Recruiting for clinical trials: Patient-centric clinical trial recruitment strategies that work

Introduction

The current model of clinical trial recruitment is inefficient. This is reflected clearly in statistics such as 80% of clinical trials in the US being delayed due to issues with recruitment and 85% of all clinical trials failing to recruit enough patients [¹, ²]. Delays in clinical trials attributed to recruitment challenges result in substantial financial, temporal, and resource costs for sponsors. Cancellation of clinical trials due to failure to recruit sufficient patients represents even larger losses.

Over 75% of the general public report a willingness to participate in clinical trials [³, ⁴], yet insufficient patient recruitment is the leading cause of early termination in randomized controlled trials (RCTs) [⁵]. So, what are the reasons for this disconnect? In an actively recruiting clinical trial, the recruiter is carrying out the following tasks: identifying potentially eligible participants and reaching out to them; informing them of the trial, the protocol, and other trial aspects; pre-screening; verifying patients’ understanding and confirming voluntary participation; conducting screening procedures; and enrolling participants [⁶]. Thus, clinical trial recruitment is much more than simply gaining participant interest; it’s also about understanding participants, connecting them with opportunities that are most suitable to their individual needs, educating and engaging them, and building positive rapport.

Clinical trials that prioritize patient-centric practices may see better patient recruitment and retention rates, potentially leading to faster achievement of recruitment targets compared to trials that do not prioritize patient-centered approaches. In this article, we will discuss how patient recruitment for clinical trials can be improved through a lens of patient centricity. The patient-centric perspective can be applied to the entirety of the patient funnel, from engaging initial interest to randomizing and informing patients, as well as to building a trusted community of research participants. This article will provide recruiters with a comprehensive set of actionable strategies that go beyond the basics and which can be directly implemented into the recruitment process. The strategies are organized into 3 main stages: preparing the trial for recruitment success, recruiting patients for the trial, and optimizing the recruitment strategy after recruitment begins.

Pre-recruitment: Preparing the trial for recruitment success

Protocol design

Effective methods for increased patient recruitment in clinical trials should be implemented as early as the protocol design stage. In patient-centric strategies, patients are viewed as key stakeholders rather than simply participants. It follows that patients should be engaged, consulted with, and considered at every stage of decision making, including the design of the trial protocol. Reach out to patient advocacy groups and give them a seat at the table. If patients are given a voice, recruiters and sponsors can better understand their needs and their concerns going into a clinical trial, and can take those considerations into account during protocol design. A patient-informed protocol and trial design can help patients feel safe and more confident in their decision to participate.

Another area for opportunity lies in the eligibility criteria. Lasagna’s Law posits that investigators tend to overestimate the number of eligible participants. Unfortunately, in reality, eligibility criteria are often too specific and end up limiting the pool of potential participants [⁷]. If the trial has been delayed for too long due to insufficient recruitment, investigators might amend the protocol to increase participant inclusivity, but this can lead to variation in participant populations pre- and post-amendment. One study of 3,400 clinical trials found that 40% of them amended trial protocols after the first subject visit, causing, on average, 4 month delays [⁷]. In one third of these cases, the amendments were found to be avoidable [⁸]. More thorough consideration of design elements in the trial protocol can prevent the need for amendments and minimize trial delays.

Eligibility criteria for clinical trials are also sometimes unnecessarily exclusionary; a need for efficient REB (research ethics board) approval tends to create a pattern of reusing old protocols and trial designs that have been previously approved by the REB [⁹]. However, this creates a reliance on predetermined eligibility criteria that might not be relevant to each study. Eligibility criteria may also unintentionally screen out marginalized communities, disregarding their disease incidence relative to that of the overall population (Power, 2022). Identifying and challenging unintentionally exclusionary criteria could increase the number of eligible participants as well as decrease recruitment time.

