(Originally presented abstract at 2019 Annual Conference San Antonio)
Sara Sampaio MD, CCRP,*, Sepideh Saroukhani MD, MS, PhD candidate, Aryn Knight BS, CCRP, Jennifer L. Chambers RN, BSN, CCRC,
Emerson C. Perin MD, PhD, FA
In this article, we describe the strategies and approaches developed at the Center for Clinical Research at Texas Heart Institute (THI) in Houston, Texas, to facilitate efficient participant recruitment for heart failure–related randomized controlled trials (RCTs). Randomized trials are typically complex in terms of the target population, protocol design, and intervention strategies — factors that can hinder the recruitment of a sufficient number of eligible participants. Thus, detailed upstream planning is crucial to guide recruitment efforts — especially in trials that focus on serious medical conditions such as heart failure — and a trained recruitment team is needed to execute protocol-specified tasks. Despite extensive literature on strategies for enhancing participant recruitment in research, little has been reported about the actual activities and experiences associated with recruitment and about the impact of organizational strategies on this work.
To improve RCT recruitment at our clinical research center, we developed a systematic approach to identifying, qualifying, and consenting clinical trial participants, and we established a division dedicated to participant recruitment. Our workflow is based on the best practices used by study staff who were recruiting participants for heart failure RCTs. Nonetheless, we believe that this structure could be used to manage and organize the recruitment processes for various types of RCT, given that the recruitment challenges inherent in heart failure RCTs are also commonly encountered in most other RCTs targeting serious medical conditions.
Randomized controlled trials are the gold standard for evaluating the efficacy and safety of medical and health care interventions, as they produce the highest level of supporting data for evidence-based medicine.1 The RCT is one of the most complex and costly study designs in which every step is prespecified in the protocol and is to be precisely executed as planned. The recruitment process, which aims to identify and enroll representatives of the target population in sufficient numbers to fulfill the sample-size and power demands of the study, requires ongoing communication and integration between the research team and potential participants.2,3
Recruitment Barriers in the Randomized Clinical Trial
Recruiting sufficient participants is key to any RCT’s success.4,5 Although several studies (including systematic reviews and meta-analyses) have investigated recruitment barriers and have aimed to identify potential strategies for improving enrollment in RCTs, slow or insufficient recruitment persists as a major problem.6-8 An analysis of registered RCTs showed that 19% of the studies were closed or terminated early because of failure to recruit enough participants.9Findings from other studies indicate that 86% of RCTs in the United States did not meet their recruitment targets within prespecified timelines,7,10 and Lamberti et al.11 found that study timelines in a group of biopharmaceutical clinical trials doubled beyond planned enrollment periods due to low recruitment rates. Furthermore, the recruitment process for trials with chronically or severely ill participants (such as those with heart failure) tends to be more laborious and requires more effort and time from the recruiting team, compared with trials targeting healthy populations or those with less-serious medical conditions.12
Heart failure is the leading cause of hospitalization among elderly populations in the United States.13,14 Its incidence is expected to increase 46% between 2012 and 2030, by which time more than 8 million US adults will have heart failure.15 Numerous RCTs are investigating ways to improve the care of patients with heart failure,14,16 although because of the high prevalence and incidence of this condition, the pool of available patients who meet eligibility criteria for heart failure RCTs and are willing to participate in them tends to be overestimated.8 Because of their high complexity, heart failure RCTs may require multiple pre-screenings and follow-ups to confirm or reconfirm eligibility depending on the number of protocol inclusion and exclusion criteria and study-specific concerns for participant safety. Such complexities could result in large numbers of screening failures and low enrollment rates. Evidence from several heart failure trials indicates that for every participant enrolled, approximately 100-150 potential participants were screened.12,17
Multiple factors may contribute to this paucity of eligible or willing participants: (1) the clinical scenario for heart failure is broad and ranges from classic symptoms (e.g., dyspnea, edema) to less common clinical presentations (e.g., severe fatigue, gastrointestinal distress, depression), any of which can be severe and debilitating14; (2) patients with heart failure tend to be older18 and sicker, with various associated comorbidities that can lead to multiple emergency department visits and hospitalizations16; (3) the severity of symptoms and complexity of the disease, especially when accompanied with loss of autonomy and inability to engage in self-care, can render patients unable or disinterested in participating19,20; (4) heart failure trials are usually complex and can have more than 50 inclusion and exclusion criteria to capture specific heart failure types and stages.12,14
Changing Recruitment Paradigms
Recruitment is the most time-consuming task of an RCT and can take up to 30% of the study timeline.21 Therefore, a well-planned recruitment process is required to avoid exceeding the study budget and planned timeline. Beyond upstream planning at the trial design level, which is crucial to guide recruitment efforts, establishing an efficient structure to execute the process will greatly facilitate prescreening and recruitment efforts.22
Recruitment is usually done by trained clinical research coordinators (CRCs). In addition, CRCs typically perform several other trial-related activities, including data collection and documentation, management and scheduling of study visits and procedures for all participants, and submission of regulatory documentation; these duties may vary, depending on the infrastructure at the study site. CRCs also work closely with study investigators, study sponsors, clinical research organizations, and monitors to administratively and clinically maintain the conduct of the trial. As only one part of these responsibilities, the recruitment process itself includes multiple specific tasks: reviewing medical records and prescreening potential participants for eligibility, providing detailed information about the study to potential participants and taking time to address their concerns and questions about the trial, obtaining authorizations for release of information (ROI) and collecting required medical records, discussing and clarifying inclusion and exclusion criteria with investigators, keeping potential participants well informed as the recruitment process moves forward, and finally, scheduling the first study visit.
