Introduction

Conducting randomized controlled clinical trials in rural and underserved pediatric populations in geographically diverse areas presents unique challenges. The National Institutes of Health formed a pediatric research network, called the Environmental Child Health Outcomes IDeA States Pediatric Clinical Trials Network (ECHO ISPCTN) that is designed to facilitate the delivery of state-of-the-art clinical trials to rural or underserved children and families [1]. Despite the support of this network, barriers to recruitment, retention, and other study activities remain.

Recruitment is the top barrier to the successful completion of clinical trials [2], and studies involving rural and underserved families face even greater recruiting challenges [3]. Experts categorize barriers to recruitment as either operational/administrative or participant-level. Operational and administrative barriers include the lack of translation services [4]; research training not connecting knowledge to practice [4,5]; lack of early engagement or ongoing relationships with the community or clinical staff by the research team [6–10]; delay between study training and recruitment resulting in lost momentum [8]; clinician time constraints [6,11,12]; fewer than expected or competition for available eligible participants [11,13]; strain on clinical resources and space [6,11]; and the need to be flexible and modify recruitment strategies [10,13]. Participant-level barriers include demographic factors such as rural, racial and ethnic minorities being skeptical of trial participation [8,14], as well as differing perceived seriousness of the relevant medical condition [8,13,14].

Although many experts agree that it is important to include rural and underserved families in clinical trials [1], including these special populations can be challenging beyond recruitment [15]. Studies struggle to retain rural families, and previous research has focused on improving retention rates for rural participants with specific approaches [16] such as repeated contacts [17]. Crocker and colleagues found that long periods between follow-up visits can be problematic [12], and Long et al. reported that participants lost interest in attending follow-up visits once the visits were thought to be unnecessary. They suggested mitigating this phenomenon by linking research activities to routine clinical visits [8].

The existing literature to date has primarily focused on participant perspectives as they are key to a successful clinical trial. However, input from clinical trials coordinators and other research staff is also important as they have valuable insights on barriers and facilitators to the clinical trials process. Previous research with clinical trials coordinators and other research staff has been limited to a focus on recruitment [13,18], but suggests that staff prefer to be involved early in the research process (i.e., during protocol development), and that research staff are often anxious about various study tasks which can interfere with study completion [13]. Specific to trials with rural and underserved children, a recent scoping review [19] found that most of the existing research on rural pediatric clinical trials consisted primarily of descriptions of study strategies, with limited research on the perspectives of study staff regarding the conduct of clinical trials with rural and underserved children.

The current paper aims to address this gap in the existing literature by using a mixed methods approach to assess study investigator and staff perspectives regarding the conduct of a multi-state randomized controlled clinical trial with rural children and their caregivers. Specifically, we report on the viewpoints of the staff for Feasibility Trial of the iAmHealthy Intervention (NCT04142034), one of the first behavioral intervention clinical trials conducted in the ECHO ISPCTN.

Methods

The iAmHealthy Feasibility Study [20], hereafter referred to as iAH was overseen by the ISPCTN Data Coordinating and Operations Center (DCOC) at University of Arkansas for Medical Sciences and their IRB acted as the central IRB for all sites. The clinical trial engaged 6 ISPCTN sites: Institutions in Delaware, Nebraska, South Carolina, and West Virginia served as clinical study sites and an institution in Oklahoma served as the study coordination site with the Kansas site leading the intervention team. The iAH trial was a pilot study that randomized recruitment methods at the site level (Consecutive, Traditional), and randomized participants at the individual level (iAH vs Control).

The study recruited children seen in participating rural clinics who were 6–11 years of age with a BMI > 85^th percentile and their primary caregiver. Caregivers signed written informed consent, and the children signed written assent. Clinic rurality was determined with the RUCA ZIP Code crosswalk version 3.1 available from the University of North Dakota [21]. The primary objective of the iAH trial was to assess key variables such as: participant recruitment, participant retention, intervention dose, and blinding. The iAmHealthy intervention was delivered via interactive televideo to caregivers and children, and included topics such as child exercise without peers, eating at social/group gatherings, increased attention to self-esteem and decreased focus on eating fast-food. The intervention is composed of 26 contact hours: 15 hours of group sessions and 11 hours of individual sessions. Groups met weekly for 12 weeks, followed by monthly for 3 months, for a total intervention period of 6 months. Baseline and post measures conducted remotely included height and weight, 3-day diet-recall and 7-day physical activity monitoring by accelerometer. The total possible compensation for iAH participation was $240: $20 consent, $20 for each month of the 6-month intervention period ($120), and $100 for completing post-intervention assessments and returning equipment. Enrolling coordinators were blinded to which group the participant was assigned. From there, the unblinded coordinator team stayed connected throughout the intervention period. The enrolling (blinded) coordinator did not have contact with participant again until the end of the study when they ensured post-measures were conducted and equipment returned. Primary outcome data from the trial were published elsewhere [22] and indicated that the vast majority of patients were recruited using the active method of recruitment (95%); data not yet published indicate that 91% of the sample was retained through the final measurement.