Accessibility

Trial accessibility is a major barrier to recruitment and participation that can take many forms. Structural barriers seem to be one of the main reasons for why patients don’t participate in clinical trials [¹⁰]. Trial site locations are a primary consideration; in the US, 70% of people live over 2 hours away from a major research site [¹¹]. This silos the pool of eligible participants - it excludes patients who live in rural communities, as they either aren’t being contacted for participation or can’t physically come to the research site. Likewise, clinical trials tend to be conducted at the same large hospitals and sites frequently selected by CROs and sponsors, thereby attracting repeat patients and limiting exposure to potential new pools of eligible participants. Expanding trial site locations, as well as replacing sites with only moderate performance records can be a potential solution [¹⁰]. Including trial sites that are reachable by foot or public transit for a wide demographic (for example, those located in large cities) can greatly increase accessibility. Consideration should also be given to how the trial design can be improved to increase geographical accessibility. Questions such as “how often will the patient need to access the site?” and “can these travel requirements be minimized?” should be considered. In the following section, we discuss how components of decentralized trials can address some of these questions.

Remuneration for participants can also help ease accessibility issues. It is often difficult for people to take time off work to travel to the site for participation, especially on a regular basis. If patients need to travel long distances to reach the site, will travel-related costs be reimbursed? Will they also receive compensation for lost work hours? Ideally, participants can be assessed for reimbursement on an individual basis; someone who is unemployed and could walk to the travel site within a few minutes would naturally incur fewer costs related to travel and time off work as compared to someone who has to leave their job early and take a cab to the site. Another way to increase accessibility is by accommodating childcare; if parents are reimbursed for the costs of childcare or if trial sites have on-site childcare services, it would make participation easier for those with dependent children.

The issue of accessibility also takes non-physical forms such as information accessibility. Up-to-date information on current clinical trials, their location(s), eligibility criteria, and other important factors for participation may be difficult for participants to find and understand. Power is aiming to address this through a patient-friendly platform that increases accessibility by centralizing clinical trial information in a way that’s easy for patients to find and understand.

Finally, when expanding trial locations, consideration should be given to where new sites will be situated in relation to the expected patient population. If a site is located in an area that has a high percentage of particular racial or ethnic minorities, the informed consent form can be translated into the language(s) that the local population speaks. As an example, for a trial site located in a neighborhood with a predominantly Hispanic population, then the site might have better success with patient recruitment if it has Spanish-speaking staff on the team and has ICFs available in Spanish as well. This can further help enhance participant understanding of the trial, thereby increasing the rate of consent. This strategy can be extended to different touchpoints throughout the trial, not just the consent form. For example, in terms of overall staff diversity, participants are more likely to engage in clinical trials if they see their diversity reflected in the trial staff, including investigators, physicians, trial coordinators, and personnel at the site (Power, 2022). Power has authored a whitepaper that has actionable recommendations for how recruiters and investigators can ensure that they’re recruiting a sample that appropriately reflects the diversity of the target population. Thoughtful consideration for ensuring diversity lends itself to a strong investigator-participant rapport, which can improve participant retention as well as recruitment in future trials.

Leveraging decentralized trial components

Clinical trial decentralization involves bringing the trial to the patient, rather than demanding the patient go to the trial [¹²]. The adoption of decentralized clinical trials (DCTs) has been accelerated by the Covid-19 pandemic, as physical access to trial sites was reduced and virtual practices became increasingly normalized. In fully decentralized trials, all of the following take place without direct contact between participants and the research team: participant recruitment, administration and delivery of the study intervention, and monitoring and reporting of health outcomes and measurements. Trials can exist anywhere along the gradient between fully centralized and fully decentralized, by selectively incorporating components of DCTs such as telehealthcare, partnering with local service providers, wearable medical devices, virtual interfaces for data recording, and home-care and home-delivery services.

When trial sites partner with local clinics, lab services, and pharmacies, participants can utilize local service providers in their community to get prescriptions filled, complete screenings, and have bloodwork, tests, and check-ups performed, the results of which can be shared digitally with the trial team. Healthcare apps allow patients to monitor and input their own data on a daily basis, and also serve to record adherence to treatment plans. Similarly, wearable devices allow for real-time and continuous data collection, omitting delays from patient reporting. Digital screening services allow patients to check in remotely while at home or at work, increasing the ease of participation. Finally, at-home care and at-home delivery services are easy ways to equip patients with the care, medicine, and resources they need to receive the treatment intervention without having to travel to the trial site.

Any new tools should be easy to use, familiar, and accessible to the patients, so they do not unintentionally replace the old barriers with new barriers in the form of access to technology. In one survey, 98% of patients revealed satisfaction with telemedicine services; the key is to use these tools appropriately and effectively [¹²]. Aiming to make the patients’ trial participation experience easier is very likely to increase the success of both recruitment and retention. Further, by engaging the broader community such as local pharmacies, the workload is decreased for site investigators who would normally be responsible for such activities.

