suggest that it endorses a product or service. A sponsor may use the University’s name to fulfill their obligations as required by law, or by otherwise requesting prior written approval from the University.

Master Agreements

Master Agreements are agreements that embody agreed-upon terms and conditions of a basic relationship between the University and a sponsor.

Once a Master Agreement is in place, an "addendum" or "study letter" is typically generated for each new study to be done under the Master Agreement. The Addendum sets forth the items particular to a certain study such as dollar amount, protocol name, and principal investigator. These Addenda are "attached" to the Master Agreement. This alleviates the need to negotiate the main terms of the agreement, as the majority of the terms are agreed upon and only the particulars need to be negotiated.

We currently have many Master Agreements in place and the UC Office of the President is working on several more. When dealing with the following sponsors, please inform them to use our Master Agreement:

  • Abbott
  • Abbott Vascular (Abbott Device Subsidiaries)
  • AbbVie
  • Aimmune Therapeutics
  • Alexion
  • Alkermes
  • Allergan
  • Alpha Oncology
  • ArcherDX
  • Arcus Biosciences
  • Amgen
  • Astellas
  • AstraZeneca
  • Atara Biotherapeutics (Template agreement)
  • Bayer
  • Biogen – IDEC
  • Boehringer Ingelheim
  • Bioverativ Therapeutics
  • Bristol Meyers Squibb
  • Clovis
  • Cook
  • Eli Lilly
  • EMD Serono
  • Geltex/Genzyme
  • Genentech
  • Gilead
  • GOG Foundation
  • Heron Therapeutics
  • Macrogenics
  • Merck
  • Novartis
  • Opko Biologics
  • Pfizer
  • Pharmacyclics
  • Pharm-Olam
  • Philips (Investigator-initiated studies)
  • Schering-Plough
  • Seattle Genetics
  • Teva
  • Tocagen
  • TG Therapeutics
  • UCB Biosciences
  • Viracta

The University of California has also adopted the Accelerated Clinical Trial Agreement (ACTA).  The ACTA provides a standardized template for industry-sponsored, multi-center studies thus streamlining the contracting process.

As of 02/08/2021

Clinical Trial Budget Considerations

Generally, industry sponsors are concerned with the total cost of conducting a project rather than the classification of costs.  As a consequence, the structure of most clinical trial budgets differs from that of grant proposal budgets.  Sponsor-provided budget templates are typically separated into up front costs, per patient costs, and items to be invoiced on an as needed basis.  Other budget issues for considerations are listed below:

Departmental Administrative Expenses

When preparing and negotiating the budget for an industry sponsored clinical trial (not investigator-initiated), be sure to cover all costs associated with conducting the trial.  Due to the unique administrative nature of clinical trials and the reduced facilities and administrative rate currently being applied to clinical trials, charging administrative expenses is required and may be recovered as a direct charge and/or by assessment of an administrative fee.

Patient Care Costs and Coverage Analysis

To obtain a coverage analysis and current research rates for patient care costs, including Pharmacy services, see Clinical Research Finance Assessment (CRFA).

Research Services

The Institute for Clinical Translational Science (ICTS) offers a variety of services to support clinical and translational studies.  For more information, see Institute for Clinical and Translational Science services.

IRB Fees

The Institutional Review Board (IRB) charges fees for the review of clinical trials from for-profit sponsors.  For a current listing of fees, please see the IRB Fees sheet.

Facilities & Administration Fees

Be sure to use the appropriate F&A rate for your study.  Further details and information is available at Facilities & Administration Fees and FAQ's about applying F&A for clinical trials.

Travel

Costs for travel to Investigator's Meetings or other study-related meetings may be managed in a variety of ways.  Be sure to clarify how such costs should be incorporated into your study budget, if appropriate.  See Special Travel Considerations for Trials for more information.

Launching and Conducting the Trial

Launching Recruitment

Coming Soon

Clinical Trial Site Visits

The ability of a sponsor of a clinical trial to conduct a site visit depends upon who authored the protocol – the Sponsor or the Principal Investigator (PI).  A clinical trial where the protocol is written by the Sponsor is referred to as a Sponsor-Initiated Clinical Trial.  A clinical trial where the PI is the author of the protocol is referred to as a PI-Initiated Clinical Trial.

Sponsor-Initiated Clinical Trials

Under Sponsor-Initiated Clinical Trials, the sponsor or its authorized representative will be entitled to examine, at mutually agreeable times during normal business hours, the facilities where the clinical trial is being conducted, the trial data, and other relevant information necessary to confirm that the trial is being conducted in accordance with the terms of the clinical trial agreement, the protocol, and applicable laws and FDA regulations.  A Sponsor or its representative that is provided access to source records for the purpose of monitoring or auditing the clinical trial cannot make a record of or disclose direct identifiers of any participating patient in the trial (including the patient’s name, street address, telephone, social security, medical record, or health plan beneficiary numbers). In the event that copies of the original source records are to be made, all direct identifiers of patients participating in the clinical trial must be redacted prior to copying or taking copies of the source documents off site.

PI-Initiated Clinical Trials

Under PI-Initiated Clinical Trials, the Institution and Principal Investigator are solely responsible for the monitoring of the clinical trial in compliance with good clinical practices. Visits by the sponsor shall be limited to the review of clinical data for the sole purpose of pursuing regulatory filings related to the study drug or device. The review of such data cannot contain patient identifiers.