Advancing the Use of Digital Health Technologies in Clinical Investigations: What the FDA RFI Means for Device Manufacturers

On March 31, 2026, FDA's Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Center for Devices and Radiological Health (CDRH), Digital Health Center of Excellence, and Oncology Center of Excellence published a Request for Information (RFI) in the Federal Register on advancing the use of digital health technologies in clinical investigations for drugs and biological products.

If your organization makes wearable sensors, implantable devices, ingestible sensors, mobile health applications, or any Software as a Medical Device (SaMD) — and especially if those products are used in clinical trials — this RFI is directly relevant to how you will be regulated over the next several years. Comments are due June 1, 2026.

This article explains what FDA is actually asking, what the regulatory structure means for device manufacturers operating under ISO 13485 and 21 CFR Part 820, and what you should do before the comment deadline closes.

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Why This RFI Matters Right Now

This RFI did not appear from nowhere. It is a direct consequence of the Prescription Drug User Fee Act VII (PDUFA VII), the FDA User Fee Reauthorization Act of 2022, which explicitly mandated that FDA support the use of digital health technologies in drug and biologics development. PDUFA VII directed FDA to develop a program for using DHTs to collect clinical trial data, with an emphasis on removing barriers to adoption and enabling remote and decentralized trial designs.

FDA delivered a first installment of that commitment in December 2023 with the publication of "Digital Health Technologies for Remote Data Acquisition in Clinical Investigations," a foundational guidance document that established baseline principles for DHT use in trials. The March 2026 RFI is the next step — a structured effort to identify where gaps remain and what specific guidance FDA needs to publish to address them.

The scope of the problem FDA is trying to solve is significant. Clinical trials increasingly depend on continuous, remote data collection from wearable sensors, smartphone-based assessments, and patient-operated devices. But the regulatory frameworks governing what makes a DHT measurement credible enough to serve as a clinical endpoint in a drug submission have remained underdeveloped. Sponsors and device manufacturers have been operating in ambiguity, relying on case-by-case FDA feedback rather than systematic guidance.

What the RFI signals is that FDA intends to fix this — and that the guidance it develops will be informed by input from the industry, including the device manufacturers who build and supply DHTs for trials. The cross-center composition of the DHT Steering Committee, with CDRH explicitly included alongside CDER and CBER, confirms that the regulatory framework being developed will involve medical device requirements, not just drug trial protocols.

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What FDA Is Actually Asking: The Four Key Question Areas

The RFI is not a general call for comments on DHTs broadly. FDA organized it around specific unresolved questions, and understanding those questions tells you exactly where the regulatory uncertainty currently sits.

1. Analytical Validation of DHT Measurements

FDA wants to understand how DHT measurements should be analytically validated — meaning, what methods and standards should govern whether a wearable sensor's heart rate measurement, a smartwatch's activity count, or an ingestible sensor's gastric pH reading is accurate, precise, and reproducible enough to rely on in a clinical trial.

This is fundamentally a verification and validation question. From an ISO 13485 perspective, it maps directly to Clause 7.3 (design and development) and the design verification requirements that device manufacturers know well. The difference is that analytical validation of a DHT endpoint must satisfy not just the device manufacturer's quality system requirements, but also the drug trial sponsor's evidence standards and ultimately FDA's acceptance criteria for regulatory submissions. Those two frameworks have not historically been harmonized.

2. Clinical Validation of DHT-Derived Endpoints

Analytical validation confirms a DHT measures accurately. Clinical validation confirms the measurement is meaningful — that changes in the measurement correspond to changes in the patient's clinical status, disease severity, or treatment response in a way that is relevant to drug efficacy assessment.

This is where FDA is encountering the most complex questions. Traditional clinical endpoints (survival, tumor response, lab values) have decades of clinical validation behind them. DHT-derived endpoints — continuous mobility data, remote sleep staging, behavioral patterns from smartphone use — are far newer, and the evidence base for their clinical meaning varies enormously by disease area. FDA is asking what standards should govern clinical validation, and whether disease-specific criteria are needed.

3. Patient-Owned Device Integration

This is the most operationally complicated question in the RFI. A growing proportion of trial participants already own smartphones, smartwatches, and fitness trackers that could, in principle, collect relevant clinical data. Using patient-owned devices in a clinical trial creates a cascade of regulatory and quality issues: device variability across manufacturers and models, software version heterogeneity, lack of calibration control, data security and privacy concerns, and the fundamental question of who bears regulatory responsibility for data collected on a consumer device being used for a drug efficacy endpoint.

