For far too long, poor medication adherence has been the elephant in the consulting room. The common, age-old problem has the potential to bring a clinical trial to its knees, and yet with no workable solution on the table, sponsors and CROs have been forced to ignore it.
But that’s changing.
Integrating advanced technologies, including smart packaging and powerful data analytics, is driving a revolution in adherence monitoring that is accelerating drug development timelines, lowering clinical research costs and making trials safer for participants.
The story so far
Poor adherence to the investigational products during clinical trials is an expensive problem.
The statistics are staggering: Each phase III clinical trial participant is responsible for an average of $42,000 in costs yet one third are non-adherent by day 100. Across all phases, 50% of patients admit to not following the dosing protocol.
It’s a problem that negatively impacts patient outcomes, leads to underestimations of product efficacy and can threaten study success.
Study power is critical in clinical trial design. The higher the study power, the higher the probability of detecting a drug’s true effect. However, when subjects do not take their medication as directed, it decreases effect size and increases variability.
As study planners know, any decrease in adherence must be met with an expensive, labor-intensive increase in the number of study participants if power is to be maintained. Nonadherence, then, has a direct effect on the cost and duration of clinical trials.
Yet traditional methods of monitoring adherence, such as pill counting, self-reporting or biomarker measurements, are simply not sensitive enough to provide holistic actionable, information. They are open to bias, only offer a snapshot of medicine-taking behavior and they place an additional burden on both sites and patients.
None of this is new information – sponsors and CROs have been facing the same problem for decades – but in the absence of a workable solution, it has been swept under the carpet.
Technological revolution
Digital adherence monitoring, which combines the power of connected packaging and powerful data analytics, is changing the conversation.
Smart packaging, like connected pre-filled syringes, for example, can collect essential information, such as whether the injection has been completed, time and date of dose, type of drug, batch number and expiration date.
This data is then transmitted to a cloud-based platform for sophisticated analysis of medication-taking behaviors. It results in visualizations that enable study teams to spot erratic dosing patterns, allowing for risk stratification, and guiding individualized interventions that take the complexity of poor medication adherence into account.
The approach can even be integrated into third-party applications, such as patient-facing apps designed to continually encourage adherence and engagement with the protocol.
Crucially, it provides a complete and accurate understanding of the patient adherence behaviors and risk indicators that matter most for study success.
Future trials
Clinical trials are undergoing two separate but interconnected revolutions – and digital adherence monitoring is playing a central role in both.
In recent years, there has been a whole-scale shift towards more patient-centered studies, at least in part, in a bid to improve retention.
For decades, sponsors and CROs have attempted to make up this shortfall by recruiting replacement participants. This strategy, however, is staggeringly expensive, and the personalized medicine age, which is restricting the pool of eligible patients, is fast rendering it unfeasible.
Non-adherence can be a dropout warning sign, and it offers clues on poor product efficacy, intolerable side effects or administration problems, all of which can result in poor retention.
At the same time, we are also witnessing the sector’s digital transformation. In recent years, a huge variety of digital health services and applications have been designed to make the long and winding road to market access shorter, faster and more efficient.
From electronic data capture to wearable sensors, each one has the potential to streamline or optimize one element of a clinical trial. But no element has a larger impact on the chances of study success than medication adherence.
The literature shows that the primary source of clinical trial failure over the last 30 years has been an inability to demonstrate efficacy.
Safety is another leading root cause of failure, but this outcome doesn’t necessarily mean the drug is unsafe. Incorrect dosing derived from poor adherence, for instance, can result in adverse events that do not accurately reflect the effect of the product.
Ultimately, the reasons for study failure are as varied and complex as the trials themselves. Yet there is a common thread that runs through the most common factors of efficacy, safety and dose selection – and that is poor medication adherence.
Turning the tide
Technological innovation is the key to disrupting the status quo, optimizing clinical trials, and finally solving the decades-old problem of poor adherence.
To embrace this potential, practice-changing, integrated tools like digital adherence monitoring ecosystems are fast becoming embedded into routine workflows, and helping to reshape the landscape to ensure efficient, robust, 21st century research.
Photo: Warchi, Getty Images
