Clinical Trial Agreements

EXECUTION OF CLINICAL TRIAL AGREEMENTS (CTA)

The University of Texas Health Science Center at San Antonio 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.

 

The Office of Sponsored Programs (OSP) is responsible for reviewing, negotiating and legally executing agreements from external funding sources. The resolution of many contractual issues requires coordination between the external funding source, Investigator and OSP; the involvement of each party is essential to a successful contractual arrangement with mutually acceptable terms. Investigators should initiate an agreement request in ERMSA and provide OSP with a copy of the proposed agreement, copy of the Protocol, and a company contact person, as early in the process as possible. IRB approval is not required in order for OSP to execute an agreement. Company contacts may initiate an agreement by emailing contracts@uthscsa.edu.

 

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 the OSP with the Sponsor:

 

AGREEMENT PARTIES
All Clinical Trial Agreements should be only between The University of Texas Health Science Center at San Antonio and the Sponsor. The Investigator is an employee of the institution and never is a named party to the Agreement.

 

INDEMNIFICATION
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 UT Health SA, the University of Texas System, its Board of Regents, Investigator, 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, including but not limited to the use of the study results by Sponsor. UT Health SA will only indemnify the Sponsor for negligent activities.

 

CONFIDENTIALITY
It is often necessary for the sponsoring company to provide information of a proprietary nature to the Investigator or his/her staff 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” within thirty (30) business days. Access to confidential information (including the protocol) must be strictly controlled and each Investigator should have a plan for assuring control. All agreements must have a time limit for information to be kept confidential by UT Health SA. Our standard language is only to allow information received from the Sponsor to be kept confidential for a period of three (3) years after the termination of the Agreement.

 

PUBLICATION
Agreements must allow the Investigator the freedom to publish results of the study. However, the company may have the right of prior review to identify proprietary or confidential information. Approval rights on publications are not granted to sponsors.

 

INTELLECTUAL PROPERTY
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 UT Health SA’s general policy that title to inventions arising from projects designed and conducted by faculty, staff or students will be owned by UT Health SA. Clinical studies originating with UT Health SA’s investigator 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. If the study design (protocol) originates with a company, then the UT System has determined that title to inventions can be granted to the company because the protocol is based on that company’s existing intellectual property.

 

INSURANCE
To support the above indemnification the sponsoring company must maintain a sufficient level of insurance. Each component of The University of Texas System is self-insured pursuant to the University of Texas System Professional Medical Malpractice Self-Insurance Plan, under the authority of Section 59 of the Texas Education Code. The Health Science Center has and will maintain in force during the term of its agreements with third parties adequate insurance to cover its indemnification obligations.

 

GOVERNING LAW
Agreements must either be governed by the laws of the State of Texas or this provision must be absent from the agreement.

 

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. UT Health SA must notify the company of any debarment or threat of debarment occurring during the term of the study and usually one year afterwards. Investigators and other staff members in the study may be required to sign such a certification.

CLINICAL TRIAL MASTER AGREEMENTS

Master Agreements are agreements that embody agreed-upon terms and conditions of a basic relationship between UT Health SA and a sponsor. Once a Master Agreement is in place, an “addendum” or “study letter” is generated for each new study to be conducted under this 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 “reinvent” in an agreement for each study with that sponsor; the major terms are agreed upon and only the particulars need to be negotiated.

 

Most Master Agreements have been developed by The University of Texas System, Office of General Counsel, although some are developed directly between UT Health SA and sponsors. UT Health SA currently has many Master Agreements in place and the Office of General Counsel is continually working revisions, renewals, and/or new agreements. When dealing with the following sponsors, please inform them to use our Master Agreement:

· Abbott Laboratories
· Alexion
· Amgen, Inc.
· Astellas Pharma
· AstraZeneca Pharmaceuticals LP
· Bayer Corporation
· Biogen/Idec
· Boehringer Ingelheim Pharmaceuticals, Inc
· Cephalor
· Eli Lilly
· Forest Research Institute
· Genentech
· GlaxoSmithKine
· Hoffman-La Roache
· Intermune
· Janssen Pharmaceuticals Company
· Merck & Co.
· NeoPharm, Inc.
· Novartis Pharmaceuticals Corporation
· Pfizer
· Pharmacyclics, Inc.
· Purdue Pharma
· Quintiles, Inc.
· Roche Laboratories
· Schering Plough
· Wyeth Pharmaceuticals Inc.

BUDGETS AND FUNDING

Company sponsored clinical studies 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 indirect costs, should be considered when determining the fixed per-patient amount. Sponsors usually use one of two options when presenting a budget. They may offer a certain amount per patient and ask that you work within that amount or they may ask you to formulate a budget for them. Regardless, it is the principal investigator’s responsibility to ensure that the amount agreed upon will adequately cover all costs associated with conducting a clinical trial. Negotiation of budget terms by the investigator may be necessary. OSP will not review budgets when negotiating the agreement with the sponsor. If requested, OSP will evaluate your budget for compliance with indirect cost calculation and provide advice to ensure your budget meets your needs.

