When a high-profile authority in the medical world such as the World Health Organization’s publishes guidelines governing best practice in clinical trials, the sector takes note.
Reading the guidelines, many will have welcomed WHO’s aims to “reform, improve and streamline” oversight and approval processes, leading to a strengthening of clinical research systems. And while the true significance of this ambition will ultimately be judged on how well the measures advocated are adopted, the wider acknowledgement of the need for change in clinical trials is a positive message for the industry to take forward.
In the section of the guidelines outlining the key scientific and ethical considerations for clinical trials, the document lists five key points that must be addressed in order to define a trial as “good”, i.e. one that is “reliably informative, ethical and efficient”. Ranked first among these key points is ensuring trials are “designed to produce scientifically sound answers to relevant questions”, under which it includes “Adherence to the allocated trial intervention” as an important area of focus.
WHO, therefore, is unequivocal in its view that adherence – in the sense of faithfully complying with the allocated trial intervention – is critical to the success of randomized clinical trials. It acknowledges the logical importance of this condition being met in order for regulators to be able to confidently determine the efficacy and safety of the therapy under trial. As an extension of this logic, it acknowledges the critical importance of evidencing this adherence using robust methodologies and rigorous data-capture techniques in order to validate the integrity of the output.
Within the ecosystem of a clinical trial, however, this logic can often fall down. It is known that large proportions of participants do not always adhere to the dosing regimen specified in the protocol and do not always accurately report dosing activity. As such, this prevents regulators from getting a true measure of exposure and clouds their ability to make informed conclusions regarding efficacy and safety. Simply put, without rigorous data on adherence to the allocated trial intervention, there is an obvious risk of misleading results and, potentially, trial failure. In these circumstances, adherence might be valued, but it is not adequately policed, promoted and protected.
The obvious question is what can be done to address the problem, and an important part of the answer lies in the fifth key point of the WHO guidance, “Good clinical trials manage quality effectively and efficiently”. Given that monitoring and measurement of adherence to allocated intervention has revealed itself to be a key risk to the integrity of trial data, so it should be considered a key priority to be mitigated within the robust framework of RBQM – with its emphasis on the Quality by Design (QbD) principles that have long been advocated by both the US Food & Drug Administration (FDA) and the European Medicines Agency (EMA).
Pragmatically speaking, this introduces further questions around the nature of how trials should be designed to ensure dosing-history data-capture is optimised. Given the flaws inherent in the human-centric methods of adherence monitoring (i.e. pill count and self-report) this places clear emphasis on the need to employ more automated digital techniques that can more reliably, efficiently and accurately track dosing activity. It is only by empowering trial regulators with this enhanced information that they can better understand true levels of exposure and form better critical judgements on efficacy and safety.
In this context, implementing automated digital methods of adherence monitoring should not be simply a considered best practice, they should be a strategic imperative driving better outcomes and stronger results. After all, it is imperative that a trial fulfils its core purpose of evaluating a treatment’s effectiveness – not simply as per the assigned protocol but in relation to true levels of exposure.
Bringing all these elements together, it appears that the clinical trial sector has a clear opportunity not just to embrace the underlying strategy for better adherence outlined by the WHO guidelines, but also to adopt the practical approaches and technologies that are known to enhance study strength through authentically better monitoring and measurement. Together, they provide both the tools and the framework for turning the theory of best practice in clinical trials into a practical reality.