Clinical Research

The Department’s Clinical Research program focuses on improving healthcare through clinical research and education. The program includes both investigator-initiated and industry-sponsored clinical projects, including NIH-supported single center and multicenter clinical trials. The program is advancing medical practice in the fields of perioperative care, chronic pain and medical devices. Investigators are practicing physicians who use clinical expertise to develop research protocols that seek to answer clinically-significant questions and test novel treatments.

  • The Perioperative Clinical Research Institute (PCRI) is led by David McIlroy, MB.BS., MD, MClinEpi, and Debra Craven, MSN, MMHC. The mission of PCRI is to:
    •    Promote a culture of large and robust clinical trials that would, in turn, provide high-quality evidence to inform perioperative practice nation-wide.
    •    Promote high-quality, high-impact clinical research tailored to the experience and expertise of individual clinicians and accessible to all members of the department
    •    Create opportunities for junior investigators to learn the process of clinical research
    •    Mentor investigators throughout the research development and implementation process
    •    Promote Good Clinical Practice (GCP) and ensure regulatory compliance

    The PCRI team provides a full range of support services, including development and submission of IRB applications, contracts management, initiation and execution of clinical studies, regulatory and compliance oversight, data management, biostatistics and biomedical informatics support. The end-goal is execution and publication of well-designed clinical research studies that address important questions, from smaller studies designed to generate preliminary, pilot or feasibility data in support of subsequent grant applications through to multi-center investigator-initiated studies.  Most of the department’s investigators are practicing physicians who use their clinical expertise to develop research protocols that answer clinically important questions.  The PCRI team consists of highly trained and broadly experienced research professionals, including research nurses, clinical trial coordinators, a regulatory specialist and administrative support.

  • Operational management of PCRI is guided by the Vanderbilt Anesthesiology Clinical Research Advisory Committee (VACRAC).  All proposed clinical research studies go through VACRAC for development and refinement. There is dedicated informatics and biostatistical support within the department, with focus on supporting studies that can lead to important clinical trials.

    VACRAC is co-chaired by Edward Sherwood, MD, PhD (Vice Chair for Research), David McIlroy, MB.BS., MD, MClinEpi (Director of Clinical Research), Pratik Pandharipande, MD, MSCI (Vice Chair for Faculty Affairs), and Matthew Shotwell, PhD (Department of Biostatistics). The committee’s membership is composed of established clinical investigators in the Department of Anesthesiology.
    Any member of the Department of Anesthesiology may submit a clinical research proposal as a 1-page on-line submission including a brief background to the clinical problem, a primary hypothesis for testing, and the likely significance of the result of the proposed study.  All proposals undergo rapid review by a small research committee, with written feedback provided, including a traffic-light style triage system and advice on what may be required to advance the project.  Resource intensive projects are typically triaged into a more intensive VACRAC studio where investigators present their proposals to senior clinical researchers within the department for real-time discussion and dialogue aimed at refining the study methodology.  

    Currently active studies include a mix of funded and unfunded studies, investigator-initiated and industry-sponsored studies, single-center and multi-center clinical trials, observational and retrospective studies.  The department and institution strongly support the initiation, development, and execution of large pragmatic trials.  Recent or current clinical trials with which we are involved include the multicenter REGAIN trial of general anesthesia vs regional anesthesia after hip fracture, the single-center COPE-iOS trial testing the effectiveness of cognitive and physical exercise to improve outcomes after surgery, a single-center study of pharmaco-genomic guided beta-blocker administration in patients undergoing cardiac surgery, large pragmatic trials of intraoperative ketamine and high-flow nasal cannula to reduce re-intubation after cardiac surgery.

    Research proposals may be submitted to VACRAC using the embedded hyperlink.

     

  • Goal:  The primary goal of the Vanderbilt Anesthesiology Innovation Grant Program is to promote investigator initiated research for early stage projects that will lead to publication and, ideally, to extramural funding.

    Innovation grants will fund:

    1. Clinical and translational research that has a high probability of improving patient care and leading to publication in top tier journals.
       
    2. High risk and highly innovative basic science unlikely to be funded by conventional mechanisms and that has a high probability of eventually leading to significant extramural funding. 

    Overview:  Faculty, staff, and trainees of the Vanderbilt Department of Anesthesiology may apply for funds to support new and innovative research initiatives in perioperative medicine. The result of the proposed work is expected to lead to publication and, ideally, a competitive application for extramural funding.

    This is a revolving application program with applications reviewed and awarded semiannually.  Applications are reviewed by the Anesthesiology Research Executive Committee which makes funding recommendations to the Chair. Projects will be evaluated on the basis of likelihood for completion, publication impact, and potential for extramural funding.  Applicants need not have a history of research productivity, but junior applicants must demonstrate committed mentorship from successful investigators.

    This program is funded by the Department from institutional development funds, profits from industry-sponsored research, technology transfer and licensing income, and philanthropic donations.  

    Budget Restrictions: Proposals should include a maximum request of $50,000.  Proposals may include requests for supplies, equipment, data analysis, and support services.  Applications may also include requests for effort support of research mentors or critical collaborators/consultants.

