SA–CME REVIEW Digital therapeutics (DTx) are defined by the Digital Therapeutics Alliance as “evidence-based therapeu- tic interventions driven by high-qual- ity soſtware programs to prevent, manage, or treat a medical disorder or disease” (DTxalliance.org). In short, there are 2 requirements to be considered a DTx. First, it must be soſtware – oſten categorized as soſtware as a medical device (SaMD). Briefly, hardware refers to physical devices such as phones, computers, tablets or sensors, whereas soſtware refers to a collection of instructions telling hardware what to do. Second, since DTx are designed to offer ther- apeutic value, they must be approved for use by recognized regulatory agencies such as the Food and Drug Administration (FDA). Digital sensors, wearable devices, virtual reality (VR) systems with therapeutic intent, and artificial intelligence (AI) devices are all examples of DTx. 2 For SaMD to enter the public markets, it must either obtain de novo premarket approval (PMA) or qualify for 510(k) clearance. Devices with 510(k) clearance can forgo clinical trials and testing if the device is “substantially equivalent” to something already on the market. For de novo PMA, clinical trials must show adequate safety, efficacy, and be either equivalent or superior to the standard of care. Even aſter FDA approval, postmarket surveil- lance must be performed to identify long-term side effects; these roughly The Emerging Role of Digital Therapeutics in Medical, Surgical and Radiation Oncology Will Jin, MD; 1* Santosh Mohan, MMCi, COPHIMS; 2 Matt Adams, BS; 3 Sarah Hoffe, MD; 4 Edmondo Robinson, MD, MBA 2 DETAILS ON PAGE 8 Affiliations: 1 Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami Health Systems and Jackson Memorial Hospital. 2 Digital Innovation, Moffitt Cancer Center, Tampa, FL. 3 Lake Erie College of Osteopathic Medicine, Bradenton FL. 4 GI Radiation Oncology, Moffitt Cancer Center Corresponding Author: Will Jin, MD, Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami Health Systems and Jackson Memorial Hospital, 1475 NW 12th Ave., Miami, FL 33136 (wxj123@miami.edu) Disclosure: Dr. Jin has a patent pending for US Patent #17091084, Real-time Ultrasound Imaging Overlay Using Augmented Reality, filed November 9, 2011, and has received a Sylvester Comprehensive Cancer Center Travel Grant 2022 and Committee of Interns and Residents Professional Development Grant 2022. No other authors have no conflicts of interest to disclose. None of the authors received outside funding for the production of this original manuscript and no part of this article has been previously published elsewhere. Abstract Digital therapeutics (DTx) are software interventions of therapeutic value supported by scientific evidence to prevent, manage, and treat a broad spectrum of physical, mental and behavioral conditions. Current data supports integration in the setting of chronic medical conditions such as diabetes, hypertension, opioid de- pendence, and insomnia. Recent clinical studies have shown emergence of DTx as potential solutions in the cancer care continuum to improve medication adherence, chemotherapy tolerance, and even overall survival. In addition, evidence suggests that these digital interventions may have a significant impact on lowering the cost of health care for current patients and cancer survivors. Given the potential financial toxicity for oncolo- gy patients, these modalities, such as digital patient-reported outcomes (PROs), are being actively investigat- ed to determine the economic benefits as well. As DTx emerge in medical, surgical and radiation oncology, further studies are needed to ensure the needs of patients are met with respect to digital literacy and equity. In this review, we will explore these new modalities and the spectrum of possible future benefits. Keywords: Digital therapeutics, digital health, patient-reported outcomes, quality of life, overall survival, software as a medical device, virtual reality ©Anderson Publishing, Ltd. All rights reserved. Reproduction in whole or part without express written permission is strictly prohibited.. Applied Radiation Oncology 9 June 2022