Clinical Trial Agreement (CTA)

CTA definition: What is the clinical trial agreement and why is it important?

A clinical trial agreement, or CTA, is a legal contract that defines the working relationship between a trial site and the sponsor (and the CRO, if applicable). In the case of multicenter clinical trials, each site must have a separate CTA with the sponsor.[¹]

The CTA lays out all the responsibilities and obligations of each party and defines all terms of the study.[¹],[²] Another name for CTA is CSA, or clinical study agreement.

Who develops the clinical trial agreement?

The CTA is typically developed by the sponsor, or by the CRO responsible for selecting sites if that is the case.

What is the difference between a CTA and CDA?

A confidentiality disclosure agreement (CDA) is another important legal contract that will likely need to be signed by the site during the site selection process, which establishes non-disclosure of confidential details of the study.[³] However, unlike a CTA, the CDA only relates to the sharing of information, dictating how and for what purposes specific types of information can be used and disclosed.[³] Thus, the CTA and CDA are both contracts signed between the sponsor and study sites, but they serve entirely different purposes.

What are the components of a clinical trial agreement?

While the clinical trial agreement will differ from trial to trial, certain sections must be included in a CTA, such as the basic components listed below:[⁴]

• Clinical trial description: An explanation that explicitly states the purpose of the clinical study, in clear language to ensure there is no confusion or room for assumption.
• Payment schedule and terms: Details that clarify expectations of the sponsor, CRO, and site regarding trial deliverables, payments, and payment timeframes.
• Sponsor, CRO, and site responsibilities: Particulars of each party’s responsibilities in regard to the study protocol as well as applicable laws and regulations. Specifics in this part should include explicit considerations of all trial operations and management tasks.
• Data records and monitoring: Explicit definition of ownership of the data collected during the trial, how often sponsors can inspect and monitor data collection, and for how long the trial data should be stored after study completion.
• Intellectual property and publication rights: Details on who owns the trial results, findings, and data records, and under what circumstances (if any) clinical trial sites can publish any study-related material, either with or without the sponsor’s prior approval.
• Insurance and indemnification terms: Details about who is responsible for compensation if a third party, such as a trial participant, is injured or harmed during the clinical trial. Note that while it is normally the sponsor who is responsible for such aspects, that may not always be the case - for example, if the trial site is single-handedly responsible for the non-compliance (this should be laid out clearly in the CTA).
• Dispute resolution guidelines: Definition of how parties will mutually resolve issues to avoid escalation. For cases involving legal action, this part should also specify which jurisdiction will manage the case, as the sponsor and trial may be in different locations.
• Contract termination terms: Details on when/under what circumstances the CTA can be terminated, i.e., in cases of fraud, federal non-compliance, etc.
• Terms for amending the CTA: Procedures for updating the clinical trial agreements, if necessary, in order to handle any unexpected situations arising during trial operations.

Case study: The importance of clarity

If all aspects of a clinical trial agreement are not defined thoroughly clearly, it leaves room for interpretation or misunderstandings, which can have serious legal ramifications.

Take, for example, the case of the $7 million USD lawsuit filed in 2000 by the sponsor Immune Response, a biopharma company, against its trial site, the University of California at San Francisco (UCSF). When the UCSF site’s researchers published negative findings from the clinical trial without the sponsor’s approval, Immune Response took legal action against UCSF. The claim resulted in UCSF filing a countersuit claiming that the signed CTA did not dictate the exact terms of publication, and thus that its researchers had permission to publish the results.[⁵] Immune Response eventually dropped the countersuit.

This is just one of many examples that serve to highlight the importance of explicit clarity in the CTA. Dealing with substantial legal action takes its toll on all parties, costing time and resources as well as affecting each party's reputation within the industry. Furthermore, such public attention lends itself to negative perceptions about clinical research and drug development efforts in general, which could ultimately be detrimental to the entire healthcare sector. Sponsors, CROs, and trial sites have a strong interest in taking the time to develop and negotiate all terms and conditions in their clinical trial agreement thoroughly to safeguard all parties' rights.