Dawn Eliashiv, Vikram R. Rao, Barbara C. Jobst, Jerzy P. Szaflarski, John D. Rolston, Lesley Kaye, Taneeta M. Ganguly, Katie L. Bullinger, Patricia Dugan, David E. Burdette, Angela Peters, Atif Sheikh, Kevin F. Haas, Dileep Nair, Lilit Mnatsakanyan, Imran H. Quraishi, Meriem Bensalem‐Owen, for the RNS System PAS Study, Michael J. Doherty, Babak Razavi, Tiffany Fisher, Christopher Skidmore, Pradeep N. Modur, Tawnya Constantino, Vicenta Salanova, Andrew J. Cole, Olga Taraschenko, Angélica Rivera‐Cruz, James W. Wheless, Nitin Tandon, Antoaneta Balabanov, Sami Aboumatar, Itzhak Fried, Cornelia Drees, Hae Won Shin, Zeenat Jaisani, Stephanie Maciver, Sanjay Patra, Edward F. Chang, Jon T. Willie, Ryder Gwinn, Travis Stoub, John M. Stern, Tami Crabtree, Cairn G. Seale, Sharon C. McFadden, Jacob F. Norman, Lise Johnson, Martha J. Morrell, Kort Elisevich, Emory Peng, Rajashi Mazumder, Tara Jennings, Melissa Johnston Esparza, Jacob Pellinen, Nitish Harid, Pue Farooque, Aline Herlopian, Lawrence Hirsch, Adithya Sivaraju, Eyiyemisi C. Damisah, Jason Gerrard, Angela Wabulya, Kristen Riley, J. Nicole Bentley, Sandipan Pati, Jessica Johnson, Kaitlyn Kirchoffer, Yvan Bamps
BACKGROUND AND OBJECTIVES: Neuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct brain stimulation device (The RNS System for focal epilepsy), the Food and Drug Administration required a prospective study to evaluate whether real-world safety and effectiveness differed from outcomes in the RCT. METHODS: This open-labeled study enrolled adult participants who met the RNS System-approved indication for use. The primary effectiveness end point was median percent change in seizure frequency at 3 years of treatment. Interim safety is presented; the primary safety endpoint analysis will be conducted at 5 years. RESULTS: ). DISCUSSION: This prospective real-world study contributes to the body of evidence that adjunctive direct brain-responsive neurostimulation provides significant and sustained reductions in the frequency of focal seizures. Seizure reductions were greater and were achieved faster than in the RCT and long-term treatment trials but were similar to a more recent retrospective multicenter real-world study. As in the preapproval studies, treatment was well-tolerated and safe, and the SUDEP rate was low. The RNS System showed similar safety and improved seizure outcomes in real-world use compared with the RCT. Improvements in efficacy may reflect changes in programming practices. Future research efforts will focus on using the brain data obtained by the device to optimize detection and stimulation paradigms for each patient. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov, NCT02403843, submitted March 26, 2015. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in adults with refractory focal-onset seizures, direct brain-responsive neurostimulation reduces seizure frequency without serious adverse events up to 3 years.