    Application Process:  Applications are to be submitted to the Chair’s office by May 1 or November 1.  Funding for successful applications will be available on July 1 and January 1, respectively.  Requests under $5,000 can be submitted at any time and will be reviewed by the Research Executive Committee on a continual basis.

    • The Anesthesiology Innovation Grant Submission Form must be completed and signed by the Principal Investigator.  Download an Innovation Grant Application here. (Word document)
    • Forms should be emailed to Dr. Ed Sherwood, Vice Chair for Research, at edward.r.sherwood@vumc.org. Applications need to be received at least 2 weeks prior to the next meeting.
    • You will receive an acknowledgment of your submission within one week.
    • Once the committee meets to discuss your application, you will receive a letter of response within 2 weeks.
    • If the committee requests further clarification on your application, you will have 10 business days to respond.
    • Once your response is received by the committee, you will get a letter of acknowledgment within one week. 
    • You will be notified about the committee’s decision within 2 weeks.

    PI responsibilities once they receive funding:  Successful applicants will be asked to submit a quarterly report to the AREC committee.  This report should include the following information:
    1.    Report date
    2.    Project title
    3.    Reporting period
    4.    Principal Investigator
    5.    Telephone number
    6.    Contract expenditures to date (as applicable):
    7.    Comments on administrative and logistical matters.
    8.    Description of scientific progress for the quarter in terms of the tasks or objectives.  Explain deviations where this isn't possible.  Include data where possible.
    9.    Present a brief statement of plans or milestones for the next quarter.

    For any questions regarding the Vanderbilt Anesthesiology Innovation Grant process, contact Dr. Ed Sherwood, Vice Chair for Research, at edward.r.sherwood@vumc.org

  • cipher

    CIPHER (Center for Innovation in Perioperative Health, Education, and Research) Innovation Grants are similar to other departmental innovation grants, but will apply specifically to projects involving perioperative medicine.

    While our care practices as a department involve the entire perioperative spectrum and chronic pain, projects in perioperative medicine that are eligible for support from a CIPHER Innovation Grant would be expected to focus on:

    • interventions made prior to surgery (e.g., pre-habilitation or risk profiling)
    • interventions made after surgery in the non-ICU setting (e.g., dynamic risk profiling, monitoring, and/or care on the wards)
    • interventions made in the operating room with longitudinal outcomes tracked after PACU discharge or discharge to home

    Awards
    CIPHER Innovation Grants may provide up to $50,000 in support for project expenses or CDA time.

    Application Process

    • Click here to access the CIPHER Innovation Grant application (Word Document).
    • Submit application to Nicki King at nicki.king@vumc.org.  Nicki will route applications to Dr. Matt McEvoy for preliminary review (project relevance).

    Review and Decision Process

    • Applications that pass preliminary review by Dr. McEvoy will be submitted to Dr. Ed Sherwood who will assemble a panel of AREC (Anesthesiology Research Executive Committee) members to review the proposal.
    • All applications will undergo review by a panel of at least 3 members of AREC.
    • AREC will communicate funding decisions or provide recommendations for necessary adjustments to the proposed project that would result in funding approval. 
  • Faculty planning a project that requires IRB approval must register the project through the following REDCap survey: http://j.mp/2CKx8p3

  • billings

    The Billings’ Laboratory focuses on developing new therapy for perioperative organ injury by conducting clinical trials and evaluating mechanisms of surgery-induced organ injury. Broadly this includes studying and manipulating the patient response to acute surgical stress to reduce morbidity, but specifically we are investigating the impact of perioperative oxidative damage as a mechanism of acute kidney and brain injury in patients having surgery.

    To decipher mechanisms of perioperative organ injury and advance the care of patients having surgery, we conduct clinical trials of novel treatments and measure the impact of these treatments on candidate pathways (mechanisms) of injury, organ injury, and patient-centered outcomes.

    For example, our 445 subject angiotensin converting enzyme inhibition or aldosterone antagonist randomized clinical trial to prevent acute postoperative atrial fibrillation demonstrated that intraoperative oxidative injury, as opposed to acute inflammation or anti-fibrinolysis, independently predicts postoperative acute kidney injury (AKI) and that perioperative statin use was associated with a decreased incidence of AKI. Based on those findings, we designed and completed the 653 Statin AKI Cardiac Surgery RCT, testing the hypotheses that short-term, high dose, perioperative atorvastatin reduces oxidative stress and AKI compared to placebo. We noted that isofurans – products of arachidonic acid peroxidation preferentially formed in conditions of relatively high oxygen tension – increased to a greater extent during surgery than F2-isoprostanes, the gold standard marker for quantifying oxidative injury in vivo. Tissue oxygen tension may be increased in vivo for two reasons, decreased consumption, as has been observed in patients with dysfunctional mitochondria, or increased delivery, as is typical among mechanically ventilated patients receiving supplemental oxygen in the operating room or ICU. We are exploring both possibilities. 