From an ISO 13485 perspective, patient-owned consumer devices are almost certainly not manufactured under a medical device quality management system. The question of whether and how to integrate their data into a regulated clinical trial — and what quality controls can compensate for the lack of manufacturer QMS compliance — is genuinely unsettled.

4. Safety Signal Detection in Continuous Data Streams

DHTs generate continuous, high-frequency data streams that traditional safety monitoring approaches were not designed to handle. A wearable sensor collecting cardiac data continuously during a trial can generate thousands of data points per participant per day. Traditional adverse event reporting relies on investigator observation and participant self-report — mechanisms that do not scale to continuous sensor data.

FDA is asking how safety signal detection should work in this context: what algorithms or thresholds should trigger safety reviews, how quickly signals must be acted on, and how to distinguish noise from genuine safety concerns in continuous physiological data. This is a data integrity and monitoring question with significant implications for trial operations and for the device manufacturers supplying the monitoring systems.

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The DHT Landscape in Clinical Trials: What Is Actually Covered

The RFI covers a wider range of technologies than the term "digital health technology" might initially suggest. FDA's definition of DHTs for clinical investigation purposes includes:

• Wearable sensors — including continuous glucose monitors, ECG patches, accelerometers, pulse oximeters, and multi-parameter physiological monitors
• Implantable sensors — devices implanted for data collection in addition to or instead of therapy delivery
• Ingestible sensors — electronic capsules that collect gastrointestinal data or confirm medication ingestion
• Contactless sensors — camera-based assessments, remote vital sign monitoring, voice analysis tools
• Smartphones and smartwatches — both as direct measurement platforms and as data aggregation hubs for other sensors
• Mobile applications — including patient-reported outcome tools, eDiaries, eCOA platforms, and symptom tracking apps
• Gamified applications — particularly in pediatric trials, where gamification is used to improve engagement and compliance with data collection

Most of these categories — particularly wearable sensors, implantable sensors, and mobile medical apps that meet the SaMD definition — are regulated medical devices. They are subject to FDA premarket review through the 510(k), De Novo, or PMA pathway, and they must be manufactured under a quality management system compliant with QMSR (21 CFR Part 820, as amended) and, by incorporation, ISO 13485:2016.

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The ISO 13485 and Medical Device Angle: Why Device Manufacturers Are Central to This Story

Much of the coverage of this RFI focuses on drug sponsors and clinical trial operations. That framing misses a critical dimension: the DHTs that will be used in these trials are, in most cases, regulated medical devices. The manufacturers of those devices face a dual regulatory burden that the RFI is beginning to address explicitly.

SaMD Classification and the 510(k) Pathway

Many DHT applications — particularly mobile apps that analyze sensor data and output clinically meaningful assessments — meet FDA's definition of Software as a Medical Device (SaMD). Under the Software as a Medical Device framework, informed by the IMDRF SaMD guidance, these applications are classified based on the significance of the information they provide and the state of the healthcare situation they address. A sleep staging algorithm used in a CNS drug trial, for example, likely qualifies as SaMD and requires premarket clearance through 510(k) or De Novo before it can serve as the basis for a clinical efficacy endpoint.

The implication for manufacturers is straightforward: your device regulatory status matters to drug sponsors. A sponsor whose trial depends on a DHT-derived endpoint built on an unclearred SaMD faces FDA scrutiny not just on the clinical validation of the endpoint, but on the regulatory status of the underlying technology. ISO 13485 certification and 510(k) clearance are not just compliance checkboxes — they are prerequisites for your product's credibility as a clinical trial tool.

Design Controls and Endpoint Validation

The RFI's questions about analytical and clinical validation of DHT measurements map almost precisely onto ISO 13485 design controls requirements under Clause 7.3. Design verification (Clause 7.3.6) — demonstrating that design outputs meet design inputs — is the direct analog of analytical validation: proving the device measures what it claims to measure with the specified accuracy and precision. Design validation (Clause 7.3.7) — demonstrating that the device meets intended use requirements — is the direct analog of clinical validation: proving the measurement is clinically meaningful for the intended patient population and use context.

Device manufacturers with mature ISO 13485 QMS implementations already have the documentation infrastructure to support both validation types. The challenge is that this documentation has historically been organized for device regulatory submissions (DHF, DMR), not for drug trial sponsor review or FDA clinical division assessment. Bridging that gap — making your design validation records accessible and comprehensible to clinical pharmacologists evaluating an endpoint — is a practical preparation task that ISO 13485-certified manufacturers can begin now.

