Digital Tools in Clinical Trials Find Opportunity During Pandemic

David Shaywitz

The current crisis represents a potentially defining moment for at least some health technologies and technology-enabled services. 

Telehealth, as discussed in my last column, is one conspicuous example, and the jury is still out. The potential benefit seems especially striking at a time when so many Americans are being told to stay at home, yet there are also serious concerns, both short-term (can existing telehealth capabilities adapt to exploding demand?), and longer-term (including not only a thicket of regulatory and reimbursement hurdles, but also challenges around data governance and trust).

Nevertheless, as Dr. Joseph Kvedar, VP of Connected Health at Partners HealthCare puts it, “telehealth is clearly making the case for how technology should be used to imagine how care and services are delivered.  I believe that there will be no turning back.”

The corresponding example from the pharma world might be the use of technology to enable remote trials. It’s an urgent consideration in light of the pandemic, which is having a predictably negative impact on clinical trials. In the last 24 hours, Lilly announced it would “delay most new study starts and pause enrollment in most ongoing studies,” while “continuing ongoing clinical trials for patients who are already enrolled.”  Meanwhile, the New York Times reports BMS has told researchers “it will put off beginning new clinical trials for at least three weeks,” “will not initiate any new sites for clinical trials until April 13” (or later), and said “studies involving healthy volunteers should be paused if they are at a natural break point until at least April 13.”

Clinical trials, like much of clinical medicine, have historically focused around global networks of brick-and-mortar centers. These centers can be stand-alone facilities, which are typical for early phase, highly monitored studies. They can also exist in large medical centers with physicians who have agreed to participate in the study. That model is quite common for larger, mid- and late-phase studies.

While operating in a site-focused fashion enables a relatively high degree of process control, it also means that studies are generally limited to subjects who can show up to a single location, often repeatedly over days, weeks, and typically months. The convenience challenge is often cited as a major reason why participation in clinical trials is so abysmally low.

This matters for many reasons: a key hurdle for clinical studies is it often really difficult to find enough patients to study, a persistent challenge which adds significantly to the length and cost of trials.It also means that many potential subjects never have the opportunity to participate because they are not located near a trial site and/or the time and travel commitments are prohibitive.

Estimates vary for just how small the percentage of eligible patients who participate in trials is. Some suggest the figure is as low as 2%; a recent study led by Joseph Unger of the Fred Hutchinson Cancer Research Center and focused on cancer patients puts the number at 8%. Foremost among the factors cited for low participation by Unger and his co-authors is that “a trial may not be available where the patient is being treated.” As they point out, “Having to travel to participate in a trial can be an overwhelming burden to patients.” 

Driven by these widely recognized needs, there has been profound interest in finding ways to increase the reach of clinical trials, which often involve the idea of the trial going to the patient, rather than the patient going to the trial. This was the driving force for Novartis to ink a high-profile deal with the remote trial company Science37 in 2018, a pact aiming to deliver 10 studies in three years (our TechTonics episode with Science37 co-founder and former-CEO Noah Craft, who stepped down in 2019, is here).

As the Novartis press release put it, “Decentralized, or virtual, trials harness digital technology to allow some or all aspects of a clinical trial to be carried out at a participant’s home or local physician’s office, rather than at a central trial site such as a large hospital…”

Improving the diversity of participants is another attraction of virtual approaches. As a Novartis executive says in the same statement, “Remote participation in research has the benefit of improving the breadth of participation from wider community and socio-economic backgrounds, while also allowing us to gather more meaningful real-world evidence in our clinical trials.”

In theory, a company that had an established, decentralized trial capability might be more robust to site-focused challenges like those associated with the pandemic. Certainly, the FDA’s recent guidance makes clear it is receptive, under the conditions of the pandemic, to remote approaches as supportive of participant safety. 

The guidance document specifically encourages sponsors to consider “alternative methods for safety assessments” such as “phone contact, virtual visit, alternative location for assessment,” and presses sponsors to “determine if in-person visits are necessary to fully assure the safety of trial participants.” 

