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Updated June 7, 2024

Clinical Trial Agreement (CTA)

With research that requires the use of human subjects, investigators and coordinators must not only respect the rights of their participants, but they must actively protect their safety and dignity as well. A legally binding document identifying the obligations of the Sponsor, Principal Investigator and the institution. The terms of the agreement include, but are not limited to, payment/budget, confidentiality, indemnification, publication, insurance, adverse events, intellectual property, duration of the research, termination of research and governing laws.

Clinical Trial Agreements (CTAs) can be categorized as follows:

• Sponsor Initiated – the protocol for the clinical trial has been written by the sponsor (e.g., a pharmaceutical or medical device company)
• PI Initiated – the protocol was written by an investigator once an Investigator has made a decision to participate in a Trial, they, directly or through a member of their team, will forward the initial draft of the CTA, budget, and any ancillary documents received from the Sponsor or CRO to C&A for review.

Assessment for Completeness

The language required to retain our accreditation with the Association for the Accreditation of Human Research Protection Programs, Inc. exceeds standard requirements for clinical trials outlined within the federal regulations.  AAHRPP Standard I-8 deals with five provisions for contracts and funding agreements that are designed to contribute to the protection of research participants in sponsored research. It is necessary to negotiate with sponsors to ensure that contracts and funding agreements include the required provisions, when appropriate, for each specific Element that is appropriate for the research under negotiation. Reviewer should ensure consistency between the consent document and the contract or funding agreement.

A CTA checklist for the language to be used in each contract or funding agreement should be completed by the Reviewer.  The checklist should indicate whether each item of required language is present in the contract or funding agreement, not applicable to the specific research protocol with justification, or that the sponsor refused to include the language with evidence attached (e.g. e-mails).

Documents to be uploaded in IRBNet:

• CTA agreement or the scope of work
• Informed Consent Form
• CTA checklist
• Correspondence on altered text or refuse to adapt

Specific Language for CTA

Subject Injury

Although AAHRPP does not require that sponsors or the organization should be responsible for paying for care for research-related injury, they do require that organizations address payment (that is, regardless of whether or not it is available) for research-related injury in the contract or funding agreement before the research starts so participants can consider this information during the consent process.

Sample Language:

[The sponsor] will provide payment to the institution for reasonable, unreimbursed medical expenses, including hospitalization, which the institution may incur as a direct result of the treatment of a subject’s injuries that directly result from the study drug or its administration during the clinical trial, as determined by [the sponsor]and the principal investigator.

Research-Related Injury. [The sponsor] shall be responsible for payment of the actual and reasonable medical expenses incurred in diagnosing and treating any injury, illness, or adverse reaction of a study subject that results from the administration of the study drug [or device] in accordance with the protocol or the proper performance of any Protocol procedure.

Reporting of Clinical Data and Findings

Element I.8.B  AAHRPP requires if the sponsor conducts monitoring of its site, the sponsor must promptly report to the organization any findings from the monitoring that could affect the safety of participants or influence the conduct of the study. This Element is not applicable when the sponsor does not monitor the site.

Sample Language:

 [The sponsor]/or CRO conducts monitoring of sites on a periodic basis throughout the study. If a monitor finds non-compliance at the site that affects safety or materially affects the proper conduct of the study, [the sponsor]or CRO shall in a timely manner notify the investigator and, if non-compliance is serious or continuing, the site.

Element I.8.C. For this Element, it is required that the sponsor send data and safety monitoring plans and reports to the organization. This should take place according to the data and safety monitoring plan that the IRB approves, including the time frames for reporting. At a minimum, data and safety monitoring reports should be sent annually.

Sample Language:

[The sponsor] shall promptly notify the investigator of any findings of (1) new and unexpected serious adverse safety events arising from [the sponsor’s] monitoring of the study that could affect the safety of subjects, and (2) trends or patterns of non-serious or expected adverse events that occur at a specificity or severity that is inconsistent with prior observations, all in accordance with the obligations set forth in 21 C.F.R. 312.32(c), 21 C.F.R. 312.55(b), 21 C.F.R. 56.108(b) and FDA's Guidance on Adverse Event Reporting to Institutional Review Boards in Clinical Trials (January 2009).

[The sponsor] agrees to provide data and safety monitoring plans to the principal investigator prior to the IRB review of the study. [The sponsor] will provide the [organization’s] principal investigator with any findings from its data and safety monitoring that could affect the safety of subjects or their willingness to participate or influence the conduct of the study. Reports of an urgent nature must be provided within ten business days; routine reports must be submitted within 30 business days. (This language is not required in the contract if these provisions are described in the protocol).

The following is acceptable language for I.8.B. and I.8.C.:

[The sponsor] shall provide notice to the institution of any findings that may (i) affect the safety and welfare of subjects, (ii) affect the willingness of subjects to continue their participation in the clinical trial, (iii) influence the conduct of the clinical trial or (iv) alter the IRB's approval to continue the clinical trial. The institution will work with its IRB and the principal investigator to disseminate this information to the subjects.

Publication

Element I.8.D. it is required that the organization’s policies and procedures have contracts or other funding agreements that require the sponsor to follow the organization’s policies and procedures regarding the publication of findings from sponsored research. This Element is not applicable if the organization has no such policy.

