The following information highlights the most frequent points of concern and confusion for Principal Investigators and their study coordinators/research administrators regarding contract negotiation for clinical trials sponsored by pharmaceutical and medical device companies, the following describes the SIU SOM guidelines for clinical trail contracting.
EXECUTION OF CONFIDENTIALITY DISCLOSURE AGREEMENTS (CDA):
SIU SOM is responsible for reviewing, negotiating, and legally executing CDAs from external funding sources. Before providing a protocol and other research documents regarding the clinical trial, the sponsor may require SIU SOM to enter into a confidential disclosure agreement (CDA). A CDA is an agreement with a sponsor to ensure that any information or materials the sponsor provides regarding the study or the company itself will only be used by SIU SOM to evaluate the feasibility of conducting the clinical trial. CDAs are also known as “Secrecy Agreements” or “Nondisclosure Agreements.” CDAs can appear in many different forms, such as in a letter or even as an item in the initial site questionnaire. The only way to identify a CDA is to read and interpret the words. All CDAs must be submitted to SIU’s Center for Clinical Research (CCR) for review and approval.
Under university policy, faculty and staff are not authorized to sign research agreements (including CDAs) on behalf of the SIU SOM. If a Principal Investigator or other staff signs such an agreement, they will incur sole responsibility and the University will be unable to provide support in the event that the terms of the agreement are breached. In addition, although the sponsor may request the Principal Investigator provide an acknowledgment signature, the Principal Investigator should never be the signatory for or the named party to the CDA or any other research agreement relating to a clinical trial. The Board of Trustees of Southern Illinois University should be the named party in the agreement which must then be signed by legal counsel and the Dean.
Once the terms of the CDA have been finalized, SIU SOM requires two (2) original, signed copies of the CDA. SIU SOM and the sponsor will each receive an original copy of the fully executed CDA. The sponsor will then provide the protocol and other research documents to the Principal Investigator for review.
Principal Investigator Responsibilities: After execution of the CDA and receipt of sponsor confidential materials, the Principal Investigator is fully responsible for understanding, knowing, and adhering to the terms of the CDA. This includes ensuring that any staff that reviews the confidential information is aware of the terms of the CDA and its obligations of confidentiality.
If the study is not pursued, the CDA often dictates what should be done with the confidential materials. Typically the confidential materials provided to the site must be destroyed. However, the CDA should include provisions that the Principal Investigator and the SIU CCR may retain one copy of the material(s) in confidential files for record-keeping purposes. Notice should be provided by the Principal Investigator to the SIU CCR if they choose NOT to pursue the project or if the Principal Investigator receives notice that the sponsor is not moving forward with the study.
If the study is pursued by the Principal Investigator, obligations contained under the CDA must be superseded by the confidentiality terms in the primary Clinical Trial Agreement (CTA).
EXECUTION OF CLINICAL TRIAL AGREEMENTS (CTA):
SIU SOM is responsible for reviewing, negotiating, and legally executing CTAs from external funding sources. The resolution of many contractual issues requires coordination between the external funding source, Principal Investigator, and SIU SOM; the involvement of each party is essential to a successful CTA with mutually acceptable terms.
Principal Investigators must complete the Submission Checklist and Questionnaire and email this form to the SIU CCR with the following documents attached:
- one editable copy of the proposed CTA,
- one copy of the protocol or protocol summary,
- one copy of the schedule of events from the protocol if the full protocol is not provided,
- sponsor’s contact information (person responsible for contract negotiation),
- draft itemized budget
The checklist also includes a Billing Compliance Worksheet and a Budget Study Worksheet. These documents should be completed and emailed to the contracting office as soon as a final budget is negotiated.
Although each CTA is reviewed on a case-by-case basis, there are a number of key issues common to most CTAs. Although not necessarily an exhaustive list, the following items are commonly negotiated by SIU SOM with the Sponsor:
Parties to the CTA: The Agreement must be between the sponsor and The Board of Trustees of Southern Illinois University for and on behalf of its School of Medicine. Principal Investigators do not have the delegated authority to contractually bind SIU SOM. Principal Investigators might be named in the CTA and asked to sign, indicating they have read and agree to the terms of the CTA. However, the Principal Investigators cannot sign for SIU SOM. If one or both of the hospitals will be used to conduct the study, such as in-patient hospitalization, imaging, pharmacy, labs, etc., then the hospital(s) must be party to the CTA as well. In this case, SIU SOM negotiates CTAs on behalf of the affiliated hospital(s). Hospital signatures are required on the final executed CTA.
