USFDA Guidance: Digital Health Software to Advanced Clinical Trial Methodologies (Jan 2026)

As innovation in healthcare rapidly expands across digital health, medical devices, and advanced clinical trial designs, regulatory expectations must evolve in parallel. Recognising this shift, the US Food and Drug Administration (FDA) released and updated several key guidance documents in January 2026, offering clarity on how emerging technologies and novel scientific approaches should be developed, evaluated, and regulated.

These guidances collectively address clinical decision support software, low-risk wellness technologies, cuffless blood pressure devices, Bayesian clinical trial methodologies, and innovative oncology endpoints such as minimal residual disease (MRD).

Guidance: Clinical Decision Support Software: Clarifying Regulatory Boundaries

In January 2026, the FDA issued an updated version of its guidance on Clinical Decision Support (CDS) Software, superseding the earlier January 2025 edition. This guidance clarifies when CDS software functions are not considered medical devices under Section 520(o)(1)(E) of the Federal Food, Drug, and Cosmetic Act.

The guidance explains that CDS software intended for healthcare professionals may fall outside FDA device regulation if it does not analyse medical images or signals, relies on well-understood medical information, supports—rather than replaces—clinical judgment, and allows clinicians to independently review the basis for recommendations. Importantly, transparency of algorithms, clarity of data sources, and avoidance of time-critical automation are emphasised to mitigate risks such as automation bias.

This guidance is particularly relevant for digital health developers, AI-driven platforms, and pharmaceutical sponsors integrating decision support tools into clinical workflows.

Guidance: General Wellness Policy: Defining Low-Risk Devices

To further support innovation while avoiding unnecessary regulatory burden, the FDA updated its General Wellness: Policy for Low Risk Devices guidance in January 2026, replacing the 2019 version. This guidance outlines FDA’s enforcement discretion approach for products intended solely to promote a healthy lifestyle and that present minimal risk to users.

The policy clearly distinguishes between wellness claims—such as improving fitness, sleep, or stress management—and medical claims related to diagnosis or treatment of disease. It also explains when non-invasive sensing technologies may still qualify as general wellness products, provided they do not guide clinical decisions or substitute for regulated medical devices.

For companies developing consumer health technologies, wearables, or wellness software, this guidance provides critical clarity on regulatory expectations and boundaries.

Guidance: Cuffless Non-Invasive Blood Pressure Devices: Strengthening Clinical Evidence

With the increasing use of wearable and sensor-based monitoring technologies, the FDA issued a draft guidance in January 2026 on Cuffless Non-Invasive Blood Pressure Measuring Devices – Clinical Performance Testing and Evaluation. This guidance addresses the unique challenges associated with validating devices that estimate blood pressure without traditional cuffs.

The document outlines expectations for clinical validation, including study design, sample size considerations, patient diversity, and performance testing under static, stability, and induced-change conditions. It also highlights the importance of early FDA engagement through the Q-Submission Program, especially for devices incorporating artificial intelligence or machine learning algorithms.

This guidance plays a key role in ensuring that innovative cardiovascular monitoring technologies meet robust safety and effectiveness standards before entering the market.

Guidance: Bayesian Methodology: Modernising Clinical Trial Design

The FDA’s draft guidance on the Use of Bayesian Methodology in Clinical Trials for Drugs and Biological Products reflects growing acceptance of adaptive and probabilistic approaches in clinical development. This guidance supports the use of Bayesian statistics to enhance trial efficiency, incorporate prior knowledge, and improve decision-making—particularly in complex or rare disease settings.

The document emphasises the need for transparency, robust justification of prior assumptions, prespecified analysis plans, and clear communication of Bayesian results to regulators. When appropriately applied, Bayesian approaches can complement traditional frequentist methods and support more flexible and informative trial designs.

Guidance: Minimal Residual Disease in Multiple Myeloma: Accelerating Oncology Approvals

In January 2026, the FDA released a draft guidance on Minimal Residual Disease (MRD) and Complete Response (CR) in Multiple Myeloma, recognising these biomarkers as potential endpoints to support accelerated approval. This guidance reflects the evolving oncology landscape, where deeper response measures are increasingly important due to improved therapeutic outcomes.

The document provides detailed recommendations on trial design, statistical considerations, assay validation, and regulatory expectations when using MRD or CR as primary endpoints. While MRD offers a sensitive measure of treatment response, the FDA emphasises the need for confirmatory trials to verify long-term clinical benefit.

This guidance is particularly significant for sponsors developing novel therapies in hematologic malignancies and seeking expedited regulatory pathways.

For pharmaceutical companies, device manufacturers, and digital health innovators, early alignment with these guidances—and proactive regulatory engagement—will be essential to achieving efficient development, smoother approvals, and sustained compliance in a rapidly evolving healthcare ecosystem.