Regulatory Pathways for Qualification and Acceptance of Digital Health Technology-Derived Clinical Trial Endpoints: Considerations for Sponsors

Abstract

Despite widespread interest and substantial investment in the adoption of sensor-based digital health technologies (sDHTs) for remote data capture in drug development trials, no drug has been approved based on an sDHT-derived primary endpoint in the United States (US). One reason for this lack of advancement is the complexity of obtaining regulatory endorsement for those endpoints within current US regulatory pathways. The goal of our review is to describe the two choices currently available to pharmaceutical study Sponsors: (i) they may navigate the traditional route of compiling the evidence to support the sDHT-derived endpoint in their investigational new drug (IND) application, requiring specific expertise and substantial resources; or (ii) they may navigate the drug development tool (DDT) pathway with the goal of qualifying their sDHT-derived endpoint as a biomarker or clinical outcome assessment applicable to a broader context of use (COU), either alone or as part of a partnership or consortium. We describe the nuances of each pathway; the evidentiary requirements for supporting an sDHT-derived endpoint and the technology used to capture it; and the impact that an sDHT's regulatory status may have on a Sponsor's decision to use it for data capture. By systematically comparing the IND and DDT pathways, our over-arching goals are to support the increasing deployment of sDHTs within the clinical research setting and help advance regulatory science in the field of digital medicine.

Figure 1

sDHT regulatory categories. *These products may be commercially available, or developed by a Sponsor specifically for the purpose of evaluating the safety and/or effectiveness of their own drug product/s. **These products meet the definition of a Class I medical device but are under enforcement discretion meaning that FDA does not intend to enforce compliance with the premarket review and postmarket regulatory requirements for medical devices. EEG, electroencephalography; FDA, Food and Drug Administration; SaMD, software as a medical device; sDHT, sensor‐based digital health technology.

Figure 2

Key attributes of the DDT qualification and IND regulatory pathways. COU, context of use; DDT, drug development tool; IND, investigational new drug; sDHT, sensor‐based digital health technology.

Figure 3

Key requirements of the sDHT evidentiary package for biomarkers and clinical outcome assessments. COA, clinical outcome assessment; sDHT, sensor‐based digital health technology. Note that the shorter list of items supporting biomarkers compared with COAs should not be interpreted to mean that the evidentiary requirements supporting a biomarker are smaller in scope than the evidentiary requirements supporting a COA.