Approaching the inflexion point? Year-end reflections on attitudes to adherence in clinical trials
AARDEX Group
AI-powered SaaS Platform Revolutionizing Clinical Trials Through Better Drug Exposure
It is said that the definition of insanity is doing the same thing over and over and expecting different results.
?
And whether or not those words were ever spoken by Einstein, it’s a sentiment with strong logic: the status quo might be a place of comfort, but it is rarely the start point for progress and improvement. Indeed, if unchallenged it can sustain practices that are unhelpful and even harmful.
?
In the pharmaceutical industry, a collective faith in science generally acts as a powerful safeguard against the risk of complacency, but as we approach 2025, there continues to be evidence of its influence in clinical trials.
?
Despite being an inherently flawed approach, returned pill count and patient self-reporting remain the dominant methods of assessing drug exposure in clinical trials. It is a method that might have been tried (but not properly) tested for many years, and those trials and tests have consistently exposed the fact that untraced human errors and unreported non-adherence can significantly impair the fundamental task of tracking candidates’ true exposure to a drug. In doing so, sponsors and regulators are unwittingly left with a weak dataset that does not accurately reflect dose accuracy, efficacy or toxicity.
In order to break out of the status quo, there must not only be recognition and acknowledgement of these flaws, but also movement from a position of awareness to one of intent and, crucially, action. Promisingly, in recent years we have seen a continued gathering of momentum around the need for a new direction to be taken when it comes to adherence monitoring in clinical trials, and it is much needed in the context of the current market, where the significant investment associated with trials has come into sharp focus.
?
Reports suggest that over the past year, there has been a significantly elevated volume of study delays and cancellations across all therapeutic areas, with small and mid-sized biopharma sponsors often struggling to access the funding required to sustain the next phase of research and development while larger pharma sponsors are realigning their product development priorities as a result of pricing pressures – particularly in the wake of the ongoing roll-out of the Inflation Reduction Act of 2022.[1]
?
This budgetary pressure amplifies the importance of eliminating at source any approaches that reduce study power, which in turn can trigger regulatory demands for aspects of a trial to be repeated or, in the worst case scenario, for the trial to be terminated.[2]
?
In addition to this impetus to minimise costs through improved integrity of trial practices, there is a complementary and growing urgency among patient advocates to set dosing at optimal levels, thereby limiting the potentially debilitating physical and mental impact of excessive toxicity. This is particularly pertinent in oncology, where groups such as the Patient-Centred Dosing Initiative are working to highlight the damaging effects on quality of life that can stem from the philosophy of establishing drug regimens based on a maximum tolerated dose.
One survey of women with metastatic breast cancer shines a bright light on this issue, with 86% of respondents reporting at least one side effect related to their treatment and a fifth (20%) saying they sought help in a hospital or emergency room setting as a result of the severity of their adverse reaction. Worryingly, just under half of respondents (43%) also said side effects led to them missing at least one treatment.[3]
?
Regulators have become increasingly cognizant of this risk. In response, the US Food & Drug Administration (FDA) has targeted improvement around dose-selection strategies for oncology drugs through Project Optimus, an initiative of the Oncology Center of Excellence (OCE).[4] The FDA states that its goal is “to?move forward with a dose-finding and dose optimization paradigm across oncology that emphasizes selection of a dose or doses that maximizes not only the efficacy of a drug but the safety and tolerability as well”.
?
The ambition of Project Optimus can be seen in the context of a wider regulatory direction of travel in recent years aimed at enhancing dose optimization during clinical trials. This includes the FDA guidance on enrichment strategies for trials (2019); the European Medicines Agency’s ICH E9(R1) addendum on estimands and sensitivity analysis in clinical trials (2020); and the FDA guidance on the use of digital health technologies (DHTs) to acquire data remotely from participants in clinical investigations (2023).[5],[6],[7]
??
Against this backdrop, the use of digital adherence monitoring presents a clear and obvious solution for addressing trial non-adherence, and companies ranging from major pharmaceuticals to niche biopharma businesses are increasingly moving from a position of readiness to a position of willingness when it comes to deploying these technologies.
?
In 2024, we have seen executives at the highest level advocate for digital enablement in trials to tackle the damaging implications of poor adherence through better and more proactive monitoring. However, all the time the clinical research community is yet to fully pivot to digital adherence, there remains gaps on the pathway from awareness to intent and action.
?
From an AARDEX perspective, our intent is clear: we continue to develop products and services that add value to partners already focused on enhancing their approach to adherence in trials, addressing their pain points and supporting their readiness by, for example, running studies inside the company.
?
At the same time, we continue to encourage others to join them on the journey, and we are optimistic that 2025 will mark the point where momentum will result in a groundswell of support behind the clear benefits of adopting different approaches to adherence monitoring. In doing so, sponsors can expect to secure a different – and far better – return from their investment in trials of potentially life-changing therapies.