Clinical Shift Towards Centralised Risk Based Monitoring Processes

By Jan Kenworthy, Clinical Research Associate at Illingworth Research



Within the last few decades, the number and complexity of clinical trials has increased considerably. With this increased complexity, comes the enhanced pressure of effectively monitoring these trials. The size, complexity and number of clinical trials mean that complete on-site monitoring is becoming a more expensive and inefficient process. However, effective monitoring is critical for the protection of subjects and the integrity of the data produced.

On-site monitoring is still required by regulations, but remote monitoring is now seen as an acceptable alternative to this process. Recent research has shown that remote centralised data monitoring, including the use of electronic data capture (EDC) systems, may be able to detect fraud more effectively. The increase in use of EDC and other technologies can reduce the reliance on on-site monitoring and result in fewer clinical monitoring visits. The FDA draft guidance on risk-based monitoring states, that risk-based monitoring, including the use of centralised monitoring and technological advances, including email, webcasts, and online training, can meet statutory and regulatory requirements under appropriate circumstances.

In order to use remote monitoring effectively, a risk assessment must be performed and included in the monitoring plan prior to the start of any clinical programme. The FDA recommends that the monitoring plan be specific for the patient population, complexity, and data integrity risks of the trial, and would include a mix of centralised and on-site monitoring. On-site monitoring is used to: perform source data verification (SDV), identify missing data, perform staff training, perform IMP accountability, and provide assurance that study documentation exists. Remote or centralised monitoring can be used to: identify missing data, perform consistency checks, identify high-risk sites, verify source data remotely, and identify screen failure rates. The extent of remote monitoring is obviously dependent on the accessibility of EDC systems and hospital or clinic electronic source data systems. Complex, adaptive or multi-dose titration studies with critical endpoints may require more on-site monitoring visits, with less remote monitoring, whereas studies with simple study designs with one investigational product may require less on-site monitoring and benefit from more remote monitoring. The FDA now encourages a greater reliance on remote monitoring, but emphasises that a risk assessment should be performed taking into account the types of data that are going to be collected in a clinical trial and the required activities required to collect these data.

Ultimately, clinical monitoring must ensure the protection of the rights, safety and well-being of clinical trial subjects, and the quality and integrity of the data.

Click the following links to access guidance documents on risk-based monitoring:

EMA Reflection Paper on Risk-Based Quality Management

FDA Risk-Based Approach to Monitoring – Draft Guidance