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Introduction1
As the pace of technological innovation has accelerated, digital health technologies (DHTs) are becoming increasingly accessible, available, and popular among consumers, clinicians, and researchers. DHTs range from hardware—such as wearable devices and sensors—to software, such as mobile phone apps that enable consumers to monitor their own health and participate in studies; telemedicine platforms to connect patients with clinical providers; and artificial intelligence to support clinical decision making. DHTs offer new modalities for capturing personal and sensitive health data from patients as they carry on with their daily lives (CTTI, 2019). These types of measurements can offer new insights into diseases with characteristics that are not yet well understood, because traditional methods of measurement rely on in-clinic methods that may represent a patient’s data from only that day or from a limited timeframe (Coravos et al., 2019a).
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1 This workshop was organized by an independent planning committee whose role was limited to identification of topics and speakers. This Proceedings of a Workshop was prepared by the rapporteurs as a factual summary of the presentations and discussion that took place at the workshop. Statements, recommendations, and opinions expressed are those of individual presenters and participants and are not endorsed or verified by the National Academies of Sciences, Engineering, and Medicine, and they should not be construed as reflecting any group consensus.
USE OF DIGITAL HEALTH TECHNOLOGY APPLICATIONS TO ADDRESS PAIN POINTS ACROSS THE DRUG DEVELOPMENT LIFECYCLE
Among the wealth of opportunities afforded by DHTs to advance patient care and shed light on the patient experience outside of the clinic setting is the potential for these technologies to improve the probability of success in drug research and development (R&D) and enable precision medicine. The expanding frontier of biomedical science has led to increasing numbers of new drug candidates in the pipeline (Pharma Intelligence, 2019), but progress from the laboratory bench to the patient’s bedside has been hampered at critical points throughout the development lifecycle, such as gaps in data collection, a lack of objective “gold standard” measurements, lack of patient centricity, study participants not accurately reflecting the broader patient population, and the need to establish comparative effectiveness in post-market surveillance.
Over time, DHTs may help transform current drug development and clinical trial paradigms. For example, DHTs can be used to enable continuous data collection, provide surrogate endpoints for efficacy, support participant engagement to improve adherence and retention, and broaden access to and increase representation of clinical research. Furthermore, DHTs can facilitate decentralized and virtual trials (Coravos, 2019a). DHTs can also provide novel ways to measure phenotypes and outcomes, thereby contributing to the advancement of precision therapeutics (Adamo et al., 2020).
Despite the promise, challenges remain regarding the selection, evaluation, verification and validation, implementation, and standardization of DHTs (Coravos et al., 2020; Goldsack et al., 2020). As DHTs have become more prominent tools in clinical care, challenges have emerged around interoperability and integration of various data types from multiple sources, the establishment of analytical and clinical validity for digital health measures with real-world clinical outcomes, buy-in from clinical providers, and reimbursement issues. Efforts to address these challenges have been hampered by the lack of “gold standard” benchmarks, best practices for data security and governance, and verification and validation among the breadth of stakeholders developing and using DHTs, among a myriad of other issues (Goldsack et al., 2020; Matthews et al., 2019; Vayena et al., 2018). Additionally, DHT applications may give rise to new issues around ethics, as well as data governance, privacy, and security.
Establishing standards and best practices would benefit from the collective work of stakeholders that seek to incorporate DHTs into the drug development lifecycle. The growth in genomics technology in the consumer space and in clinical care may offer useful lessons and caveats for
the incorporation of DHTs into drug R&D (Tung et al., 2018). Optimizing the role of DHTs in drug development may involve collaboration among a broad range of stakeholders from across sectors—including consumers, patients, clinicians, regulators, biopharmaceutical companies, academics, and technology developers—to share insights, experiences, and lessons learned.
ORGANIZATION OF THE WORKSHOP
On March 24, 2020, a 1-day public workshop2 titled The Role of Digital Health Technologies in Drug Development was convened by the Forum on Drug Discovery, Development, and Translation (the forum) and the Roundtable on Genomics and Precision Health (the roundtable) of the National Academies of Sciences, Engineering, and Medicine. This workshop builds on prior efforts by the forum to explore how virtual clinical trials facilitated by DHTs might change the landscape of drug development (NASEM, 2019). The roundtable has previously examined how precision health might be accelerated by applying lessons learned from direct-to-consumer genomics to DHTs (Tung et al., 2018). The roundtable has additional convened working groups focusing on digital health and precision therapeutics. Furthermore, both the forum and the roundtable have explored how drug discovery value can be derived from large-scale genetic resources (NASEM, 2016). To explore the challenges and opportunities in using DHTs for improving the probability of success in drug R&D, enabling better patient care, and improving precision medicine, the workshop featured presentations and panel discussions on the integration of DHTs across all phases of drug development. The workshop comprised four sessions, which were structured to mirror the drug development lifecycle by examining the role of DHTs in (1) characterizing disease, (2) recruitment and safety trials, (3) pivotal trials, and (4) post-market surveillance. Specific ethical and regulatory considerations were also explored during an ethics briefing and a regulation-focused fireside chat. Throughout the workshop, participants considered how DHTs could be applied to achieve the greatest impact—and perhaps even change the face of how clinical trials are conducted—in ways that are also ethical, equitable, safe, and effective.
In March 2020, when this workshop was convened, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), was spreading around
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2 The workshop Statement of Task, workshop agenda, planning committee biographical sketches, and speaker biographical sketches can be found in Appendixes A, B, C, and D, respectively.
the world. On March 11, 2020, the COVID-19 outbreak was declared a pandemic by the World Health Organization. At the time, evolving guidance from public health and regulatory authorities3 coupled with widespread measures to mitigate the spread of COVID-19 spurred an abrupt transition to reliance on digital technologies to facilitate many clinical, personal, and professional interactions. The emerging pandemic imbued the workshop with a sense of urgency to develop strategies to rapidly advance DHTs. Throughout the workshop, participants considered specific opportunities for DHTs to support drug development and decentralized clinical trials in the context of the evolving pandemic.
ORGANIZATION OF THE PROCEEDINGS
This Proceedings of a Workshop is structured into seven chapters. Chapter 2 provides an overview of ethical and regulatory considerations that pertain to the use of DHTs in drug development. Chapter 3 focuses on the use of DHTs in pre-clinical research and how they can support characterizing disease. Chapter 4 focuses on opportunities and challenges related to incorporating DHTs in early stages of clinical trials, in which they can help inform recruitment and contribute to safety trials. Chapter 5 centers on the use of DHTs in pivotal trials, which provide the evidence on which critical regulatory decisions are based. Chapter 6 describes the role that DHTs can play in supporting post-market surveillance, comparative effectiveness research, and patient centricity. Chapter 7 features reflections on the workshop and key takeaways highlighted by the workshop’s co-chairs, Jennifer Goldsack, executive director of the Digital Medicine Society, and Joseph Menetski, associate vice president of Research Partnerships and director of the Biomarkers Consortium at the Foundation for the National Institutes of Health.
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3 The U.S. Food and Drug Administration released the guidance “Conduct of Clinical Trials of Medical Products During COVID-19 Public Health Emergency.” See https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-guidance-conduct-clinical-trials-medical-products-during-covid-19-public-health-emergency (accessed June 16, 2020).
