Clinical development is at a crossroads. The demand for faster more cost-effective drug development is forcing the the need for transformation. According to Tufts Center for the Study of Drug development it can take 10 years and up to $2.6 billion dollars to develop a new drug, with 80 percent of the total drug development time and costs associated with clinical trials. We simply have to do better. Our patients deserve new and more efficient methods for executing clinical trials. And one area that offers potential improvements is in the way we monitor risk.

A significant proportion of the time and expense of conducting a clinical trial is tied to monitoring for risks. In a traditional trial, this process is conducted by on-site monitors who arrive for pre-scheduled visits to compare site documentation with trial protocols in order to verify that patients are being treated according to the plan and no risks or issues have emerged to compromise patient safety or data integrity.  In today’s world of innovative technology, the monitoring process can be much more dynamic and efficient for our sites, our pharma customers and our patients. This is in part, why the clinical research industry is moving toward a risk based monitoring (RBM) approach that promises to make this process a lot more efficient. During a workshop at the 2016 DIA meeting this month, I will be presenting on the impact RBM has on site performance, and exploring how companies, and our investigator sites, can use this strategy to reduce risks while improving patient safety and study quality.

The benefits of RBM

An RBM approach allows us to take advantage of electronic data capture systems and statistical assessment models to conduct a more dynamic risk monitoring program. This centralized approach provides an opportunity to watch for trends across all sites on a trial rather than assessing each site individually; in doing so we can more quickly identify outliers that require mitigating actions in response to specific risks.

This event-driven approach, means monitors and sponsors can focus their resources on preventing or mitigating risks to data quality and patient safety, rather than spreading monitoring resources evenly across every site regardless of their performance. This helps them make faster, more informed decisions, which can improve patient safety, increase study quality, and enhance trial management efficiency.

This isn’t just the opinion of sponsors and CROs, RBM is supported by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and several industry consortia, including Transcelerate, which launched the Risk-Based Monitoring Initiative in 2012 to help improve the quality and efficiency of RBM.

Myths debunked

Initially there was a great deal of uproar about RBM, with critics suggesting it was a way for sponsors to impose monitoring work back onto the sites. But in truth, an effective RBM program can offer benefits for the sites as well as sponsors and CROs.

Myth #1Lack of visits means more work for site staff. One of the big concerns with RBM is that if monitors stop doing on-site visits, the site staff will be forced to conduct all of the administrative tasks they formerly performed, then report that information to monitors via monthly phone calls or fax exchanges. But that’s not how a true RBM model works.

Reality: Compliant sites have less work. In an effective RBM program, a monitor will conduct initial on-site visits to identify any concern areas, and to make sure the staff understand the requirements of the protocol and the RBM model. Once monitors are confident that a site has what it needs to achieve data compliance, they will track the sites progress and outcomes remotely via a centralized data capture system, analyzing data from all of the sites simultaneously to identify trends that require attention. This means that as long as a site is meeting all of the protocol requirements and recording the necessary data, they will spend less time on monitoring tasks, which frees them to focus more energy on managing the trial.

Myth #2: Fewer visits means higher risk. Critics also worry that if monitors stop going to sites it means that monitoring just isn’t happening, creating room for problems to fester.

Reality: More time and resources are spent addressing risks sooner: As the FDA guidance document so succinctly states: “A risk-based approach to monitoring does not suggest any less vigilance in oversight of clinical investigations.” Instead, using analytics and technology they can more quickly identify outliers, and focus more time and resources on dealing with these real risks to human subject protection and trial integrity, rather than spending much of their time reviewing paperwork at sites that have repeatedly demonstrated compliance.

Quintiles recently conducted an analysis of feedback from investigators in both RBM and traditional studies, which shows that RBM studies have on average four percent fewer errors than traditional studies. In other words – quality improved with RBM even as the burden of monitoring was reduced.

Myth #3: Sites lose their connection with the CRA. Some sites view monitor visits as an opportunity to build a relationship with the CRA, and they worry the loss of these visits means that relationship will suffer. But they don’t have to meet face-to-face with these monitors to build a strong connection.

Reality: Relationships are even stronger. With RBM, monitors may not always be on-site, but they are always available to talk, and still schedule regular, agenda-driven conversations with site leaders. These conversations focus on the needs of the site and questions investigators have about the trial and their performance. As a result, these relationships actually improve –our analysis shows investigators in RBM studies were more likely to say their monitors communicate effectively, and that they have a good working relationship than those in traditional studies.

RBM requires a fundamental change in the way we think about risk management, and change can be difficult to embrace. Once sites participate in an effectively run RBM study and see the benefits that this approach brings, it’s not hard to make the switch. 

Topics in this blog post: Biopharma, Clinical Trials, Data and Technology, EMA, FDA, Risk