This segment of the four-part workshop focused on practical applications of technology to transform the clinical trials enterprise for 2030. Participants considered ways that thoughtful and deliberate use of digital technologies could support the goals of improving person-centeredness and inclusivity of clinical trials and ensuring resilience, sustainability, and transparency in the clinical trials enterprise.
THE ROAD TO 2030: PERSPECTIVES FROM THE FIELD
Frontline Experience: A Panel Discussion
In this session, three panelists described how they are working to apply technology practically in pursuit of an improved clinical trials enterprise. Panelists included Tara Hastings, senior associate director for Patient Engagement at The Michael J. Fox Foundation for Parkinson’s Research; Jan Benedikt Brönneke, director, Law and Economics of Health Technologies at the health innovation hub (hih) of the German Federal Ministry of Health; and Bradford Hirsch, chief executive officer (CEO) of SignalPath Research. To open the session, Jennifer Goldsack, executive director of the Digital Medicine Society and session moderator, said that an enhanced clinical trials enterprise for the future does not necessarily require more technology, but, rather, more solved problems. Current and emerging technologies are “tools in the toolbox” that can help drive the enterprise to become safer, more effective, more efficient, and more equitable.
“Tools in the Toolbox”
Hirsch stated that the technology needed to drive change in the clinical trials enterprise already exists. What is lacking is coordination and an understanding of how to effectively use that technology to advance clinical trials. For example, he said stakeholders may not be familiar with currently available operational technology for clinical trial sites (e.g., tools
for regulatory document management, operational management for trials, and payment infrastructure). There is an opportunity to bring together different technology products to integrate the generation of clinical trial data and collection of real-world data, he said, while preserving essential patient–clinician relationships.
Hastings added that technology can help inform patients on clinical trial participation. Technology can also be deployed to help reduce the burden of trial participation, especially for patients with progressive disorders, such as Parkinson’s disease (e.g., by reducing the number of in-person visits required). She noted, however, that technology is not a silver-bullet solution for engaging more people in research. Studies funded by The Michael J. Fox Foundation for Parkinson’s Research have found that barriers to participation include time, acceptability, and language barriers, but also access to technology. This means it is important to find ways to be inclusive and to connect with those in the community who may not have wireless Internet access or the ability to use it, for example.
Bidirectional Information Flow
Hastings pointed out that technology is “a two-way street.” It is not just about what trial participants may contribute to research, but also what the clinical trials enterprise can give back to participants and their providers that could better inform their own health care and choices. The bidirectional flow of information can help enable more productive conversations between patients and their providers and offer patients more insight into their own care, she said.
As Germany has been implementing the use of digital health technologies to enhance the delivery of health care following the passage of the Digital Health Care Act in 2019,1 it has become clear that there are opportunities to use these tools for clinical evidence generation as well, Brönneke said. However, patients in Germany have expressed concern that their data could be misused. The European Union General Data Protection Regulation (GDPR) addresses data privacy, including the use of patient data and the sharing of data for purposes other than those originally intended. While implementation of the GDPR promotes trust among patients, Brönneke described the regulation as restrictive to the point of reducing the potential benefits that could be derived from the data.
As mentioned above, the bidirectional flow of data can provide direct benefits to patients, and Brönneke observed that “people are much more
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1 For more information about the law, see a summary written by hih at https://hih-2025.de/dvg-a-summary-of-germanys-new-law-for-digital-health-applications (accessed August 3, 2021).
willing to give their data when they have the feeling that they are getting something out of it.” For example, he noted that many people freely share personal information on social media because they feel they receive something of value in return. Similarly, patients are more likely to share their health data when they feel included in the clinical research process. As an example, Brönneke mentioned the digital health applications process in Germany. This process allows for research use of the real-world data associated with digital therapeutics, and patients who share their data via an approved digital health application receive direct and timely feedback.
