Risk-based monitoring (RBM) is heralded as the new solution to all troubles in clinical research – the exorbitant complexity, the ridiculous costs, the nerve-wracking SAEs. Sponsors and CROs are gradually adopting RBM, but many still hesitate to jump on the bandwagon. The questions are endless:
- What is RBM even about?
- Do we know how to do it?
- Can we even do it by ourselves?
- Can someone else do it?
RBM is a risk-based assessment and mitigation plan that should be included in every monitoring strategy. The measure was first mandated by the ICH in 2016 – for good reason. The rationale behind its adoption is to safeguard patients’ safety and data quality, and RBM is becoming more popular as regulators are growing more risk-averse over the years.
Sometimes RBM and centralized (also called central or remote) monitoring are used interchangeably, but they shouldn’t be. RBM is an addition to a monitoring strategy, whether on-site or centralized (or both). For example, all monitoring activities can be done in person with RBM, remotely without RBM, or both physically and remotely with or without RBM. Centralized monitoring does not automatically include RBM practices, but they can complement each other.
Given such combinations, sponsors may experience a hard time arriving at one definitive strategy. There are no concrete instructions, and planning a successful RBM design can be challenging. Even so, we believe investing in an experienced partner to help you with RBM design is worthwhile. RBM can be an indispensable tool for your trial’s success, and we will outline a few criteria in this blog that could be helpful in finding the right RBM specialist.
No Standard Approach
The biggest challenge is that there is no standard approach to RBM, nonetheless, sponsors and CROs are scrambling to implement this strategy in their monitoring plans. The FDA does provide some guidance, which may be vaguely received at times given the variability in study designs. For instance, the agency suggests a healthy mix of on-site and centralized/remote monitoring in tandem with RBM support, but nothing more in terms of concrete planning instructions.
Herein lies problem #1: “How should I allocate my resources on monitoring on-site versus remotely?” 100% centralized monitoring is risky because critical deviations or data anomalies can be overlooked, not to mention that your sites will feel neglected as time goes on. Alternatively, performing 100% SDV in person is very costly. In addition to paying your CRA, your budget will swell with costs like lodging and travel adding up. Additionally, blindly sending monitors to sites without any preceding knowledge can be an inefficient use of their time.
There is also problem #2: once you have figured out the “sweet spot” in terms of on-site versus central monitoring ratio, you will need to again allocate your resources on targeted versus triggered RBM strategies. Would you rather plan a risk-mitigation strategy ahead (targeted) or wait until something happens (triggered), like a massive chain of adverse events or deviations? Targeted monitoring is often Biorasi’s preferred strategy, though admittedly, it is consuming during planning stages. The FDA does list examples of critical data (like study endpoints and ICF verifications) that you can use to craft a targeted RBM plan, but the focal points will be very different per study.
Outsourcing
Creating a viable risk-mitigation strategy can be overwhelming for sponsors (especially startups) who could benefit from external assistance. If you, as a sponsor, plan to delegate such planning to a CRO, be conscious with who you choose to partner with.
RBM can provide great value, but it is important to note value is not just about cost. The quality of the product – in this case, the delivery of a successful trial – is the most important outcome. Try to avoid CROs who promise the moon at an unbelievable bargain, but in actuality are unable to prepare a solid RBM plan. The “bargain” may end up costing you more when the cheap, but badly designed, RBM plan ultimately fails your study, because by then you will have to restart from scratch, either by yourself or with a new CRO.
Consider this: A sponsor needing help with an Alzheimer’s trial hires a CRO, who promised a low-cost RBM implementation plan with lots of centralized monitoring. The reasoning is to reduce IMVs (interim monitoring visits) and thus overall costs, which seems good on paper. Five months in, queries start piling up, adverse events are unresolved, and deviations are endless. The CRO does not have the budget to travel to sites to resolve errors, and the email chains back and forth accomplish little. The neglected staff at these sites grow frustrated and so does the sponsor. The sponsor eventually will spend even more time and resources to salvage the study, and this unfortunate disaster could’ve been avoided had a slightly costlier, but more qualified CRO was selected to execute this project from the get-go.
What should I look for in a CRO?
From our experience in rescuing trials with faulty RBM designs, especially in therapeutic areas like neurology, there are at least 2 key factors to consider:
- The CRO must have a great working relationship with their sites. Many sites are reluctant to adopt RBM because of perceived reasons, like IT difficulties and greater administrative burden. A well-trusted CRO should be able to convince their sites how RBM will optimize everybody’s time and effort. In addition, a good portion of site staff (17%) do not feel capable of participating in central monitoring, which is an important component of an RBM plan. The same CRO should be able to cordially mitigate this lack of expertise, and this brings us to the second item – training.
- The CRO must have a solid training program to resolve and prevent any shortcomings that the sites might have. For example, detailed IT training is usually more pressing for ex-US sites that need help with EDC systems. This is especially important in RBM plans with centralized monitoring, where proper data input will allow remote monitors to detect and resolve anomalies or deviations in a timely fashion. Good training will also establish an efficient work flow and alleviate the fear of pursuing unnecessary administrative burden.
We do plan to discuss RBM in-depth in a future white paper. Stay tuned for more updates.
