Globally, our industry is becoming much more focused on reducing clinical trial complexity and drug development costs. Increasingly, trials are taking an adaptive or risk-based approach to monitoring studies.
Supported by the ICH-GCP R2 publication, this approach focuses on what is critical to support the endpoints of the study, and to ensure subject safety and GCP compliance. With consideration of the data and processes available to review centrally using advancing technologies, this approach can increase quality, save time, and improve cost-effectiveness.
What sites can expect
The day-to-day running of a trial at a site will see little impact from a risk-based or adaptive approach to monitoring. Principal Investigators (PIs) and site staff will continue managing their subjects, and site, in compliance with the protocol, regulatory requirements, and ICH-GCP; and with support provided by their Clinical Research Associate (CRA) and the project team.
However, an adaptive monitoring approach includes consideration for what data and processes can be reviewed centrally, or off-site. Because of this, the site will see a difference in how their support is provided.
Sites are used to seeing their CRA regularly during on-site visits and working with them to resolve any site issues including data, protocol, or GCP compliance issues. With an increase of monitoring occurring off-site, this support will shift from a CRA sitting with the site during an onsite visit to a monitor speaking to the site via offsite visits. At PRA, a Central Monitoring Associate (CMA) will provide this offsite support.
In many cases, this has led to investigative sites feeling that adaptive monitoring means they will never get to see the CRA. Or even more concerning to the site, that they will only see their CRA if the central review of data suggests there is a performance problem at the site.
While it is true that the sites may see their CRA less frequently, the sites should feel reassured that they will have offsite support. The level of offsite support is tailored to the needs of the specific study taking into account what can be reviewed centrally, or offsite, but also through consideration of the overall risk rating for the study (i.e., complex protocols or patient populations may justify more onsite time).
The Offsite Interim Monitoring Visits (OIMV) represent the biggest change for the site. These visits are conducted centrally to ensure the rights and well-being of subjects and that site staff are conducting the trial in compliance with the protocol, ICH, GCP, and regulatory requirements. These visits ensure that reported data is collected and entered in a timely way. While offsite monitoring may mean more reliance on the site to review their records to support OIMV discussions, the objective of off-site monitoring is to drive overall quality and compliance in much the same way onsite visits historically have.
Benefits are clear
Advancing technologies allow us to review more and more data centrally with functionalities constantly improving and expanding. From a site perspective, this means more targeted discussions will be held using the centrally analyzed data. Importantly, this allows assessment of trends and/or anomalies in the data to be performed in the most proactive way. This review will help decrease risk exposure to subjects, sites, and the sponsor, as the study will “adapt,” either at a study or site level, based on what the data is showing us. This is the core benefit of risk-based or adaptive monitoring for all subjects, sites, and sponsors.
Sites should be comforted that data is being reviewed in a more proactive way and concerns, trends, and anomalies can be addressed faster. Proactively addressing what the data is telling us benefits everyone involved in the trial. Ultimately, this means patients are not exposed to unnecessary risk, and where adaptation to a trial is required, this action is taken in a timely way.
In terms of challenges, some sites might struggle because their CRA is not present on the site as often. In particular, sites new to research or GCP may find this challenging; however, the proactive and targeted response to data review should counter-balance this.
While the industry settles into a more adaptive approach to site monitoring, the education of sites on how this benefits them will be critical to ensure seamless partnerships continue with our investigative sites. Providing a cohesive partnership ensures everyone—from sponsor to site, and from site to subject—benefits from this changing approach.