Adherence and Patient Retention in Rare Disease Trials
In rare disease trials, every patient is hard to replace. Our final ICH chapter looks at how poor adherence becomes a first step to dropout.
The knock-on effect is a simple and familiar concept, but it is one that can have surprisingly potent implications.
In straightforward situations, just one unexpected event has the potential to trigger a cascade of subsequent undesirable results. And in the context of more complex ecosystems, this chain of impact can be felt in orders of magnitude.
In clinical trials, this fragility is certainly apparent, particularly in the case of trials for rare diseases, where challenges abound in recruiting, retaining, monitoring and supporting patients throughout the process. Any weaknesses in this delicate chain can have negative knock-on effects that are felt further downstream.
So far in this article series we have considered how patient retention can be a major factor for the derailment of trials, a situation compounded in rare disease trials by inherent recruitment difficulties. We have also explored the poignancy of retention problems in light of tighter regulatory expectations ushered in with ICH E6(R3). Finally, we have considered how adherence is central to these challenges and how, despite sometimes being overlooked, it can be a positive catalyst for supporting patient engagement, thus minimising dropouts, reducing the risk of trial failures, and promoting greater alignment with an updated regulatory landscape shaped by quality outcomes.
In this final chapter, we look at the logical question of how, practically speaking, the issue of adherence can be addressed. If, as outlined, it plays such a pivotal role, what approaches can clinical teams implement to promote greater levels of compliance among a higher proportion of the trial cohort and avoid the damaging knock-on effects caused by non-adherent behaviours?
At Pill Connect, our philosophy is not rooted in wholesale re-engineering of trial protocols to achieve this aim. Rather, we believe that by introducing subtle changes in how the issue of adherence is addressed, there is potential to realise significant advantages for engagement and retention. Simply put, with greater clarity on adherence, clinical teams have greater visibility of acrucial potential area of weakness. This then opens the door to pre-emptive action and limits the risk of important drop-out risk signals getting lost in the wider noise of the trial.
Our solution is centred on proprietary smart dispenser technology that integrates with oral dosage containers. The device simply replaces the existing plastic cap and, in doing so, introduces monitoring sensors that register and record in real-time when trial drugs are dispensed. Immediately, clinical teams are equipped with objective data on dosing behaviour, providing a powerful indicator of adherence patterns – both compliant and not.
This has particular benefits where dosing occurs outside of a clinic environment and not under the supervision of a healthcare professional (HCP). In these scenarios, the potential for deviations from the protocol are increased, but the only evidence relating to adherence might be in the form of retrospective pill count, which cannot communicate dose timing. Alternatively, co-ordinators might need to rely on a patient diary – a subjective record that is prone to inaccuracy, bias and even falsification.
Conversely, with real-time data on adherence, clinical teams have advanced insight into how well they a patient is following the protocol and, by association, how well-engaged they are with the trial itself. If these signals indicate deviation and weakening compliance, teams are given a valuable window of opportunity to address any issues or concerns before they escalate. Without intervention, this non-adherent activity will ultimately feed through into poor data on exposure to the trial drug or, worse, it will be a pre-cursor to drop-out. With poor retention, overall trial power is weakened, or the viability of the trial itself can be put at risk.
Whilst adherence by itself cannot guarantee trial success, accounting for it removes a critical vulnerability in the retention chain. Of course, many factors must align for this outcome to occur, but its significance underlines the importance of exploring mechanisms that can conspire to prevent it from happening. Like the knock-on effect, adherence should be a simple concept – a straightforward case of taking the prescribed medication as indicated – but our fallibilities as humans can trigger unexpected behaviours and undesirable outcomes. Equipped with a real-time view of those behaviours, however, clinical teams are better placed to prevent retention problems and promote the quality outcomes demanded by regulators today.