At the conclusion of the trial, study staff at each of the 6 sites and those involved in the intervention delivery or other aspects of the protocol were invited to participate in the current study which included 2 questionnaires. Study staff included site principal investigators, study coordinators, and study support staff from each site (referred to henceforth as “study-site personnel”), as well as staff involved in the delivery of the behavioral intervention or the collection of measures (referred to henceforth as “non-study site personnel”). Both questionnaires were distributed using the REDCap [23,24] web application managed by the DCOC shortly after trial activities concluded. The surveys were designed by study leadership to elicit information from all study personnel on their overall satisfaction with recruitment options, intervention arms, and the overall feasibility of the iAH study.

It is important to note that the iAH study began recruitment February 3, 2020, with some of the first activities taking place in person then rapidly transitioning to remote procedures with the outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic. End of recruitment was June 7^th, 2020, and study completion was March 25, 2021.

Survey 1: Recruitment

In addition to site and study role, Survey 1 involved 8 questions (Table 1); one that asked for a numerical rating of the three recruitment methods (Consecutive/Retrospective, Consecutive/Prospective, Traditional), and others that solicited open-ended comments regarding recruitment activities. The Consecutive/Retrospective method involved recruiting patients with healthcare visits from the prior year prescreened for likely eligibility and contacted first via letter, then phone. The Consecutive/Prospective method involved recruiting participants who were prescreened for likely eligibility during their healthcare visits. The Traditional method involved recruiting participants who self-identified after seeing flyers, emails, social media, and newsletters.

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Table 1. Survey 1.

https://doi.org/10.1371/journal.pone.0333229.t001

Survey 2: Overall study conduct

In addition to site and study role, Survey 2 involved 8 qualitative questions (Table 2) on retention and study procedures.

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Table 2. Survey 2.

https://doi.org/10.1371/journal.pone.0333229.t002

Results

Descriptive statistics were used to summarize quantitative results. For qualitative analyses, free text in both surveys was analyzed using the Morgan and Krueger [25] approach which focused on thematic analysis. Each coder (KF, BJ, CM, SGS, ASW) reviewed responses individually to generate an initial code set and then coded the data. Afterwards, coders participated in a series of meetings with an experienced qualitative researcher (AD) to discuss individual coding decisions and iteratively determined themes using a consensus-driven approach. As themes were defined and finalized, earlier coded responses were reassessed and recoded or re-categorized as needed to ensure consistency. All coders agreed that thematic saturation was reached and then quotes to support the final set of themes were identified. These preliminary results were presented to the full research team for review and opportunity for feedback. Consensus was reached amongst the group in determining the final themes and quotes.

Survey 1 had a 90% response rate (27 of 30 participants), and Survey 2 had an 83% response rate (25 of 30 participants). Table 3 describes the breakdown by role of the personnel that participated in each survey. Study support and regulatory staff had the lowest response rates (2 of 4 and 1 of 4 for Survey 1 and Survey 2 respectively). Quantitative results (Table 4) indicate most respondents were neutral about all recruitment methods (Mdn = 3, IQR = 1.0–1.5). Fourteen respondents reported that they did not participate in recruitment but still rated the recruitment options, raising questions about the validity of responses to this question. Primary investigators (n = 5) found the Consecutive Retrospective option to be not at all difficult (Mdn = 1, IQR = 2.0) and the other two options to be slightly difficult (Mdn = 2, IQR = 0.0–1.0). Coordinators that recruited participants considered Consecutive Retrospective and Consecutive Prospective slightly difficult (Mdn = 2, IQR = 2.0) while the median for the Traditional method was slightly higher (Mdn = 2.5, IQR = 2.5).