Recruiting for clinical trials: Six patient-centric recruiting strategies

In this section, we outline six strategies for effective, patient-centric recruitment that sponsors and investigators can incorporate.

1. Understanding the patient population for a given clinical trial

One important aspect of a successful recruiting effort is concise identification of the target audience so that messaging can be tailored. It’s essential to understand certain things about the trial’s target patient population, such as how patients speak about their condition, where patients go to look for information or help, and what might motivate patients to search for or participate in a trial. Consider asking some of the following questions:

Patient

• What demographic of the population is most affected by the condition being investigated?
• What patient health status is required (i.e. healthy, or moderately or severely affected by a given condition)?
• How does the nature of the condition being studied impact the daily lives of the patients?
• At what stage of their healthcare journeys are the patients?

Patient in relation to others

• What’s the disease incidence? Is it a rare disease? Is it a common disease?
• Is it hereditary?
• Do the patients tend to rely on caregivers?

Patient in relation to trial

• How much previous experience do the patients have in clinical trial participation?
• What is the nature of the clinical trial? Is it observational or interventional? Is it an acute intervention (i.e. surgery or treating a flare-up?) or a long term intervention (i.e. prolonged use of pharmaceuticals)? Does it investigate a new treatment or aim to confirm the efficacy of existing interventions?
• What are the main concerns patients might have about participating in clinical trials?
• How could participating in this study affect the personal lives of the participants?

The next step is to utilize this information to adapt outreach efforts. For example, if the study population is elderly, are there more suitable means of outreach that are more accessible to those patients? If patients are usually filling prescriptions online, digital marketing campaigns might be more suitable for catching their attention. If they’re going in person to the pharmacy, physical posters might be a better option.

At this stage, it’s also important to consider the main deterrents expressed by patients as to why they choose not to participate in clinical trials. For example, one concern may be fear of being randomly assigned into a treatment condition that the patient perceives as harmful or inferior to the alternative treatment [¹³]. If the trial has a placebo arm but will offer the intervention to the placebo group once data collection is completed, that would be an important message to communicate.

Overall, outreach strategies should remain personable; patients want to feel heard and valued as an integral part of the clinical research process.

2. Choosing the right mix of recruitment strategies for the clinical trial’s needs

Once the target population is well characterized and understood, it is easier to choose the recruitment platforms that are best suited for reaching the desired audience. Below is a list of strategies that could be used:

Physician referral networks

• One study revealed that 64% of patients would prefer to hear about clinical trial opportunities from their primary medical practitioners [¹⁴].
• Recruiters can build a network of healthcare practitioners by reaching out directly to clinics, offices, and professionals in the relevant geographic area(s), as well as specialists in certain fields.
• A set of trial messaging can be prepared for healthcare practitioners to share with their patients if interested.
• Recruiters can act as a research liaison, making themselves available to patients who express interest via their healthcare practitioner.

Patient advocacy groups and non-profit partners

• Trial sponsors and sites can establish themselves as a positive and consistent presence in the patient community, and share educational resources. Being a consistent source of information and opportunity and allowing patients to reach out can help in establishing this presence as well as trust.

Analytics platforms

• A large share of information on clinical trial reports is buried in unstructured text, rather than being searchable or structured [15]. Analytic platforms can uncover and synthesize high volumes of information that can provide insight into patient demographics, how to reach them, and how to optimize a given recruitment strategy.

Digital recruitment campaigns

• Online platforms can be highly effective tools for recruiting potential participants.
• Social media campaigns allow recruiters to cast a wide net and tailor their messaging to be as broad or as specific as needed.
• Digital advertising may involve diverse platforms such as: Facebook, Instagram, Twitter, Reddit, and Google amongst others.

Physical, traditional media outlets

• Newspapers, magazines, billboards, posters, radio spots, and fliers.

