Most companies outsource their clinical trial activities, however it is the sponsor who is entirely responsible for the clinical trial performance. Without mirroring the work of the CRO, the sponsor has to be in lead of the clinical evaluation process and needs a reliable overview of study progress and performance.
Especially small or medium-sized biopharmaceutical enterprises, and medical device companies moving into early phase clinical trials are struggling with the definition and integration of a study oversight that complies with the ICH-GCP E6 (R2) guideline considering the increased scale, complexity and cost of clinical trials.
Define your study specific KPIs
Effective oversight is only possible when a pragmatic clinical trial management plan and a solid communication and escalation plan are in place. The centrepiece of oversight management is the definition of standardised and tailored metrics or key performance indicators (KPI). The sponsor should use KPI to identify problems before the trial is adversely affected. Risks can be timely mitigated and the study conduct can be improved.
Thus, the first step is to find out which KPI are relevant for the sponsor to perform oversight. These can be simple metrics like number of patients compared to the plan or ratio of data for a defined process. They can be compared to industry standards or on a study level with defined acceptance level of deviation.
KPIs should at least cover the analysis of:
- performance quality
- patient safety
- financial controlling within a clinical trial;
It can be extended to cover a full clinical development programme. Many KPIs have to be tailored to the respective clinical trial, as they depend on the scope of the trial, the indication, and the number of parties involved. For example, the number of patients to be enrolled depends on the indication. The set-up of the database depends on the number and complexity of the case report form pages, and, therefore, the timelines must be carefully devised between the teams, and realistic assumptions have to be agreed upon.
Other metrics such as the time needed to set up the tools, process descriptions, database, and statistical plans are important. Not only to show the progress, but also to provide information about performance and management skills of the CRO and sponsors alike. The set-up of the starting tools is often a challenge for a small-sponsor team to comply within the turnaround time.
Communication is key
The application of a clinical trial oversight system needs a strong alignment between sponsor, CRO and other vendors, as the tools are only efficient and effective when all parties have a common understanding of the desired content and goals. This agreed understanding needs to be reiterated throughout the whole period of the working relationship, which goes hand-in-hand with establishing transparent communication between sponsor, CRO, and other vendors involved.
The set-up timeline, as well as the review time of the project plans, can be a bottleneck if a small-sponsor team has to review and approve a high number of operational documents coming from different sources such as clinical operations, data management, interactive web response systems, drug supply and laboratory manuals. Therefore, each small delay can have a huge timeline impact as resources would be overbooked and the start of enrolment would be at risk. The resources needed can be easily underestimated by the sponsor, but when applying suitable metrics, the timelines and corresponding resources can be proactively tracked and steered. Such metrics can also be applied as an indicator of whether enough resources are available at the CRO.