Contract research organizations (CROs) provide valuable support to clinical trial sponsors, who nonetheless remain liable for the conduct of their trials. We offer tips to protect against three common challenges that can arise during CRO-managed clinical trials: (1) the sponsor’s level of oversight, (2) a high turnover of CRO staff, and (3) the risk of poor performance by the CRO.
Sponsor’s Level of Oversight: Under most legal regimes, the sponsor remains responsible for the conduct of a clinical trial even if it outsources some or all of that trial to a CRO. The sponsor should therefore exercise appropriate oversight while protecting against the risk that the CRO seeks to shift liability for its own contractual obligations to the sponsor.
The following contracting tips help facilitate a sponsor’s oversight of the conduct of a clinical trial.
- Clinical Trial Agreements: Clinical Trial Agreements (CTAs) regulate the relationship between the sponsor and the site and investigator carrying out the clinical trial. A sponsor that tasks a CRO with negotiating the CTAs should provide the CRO with templates, negotiation guidelines, and the main requirements to be included in those agreements. As explained below, the contract party to the CTAs should be the sponsor, not the CRO.
- Effective control: To facilitate the sponsor’s effective control over the trial, the sponsor-CRO agreement should stipulate that the sponsor has the right to conduct audits with respect to the study at the CRO and any sub-CRO, such as Good Clinical Practice, Good Programming Practice, data protection, and financial audits. The sponsor should also have the right to stop any study-related activity at any time.
- Information sharing: To ensure its continued access to important documents and know-how, the sponsor should require regular status meetings with relevant CRO personnel and an unconditional duty that the CRO provide all trial-related documents requested by the sponsor.
- No waiver: The sponsor-CRO agreement should specify that the sponsor’s oversight does not waive or otherwise release the CRO from its contractual liability toward the sponsor. Similarly, the sponsor should be reluctant to agree to limiting the CRO’s liability.
High Turnover of CRO Staff: Many CROs face a high staff turnover which can cause delay and risk losing the CRO’s know-how related to the specific clinical trial. Delays cost money, and the loss of know-how can lead to repeat or unsatisfactory work and require increased time investment by the sponsor.
A sponsor can mitigate these risks even before selecting a CRO by asking about the average employment term of the CRO’s staff. This should factor into the sponsor’s decision when selecting among competing CROs. In addition, the following provisions in the contract between the sponsor and the CRO can further help protect a sponsor against the risks caused by high CRO staff turnover.
- Review of training records: The sponsor should specify the level of expertise required of CRO personnel allocated to the clinical trial and require the right to review the training records of those personnel.
- Replacement of personnel: The CRO should agree to not replace personnel without the sponsor’s prior agreement and should promptly notify the sponsor when replacement is needed. The sponsor should require that replacement personnel be equivalently qualified and experienced.
- Responsibility for costs and delays: The contract should require the CRO to compensate the sponsor for costs incurred as a result of delay and should further specify the penalties that will apply in the event of delays.
Poor Performance by the CRO: The success and value of a clinical trial can be jeopardized when a CRO performs poorly. A sponsor must therefore be able to measure the quality of the CRO’s performance and obtain effective relief when that performance is unsatisfactory. This includes the right to transfer management of the trial to the sponsor (or another CRO) as needed, which can present logistical challenges for large trials.
The following contracting tips help protect against poor performance by a CRO and simplify the transfer of the study management to the sponsor.
- Incentives and remedies: The sponsor-CRO agreement should clearly define the CRO’s deliverables and key performance indicators and include incentives for good performance (e.g., for reaching milestones early). It should also set out remedies for underperformance (e.g., transfer of the study, termination of the sponsor-CRO agreement, or liability for costs).
- Deviation notice: The CRO should be required to provide notice to the sponsor if it significantly deviates from the agreed standard of services; the relevant laws, regulations, and regulatory guidelines; or the sponsor’s or CRO’s procedures. The sponsor-CRO agreement should also define the relevant threshold that triggers the notice obligation (i.e., define what constitutes a “significant” deviation in that particular study, as this is difficult to define in the abstract).
- Replacement: The sponsor should require the right to request replacement of nonperforming or otherwise unsuitable CRO personnel.
- Trial agreements and transfer: To allow the sponsor to maintain control and assume management of the clinical trial if needed, only the sponsor (not the CRO) should be party to the CTA and other trial-related contracts. The sponsor can mandate the CRO to carry out the logistics of the trial, including signing contracts or making payments on its behalf.
These potential protections against common risks are more fully elaborated with a practical illustrative scenario in a recent article for In Vivo, a global publication in the life sciences space, which you may find here: Conducting Clinical Trials with CROs: Three Common Risks.
Avid readers of our Briefing might also remember Olivier Goarnisson’s article on Contract Research Organizations: Ensuring That Sponsors of Clinical Studies Meet Their Oversight Obligation in our February 2020 issue.