ESPO and Health Sciences Section Symposium: Conducting Clinical Trial Research During the COVID-19 Pandemic: Transforming Research Practice for the Future

The COVID-19 pandemic caused significant disruptions for people and institutions across healthcare settings. Clinical trials are an important research tool to test interventions in real-world healthcare settings and provide high quality evidence that supports older adults’ longevity and wellness. Clinical trialists must consider how to account for unpredictable and ever-changing environmental contexts. The COVID-19 pandemic is a specific example of a changing context that impacted all stages of the clinical trials process from planning, to administration, and outcomes. Reflecting on ways clinical trialists navigated their studies during the COVID-19 pandemic may unlock opportunities to design flexible clinical trials that meet the needs of older adults in real-world environments. This symposium highlights five clinical trials for older adults that occurred during the COVID-19 pandemic. Dr. Carpenter will discuss lessons learned in implementing a palliative care intervention in nursing homes. Brianna Morgan will describe the pivots needed to complete a clinical trial testing an advance care planning website for nursing home residents with dementia. Dr. Nuckols will describe obstacles and opportunities to implementing a randomized controlled trial on hospital nursing units, including implications for medication safety. Dr. Pevnick will highlight barriers and facilitators to implementing a pharmacist-led intervention to reduce hospital readmissions. Dr. Stark will share novel procedures for conducting clinical trials in the community that reduce burden for older adult participants while maintaining fidelity. Presenters will address practice transformations that researchers can bring forward to design flexible clinical trials that meet the needs of older adults in different healthcare contexts.

Chronic respiratory diseases other than asthma in children: the COVID-19 tsunami

Coronavirus disease 2019 (COVID-19) affects all components of the respiratory system, including the neuromuscular breathing apparatus, conducting and respiratory airways, pulmonary vascular endothelium, and pulmonary blood flow. In contrast to other respiratory viruses, children have less severe symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A minority of children experience a post-infectious inflammatory syndrome, the pathology and long-term outcomes of which are poorly understood. The reason for the lower burden of symptomatic disease in children is not yet clear, but several pathophysiological characteristics are postulated. The SARS-CoV-2 pandemic has brought distinct challenges to the care of children globally. Proper recommendations have been proposed for a range of non-asthmatic respiratory disorders in children, including primary ciliary dyskinesia and cystic fibrosis. These recommendations involve the continuation of the treatment during this period and ways to maintain stability. School closures, loss of follow-up visit attendance, and loss of other protective systems for children are the indirect outcomes of measures to mitigate the COVID-19 pandemic. Moreover, COVID-19 has reshaped the delivery of respiratory care in children, with non-urgent and elective procedures being postponed, and distancing imperatives have led to rapid scaling of telemedicine. The pandemic has seen an unprecedented reorientation in clinical trial research towards COVID-19 and a disruption in other trials worldwide, which will have long-lasting effects on medical science. In this narrative review, we sought to outline the most recent findings on the direct and indirect effects of SARS-CoV-2 pandemic on pediatric respiratory chronic diseases other than asthma, by critically revising the most recent literature on the subject.

The Impact of Same Day Infusion Treatment Protocols for Uncomplicated Vaso-Occlusive Crises within an Embedded Sickle Cell Care Model

Background: Infusion Center (IC) based care of uncomplicated sickle cell disease (SCD) vaso occlusive crises (VOCs) is very effective and results in better outcomes. At low volume sickle cell programs, it is challenging to acquire resources for a dedicated infusion program. Our goal was to create an embedded infusion program within our cancer center infusion services utilizing existing resources to improve the quality of care for our SCD patients. Methods: A multi-disciplinary team consisting of a Nurse Case Manager, Advanced Practice Provider, MD, IC scheduler and IC charge nurse was assembled. An agreement was made between the SCD team and IC leadership that at least one time slot would be made available for a SCD VOC visit every day. A workflow was created and all team members were educated regarding the workflow. Visit numbers for IC visits, emergency department (ED) and inpatient (IP) hospitalizations were collected from the EMR and compared for pre IC development (Jan 1, 2017- Dec 31, 2018) and post IC (January 1, 2019 - Dec 31, 2020). Results: Between 2017-2020, 182 patients with SCD were seen in the emergency room and 163 patients in our outpatient clinics. After the institution of an IC based care plan in January 2019, IC visit volume increased (270 visits pre IC vs.1076 visits post IC). ED treat and release (not requiring admissions) visits decreased from 373 visits pre IC to 286 visits post IC. The number of inpatient admissions did not change significantly during this time frame. However, the percentage of admissions from the ED increased (43% pre IC to 50% post IC), indicating a higher complexity of patients seeking care from the ED. 10 of 35 patients who used the IC in 2020 had no acute visits (ED or IP) in 2020, while these individual patients had a total of 37 ED visits in the pre IC timeframe, of which 20 were inpatient admissions with a total length of stay of 137 days and 17 treat and release episodes at the ED. Conclusions: Our project successfully utilized existing infusion based resources to facilitate outpatient management of acute uncomplicated SCD VOCs. This project presents an effective strategy that can be utilized by smaller volume sickle cell programs who do not have a stand alone infusion program to improve the quality of care for their SCD patients. Disclosures Gopal: Pharming: Consultancy; GBT: Consultancy; Alexion: Speakers Bureau; Rigel Pharmaceuticals: Other: Clinical Trial, Research Funding.

