Digital Therapeutics: Strategic, Scientific, Developmental, and Regulatory Aspects

462 Pages·2022·26.738 MB·English

by  Oleksandr Sverdlov, Joris van Dam

Digital Therapeutics
Strategic, Scientific, Developmental,
and Regulatory Aspects
One of the hallmarks of the 21st century medicine is the emergence of digital
therapeutics (DTx)—evidence-based, clinically validated digital technologies to
prevent, diagnose, treat, and manage various diseases and medical conditions.
DTx solutions have been gaining interest from patients, investors, healthcare
providers, health authorities, and other stakeholders because of the potential
of DTx to deliver equitable, massively scalable, personalized and transformative
treatments for different unmet medical needs.
Digital Therapeutics: Strategic, Scientific, Developmental, and Regulatory
is an unparalleled summary of the emerging field of digital therapeutics which is
poised to become the fastest growing area of the biopharmaceutical and digital
medicine product development. This edited volume intends to provide a sys-
tematic exposition to digital therapeutics through 19 peer-reviewed chapters
written by subject matter experts and industry leaders in this field.
Chapman & Hall/CRC Biostatistics Series
Series Editors
Shein-Chung Chow, Duke University School of Medicine, USA
Byron Jones, Novartis Pharma AG, Switzerland
Jen-pei Liu, National Taiwan University, Taiwan
Karl E. Peace, Georgia Southern University, USA
Bruce W. Turnbull, Cornell University, USA
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Digital Therapeutics
Strategic, Scientific, Developmental,
and Regulatory Aspects
Edited by
Oleksandr Sverdlov and Joris van Dam
First edition published 2022
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British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library
ISBN: 978-0-367-86159-9 (hbk)
ISBN: 978-1-032-37408-6 (pbk)
ISBN: 978-1-003-01728-8 (ebk)
DOI: 10.1201/9781003017288
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Contents
Preface vii
List of Abbreviations xi
Editors xvii
Contributors xix
1 Digital Therapeutics within the Digital Health Landscape: Foundational
Aspects 1
Megan Coder
2 Sector Perspective: Digital Therapeutics in Behavioral Health 17
Lisa A. Marsch
3 Navigating the Code to Commercial Lifecycle of Digital Health Apps:
Defining and Defending Your Strategy for Success 33
Brian Clancy
4 Designing and Delivering a DTx Clinical Research Program: No Need to
Re-invent the Wheel 59
Colin A. Espie and Alasdair L. Henry
5 Statistical Designs for Developing Personalized Mobile Treatment
Interventions 99
Tianchen Qian, Eric Cohn, and Susan A. Murphy
6 Statistical Approaches in the Development of Digital Therapeutics 121
Oleksandr Sverdlov, Yevgen Ryeznik, Sergei Leonov, and Valerii Fedorov
7 Health Economics Aspects of Digital Therapeutics 161
Jennifer Lavanture and Owen McCarthy
8 Healthcare Data Ownership and Privacy: A Perspective for Digital
Therapeutics 177
Ximena Benavides and Greg Licholai
9 Building the Story of Scientific Evidence for Digital Therapeutics: Trials,
Meta-Analysis, and Real-World Data 195
Derek Richards, Angel Enrique, Jorge Palacios, and Nora Eilert
10 US Regulatory Pathways for Digital Therapeutics 219
Michelle Rubin-Onur and Allison C. Komiyama
v
vi Contents
11 Building Digital Health and Therapeutic Solutions for the Future:
What’s Required for Success? 245
Anand K. Iyer
12 Digital Therapeutics for Sleep and Mental Health 261
Peter Hames and Christopher B. Miller
13 DTx for the NEXT three billion! 281
Abhishek Shah
14 Akili: A Novel Approach to Clinical Intervention with Digital
Therapeutics 293
Elena Canadas and Anil S. Jina
15 SilverCloud Health: Online Mental Health and Wellbeing Platform 307
Derek Richards, Angel Enrique, Jorge Palacios, Nora Eilert, Daniel Duffy, Gavin
Doherty, Jacinta Jardine, Noemi Vigano, and Karen Tierney
16 Digitally Augmenting Therapies: A DTx Opportunity for Pharma
Portfolio Development 331
Benjamin D’hont and Romain Marmot
17 The Convergence of Digital Health Technologies: The Role
of Digital Therapeutics in the Future Healthcare System 351
Joris van Dam, Justin Wright, and Graham Jones
