Key Takeaways from Roundtable on Digital Innovation in Clinical Trials

In September 2020, Pharmaceutical Executive hosted a roundtable (sponsored by Clarivate^TM, a global leader in providing solutions to accelerate the life cycle of innovation) to discuss the landscape of digital innovation in the life sciences industry. The discussion, moderated by Pharmaceutical Executive’s Editorial Director Lisa Henderson, featured former 23rd FDA commissioner Scott Gottlieb, MD; digital health and social pharma innovator Shwen Gwee; and Joel Haspel, SVP Strategy, Science Group at Clarivate.

The speakers covered a range of topics, from the impact of COVID-19 on the pace of digital technology adoption to the likelihood of data from devices replacing traditional primary endpoints. The following article highlights key takeaways from their discussion and provides insight into digital technologies’ future in clinical trials.

Over the past decade, sponsors have faced similar challenges across the industry: diminishing R&D returns, increasingly complex trials, and low patient recruitment and retention for the rising number of trials. For many years, digital technologies have promised to address these issues by reducing trial costs, generating better patient insight through real-world evidence, improving patient recruitment and retention, and more. These advantages spurred sponsors to experiment with ways to increase technology use and decentralize clinical trials. In fact, according to Haspel, more than 13,000 trials over the past nine years took advantage of digitization, marking a 40% increase in the use of digital technologies (e.g., data collection through wearables, smart phone, and tablets) in clinical trials over the past five years across therapeutic areas including diabetes, stroke, obesity, anxiety, mental health.¹

Although the landscape was already trending toward digitization, the COVID-19 pandemic accelerated the transition toward digital solutions that would align with public health guidelines. In fact, regulators have showed support of these tools by affording sponsors some additional flexibility to use them. With the FDA’s 2017 publication of the Digital Health Innovation Action Plan (DHIAP) and the recent guidance delivered by regulatory agencies on conducting clinical trials during the COVID-19 pandemic, the foundation was laid for a re-assessment of using digital technologies in trials.

Stated Gottlieb, “The importance is balancing that flexibility with any deviations in a protocol versus patient’s and data safety. But if a patient’s safety is at risk, then being able to move to remote visits and remote monitoring as long as it fits within the protocol is allowed.”

The FDA’s guidance on telehealth, remote technology for clinical outcome assessments, and remote site monitoring brought clarity and continuity to trial operations. Flexible study teams were able to turn to technology to provide operational continuity, with 85% of sponsors and CROs polled reporting a transition to remote visits on at least one of their trials^.2 The transition occurred rapidly, and Gottlieb likened the pace to compressing five years of migration to digital platforms into a seven-month period.

Sponsors that did not make the transition faced setbacks. As shown in Figure 1, the pandemic and social distancing requirements have forced trials with on-site patient check-ins to be delayed or canceled, and those that have continued have been unable to recruit patients effectively.

Virtual physicians’ appointments are not a new development, but they have become widely adopted in the wake of the pandemic. Medical centers have changed the way they operated, placing safeguards around access to facilities to prevent the virus’s spread. In addition, many patients have opted to use telemedicine, particularly those with pre-existing conditions that put them at higher risk of suffering complications from the virus.

Likewise, clinical trials transitioned to remote visits and using technology to improve the patient experience while reducing the burden of collecting data—which is good news for patients in terms of convenience. Haspel stated that 47% of healthcare executives³are either considering or already using patient-centric approaches like digital sensors in clinical trials. “The less we rely on the patient to do something to record those digital endpoints, the more they can just go about their day, that’s what makes it innovative in a way that is going to deliver value,” he said.

Defining Innovation in Digital Health Technologies

What is digital innovation? During the roundtable, digital health and social pharma innovator Shwen Gwee framed digital innovation as “The successful implementation of a creative new [digital] solution for a traditional problem.”

He also separated the types of innovation relevant to a corporation’s activities: incremental or disruptive, both of which are important to drive clinical trials forward.

Former FDA commissioner Scott Gottlieb, MD, expanded upon this idea, stating that real disruption leads to data collection that is more clinically relevant. One example would be developing a test capable of capturing biophysical performance in a longitudinal manner that is not episodic. For example, a patient who performs a six-minute treadmill test during a protocol-specified visit in a muscular dystrophy trial may experience fluctuations in performance or motivation. Capturing data only at regularly scheduled visits may not show improvement. Developing a tool that periodically records performance outside of a typical site environment could lead to more clinically relevant data if validated to a level of regulatory rigor.

This trend is likely to continue after the COVID-19 pandemic ends; 70% of clinical trials are expected to incorporate digital sensors by 2025 to monitor key endpoints like vitals.⁴ “I think it is going to sustain,” Haspel says. “We drive toward efficiencies within society. Some of healthcare’s barriers have been lowered, and that opens the door for trials.”