Coordination and Integration of Technical Solutions to Improve the Patient Experience
Hirsch shared his personal experience as a recent participant in a COVID-19 vaccine clinical trial, summarizing the experience as “a bit of a mess.” What was intended to be an hour-long initial visit lasted more than 6 hours. This was due, he said, to a lack of coordination across the multiple technology elements from five different vendors that were being used for the trial (e.g., the eConsent platform, the app for receiving payment for participation, the app for reporting symptoms). He suggested that the challenge was not the technology itself, but rather the lack of coordination. Technologies used for a trial should be coordinated in advance and deployed in a way that focuses on the user experience, educating trial participants and engaging them in the process.
Technology solutions are siloed, in part, because they are expensive and complex to develop, Hirsch said. Solutions must correctly follow data privacy and security regulations to protect patient information and the integrity of trial data. What is needed, Hirsch said, is agreement among regulatory agencies on what policies and oversight are necessary to govern and coordinate use of digital health technologies in clinical trials, such that relevant policies are streamlined and more easily understood by developers working in different areas. In addition, he said, there is a need for better coordination among technology developers and other stakeholders working within those defined policies. Developers are not opposed to eliminating the siloes, he said, but there must be investment in infrastructures that can support and facilitate alignment.
Brönneke suggested that responsibility for coordination falls primarily on the technology developers, but he added that more encouraging regulatory policies would have a positive impact. He observed that siloed data are barriers to coordination. In Germany, the health care system is encouraged to increase the interoperability of health data by using Fast Healthcare Interoperability Resources profiles and the internationally
standardized SNOMED CT terminology2 for recording clinical information.3 He noted that regulatory acceptance of real-world evidence varies by country and remains limited in some places, and suggested that regulatory frameworks could include broader definitions of acceptable clinical trials (e.g., prospective cohort studies).
Hastings emphasized the need for co-development of clinical trial technologies with the people the products are intended to serve. As an example, she said that a wearable device, such as a watch, can be useful for many people, but people with Parkinson’s disease often have difficulty managing the watchband, and the watch can snag on clothing during tremors. In addition, she said that “sponsors have the opportunity to work with patients to understand how technology actually get[s] integrated.” She suggested that walking a patient through a mock study visit could help identify challenges and areas where technology might be able to improve the participant experience. Hastings noted that it is challenging to measure the return on investment of patient involvement in drug development, and it can therefore be difficult to justify extending project time lines to allow for gathering patient input. She suggested that stakeholders work collectively to identify potential measures and to educate investors about both the value of designing technology up front to meet patient needs and the risks of not doing so. Her vision for 2030 is that study participants would not have to manage many different technology elements (e.g., a watch, an app) to achieve the same outcome. Uncoordinated technology elements can also create confusion for regulators and payers, she noted. Hastings said the patient community is ready and willing to contribute to finding solutions and that advocacy groups can play a role by serving as precompetitive conveners.
A unified trial experience for patients should include technology elements that flow together, and coordination of technology across the clinical site experience to ensure that trials are efficiently executed and necessary datasets are obtained, Hirsch summarized. The architecture to support integration across technology products exists, he said, but regulatory policies must be coordinated. Thinking intentionally about the patient experience and the site experience “cascades into a better experience for participants, higher accessibility, and generation of higher quality, more accessible data,” Goldsack concluded.
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2 For more information on SNOMED, see https://www.snomed.org (accessed July 26, 2021).
3 For more information on the SNOMED CT policy adopted by the German Federal Institute for Drugs and Medical Devices, see https://www.bfarm.de/EN/Code-systems/Terminologies/SNOMED-CT/_node.html (accessed August 3, 2021).
THE ROAD TO 2030: VISIONS OF WHAT IS POSSIBLE
Speakers in this session provided examples of collaboration and innovation toward implementing digital technologies in clinical trials. Janice Chang, chief operating officer at TransCelerate, discussed some of the lessons learned from the response by TransCelerate member companies to the COVID-19 pandemic and shared her perspective on the role of technology in moving toward 2030. Pamela Tenaerts, chief scientific officer at Medable and former executive director at CTTI, discussed implementing technology to enable decentralized clinical trials in a responsible way. The session was moderated by Anita Allen, professor of law and philosophy at the University of Pennsylvania Carey Law School.
