Research capacity and limitations in Canadian paediatric emergency departments: An observational study on biomarker discovery

Abstract

Background

Paediatric research is essential to acquire effective diagnoses and treatment for children, but it has historically been under-prioritized. The PRIMED study aimed to characterize the bio-profiles of children with appendicitis and investigate their use as a clinical prediction tool. We evaluated the clinical research capacity of several Canadian paediatric emergency departments (EDs) and described both the challenges experienced in the implementation of the PRIMED study and the strategies which were used to improve local research capacity.

Methods

Eleven paediatric EDs across Canada provided basic demographic and administrative data along with laboratory- and human-resource availability during the PRIMED study enrollment. Data were summarized using descriptive statistics.

Results

Fewer than half of the study sites (5/11, 45%) had access to a laboratory that would process research samples 24 hours per day. Four study sites (36%) only enrolled patients during business hours (8:00–17:00). There was no nighttime coverage for patient enrollment and sample collection. Only three study sites (27%) had enrollment hours that captured over 75% of the potential study participants. Over half of the study sites (6/11, 55%) developed novel processes to enable study success, for example, creating graduate student on-call schedules and hiring bioscience-trained site coordinators to process samples.

Interpretation

Despite site-specific efforts to overcome resource barriers, the gap in clinical research capacity at academic paediatric EDs remains a significant concern. University research institutes and paediatric hospitals should invest in infrastructure and human resources to increase after-hours research capacity to optimize child health and wellness outcomes.

Children have both physiological and developmental differences from adults and paediatric research is necessary to find effective treatment options for children (1,2). Historically, paediatric research has been under-prioritized and has received less funding than clinical research focused on adults (1,3,4). Paediatric research studies are more likely to be cross-sectional or epidemiologic, whereas studies involving adults are more likely to be randomized controlled trials (RCTs) (4). Additionally, the number of adult RCTs published annually in general medical journals has increased over four times faster than the number of paediatric RCTs (5,6).

Conducting research in high-acuity and high-volume paediatric emergency departments (EDs) that treat patients 24 hours per day creates additional challenges (7–12). Identifying EDs with sufficient patient volumes is challenging, especially if there is heterogeneity in the data systems used at different hospitals (7,8). Studies have reported not having sufficient resources and research staff with uniform training to identify and enroll participants (9–12). Clinical staff have also reported difficulties in balancing a heavy workload with research study participation in the ED (9,11).

The Precision Medicine for Improving the Diagnosis of Pediatric Appendicitis in the Emergency Department (PRIMED) study aimed to characterize the metabolic and proteomic bio-profiles of children with appendicitis and investigate the use of these bio-profiles as a clinical prediction tool. Throughout the study implementation, the team encountered challenges related to a mismatch between patient presentations in high-acuity, high-volume paediatric EDs, and human- and laboratory-resource availability for clinical research projects. The objectives of this article are to demonstrate the challenges experienced in the planning and implementation of the PRIMED study and describe the novel processes used to enable success.

METHODS

PRIMED study description

The PRIMED study was a prospective multicenter cohort study. The team sought to characterize and compare the bio-profiles of children with acute appendicitis to those with non-appendicitis abdominal pain, and compare these bio-profiles to diagnostic tools traditionally used, such as imaging and laboratory investigations. The study was conducted according to the guidelines of the Declaration of Helsinki; each study site obtained approval from their Research Ethics Board, and parental consent was obtained.

Study setting and population

Eleven EDs at different Pediatric Emergency Research Canada (PERC) sites in seven Canadian provinces participated in the PRIMED study. PERC is a network of 15 Canadian tertiary children’s hospitals that facilitates research collaboration and multicenter trials. PERC is focused on generating and disseminating knowledge to ensure that children seen in general EDs receive the same quality of care as those treated in paediatric tertiary care centers (12,13). The study sites were the Alberta Children’s Hospital (Calgary—lead site), the BC Children’s Hospital (Vancouver), the Stollery Children’s Hospital (Edmonton), the Jim Pattison Children’s Hospital (Saskatoon), the Children’s Hospital of Winnipeg, the Children’s Hospital at London Health Sciences Centre, the McMaster Children’s Hospital (Hamilton), the Kingston Health Sciences Centre, the Children’s Hospital of Eastern Ontario (Ottawa), the Centre Hospitalier Universitaire Sainte-Justine (Montréal), and IWK Health (Halifax). Enrollment began in 2019 and was completed in December 2021.