18 Decentralized Clinical Trials: A New Paradigm for New Medical
Product Development and Digital Therapeutics 373
Isaac R. Rodriguez-Chavez and Greg Licholai
19 The Past, Present, and Future of Digital Therapeutics 405
Sarah Cronin, Sophie Madden, Laura Ardill, Kate O’Reilly, Alette Brinth,
Chandana Fitzgerald, and Tess Huss
Index 431
Preface
One of the hallmarks of 21st-century medicine is the emergence of digital therapeutics
(DTx)—evidence-based,clinicallyvalidateddigitaltechnologiestoprevent,diagnose,treat,
andmanagevariousdiseasesandmedicalconditions.DTxsolutionshavebeengaininginter-
estfrompatients,investors,healthcareproviders,healthauthorities,andotherstakeholders
because of the potential of DTx to deliver equitable, massively scalable, personalized and
transformative treatments for different unmet medical needs. However, due to novelty of
the topic, there is a lack of systematic exposition of DTx and their role in healthcare. The
present book is one of the first attempts to present a comprehensive summary of current
strategic, scientific, regulatory, and operational aspects of DTx development.
Mankind has a long history of utilizing science and technology in medicine to improve
andextendhumanlife.Sciencefictionliteratureisrepletewithdifferentvisionsofthefuture
medicine and healthcare. One common theme of these insights is undeniable—the future of
medicinewillbeincreasinglytechnological;itwillinvolveinnovativeapplications(andcom-
binations) of science, artificial intelligence, machine learning, advanced pharmacy-on-chip
technology, nanotechnology, virtual reality, telemedicine, and other advanced technologies.
While technology itself does not obviate the need for having human medical intervention,
healthcare professionals inevitably need to acquire new knowledge and master the technol-
ogy in order to maximize the benefit for the patients and the public health system.
As we write this Preface in early 2022, we can confidently say that humanity is already
in the data and digital age. Data is the “new oil” of the 21st century. Data is ubiquitous
in all areas of our life, and healthcare is no exception. We are witnessing the emergence
of increasingly powerful digital technologies that can help us acquire various types of clini-
callyimportantdataonanindividualsubjectlevelthatcanbeutilizedinmakingintelligent
treatmentdecisions.Suchdata,whenusedproperly,carriesbigpromiseindevelopinginno-
vative therapeutic solutions that can potentially improve access to healthcare and address
medical needs of many underserved populations.
Digitaltherapeuticsareemergingasanimportantnovelclassofhealthcareandmedicine.
To demonstrate clinical utility and to earn public trust in those novel therapies, it is essen-
tial that clinical research is conducted to support any claims for these products and that
such data be transparently shared and published, or validated by a third party such as
a regulatory health authority. In this sense, DTx products are similar to new drugs and
medical devices; i.e. digitaltherapeutics must demonstrate favorable risk-benefit properties
in clinical trials before they are marketed. DTx may be very diverse in terms of mecha-
nism of action, mode of delivery, and purpose. The development of these products should
be patient-focused, science-based, and technology-driven, and it should borrow the best
practicesfromthebiopharmaceuticalandmedicaldeviceindustries,whileatthesametime
benefittingfromsomeoftheuniqueaspectsofDTx—suchaseaseofaccess,remotetracking
and monitoring, and rapid development cycles.
Overthepastfiveyears(2018–2022),therehasbeenexplosivegrowthinthefieldofDTx,
accelerated further by the unique challenges of a worldwide pandemic. Some successes are
alreadyhappeningglobally(e.g.regulatoryclearanceofsomeprescriptiondigitaltherapeu-
tics in the US, Europe, and Japan), while at the same time we are also witnessing some
vii
viii Preface
setbacks. It is essential to learn the lessons from all these experiences and move the overall
field forward, applying the best science, utilizing state-of-the-art technology, and recycling
inferior or outdated approaches.
