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Clinical Trial FAQs
NIH Clinical Trial Definition
“A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.”
International Committee of Medical Journal Editors (ICMJE) Clinical Trial Definition
“Any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes.” Health-related interventions include any intervention used to modify a biomedical or health-related outcome (for example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and process-of-care changes). Health outcomes include any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events.”
- Phase I - Researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
- Phase II - The study drug or treatment is given to a larger group of people (hundreds) to see if it is effective and to further evaluate its safety.
- Phase III - The study drug or treatment is given to large groups of people (hundreds to thousands) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
- Phase IV - Studies conducted after the intervention has been marketed. These studies are designed to monitor the effectiveness of the approved intervention in the general population and to collect information about any adverse effects associated with widespread use.
A master agreement is a pre-negotiated contract between parties that reduces the need to renegotiate common language and allows focus to be placed on specific study work orders, protocols, and budgets. The negotiation time for each specific clinical trial can be reduced by utilizing a Master CTA that is already in place and only the study specific work order and budget needs to be negotiated.
- a) Get all sponsor documents to OSP as soon as you receive them, including the Study Protocol, proposed budget, and informed consent documents once revised into Yale’s required format (which will be reviewed and revised by OSP as needed for consistency with the contract and budget prior to the Department returning the edited version to Sponsor for sign-off and subsequent submission by the Department to the IRB). Please provide the initial package of documents from the sponsor to your contract representative in OSP.
- b) Understand the protocol and what is being asked of your Department.
- c) Help to negotiate the budget as early as possible.
- d) Send the transum (or expedited review form)
- e) Remind your Department faculty and staff to refrain from signing any contract document (whether sent from the Sponsor or accessed electronically as part of a feasibility survey) unless it has been directed to them by OSP following negotiations with the Sponsor.
- f) Inform OSP of any unique circumstances with the clinical trial (e.g., external individuals providing study services, or ancillary research or non-clinical trial components to be undertaken).
|Budget and payment terms||Must be agreed to by all parties.|
|Confidential information||Exchange of information should be in writing and marked “Confidential”.|
|Data ownership||Study information that is part of the patient’s medical record or which may be otherwise developed by Institution staff which is not confidential information of Sponsor.|
|Biological sample ownership||Tissue, blood, cell lines, antibodies, DNA, RNA, etc.|
|Inventions/Intellectual Property (IP)||Balance to protect sponsor’s IP rights in drug or device while leaving an avenue for separate university inventions. Typically, Investigator Initiated Agreements (IIA) require more flexibility on IP terms for the University.|
|Publication/Publicity/Use of Name||Allow removal of Sponsor’s confidential material, but Yale always retains the final right to control publication without significant delay. Ensure that delay to publication does not exceed 90 days in total from first disclosure to Sponsor.|
|Subject injury||Yale ensures protection of clinical subjects from costs associated with their participation. Sponsors are required to pay for subject injury costs in an investigational clinical trial.|
|AAHRPP||Language required to retain our HRPP/IRB accreditation exceeds standard requirements for clinical trials outlined within the federal regulations. Sponsors sometimes have difficulty with the additional timeframe reporting requirement.|
|Operational business requirements||Requirements of a CRO or Sponsor which conflict with Yale SOPs may delay negotiations in efforts to achieve workable solutions (e.g. requirement to use a PO number, Sponsor/CRO electronic systems for negotiating budgets or invoicing, duplicative Sponsor/CRO supplier forms that may conflict with contract terms, etc.).|
No. Although Yale faculty members who serve as Principal Investigators have mandated oversight and responsibility for the conduct of a clinical trial, the University shields them from contractual obligations to sponsors by including them in the clinical trial agreement as employees/faculty members of the University. Yale University assumes the obligations contained within the agreement on behalf of its faculty and staff directly involved in the conduct of a clinical trial. Nonetheless, Yale faculty members retain their regulatory and legal obligations as a Principal Investigator or sub-investigator as applicable. Limiting the number of parties to the contract also may assist in speeding up the negotiation process.
A Confidential Disclosure Agreement (CDA), sometimes known as a “Confidentiality Agreement” or “Non-Disclosure Agreement,” is a legally enforceable contract that ensures the confidentiality of information that one party discloses to another party. A signed CDA may be required before an industry sponsor agrees to disclose its proprietary information (e.g., the study protocol) to an investigator. The CTA team is responsible for reviewing, negotiating and executing CDAs related to the evaluation of industry-supported clinical trials conducted at Yale. Faculty members are not authorized to sign CDAs for industry-funded clinical trials; all terms are negotiated by and signed by OSP.