The Agency goes on to note that depending on the circumstances, some “investigational products that are normally administered in a health care setting” might be given some other way (“e.g. home nursing or alternative sites by trained by non-study personnel”). The Agency even suggested the possibility of “the use of virtual assessments” for efficacy evaluations. Collectively, the document at a minimum highlights the potential of a remote clinical trial capability, which would seem useful in the context of this crisis. 

My best guess, however, is that remote trial monitoring is still such an emerging capability that few, if any, pharmas have it available as a ready substitute for in-person visits; this may not even be appropriate for many study protocols. Some experts such as Andrew Matzkin, a partner at the consultancy Health Advances, believe that decentralized clinical trials may be a promising concept that could work technologically, but still need to provide more evidence, demonstrate real world usability, establish credibility, and  describe a reliable path to commercial scale before they’re likely to gain general acceptance.

Perhaps for a few very high priority trials that are already underway, pharmas are likely to do every possible thing they can to keep these studies advancing. Pharma companies will try to use remote capabilities and deployed specialists to perform the necessary evaluations, assessments, and (where required) dosing. Especially at a time when health systems and healthcare workers are already so overwhelmed, any success from this approach is likely to be extremely limited.

At times of crisis, it’s often said that the startups that benefit the most aren’t those that are formed in the heat of the moment to address the emergent needs, but rather those that were created years back, and are poised, for lack of a more tasteful term, to take advantage of the moment. 

Two startups in this space are Evidation Health and Koneksa Health, which both offer flavors of what might be called “digital tool enablement as a service.” While neither seem positioned to save pharma from the trial continuity crisis, the value of their capabilities is likely to be evaluated and recognized at this moment.

Evidation Health, led by Deb Kilpatrick (her TechTonics episode here), is perhaps best known in recent days for its partnership in the “Heartline” 150,000 person study – “a big deal of digital health” according to CNBC’s Chrissy Farr – recently launched by J&J and Apple. Heartline’s website says Evidation “provides the technology and study operations that enable the Heartline app and study experience for participants.” Their role, Kilpatrick says, is as the “software-based virtual site,” explaining that Evidation’s research platform enables a contemporary, decentralized research experience for older adults mediated entirely through the iPhone while collecting and processing their (explicitly consented) research data.

Evidation believes its secret sauce is gleaning insight from the data generated by these digital tools – information the company refers to as “person-generated health data, or PGHD), a distinctly non-trivial task accomplished by the data science team build by co-founder Luca Foschini. Evidation’s approach has been used in studies of the flu, as well in a recently-launched longitudinal program seeking to better understand the perceptions, experience, and health of Americans in response to the pandemic; using its already-deployed patient engagement app called Achievement, the company hopes to integrate surveys and digital measurements from users who opt-in; as of March 18, over 100,000 people apparently had.

If Evidation’s focus is obtaining meaningful clinical insights by analyzing what it would describe as high-quality, person-generated health data from consumer devices and engagement apps, Koneksa Health is especially focused on the validation of remote measures for use in traditional clinical trials, and supporting pharma stakeholders who make go/no-go decisions, as well as the regulatory authorities who must accept digital measures in place of, or in addition to, the current gold standard. (My simple-minded dichotomy sees Koneksa focused on pre-approval trials, and Evidation capturing value from post-approval studies and other research; in reality, the capabilities of these two companies presumably overlap).

Koneksa’s focus, says founder and CEO Chris Benko (his TechTonics episode here) is the use of patient-focused digital biomarkers (e.g. remote, device and app based measures of pulmonary function, activity, sleep, vital and hefty signals) to support development of novel therapeutics.”

Benko’s view is that the current crisis, and the FDA’s response, “will require technology tools already designed as fit-for-purpose clinical trial tools,” adding “Koneksa has been deploying tools like this into clinical trials since we launched in 2015.”

Bottom Line: While no company seems poised to save pharma from the clinical trial interruption the pandemic has necessitated, the urgent search for partners with digital capabilities may accelerate the growth of startups like Koneksa and Evidation who are progressively establishing themselves in this nascent and promising space.

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