Clinical trials – overcoming the barriers to improved enrolment and retention

When the cold regulations and requirements of clinical trials meet the overheating elements of human behaviour, the mists of confusion and misunderstanding often prevail.

They form a recruitment and retention weather front with a negative forecast on research schedules and budgets – lifting the fog is a pharma mission for the ages.

The principle of trial enrolment received a welcome boost during COVID-19 when the public benefit of testing vaccines drew global attention and approval. Efforts are continuing to build on that base, with the UK government pouring £400m into programmes supporting clinical research.

The aim is to make it easier to conduct clinical trials and, critically, much more attractive to patients to enrol and stay enrolled when human behaviour and the impact of everyday pressures creates barriers.

The European Clinical Research Infrastructure Network (ECRIN) has framed its meeting in Madrid on 20 May – International Clinical Trials Day – with the tag line: ‘How do we progress from discussion to action in ensuring the appropriate populations are taken into account in the design of a clinical study?’

All in-person places for the congress have been taken and its patient engagement module on the complexities of communicating with patients from culturally diverse backgrounds and sharing best practice is in high demand.

The energy and intent to create a more welcoming and effective clinical trials climate for patients is there but the obstacles remain significant. Enrolment resistance is still a strain of human behaviour that can remain immune to persuasion while triggering ruinously high drop-out rates.

‘Interviewing patients at the outset to better understand their everyday life and bring that into the trial design process is incredibly valuable’

“There is a clear sense that we are not getting the best from clinical trials in terms of serving the patients who enrol in them as well as the pharmaceutical industry’s ambition for them. I don’t think it is catastrophic because we are doing some things well but there is definitely room for improvement,” says Rob Horne, Professor of Behavioural Medicine at the School of Pharmacy, University College London, a world-leading expert who has spent 30 years researching psychological and behavioural factors in treatment adherence.

“Many clinical trials experience delays due to slow recruitment and retention is also a challenge, with drop-out rates of 20% not being atypical. Both are hugely costly. It is essential to get the best value from clinical trials and it is clear that there are opportunities to enhance both recruitment and retention by addressing human behaviour.”

Professor Horne has developed internationally recognised frameworks and tools to support patient engagement and adherence and believes these principles can be applied to improve clinical trials efficiency and efficacy. He also founded the consultancy Personia Health, in partnership with University College London, which applies his proven tools and techniques to support patient engagement and improve health outcomes.

“By applying what we’ve learned from 30 years’ worth of global research across all diseases in understanding the barriers to engaging with treatment, we can start to improve the way in which we communicate and support people, and start to increase participation rates,” he says.

“At the core of this is an understanding of how we work as humans and how we respond to advice. There are many reasons why someone might refuse the opportunity to engage in a trial or drop out early but they boil down to two fundamental issues: ‘can’t’ and ‘don’t want to’. Most efforts to improve engagement focus on providing good information and making it easier for patients to participate. This is helpful but we can do more if we take into account the perceptions as well as practicalities of participation.

“Patients do not come as blank sheets that you can write instructions on – they have pre-existing beliefs about clinical trials and medicines. These can lead them to conclude that taking part is not a good idea for them. By understanding those, you can change the way a trial is presented and discussed, and offer better quality support and information to help patients make informed choices – help them not refuse to take part in a trial or drop out for the wrong reason.”

His validated tools and frameworks provide a light in the murky cloud of patient communication and engagement and he adds: “At Personia, we work with patients to understand their perspectives and we know how to talk about medicines and clinical trials in a way that can present them in a different light so that people can re-evaluate their resistance and realise that a trial might be good for them despite their initial beliefs.

“This is a big opportunity for pharma as it means it could tailor its messaging to support the needs of individual patients to overcome their perceptual and practical barriers.”

Talk of targeting communication down to an individual level can provoke financial vapours, but Professor Horne believes research intelligence combined with digital tools makes this achievable without breaking the budget.

“Tailoring to the individual is the gold standard and recent advances in the digitalisation of clinical trials offer an opportunity [to increase engagement and retention],” he observes.  “We have developed digital coaching tools that can be used to tailor support to the needs of the individual to support engagement and retention. It uses validated profiling tools and messaging to uncover and address any misplaced beliefs, concerns or misconceptions and help patients get the best from a clinical trial.

