Building sustainable patient-centric trials to weather the storm of COVID-19 involves the utilisation of smart connected devices and packaging to reduce the burden on patients
Rapid drug development may have been the story of 2020, however, it’s no secret that huge numbers of clinical trials were also placed on hold when the pandemic hit. In fact, an estimated 80% of non-COVID-19 studies were stopped or interrupted by the crisis (1).
Now, as the industry reboots the clinical research system, we face a golden opportunity to rethink, realign, and rebuild around the needs of those who matter most – the participants. The last year has proved that it is possible, viable, and feasible to use digital health to design and perform patient-centred trials. It has also demonstrated that connected smart devices and packaging can play an important role within this new generation of remote trials by helping teams to monitor a crucial barometer of patient engagement – medication adherence.
The industry has been shifting towards the patient-centric clinical trials paradigm for some time. The reasons why run the whole length of the drug development pathway. Involving the end users in candidate and target selection ensures developers are working to solve a problem that actually exists. Put simply, developers do not know what they do not know, and the gulf between what researchers and patients think of as important outcomes is often wide.
A focus on patient centricity can also help ease the age-old problem of recruitment and retention. Fewer than 5% of all those eligible for clinical trials enrol, and the global average dropout rate is around 30%. Patient centred study design can minimise protocol burden, so as to maximise the chances that people not only sign up, but are able to stay the course. By giving developers a better idea of how their products are used, received, and valued, patient-centric clinical trials also provide rich insights for use in post-approval marketing.
The industry agrees: more patient centric trials lead to better products and a higher return on investment – and that is no small victory at a time when it can cost anywhere between $314 million to $2.8 billion to develop and bring a new medicine to market (2).
What Makes a Patient-Centric Trial?
Patient engagement is key to not only designing better trials, but conducting them. By keeping people interested and involved in the study at hand, sponsors and CROs can be sure they are collecting the most robust data, and are avoiding dropouts. However, embracing the potential of this new approach relies on shifting from a site-centric to a patient-centric model in a way that avoids placing additional pressure on-site staff. We need innovative methods to both foster and monitor engagement.
This is where digital health approaches are stepping into the breach and proving their worth. When COVID-19 hit, remote monitoring became a necessity. Social distancing regulations, stay-at-home orders, and infection control measures made it simply impossible for study participants – and in many cases site staff – to get to trial centres. Contrary to what many believed before the pandemic, the necessity driven shift from on-site to remote monitoring has been achieved and successful. Researchers’ data quality concerns have been allayed, and teams have been quick to appreciate the convenience benefits for both staff and patients. However, fewer contacts between site teams and study participants means fewer opportunities to gauge engagement in the trial and its protocol.
Medication Adherence: A Barometer of Engagement
Adherence to medication is widely accepted as a marker of engagement with disease management in long term conditions (3). What’s more, poor adherence can be a sign of poor product efficacy, intolerable side effects, or administration problems that study teams need to know about.
Reliable and precise measures of adherence to medications are a barometer of efficacy, product practicalities, and patients’ engagement in the study. Yet, all this invaluable information is often overlooked. In fact, compliance to treatment protocols is a long-standing – not to mention expensive – problem in the world of clinical development. Each Phase III trial participant is responsible for an average of $42,000 in costs, yet studies have shown that 30% are non-adherent by day 100
(4-5). Across all clinical trial phases, 50% of participants admit to not adhering to the dosing regimen set out in the protocol (6). It drains study power, which has a direct effect on the cost and duration of clinical trials. Crucially, it can delay the approval of investigational products – at a cost of between $600,000 and $8 million a day in lost revenue (7).
It has, until now, been a tough nut to crack. Validated adherence measures are few and far between, and those that do exist are non-standardised and imperfect.
Even when study teams are able to establish nonadherence, they are then faced with the dilemma of what to do about it. The reasons people do not take their medicine as directed are so multiple that interventions need to be personalised to both the drug and the patient. However, digital health, including remote adherence monitoring, provides the opportunity to move away from a one-size-fits-all approach.
