Digital health tech in clinical investigations: FDA issues draft guidance

Regulatory NewsRegulatory News | 05 January 2022 |  By 

The US Food and Drug Administration, as part of an end-of-year spate of guidance documents, has issued a draft guidance for sponsors who wish to use digital tech to aid in remote clinical data acquisition.
Digital health technologies (DHTs) stand to benefit clinical investigations in a multitude of ways, but regulatory considerations have to be weighed as the technologies are employed, noted the agency in setting out the background for the draft guidance, issued in late December 2021.
“Advances in sensor technology, general-purpose computing platforms, and methods for data transmission and storage have revolutionized the ability to remotely obtain and analyze clinically relevant information from individuals,” wrote FDA.

Not only does the use of DHT offer the opportunity to collect data on a near-continuous basis, but remote data collection may also be less burdensome when travel to clinical trial sites is difficult. Also, DHTs can allow direct recording of data from individuals such as infants and some people with cognitive impairment who otherwise could not provide direct report of their clinical experience.
The DHTs encompassed in the guidance include systems that make use of computing platforms together with sensors and/or software that are connected to the platform and used for health-related purposes. Some of the types of data that can be acquired remotely include blood glucose, blood sugar, and physical activity. These data, in turn, can be run through algorithms that “translate these data into clinical events or characteristics that may be of interest,” such as hypo- or hyper-glycemic events, according to FDA. DHTs can be made up of hardware and its accompanying software, as with the continuous glucose monitors that use software algorithms.
Although DHTs might meet the definition of a medical device, most regulatory requirements for devices will not apply to DHTs used in clinical investigations, so long as the investigation is compliant with 21 CFR part 812. Sponsors should notify FDA early in the clinical investigation program about their intent to incorporate DHTs into clinical investigations.
Alternatively, sponsors may choose to qualify a DHT as a drug or medical device development tool, “for a specific context of use,” through a number of avenues available through FDA’s Centers.
The draft guidance lays out considerations in selecting a fit-for-purpose DHT for a clinical investigation, including the population to be investigated and DHT design and operation, including power needs, operational specifications, and environmental, security and privacy factors. Sponsors should also consider whether using patient-owned DHTs or computers may be a feasible option in some investigations; the draft guidance lays out safety and accuracy guardrails if sponsors decide on this approach.
The submission should include an explanation of how a DHT is fit for purpose, and basic information about the technology — manufacturer technical specifications may suffice, notes FDA. Sponsors should also include information about usability and the investigation’s DHT data integrity plan.
Verification and validation of the selected DHT will ensure that the technology is fit for the purposes of the clinical investigation, writes FDA in the draft guidance. Benchtop studies are a good starting point, but the studies “should include demonstration that the clinical event or characteristic to be assessed (e.g., step count or heart rate) is consistently and appropriately measured in the population of interest,” cautions the agency.
However, sponsors may be able to make use of verification and validation data already gathered by manufacturers or other users or vendors of DHTs. The draft guidance provides specific examples of verification and validation steps for sensor-based DHTs, DHT software, and general-purpose computing platforms, going into some detail for sensors. Here, validation may include such steps as comparing the precision and accuracy of a step counter worn on the waist versus the hip, calibration for stride length, and comparison with a validated reference means of measurement.
“Usability studies are a critical component in confirming the suitability of the DHT and/or general purpose computing platform for the proposed clinical investigation,” writes FDA in the draft guidance, which provides specific considerations for usability of DHTs in a clinical investigation.
Submissions should also describe which clinical endpoints will be collected from a DHT; if a novel endpoint is proposed, sponsors should provide additional information about how the endpoint relates to other well-established endpoints and should describe reliability of the proposed endpoint.
The submission’s statistical analysis plan should incorporate analysis of DHT data, addressing how missing or erroneous data will be handled, as well as defining and prespecifying endpoints and per-participant source data.
The draft guidance includes a section on risk considerations, covering clinical risks, including the risk of direct injury from the DHT and the risk of erroneous data; cybersecurity and privacy risks; and informed consent considerations unique to DHTs.
Data from DHTs – “including all relevant associated metadata” – must be stored and transferred securely and handled as other trial-generated electronic data would be. Sponsors should include their plan for DHT data and metadata collection, transfer and storage in the submission.
An “other considerations” section at the end of the draft guidance includes such items as the potential for electronic interference between devices, the need for adequate participant training, and the necessity of having a safety monitoring plan that addresses what will happen if DHTs register abnormal readings during the investigation.
A glossary and two appendices accompany the draft guidance; one appendix gives concrete examples of how DHTs might be used in clinical investigations, while the second walks sponsors through an example of how a DHT would be selected for a hypothetical clinical investigation.


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