Software Trapped in a Hardware Rulebook

Prescription digital therapeutics (PDTs) — software-based interventions that deliver evidence-based therapeutic treatments — are reviewed using FDA regulatory pathways designed for physical medical devices. These pathways (510(k), De Novo, PMA) assume a static, manufactured product, but PDTs are iteratively developed software requiring frequent updates, posing unique placebo-control challenges in clinical trials, and potentially delivered on platforms different from those tested in pivotal studies. The FDA has found that several authorized PDTs were tested on prototype platforms different from the final marketed product, undermining the clinical evidence basis for authorization. No regulatory pathway exists that is specifically designed for the characteristics of software-as-therapy.

The global digital therapeutics market is projected to reach $13 to $15 billion by 2028, with hundreds of products in development for substance use disorders, insomnia, chronic pain, diabetes, ADHD, and depression. Regulatory pathway misalignment increases development costs, extends time-to-market, and creates uncertainty that deters investment. The failure of Pear Therapeutics — the first company to receive FDA authorization for a PDT — in 2023 was attributed in part to the difficulty of operating within a regulatory-reimbursement framework designed for physical devices.

The De Novo pathway has been used for first-in-class PDTs such as reSET (substance use disorders) and EndeavorRx (ADHD), but it was not designed for software products. The FDA's Breakthrough Device Designation has been applied to some digital therapeutics, but it accelerates review rather than addressing the fundamental pathway mismatch. In January 2025, the FDA updated its Clinical Decision Support and general wellness guidance documents, adopting a more permissive approach to some digital health tools, and withdrew its SaMD clinical evaluation guidance, signaling a shift in strategy. However, reducing regulatory burden also risks reducing evidentiary standards. Many 510(k)-cleared digital health devices lack direct evidence of effectiveness, relying on equivalence to predicates — a problematic assumption for software, where small UI/UX changes can dramatically alter therapeutic engagement. Developing credible placebo controls for digital interventions remains extremely difficult because user interaction, design features, and engagement are integral to the therapy, and full blinding is rarely achievable.

A regulatory pathway specifically designed for software-based therapeutics — one that accommodates iterative development, platform-agnostic evidence standards, and adaptive trial designs — would address the structural mismatch. This could draw on models from software certification in other safety-critical domains (aviation, automotive) where continuous updates are managed through structured change-impact assessment rather than full re-certification. Consensus on appropriate clinical trial designs for PDTs, including standardized approaches to placebo controls and outcome measurement for software interventions, would provide the evidentiary foundation.

A student team could conduct a systematic comparison of regulatory pathways for software-based therapeutics across jurisdictions (FDA, EMA, PMDA, TGA) to identify which elements of non-U.S. frameworks address the gaps in the current FDA approach. Another entry point would be designing and testing a sham digital therapeutic control condition for a specific therapeutic area, addressing the placebo-control methodology gap. Relevant skills include regulatory science, clinical trial design, software engineering, and behavioral science.