Data Integrity and Continuous Data Streams

ISO 13485 Clause 4.2 (documentation requirements) and Clause 4.2.4 (records) establish data integrity requirements covering traceability, legibility, retrievability, and protection from unintended modification. These requirements were designed primarily for manufacturing and quality records, but their underlying principles — that records must be complete, accurate, and protected — apply directly to the continuous data streams that DHTs generate in clinical trials.

FDA's concern about safety signal detection in continuous data streams is also a data management concern. A wearable sensor collecting 72-hour Holter-equivalent ECG data for a drug trial generates a volume of data that cannot be manually reviewed. The algorithms, thresholds, and automated review systems that flag potential safety signals must themselves be validated — a software validation requirement under ISO 13485 Clause 7.5.6 and IEC 62304. The integrity of the signal detection system is as important as the integrity of the sensor.

21 CFR Part 820 QMSR: The Dual-Standard Challenge

DHT manufacturers supplying devices for drug trials face simultaneous oversight from CDRH (which regulates their device) and from CDER or CBER (which regulates the drug trial in which their device is used). The QMSR, effective February 2, 2026, harmonized 21 CFR Part 820 with ISO 13485:2016, which reduces one layer of duplication. But drug trial requirements under 21 CFR Parts 312 and 511 (Investigational New Drug/IND requirements), Good Clinical Practice (GCP) obligations under ICH E6, and electronic data standards under 21 CFR Part 11 all apply to DHT data collected in a trial — independent of whether the device itself is QMSR-compliant.

This means the compliance surface for DHT manufacturers participating in clinical trials is wider than for device manufacturers who only supply to clinical care settings. ISO 13485 certification is necessary but not sufficient.

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The Unresolved Validation Problem: The Biggest Business Implication

The most commercially significant issue the RFI is trying to address is the absence of standardized criteria for DHT endpoint acceptance. Right now, when a drug sponsor wants to use a wearable sensor's continuous activity data as a primary efficacy endpoint in an NDA submission, there is no published, systematic framework that tells them what analytical and clinical validation evidence FDA will require. The sponsor must negotiate this with the relevant FDA division through the IND process — essentially reinventing the wheel for each study in each disease area.

This creates a cascading problem for device manufacturers. If sponsors cannot predict what validation evidence FDA will accept, they cannot specify what they need from the device manufacturer to support that evidence. And if device manufacturers cannot predict what specifications they need to build to, they cannot design the validation programs their product will require to be credible in a drug submission.

The absence of standards also disadvantages smaller manufacturers. Large DHT companies can afford to develop custom validation programs for each sponsor-drug combination. Smaller manufacturers — particularly those with wearable sensors positioned to serve multiple sponsors across multiple therapeutic areas — face a recurring investment in bespoke validation work that never accumulates into reusable regulatory capital.

FDA is explicitly asking the industry for input on how to solve this. The comment period is, in a meaningful sense, an invitation for device manufacturers to tell FDA what standards framework would make their products most readily usable in drug trials. Organizations that engage substantively with the analytical and clinical validation questions in the RFI will be in a position to influence the frameworks that govern their market for years.

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Patient-Owned Devices: The Regulatory Wild Card

The patient-owned device question deserves extended attention because it creates a regulatory discontinuity that no existing framework cleanly addresses.

A consumer smartwatch used in a clinical trial occupies an ambiguous regulatory space. The device itself is not cleared or approved as a medical device for the specific measurement use — it may be a general wellness device, or it may be cleared for a different indication than the one being used in the trial. It was not manufactured under an ISO 13485 QMS. It may have received software updates between enrollment and completion that changed measurement algorithms. The participant may have used it inconsistently, dropped it, or set it to low-power mode during data collection periods.

None of these problems are insurmountable, but each requires a quality control and data integrity response. FDA is asking the industry to propose how to handle them. The most defensible approach for drug sponsors who want to use patient-owned devices involves partnering with device manufacturers who can provide model-specific analytical validation data, device lock procedures to prevent software updates during the trial, data completeness monitoring, and protocol-specific calibration instructions.

For ISO 13485-certified DHT manufacturers, the patient-owned device question creates an indirect business opportunity: organizations that have invested in robust analytical validation documentation are better positioned to provide the technical evidence packages that sponsors need to support patient-owned device use than consumer electronics manufacturers who have no regulatory affairs infrastructure.