Not surprisingly, CRC workload has been reported as one of the key factors that interrupts participant recruitment.22 The negative impact of CRC workload on recruitment success might be minor at the beginning of a study; however, as the study moves forward, tasks related to enrolled participants in the trial are likely to take priority over tasks related to new participant recruitment, disrupting ongoing enrollment.
Methods and Results
The principal goals of an RCT recruitment process are to identify potential participants, to prescreen their medical records to determine eligibility, and to enroll the requisite number of eligible participants within planned study timelines. Maintaining an efficient process for achieving recruitment goals throughout an RCT requires optimal allocation of time and staffing to efficiently manage the pool of potential participants and to ensure that all possible candidates receive the attention and information that they need to become an enrolled participant. Our objective was to create a preplanned, standardized process to follow whenever we reach out to a potential participant.
We took a two-pronged approach. First, we listed all recruitment tasks, mapping every step from the initial contact with the potential participant to his or her enrollment. On the basis of whether specified tasks were administrative or clinical in nature, we designed a dedicated recruitment team that would be equipped and able to carry out these tasks. Second, we created a recruitment division within our clinical research center to centralize the entire recruitment and prescreening process for all of our clinical research trials and to facilitate staff training and oversight.
Standardizing Recruitment Activities
The first step toward systematizing our recruitment process was to gain knowledge about the factors that were affecting recruitment at Texas Heart Institute, from both site and participant perspectives. We interviewed stakeholders (e.g., clinical staff, patients, trial participants) and observed our process to understand its strengths, weaknesses, and gaps; we supplemented this knowledge with an extensive literature search of known barriers to successful recruitment. For example, lack of understanding about the randomization process is one reason that potential participants may be reluctant to enroll in an RCT; they are more likely to feel comfortable about participating if they are well informed about the study. Thus, study staff must be able to take time to explain and clarify various study-related concepts, such as the principle of clinical equipoise, the rationale behind randomization, and the need for having a placebo group. Additionally, potential participants should be given sufficient time to think about the study and the required procedures, consult with their health care providers, and ask questions before consenting to participate. This process requires staff who are available to respond to potential participant questions and concerns in a timely manner.
Once we better understood our own recruitment processes, we listed all of the tasks involved in the process and noted their sequences, integrations, and interdependencies. For example, medical records cannot be accessed before a potential participant returns the signed ROI authorization form, and prescreening is not possible until relevant medical records can be obtained; in addition, many tasks require multiple follow-ups to move the process forward. We then used cross-functional process mapping (CFPM) to arrange these tasks into an organized workflow with clear division of responsibilities. This provided a standardized, evidence-based foundation for establishing and staffing the new recruitment division within our clinical research center.
Cross-Functional Process Mapping
Process mapping techniques are management tools used to design and reengineer processes and to improve workflows or outputs. Recently, they have gained popularity in health care settings and have been widely used, especially in health care quality-improvement projects.23 The key advantage of process maps is that they provide a concise visual demonstration of task interdependencies and integrations, such that the average adult should be able to clearly understand the process, regardless of his or her position or educational background.