COVID-19 has proved to be a gold mine for digital health evidence. By accelerating the shift to remote monitoring, it has proved that the approach is not only viable, but, in many cases, preferable. One way this has been borne is through the increased use of connected smart devices and packaging to monitor adherence and keep track of engagement.
Digital monitoring gives trial leaders an invaluable insight into adherence behaviours, allowing them to identify and correct problems before they interfere with study results. Smart drug packaging can record dose administration and transmit that information to the study team for analysis. The team can then take a personalised approach to re-engage with the participant and mitigate any problems. In essence, the packaging monitors, and the study team uses the resulting data to manage adherence.
Connected pre-filled syringes, for example, can collect essential information, such as if the injection has been completed, time and date, type of drug, batch number, and expiration date. This information is then sent to a cloud-based platform that provides sophisticated analysis of medication-taking behaviours, and creates powerful visualisation and focused feedback for both study teams and participants.
It can even be integrated into third-party applications – such as patient-facing apps designed to build engagement and encourage adherence.
Crucially, this approach works. Studies have shown that smart device and package monitoring is 97% accurate, compared to 60% for pill counting, 50% for healthcare professional rating, and just 27% for self-reporting (8). What’s more, it provides a complete understanding of the patient adherence behaviours and the risk indicators that matter most for study success and subject engagement (9).
Patient-Centric Adherence in the Digital Era
The clinical research community has been working towards the creation of more patient-centric studies for some time. In the highly competitive, fast-moving world of pharmaceutical development, organisations are always looking for ways to make better products and improve return on investment.
The COVID-19 pandemic gave the sector the impetus to utilise digital health in the creation of more convenient trials – and digital health has not disappointed.
Remote monitoring, however, means fewer contact points, and fewer opportunities for site staff to connect with participants.
Connected smart packaging provides organisations with the ability to use medication adherence as a marker of engagement and take tailored action when necessary. Because, when measured and reported accurately, adherence can open a window into a participant’s perspective on a trial, and, therefore, contribute to the chances study success.
- Visit: www.appliedclinicaltrialsonline. com/view/covid-19-and-its-impacton-the-future-of-clinical-trialexecution
- Visit: jamanetwork.com/journals/ jama/article-abstract/2762311
- Brown MT and Bussell JK,
Medication adherence: WHO cares?
Mayo Clinic Proceedings 86(4): pp304-14, 2011
- Visit: aspe.hhs.gov/system/files/ pdf/77166/rpt_erg.pdf
- Blaschke TF et al, Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories, Annu Rev
Pharmacol Toxicol 52: pp275-301, 2021
- Visit: bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.14240
- Visit: www.pharmafile.com/news/ 511225/clinical-trials-and-theirpatients-rising-costs-and-how- stem-loss
- El Alili M et al, A scoping review of studies comparing the medication event monitoring system (MEMS) with alternative methods for measuring medication adherence, Br J Clin Pharmacol 82(1): pp268-79, 2016
- Vrijens B and Urquhart J, Methods for measuring, enhancing, and accounting for medication adherence in clinical trials, Clin
Pharmacol Ther 95(6): pp617-26, 2014
Bernard Vrijens is Scientific Lead at AARDEX Group and Invited Professor of Biostatistics, Liège University, Belgium. He holds a PhD from the Department of Applied Mathematics and Informatics at Ghent University, Belgium. Bernard currently leads a research programme investigating the most common errors in dosing using a simple, but robust taxonomy – particular dosing errors that can jeopardise the efficacy of a drug – and the optimal measurement-guided medication management programme that can enhance adherence to medications and maintain longterm persistence. He is also the co-author of seven book chapters, over 100 peer-reviewed scientific papers, and named as inventor on six patents. Bernard is a founding member of the International Society for Medication Adherence, and an active member of several EU- and US-funded collaborative projects around the theme of adherence to medications.
This article is taken from International Clinical Trials August 2021, pages 46-48. © Samedan Ltd