Scrybe: A Secure Audit Trail for Clinical Trial Data Fusion

Clinical trials are a multi-billion dollar industry. One of the biggest challenges facing the clinical trial research community is satisfying Part 11 of Title 21 of the Code of Federal Regulations and ISO 27789. These controls provide audit requirements that guarantee the reliability of the data contained in the electronic records. Context-aware smart devices and wearable IoT devices have become increasingly common in clinical trials. Electronic Data Capture (EDC) and Clinical Data Management Systems (CDMS) do not currently address the new challenges introduced using these devices. The healthcare digital threat landscape is continually evolving, and the prevalence of sensor fusion and wearable devices compounds the growing attack surface. We propose Scrybe, a permissioned blockchain, as a method of storing proof of clinical trial data provenance. We illustrate how Scrybe addresses each control and the limitations of the Ethereum-based blockchains. Finally, we provide a proof-of-concept integration with REDCap to show tamper resistance.

Relationship of Alberta Stroke Program Early CT Score (ASPECTS) with the outcome of ischemic stroke and the neurocognitive stroke biomarkers

Background Reliable and acceptable biomarkers are needed to anticipate the outcome and cognitive impairment following ischemic stroke. The goal of this research is to examine the association of ASPECTS with cognitive decline, biomarkers of stroke, and acute ischemic stroke outcomes. This study included 120 patients with ischemic stroke in the middle cerebral artery region. The initial NIHSS, non-contrast CT brain assessed by ASPECTS, and the biomarkers of cognitive decline such as ESR, CRP, S100B, MMP9, and glutamate were investigated. The Montreal Cognitive Assessment and modified Rankin scale (mRS) were evaluated after 3 months. Correlations between ASPECTS, MoCA, biomarkers of cognitive impairment, and mRS were done by Spearman correlation. Results The incidence of cognitive impairment in our patients was 25.8%. Stroke biomarkers (ESR, CRP, S100B, MMP9, and glutamate) were significantly increased in cognitively disabled individuals with significantly lower mean MoCA scores than in cognitively intact patients. There was a strong direct correlation linking the initial ASPECTS and total MoCA test score after 3 months follow-up. Cases with unfavorable outcomes were older, more incidence of hypertension, and had higher average initial NIHSS (P < 0.05). While the average ASPECTS scores for the favorable outcome group of patients were significantly higher and there was a significant negative correlation between the initial ASPECTS and modified Rankin Scale score. Conclusions ASPECTS is a reliable scale to identify the extent of acute ischemic injury and could participate in assessing the outcome. ASPECTS and particular neurocognitive stroke biomarkers will enable the early detection of post-stroke cognitive impairment. Trial registration Registration of Clinical Trial Research: ClinicalTrials.gov ID: NCT04235920

Making the Leap: from Experimental Psychopathology to Clinical Trials

One important aim of experimental psychopathology research is to inform development of new interventions derived from basic science. However, testing whether a newly developed intervention is in fact effective requires moving from experimental studies to clinical trials, and this transition can pose many problems. These problems stem not only from the inherent complexity of even the simplest clinical trial, but also from differences between experimental psychopathology and clinical trial research that may not always be obvious to researchers immersed in only one of these specialist areas. In this paper we explore some of these complexities, and discuss when a clinical trial may, or may not be, the best next step in the translational process. We then consider some of the ins and outs of clinical trials methodology, from design and planning through to reporting, with the aim of providing a guide for experimental psychopathology researchers thinking of making the leap from their experimental studies of mechanisms to clinical trials of novel interventions. We hope that this can help increase the chance of successful clinical translation and novel treatment development from basic science.