Collaboration in Action: The TransCelerate COVID-19 Response
TransCelerate is a global not-for-profit entity that serves as a catalyst for industry-wide collaboration, Chang said. More than 1,000 experts from 20 member companies are working together on more than 30 projects that align with TransCelerate’s three strategic priorities: (1) harmonize process and share information; (2) improve the patient and site experience; and (3) enhance sponsor efficiencies and drug safety.4 Chang emphasized that TransCelerate works diligently and proactively to ensure that different stakeholder groups are engaged in these projects, including regulatory authorities, clinical sites, CROs, technology vendors, and others.
Pandemic Response
Since the early days of the COVID-19 pandemic, Chang said there has been an “unparalleled willingness” by TransCelerate member companies to share, learn from each other, and collaborate to identify solutions for maintaining trial continuity during the pandemic. Product sponsors deployed a range of novel and non-traditional technologies, tools, and methods in a crisis-response environment. Practical solutions launched by TransCelerate included, for example, a COVID-19 data-sharing module in TransCelerate’s existing DataCelerate platform and a protocol deviation toolkit, which she said are available not just to member companies, but to any qualified stakeholders.
Chang highlighted some of the considerations when implementing novel, non-traditional continuity tools and technologies during a crisis. For example, it is important to ensure that tools and technologies intended
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4 For more information about TransCelerate, see https://www.transceleratebiopharmainc.com (accessed July 1, 2021).
to reduce the burden on participants do not inadvertently increase the burden on sites, and vice versa. Additionally, stakeholders should consider how tools and technologies are delivered to patients and sites and how training can be effectively deployed in a virtual setting. She added that it is critical to ensure that data integrity and privacy are not compromised when implementing new tools and technologies for data collection. She referred participants to the TransCelerate website for information on these and other resources, including a paper sharing best practices and assessing how the lessons learned from the COVID-19 response could inform modernization of the clinical trials enterprise after the pandemic.5 Stakeholders in the clinical trials ecosystem now have an opportunity to create lasting change by shifting to a collaborative mindset, she said. She closed by paraphrasing a popular adage: “To change fast, go alone. To go far, we have to go together.”
Reprioritizing for the Future
Responding to the COVID-19 pandemic in an agile manner presented TransCelerate with opportunities to evolve and to reprioritize its collaborative initiatives around two main themes. The first theme, modernization, involves incorporating new and innovative technologies and processes that simplify and improve participant experiences while ensuring that participant safety and data reliability are maintained, Chang explained. The second theme centers around enabling a more dynamic data ecosystem to amplify the power of the vast amounts of data being generated and accelerate product development. Initiatives are focused on data usage, versatility, and accessibility.
Chang observed that, compared with other industries, the clinical trials enterprise is “a little stuck when it comes to … adopting innovative technologies,” and said the industry has “an obligation to … evolve the way we conduct our research and development activities.” She emphasized the need to thoughtfully consider which tools, technologies, and processes implemented during the COVID-19 pandemic response could be adopted more broadly across the clinical trials enterprise, noting that not all will be sustainable outside of a crisis response.
Technology-Enabled Decentralized Clinical Trials
Tenaerts asserted that “We need to improve our evidence-generating system so that we can answer more questions about what will impact
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5 See https://www.transceleratebiopharmainc.com/initiatives/modernizing-clinical-trial-conduct (accessed July 1, 2021).
health.” Medable is working to enable decentralized clinical trials thorough appropriate and responsible use of technology.6 Decentralized clinical trials are still clinical trials, Tenaerts said, and should (1) ensure participant safety and patient-centricity; (2) deliver reliable, actionable data to decision makers, including care providers, patients, and regulatory agencies; and (3) improve participant and site satisfaction with the clinical trial process. Several individual workshop participants, including Robert Califf of Verily Life Sciences (see Chapter 2) and breakout participants summarized in Chapter 3, emphasized that the practical application of digital health technologies can improve access to clinical trials for participants who may not live near traditional brick-and-mortar clinical trial sites.
Drawing on her prior experience at CTTI, Tenaerts emphasized the importance of engaging all stakeholders in clinical trials when seeking solutions to difficult problems. In developing clinical trial solutions for decentralized trials, she said that Medable has included experts in product design and technology as partners in the discussions. Although these stakeholders might not have extensive clinical trials experience, they bring a different perspective and can help formulate new approaches to address persistent problems, she said.
