Studies on Prescription Digital Therapeutics Lack Rigor, Inclusivity

The clinical evidence supporting prescription digital therapeutics (PDTs) is lacking, with studies frequently excluding older adults and people not proficient in English and missing race and ethnicity information of study participants, according to a new study.

Published in Health Affairs, the study aimed to identify emerging trends in the clinical evidence backing PDTs authorized by the United States Food and Drug Administration (FDA).

Researchers from the University of California San Francisco, Medical University of South Carolina, and Yale University conducted a retrospective cross-sectional analysis of clinical studies of PDTs. These PDTs were authorized by the FDA and available on the market as of November 29, 2022. The most common clinical condition these technologies targeted was diabetes (25 percent).

Overall, the researchers included 20 PDTs from 18 manufacturers in the study. There were 117 clinical studies associated with the PDTs in the study sample, with a median of 5.5 studies per PDT.

Of the 117 clinical studies, 94 (80.3 percent) were interventional, in which patients were enrolled and assigned to groups receiving PDTs and control groups, and 23 (19.7 percent) were observational cohorts, in which researchers did not assign patients to receive PDTs. Eighty-one studies (69.2 percent) were funded by PDT manufacturers.

Additionally, 82 (70.1 percent) did not use any blinding, and 46 (39.3 percent) had explicit language proficiency requirements for participants. Of the 46 with language requirements, 43 (93.5 percent) required English.

Further, 58 studies reported the age of participants, with 41.8 years being the mean age. Forty-six of the 98 non-pediatric studies (46.9 percent) had an upper age limit. The median upper age limit was 75. Race was reported in only 32 studies (47.1 percent) and ethnicity in 11 (16.2 percent).

None of the PDTs received FDA authorization through premarket approval, the “FDA’s most rigorous review pathway used for high-risk devices,” according to the study. Eight PDTs (40 percent) had no clinical studies referenced in FDA decision summaries for authorization.

Only two PDTs (10 percent) were evaluated in at least one randomized, blinded, multicenter study without a language proficiency requirement, with a clinical primary endpoint, and in which all primary endpoints were met.

“In this cross-sectional analysis of clinical studies of FDA-authorized prescription digital therapeutics as of November 29, 2022, we found important limitations in the rigor of evidence, " the authors wrote.

The findings indicate several opportunities to strengthen the PDT evidence base, including PDT manufacturers undertaking more rigorous clinical studies and the FDA establishing higher standards of evidence.

“Although the growing number of FDA authorized prescription digital therapeutics has the potential to improve patient outcomes, greater use of rigorous standards of evidence, such as randomization, blinding, and multicenter implementation with follow-up duration appropriate for the conditions being diagnosed or treated, is needed to generate confidence in their safety and effectiveness,” the researchers concluded. “Exclusion of older adults and people not proficient in English from clinical studies of prescription digital therapeutics should be ended, and diverse populations should be enrolled.”

An advisory report by the Substance Abuse and Mental Health Services Administration (SAMHSA) also noted the importance of health equity in digital therapeutics adoption and use.

The report, released in July, states that digital therapeutics are projected to grow in the coming years. However, it emphasized that access to technology, digital literacy, cultural appropriateness, and affordability are critical considerations amid its growing popularity.

Further, the FDA recently created a Digital Health Advisory Committee to support efforts to explore the scientific and technical issues related to using digital health technologies, including remote patient monitoring, artificial intelligence/machine learning (AI/ML), virtual reality, digital therapeutics, and wearable devices.

The FDA will solicit views and advice from the committee to support the safe, effective, and equitable regulation of these digital health technologies.