Children under 18 presenting with abdominal pain were screened for enrollment by research personnel during enrollment hours, which varied by site. Those with suspected appendicitis (defined as patients who had possible appendicitis with laboratory tests, a surgical consult, or an ultrasound ordered) were eligible to participate in the study.

PRIMED sample collection and analysis

Enrolled study participants had research blood and urine samples collected before an ED diagnosis had been confirmed. A research team member performed an interview with the study participant or their caregiver, and a case report form was filled out by the treating ED physician. A medical record review was completed for all enrolled study participants.

Research blood and urine samples were analyzed using a precision medicine parallel cohort approach to create bio-profiles that differentiate children with acute appendicitis from those with non-appendicitis abdominal pain. Each site was responsible for initial blood and urine sample processing, which involved centrifuging and freezing samples according to study standard operating procedures. All study specimens were sent to the lead research site. Research sample analysis included nuclear magnetic resonance spectroscopy, mass spectrometry, and multiplex inflammatory protein mediator profiling.

Data collection for this manuscript

Basic demographic data and resource availability for each study site were collected in collaboration with the PRIMED investigators and research coordinators. Each research coordinator described the local processes of study implementation at their site using a standardized process (Supplementary Appendix 1). Descriptive statistics were used to analyze the data.

The study sites were characterized using basic demographics, patient enrollment, enrollment capacity, and sample collection, processing, and storage. Average daily enrollment hours were compared to laboratory sample processing capacity at each site, and a heat map was developed comparing triage visits by hour to patient enrollment hours at each site (Figure 2). Data from the Alberta Children’s Hospital 2020 to 2021 fiscal year annual report was used to determine the number of annual ED visits by triage hour. Using this as proxy data for other sites, the estimated percentage of children that are likely presenting during each site’s enrollment hours was calculated.

RESULTS

All eleven participating tertiary hospitals provided ED demographics and human- and laboratory-resource data. Table 1 describes the characteristics of the sites involved in the study.

Enrollment hours varied across the sites (Figure 1). Most sites began enrollment between 8:00 and 9:00 and finished between 17:00 and 22:00, with one site collecting samples until 23:00. There was no nighttime coverage for patient enrollment and sample collection (between 23:00 and 7:00) at any of the sites.

Human resources and laboratory facilities

Study sites implemented a variety of methods to collect, process, and store the research samples, for example, using different team members for sample collection and processing, and employing both research and clinical laboratories for sample processing and storage (Table 1).

Enrollment and laboratory processing hours

Enrollment hours ranged from 7 to 14 hours per day. Most ED visits occurred between 8:00 and midnight, with the peak being between 17:00 and 21:00. Five sites (45%) had enrollment hours that covered the entire 17:00 to 21:00 peak, four sites (36%) only enrolled patients outside of these peak hours, and the remaining sites (2/11, 18%) had enrollment hours that covered just part of the 17:00 to 21:00 timeframe (Figure 2).

Less than half of the sites (5/11, 45%) had access to laboratories that were able to process research samples for 24 hours per day; 6 out of the 11 sites (55%) were unable to process research samples for over 12 hours. Five study sites had access to laboratories that were able to process samples anytime, but the study sites were only able to collect samples for 12 hours or less each day (Figure 1). There was variation in the research sample processing locations, with six sites using a clinical laboratory and five sites using a research laboratory. Research laboratories were used at the sites where the study team did not have support from the clinical laboratories to process samples. Approximately half of the study sites (5/11, 45%) required novel methods to increase their research capacity to participate in the PRIMED study, such as hiring bioscience-trained laboratory coordinators to process samples or using a graduate student on-call schedule to process samples during evenings and weekends.