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Table 3. Roles of survey participants.

https://doi.org/10.1371/journal.pone.0333229.t003

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Table 4. Quantitative findings.

https://doi.org/10.1371/journal.pone.0333229.t004

Regarding qualitative analyses, six major themes were identified and reached saturation, with specific quotes supporting each theme presented in Table 5.

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Table 5. Qualitative themes and supporting quotes.

https://doi.org/10.1371/journal.pone.0333229.t005

Discussion

The purpose of the current paper was to use a mixed methods approach to assess study staff perspectives regarding the conduct of a multi-site pediatric randomized controlled clinical trial with rural or underserved children and their caregivers. The iAH study was a first of its kind clinical trial evaluating the feasibility and effectiveness of different recruitment strategies. The study found that sites reached full enrollment using the active (consecutive) method and no sites had success with traditional recruitment [22]. However, our quantitative survey results indicated study staff had no preferences among Consecutive (Prospective, Retrospective) and Traditional recruitment approaches, with all recruitment approaches receiving similar ratings. This is surprising as the three methods were not equivalent in terms of effort. For the traditional method, simple activities such as posting flyers or sharing an announcement on Facebook were implemented, which required much less effort than calling families who had been recently seen in the clinic (retrospective) or approaching the families when they were in the clinic for a visit (prospective). Other studies indicate, for example, that calling families or approaching them in clinic can be anxiety provoking for coordinators [13].

Effective recruitment strategies vary by study, population and other factors. Additionally, with the move since COVID-19 to more remote study visits and activities, the challenge of study enrollment has only increased in complexity. Finding successful and practical strategies that are not onerous on study staff are powerful tools in a site’s recruitment toolkit. Study staff without direct recruitment responsibilities seem to have enough knowledge of recruitment processes to form an opinion about how those efforts are going. They are involved in study meetings and likely hear how recruitment is going and work closely enough with those who are recruiting to draw their own conclusions. While their opinions may not be the most relevant, they still have value. Additionally, while these study staff answered the quantitative question about recruitment, they did not answer the qualitative portion.

Qualitative findings indicate that study staff believed families felt overwhelmed by study procedures wanted larger and more timely payment for study incentives and felt that a personal connection between themselves and families was important to successful study retention. Regarding the perception of participant burden, previous research suggests a disconnect between participant and staff perceptions. Shilling and colleagues [27] found that the research staff concerns that parents would be burdened by being approached to participate in research were largely unfounded, with most parents viewing the chance to participate as an exciting opportunity. Existing research suggests that the perception of study-related burden may differ by race, with those who identify as white more likely to decline participation due to perceived burden, and those who identify as Black more likely to decline due to lack of interest or family pressures [28]. Awareness of ongoing trials is also a major limiting factor to participation in clinical trials among underserved communities [3], but by using the active Consecutive recruitment methods (Prospective, Retrospective), the iAH study was able to overcome this issue [22].

Previous research with medical and research professionals supports the importance of building personal connections to successful recruitment and suggests specific behaviors that can promote positive relational interactions including “listening to personal information, expressing empathy, and then providing reciprocal self-disclosures.” [17]. Study staff enthusiasm for both the iAH behavioral intervention, and for working with underserved, rural populations are factors that may have facilitated personal connections with participants.

The current study is not without limitations. It was limited to 6 sites, which may not be representative of all sites. Second, due to staffing changes at 1 of the 6 sites, responses to questionnaires do not equally represent each site. Third, the study procedures described herein (various types of recruitment, remote behavioral intervention) may be limited to research groups conducting similar studies. Finally, because the staff who participated in this project were part of a national pediatric clinical trials network (the ECHO ISPCTN) their opinions may be significantly different than staff who are not part of a supported network.

Conclusions

Study investigators, coordinators and other research staff are critical to the conduct of clinical trials with rural and underserved children and families and future research is needed to raise the voices of these key partners in clinical trials conduct. These staff are often open to various recruitment methods, and are enthusiastic about working with underserved, rural families. They report that they believe families can be overwhelmed by study procedures, and that a personal connection with families can facilitate study conduct, both of which should be addressed in future studies. These findings could have important implications for investigators hoping to bring pediatric clinical trials to rural and underserved families.

Acknowledgments

We would like to acknowledge and thank the many wonderful research staff in our network who participated in this project.