Connected digital products have steadily become more prominent among clinical research efforts since the start of the millennium, according to new data published Friday in NPJ Digital Medicine.

In reviewing every trial registered with ClinicalTrials.gov between the years 2000 and 2017, a group of Harvard researchers found the use of these tools increasing with a compound annual growth rate (CAGR) of 34%.

"The use of digital products to remotely monitor patients in clinical research is not new; in fact, some early digital measurement products, such as Holter monitors and continuous blood glucose meters, have been used in clinical trials for decades," the researchers wrote in NPJ Digital Medicine. "Yet, there is a dearth of data on how often and in what context such products have been integrated into clinical research – information that has implications for stakeholders across the research ecosystem."

TOPLINE DATA

Across the 18-year study period, the researchers found the number of registered clinical trials using these devices grew more than tenfold, from just eight trials in 2000 to roughly 1,170 trials in both 2017 and 2018.

In total, the team identified nearly 6,400 such trials – but notably did not include the 1,177 initiated in 2018 in their 34% CAGR calculation, due to incomplete submission reporting for the full year.

While these trials often took the form of evidence-generating studies, the researchers noted that approximately 13% were designated as an FDA-defined development stage trial or a phase 4 post-marketing study. (For reference, 52% of all ClinicalTrials.gov data during the time period were designated as an FDA-defined phase.) Meanwhile, 19% of the connected digital product trials had an industry sponsor or collaborator (compared to 34% of ClinicalTrials.gov's total records).

The researchers described an evolution in the types of connected products included across the years, with smartphone-enabled products and mobile apps spiking from 2015 onward.

They also laid out four primary connected digital product use cases for which these trials were designed: as a validation of the product's functionality; as a test of its clinical usability; to use the product as a data-collection tool for another intervention; or to measure the product as the primary intervention (à la digital therapeutics).

HOW IT WAS DONE

Before conducting an automated text search of ClinicalTrials.gov's database, the researchers identified a list of connected digital products using relevant product lists from the Scripps Research Digital Health Library, Elektra Labs' Atlas resource, the CTTI Mobile Technologies Database and Frost and Sullivan's 2016 Wearable Technologies Report. These were used to build search terms for each identified product alongside general search terms such as "smartphone" or "smart watch" when reviewing the database's registered studies.

In total, the team generated over 1,000 search terms for their review, but noted that some studies may still have been missed "because ClinicalTrials.gov does not require trial sponsors to disclose whether the data measurement tools used in the trial are connected digital products."

All trials included in the analysis must have at least begun to recruit its participants between 2000 and 2018. Researchers also reviewed a random sample from each year to ensure that their search was performing reliably.

THE LARGER TREND

The growing number of connected digital product clinical trials is clearly an important step for developers looking to validate their devices and software for broader use within healthcare, but these numbers also indicate a changing landscape for other major stakeholders.

"For pharmaceutical manufacturers and contract research organizations, the emergence of connected digital products into the clinical research space presents an opportunity to include novel trial endpoints that use real-world evidence," the researchers wrote. "For patients, connected digital products can reduce the burden of trial participation and increase the inclusivity of clinical research by fostering remote monitoring and encouraging the enrollment of individuals who might otherwise be unable to participate due to socioeconomic circumstances or travel limitations."

Digital clinical trials come in many forms, and several prominent pharma leaders have voiced their support for greater adoption of these technologies. The past few years alone have seen more than a handful of major digital-trial launches and completions from big names like Johnson & Johnson, Verily and Apple.

IN CONCLUSION

"To achieve broad adoption in clinical practice, verification and validation of connected digital products will be essential and, like other interventions, ongoing vigilance regarding their safety, efficacy, and usability will be valuable for clinicians and regulators. Future analysis in this area should explore in more detail the context in which different organizations are using connected digital products to bolster their research efforts," the researchers concluded.