By incorporating mobile technology into clinical trials, we are able to generate novel endpoints. These novel endpoints may be 1) new endpoints that are not currently used, or 2) existing endpoints that can now be measured in new and possibly better ways using mobile technology. Despite the evolution of mobile technology capable of monitoring and measuring data, it remains uncommon for clinical endpoints generated by such technology to be used in clinical trials.

Preliminary work undertaken by this team identified a pressing need to explore further novel endpoints generated using mobile technology in clinical trials. Until the process for developing these novel endpoints is clarified, the benefits of incorporating mobile technology into clinical trials cannot be fully realized.

While CTTI’s initial Novel Endpoints project provided recommendations and resources to identify, select, and develop novel endpoints resulting from the use of DHTs, there are currently few examples of novel endpoints derived from a DHT to serve as a standard of evidence to support a labeling claim submitted to regulators. To fill this requirement, CTTI started a follow-on project to create recommendations and resources for establishing and using meaningful, DHT-derived novel endpoints for regulatory decision-making.

The Novel Endpoints Project and the Novel Endpoints Acceptance Project.

Describe best practices for developing novel endpoints, generated using mobile technology, for use in clinical trials.

As part of its acceptance project, CTTI will:

• Create a standardized glossary of terms for DHT-derived novel endpoints
• Identify gaps, barriers to, and solutions for using DHT-derived novel endpoints related to functional measures and/or other clinical outcome assessments as the key endpoints in clinical trials for labeling claims
• Describe the evidence used to support DHT-derived novel endpoints in successful regulatory approvals of labeling claims

For the Novel Endpoints work, the use of novel endpoints will improve the clinical meaningfulness of study outcomes.

Results from the Novel Endpoint Acceptance project will increase the use of meaningful, DHT-derived novel endpoints as key endpoints in clinical trials for regulatory decisions.

The Novel Endpoints project used the following methods to support the project objectives: 

• Complile pivotal examples on the development and use of technology to measure novel, objective endpoints in clinical studies
• Conduct a systematic literature review to identify and describe attempts to develop and use technology to measure novel, objective endpoints in clinical studies, for publication
• Write descriptions of the pathways for the development of novel endpoints, generated by mobile technology, for use in clinical trials by writing four use cases
• Use findings from the systematic literature review and use cases to inform recommendations on best practices for developing of novel endpoints, generated by mobile technology for use in clinical trials

The Novel Endpoint Acceptance project team will engage in the following actions to support the project objectives:

• Map existing glossaries and evaluate consistency in terms compared to the FDA-NIH BEST glossary
• Conduct a literature review and landscape assessment to identify case examples of success
• Interview representatives from select case study teams
• Utilize case examples to help enhance FDA COA roadmap with DHT considerations
• Convene multi-stakeholder expert meeting

For Novel Endpoints, CTTI convened a multi-stakeholder expert meeting to draft use cases, each developing a particular novel endpoint. Meeting attendees explored the use of accelerometers to measure treatment benefit in clinical trials of heart failure, Parkinson’s disease, and Duchenne muscular dystrophy, and the use of continuous glucose monitors to measure treatment benefit in clinical trials of diabetes. In addition to the four use cases, a meeting summary is available that highlights themes from these discussions.

A set of recommendations were distilled from the meeting findings and related discussions. The recommendations, which are expected to have short-, medium-, and long-term benefits when applied in clinical trials, are grouped into two main sections. The first, which focuses on optimizing the selection of novel endpoints, identifies the following key recommendations:

1. Patient’s voices must drive the identification of novel endpoints;
2. Select the mobile technology after selecting an outcome assessment; and
3. Use a systematic approach to identify key novel endpoints.

The second section provides recommendations on practical approaches to developing novel endpoints, including:

1. Foster collaboration among key stakeholders;
2. Create technical standards for assessments derived from mobile technology;
3. Engage with regulators; and
4. Include novel endpoints as exploratory endpoints in existing clinical trials and observational studies.

These major recommendations are presented in detail, along with complementary materials that include an interactive tool for choosing among possible novel endpoints for development, a quick reference for interacting with regulatory authorities during the process of novel endpoint development, a summary of required steps in novel endpoint development, a plain-language process summary, and detailed, disease area-specific use cases.

The team has also conducted a systematic review of published clinical studies that have employed novel endpoints. The resulting paper will be posted here following publication.

The Novel Endpoints Acceptance project is expected to yield the following:

• Best practice recommendations on the “standards of evidence” needed to qualify a DHT-derived novel endpoint
• Glossary of terms for digital health endpoints
• Summary of interview results
• Enhanced FDA COA roadmap that incorporates digitally derived endpoint considerations
• Expert meeting summary