Tenaerts highlighted the following three main areas where technology-enabled decentralized clinical trials can face barriers to adoption and implementation:
- Regulatory. A key consideration for implementing new technologies in clinical trials is whether such changes to methodology will meet regulatory requirements, Tenaerts said. Acceptability might also vary depending on the country and agency.
- Legal. There are a host of potential legal considerations when implementing new technologies in clinical trials. For example, state licensing boards have different requirements for the practice of telemedicine. Although some licensing requirements were temporarily suspended during the COVID-19 pandemic response, Tenaerts observed that many are being reinstated as the pandemic continues. Authentication of users can be challenging when appointments or interactions are not done in person and involve parties without an established provider–patient relationship, and laws dealing with authentication practices such as electronic signatures vary by country.
- Practical. A key practical consideration for implementing innovative technologies in clinical trials is building trust in the new
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6 For more information about Medable, see https://www.medable.com (accessed July 1, 2021).
- systems, Tenaerts said. She also pointed out that just because something can be done does not mean it should be done. Using decentralized methods can lead to “loss of human connection,” and she said it might be better to retain some in-person encounters by using local laboratories and imaging centers, or arranging for local nurses to visit trial participants’ homes. Basic human nature can also be a hurdle, and changing behavior can be difficult. Studies in behavioral economics show that people often choose the perceived easiest option to avoid having to make a complex decision, and focus on the immediate returns rather than longer term implications of their decisions. Professional hesitancy is also a barrier, she said, as there are often concerns that poor trial outcomes might be blamed on the use of the new methodology.
To overcome these hurdles, Tenaerts said the clinical trials community needs to generate data that characterize the performance of technology-enabled decentralized clinical trials. This includes evidence demonstrating how technology helps to keep trial participants safe with regard to both potential adverse events, and data privacy and security concerns. It is also important to demonstrate that conducting technology-enabled decentralized trials does not adversely affect the clinical trial data in any way. For example, evidence is needed to demonstrate that enrollment is representative and inclusive, and that the resulting clinical trial data are actionable and reliable. Tenaerts pointed out that the use of technology can potentially improve the data collection process, but without caution and careful monitoring can also introduce systematic bias or error. Data are also needed that demonstrate how conducting technology-enabled decentralized trials leads to a better trial experience for both participants and sites, and enhances trust in the clinical trials enterprise.
Tenaerts noted that some trials conducted during the COVID-19 pandemic were decentralized out of necessity (i.e., they were deemed to be critical trials, and decentralization was necessary to keep the trials going). The question, she said, is how to build on this base of experience and expand the use of decentralized trials. She noted that the FDA Oncology Center of Excellence is now requesting that data collected remotely be specifically tagged in an effort to better understand the impact of decentralizing trials (e.g., How does decentralization impact the rates of missed visits and missing data? What is the impact of remote administration of the investigational product on compliance?).
Short-Term Goals for Applying Technology to Simplify Clinical Trials and Improve the Patient Experience: Panel and Breakout Discussion Highlights
Following the panel discussion, online participants were divided into virtual Zoom breakout rooms to consider how technology might be applied toward achieving the vision of the 2030 clinical trials enterprise. In this breakout session, groups focused on two goals: enabling a more person-centered and easily accessible clinical trials enterprise; and simplifying trials (e.g., less active data collection, fewer site visits, reduced costs) while still generating high-quality data and robust answers to relevant clinical questions. Participants discussed practical applications of technologies, barriers to implementation and use, and where and by whom these technologies would be used relative to these goals. Upon reconvening in plenary session, Goldsack briefly reflected on the panel and breakout group discussions.
Participants discussed how to engage with target populations “thoughtfully, deliberately, using technology as a new tool in the toolbox, with eyes on patient safety and getting the best data that we can,” Goldsack summarized. Comments addressed ways in which the use of technologies could lead to greater success in implementing concepts such as inclusivity by design and taking a person-centric approach. It was pointed out, Goldsack relayed, that clinical trial workflows will evolve as technologies are implemented, and they might look different from today’s workflows, perhaps with different actors and occurring in different places (e.g., pop-up clinics for vaccinations). She added that thinking about change management and new ways of working is as essential to success as implementing new technologies. Goldsack and Amy Abernethy, former principal deputy commissioner for food and drugs at FDA, discussed taking a “product mindset” when building and deploying technologies for the future clinical trials enterprise. Examples are developing modules that could be coordinated and integrated, and creating minimal viable products for user feedback. In doing so, Goldsack explained, “we are able to deliver to the target user a product that is inherently valuable and inherently appealing.”
Long-Term Goals for Applying Technology to Improve Trial Diversity and Inclusivity: Panel and Breakout Discussion Highlights
In this breakout session, groups focused on the role of technology in achieving the goal of establishing a clinical trials enterprise that is more diverse, equitable, and inclusive, and the goal of establishing a national network of community-based clinical trial sites. Participants discussed practical applications of technologies, barriers to implementation and use,
and where and by whom these technologies would be used relative to these goals. Upon reconvening in plenary session, Allen briefly reflected on the panel and breakout group discussions.
As discussed throughout the panels and breakout groups, “we need to find ways to connect to underserved communities,” Allen summarized. This includes more community-based programming and workforce training, for example. In developing clinical research training opportunities for the clinicians and staff in underserved communities, participants discussed that the clinical research enterprise needs to learn first from them about their training needs and resource challenges. It was pointed out that simply implementing technologies to decentralize trials will not solve all the challenges these community clinicians are facing.
Another topic of discussion, Allen noted, was the importance of developing culturally competent approaches to implementing new technologies. Different communities and cultures access and use technology differently, and failure to understand this could exacerbate health disparities. It was also noted that there are many variations within a given broad population or cultural group, and there is a need to understand local context (e.g., the five main Census categories for race are composed of many different cultures). Discussion also continued on need to build trust in the clinical research enterprise and clinical trials.
Finally, participants discussed who in the clinical trials ecosystem is responsible for implementing the technology changes that could advance the diversity and inclusiveness of clinical trials. “It is a broad participation of all the stakeholders,” Allen summarized, including government, regulators, patients, clinicians, and others.
REFLECTIONS ON REALIZING THE POTENTIAL OF TECHNOLOGY IN CLINICAL TRIALS
Andy Coravos, co-founder and CEO of Elektra Labs (renamed HumanFirst since the time of the workshop); Eric Perakslis, chief science and digital officer at the Duke Clinical Research Institute; and Sam Roosz, co-founder and CEO of Crescendo Health reflected on realizing the vision of a transformed clinical trials enterprise through the thoughtful and responsible deployment of technologies. The discussion drew from an associated Health Affairs blog post in which they envision how the lives of four fictional individuals could be changed with the integration of technologies into the clinical trials enterprise.7 The discussion was moderated by Esther Krofah.
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7 This discussion is based on a blog post titled The Future of Clinical Trials: How Will New Technologies Affect the Lives of Participants?, available at https://www.healthaffairs.org/do/10.1377/hblog20210505.673654/full (accessed July 1, 2021).
Applying Digital Health Technology in Clinical Trials
Krofah and Roosz noted that a recurring theme during this part of the workshop was that, in some cases, clinical trial conduct and trial participant experience could be improved through the practical use of existing digital health technologies. Panelists discussed some of the considerations for stakeholders seeking to better integrate digital health technologies into clinical trials.8
Recognizing that the time is now and acknowledge that these technology approaches are implementable. Roosz said there is an opportunity to move quickly to selectively implement new technologies in appropriate clinical trials that can help deliver meaningful products to patients. “We do not need to build all these new technologies,” he said. “We already have them sitting at our fingertips.” He called on participants to “suspend disbelief about what is possible” and break the habit of meeting any new proposal with counterarguments about why they should not be tried. Start from the position that implementation of a particular technology to advance a specific clinical trial is achievable, and then work to address the logistical and institutional challenges.
Focusing on collaboration, inclusion, and trust. Reflecting on his career in technology, Perakslis said “the technology has not been the hard part. It is collaboration. It is trust. It is listening that tends to be difficult.” He agreed there are digital health technologies already available and said the focus should not be on developing another app, data network, or database. The focus should be on fostering cooperation and promoting inclusion and trust, and he emphasized the importance of working with existing networks of doctors and community health workers. Roosz agreed and said trust is the core of any relationship between a patient and a care provider, whether as part of routine clinical care or in the context of a clinical trial. He suggested that each time a patient interacts with the health system, it is an opportunity to foster trust in clinical trials, and identify potential areas of hidden bias or inaccessibility in these encounters. He added that engagement of people in their communities (“on their turf”), by providers who look like them and speak their languages, is one key way to start building trust.
Taking a holistic approach to data governance. Although much attention is given to issues of data privacy, Coravos suggested that it is more important to talk about data governance—who gets access to what data and when. Patients should be able to trust that their information is secure
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8 Coravos also referred participants to The Playbook, a guide for developing and deploying digital clinical measures in clinical trials, health care, and public health developed by the Digital Medicine Society. See https://playbook.dimesociety.org (accessed July 1, 2021).
when they use digital health technologies, and there is ongoing discussion about how to balance data security with usability of the technology. She emphasized that a holistic approach to governance of health data should include non-discrimination protections for patients. Roosz noted that other elements of good data governance including transparency of how data are handled, and consent from patients for how their data are used. Reporting information back to trial participants is important, he said, “so that they, as a contributor and a partner in this clinical trials enterprise, are able to celebrate with the investigators the results and learnings from that study.”
Meeting people where they are. When designing a clinical trial, start with an understanding of what measures and outcomes matter to patients, Coravos said. Then determine if technology provides solutions participants want. Coravos suggested that patient-centeredness is about making sure the patient has choices. Do not make assumptions about what patients do or do not want, she said. For example, some patients might not want to draw their own blood sample, even if the technology to do so is available. Some people might prefer more support when collecting and providing their data in a trial.
Better integrating the practice of medicine and the development of medical products. There are gaps in knowledge between experts who specialize in developing medical products and practicing clinicians. “To move clinical trials into the community, we have to create the right type of overlap so that we … have more fluency between research and care,” Perakslis said. As an example of potential overlap, he noted the similarities between a clinical trial case report form and the EHR entries for a clinical care visit, but emphasized only the information in the case report form is included in a clinical trial while the natural history collected in the EHR is often lost. He advocated for considering how providers could better use patient care interactions as opportunities to engage people in clinical research, and using technologies to make the integration more seamless for patients and providers.
Potential Next-Step Actions for Stakeholders
Krofah asked panelists to suggest next-step actions by stakeholders in the clinical trials enterprise to begin implementing technologies toward their vision for 2030 now. They suggested the following actions:
- Modeling what has worked in other venues. Perakslis mentioned hospice care as an example of a successful “click and mortar” business model (i.e., one that functions both online and in person). Hospice is a domain of care that rapidly moves a person from
- clinical care to personalized care at home or in a dedicated facility. He proposed that moving a person into a clinical trial directly from a care encounter could happen in a similar manner. For example, an individual could be referred for a trial, then trial staff could conduct a home visit, using digital technologies for collecting and moving data. This approach, deploying both humans and technology, could be a good first step as the system evolves toward decentralized trials.
- Actively participating in process of policy making and rule making. Coravos pointed out that proposed rules and regulations are posted for public comment, and regulators are required to review all comments submitted. She described this as a powerful way for individuals to contribute to the policy-making process. Social media posts and online discussions may be widely read or viewed, but comments submitted to regulators during open comment periods directly inform policy decisions. Roosz agreed and encouraged participants to take opportunities to submit comments as stakeholders by profession and as individuals. Coravos noted that there are opportunities for collaboration to help develop prototypes for rules that have not yet been written, and to test them in different settings. “Make the change that we would like to see,” she said.
- Picking one technology solution and taking the first step. Roosz emphasized that the problems with integrating and scaling new technologies in clinical trials do not need to be solved all at once. He encouraged those who are conducting studies to choose one or several new methodologies, use them, and solicit feedback from stakeholders on how they impacted the conduct of the trial and the patient experience. “We might be surprised with the quality that these new approaches actually bring to what have been pretty unchanging methods in the past,” he said.
