Our industry is challenged to make drug development a more efficient process while delivering high quality results on time
and within budget. The common knowledge in the industry is that clinical trials have become more complex and drug development
costs continue to rise. However, the results and deliverables may not meet the levels of quality required for successful marketing
applications. Put simply, the costs of failure are costing us all too much. The CRO industry as a whole must refine its services
and deliverables and take the time to complete due diligence on the front end, in order to streamline the trial process and
deliver projects as promised. As an industry, we have to increase our levels of strategic and tactical knowledge so that the
insight we provide to our clients will ultimately deliver development programs of the highest caliber. Risk-based monitoring
(RBM) is an approach that can actually save time and cost as it contributes to the efficient conduct of clinical trials.
Monitoring and its purpose
Sponsors of clinical trials must provide oversight to protect the rights, welfare, and safety of human subjects and the quality
and integrity of data that are obtained during the trial.1, 2 With the technology and tools that have become available over the past 25 years, pharmaceutical development need not be bound
to the same methods of monitoring that were being used in the 1980s. This is why the FDA and EMA are encouraging the use of
modern methods for monitoring the progress, safety, and quality of clinical trials. In spite of encouragement from regulatory
authorities, adoption of RBM and other innovative approaches has been slow. If we don't use them, we cannot benefit from them.
Risk-based monitoring—what is it?
Risk-based monitoring identifies the sources of risk that diminish the objectives of clinical development programs. Those
objectives have already been stated: "protect the rights, welfare, and safety of human subjects and the quality and integrity
of data." After these sources are identified, they are monitored during the course of a development program. This is where
the "risk" aspect of RBM originates—risk is not part of RBM because less information is examined than would conventionally
be examined and therefore it is "riskier" but costs less, so it is justified. Rather RBM carefully examines:
- What sources impose meaningful threats to the objectives of clinical development?
- What signals from those sources will be considered and how frequently they will be considered?
- What level of signal intensity from those sources will trigger an action, such as increased monitoring (on-site or remote)
attention, or intervention and correction?
Risk-based monitoring may be difficult to understand because it regularly uses multiple methods to meet monitoring requirements
that are present; it is not just one technique. The EMA noted,2 potential "adaptations to conventional GCP methods" when RBM is used. In doing so, the EMA suggests these might include
adaptations to on-site monitoring visits, sample/focused/targeted source document verification, or centralized monitoring
(both manual and electronic are possible). The various methods that can be employed may reduce the number of on-site visits
required, however, crucially, this doesn't mean less information is being monitored. To obtain the expected benefits, the
way in which the necessary information is monitored, compiled, analyzed, and interpreted must be better than conventional
methods. Given the tools we have today, including major advancements in electronic data capture, we know that many of the
associated tasks can be completed more frequently and at less cost through RBM than through conventional, on-site monitoring
methods. Centralized monitoring can improve our ability to capture data anomalies, fraud, and safety concerns, and identify
these threats more rapidly because of the whole-study or whole-program view, and because of the continuous, timely stream
of data flowing into the centralized group. The fact that these broad issues can be detected and addressed throughout the
course of a study means that the traditional end-of-study flurry of activity that can be so demanding and prone to error can
be reduced in its magnitude. "Last minute" is no longer a required expectation.
Operational metrics can also be collected and interpreted by a centralized group. This characteristic enables the delivery
of information to on-site monitoring personnel, resulting in more critical, productive, and efficient site visits.
Risk-based monitoring should not be considered a turn at the roulette wheel. It is not a throw of the dice, or even the development
of computationally intense statistical algorithms aimed at establishing a sampling method, which itself reduces the amount
of work required on a clinical study. RBM is instead a set of methods that, when applied throughout the planning and conduct
phases, results in safer, less costly, and more successful studies; with the emphasis on higher quality.