Risk based quality management (RBQM) in clinical trials centers on detecting, addressing, preventing, and mitigating risks and threats that could undermine patient safety, trial processes, and data integrity. The overall goal in this quality by design (QbD) approach is not to eliminate all errors, but instead to focus on reducing errors that matter and would otherwise threaten trial outcomes or patient safety. RBQM is a cross-functional framework enhanced by proactive risk monitoring and mitigation to ensure patient safety and overall data quality. Despite the fact that central monitoring can significantly help with overall data quality, adoption by industry is still sporadic and slow (Fig. 1).

RBQM landscape survey results for ongoing studies 2019–2022

The Association of Clinical Research Organizations (ACRO) is a trade association of global clinical research organizations (CROs) and technology companies. ACRO’s mission is to collaborate with regulators, policymakers, and other industry stakeholders, and help inform policy that fosters efficient, effective, and safe conduct of clinical research. We previously reported results in 2021’s Risk-Based Monitoring in Clinical Trials: Past, Present, and Future [1] and 2023’s Risk-Based Monitoring in Clinical Trials: 2021 Update, which includes all studies, all phases, and a wide range of indications and trial sizes. [2] The 2022 landscape survey has shown an overall, if uneven, rise in trials reporting at least one RBQM component. Our 2019 landscape survey of 6513 ongoing studies that year found just under half contained at least a single RBQM component; in our 2022 report on 4958 ongoing studies, more than three quarters contained at least a single RBQM component. The RBQM component definitions remained the same each survey year, in order to look at adoption trends over time. (See Table 1). Over the four years covered by our reports, an upward trend in all components was observed (See Fig. 1).

There are some important call outs to note in the data. The survey in 2022 found 65% of new study starts which have adopted centralized monitoring also reported reducing both SDR and SDV (Fig. 2). Interestingly, between 8 and 18% of new study starts reduced SDR and/or SDV without implementing centralized monitoring. This was common practice beginning around 2005 when risk-based monitoring was first gaining traction and companies were sampling subjects, subject visits or data points and the data visualization tools and technologies which support centralized monitoring were unavailable, immature and/or unproven in their value and return on investment. However, centralized monitoring was introduced in FDA’s 2013 guidance, Oversight of clinical investigations—a risk-based approach to monitoring to supplement and/or reduce the extent or frequency of onsite monitoring. The industry best practice among CROs and many sponsors has been to supplement any reductions in SDR and SDV with centralized monitoring to increase confidence in patient safety oversight and data integrity.

RBQM landscape survey results for new study starts 2019–2022

To quote the guidance, “a recent review of on-site monitoring findings collected during a multi-center international trial also suggests that centralized monitoring can identify the great majority of on-site monitoring findings. The review determined that centralized monitoring activities could have identified more than 90% of the findings identified during on-site monitoring visits” [3].

In early implementation of reductions in SDR and SDV, it was common for SDV to be reduced slightly (i.e., 70% of data undergoing transcription checks) but SDR to still occur at or near 100%. As centralized monitoring processes, tools and technologies have become more sophisticated and efficient in their ability to aggregate data across data sources and improve identification of issues and to monitor for data outliers, anomalies and trends, the reductions in SDR and SDV have continued to increase. Today, it is common to see sampling of patients or patient visits for SDR and not uncommon for some patients or patient visits to undergo very little or no SDV. It is virtually undisputed that centralized monitoring provides capabilities that are more timely, accurate, reliable, valuable and efficient than traditional onsite monitoring activities like SDR and SDV. It is important to note that onsite monitoring, including sampling of SDR/SDV is still recommended in most studies, but we continue to see steady reductions.