Send an email to the appropriate GCAT box, along with a completed Transmittal Summary (Tran Sum) Form (see http://your.yale.edu/policies-procedures/forms/1304-fr03-transmittal-summary-tran-sum-form) and a copy of the draft or proposed clinical trial agreement (CTA), as well as the draft budget, informed consent document(s), Sponsor Protocol, and contact information for the industry sponsor. If you know who your clinical trial contract manager is within OSP, please copy that individual on the email submission to the GCAT box. The GCAT assistant will set up a record in IRES and your clinical trial contract manager will be assigned to review that record.
Yes. Please ensure that all Informed Consent documents are provided to your OSP Contract Manager for approval prior to submission to the Sponsor or IRB to ensure that Economic Consideration and Subject Injury Terms are consistent with the negotiated terms of the CTA. OSP will assist in the negotiation of this section directly with the sponsor if necessary.
OSP is committed to providing transparency regarding the status of contracts in review, and uses the InfoEd (IRES) PT system to track clinical trial agreements. Certain department personnel should have access to IRES PT to monitor CDA and CTA progress by reviewing comments in the IRES PT record.
View the Quick Guide on How to Check the Status of an Agreement
A subject stipend is a payment that a research participant may receive as compensation for their time and/or the inconvenience of participating in the clinical trial. Such payments are typically fixed amounts that are paid based on the completion of a study visit. These costs are generally included as part of the per-visit cost paid for by the funding agency and are typically separate from the reimbursement for out-of-pocket expenses as listed below.
Subject reimbursement is when a research participant is reimbursed for certain expenses incurred during their participation in a clinical trial. Typically, a research subject will be required to provide receipts for the reimbursable activity such a mileage, parking, lodging or meals, and the Sponsor may limit such reimbursement (e.g., mileage is paid for research participants who travel more than a set number of miles to come to Yale for their study visits or for hotel visits up to a specified amount per day).
The clinical trial indirect cost rate of 30% is an additional charge that must be applied above the total direct clinical costs, and helps to cover a small part of the infrastructure costs at the University. The 30% indirect rate is charged for clinical trials because it is anticipated that the research will be conducted primarily within clinical space. Any exceptions to this rate would require an approved waiver before the contract can be finalized.
An individual must meet the criteria set out in the Yale University Faculty Handbook in order to serve as a Principal Investigator on a Yale research study, such as a clinical trial. Researchers not meeting these criteria who wish to serve as PI require special approval. Approval is study-specific, and must be obtained for each research project to be conducted. A PI Status Request Form must be completed and signed by the Dean prior to submission of the transum and other study documentation to OSP.
In the event that the Principal Investigator of a clinical trial needs to be changed (e.g., the faculty member is leaving the University), OSP must be notified of the change in order to negotiate an amendment to the clinical trial agreement with the sponsor to reflect the change of the Principal Investigator. Similarly, the IRB must be notified of the change in PI for that particular protocol and must approve such change.
The provision requires that: “… any applicable manufacturer that provides a payment or other transfer of value to a covered recipient (or to an entity or individual at the request of or designated on behalf of a covered recipient)” will have to report certain information.
- Covered recipients are physicians or teaching hospitals.
- Reports must include the covered recipient’s name, business address, specialty & National Provider Identifier, amount of payment, dates, the form of payments, nature of the payment
- Nature of payments include consulting fees, services other than consulting, honoraria, gifts, CME compensation, grant, entertainment, food, travel, education, research, charitable contribution, royalty/license, current or prospective ownership interest.
Corporate Integrity Agreement (CIA) is an enforcement tool used by the Office of the Inspector General (OIG) within the Department of Health and Human Services (HHS), to improve the quality of health care and to promote compliance to health care regulations. A CIA:
- Requires the amendment of all current research contracts and vendor contracts with CIA specific language
- Inserts CIA language in future contracts
- Could affect current and future budgets with that sponsor if amounts paid were higher than fair market value (FMV)
- Requires the sponsor to increase tracking of research funding
Cooperative group clinical programs are large scale clinical trials conducted across the nation by distinctive groups, but under a national organization funded by a large award or U10 funding mechanism, as with the NCI. A contractual agreement with one group allows the University to participate with any of the groups under the larger organization. These cooperative studies are considered clinical procedural reimbursements for data entered into a national database.