Clinical trial participants are difficult, expensive and time consuming to recruit, making them one of a study’s most valuable assets. Yet, across the industry, dropout rates are notoriously high.
As drug development becomes ever more costly, targeted, and complex, every enrolled subject is more important than ever. Investing in patient engagement strategies that facilitate enrollment and keep people on board, on track, and on drug could be the answer developers have been looking for.
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The problem with recruitment
Clinical trial recruitment is a huge challenge to drug development, contributing the study delay and even failure.
A 2018 review of factors associated with the failure of clinical trials, by David Fogel, described it as a “long-standing problem”. A study of 114 trials in the UK, it said, found just 31% had met their enrollment goals, and one-third of publicly funded trials required a time extension because they failed to meet initial recruitment goals.
Some reports estimate that as many as 50% of trials start late because they fail to recruit enough participants in the allotted time. This is a significant figure when delays can result in between $600,000 and $8million a day in losses.
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Lack of awareness, fear or misconceptions around what a clinical trial entails, as well as strict eligibility criteria are all contributing factors to low recruitment rates, and together they serve to create a narrowing funnel of willing and suitable candidates.
For all these reasons and more, it can cost an average of $6,533 to recruit just one patient to a clinical study. It means recruitment accounts for a substantial proportion of the estimated $314 million to $2.8 billion it can cost to develop and bring a new medicine to market.
The problem with retention
As most sponsors and CROs are painfully aware, recruitment is only half the battle. Even when studies have enrolled enough people to start testing, around 30% of participants end up dropping out. And the longer the follow-up, the higher the dropout rate.
The reasons are varied, but they include the financial and logistical implications of attending site visits, and a lack of understanding of the trial protocol. Whatever the reason, the impact cannot be overestimated.
When a trial suffers too many dropouts, whether that is based on projected or actual enrollment, the trial can become underpowered. It might not have enough data to effectively demonstrate a statistically significant clinical benefit, or the product’s safety.
Fogel in his 2018 review, said: “Underpowered clinical trials are problematic. The sponsor may adapt to low enrollment by expanding the number of sites (perhaps in additional countries, with corresponding costly protocol amendments and delays in further research), increasing funds allocated to the study in an effort to meet minimum enrollment.”
This burden, he went on, sometimes necessitates eliminating certain planned tests in order to reallocate available funds and, in turn, certain endpoints may have an insufficient sample size to detect an important result.
For decades, sponsors and CROs have attempted to make up this shortfall by recruiting replacement participants. But not only is this strategy staggeringly expensive, the personalized medicine age is fast rendering it unfeasible
With the development of more complex, more targeted drugs, clinical trial eligibility criteria are more restricted. Trials of products aimed at smaller patient populations, such as those with a particular genetic mutation, for example, have a smaller pool of potential candidates to draw from, making “back to the drawing board recruitment” an approach of diminishing returns.
Retaining the initial intake of enrolled participants, then, has never been more financially or scientifically important.
Engaging your participants
Focusing on patient engagement can help overcome the long-standing challenge of retaining clinical trial participants by giving people everything they need to become – and remain – invested in the process.
This journey starts at the very inception of a trial. Patient-centered study design can minimize protocol burden by ensuring it does not include, for example, an unrealistic number of site visits or invasive procedures.
Before enrolment, teams need to work with participants to ensure they understand exactly what is expected of them, and what they can expect from the trial. Consent forms, for example, should be written in a way that accounts for varying levels of health literacy to give people the best chance of going into the process with their eyes wide open.
To be successful, though, engagement strategies must run the length and breadth of the study, constantly checking in with participants to ensure they are on track and offering support where and when it is needed.
This may sound challenging, especially as the sector moves further towards the decentralized model and removes many face-to-face interactions.
However, by focusing on medication adherence, teams can consistently monitor participants for the signs of waning engagement that can lead to dropouts.
Adherence: A barometer of engagement
Adherence to medication is widely accepted as a marker of engagement with disease management in long term conditions. The approach has just as much to offer in the clinical trial space.
Monitoring medication adherence can provide a wealth of insights on the participants’ investment in the study. Non-adherence can be a drop out warning sign. It offers clues on poor product efficacy, intolerable side effects, or administration problems, all of which can result in poor retention.
Measuring medicine taking behavior can be challenging, however. Traditional validated adherence measures are few and far between, and those that do exist are non-standardized and imperfect.
Furthermore, even when study teams establish non-adherence, they are then faced with the dilemma of what to do about it. The reasons for poor adherence are multiple, and interventions must be personalized to both the drug and the patient.
Digital adherence monitoring can help by integrating smart packaging and powerful analytics to spot when people might need additional support to stay on track.
Digital approach
Digital adherence monitoring can improve recruitment, by reducing the burden that may put people off enrolling in the first place, and improve retention, by helping teams to keep people engaged in the study.
Smart drug packaging automatically records dose administration. Connected smart blisters, for example, can collect not only time and date of pill removal but also which pill cavity is opened, the number of tablets removed, kit number, and expiration date.
It means that dosing histories are compiled without participants needing to keep diaries or record themselves taking their medicine, for example.
The captured information is then transmitted to a cloud-based platform, which provides sophisticated analysis of medication-taking behaviors, and creates powerful visualization 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 throughout the study.
Study teams can use this information to spot those whose engagement may be waning and deploy personalized interventions to mitigate any problems.
This approach works – the closed feedback loop of active monitoring and targeted action can increase engagement, resulting in an up to 50% reduction in dropouts.
Ultimately, digital adherence monitoring is 97% accurate, compared to 60% for pill counting, 50% for healthcare professional rating, and just 27% for self-report, and it provides a complete understanding of the patient adherence behaviors and the risk indicators that matter most for subject engagement and study success.
Photo: imtmphoto, Getty Images
Bernard Vrijens is the Scientific Lead, AARDEX Group and is the Invited Professor of Biostatistics, Liège University in Belgium
He currently leads a research program investigating (a) the most common errors in dosing using a simple but robust taxonomy, (b) particular dosing errors that can jeopardize the efficacy of a drug, and (c) the optimal measurement-guided medication management program that can enhance adherence to medications and maintain long-term persistence.
Dr. Vrijens is also the co-author of seven book chapters, over 100 peer-reviewed scientific papers, and named as inventor on 6 patents. He is a founding member of the International Society for Medication Adherence (ESPACOMP), and an active member of several EU- and US-funded collaborative projects around the theme of adherence to medications. Dr. Vrijens holds a PhD from the Department of Applied Mathematics and Informatics at Ghent University, Belgium.
