Incorporating digitally derived endpoints within clinical development programs by leveraging prior work

Abstract

Digital health technologies (DHTs) enable remote data collection, support a patient-centric approach to drug development, and provide real-time data in real-world settings. With increasing use of DHTs in clinical care and development, we expect a growing body of evidence supporting use of DHTs to capture endpoint data in clinical trials. As the body of evidence grows, it will be critical to ensure that available prior work can be leveraged. We propose a framework to reuse analytical and clinical validation, as well as verification data, generated for existing DHTs. We apply real life case studies to illustrate our proposal aimed at leveraging prior work, while applying the V3 framework (verification, analytical validation, clinical validation) and avoiding duplication. Utilizing our framework will enable stakeholders to share best practices and consistent approaches to employing these tools in clinical studies, build on each other’s work, and ultimately accelerate evidence generation demonstrating the reproducibility and value add of these new tools.

Fig. 1. A strategic approach to incorporating a digital health technology and digitally derived endpoint within a clinical development program.

To demonstrate that the digital health technology (DHT) is fit-for-purpose in regulatory decision making, all of the steps here should be completed, but the order of execution and when they are completed, in terms of drug development phases, may vary. Certain drug development programs may not follow the precise three-phase structure shown here, and some activities shown here may be completed in parallel with one another. In a regulatory context, the concept of interest is the aspect of an individual’s clinical, biological, physical, or functional state, or experience that the assessment is intended to capture (or reflect). Context of Use is a statement that fully and clearly describes the way the medical product development tool is to be used and the regulated product development and review-related purpose of the use. V3 framework refers to a three-stage process of Verifying, analytically Validating, and clinically Validating a Biometric Monitoring Tool (BioMeT) to demonstrate it is fit-for-purpose for gathering data in a clinical trial.

Fig. 2. A Framework for leveraging prior work to demonstrate a digital health technology (DHT) and digitally derived endpoint are fit-for-purpose—an overview.

Prior Work can and should be leveraged in all scenarios where available and appropriate, shading indicates when additional work may or likely will be needed. The light gray shading indicates no additional work is needed. Sponsors can leverage prior work for all aspects of verification, validation, and usability. The medium gray shading indicates additional work may be needed. Sponsors will need to confirm what work can be leveraged, determine if additional work is needed, and perform needed work to support certain activities. The dark gray shading indicates additional work likely is needed. Sponsors will need to generate most data de novo.

Fig. 3. A framework for leveraging prior work to demonstrate a digital health technology (DHT) and digitally derived endpoint is fit-for-purpose—the detail.

Prior Work can and should be leveraged in all scenarios where available and appropriate, shading indicates when additional work may or likely will be needed. The light gray shading indicates no additional work is needed. The medium gray shading indicates additional work may be needed. The dark gray shading indicates additional work likely is needed.

Fig. 4. A framework for leveraging prior work to demonstrate a digital health technology (DHT) and digitally derived endpoint is fit-for-purpose—case study in remote monitoring sleep parameter in home setting.

Prior Work can and should be leveraged in all scenarios where available and appropriate, shading indicates when additional work may or likely will be needed. The light gray shading indicates no additional work is needed. The medium gray shading indicates additional work may be needed. The dark gray shading indicates additional work likely is needed.