Improvements will be needed in the quality and delivery of virtual trial visits; however, in a recent survey, only 19% of patients stated their experience in the trial improved with televisits, while 31% said their experience worsened.⁵

Also, sponsors have some work to do to continue to assimilate digital tools into trials in terms of proving to regulators they are appropriate. As Gottlieb noted, “It’s going to take a lot of work to validate more of these tools to the satisfaction of regulators so that they can be recognized as something that’s going to allow for the collection of information in the same rigorous fashion that a site-based assessment might be. The work’s being done, and I think that’s going to be accelerated. This has been a secular shift that’s been underway for a period of time.”

In agreement is Gwee, who said there must be an end-to-end assessment of how to implement digitization more successfully. He stated, “There’s been a lot of experimentation for many years about how we can go to virtual clinical trials and decentralized trials. Most of those have been experiments that have taken place over the last few years and were not necessarily fully implemented as a standard way we do things.”

For instance, patient-centricity will be an essential aspect of rethinking trial design. Gottlieb explained that sponsors “need to think of ways to design trials in a fashion that’s accessible to patients, that’s comfortable for patients, especially as sponsors are trying harder and harder to enroll patients that represent a more diverse population.”

As digital technologies evolve, improving the patient experience will be critical to solving the difficulties sponsors have found recruiting patients.

The ubiquity of devices such as the Apple Watch, which can collect data in a validated, compliant manner, will help drive digital tools’ adoption. Amazon has actively been working on devices to capture medical data, and Verily, owned by Google’s parent company Alphabet, has developed a suite of tools and software to collect and integrate data across systems.

Pharmaceutical companies have traditionally been more comfortable partnering with larger organizations, and the high level of testing with which big tech is accustomed to lends itself to validating clinical tools. As Gwee stated, “the level of trust between them and the type of rigor they have with their systems and devices enables them to develop a more consistent and enterprise-level type of approach.”

In the past several years, the FDA has created a regulatory framework to encourage the validation and adoption of various tools. The agency’s approach is not designed simply to make trials more efficient or to lower costs through technology, but to leverage digital innovation to improve patient outcomes and safety, and to yield more clinically significant data. The goal is to improve the quality of the data, and sponsors should seek to incorporate the guidance to bolster submissions.

Gottlieb explained two ways in which innovative tools can gather more clinically significant data: by expanding the geography of collection and increasing the device’s sensitivity. By gathering more data outside the typical site setting, sponsors will amass data in a more holistic context, leading to new insights. A tool that uses the built-in functionality of a mobile phone or another commercially available device has the possibility of collecting data without adding a burden to the patient. Folding episodic data capture into a patient’s existing routines puts the data in context and the individual’s experience at the forefront.

The quality of data will also benefit from increased sensor sensitivity that can detect more granular changes to a patient’s condition, giving sponsors a better understanding of a treatment’s impact. If used outside of the site setting, sensors may also reduce the timelines required to gain useful data by demonstrating effects in a shorter window.

Apart from medical devices, there is no precedent for readouts from digital tools being used to replace a primary endpoint. Although there has not been a digital tool that accurately measures variables used as a primary endpoint, it is not an unreachable goal. Haspel said, however, “The time is right for it, but I don’t think the precedent has been set yet.”

Sponsors will need to rethink their approach to endpoints as new technologies become available. The traditional model defined endpoints clearly in advance, then collected data to support the endpoints. The opportunity to collect data at a much larger scale has enabled companies to propose endpoints based on analyzing the information collected.

Gwee explained the situation: “We’re moving to a world where we’re collecting more data than we have had initially planned because we’re no longer just restricted to what we’re defining as what we need to measure. We’re also looking at the surrounding data that we’re collecting, and we’re doing it in a patient’s natural setting. We’re starting to understand the many factors that may affect their disposition and the outcomes that a particular therapy might be driving. I think that’s all going to be interesting as we start to analyze this broader set of data than just what is being collected for that specific therapy.”

When seeking to introduce substantive change through innovation, a significant obstacle to overcome is the cost of researching and developing the idea. In rare disease populations, or therapeutic areas like pain that have to overcome the inherent subjectivity of the patient’s experience, these costs prohibit most sponsors from developing a tool for use in a program or study. Validating new tools in the context of an individual trial can strain both financial and human capital, particularly when elevating them to the level of regulatory rigor. However, as recent collaborations on biomarker assays by the Critical Path Institute, pharmaceutical and biotechnology companies can provide significant value to the research community and patients when they work together in therapeutic areas they share in common.

Gottlieb believes the opportunity to work together can fuel additional innovation. “I think, especially for sponsors who are engaged in certain therapeutic spaces and are going to be engaged in the basis for the long run,” he states, “those sponsors coming together through some kind of consortium in a pre-competitive way to pool resources, to validate tools that can then be shared in the public domain. That’s the way I think we’re going to accelerate the use of these tools in a regulatory fashion.”

The potential for collaboration extends beyond sponsors working together on a tool to the idea of data sharing. Haspel sees digital as an area where sharing becomes a possibility if it is not connected to seeking approval for a therapy. “There are a lot of failures along the way,” he says, “that are not being shared or communicated. If they were, it might accelerate and move things forward faster.”