In particular, CFPM technique encompasses an especially broad level of detail; it is useful for identifying flaws and bottlenecks (such as duplication of effort) that could make a process inefficient. A CFPM workflow can be easily communicated to all team members: Within a single diagram, CFPM delineates all activities involved in the process, the functional unit that performs each activity, the sequences of tasks, their interdependencies, and key decision points, quickly providing a profound understanding of the entire process. Accordingly, CFPM workflows are useful for training purposes as well. Considering these advantages, we decided to use CFPM to model the proposed workflow in the recruitment division.
The CFPM workflow starts with a triggering event, which in our case is when a potential participant reaches out to our recruitment division or we receive a new referral from a physician or other medical staff. Vertical bands (so-called “swim lanes”) represent the functional units within the division. Personnel assigned to each functional unit are responsible for the tasks that are shown within its swim lane.24 Tasks are presented using basic flowchart shapes (Fig. 1), each of which has an underlying functional meaning as to the type of task within the process. Detailed task-specific instructions or documents may accompany the map as needed to clearly articulate a given task.
To create our workflow process map, we determined which recruitment activities required clinical knowledge so that we could classify each task as either clinical or administrative. We then used these classifications to map the structure for our recruitment division, for which we established three distinct functional units: the recruitment assistant, a non–clinically trained individual who handles strictly administrative tasks; the recruitment coordinator, a clinically trained individual who handles the initial clinical recruitment tasks, thus relieving some of the CRC’s extensive workload; and the CRC, who handles the remaining clinical recruitment tasks (Fig. 2).
The recruitment assistant handles nonclinical administrative tasks in the recruitment process. Overall, the recruitment assistant is responsible for ensuring that potential participants receive requisite information and other resources about the trial(s) of interest and that their concerns and questions are adequately addressed throughout the prescreening process. To equip the recruitment assistant with needed skills and knowledge, we provide training specific to the aims and processes of the clinical trials for which we are actively enrolling participants.
The recruitment assistant’s key responsibilities include making the first contact with potential participants who reach out or are referred to the center and staying in touch with them throughout the prescreening process. These activities do not require a clinical background; thus, we find it more beneficial to have an assistant experienced in customer relations. Indeed, the quality of the first encounter and the manner in which the research study is communicated could substantially influence a potential participant’s decision to take part in the research.
After receiving an inquiry from a potential participant or a referral from one of our recruitment sources, the recruitment assistant responds to the potential participant within 48 hours. Following Good Clinical Practice guidelines, the recruitment assistant uses institutional review board–approved scripts to guide his or her communications with potential participants throughout the process. The initial discussion includes general information about clinical research, how investigational therapies differ from current FDA-approved treatments, and available clinical trials at our institution. If the potential participant is interested in enrolling in one of our RCTs, the recruitment assistant asks for permission to administer a questionnaire that has broad questions about the potential participant’s medical history in order to determine if initial inclusion criteria will be met. All of the information obtained is entered into our clinical trial management system.
If no reason for exclusion is identified, access to the potential participant’s medical records is necessary for the prescreening process to continue. We have developed a standardized information package to be sent to the potential participant by the recruitment assistant; this package includes an ROI authorization form to be signed by the potential participant, study brochures, a copy of the informed consent document, and contact information for the study team. Once the ROI form is signed and returned, the recruitment assistant requests all necessary medical records within 48 hours. Follow-up calls to health care providers and to the potential participant also take place within specific timeframes (Fig. 2). After all medical records are retrieved, the recruitment assistant creates and organizes the potential participant’s file in accordance with our standard operating procedures and transfers it to the recruitment coordinator for review.
To address complex or clinical questions, the recruitment assistant connects potential participants with staff who have relevant expertise, such as the study CRC, research nurses, managers, or investigators. In addition, the recruitment assistant updates the clinical trial management system throughout the prescreening process to document all interactions with potential participants and to revise their status as needed. Finally, if a non–self-referred potential participant becomes unwilling to participate or is found to be ineligible during prescreening, the recruitment assistant provides feedback to the potential participant and to the referral source.
If a non–self-referred individual does enroll in a trial, the recruitment assistant follows up with the referring physician to keep him or her abreast of the patient’s status in regard to study participation.
The recruitment coordinator is a person with a clinical background who is experienced in clinical research—for example, a research nurse, registered nurse, nurse practitioner, physician’s assistant, medical graduate, or foreign medical graduate. The recruitment coordinator handles the prescreening tasks that are clinical in nature; he or she oversees the prescreening and recruitment activities for all trials being conducted at Texas Heart Institute, supervises the work done by the recruitment assistant, and supports the recruitment assistant when needed.
