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.
An investigator-initiated clinical trial is a clinical trial that is conducted based upon a protocol authored by a Yale investigator(s), or for OSP negotiation purposes, includes clinical trial agreements (CTAs) in which Yale is a site for an IIT of another institution (e.g., when an investigator the other institution authored the protocol). The terms of an IIT agreement are often much different than the terms of a CTA for an industry-sponsored clinical trial.
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 for which only the study specific work order and budget will be negotiated.
- Get all necessary sponsor documents to OSP via IRES PD as soon as possible, including the draft clinical trial agreement, sponsor correspondence, draft budget, and payment schedule .
- Understand the protocol and what is being asked of your Department
- Work to negotiate the budget as early as possible
- 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.
- 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 Yale (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 Trial Agreements (IITs) require more flexibility on IP terms for the University.|
|Publication/Publicity/Use of Name||Allow removal of Sponsor’s confidential material, but the University always retains the final right to control publication without significant delay. The delay for publication should 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 University 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 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. The 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, 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 and signed by OSP.
A new IRES PD record must be created in order for a new clinical trial agreement to be negotiated by OSP. For instructions on how to create a clinical trial record, please review the PD Quick Guide. Your clinical trial contract manager will be assigned to review that record.
Neither the PI nor the Business Office need to provide informed consent documents (ICF) to OSP for review prior to submission to the Yale HRPP/IRB.
The Clinical Trial Agreements team in the Office of Sponsored Projects (OSP) is responsible for confirming that clinical trial consent forms (ICFs) are consistent with the clinical trial agreement and the budget, when ICFs describe the following:
- Payments to research participants for participation in the clinical trial (i.e., stipends),
- Reimbursements to research participants (e.g., for travel costs),
- Costs of research procedures, and
- Who may cover the potential costs associated with diagnosing and treating research-related injuries.
Typically, ICFs include specific sections on study participants’ expected costs and payments, as well as provisions addressing the potential coverage of research-related injuries (e.g., “Economic Considerations” or “In Case of Injury” sections). Some ICFs may include these provisions under different headings.
OSP and the Human Research Protection Program (HRPP) have developed a process that allows investigators to submit new clinical trial protocols in IRES IRB system without first seeking OSP’s review of the ICFs. The HRPP staff requests a member of the OSP Clinical Trial Agreements team to complete the consistency review using IRES IRB. If any inconsistencies are identified, the HRPP and/or Yale IRB will communicate the request for revisions directly to the Principal Investigator (PI) and the PI Proxy.
Requested revisions must be incorporated into the ICFs before the study receives final approval. The clinical trial sponsor should approve the final version of the ICF prior to the submission to the IRB. If the sponsor or the PI proposes additional revisions, OSP may have to conduct additional assessment of the consistency, per HRPP request.
Although the IRB is responsible for reviewing and approving the overall content of ICFs, OSP and HRPP work closely together to ensure that the proposed language is consistent with the clinical trial agreement and budget and is written in language understandable to a study participant.
If you have questions about the consistency review performed by OSP, please contact Jeri Barney at email@example.com. Questions about the HRPP and IRB processes can be directed to Monika Lau at firstname.lastname@example.org or email@example.com.
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. The PI and 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 the Chair of the proposed PI’s home department, as well as the Dean, Provost or Senior Associate Provost for Research Administration that has oversight responsibility for the proposed PI’s department prior to submission of the appropriate study documentation to OSP via IRES PD.
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.
Yale Policies and Procedures
- Yale IRB Policy 110 Institutional Review Board Review Fees
- Yale IRB Policy 410 Recruitment of Research Participants
- Policy 1316 Effort Commitment: Managing Effort Associated with Sponsored Projects
- Yale Human Research Protection Program (HRPP) Frequently Asked Questions (FAQs)
- Yale Center for Clinical Investigation (YCCI) - New Study setup for Oncore
- National Coverage Determination (NCD) for Routine Costs in Clinical Trials (310.1)
- ClinicalTrials.gov - a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world.
- List of all of the active corporate integrity agreements