Estimated research coverage

Table 2 shows the estimated percentage of ED patients that presented during enrollment hours at each site. Four of the participating sites (36%) had enrollment hours that captured less than half of the children who presented to the ED. Only three sites (27%) had enrollment hours that captured over 75% of the potential study participants.

Innovative strategies to meet research needs

Despite significant challenges in meeting research needs, we observed encouraging innovative strategies used at PRIMED study sites to improve research capacity. Some sites hired research coordinators with laboratory skills that could process research samples. One site used a graduate student on-call schedule to process after-hours samples. Graduate students were called to transport and process samples in the research laboratory after regular business hours. This process expanded the number of samples that the study site was able to collect and increased graduate student exposure to clinical research and the development of laboratory skills. Research capacity was also improved by training and using PEM research program volunteers. At four of the study sites (36%), undergraduate and graduate students were chosen through a competitive application process and trained to enroll potential study participants. These sites had some of the highest number of enrollment hours with coverage up to 12 hours each day, including weekends.

DISCUSSION

This study explored the challenges of conducting clinical research in several paediatric EDs across Canada, and identified key barriers that have limited the research capacity at PRIMED study sites. We found a gap in the number of hours that patients could be enrolled into studies and the hours that laboratory samples could be processed. There was also a mismatch between study enrollment hours and when most children presented to the ED.

Enrollment hours and barriers

The enrollment hours at most study sites (8/11, 73%) were unable to capture over 30% of potential study participants due to limited research staff availability. Most sites collected samples during daytime hours, few sites collected samples in the evenings, and no sites collected samples overnight (23:00–7:00). This likely decreased the number of samples that each site was able to collect. Roper et al. encountered similar difficulties and were unable to enroll patients in the evenings and weekends (14). To ensure that sufficient study participants were enrolled, small non-financial incentives were provided to staff, and study materials were placed in common areas to remind staff to enroll eligible participants. They found that regular support and communication from the research team and strong leadership at each site were valued by clinicians (14). Kaur et al. similarly found that limited research staff hours hindered recruitment for a multicenter paediatric ED study in the UK, noting that research staff were not available during peak patient flow times (9). Other barriers identified included the need for clinicians to balance research study enrollment with a heavy clinical workload and an inadequate number of trained research staff. However, the clinical team’s perception of the importance of the research question, simple inclusion criteria, and having a research team to assist with study enrollment facilitated study participant recruitment. They also suggested hiring research staff outside of regular business hours to improve recruitment (9).

Clinical laboratory support

Most of the study sites did not have clinical laboratory support with resources and personnel to process study samples, or the laboratory was only able to process samples part of each day. There was a mismatch between the number of hours that patients could be enrolled each day and the number of hours that samples could be processed in the laboratory at nearly half of the study sites (Figure 1). This indicates a gap between the available research resources and potential study enrollment. Other studies have similarly reported difficulties in study participant enrollment due to a lack of site resources and have either failed to meet their recruitment targets, thus lowering the impact of their findings on clinical practice, or have extended their recruitment time, thus increasing costs (8,10). The discrepancy between available resources and potential enrollment, which was seen in the EDs in the PRIMED study, could similarly impact research capacity in all acute care settings that operate 24 hours per day. Timely collection of study samples is vital because disease progression and ongoing ED management might alter a patient’s physical and biological status; waiting until business hours the following day to collect samples might yield results that are not representative of the patient’s status at the time of presentation.

Additional challenges in PEM research

There are other documented challenges in conducting research in busy paediatric EDs (7–11,14). Clinical staff have reported hesitation in approaching parents for consent, for fear of creating an additional burden in an already stressful situation and difficulties in balancing a demanding clinical workload with patient enrollment (8–11). However, dedicated research nurses have been able to increase both the identification of eligible patients and patient enrollment into PEM studies (10,15). Hiring research staff can be used as a strategy to increase study participant enrollment. Additionally, providing sites with written expectations, roles and protocols, and having strong leadership at each site and regular communication with each site can facilitate research participant recruitment (11,14).