“Even if you don’t use a tailored approach, you can start to think about how you communicate the trial; ask if is it sensitive to the way in which people are likely to think about taking part, and make sure you are talking their language and tapping into their sets of beliefs rather than pushing something on them, because that’s often what it feels like for patients. Messaging is key and we have developed a way of talking about medicine and trials that connects and supports informed choice and engagement.”

‘Patients do not come as blank sheets that you can write instructions on – they have pre-existing beliefs about clinical trials and medicines’

The regulatory push is for more patient involvement and real-world evidence across clinical trials to enhance therapy development and this has created a richer patient-centred research landscape. A recent paper valued the progress, advocated strong patient influence throughout the entire trial profile and reinforced extra benefits such as defining unmet needs and formulating research priorities.

Beverly Romero, Senior Principal at Sprout Health Solutions, believes that pharma is switched onto the potential of energising patient engagement but is still working out how to best capture patient insights at the very beginning of the drug development process, starting even before phase 1 trials, to ensure that those activities bring impact and value throughout the drug life cycle.

“Involving patients early in the clinical trial process has long-term benefits because they know and see things that clinicians or investigators don’t. The patient perspective is a potent tool,” she says. “Interviewing patients at the outset to better understand their everyday life and bring that into the trial design process is incredibly valuable.

“We guide patients through reviews of clinical trial protocols and the schedule of assessments so that they can candidly let us know if it seems realistic or burdensome. That feedback helps our clients improve their trial protocols and avoids potential issues down the line.

“Too often, patients either do not start a trial or drop out because they cannot get to the sites. We need to understand the potential barriers patients might face, such as travel to clinical sites or time away from work and family, and discuss them as early as possible so it is easier for the patient to participate and remain in the trial.”

Digital monitoring is removing some of the logistical burdens that deter patients and the UK government’s backing of 20 new, strategic trial sites shows that public and private efforts are being made to resolve issues.

“Not involving patients appropriately and early could cost a lot of time and money,” adds Beverley. “Sprout Health Solutions champions patient engagement across healthcare with evidence-based research aimed at transforming behaviours and outcomes.

“We are seeing more examples of good practice that really does elevate a clinical trial. For example, one important way to ensure the patient voice is captured in the drug development process is to select well-developed and appropriate patient-reported outcome measures that capture concepts that really matter to patients, while also meeting regulatory requirements.

“It is important to involve patients in both the development and implementation of these measures to make sure that the questions asked are relevant, important and not overly burdensome. Selecting and developing these measures is one of the key services we provide our clients at Sprout.”

The fall-out from poor patient engagement radiates across organisations and Beverly comments: “We recently supported a company that did not follow due process with getting patient buy-in to the trial and they were pulled up by the FDA, which said it wanted to see more diversity in the sample and more input from the target population. We recognise that it can be challenging for companies to balance budget and timeline constraints with the need for robust patient engagement in the planning of the trial protocol but, unfortunately, this client ended up losing time and they spent more money. Our team were able to conduct the research and deliver the additional patient-centred evidence the regulators required but, in hindsight, the company would have benefited from a thoughtful, upfront investment.

“It would be better if pharma companies considered the need for robust patient engagement throughout the drug development process and embedded it in their structure.  All the teams involved in drug development must feel the value it brings. Regulatory are looking for evidence of patient engagement and a clear description of how patients have been involved. They want to see robust patient-reported outcome measures included in the protocol and patient experience data to support regulatory submissions.

“The pharma industry is not standing still and there is positive change and progress. The decentralised trial movement that has kicked off since COVID-19 is growing, and more innovative ways are emerging of collecting patient data – such as wearables and sensors, as well as video data collection – to remove logistical barriers.

“Getting it right makes a huge difference to patient engagement, trial outcomes and regulatory success. It is the best feeling to know we are making a meaningful impact on people’s lives.”

Professor Horne agrees, commenting: “Patient engagement is key to cost-effective trials. Advances in behavioural science can now be applied to enhance messaging and patient support in a way that helps get the best from clinical trials.”

References are available on request.