Indemnification and Subject Injury: University policy requires that for-profit clinical trial sponsors fully indemnify the University for its participation in the clinical trial, including reimbursement for the costs of treating subjects who are injured as a direct result of participating in a trial. These provisions ensure that risks and liabilities are not inappropriately passed to the University, and that medical treatment for injured human subjects is promptly provided and paid for by the sponsor.
The sponsoring company must agree to indemnify and hold harmless SIU, the Principal Investigator, and the hospital(s), and all trustees, officers, agents, and employees of the Institution and hospital(s).
Costs for treatment of protocol-induced injury to subjects: The sponsor must assume full responsibility for the reasonable and customary cost of medical diagnosis and treatment for protocol-induced injuries, illness or adverse reactions to study subjects. It is not acceptable for a sponsor to restrict its responsibility for payment for treatment of protocol-induced injuries to only those injuries directly associated with the administration/use of the study drug or device. Sponsor must also be responsible for injuries related to procedures/interventions that are performed solely to satisfy the requirements of the protocol.
It is also not acceptable for the sponsor to limit its responsibility to immediate or emergency care for protocol-induced injuries. It is not acceptable for such arrangements to require billing of third-party, payors, including government healthcare programs or insurance companies, in lieu of recovery of such costs directly from the sponsor, nor is it acceptable for sponsors to cover only those costs that government or insurance providers do not. Sponsors may not include provisions restricting participation of human subjects on the basis of medical insurance coverage status or the subject's ability to pay. Additionally, sponsors may not make payment for injury or illness conditional on the subject following instructions.
There may be times when payment for protocol-induced injuries by the sponsor may not apply to a specific trial. Exceptions will be considered, on a case-by-case basis, for company-sponsored clinical trials.
A section of the informed consent document describing payment for protocol-induced injuries must reflect accurately the language in the Clinical Trial Agreement covering the topic of payment for subject injury. In the event that a Clinical Trial is deemed to be exempt from this policy, the informed consent document must state accurately how payment for treatment of protocol-induced injuries will be handled, if such payment is available. If there are no funds available to pay for the costs of treatment of the subject injury, it must be stated clearly that treatment of subject injury will be provided by SIU SOM, but study subjects will be responsible for payment for this treatment. The informed consent document must accurately reflect the payment for subject injury language outlined in the contract and final SIU Medicine IRB approval is contingent on reconciliation of such language in the informed consent document.
Note: Some sponsors prefer to address Indemnification, as well as subject injury terms in a separate Letter of Indemnification (LOI). This is acceptable as long as the LOI is expressly incorporated in the CTA as an attachment or exhibit to the CTA.
Confidentiality: Written confidential information should be stamped as such and oral communication should be reduced to writing and stamped "confidential" within thirty (30) business days of disclosure. Access to confidential information (including the protocol) must be strictly controlled and each Principal Investigator should have a plan for ensuring confidentiality. All CDAs and CTAs must have a time limit for information to be kept confidential by SIU SOM. Additionally, the CTA should include a provision that SIU SOM may release confidential information if it is required by court order, statute, or regulation to be disclosed.
Publication: Freedom to publish and disseminate research results is a basic tenet of the University. The CTAs must allow the Principal Investigator the freedom to publish results of the study. However, the sponsor may have the right of prior review (without reference to “approval” or “consent”) to identify proprietary or confidential information. Additionally, in the case of a multi-center study, the sponsor will usually request that the investigators not publish individually prior to the production of a multi-center publication.
Intellectual Property: The drug or device being tested in a clinical trial is typically owned by the sponsoring company and already covered by patent protection. Industry sponsors of clinical trials often require rights to intellectual property developed during the course of a clinical trial. The types of rights requested range from license options to assignment of ownership. These requests will be considered on a case by case basis.
Insurance: To support its indemnification obligations under the CTA, the sponsor must maintain a sufficient level of insurance. The language required by SIU Office of Risk Management for sponsor insurance requirements is as follows:
“During the term of this Agreement, and for three (3) years after its termination, Sponsor shall maintain commercial general liability insurance with a limit of not less than $5,000,000 per occurrence and $10,000,000 aggregate for bodily injury, property damage, personal injury, products-completed operation, and blanket contractual coverage including but not limited to the liability assumed under this Agreement. Such insurance policy/policies shall be issued by companies with a current A.M. Best rating of B+:VI or better. Sponsor shall furnish to Institution all original Certificate(s) of Insurance evidencing the required coverage to be in force on the effective date of this Agreement and with Institution named as an additional insured. The receipt of any certificate(s) does not constitute an agreement by the Institution that insurance requirements have been met. Failure of the Institution to obtain certificates or other insurance evidence from Sponsor shall not be deemed a waiver by the Institution. The policies shall be endorsed stating that they shall not expire, be cancelled, suspended, voided or materially changed without 30 day written notice by certified mail to the Institution. When policies are renewed or replaced, any retroactive date must coincide with or precede commencement of the Study. A claims-made policy that is replaced or not renewed must have an extended reporting period not less than 2 years.”