Other institutions have used innovative strategies to overcome these challenges. A program that gave undergraduate course credit to nursing students for working as research assistants was established at the St. Louis Children’s Hospital. The program allowed student nurses to apply theoretical learning, increased their research experience, and provided valuable mentorship opportunities (16). Additionally, Stang et al. found that 87% of caregivers were comfortable being approached by trained undergraduate student volunteers, further supporting the use of volunteer research assistant programs to increase research capacity in the ED (17).

Tertiary academic hospitals and research centers are intended to lead innovations in science and medicine to improve clinical practice and patient care. However, our data show that many Canadian paediatric centers do not have the infrastructure needed to optimally participate in multicenter studies in which time-sensitive laboratory sample collection and processing are necessary. Improved access to both human resources and laboratory facilities is required to increase the research capacity in tertiary academic hospitals across the country. Research institutes at each university should prioritize supporting their clinical environments in conducting studies by ensuring adequate research and laboratory staffing and access to laboratory resources.

Limitations

There were several limitations in our study. The PRIMED study sites were all tertiary university-affiliated paediatric EDs in urban centers that have access to a variety of equipment for patient care and staff with specialized training, and the results of our study might not be generalizable to other paediatric or ED settings. We report data specifically from the participating PRIMED sites, which did not include the four paediatric EDs in Canada not participating in the PRIMED study, each of which may have different resources and capacity. The PRIMED study only included paediatric EDs in Canadian hospitals in a public healthcare system. Our results might not be applicable to other regions that have private or two-tiered public and private systems. To calculate percentage of children presenting during enrollment hours, we used hourly enrollment data from the Alberta Children’s Hospital (lead site) as proxy data across the study sites, due to data availability. We anticipate this data to be representative of hourly census across the participating sites, with peak percentage of presentations occurring during evening hours.

The limitations in patient enrollment and biological sample processing hours in tertiary paediatric EDs in Canada restrict much-needed bioscience and translational research capacity. While innovative strategies such as volunteer programs, hiring bioscience-trained site coordinators to process samples, and graduate student on-call schedules increase capacity, significant gaps in enrollment coverage persist. Paediatric hospitals and university research institutes should invest in sustainable human resources and infrastructure to truly strengthen the future of child-focused bioscience and translational research studies, and ultimately improve emergency care for children across the country.

SUPPLEMENTARY DATA

Supplementary data are available at Paediatrics & Child Health Online.

FUNDING

This research received funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute.

DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

CONFLICT OF INTEREST

All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

CONTRIBUTORS’ STATEMENT

Dr Elena Mitevska drafted the manuscript, performed data statistical analyses and data interpretation, revised the manuscript, and approved the final version of the manuscript to be published. Dr Beata Mickiewicz conceptualized and designed the study, collected the data, revised, and critically reviewed the manuscript for important intellectual content, and approved the final version of the manuscript to be published. Leslie Boisvert, Christine Bon, Redjana Carciumaru, Ramona Cook, Tyrus Crawford, Joan Dietz, Melanie Doyle, Eleanor Fitzpatrick, Angela Hui, Karly Stillwell, and Adriana Trajtman collected the data and approved the final version of the manuscript to be published. Drs Darcy Beer, Maala Bhatt, William Craig, Jocelyn Gravel, April Kam, Ahmed Mater, Anne Moffat, Naveen Poonai, and Vikram Sabhaney revised and critically reviewed the manuscript for important intellectual content, and approved the final version of the manuscript to be published. Dr Graham C Thompson conceptualized and designed the study, coordinated and supervised data collection, was responsible for funding acquisition, revised and critically reviewed the manuscript for important intellectual content, and approved the final version of the manuscript to be published. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

References