    To assess the effect of mitochondrial function on postoperative kidney, brain, and heart injury, we have measured mitochondrial DNA copy number, arterial lactate pyruvate ratios, and leukocyte PGC1alpha mRNA expression in patients undergoing cardiac surgery and have discovered that intraoperative mitochondrial dysfunction predicts postoperative AKI and delirium and that these markers of mitochondrial dysfunction are associated with increased concentrations of isofurans. To assess the effect of excess oxygenation we designed and initiated the Risks of Oxygen during Cardiac Surgery (ROCS) trial to test the hypothesis that physiologic oxygenation (normoxia) decreases the production of reactive oxygen species, oxidative damage, and organ injury compared to hyperoxygenation (hyperoxia). 

    The effect of oxygen administration during surgery is a major interest of the Billings’ Laboratory. In addition to the ROCS trial, the lab is designing a cluster-randomized, cluster-crossover pragmatic multicenter clinical trial to test the hypothesis that intraoperative normoxia or hyperoxia oxygenation targets affect kidney, brain, heart, and lung organ injury. Dr. Billings was recently awarded a seed grant from the Association of University Anesthesiologists to develop this project and will be submitting a proposal for a large grant to fund this trial, Intraop Ox, in 2019. Dr. Marcos Lopez, an assistant professor of anesthesiology in the division of critical care medicine who is in the lab, is investigating the effect of intraoperative oxygen administration on endothelial function with the support of a Foundation of Anesthesiology Education and Research Mentored Research Training Grant. He measures brachial artery flow mediated dilation and peripheral artery tonometry prior to surgery and at ICU admission and endothelial-dependent and -independent vasorelaxation in arterioles harvested from mediastinal fat in patients randomly assigned intraoperative normoxia vs. hyperoxia.

  • schlesinger

    Joseph Schlesinger, MD, is an Assistant Professor in the Department of Anesthesiology and Division of Critical Care Medicine at Vanderbilt University School of Medicine. After earning his Bachelor of Arts in Music with a concentration in Jazz Piano Performance from Loyola University in New Orleans, Dr. Schlesinger earned his Doctor of Medicine degree from the University of Texas Health Science Center at Houston. He completed residency training in Anesthesiology followed by a fellowship in Critical Care Medicine at Vanderbilt University. While in training, Dr. Schlesinger became a B.H. Robbins scholar. His mentor, Mark Wallace, PhD, is the director of the Vanderbilt Brain Institute. Dr. Schlesinger’s research interests include multisensory integration, human factors, aural perception, temporal precision, alarm development, patient monitoring, and medical education. This work led to the prestigious 2014 Education Specialty Award from the Society of Critical Care Medicine. 

    His lab focuses primarily on the research of auditory medical alarms and biomedical engineering device development to improve the alarmscape and patient safety.

    Dr. Schlesinger has many international partnerships. He is a faculty member in the Critical Alarms Lab in The Netherlands: https://delftdesignlabs.org/criticalalarmslab/
    The Critical Alarms Lab (CAL) aims to shape the future of product-user interactions in complex environments through information design. CAL unites researchers and students in projects related to alarm design, sound design and information design in a man-machine environment.

    Dr. Schlesinger is a faculty member in the Department of Electrical and Computer Engineering at McGill University and a research faculty member in The Centre for Intelligent Machines: http://www.cim.mcgill.ca/
    The Centre for Intelligent Machines (CIM) is an inter-departmental inter-faculty research group which was formed in 1985 to facilitate and promote research on intelligent systems.
    Intelligent systems and machines are capable of adapting their behaviour by sensing and interpreting their environment, making decisions and plans, and then carrying out those plans using physical actions. The mission of CIM is to excel in the field of intelligent systems, stressing basic research, technology development and education. The members of CIM seek to advance the state of knowledge in such domains as -- robotics, artificial intelligence, computer vision, medical imaging, haptics, systems and control, computer animation and machine and reinforcement learning.
    This is being achieved by collaborative efforts involving researchers with very different interests - CIM faculty and students come from the School of Computer Science, Department of Electrical and Computer Engineering, and the Department of Mechanical Engineering. Many of CIM's researchers are members of REPARTI, Regroupement stratégique pour l'étude des Environnements PARTagés Intelligents répartis - The Center for the study of distributed intelligent shared environments. It is this diversity of interests along with the spirit of collaboration which forms the driving force behind this dynamic research community.

    Dr. Schlesinger has partnered with Ben-Gurion University and mentors graduate students in human factors research as a part of the Human Systems Integration in Healthcare research group: https://www.hsi-h.com/
    The Human Systems Integration in Healthcare research center is dedicated to the study of the interaction between professional operators and systems in healthcare.

    Initiated by researchers from Ben-Gurion University of the Negev’s Department of Industrial Engineering and Management, the center promotes diverse interdisciplinary research to increase understanding of the capabilities and limitations of professional operators, the characteristics of the healthcare environment, and their interface, in an effort to improve the interaction between clinicians and the healthcare system.

    Finally, at Vanderbilt, Dr. Schlesinger is a faculty member in the School of Engineering and the Department of Hearing & Speech Sciences, where his research space is in the anechoic chamber laboratory. His work has been published in high impact literature and featured on CNN.