Some of this language may be revised if the sponsor is self-insured. The sponsor must provide a satisfactory certificate (or evidence) of insurance before SIU SOM will sign the CTA.
Clinical Trial Master Agreements: Master Agreements are agreements that embody agreed-upon terms and conditions of a basic relationship between SIU SOM and a particular sponsor.
Once a Master Agreement is in place, a "study-specific, agreement" or "work order" is generated for each new study to be conducted under this Master Agreement. This agreement sets forth the items particular to a certain study such as the protocol name, the Principal Investigator and the payment terms/amounts. This alleviates the need to "reinvent the wheel" for each agreement; as the major terms are agreed upon and only the particulars need to be negotiated.
SIU has several Master Agreements in place. Contact the SIU CCR for a current list of sponsors.
Clinical Trial Amendments: An amendment changes the terms of a previously executed agreement. All contract amendments must be processed by SIU CCR.
Principal Investigator Responsibilities: After execution of the CTA, the Principal Investigator is fully responsible for understanding, knowing, and adhering to the terms of the CTA and must follow Good Clinical Practice (GCP) guidelines as well as any regulation related to human subject research protections.
Budgets and Funding: Principal Investigators are responsible for following the guidelines and SIU SOM policies when developing the study budget. All costs necessary to conduct the study, including salaries, fringe benefits, document storage costs, supplies, indirect costs, and pharmacy fees (when applicable) 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 respective Principal Investigator’s responsibility to ensure that the amount agreed upon will adequately cover all costs associated with conducting a clinical trial. SIU CCR will review budgets and may provide assistance or advise study coordinators when negotiating the agreement with the sponsor; however, negotiating the budget is the responsibility of the Principal Investigator and study coordinator. SIU CCR will also evaluate the budget for compliance with indirect cost policies to ensure that your budget falls within institutional guidelines. Principal Investigators and/or their research coordinators may contact the SIU CCR for assistance with clinical trial budget development.
Indirect Costs (F&A): The current negotiated indirect cost rate (ICR) for industry-sponsored clinical trials is 28%. The ICR is also known as the Facility and Administrative (F&A) rate. The CCR will be responsible for ensuring that all indirect cost fees are appropriately included in the study budgets prior to contract execution.
Fringe Benefits: When budgeting salary for investigator and staff time for the study, the budget must take into account both salary and fringe benefits. Fringe benefits are calculated based on the total salary expense. Fringe benefits will be automatically deducted when salary is paid from a study account. Current SIU SOM fringe benefit rates.
SIU Medicine IRB Fees: Initial full board review of studies is $2,500. Continuing review fees are $750. Sponsor-required protocol amendments are $500. These fees only apply to industry-sponsored clinical research. Fees will not be charged for Federal, non-profit foundations, or investigator-initiated studies.
These institutional review board (IRB) fees should be included as a line item in the budget as an upfront, non-refundable item. All fees are the responsibility of the Principal Investigator. In the case when a sponsor requests or requires IRB review prior to contract execution, the Principal Investigator will need to obtain written confirmation from the sponsor that they will pay the IRB review fee even in the event the contract is not executed.
Contract Processing Fee: There is a contract processing fee of $500 which should be made payable upon execution of the CTA. If a sponsor prefers to fold this fee into the non-refundable start-up fee that is acceptable but the Principal Investigator and/or coordinator should increase the fee accordingly with the knowledge that this fee will be taken out by SIU CCR.
Payment Schedules for Clinical Trials: Sponsors 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. Sponsors will oftentimes want to pay us at the end of the project versus the beginning of the project. The majority of the work will occur at the beginning of the trial and SIU SOM should be paid accordingly.
The Research Coordinator should ask for a reasonable initial payment that will cover the startup costs, preferably non-refundable. This amount should be adequate to cover all direct and indirect costs incurred with initiating a trial, including the IRB fee, in the event that the trial never begins. In addition, it may be appropriate for some studies to include a non-refundable study close-out fee. Please consult the SIU CCR for guidelines regarding inclusion of the non-refundable fees in the study budget.
W-9, IRS Identification, and Payment Information: The SIU CCR prepares all W-9 forms requested by sponsors as the form requires institutional signature. Checks from the sponsoring company should be made payable to Southern Illinois University (Tax ID# 37-6005961) and mailed to:
SIU School of Medicine
C/O Revenue Accounting
P.O. Box 19607
Springfield, IL 62794-9607
Clinical Trial 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 Principal Investigator or his/her Department.
Contact for Clinical Trial Contracting:
Center for Clinical Research