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What Your Organization Should Do Before June 1, 2026

The RFI comment deadline is June 1, 2026. Here is a practical action plan for medical device quality managers, regulatory affairs professionals, and DHT manufacturers.

Step 1: Read the RFI Directly

The full text is available at federalregister.gov/documents/2026/03/31/2026-06184. Review the specific questions FDA posed — they are organized into categories, and your response should track to the questions most relevant to your product type and therapeutic area.

Step 2: Assess Your Stake in Each Question Area

Not every question in the RFI is equally relevant to every organization. Prioritize your comment based on where FDA's guidance decisions will have the greatest impact on your product strategy:

• If you make wearable sensors, the analytical validation standards question is your primary concern.
• If you develop SaMD for clinical assessments, clinical validation criteria and disease-specific endpoint acceptability are most important.
• If you manufacture consumer devices that trial sponsors might want to use, the patient-owned device question is directly relevant.
• If you provide continuous monitoring systems, safety signal detection standards matter most to your product design requirements.

Step 3: Map Your ISO 13485 Design Validation Records

Regardless of whether you submit formal comments, begin the internal exercise of mapping your existing ISO 13485 design verification and validation records to the DHT endpoint validation framework FDA is developing. Where does your Design History File document the analytical performance of your sensor? Where does your design validation demonstrate clinical utility for the populations who will use the device in a trial? Identifying these records now positions you to respond quickly when drug sponsors make formal requests for technical support packages.

Step 4: Engage Cross-Functionally

The RFI sits at the intersection of medical device quality (ISO 13485, QMSR), clinical pharmacology (IND requirements, GCP), and digital health regulation (SaMD, DHT guidance). A strong comment — or a strong internal response to the guidance that will eventually emerge — requires input from your regulatory affairs team, your quality engineering team, your clinical affairs function (if you have one), and ideally, any clinical pharmacologists or biostatisticians you work with on trial design. Siloed responses will miss important dimensions of the problem.

Step 5: Monitor the Docket and Schedule Your Comment

Submit your comment via regulations.gov well before the June 1, 2026 deadline. Docket numbers can experience late-submission technical issues, and substantive comments benefit from time for internal review cycles. Aim to have a final draft ready by mid-May. FDA reads all comments submitted within the docket period, and well-documented, data-supported comments from device manufacturers carry significant weight in shaping the guidance that follows.

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Looking Ahead: What the RFI Signals About FDA's Three-Year Roadmap

FDA does not publish RFIs as academic exercises. The pattern established by the December 2023 foundational DHT guidance — followed by this information-gathering RFI — suggests a three-phase regulatory development trajectory that DHT manufacturers should be planning for now.

Phase 1 (2023-2026): Framework establishment. The December 2023 guidance established foundational principles. This RFI closes known gaps in that framework by collecting data on the most technically complex unresolved questions. This phase is drawing to a close.

Phase 2 (2026-2028): Technical guidance development. Following the RFI comment period, FDA's DHT Steering Committee will develop specific technical guidance documents addressing analytical validation standards, clinical validation criteria, and likely disease-area-specific endpoint frameworks for high-priority therapeutic areas (oncology, neurology, cardiovascular). CDRH's involvement in the Steering Committee means device-specific quality requirements will be embedded in these documents. ISO 13485-certified manufacturers who engaged with the RFI will see their input reflected in the resulting frameworks.

Phase 3 (2028-2030): Enforcement and expectation-setting. As guidance documents are finalized, they will begin to shape FDA review expectations for drug NDA and BLA submissions that include DHT endpoints. Sponsors will flow down those expectations to device manufacturers through clinical trial agreements and technical specification requirements. The organizations positioned to meet those requirements will be the ones that began preparing during Phase 2 — and who shaped the requirements during Phase 1 by engaging with this RFI.

The connection to decentralized clinical trials (DCTs) reinforces this trajectory. FDA has been actively developing the DCT regulatory framework in parallel, and DHTs are the enabling technology for remote trial designs. As DCTs become more common, DHT use in trials will scale from a specialized approach to a standard feature of late-phase drug development. The device manufacturers who have established the regulatory infrastructure to support clinical-grade data collection will have a significant commercial advantage in that market.

