Digitizing clinical trials

O T Inan¹, P Tenaerts², S A Prindiville³, H R Reynolds⁴, D S Dizon⁵, K Cooper-Arnold^{6

7}, M Turakhia⁸, M J Pletcher⁹, K L Preston¹⁰, H M Krumholz^{11

12

13}, B M Marlin¹⁴, K D Mandl¹⁵, P Klasnja¹⁶, B Spring¹⁷, E Iturriaga¹⁸, R Campo¹⁸, P Desvigne-Nickens¹⁸, Y Rosenberg¹⁸, S R Steinhubl¹⁹, R M Califf^{20

21}

Affiliations

¹ School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30332 USA.
² Clinical Trials Transformation Initiative, Duke University, Durham, NC 27708 USA.
³ Coordinating Center for Clinical Trials, Office of the Director, National Cancer Institute at the National Institutes of Health, Bethesda, MD 20892 USA.
⁴ School of Medicine, New York University, New York, NY 10003 USA.
⁵ The Lifespan Cancer Institute, Brown University, Providence, RI 02912 USA.
⁶ National, Heart, Lung and Blood Institute at the National Institutes of Health, Bethesda, MD 20892 USA.
⁷ Present Address: Fortira at AstraZeneca, Gaithersburg, MD 20877 USA.
⁸ VA Palo Alto Health Care System and the Center for Digital Health, Stanford University, Stanford, CA 94305 USA.
⁹ Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143 USA.
¹⁰ Intramural Research Program of the National Institute on Drug Abuse at the National Institutes of Health, Baltimore, MD 21224 USA.
¹¹ The Center for Outcomes Research, Yale New Haven Hospital, Yale University, New Haven, CT 06510 USA.
¹² Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510 USA.
¹³ Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut 06510 USA.
¹⁴ College of Information and Computer Sciences, University of Massachusetts at Amherst, Amherst, MA 01003 USA.
¹⁵ Computational Health Informatics Program at Boston Children's Hospital, Departments of Biomedical Informatics and Pediatrics, Harvard Medical School, Boston, MA 02115 USA.
¹⁶ School of Information, University of Michigan, Ann Arbor, MI 48109 USA.
¹⁷ Northwestern University Feinberg School of Medicine, Chicago, IL 60611 USA.
¹⁸ National Heart, Lung, and Blood Institute at the National Institutes of Health, Bethesda, MD 20892 USA.
¹⁹ Scripps Research Translational Institute, La Jolla, CA 92037 USA.
²⁰ School of Medicine, Duke University, Durham, NC 27710 USA.
²¹ Verily Life Sciences and Google Health, South San Francisco, CA 94080 USA.

PMID: 32821856
PMCID: PMC7395804
DOI: 10.1038/s41746-020-0302-y

Review

Digitizing clinical trials

O T Inan et al. NPJ Digit Med. 2020.

. 2020 Jul 31:3:101.

doi: 10.1038/s41746-020-0302-y. eCollection 2020.

Authors

Affiliations

¹ School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30332 USA.
² Clinical Trials Transformation Initiative, Duke University, Durham, NC 27708 USA.
³ Coordinating Center for Clinical Trials, Office of the Director, National Cancer Institute at the National Institutes of Health, Bethesda, MD 20892 USA.
⁴ School of Medicine, New York University, New York, NY 10003 USA.
⁵ The Lifespan Cancer Institute, Brown University, Providence, RI 02912 USA.
⁶ National, Heart, Lung and Blood Institute at the National Institutes of Health, Bethesda, MD 20892 USA.
⁷ Present Address: Fortira at AstraZeneca, Gaithersburg, MD 20877 USA.
⁸ VA Palo Alto Health Care System and the Center for Digital Health, Stanford University, Stanford, CA 94305 USA.
⁹ Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143 USA.
¹⁰ Intramural Research Program of the National Institute on Drug Abuse at the National Institutes of Health, Baltimore, MD 21224 USA.
¹¹ The Center for Outcomes Research, Yale New Haven Hospital, Yale University, New Haven, CT 06510 USA.
¹² Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510 USA.
¹³ Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut 06510 USA.
¹⁴ College of Information and Computer Sciences, University of Massachusetts at Amherst, Amherst, MA 01003 USA.
¹⁵ Computational Health Informatics Program at Boston Children's Hospital, Departments of Biomedical Informatics and Pediatrics, Harvard Medical School, Boston, MA 02115 USA.
¹⁶ School of Information, University of Michigan, Ann Arbor, MI 48109 USA.
¹⁷ Northwestern University Feinberg School of Medicine, Chicago, IL 60611 USA.
¹⁸ National Heart, Lung, and Blood Institute at the National Institutes of Health, Bethesda, MD 20892 USA.
¹⁹ Scripps Research Translational Institute, La Jolla, CA 92037 USA.
²⁰ School of Medicine, Duke University, Durham, NC 27710 USA.
²¹ Verily Life Sciences and Google Health, South San Francisco, CA 94080 USA.

