Research Spotlight

Inspired by positive experiences as an undergraduate, I signed up for the opportunity to gain research experience during residency in the Columbia University Apgar Scholars program. When Dr. Margaret Wood advised me, as a junior resident, that a career conducting clinical research path would require additional research methods training and dedicated time away from patients, I was astonished. Clinical work is exciting and energizing. The roles are clear, the gratification can be immediate, and positions are secure. In contrast, early in my clinical training, reinvesting my efforts in a parallel but separate career path felt uncertain and risky. I could not imagine, at that time, how complementary my clinical and research work would become.

Ten years later, I remain grateful for Dr. Wood's advice. I've had clinical education and leadership roles in my early career but have found none more consistently engaging than research work. Despite successful early research experiences, it took me several years to gain enough training and experience to commit to a research-focused career. Finding the right balance between clinical and research work is an ongoing challenge; like many clinician-scientists, I see the clinical care I deliver inextricably linked to the questions I'm working to answer.

As an Apgar Scholar, I began to work with SOCCA member Dr. Hannah Wunsch, who has been my longest-serving mentor, collaborator, and cheerleader. As the inaugural Columbia Apgar Scholar and leader in critical care health services research (now holding a Canada Research Chair), her work has transformed our understanding of critical care delivery in the US and around the world.

One central theme in health services research is variation in care delivery. In perioperative medicine, practice variation is present in many aspects of care, from the decision to perform surgery, the type of anesthetic administered, the approach to mechanical ventilation, and ICU admission. Clinical practice variation is not necessarily a problem. Still, it may indicate a lack of supporting evidence, equipoise among clinicians, or local barriers to providing evidence-informed care. Variations like these are measurable and attributable to individual clinicians, groups, or hospitals. Notably, when differences in practice are associated with differences in outcomes, these observations may inform research, policy, and clinical care. In some instances, we can use advanced biostatistical methods to make causal inferences about the relationships between differences in care delivery and outcomes meaningful to patients and health systems. This approach is especially compelling when examining questions unanswerable (due to practical or ethical challenges) with randomized trials.

With Dr. Wunsch and her network of collaborators and mentees, I have used these methods to examine questions informed by clinical experiences. I was a first-year resident during a national norepinephrine shortage. One of my first projects with Dr. Wunsch examined the effects of that shortage on vasopressor use and outcomes of patients with septic shock. Drug shortage is a perennial problem in American healthcare. Still, our study was one of the largest to describe an increased risk of in-hospital mortality among patients with septic shock admitted to hospitals using lower than expected amounts of norepinephrine during the shortage.

This project led to other studies focused on medication use for shock, where vasopressors may be ubiquitous. Still, in many conditions, evidence supporting the selection of specific medications is limited. During that time, my collaborators and I witnessed great enthusiasm for administering vitamin C, hydrocortisone, and thiamine (HAT therapy) for patients with septic shock. While randomized trials were ongoing, we used clinical and pharmacy records in a large cohort of patients with septic shock to describe the adoption of HAT therapy in US hospitals. Not only did our study describe rapid uptake of the therapy, we captured enough patients to conduct comparative effectiveness analyses. Our findings added to the growing number of clinical trials that did not demonstrate treatment benefits. While drafting that manuscript, I noticed that several investigators, inspired by the original HAT therapy study, conducted follow-up studies with results likely influenced by unrecognized immortal time bias. This bias is a frequent problem in observational studies in critical care, in part because methods used to address other study problems (such as confounding) can't reduce it. Therefore, we developed a set of tools for readers, reviewers, and investigators to identify and mitigate the influence of immortal time bias in their work.

While a faculty member at the University of Texas Health San Antonio, our affiliated hospital transformed an out-of-use operating room and PACU into a dedicated space for clinical management and recovery of organs from deceased donors after brain death. Working in that unit, I grew increasingly interested in the US organ donor identification and management system. I was surprised to learn that the care we provide to deceased organ donors in the ICU and ORs is not well characterized. Applying health services research methods to examine care delivery in this unique population is a necessary first step to help us understand how to better care for organ donors and the thousands of patients waiting for transplants.

I moved to the University of Pennsylvania in the fall of 2020 and have focused on building additional mentorships and collaborations with health services researchers, clinical trialists, and implementation scientists. I have been leveraging new resources (like the Leonard Davis Institute for Health Economics) to build a new research program and understand the implications of the work on US healthcare policy. I've received funding from the University of Pennsylvania McCabe Foundation to support observational projects examining the delivery of anesthetic care to deceased organ donors during recovery procedures. This January, I became a Learning Health System Scholar in the AHRQ/PCORI K12 Transforming the Generation and Adoption of Patient-Centered Outcomes Research in Practice program. The opportunity will help me develop a deceased organ donor-focused learning healthcare system to understand organ donor care delivery and establish an infrastructure for high-quality observational and interventional authorized donor research. Work from this mentored research grant will inform future K23 applications

As mentorship and collaboration have been instrumental in my early career development, I'm proud to represent the diverse group of investigators who belong to SOCCA as a member of the Research Committee. I will serve as the Chair of the Subcommittee on Research Collaboration next year. With my Co-Chair Dr. Marc Lopez, we are developing an interactive database of SOCCA members and their research expertise to foster cross-institutional invitations to speak and collaborate. I'm proud to be joining the new SOCCA Women in Critical Care initiative (founded by Dr. Shahla Siddiqui) and look forward to contributing to the group's mission. I look forward to future collaboration with SOCCA leaders to support the research efforts of our members and to mentor the next generation of students and trainees early in their research careers.

Author

Emily A. Vail, MD, MSc.

Research Committee; Co-Chair, Subcommittee on Research Collaboration

Assistant Professor of Anesthesiology & Critical Care at the Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania