Don’t lose your patients

A glance at the international database of clinical trials, clinicaltrials.gov, highlights approximately 56 million open spaces. Despite this, only about five million people actually participate each year. A 2015 study published in Clinical Trials reported that nearly one fifth of trials are either closed or terminated early as a result of being unable to recruit sufficient participants. Even if studies are not prematurely ended, inadequate patient numbers can substantially delay a trial, sometimes doubling anticipated time frames. This has significant tangible and non-tangible consequences, which range from hindering efforts to diagnose, treat and prevent disease, through to having a demoralising effect on patients and investigators.

It is clear that patient recruitment is an ongoing challenge, but in many ways, the landscape remains the same. “Not a lot has changed in terms of what the barriers are,” says Elizabeth Mahon, global feasibility TA head, oncology at Johnson & Johnson. “There's a general lack of awareness and education around clinical trials. There is also a fundamental struggle with eligibility, time commitment and trial design. Even if you are willing to participate, there are barriers to actually participating.”

Kelly McKee, head of patient recruitment rare diseases at Vertex Pharmaceuticals, agrees about the lack of knowledge. “Most people in the US don’t know a living scientist or what a clinical trial is,” she says. “We can’t just rely on the people that we know. We need to partner with communities that aren’t the same as us.”

Lack of awareness isn’t a problem for all patient groups, however. “Some are well versed about their options, but other patient communities are not,” says McKee.

Mahon agrees, “Oncology and rare diseases tend to be a patient population that is very well educated about the disease, as well as the different treatment options,” she says. “This includes perceiving the clinical trial as a treatment option.”

Although knowledge is an important part of boosting the willingness of people to participate in clinical trials, it is not the whole picture. Embracing patient centricity right from the early planning stages is the key to not only successful recruitment but also maintaining patient engagement.

This involves digging deeper, not only with patients but with those around them. “I think we’ve made a lot of efforts specifically around trying to better understand the patient population, not just from an eligibility criteria perspective, but also really understanding the patient and their lives, what’s going on and how to help them participate,” says Mahon. “Participating influences not only the person but their community, their whole family.”

Up to data

There are a number of methods that can be used to gain this information “We do a lot of surveys, advocacy groups, focus groups with patients, and have discussions with investigators to gather insight on what can be done, what eligibility criteria can be altered and what patients actually look like in the real world,” says Mahon. “There is a huge volume of data out there, and being able to look at it and make adjustments – through modelling or other activities – enables us to be able to find out what minor details to the eligibility criteria might mean to the overall eligible patient pool.”

Liaising with healthcare professionals is another important strategy in boosting recruitment and inclusion. “The infrastructure of how clinical trials are executed makes it harder to recruit a diverse patient population,” says McKee. “Physicians aren’t aware of trial opportunities so they aren’t recommending them.”

Greater collaboration with investigators can also be hugely valuable. “We’ve recently used an approach called ‘Better trials. Made together.’,” says Mahon. “We recognised that where we have more of a partnership with the patients and the investigators, to provide input into the design and give that feedback early on, it helped all the way around.”

Participant recruitment strategies can also have implications for inclusivity, which is another ongoing and unresolved issue within clinical trials. “Not everyone is treated at those large, nationally renowned research centres,” says Mahon. “There needs to be an outreach and better participation among more community-based centres, particularly when there is a component to that patient population where disease prevalence might be more skewed towards certain racial, gender or age groups.”

Gaining a comprehensive picture of the lives and experiences of patients provides benefits far beyond the immediate trial. “It’s important to understand your patient population, and design strategies and tactics to enrol patients that mirror the population that will eventually be taking the medicine you are developing,” explains McKee.

Ensuring that trial design is convenient for patients is also imperative in ensuring that sufficient numbers are recruited. “We design scientifically beautiful clinical trials that look perfect on paper; however, patients who fit into those beautifully scientific protocols may be hard to find and may not even exist,” McKee admits. “We also ask a lot of our clinical trial participants. We ask them to travel to and from investigator sites for a lot of visits, and we ask them to undergo a lot of procedures.”

Communicating the demands clearly to patients can help not only with recruitment but also with engagement. “You’re getting that consent form when you may also just be getting a diagnosis or you may have had a diagnosis, but it’s just a lot of information coming at you,” says Mahon. “Because, if you know what you’re getting into and the time commitment, and what your visits and your life is going to look like for the duration of the trial, there are fewer surprises and perhaps a greater willingness to stay in the study.”

There are also some established tools that can be used to optimise recruitment. The Clinical Trial Transformation Initiative has published recommendations on streamlining and accelerating clinical trials, which aim to ensure the highest standards of quality and participant protection. Such strategies include moving patient recruitment further upstream in clinical trial planning, including an inclusive and diverse patient voice, and taking into consideration the needs of all stakeholders.

Taking a holistic view of patient recruitment is key, rather than focusing on isolated activities “Patient journey mapping, patient recruitment and retention plans, and communication plans are all essential parts of improving clinical trial awareness and recruitment,” says McKee.

Question everyone

Sometimes the requirements of patients may not be particularly onerous but can easily be overlooked in the trial design process. Asking questions directly to patients is crucial.

“Do we need to provide transportation that helps them get to the study visits, or reminder tools? Gathering this information upfront and being able to plan for it not only helps with recruitment but, in the long term, retention and outcomes of the study,” says Mahon.

These needs can be greater for certain populations. For oncology patients, for example, considering the stage of the disease and how that impacts upon participation is also imperative. “If they are newly diagnosed they’re not necessarily going to the big cancer centres, they may be going to more of a community-based centre,” says Mahon. “So it’s more a matter of looking at the right type of site and partnering with research sites to enhance their recruitment or referral network.”

Trials that are conducted partially remotely can be particularly suited to these patients. These direct-to-patient trials are starting to be discussed more within the industry, but implementation remains at an early stage.

“If you go to a lot of conferences within the industry, there are a lot of different vendors out there and companies, including us, who are presenting on things that are being looked at and considered,” says Mahon. “There is a lot of information sharing in that form, which is encouraging – whether it is wearable devices to be able to monitor patients over the course of the day so they don’t have to visit the study site; whether you can have home health aides drawing blood so that you’re not having to go for routine blood draws; or skype visits, and other video conferencing, for that routine check in, so that you’re still having an appointment but not necessarily having to be physically there to do it.

Such strategies can make a huge difference to patients, particularly those with a high disease burden, such as oncology patients. “You’re talking about a very sick population, so the easier you can make their life and the more comfortable that you can make them during treatment, the better,” says Mahon.

Social sciences

So, what does the future look like for patient recruitment in clinical trials?

“Social media; everyone is cautiously approaching that,” says Mahon. “There are a lot of conversations about what the appropriate use of that is for recruitment and whether that’s a good or bad thing.”

Such channels can provide not only a method of recruitment but also the ability to connect patients with each other. “We’ve been looking at supporting and developing patient communities so that they’re connected to others who share a disease or experience of having participated in a trial,” says Mahon. “I think that is going to be another opportunity for awareness, recruitment and retention.”

Adopting a patient-centric approach can also help to change the perception of clinical trials themselves. “I’d also like to see the way we talk about clinical trials change, where they are seen by more people as a choice and not as a last resort,” says McKee. “We should be celebrating the value that every patient brings in making new medicines possible.”