The Office of Clinical Research and Clinical Trials Office can also assist with budgets.

INDIRECT COSTS
Indirect costs for human clinical studies and all other industry-sponsored studies are assessed at the flat rate of 30% of actual cash received. To estimate indirect cost when the direct costs are known, add 30% of the direct costs. The sum of these two figures is the per-patient amount. Example: If $1,000 is needed to cover direct costs, 30% or $300 should be added for indirect, bringing the total to $1,300 per patient.

Basic Indirect Cost Recovery Example:

$1,000 check received from sponsor for a clinical trial.
Calculation: $1,000/1.30=$769 Direct Cost

DEPARTMENTAL FEES
The below departments assess an additional fee for all industry clinical agreements. The departmental fee should always be added in your budget as a direct cost line item and not as indirect cost. Certain divisions also may charge such a fee. Please contact your departmental administrator or OSP for the fee that your department or division charges.

Administration fee by department:

• Biochemistry 10%
• Medicine 10%
• Neurology 10%
• Neurosurgery 10%
• Psychiatry 5%
• Pathology 5%
• Orthopaedics 10%
• Pediatrics 10%

 

Example
(Medicine 10%): $1,000 check received from sponsor

Calculation:	$1,000 / 1.30 = $769.23	Direct Cost after (30%) IDC
	$1,000 – $769.23 = $230.77	Institutional IDC
	$769.23 / 1.10 = $699.30	Direct Cost after (10%) Dept Fee
	$769.23 – $699.30 = $69.93	Dept Fee
	$1000 – $230.77 (IDC) – $69.93 (Dept Fee) = $699.30	True DC

IRB Fee

The fee for initial review of a single protocol is $2500. This fee applies only to commercial companies who are sponsoring a drug or device protocol. Clinical trials supported by federal funds do not incur this fee. All investigators submitting commercial sponsored clinical trials to the OSP are required to include a line item in the study budget for the IRB fee. This will be a one-time fee only, no F&A (indirect) cost will be assessed against the fee, and no additional charges will be assessed for the required annual re-review or protocol amendments.

The IRB Office will invoice sponsors for this fee unless alternate arrangements are made by the investigator.

PAYMENT SCHEDULES FOR CLINICAL TRIALS

For company-prepared protocols, sponsors normally make payments on a basis of costs per patient, with a payment schedule based on interim milestones of certain treatments/visits achieved. Other study costs (i.e. pharmacy fees, advertising/patient recruitment costs, patient stipends, or costs for certain procedures performed as necessary such as pregnancy tests or radiology procedures) may also be paid separately from standard costs per patient.

For Investigator-initiated protocols, sponsors will usually specify certain enrollment milestones that must be achieved before payment is made.

Pay close attention to the timing and requirements of the milestones. Payment schedules may be appended to the contract as a table or narrative, or may be written as a paragraph within the contract. Please see below for an example of a common payment schedule for a trial with 10 patients at $2500/subject.

Common Payment Schedule

Payment No.	Milestone	Payment Amount
1	Initial Payment upon drug shipment + IRB fee upon invoice	$4500
2	After 3 subjects completed	$7500
3	After 2 subjects completed	$5000
4	After 2 subjects completed	$5000
5	Final payment after all Case Report Forms are completed, queries are resolved and close out visit is complete	$5000

A preferred payment schedule would be one that provides a greater proportion of funding earlier in the study, such as in this example:

Preferred Payment Schedule

Payment No.	Milestone	Payment Amount
1	Initial Payment + IRB fee upon contract execution	$6500
2	After 3 subjects randomized	$7500
3	After 2 subjects completed	$5000
4	After 2 subjects completed	$5000
5	Final payment after all Case Report Forms are completed, queries are resolved and close out visit is complete	$3000

An initial payment may be equal to or include the costs per patient for one study subject, or it may be a separate item for start-up costs. If an initial payment is based on costs for one subject, the sponsor may require subsequent payments be reduced by such amount to recover that cost. Occasionally, proposed contract terms indicate that initial payment will not be sent until a subject is randomized. This situation is not acceptable. OSP will not set-up your project/grant until a payment has been received from the sponsor. If a subject is never randomized, no payment will be received; yet the study will have incurred costs that will not be reimbursed. Instead, the investigator should ask for a reasonable initial payment that will cover startup costs. This amount should be adequate to cover all costs incurred with initiating a trial (including the IRB fee) in the event that the trial never begins.

Look at your milestones for payment. Will you be paid on completion of Case Report Forms? That may mean waiting until the monitor has reviewed the CRF’s and sent them into data management. Will you be paid on completion of a subject’s participation in the trial? This may delay payments. An ideal schedule will reimburse after a reasonable amount of subjects have randomized or after a certain number of visits are completed so that your study account does not run in a deficit.

