As clinical trials have become increasingly complex, clinical trial oversight has become more difficult to standardise. To facilitate improved standardisation, risk-based monitoring (RBM) approaches are progressively being implemented by oncology-focused pharma, biotech and CROs alike.
Reduced source data verification (SDV)
RBM is not a new concept as it has been around for over 15 years; we are just seeing more implementation of it now. For example, the trial sponsor can spend a considerable amount of time likening data in case report forms (CRFs) with original source data, so implementing RBM here can support reduced site visits and SDV monitoring. Early identification of any challenges e.g. where select data may be inaccurate, can facilitate improved trial efficiency – ultimately reducing development costs and improving cycle times for oncology trials. While RBM can support SDV efficiency, protocol design must also be considered as this is a critical element of the trial. This is still a key area for improvement when it comes to RBM and there are certainly opportunities for trial sponsors and RBM vendors alike to explore.
Regulatory considerations
As yet there is no distinct monitoring approach that is fitting for each and every clinical trial; however the FDA’s current guidance indicates specific features of monitoring plans that should be implemented across all trials (including oncology trials). The current guidance explores centralized monitoring, specific standardizations and processes that are well defined to ensure timely access to data and documentation. Risks are assessed and prioritized based on 1) likelihood of errors occurring 2) impact of such errors on human subject protection and trial integrity, and 3) extent to which such errors would be detectable. Building on this, the main considerations for a trial sponsor include: harnessing critical data and processes, ensuring informed consent is appropriately obtained, adhering to eligibility criteria, supporting appropriate product accountability, assessing study endpoints alongside safety measures, and accurate adverse event reporting. The aim is to driving forward trial integrity, alongside supporting patient-centricity. Regulatory guidance can be met with opposition, however opposing parties still recognize the significance of implementing RBM and the opportunities it spotlights.
CROs and RBM
Technological advances e.g. the use of real-time EDC in trials can allow studies to be monitored almost in real-time. For example, some CROs have EDC systems for targeted monitoring and this is particularly advantageous for oncology trials -allowing the trial sponsor to have constantvisibility into trial data. Clinical Monitoring Services (CMS) offered by vendors with RBM capabilities can be designed to complement the study protocol and the trial sponsor’s goals. Trial sponsors may adopt an electronic study start up solution allowing them to harness real-time access to status updates, facilitating quicker reactions;as opposed to communicating with the CRO each time for this information.The overall aim is to guarantee study conduct transpiresin relation to protocol while adhering to GCP guidelines.
In summary, the main aim for RBM is to reduce the number of monitoring visits and this has been achieved successfully across a number of trials globally. Looking specifically at oncology trials, RBM can mean faster recruitment and focus time more effectively to provide the most value to investigator staff.There is still a lot of breathing room for RBM in oncology trials; with collaborative approaches between trial sponsors, RMB vendors and regulatory bodies driving forward innovation and yielding positive clinical outcomes.