PMID: 32821856
PMCID: PMC7395804
DOI: 10.1038/s41746-020-0302-y

Abstract

Clinical trials are a fundamental tool used to evaluate the efficacy and safety of new drugs and medical devices and other health system interventions. The traditional clinical trials system acts as a quality funnel for the development and implementation of new drugs, devices and health system interventions. The concept of a "digital clinical trial" involves leveraging digital technology to improve participant access, engagement, trial-related measurements, and/or interventions, enable concealed randomized intervention allocation, and has the potential to transform clinical trials and to lower their cost. In April 2019, the US National Institutes of Health (NIH) and the National Science Foundation (NSF) held a workshop bringing together experts in clinical trials, digital technology, and digital analytics to discuss strategies to implement the use of digital technologies in clinical trials while considering potential challenges. This position paper builds on this workshop to describe the current state of the art for digital clinical trials including (1) defining and outlining the composition and elements of digital trials; (2) describing recruitment and retention using digital technology; (3) outlining data collection elements including mobile health, wearable technologies, application programming interfaces (APIs), digital transmission of data, and consideration of regulatory oversight and guidance for data security, privacy, and remotely provided informed consent; (4) elucidating digital analytics and data science approaches leveraging artificial intelligence and machine learning algorithms; and (5) setting future priorities and strategies that should be addressed to successfully harness digital methods and the myriad benefits of such technologies for clinical research.

Keywords: Clinical trials; Translational research.

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Conflict of interest statement

Competing interestsM.T. reports grants from Janssen Inc, personal fees from Medtronic Inc, grants from AstraZeneca, other from AliveCor, personal fees from Abbott, grants from Boehringer Ingelheim, personal fees from Precision Health Economics, personal fees from iBeat Inc, grants and personal fees from Cardiva Medical, personal fees from iRhythm, grants from Bristol Myers Squibb, grants from American Heart Association, grants from SentreHeart, personal fees from Novartis, personal fees from Biotronik, personal fees from Sanofi-Aventis, personal fees from Pfizer, grants from Apple, outside the submitted work; and Dr. M.T. is an editor for JAMA Cardiology. B. Spring is on the Scientific Advisory Board for Actigraph. O.T.I. is a Scientific Advisor for Physiowave, Inc. and a Co-Founder and Scientific Advisor for Cardiosense, has research funding for his lab from Hill-Rom Services, Inc. and Murata Americas, and has IP licensed by Physiowave, TandemLaunch, and Cardiosense. Dr. K.D.M.’s research lab receives philanthropic support from Eli Lily and he has consulted on using real world evidence for Merck. M.J.P. is supported by the NIH to develop and maintain a research platform to support digital trials and mHealth data collection. S.R.S. has served as a medical advisor for Janssen, Otsuka, Livongo, DynoSense, BioSense, and Spry Health. H.R. has received donations of OCT catheters for a research study from Abbott Vascular and telemetry monitors from BioTelemetry, Inc. Dr. Krumholz works under contract with the Centers for Medicare & Medicaid Services to support quality measurement programs; was a recipient of a research grant, through Yale, from Medtronic and the Food and Drug Administration to develop methods for post-market surveillance of medical devices; was a recipient of a research grant with Medtronic and is the recipient of a research grant from Johnson & Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation, from the Martin/Baughman Law Firm for work related to the Cook Celect IVC filter litigation, and from the Siegfried and Jensen Law Firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a participant/participant representative of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook, and the Physician Advisory Board for Aetna; and is the co-founder of HugoHealth, a personal health information platform, and co-founder of Refactor Health, an enterprise healthcare AI-augmented data management company.R.C. reports employment with Verily Life Sciences and Google Health, board membership at Cytokinetics, and status of former commissioner of the US FDA.

Figures

**Fig. 1. Summary of the key elements of a digital clinical trial.**
Three elements discussed in this paper include digital recruitment and retention, digital health data collection, and digital analytics.

See this image and copyright information in PMC

References

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1. Anderson, D. Digital R&D: Four Ways to Maximize Patient Engagement in Clinical Trials, Deloitte Consulting LLP. 25 Jun 2018.
1. NIH NHLBI. Digital Clinical Trials Workshop: Creating a Vision for the Future.https://www.nhlbi.nih.gov/events/2019/digital-clinical-trials-workshop-c.... Accessed 10 Jun 2020.
1. National Institutes of Health, National Center for Complementary and Integrative Health. The NIH Collaboratory Launches a New Resource on Methods and Best Practices for Pragmatic Clinical Trials. https://nccih.nih.gov/research/blog/collaboratory-living-textbook. Accessed 23 Mar 2020.

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Digitizing clinical trials

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Digitizing clinical trials

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Conflict of interest statement

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