Sponsors may also choose to hold back a significant portion of payment until all study activities are complete. Ensure that this is not an excessive amount. 10% of the total budget would be ideal. Final payment may or may not depend upon waiting until ALL sites are closed or until the study database has been closed. Pay close attention to this because it can mean that final payments may be delayed for an unreasonable amount of time.

An ideal payment schedule would include the following:

• Non-refundable initial payment that includes IRB fee and startup costs
• Regular payments with realistic milestones
• Final payment made upon study closure at your site
• Invoicing permitted for other costs (i.e. equipment, advertising, etc)

Screen failures and early withdrawal of a study subject:
Not every subject enrolled in a trial will complete the trial. Ensure that the budget and payment schedule provide for these circumstances adequately.

W-9, IRS IDENTIFICATION, AND PAYMENT INFORMATION

Tax ID# 74-1586031

OSP prepares all W-9 forms requested by sponsors. This form requires official institutional signature. The Components of the University of Texas System are not tax exempt under the provisions of Internal Revenue Code (IRC) Section 501 (c)(3). However, UT Health SA is exempt under Section 170 of the Internal Revenue Code. The University of Texas System and its component institutions received a favorable letter ruling (a seven-page document) dated March 20, 1984 confirming this status. A complete copy can be viewed by clicking the link below. A 1099 is not needed to be complete by the company for UT Health SA.

Checks from the sponsoring company should be made payable to The University of Texas Health Science Center at San Antonio and mailed to the attention of the Investigator or study coordinator.

Tax Status Letter

CLINICAL TRIAL PROJECT/GRANT SET-UP

To obtain a UT Health SA project/grant number for a clinical study, the following documentation is required: creation and submission of agreement request in ERMSA, a copy of the study protocol, a signed written agreement between the sponsoring company and UT Health SA, Institutional Review Board (IRB) approval, and an initial payment received from the Sponsor. Project will be set up under PeopleSoft fund group 48002.

CLINICAL TRIAL PROJECT/GRANT CLOSE-OUT

At the conclusion of any clinical trial study 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 indirect) have been properly charged and documented, the cash balance will be made available to the Investigator but will be under the ownership of the department. For example, if an investigator leaves the institution, he/she must receive approval from their departmental chair before funds can be transferred to the new institution. Also the project can be deactivated and the residual balance transferred to a 48001 project upon official request from the investigator once the study is completed.

CLINICAL TRIAL AMENDMENTS

An amendment changes the terms of a previously executed agreement. To request an amendment, submit an Amendment Request from the original agreement record in ERMSA.  If you are unable to find the original agreement in ERMSA, contact the Agreements Team via email at ERMSAhelp@uthscsa.edu for assistance.

HELPFUL LINKS

Clinical Trials.gov
ClinicalTrials.gov provides regularly updated information about federally and privately supported clinical research in human volunteers. ClinicalTrials.gov gives you information about a trial’s purpose, who may participate, locations, and phone numbers for more details.

REGISTRATION OF CLINICAL TRIALS
The Office of Clinical Research administers the UT Health SA’s ClinicalTrials.Gov Protocol Registration System (PRS).

As a reminder, the Food and Drug Administration Amendments Act of 2007 (FDAAA or US Public Law 110-85) requires mandatory registration and results reporting for applicable clinical trials (ACTs) defined as:

1. Trials of Drugs and Biologics: controlled clinical investigations (other than Phase I investigations) of a product subject to FDA regulation; and
2. Trials of Devices: controlled trials with health outcomes of devices subject to FDA regulation (other than small feasibility studies) and pediatric post market surveillance.

The UT Health SA Principal Investigator of any investigator-initiated applicable clinical trial (regardless of source of funding) is responsible for registering the trial, maintaining the registration until trial completion, and reporting of results.

The law requires registration of ACTs within 21 days of the first participant’s enrollment into the study. Should an investigator plan to publish findings, the registration of a clinical trial must occur prior to enrollment of the first participant. Results reporting must take place within 12 months of the primary completion date. Noncompliance can result in significant financial penalties.

Helpful information on registration and reporting requirements can be found on the ClinicalTrials.gov site at http://prsinfo.clinicaltrials.gov/s801-fact-sheet.pdf.

Presentations with audio and slides relevant to providing data to ClinicalTrials.gov are available at http://prsinfo.clinicaltrials.gov/.

Contact the OCR office at OCRmail@uthscsa.edu to request PRS user accounts for registration of studies or if you have any questions or concerns related to ClinicalTrials.gov registration and reporting requirements.

CLINICAL STUDY AGREEMENT TEMPLATE:

Clinical Study (.doc)

If unable to open document, please email contracts@uthscsa.edu and the editable version can be emailed.