Worldwide, 90% of clinical trials suffer from slower-than-expected enrollment [1] and roughly one in five studies terminate early or settle for a smaller total sample size than desired [Reference Carlisle, Kimmelman, Ramsay and MacKinnon2]. Moreover, under-enrollment of racial and ethnic minority populations is endemic – the Food and Drug Administration reports that 75% of participants in drug therapeutic trials are white [3], while 40% of the US population identifies as a racial or ethnic minority [4]. Poor recruitment and retention performance are costly to researchers and sponsors and detrimental to public health when advances fail to materialize or do not benefit all [Reference Huang, Bull, Johnston McKee, Mahon, Harper and Roberts5].
The Recruitment Innovation Centre (RIC) [Reference Wilkins, Edwards and Stroud6], part of the Trial Innovation Network’s collaborative initiative within the Clinical and Translational Science Award (CTSA) Program, is tasked with addressing critical roadblocks in clinical research [Reference Harris, Taylor, Thielke, Payne, Gonzalez and Conde7]. The RIC consults with CTSA hubs and their research teams on strategies to increase clinical trial enrollment by developing, testing, and sharing innovations to enhance participant recruitment and retention. After 220 consultations with investigators nationwide, the RIC has compiled four primary recommendations for addressing common pitfalls in recruitment and retention (Fig. 1). These recommendations were determined by consensus among eight RIC consultants after evaluating common challenges described by investigators during their recruitment consultations.
Fig. 1. The top four recruitment and retention recommendations from the Recruitment Innovation Center.
Recommendations
Recommendation #1: Proactively assess recruitment and retention barriers and develop mitigation strategies
Investigators often fail to plan and prepare for recruitment and retention issues that can significantly impact the success of their clinical trial. Once embarked on recruitment, researchers can encounter unanticipated challenges. An important first step of any clinical trial is to proactively identify potential obstacles based on previous experience, trial-specific details, and characteristics of the target population. Once barriers have been ascertained, study teams should develop a remediation plan before beginning enrollment.
A risk assessment planner can be a helpful tool. The RIC-developed Risk Register [8] assists investigators to identify possible risks, appraises the likelihood that these risks will occur, and evaluates the potential impact on the trial. Study teams use this assessment to calculate a subjective “risk score” ranging from 2 to 10, with higher scores indicating greater risks to recruitment and retention. Risk scores can then be used to help prioritize decisions to mitigate barriers and minimize their impact. Table 1 illustrates potential barriers, associated risk scores, and recommended mitigation strategies for an example study.
Table 1. Examples of recruitment barriers, risk assessment, and mitigation strategies
Probability of Risk Occurring ranges from 1 (Rare) to 5 (Highly Probable); Impact of Risk ranges from 1 (Very low) to 5 (Very high); Calculated Risk Score ranges from 2–3 (Accept the risk), 4–6 (Mitigate the risk), 7–8 (Transfer the risk), to 9–10 (Avoid the risk).
In addition to proactively identifying risks, study teams should consider using the RIC-developed Recruitment and Retention Plan Template [8] to further delineate recruitment and retention strategies that can be used throughout the life of the trial.
Recommendation #2: Prioritize the participant journey: Minimizing burden and returning value
The needs and preferences of research participants are often overlooked or not fully considered when designing clinical trials. Unnecessarily burdensome study visits, inadequate reimbursement for costs of participating and not returning study results or other information of value to participants can contribute to lackluster study enrollment and high attrition. Strategies that focus on the participants include:
Clear, consistent, and timely communication. The manner and type of information shared with potential participants is critical to influencing participation. A clear plan for communicating study expectations during the enrollment phase and throughout study duration may ease anxiety about participation and demystify the trial experience. Study materials and communication should aim to be engaging and understandable across a wide range of literacy levels.
Adequate compensation. Study teams should compensate volunteers as a way of honoring the time and effort they are contributing to the study and help offset any costs to participating.
Reduction of participant burden. Study design and implementation may unintentionally create barriers that hinder participation. Researchers should map out the participant journey to identify unnecessary or overly burdensome procedures that can be minimized or eliminated.
