INTRODUCING THE RELIEF REGISTRY Dr. Jaron Rabinovici Sheba Medical Center, Israel

Personal Experience with Focused Ultrasound  Performed the second uterine fibroid FUS treatment (First treatment at Harvard Medical School) Participated in the first studies, pivotal study Since then more than 300 uterine fibroid treatment at our Center  Treated the first patient who got pregnant after FUS Published the first “pregnancy paper” on 52 pregnancies after  Introduced the possibility to treat adenomyosis First study to demonstrate clinical efficacy and safety  Head of gynecological activity of Insightec Focused Ultrasound Center at Sheba Medical Center, Israel  Many invited lectures © 2013 by Focused Ultrasound Foundation

Acceptance of Focused Ultrasound Treatment for Uterine Fibroids  Over the last decade ~ 10,000 treatments in ~ 100 centers!  Centers that managed to obtain some form of reimbursement managed to perform many procedures! © 2013 by Focused Ultrasound Foundation

Problems in the Implementation of Focused Ultrasound for Fibroids  New technology Physicians are conservative and “afraid” of new/unfamiliar approaches Focused Ultrasound is available only in a limited number of centers High “entry fee” Need for good and extensive scientific data Most data based on one center, limited observational studies Need for extensive post-marketing experience Lack of extensive long-term experience/data  Multiple Alternatives Big competition, “difficult sale”  Treatment price Limited adoption by insurance carriers © 2013 by Focused Ultrasound Foundation

Problems in the Implementation of Focused Ultrasound for Fibroids  New technology Physicians are conservative and “afraid” of new/unfamiliar approaches Focused Ultrasound is available only in a limited number of centers High “entry fee” Need for good and extensive scientific data Most data based on one center, limited observational studies Need for extensive post-marketing experience Lack of extensive long-term experience/data  Multiple Alternatives Big competition, “difficult sale”  Treatment price Limited adoption by insurance carriers © 2013 by Focused Ultrasound Foundation

“Needed” Studies for Focused Ultrasound Randomized Controlled Studies?  RCT’s vs “gold standard” (which?) Difficult to impossible to perform. Random decision of invasive versus non-invasive treatment? Difficult recruitment, very expensive, variable results from various centers can affect outcome, examines a predefined patient population. © 2013 by Focused Ultrasound Foundation

Prospective entry of consecutive patients can provide data on clinical procedures – “real life” Able to gather data on many patients within a limited time frame and follow them up for a prolonged period of time The resulting reports and publications should provide a large body of evidence that will be difficult to disregard “Needed” Studies for Focused Ultrasound Registry Studies? © 2013 by Focused Ultrasound Foundation

Gathering Evidence, Expanding Access Focused Ultrasound for Uterine Fibroids  Registry Goal: Provide large scale evidence on safety, efficacy and long-term durability of Focused Ultrasound, to facilitate reimbursement and drive rapid patient and physician acceptance © 2013 by Focused Ultrasound Foundation

 REgistry for Leiomyoma: International Efficacy of Focused Ultrasound  3-year, single-arm, prospective, global registry  1,000 women treated with MR-guided FUS at 30+ treatment sites  Led by Steering Committee of international, leading experts  Funded by philanthropy and industry © 2013 by Focused Ultrasound Foundation

Steering Committee  Chair: Jaron Rabinovici, MD, Sheba Medical Center, Israel  Anne Roberts, MD, University of California, San Diego  Elizabeth A. Stewart, MD, Mayo Clinic, Rochester  Robert K. Zurawin, MD, Baylor College of Medicine, Houston  Elizabeth David, MD, Sunnybrook Health Sciences Centre, Toronto, Canada  Wladyslaw M. Gedroyc, MD, St. Mary's Hospital, London, UK  Young-Sun Kim, MD, Samsung Medical Center, Seoul, South Korea  Matthias Matzko, MD, Amper Kliniken, Dachau, Germany  Harsh Rastogi, MD, Indraprastha Apollo Hospital, New Delhi, India © 2013 by Focused Ultrasound Foundation

 Hypothesis: Focused Ultrasound will provide a durable improvement for women with symptomatic uterine fibroids. RELIEF Registry Hypothesis © 2013 by Focused Ultrasound Foundation

 Primary Objectives: Provide large scale evidence on the safety and long term efficacy of Focused Ultrasound for the indication of symptomatic uterine fibroids  Secondary Objectives: Assess the impact of the treatment on medical resource utilization and pregnancy outcomes RELIEF Registry Objectives © 2013 by Focused Ultrasound Foundation

 Primary endpoints: Treatment effectiveness using UFS-SSS Need/reason for alternative treatments Treatment safety using adverse events  Secondary endpoints: Treatment satisfaction Recovery using return to work and/or normal activities  Exploratory endpoints: Medical resources utilization Pregnancy outcomes General health-related quality life RELIEF Registry Outcomes of Interest © 2013 by Focused Ultrasound Foundation

 Target –1,000 women in two years, three years follow-up.  Approximately 30 sites in: North America - U.S., Canada Europe - Germany, United Kingdom Asia - Korea, India, Israel  Each site will enroll approximately 50 consecutive patients who receive Focused Ultrasound RELIEF Registry Registry Design © 2013 by Focused Ultrasound Foundation

~30 Sites Treatment form completed Self-report 1 month, 6 month, year surveys 1 month, 6 month, year surveys Complete study Complete study Baseline: Demographics Gynecologic history Uterine, fibroid anatomy Future fertility Symptoms and QoL Follow-up Measures: Additional treatments Treatment Satisfaction Resource utilization Pregnancy outcomes AEs Symptoms and QoL Treatment Information: Duration, Number of fibroids Treated fibroids Fibroid volume, NPV AEs P ROTOCOL Treatment Complete baseline Survey Complete baseline Survey 1,000 planning to be treated using focused ultrasound 1,000 planning to be treated using focused ultrasound © 2013 by Focused Ultrasound Foundation

 Inclusion Patient is —Intended to be treated for symptomatic uterine fibroids by focused ultrasound (consistent with local labeling) —Able to communicate over the phone/internet and can complete study questionnaires —Willing to be followed for three years  Exclusion Patient is —Pregnant at time of treatment —Post-menopausal RELIEF Registry Patient Population © 2013 by Focused Ultrasound Foundation

 Treatment guidelines  Structure  Baseline data  Short-term results  Mid-term results  Long-term results  Other analyses TBD RELIEF Registry Publications © 2013 by Focused Ultrasound Foundation

 Enrollment to begin second half this year  Sites to come onboard soon – potential US locations to include: Bethesda, MD Boca Raton, FL Boston, MA Charlottesville, VA Chicago, IL Columbus, OH Houston, TX Nashville, TN Rochester, MN San Diego, CA San Francisco, CA Stanford, CA RELIEF Registry Status © 2013 by Focused Ultrasound Foundation

REFERRING PATIENTS TO RELIEF  Every patient treated in the U.S. will be eligible for the registry  RELIEF will systematically collect data and provide evidence-based recommendations for patient selection and outcomes © 2013 by Focused Ultrasound Foundation