Quanticate CRO Blog

This blog explores the statistical methods used in Risk Based Monitoring (RBM) and how the result of such statistical methods enables improved data integrity across a clinical trial.

The ICH E6 on Good Clinical Practice was updated on 9 November 2016, the first addendum for 20 years. Sections 5.0 on Risk and 5.18.3 on Extent and Nature of Monitoring in particular created an increased need for Risk-Based Monitoring (RBM) and Centralized Monitoring (CM). The details of how this may be covered and the increasing evolution of a risk in the industry have been noted. The required changes involved create a number of different team roles. These include opportunities for biostatisticians and statistical programmers - players who may not have been so directly involved in onsite monitoring, a more traditionally clinical domain.

The ICH Guidelines for Good Clinical Practice (E6) has morphed into the international standard for clinical trial conduct since its inception twenty years ago. However, within that period, clinical research has changed dramatically and it is a credit to it’s authors that ICH GCP remains relevant today, with only one previous notable update seen in response to electronic data capture (EDC) technologies being widely utilized by the industry. 

With a growing trend towards the use of risk based monitoring, and with new technologies available to support this alternative to traditional onsite monitoring, there remains inertia to implement this approach. Having discussed remote monitoring capabilities with industry peers, we have identified the root cause of this reluctance as an intrinsic fear of flouting regulatory compliance within the conduct of a clinical trial.

Risk Based Monitoring is a term that is not new to the pharmaceutical industry. With increasing demand for budget reduction and reduced time to submission in drug development, both sponsors and vendors are seeking ways to reduce costs whilst still maintaining and potentially improving the quality of the data collected in clinical trials. Study costs can rise considerably for clinical trials with a large number of sites, especially across multiple countries. Risk Based Monitoring can reduce study costs considerably as there is a reduction in the need for CRAs to travel to sites, especially when coupled with a remote monitoring component. Also a reduction in the need to monitor all clinical trial sites and 100% of trial data, as those which are identified as more risk prone are visited more frequently according to targeted or triggered formulas. Even the FDA understands and encourages the desire to move away from 100% source data verification. Why therefore is the general mind-set in clinical operations exhibiting a degree of inertia to change with regard to RBM techniques? 

During drug development the cost of clinical trials can rise significantly for studies that require several monitoring visits across multiple sites. Traditional monitoring techniques account for a large portion of these costs. Pharmaceutical companies absorb the costs of travel when their own Clinical Research Associates (CRAs) visit sites, while Full Service CROs normally charge clients these travel costs as pass through charges. It is estimated that remote monitoring in clinical trials could reduce travel costs (including unproductive time spent travelling) by up to 30%, and in theory the practice should be scalable across small to large clinical studies over several clinical trial phases[1]. The unproductive travel time saved also means CRAs have more time available for monitoring activities, aiding with the current CRA shortages[2].