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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 provide OSP with a copy of the proposed agreement, Certificate of Proposal (COP), 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. To expedite the process even before submitting a COP or protocol, please have the company contact send the agreement electronically to Mark Gallyoun, at gallyoun@uthscsa.edu. It is policy of the University of Texas System to have its component institutions negotiate agreements electronically.
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 the Health Science Center, 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. The Health Science Center will only indemnify the Sponsor for negligent or willful 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 confidential by the Health Science Center. Our standard language is only to allow information received from the Sponsor to keep confidential for a period of three (3) after the termination of the Agreement.PUBLICATION
Agreements must allow the Investigator the freely to publish results of the study. However, the company may have the right of prior review not approve to identify proprietary or confidential information.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 the Health Science Center's general policy that title to inventions arising from projects conducted by faculty, staff or students will be owned by the Health Science Center. 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.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 59.01 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. The Health Science Center 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 UTHSCSA and a sponsor. Once a Master Agreement is in place, an "addendum" or "study letter" is generated for each new study to be done 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 the wheel" for each agreement; the major terms are agreed upon and only the particulars need to be negotiated.We currently have many Master Agreements in place and our University of Texas System, Office of General Counsel is currently working on several more. When dealing with the following sponsors, please inform them to use our Master Agreement:
· Abbott Laboratories
· Amgen, Inc.
· AstraZeneca Pharmaceuticals LP
· Bayer Corporation
· Boehringer Ingelheim Pharmaceuticals, Inc
· DuPont Pharmaceuticals Company
· Eli Lilly
· GlaxoSmithKine
· Hoffman-La Roache
· Janssen Pharmaceuticals Company
· Merck & Co.
· NeoPharm, Inc.
· Novartis Pharmaceuticals Corporation
· Organon Incorported
· Pfizer
· Pharmacyclics, Inc.
· Quintiles, Inc.
· Rohn-Poulenc Rorer
· Schering Plough
· Syntex
· Upjohn
· Warner-Labert
· Weyth Pharmaceuticals Inc.
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 investigators responsibility to ensure that the amount agreed upon will adequately cover all costs associated with conducting a clinical trial. 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 advice to ensure your budget meets your needs.
INDIRECT COSTS
Indirect costs for human clinical studies and other related agreements are assessed at the flat rate of 20% of actual cash received. To estimate indirect cost when the direct costs are known, add 20% 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, 20% or $200 should be added for indirect, bringing the total to $1,200 per patient.Basic Indirect Cost Recovery Example:
$1,000 check received from sponsor for a clinical trial.
Calculation: $1,000/1.20=$833.33 Direct CostDEPARTMENTAL FEES
The following departments access an additional fee for all clinical and other related non-governmental agreements: Biochemistry, Medicine, Pathology, Psychiatry, and Surgery. The departmental fee should always be added in your budget as a direct cost line item and not as indirect cost. Please contact your departmental administrator or OSP for the fee that your department charges.Administration fee by department:
•Biochemistry 10%
•Medicine 10% (Division of Nephrology 5%)
•Psychiatry 5%
•Pathology 5% (processed by dividing)
•Surgery 5%
•Orthopedics 10%
Example: $1,000 check received from sponsor
Calculation: $1,000/1.20=$833.33 Direct Cost after IDC $1,000 – 833.33=$166.67 Institutional IDC $833.33 x .05=$41.67 Dept fee $833.33 - $41.67=$791.66 True DC VETERANS ADMINISTRATION (VA) FACILITY FEE
Whenever a any portion of a study is being conducted by a principal investigator at the Veterans Administration Hospital a VA facility fee will be assessed at 5% of the total departmental direct cost received. If the study is being conducted at the VA, please use the following calculations when preparing the budget:
Example: $1,000 check received from sponsor without departmental fee
Calculation: $1,000/1.20=$833.33 Direct Cost after IDC $1,000 – 833.33=$166.67 Institutional IDC $833.33 x .05=$41.67 VA Fee $833.33 - $41.67=$791.66 True DC
Example: $1,000 check received from sponsor with departmental fee
Calculation: $1,000/1.20=$833.33 Direct Cost after IDC $1,000 – 833.33=$166.67 Institutional IDC $833.33 x .05=$41.67 Dept fee $833.33 x .05=$41.67 VA Fee $833.33 - $83.34=$749.99 True DC
Effective September 1, 2003, the fee for the initial review of a single protocol is $2,000. 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 OSP will serve as the collection point for the IRB fee and will deposit the fee into an institutional project/grant established to support the IRB.
PAYMENT SCHEDULES FOR CLINICAL TRIALS
W-9, IRS IDENTIFICATION, AND PAYMENT INFORMATIONSponsors will usually specify certain 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 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.
Payment No.
Milestone
Payment Amount
1
Initial Payment upon drug shipment
$2500
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:
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
$2500
Occasionally, 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 and you have incurred costs that will not be reimbursed. Instead, ask for a reasonable initial payment that will cover your 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 milestone 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 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 closure at your site
- Invoicing permitted for other costs (i.e. equipment, advertising)
Screen failures and early termination
Not every subject enrolled in a trial will complete the trial. Ensure that the budget and payment schedule provide for these circumstances adequately.
Tax ID# 74-1586031CLINICAL TRIAL PROJECT/GRANT SET-UPOSP 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, the Health Science Center 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 of the ruling is available by contacting OSP. A 1099 is not needed to be complete by the company for the Health Science Center.
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.
To obtain a Health Science Center project/grant number for a clinical study the following documentation is required: a completed and signed Certificate of Proposal (COP), a copy of the study protocol, a signed written agreement between the sponsoring company and the Health Science Center, Institutional Review Board (IRB) approval, an a initial payment received from the Sponsor. Project will be set up under PeopleSoft fund group 48002 (Legacy “T” account).
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 another 48002 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. If the amendment increases the dollar amount of the contract, you will need to complete a new Certificate of Proposal (COP). Do not add the increase to the original budgeted amount when preparing the COP. If the amendment deals with other non-monetary issues such as extending the timeline of the study, a COP is not required. Simply fax, email, or send a hard copy of the amendment for OSP processing.
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 TrialsCLINICAL STUDY AGREEMENT TEMPLATE:
Clinical Study