Return of value for participation. Investigators should acknowledge volunteers’ contributions and provide value to research participants. This should go beyond participant compensation and could include an array of benefits, such as returning study findings to participants, connecting them with others in the same disease community [Reference Wilkins, Mapes, Jerome, Villalta-Gil, Pulley and Harris12], and acknowledging their contributions in manuscripts, presentations, and other dissemination activities.
Recommendation #3: Data-driven site selection
When selecting sites for a multicenter clinical trial, investigators often choose sites where there are known colleagues, previous collaborations, or other personal preferences. To locate the strongest sites, however, investigators should use an informed approach that utilizes multiple sources of both quantitative and qualitative data.
Investigators should evaluate the availability of the target population to be recruited at each site. Electronic health record (EHR) data can be analyzed to determine whether an appropriate volume of patients with the specified health condition exists at a potential site [Reference Nelson, Drury and Hood13]. Other data sources can be leveraged to assist in site identification and selection, including public health datasets and population-level data. Next, investigators should confirm each site possesses the resources and capacity to recruit and enroll the target participant demographics. These resources may include adequate effort allocation for research staff, proper equipment, and expertise in recruiting diverse populations.
Recruitment feasibility assessments for candidate sites should also include the evaluation of competing trials in similar medical domains. These trials may be vying for the same patient population or competing for a clinician’s time, staff, or site resources. Information from ClinicalTrials.gov [14], including details on study phase, expected enrollment dates, and participating sites, can be paired with site-reported patient estimates to help identify risks and proactively inform remediation strategies. This could include investigators collaborating with other study teams on recruitment strategies that might benefit both trials.
Recommendation #4: Engage stakeholders at every step for greater impact
Stakeholder engagement has long been encouraged in clinical trials to ensure study relevance, enhance recruitment and retention, and maximize the impact of results [Reference De las Nueces, Hacker, DiGirolamo and Hicks15]. Study teams, however, are often unaware of how best to engage key stakeholders or understand how doing so can contribute to their clinical trial in a meaningful way.
Research stakeholders are individuals, groups, and organizations that have a stake, interest, or could be affected by the conduct and results of a research study. These may include community members, patients, community-based organizations, and advocacy groups, as well as health care providers and clinicians. Research teams can involve key stakeholders in the planning, design, and implementation of their study by collecting and integrating their feedback [Reference Boyer, Fair and Joosten16]. Helpful methods may include:
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Obtaining input on recruitment strategies, materials, and messaging from members of the target study population, such as through a community engagement studio [Reference Joosten, Israel and Williams17–Reference Israel, Farrow, Joosten and Vaughn19]
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Forming a Community Advisory Board that includes representatives from diverse communities to give feedback on recruitment and retention methods to increase the representation of underrepresented groups [Reference Newman, Andrews, Magwood, Jenkins, Cox and Williamson20,Reference Kubicek and Robles21]
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Partnering with trusted local and national community organizations to raise awareness of the trial among diverse populations [Reference Michaels22,23]
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Building mutually beneficial relationships with health care providers and requesting their assistance in patient referrals [Reference Michaels24]
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Acknowledging community stakeholders and partners in scientific manuscripts and dissemination activities or including them as co-authors
Resources
Enrolling and retaining a sufficient, representative participant population for clinical trials can be challenging. The four primary recommendations presented in this paper represent a consensus of opinion among eight RIC consultants, gleaned from several years of consultation experience with study teams. A more detailed account of the RIC’s consultations, recruitment resource implementation, and resource evaluation plans has been previously reported on [Reference Wilkins, Edwards and Stroud6]. Investigators can obtain assistance in incorporating these recommendations by accessing free tools and resources on the TIN website, through their local CTSA liaisons, or by submitting a proposal request for a RIC consultation. Future evaluations of RIC resources will also be deposited in the TIN website for public access. Asking the right questions, documenting and prioritizing plans, following through, and monitoring and adjusting strategies as the study accrues participants is the most promising road to recruitment success.
Disclosures
The authors have no conflicts of interest to disclose.
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