Patient-centric recruitment platforms

• Patient-centric recruitment platforms like Power provide a platform for patients and researchers to connect seamlessly; patients can search for clinical trials for their specific condition and in their location and researchers can connect with them directly through the platform

3. Providing clear information so patients can make an informed decision

The link between clear communication and successful recruitment and retention can’t be underestimated. One reason why patients may withdraw from clinical trials is not understanding the trial design or protocol, along with confusion around what’s expected of them [4]. There are many strategies to ensure patients are educated enough to make an informed decision. These include:

1. Avoid jargon: Use plain language when possible, avoid complex medical and scientific terms, and ensure that potentially confusing terminology is explained.

2. Focus on active consent, not passive consent: Simply presenting documents such as consent forms to patients transfers the burden of understanding to them. Explain what’s contained in the document, emphasize the importance of reading it in its entirety, and indicate who they can speak to if they don’t understand it or if they require a verbal explanation.

3. Be transparent and specific: Provide patients with step-by-step directions regarding what is expected of them pre-, mid-, and post-trial. Offer this information willingly, not just upon request.

4. Verify understanding: Once patients have been provided with information, questions can be asked to ensure they’ve understood the messages. Consider asking them to explain the most important aspects back, and be present for the learning process. Establish a point of contact (an individual or group of individuals) on the trial team that is accessible to patients to answer questions, address comments, and clarify concerns. Provide this contact information to the patient so they don’t feel that their opportunity to learn about and understand the trial is limited to one meeting.

5. Share extra resources: Give patients the tools to explore topics further if they are interested or don’t feel they have enough information to make an informed decision. Power is an example of an accessible and comprehensive resource that connects patients to information on medical conditions, treatment interventions, completed and ongoing clinical trials, and more, so patients can better understand their role as a participant in clinical research.

4. Making eligibility criteria for the clinical trial easy to understand

A 2021 study revealed that up to 7% of eligibility criteria for studies on clinicaltrial.gov were completely incomprehensible [16]. Some general rules for improving the clarity of eligibility criteria are to ensure that they:

• Are binary (i.e. they all have a ‘yes’ or ‘no’ response)
• Include a type of assessment (which can be checked by referring to previous medical notes)
• Are anchored to a timeline with the trial (i.e. within x amount of days from the trial start date)

Likewise, it’s recommended to remove redundancies to enhance clarity. For example, an exclusion criteria of ‘not meeting all the inclusion criteria’ is not necessarily the most straightforward to convey this point. Replace medical jargon with common/layman’s terms where possible, and if not possible, make sure to explain the terminology. Here are some examples of improving clarity and comprehension:

• Rather than ‘women ≥ 50 years of age’, try ‘patients of female sex age 50 and older’.
• Rather than ‘unifocal breast cancer’, try ‘unifocal breast cancer, meaning there is a single tumor in the breast’.
• Rather than ‘Eastern Cooperative Oncology Group (ECOG) 0, 1’, try ‘Eastern Cooperative Oncology Group (ECOG) is a standardized performance scale that measures a cancer patient’s level of functioning and independence. This is a 6-point scale (from 0-5). Participants must score either 0 or 1 to be eligible for participating, indicating high levels of functionality and independence’.

5. Creating a positive experience for the patient

Participation in a clinical trial is a journey for the patient, and recruiters can focus on key touch points throughout that journey. This includes ensuring that the lead investigator and the site staff are approachable, available, and carry positive demeanours. This might be especially important when working with a group of participants for whom clinical trials are a novel experience. If participants feel that staff are not available or interested, they are more likely to withdraw and less likely to return as a participant for future clinical trials. It’s equally important that the medical practitioners administering the intervention are enthusiastic, as investigator enthusiasm has been cited as one of the most important factors for successful recruitment at the trial site [⁷].

From the first call or point-of-contact to educating the participant, screening and onboarding, administering interventions, and follow-up visits and check-ins, the patient should feel valued. Patients deserve to be informed at every point in their journey, presented with easily digestible information, and should feel comfortable to ask questions, which requires staff that are approachable. As mentioned previously, one key consideration here is to hire diverse site staff. Historic mistrust of the healthcare system within marginalized communities can be a barrier to participation; one way to mitigate this is to ensure the diversity sought for amongst patients is reflected in staff.

