Poor medication adherence during clinical trials can skew results, leading to underestimations of product efficacy, inaccurate pharmacokinetic/pharmacodynamic calculations, and even put participant safety at risk.1
Research has shown that up to 50% of people who take part in drug development research do not take their medicines as prescribed.1 Despite this, there remains no systematic approach to the measurement, analysis, interpretation, or reporting of adherence in studies.2
In the past, the limitations of traditional methods, such as pill count and self-report, have hindered the industry’s efforts to grasp the nettle. But advanced, digital approaches have now emerged to transform the landscape.
In a recent Q&A hosted by Bernard Vrijens, Scientific Lead, AARDEX Group, Matt Bolton, Director of Clinical Supply Technology and Innovation at Merck, and Ning Yu, Director of Product and Technology Innovation at Biogen, discussed the potential of digital adherence monitoring and shared their experiences of implementing this new approach.
How Can the Digitalization of Clinical Trials Improve Medication Adherence?
“We have seen a huge increase in pharmaceutical companies using digital tools to improve clinical trial success,” said Yu, adding these included adherence tools, such as smart packaging.
Such changes have been part of a wider shift in the industry to become more patient-centric, to reduce the number of site visits, and to make research more efficient, Bolton said. “No medication will work if people do not take it correctly,” he went on.
“Adherence in the real world probably is not as good as people assume it is. One solution is monitoring adherence and developing strategies to improve poor adherence in clinical trials. This could include interventions to determine why patients may be struggling and trying to remove barriers.”
Digital solutions provide an avenue to achieve this aim, but “not all tools are equal”, added Yu. “There is a lot of variation in terms of compatibility and outcome reports. We have to look very carefully at which tools to use.” One major consideration, he went on, was whether the tool created an additional burden for patients.
Bolton agreed: “The term we like to use is ‘frictionless’, because anything you can do to reduce the patient burden will significantly impact the success of the solution you are trying to implement.”
What Methods for Adherence Measurement Currently Exist, and How do They Differ?
Among the most commonly used methods are pill count, in which patients return the package to the study site for inspection, and self-report or e-diaries, in which patients record their own doses, explained Yu. “But there are a lot of studies that show these do not really capture the dosing event,” he added. Biogen has also used smart, or connected, packaging, which electronically records when a dose is removed from the container, said Yu.
“We have found smart packaging – so that’s smart blister packs, smart bottles or bottle caps – to be quite successful,” said Bolton. “They associate a time and date stamp with when the package was opened. While you do not necessarily know that the medication was ingested, it does give you a strong indication that the drug product was dispensed, and that correlates to a dosing event.”
The data is then exported by the patient, via an app, or the research site, at clinic visit, to a data analytics platform that highlights anomalies, such as missed or erratic doses, and guides individualized interventions.
Using this technology, Bolton said, sites had found incidences of patients who had removed a month’s worth of tablets just hours before an on-site pill count. “From that, you can make some pretty strong inferences to determine what was or was not happening in that specific participant,” he said, adding that all the information was collected automatically, making the approach frictionless for the patient.
What is The Industry’s Current Stance on Measuring Adherence in Clinical Trials?
Yu and Bolton both agreed that measuring adherence was vital to the success of drug development programs, and that advanced digital solutions provided the tools to do just that. Different sections of the industry, however, are at different stages of their adherence journey.
Yu said that Biogen worked in neurodegenerative diseases, which are particularly prone to poor medication adherence, and that this had placed an added emphasis on the organization’s approach. “We are beginning to ask the question, ‘how do we improve adherence?’. We are doing a variety of things, but we are also learning from each other, from what other companies are doing, and trying to implement those learnings into our trials.”
Merck started to “invest heavily in the exploration and utilization” of smart packaging and digital adherence monitoring “several years ago”, said Bolton. “You need to get started to really understand what it can do for you. It takes time, but it is really worthwhile, and we have been seeing a lot of benefits.”
If We Have Evidence to Show the Value of Digital Adherence Monitoring, Why Isn’t it Used as a Matter of Course, and How Can We Change That?
Education and awareness are the key words here, Bolton and Yu agreed. “You need to understand the capabilities of the technology and what the available solutions are, and you need to understand how to match them to your use case,” said Bolton. “But you also need to work with study teams to reinforce the idea that adherence is a problem because not everyone understands that.”
Collecting and sharing use cases is central to overcoming this hurdle, he went on. “You need to be able to demonstrate its use and have conversations that can dispel some of the myths around the complexity and cost of these approaches. You need to be an advocate for bringing these solutions in, and as you build the case studies you will start to break down some of the barriers.”
Expanding on Bolton’s thoughts, Yu added: “There is a process of bringing people together to believe in the technology, and to understand what it takes to implement it, because this is cross-functional. “The more you can do to demonstrate that this has been done before, that this is feasible, the better chance you have of getting more people on board.”
How Can Sponsors Ensure the Effective Implementation of Digital Adherence Monitoring?
Collaborative working is the key to success, whether talking supply chain resilience, packaging-type selection, or hardware/software integration.
“We first started to consider digital packaging just before COVID,” Yu said, explaining the pandemic had led to shortages of electronic components that increased both prices and lead times. “Working with a partner was important. (AARDEX Group) understood what they could do to help us and what we could do to help ourselves mitigate some of the risks going forward: things like having buffer stock to absorb the flash situation and ordering early to ensure there was enough time to handle future supply.” While the supply chain issues are beginning to resolve, that collaborative approach is something Yu said he was keen to continue.
Bolton and Yu also pointed to the value of ARRDEX Group’s ecosystem approach. It allows sponsors to choose from several connected packaging options from a variety of trusted manufacturers, all of which are compatible with AARDEX Group’s adherence analytics software.
“We need to take the platform approach because we do not want to reinvent the wheel every time,” said Yu, adding that, at the same time, some degree of flexibility was essential for continual improvement. “We learn from each trial, and then we work with our partners to improve the next one. One thing we learned from our pilots is that we do not need to work with the same manufacturer each time we introduce a new trial,” he said.
The ecosystem approach, which links sponsors to a network of trusted manufacturing partners and ensures hardware/software integration even when suppliers change, is integral to this, explained Yu, adding that, in essence, “it’s a team sport”.
- To hear the full discussion, watch the webinar here
- Eliasson, L., Clifford, S., Mulick, A., Jackson, C., & Vrijens, B. (2020). How the EMERGE guideline on medication adherence can improve the quality of clinical trials. British Journal of Clinical Pharmacology, 86(4), 687-697.
- Giovanazzi, A., Jones, K., Carr, R. M., Fairhurst, C., Backhouse, M. R., & Adamson, J. (2022). Current practice in the measurement and interpretation of intervention adherence in randomised controlled trials: A systematic review. Contemporary Clinical Trials, 106788.