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Key Takeaways

• This is a Request for Information, not a final rule. FDA/CDER/CBER/CDRH are gathering input to shape future guidance on DHTs in clinical investigations. Comment deadline: June 1, 2026 via regulations.gov.
• PDUFA VII mandated this work. The RFI is not discretionary — Congress directed FDA to develop a program supporting DHTs in drug and biologics development, and this is the structured execution of that mandate.
• Most DHTs are regulated medical devices subject to ISO 13485, QMSR (21 CFR Part 820), and premarket clearance requirements. CDRH sits on the DHT Steering Committee precisely because device quality requirements are central to the framework being developed.
• ISO 13485 design controls are directly relevant to analytical and clinical validation of DHT endpoints. Design verification (Clause 7.3.6) maps to analytical validation; design validation (Clause 7.3.7) maps to clinical validation. Manufacturers with mature QMS implementations have a documentation foundation that supports DHT endpoint credibility.
• The unresolved analytical and clinical validation standards are the most significant commercial bottleneck for DHT manufacturers seeking to serve drug trial sponsors. Organizations that comment substantively on FDA's validation questions can shape the standards they will later be required to meet.
• Patient-owned device integration remains the most operationally complex unsettled question — and creates an indirect advantage for ISO 13485-certified manufacturers over consumer device companies without regulatory quality infrastructure.
• Plan for a three-phase regulatory trajectory through 2030, with technical guidance documents emerging in 2026-2028 and enforcement-level expectations taking shape as DCTs become standard in late-phase drug development.

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If your organization makes DHTs that are used or could be used in clinical investigations, this RFI is one of the more consequential regulatory actions of the past several years — not because it creates immediate compliance obligations, but because it will determine the compliance obligations you face in 2028 and beyond. The time to engage is before June 1, 2026.

For guidance on how ISO 13485 design controls, data integrity requirements, and SaMD quality frameworks position your organization for the DHT clinical trial market, visit certify.consulting or explore our resources on ISO 13485 design controls, FDA 510(k) and ISO 13485 integration, and regulatory submissions support.

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Frequently Asked Questions

What is FDA's June 1, 2026 deadline for digital health technologies in clinical trials?

FDA published a Request for Information (RFI) on March 31, 2026 (Federal Register Document 2026-06184) seeking public input on advancing the use of digital health technologies in clinical investigations for drugs and biological products. The comment deadline is June 1, 2026. Organizations can submit comments via regulations.gov. This is not a final rule — it is an information-gathering step that will shape future FDA guidance on DHT use in clinical trials.

Do DHTs used in clinical trials need to comply with ISO 13485?

Yes, in most cases. Many DHTs used in clinical investigations — including wearable sensors, implantable sensors, contactless sensors, and Software as a Medical Device applications — are regulated medical devices subject to FDA's Quality Management System Regulation (QMSR, 21 CFR Part 820) and, by incorporation, ISO 13485:2016. Manufacturers of these devices must maintain a compliant quality management system regardless of whether their device is used in a standalone clinical context or as part of a drug or biologics trial.

What is the DHT Steering Committee and why does it matter?

FDA established a DHT Steering Committee with cross-center representation from CDER (drugs), CBER (biologics), CDRH (medical devices), the Digital Health Center of Excellence, and the Oncology Center of Excellence. This structure is significant because it means the regulatory requirements flowing from this RFI will involve CDRH — the center that oversees medical device quality and premarket submissions. DHT manufacturers face oversight from both the drug trial sponsor's regulator (CDER/CBER) and their own product regulator (CDRH) simultaneously.

What is the difference between analytical validation and clinical validation for DHTs?

Analytical validation confirms that the DHT accurately, reliably, and consistently measures what it claims to measure — verification that the sensor and algorithm perform correctly. Clinical validation confirms that the DHT-derived measurement is meaningfully related to the clinical concept of interest, such as a disease state, symptom severity, or treatment response. Both are required for a DHT endpoint to be accepted in a drug or biologics regulatory submission. ISO 13485 design controls (Clause 7.3) and ISO 14971 risk management directly support both validation activities.

What should ISO 13485-certified DHT manufacturers do about this RFI?

DHT manufacturers should review the RFI text at federalregister.gov/documents/2026/03/31/2026-06184, assess whether your organization has a stake in the analytical validation standards, patient-owned device protocols, or continuous data safety monitoring questions, and consider submitting substantive comments before June 1, 2026 to shape future guidance affecting your product category. Begin mapping your existing ISO 13485 design validation records to the DHT endpoint validation framework FDA is developing. Consulting with a regulatory affairs professional who understands both the device and drug trial regulatory frameworks will help you assess your organization's full exposure and opportunity.

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Last updated: April 15, 2026