1. Challenges in Conducting Multi-Center Clinical Studies: Results from the Rapid Empiric Treatment with Oseltamivir Study (RETOS) Kendra Thompson, Kelly Carrico, Tiffany Lindeman, Amy Holloway, Greg Whittington, Paula Peyrani, Ruth Carrico, Division of Infectious Diseases, University of Louisville, Robley Rex VA Medical Center ABSTRACT Background: Multi-center clinical studies are becoming the standard approach for the study of new medical interventions. Although using multi-center trials have the ability to enroll a large number of patients, coordination of a clinical trial across various hospitals has generated new challenges in clinical research. Understanding these challenges from the perspective of quality improvement is critical for the success of the trial. The objective of this study was to describe the challenges encountered while implementing a multi-center study and to describe their causes and solutions. Methods: RETOS is an ongoing, randomized, prospective clinical trial to evaluate the impact of rapid empiric treatment with oseltamivir on the outcomes of hospitalized patients with symptoms of a lower respiratory tract infection (LRTI). All patients admitted to 8 hospitals in Louisville, KY from December 2010 to March 2012 with symptoms of a LRTI were invited to participate in the study. A focus group was established to determine challenges as well as causes and solutions for each. Results: A total of 12 challenges were identified. Nine of these challenges were considered related to study team issues, while 3 were considered related to hospital issues. The scope of these challenges ranged from physician refusal of patient enrollment to navigating various medical record systems in each participating institution. Conclusions: This study indicates that during the implementation of a multi-center clinical trial, investigators will identify important challenges. A system based on quality improvement methods should be integrated into the clinical trial process in an attempt to identify issues early in the study in order to rapidly implement appropriate solutions. INTRODUCTION RESULTS (Cont’d) Coordinator TrainingPhysician TrainingHospital Training Medical Record Training Laboratory Staff Training Pharmacy Staff Training Figure 2: Focus Group RETOS is an ongoing randomized prospective clinical trial to evaluate the impact of rapid empiric treatment with oseltamivir on the outcomes of hospitalized patients with symptoms of a lower respiratory tract infection (LRTI). Adult patients admitted to 8 hospitals in Louisville, KY (Figure 1) from December 2010 to March 2012 with symptoms of a LRTI were invited to participate in the study. A focus group was created to determine the challenges encountered during the study as well as solutions to those challenges. The focus group included the principal investigator, sub- investigators, co-investigators, study coordinators and research associates as shown in Figure 2.. If clinical trials are to be successful, it is pertinent that a quality improvement system is integrated into the clinical trial process to identify challenges and improve processes. This becomes particularly significant when conducting multi-center studies. In most cases, multi-center studies have the ability to enroll a large number of study participants. This allows for a larger data set to analyze, often resulting in better generalizability. 1 Since multi-center studies are becoming the standard approach in research, it is important to understand that new challenges can surface. The objective of this study is to describe the challenges encountered while implementing a multi-center study and to describe their solutions. MATERIALS AND METHODS Figure 1: 8 Participating Hospitals Table 1: Challenges and Solutions Principal Investigator Research Associates Research Coordinators Sub- Investigators Co- Investigators In our study we found that many challenges will surface during the execution of a multi-center clinical trial. Identifying these challenges and finding the primary issue within each challenge by using a system based on quality improvement methods, should be integrated into the clinical trial in order to rapidly implement appropriate solutions to the challenges. The resolution of these issues, such as those relating to training, communication systems and auditing processes are very important and should be Implemented throughout the study ChallengesSolutions Hospital Physician refuses to allow their patient to be enrolled into study. The PI held education sessions with physicians to outline the details of the study. Credentialing research coordinators as hospital staff is time consuming as well at expensive. The study team worked with hospitals to develop specific credentialing requirements for study coordinators. Patients being transferred or discharged without their remaining study medication. The study team developed nurse education sheets, pharmacy education sheets, and notification sheets to be placed in the chart. Study Team All patients enrolled in study required daily follow-ups while in the hospital. The study team assigned 1 person to follow up on all patients and 1 person to do enrollment. All patients enrolled in study required follow-up telephone calls at 1 month, 6 months, and 1 year from enrollment. The study team implemented a weekly auditing system to ensure all patients were being called on time. Patients needed to be enrolled on the weekends. The study team developed a rotating weekend schedule to ensure all hospitals were covered during the weekends. Acquiring and accounting for study medication. The study team determined a central location for the study medication to be kept. Study coordinators were responsible for the tracking and delivery of medication at their hospital. Specimen collected at outlying hospitals need to be transported to the ID laboratory in a timely manner. The study team used a specimen delivery service to transport all samples from outlying hospitals to the ID laboratory. Patients need to be enrolled within 24 hours of admission to the hospital. The study team screened twice a day, 7 days a week. Each coordinator needs to be able to navigate all hospitals and medical record systems. Study coordinators were responsible for developing a manual for their hospital. Walk throughs and medical record training were done in small groups for each hospital. There is a difference in background knowledge of study coordinators with MD and without MD. The study team conducted multiple trainings prior to the start of the study to ensure all coordinators were knowledgeable about the study. There are many different forms that are needed for each patient. The forms are constantly being updated and improved. Patients need to be enrolled with the most current versions of each form. The study team implemented an auditing system to ensure the proper forms are being used. The most current versions of each form were kept in a central location. Figure 3: Stop light card listing physician agreement Figure 4: Training Diagram CONCLUSIONS MATERIALS AND METHODS (Cont’d) RESULTS Throughout the study a total of 12 challenges were identified. These challenges were discussed and categorized into two groups: study team or hospital. Nine of these challenges were considered related to study team issues, while three were considered related to hospital issues. Challenges and solution for hospital and study team are shown in Table 1. Stop light card listing physicians names and enrollment agreement is shown in Figure 3. Training processes are shown in Figure 4. REFERENCES 1.Weinberger, M., Oddone E.Z., Henderson, W.G., smith, D.M., Huey, J., Giobbie-Hurder, A., Feussner, J.R.. (2001). Multisite randomized controlled trials in health services research: scientific challenges and operational issues. Medical Care, 39.