JMIR Publications

ABSTRACT

Background:

Digital therapeutics (DTx) have attracted attention as the substitutes or add-ons to conventional pharmacotherapy. The number of clinical trials for DTx has increased recently and one of the main targets for DTx is psychiatric disorders. Generalized Anxiety Disorders (GAD) is one of the most common and notable psychiatric disorders and it’s known that the magnitude of placebo effect in the pharmacotherapy is quite large. The randomized clinical trials (RCTs) with digital shams are the most reliable clinical trials to evaluate the safety and efficacy of DTx. However, the effect size and the associated factors of digital shams on GAD have not been investigated although they are critical to assess the true treatment effect of DTx.

Objective:

The objectives of this study were to identify RCTs with digital shams as comparators which evaluated GAD assessment scores, to review the characteristics of the RCTs and of the digital shams in the systematic review, and to investigate the effect size and the associated factors in the meta-analysis.

Methods:

The RCTs evaluating the GAD assessment scores by setting digital shams as comparators were identified by searching the database of PubMed, Web of Science and Scopus in July 2024. The characteristics of the RCTs and of the digital shams were reviewed systematically. The meta-analysis including sub-group analyses and meta-regressions were conducted to investigate the effect size and the associated factors of the digital shams.

Results:

54 RCTs were included in the systematic review and 32 RCTs with 3 GAD assessment scores were included in the meta-analysis with a total of 5311 participants. The pooled effect size of digital sham for all the included studies was large (Hedge’s g=0.28, 95% CI 0.18 to 0.38). The sub-group analyses showed the significant difference in the effect size among target population (p=.03), sham approach (p=.02) and baseline values (p=.02). The meta-regressions also indicated that the primary psychiatric patients in the target population (p=.01), removed type in sham approach (p=.04) and high baseline values (p=.02) were associated with the effect size of digital shams.

Conclusions:

This study showed the large effect size of digital shams on GAD assessment scores, which is consistent with the large placebo effect in pharmacotherapy. Target population, sham approach and baseline values were also identified as the associated factors of the effect size. It would be effective to create the study protocols for the DTx trials with digital shams by considering the factors identified in this study.