Sample Language:

[The sponsor] acknowledges and accepts the interest of the [organization] in the non-commercial publication of the results, independent of a positive or negative outcome of the study. With respect to any proposed publication or presentation of the results of the study, the organization and/or investigator agree to submit to [the sponsor] a copy of the proposed publication or presentation at least two months prior to the submission thereof for publication or the date of such presentation in order to allow [the sponsor] to review it. Any manuscript for publication submitted to [the sponsor] shall be reviewed without unreasonable delay and approval shall not be withheld unreasonably. If [the sponsor] does not notify [the organization] within thirty days of the [the sponsor’s] receipt of the intended publication, [the organization] shall be free to publish. In the case a difference of opinion between [the sponsor] and [the organization], the contents of the publication will be discussed in order to find a solution that satisfies both parties. [The organization] acknowledges that in the case of multi-center studies the results of the study are to be published only through coordination by [the sponsor] in order to combine the results of all participating centers. [The organization] shall be free to publish the results of their center provided the overall results have not been published with twenty-four months from the completion of the study, subject to compliance to the remaining terms set forth in the section. [The sponsor] may recommend any changes to the publication it reasonably believes are necessary for scientific purposes. [The organization] agrees that the implementation of such recommended changes shall not be unreasonably refused. If [the sponsor] informs[the organization] that such publication could be expected to have an adverse effect on the confidentiality of any of [the sponsor’s] confidential information, [the organization] shall prevent the publication unless the confidential information can be deleted from the publication without detriment effect on the scientific correctness of the publication. If the publication could in [the sponsor’s] view have an adverse effect on the ability to obtain patent protection for any invention, [the sponsor] may request a delay of the publication for a reasonable period of time in order to permit the preparation and filing of any desired patent application by or on behalf of [the sponsor], such period, however, not to exceed three months from the date on which [the sponsor] received the intended publication for review. [The sponsor] may request a further delay of publication only in the case when a patent application has been filed and the prior application is incomplete and subject matter has to be added to the application during the priority year. In this case [the sponsor] may request a delay of any publication until the competition of the priority application. [The sponsor] shall not unduly delay such completion. The organization and/or investigator shall comply with all applicable requirements regarding disclosure of industry support (financial or otherwise) in connection with such publications and presentations. [The organization] shall impose the same obligations on publication as set forth in this section on all study team members. The obligation set forth in this section shall survive for a period of ten years upon early termination or expiration of this Agreement. Publication. [The organization] shall be free to use the results of the research and clinical study for its own teaching, research, education, clinical, and publication purposes without the payment of royalties or other fees. [The organization] shall submit to [the sponsor] for its review, a copy of any proposed publication resulting from the research at least thirty (30) days prior to the date of submission for publication, and shall consider in good faith all comments provided by [the sponsor] during that review period. If [the sponsor] determines that the proposed publication contains patentable subject matter which requires protection, [the sponsor] may require the delay of publication for a period of time not to exceed sixty (60) days for the purpose of filing patent applications. {If multicenter study, may insert language agreeing to delay publication until the earlier of the multicenter publication, or one year after the end of the study, but with a firm commitment from Sponsor to encourage publication}.

Element I.8.E It is required that the organization’s policies and procedures have contracts (or other funding agreements) that require the communication of findings from a closed research study to the researcher or organization when those findings directly affect participant safety. The sponsor’s experience and expertise should be relied upon to specify the timeframe.

Sample Language:

Following completion of this study under this contract, if [the sponsor] becomes aware of relevant findings from the study data that would directly affect the safety of the former study subjects, [the sponsor] shall promptly (or in a timely manner appropriate to the level of risk) notify the institution of such relevant finding so that the institution may communicate such findings to the former study subjects. [The sponsor] shall determine the relevance of the findings and the institution shall inform the former study subject as appropriate. [The sponsor’s] reporting obligation shall continue for two years following completion of the study conducted under this contract or until the occurrence of a triggering event (such as a data lock).

The following is acceptable language for I.8.B, I.8.C. and I.8.E.:

During and for a period of at [specify a period of time appropriate to the specific study, for example, least two years; or specify a triggering event, for example, completion of data analysis] after the completion of the study, [the sponsor] shall promptly (or in a timely manner appropriate to the level of risk) report to the investigator any information that could directly affect the health or safety of past or current study subjects or influence the conduct of the study, including but not limited to the study results and information in site monitoring reports and data safety monitoring committee reports as required by the protocol. In each case, the investigator and [the organization] shall be free to communicate these findings to each study subject and the IRB.

Sponsor Refuse Specific Language

Once sponsors understand the requirements they usually are willing to include them in the contracts and funding agreements. If a sponsor refuses to include the requested language, immediately inform senior officials and/or general counsel at your organization who are in the position to make decisions about pursuing the research protocol. For example, if the sponsor will not provide data and safety monitoring reports, the IRB will have no basis to assess risk at continuing review and thus the research cannot be approved.

Any discrepancies between the informed consent language must be modified to become consistent with the CTA.

Utilize good communication between the IRB and the unit that negotiates contracts and funding agreements.  Documentation of sponsor’s failed negotiation should be sent to IRB.