6. Keeping patients engaged in the clinical trial process

Patient retention is as important as initial patient recruitment. Roughly 30% of patients drop out of clinical trials [¹⁷]. Patient dropouts in clinical trials can result in significant financial losses, as well as losses of valuable time and data, and may affect the reputation of the trial. By keeping patients engaged throughout the clinical trial process, retention can be maximized, which translates into improving the completion and success rate of clinical trials. Some things that can help include:

Clear and frequent communication: Clinical trial staff should establish clear lines of communication with trial participants from the outset, ensuring that they understand the requirements of the trial and have access to support if needed. Regular check-ins and updates can help build trust and foster a positive relationship between participants and staff.

Personalized support: Depending on the trial's resources and available personnel, staff may consider providing dedicated support to each participant, such as a patient support liaison. This may help participants feel more connected to the trial and ensure that their individual needs and preferences are addressed.

Flexibility: Trial staff should be flexible and accommodating when scheduling appointments, tests, and follow-ups, taking into account the needs and preferences of each participant.

It’s key to remain in contact with participants throughout the entire duration of the clinical trial (and often even after), so that they feel valued and welcome to express any concerns they may have. Establish consistent touch points (times) for members of the research team to check in with participants. This could be done through phone calls, emails, regular mail, apps, or video calls.

Sponsors should also strongly consider utilizing patient follow-up services. Follow-up is essential both for monitoring patient health and for receiving feedback about the trial experience. Ask patients what worked for them and in which areas there was room for improvement. Understand the positives and negatives of their experience and integrate that feedback into future trials.

Optimizing the clinical trial recruitment strategy in real-time

Recruitment strategies should be monitored and optimized as recruitment is in progress. Continuously evaluate progress to stay on track - What is the clinical trial accrual target, and is the current progress on track toward meeting it? If not, why? There are different ways to calculate clinical trial recruitment rate, with the best method being dependent on the metric(s) selected for monitoring. One way is to assess the number of patients recruited at each site over a given period of time, indicating the success of individual trial sites. At the trial level, the general method is to divide the total number of patients recruited thus far by the number of trial sites recruiting, then divide that by the period of time elapsed since recruitment began. This will give an accrual rate in the form of the number of patients per site per month/week/etc. Assessing recruitment progress in an ongoing fashion, according to the metric(s) that are identified as being most relevant to the specific trial and its recruitment goals, may allow investigators and recruiters to identify areas for improvement early enough that acute changes can be made to speed-up recruitment and reach the original recruitment target on time [¹⁸].

Key takeaways

Research findings indicate that current approaches for recruiting and retaining patients for clinical trials are not optimal. Optimization of recruitment strategies begins as early as protocol design; engage patients in this process and ensure they are valued as key stakeholders. Increase the physical accessibility of trial sites; shift from clustering all trials at large research institutions to creating community connections so that patients can rely on their local services as a liaison to the research team. Integrate components of decentralized clinical trials, like delivery services, at-home care, and healthcare apps, so patients are less burdened by the time and cost of traveling to and from the trial site. Increase communication by appointing a designated patient liaison on the trial team, hiring diverse, multilingual site staff, avoiding medical jargon, and being specific and upfront about expectations and resources for patients.

Once it's time to engage in active recruitment, ensure patients are made aware of trial opportunities by understanding the specific needs and characteristics of the key population and providing them with information based on those needs. Leverage communication and media platforms that the target population for the trial normally engages with.

Once participants’ attention is captured, efforts should be made to ensure they feel welcomed as well as informed and educated about the trial itself. Eligibility criteria should be written in plain language, and medical terminology should be explained clearly so patients can better understand why they’ve been recruited and what the study involves. Likewise, the informed consent process can be used to be specific and clear regarding the expectations of the patient and to double check to make sure they’ve understood. Creating a positive experience for the patient, where they feel heard and valued, is paramount to reducing dropout rates. Finally, establish open lines of communication between trial staff and patients; check in with patients, send reminders, ask for feedback, and accommodate their needs. Keeping patients engaged for the duration of the trail will aid in participant retention.

Finally, once the initial recruitment process has begun, the recruitment strategy can be actively monitored in order to make adjustments on the fly. Identify successes and weak points. What strategies are successfully engaging the most patients? Can more resources be allocated to those strategies to enhance recruitment? Are any of the strategies failing to provide tangible results, and if so, can they be dropped altogether to refocus resources on strategies offering better returns? Ask for ongoing feedback from the research and site staff, as well as the patients, and aim to implement it in a timely manner. Utilizing a combination of the tactics outlined in this article can help increase patient recruitment.