This edited volume intends to provide a systematic exposition to digital therapeutics
through19peer-reviewedchapterswrittenbysubjectmatterexpertsinthisemergingfield.
We suggest this book will be important for several reasons:
1. The book will provide the taxonomy of the concepts and a navigation tool for the field
of digital therapeutics. As mentioned in the Boston Globe (Friday, July 5, 2019), “no
onereallyknewwhatdigitaltherapeuticswere10yearsago.Today,there’sstillnogood
definition.”Wethinkitishightimeforarigorousbook-lengthpresentationofthistopic.
2. The book will cover important strategic aspects of the DTx industry, thereby helping
investors, developers, and regulators gain a better appreciation of the potential value of
DTx. In this regard, the first four chapters provide important background:
• the foundational aspects of the DTx industry (Chapter 1);
• the DTx behavioral health sector perspective (Chapter 2);
• the code-to-commercial lifecycle of digital health application development (Chap-
ter 3); and
• the DTx clinical research program strategy (Chapter 4).
3. The book will expound on many existing and emerging state-of-the-art scientific and
technological tools, as well as data privacy, ethical and regulatory considerations for
DTx product development. The following chapters address these issues:
• themicro-randomizedtrial(MRT)designfordevelopingpersonalizedmobiletreat-
ment interventions (Chapter 5);
• an integrated scientific learning approach combining statistics, pharmacometrics,
and data science in the development of DTx solutions (Chapter 6);
• health economics aspects of digital therapeutics (Chapter 7);
• healthcare data ownership and privacy issues (Chapter 8);
• building the story of scientific evidence for digital therapeutics (Chapter 9); and
• US regulatory pathways for digital therapeutics (Chapter 10).
4. Thebookwillpresentseveralcasestudiesofsuccessfuldevelopmentofsomeofthemost
remarkable DTx products:
• the journey of a company that developed the first US FDA-cleared Software as a
Medical Device for managing type 2 diabetes (Chapter 11);
• thesuccessstoryofacompanythatdevelopedanddeliveredatscaleaDTxsolution
for sleep and mental health (Chapter 12);
• the digital therapeutics for “the next three billion” (Chapter 13);
• the success story of a company that developed a global online platform for mental
health and well-being (Chapter 14);
• the success story of developing the first prescription digital therapy delivered as a
video game (Chapter 15); and
• the “digitally-augmenting” therapies as new value drivers for the pharmaceutical
industry (Chapter 16).
Preface ix
5. The book will provide some perspectives and forward-looking statements on the future
of digital medicine:
• the convergence of digital health technologies and the role of digital therapeutics
in the future healthcare system (Chapter 17);
• the decentralized clinical trials model to accelerate clinical development of digital
therapeutics (Chapter 18); and
• the business leaders’ perspective on the past, present, and future of the DTx in-
dustry (Chapter 19).
We hope this book will be useful for a broad audience, including but not limited to:
• Business leaders working in public health, healthcare, digital health, information tech-
nology, and biopharmaceutical industries.
• Researchers working on the design and analysis of clinical trials to develop, test, and
validate investigational DTx products.
• Regulatory scientists who are involved in the review of DTx products.
• Faculty and students who are involved in interdisciplinary research on digital health
and digital medicine. Some chapters from this book can be used as special topics in
graduate-level courses on innovation in clinical research and digital medicine.
Acknowledgments
We would like to express sincere gratitude to many people without whom this book would
not be possible: the CRC Press Acquisition Editors John Kimmel and David Grubbs for
theirpatienceandguidanceduring2019–2022;ShashiKumarandYevgenRyeznikfortheir
masterful help with LATEX and Overleaf; Arkadiy Pitman for his rigorous and constructive
criticisms on digital therapeutics that helped enormously in the development of Chapter 6
of this volume; the contributing authors of the chapters who survived this marathon with
us; the reviewers for their valuable and constructive feedback; and most importantly the
many patients who volunteered their time, their insights and their health in one or other
digital therapeutics clinical research study—they are the true pioneers of a healthier future
for all.
Oleksandr Sverdlov, PhD
Joris van Dam, PhD