Accuracy of Conflict-of-Interest Disclosures of Physician-Authors Publishing in High-Impact U.S. Medical Journals: A Comparison of the Journal of the American Medical Association and the New England Journal of Medicine

Objective: To assess the accuracy of self-reported financial conflict-of-interest (COI) disclosures in the New England Journal of Medicine (NEJM) and Journal of the American Medical Association (JAMA) within the requisite disclosure period prior to article submission. Design: Cross-sectional investigation. Data Sources: Original clinical-trial research articles published in NEJM (n = 206) or JAMA (n = 188) from January 1 to December 31, 2017; self-reported COI disclosure forms submitted to NEJM or JAMA with the authors published articles; Open Payments website (from database inception; latest search: August 2019). Main outcome measures: Financial data reported to Open Payments from 2014 to 2016 (time period that included all subjects requisite disclosure windows) were compared to self-reported disclosure forms submitted to the journals. Payments were defined as those not associated with a research study or formal research funding. Payment types were categorized as disclosed, undisclosed, indeterminate, or unrelated. Results: Thirty-one articles from NEJM and 31 articles from JAMA met inclusion criteria. The physician-authors (n = 118) received a combined total of $7.48 million. Of the 106 authors (89.8%) who received payments, 86 (81.1%) received undisclosed payments. The top 23 most highly compensated received $6.32 million, of which $3.00 million (47.6%) was undisclosed. Disclosure rates were the equivalent between the top 23 and the entire sample. Conclusions: High payment amounts, as well as high proportions of undisclosed financial compensation, regardless of amount received, comprised potential COIs for two influential US medical journals. Further research is needed to explain why such high proportions of general payments were undisclosed and whether journals that rely on self-reported COI disclosure need to reconsider their policies.

Clinical trial research on COVID-19 in Germany – a systematic analysis

Background: In 2020, the COVID-19 pandemic led to an unprecedented volume of almost 3,000 clinical trials registered worldwide. We aimed to describe the COVID-19 clinical trial research agenda in Germany during the first year of the pandemic. Methods: We identified randomized clinical trials assessing interventions to treat or prevent COVID-19 that were registered in 2020 and recruited or planned to recruit participants in Germany. We requested recruitment information from trial investigators as of April 2021. Results: In 2020, 65 trials were completely (n=27) or partially (n=38) conducted in Germany. Most trials investigated interventions to treat COVID-19 (86.2%; 56/65), in hospitalized patients (67.7%; 44/65), with industry funding (53.8%; 35/65). Few trials were completed (21.5%; 14/65). Overall, 187,179 participants were planned to be recruited (20,696 in Germany), with a median number of 106 German participants per trial (IQR 40 to 345). From the planned German participants, 13.4% were recruited (median 15 per trial (IQR 0 to 44). Conclusions: The overall German contribution to the worldwide COVID-19 clinical trial research agenda was modest. Few trials delivered urgently needed evidence. Most trials did not meet recruitment goals. Evaluation and international comparison of the challenges for conducting clinical trials in Germany is needed.

Capacity Building for a New Multicenter Network Within the ECHO IDeA States Pediatric Clinical Trials Network

Introduction: Research capacity building is a critical component of professional development for pediatrician scientists, yet this process has been elusive in the literature. The ECHO IDeA States Pediatric Clinical Trials Network (ISPCTN) seeks to implement pediatric trials across medically underserved and rural populations. A key component of achieving this objective is building pediatric research capacity, including enhancement of infrastructure and faculty development. This article presents findings from a site assessment inventory completed during the initial year of the ISPCTN.Methods: An assessment inventory was developed for surveying ISPCTN sites. The inventory captured site-level activities designed to increase clinical trial research capacity for pediatrician scientists and team members. The inventory findings were utilized by the ISPCTN Data Coordinating and Operations Center to construct training modules covering 3 broad domains: Faculty/coordinator development; Infrastructure; Trials/Research concept development.Results: Key lessons learned reveal substantial participation in the training modules, the importance of an inventory to guide the development of trainings, and recognizing local barriers to clinical trials research.Conclusions: Research networks that seek to implement successfully completed trials need to build capacity across and within the sites engaged. Our findings indicate that building research capacity is a multi-faceted endeavor, but likely necessary for sustainability of a unique network addressing high impact pediatric health problems. The ISPCTN emphasis on building and enhancing site capacity, including pediatrician scientists and team members, is critical to successful trial implementation/completion and the production of findings that enhance the lives of children and families.