The recruitment coordinator reviews medical records, maintains a prescreening log, and fills out a chart summary and a study-specific inclusion and exclusion criteria checklist. If additional medical records are needed to complete the prescreening, the recruitment coordinator asks the recruitment assistant to request the required records. After completing the prescreening process, the recruitment coordinator contacts the potential participant to review the medical history, resolve any outstanding issues, and answer any questions about the study and the previously sent informed consent document. Throughout this process, the recruitment coordinator and recruitment assistant update the potential participant’s status in the clinical trial management system.
If the prescreening review of the medical records indicates that the potential participant is not eligible for the current clinical trial(s), this information is entered into the study’s prescreening log and shared with the CRC. The prescreening log must be kept updated by the recruitment coordinator, as it is an important tool in evaluating the trial’s recruitment outcome.
Clinical Research Coordinator
When a potential participant meets all prescreening inclusion criteria and no exclusion criteria are identified, his or her file is sent to the CRC (Fig. 2), who contacts the potential participant to discuss enrollment. If the potential participant is willing and able to proceed, the CRC schedules the initial study visit, during which the participant will sign the informed consent document and complete any baseline tests required by the study protocol.
The recruitment process is complete once the participant signs the informed consent document. The CRC will continue to monitor and communicate with the participant throughout the trial.
The RCT recruitment process includes attracting, shortlisting, selecting, and enrolling suitable study participants. The success of this process depends on having access to a pool of potential participants and efficiently performing all tasks until the potential participant becomes an enrollee by signing the RCT informed consent document. Rapidly evolving electronic health record systems, patient portals, and many other resources and advertising campaigns have increased public awareness about RCTs and have facilitated access to potential participants. Findings from a recent national public survey show that approximately 90% of the US population agree that RCTs are important for improving health,25 and more than 70% of Americans are at least somewhat willing to participate in clinical trials.25-27 Even so, lack of resources to handle all received inquiries (e.g., calls, emails, letters) and referrals in a timely manner remains problematic for many sites recruiting RCT participants.27
We found that visualizing our recruitment procedures and staffing gave us a better understanding of the entire process. First, we noticed that the administrative workload during recruitment can be extremely heavy and may interfere with the many other responsibilities that CRCs take on in conducting RCTs. By adding administrative assistance to the recruitment team, we modified the process and directed the administrative workload away from the CRC. Having another team member available to speak, respond, and answer questions facilitates constant contact with participants, maintains active communications with referral sources, and promotes potential participant education while alleviating the CRC’s workload. Notwithstanding, the CRC is responsible for the overall conduct of the trial, and his or her involvement in the recruitment process is essential. In other words, in the new setting, the recruitment team and the CRC work in harmony to make sure that the recruitment process follows institutional review board requirements, Good Clinical Practice guidelines, and the study protocol.
Second, visualizing the workflow enabled us to identify delays, redundant work, unnecessary complexities, and critical failure points in our recruitment process. By modifying the process and clearly delineating the roles and responsibilities of the various recruitment team members (along with their interdependencies), we were able to create a recruitment workflow that contains as few tasks and staff as necessary, thereby promoting efficiency.
Third, developing this workflow has facilitated staff training and process consistency during the conduct of our institution’s RCTs.
Careful planning and the development of strategies to manage administrative and prescreening workload has enabled constant and consistent RCT recruitment efforts and activities at our center. In addition, maintaining active communications with potential participants and referral sources has increased their engagement with the center and has motivated referral sources to refer more potential participants.
This model contributes to a common understanding of the recruitment process. Although this workflow is based on the best practices by CRCs working on heart failure RCTs at Texas Heart Institute’s Center for Clinical Research, we believe that the process we undertook is highly adaptable and will be useful for systematizing and managing the recruitment process in many other types of RCT. The goals, steps, functional units, and personnel required to meet any given institution’s needs can easily be determined, organized, and mapped by using these techniques.
This work was supported by general funding from the Texas Heart Institute.
The authors report no known conflicts of interest associated with this publication and no significant financial support for this work that could have influenced its outcome.
Jeanie F. Woodruff, BS, ELS, contributed to the editing of the manuscript.
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Fig. 1. Basic flowchart shapes and their functional meanings.
Fig. 2. Recruitment workflow diagram. CTMS: clinical trial management system; ROI: release of information authorization form; SOP: standard operating procedure. Reprinted with permission from Texas Heart Institute.