Program: Digital Health Trials

About This Program

Project:

Novel Endpoints

overview icon Overview

Developing and Qualifying Novel Endpoints

 

Best practices for identifying, selecting, and developing novel endpoints from technologies have been lacking – until now. CTTI has clarified a pathway for developing novel endpoints from digital health technologies (DHTs) and created recommendations for terminology, data collection, and reporting. Stakeholders can use these resources to develop novel endpoints that:

 

  • Convey an objective and more accurate representation of the patient experience than traditional endpoints. 
  • Are potentially meaningful to a broader range of stakeholders, including patients and providers
  • May help identify unmet patient needs
  • Can be used as exploratory endpoints in existing interventional clinical trials & observational cohort studies

CTTI is also currently working to create additional recommendations and resources to drive the practical use of novel, digitally derived, functional outcomes as key clinical trial endpoints that can support regulatory labeling claims – further helping to unlock the opportunities provided by DHTs.

quick links icon Quick Links to Top Deliverables

Discover Additional Deliverables Generated From This Project

Digital Biomarkers

Use of Mobile Devices to Measure Outcomes in Clinical Research, 2010–2016: A Systematic Literature Review, published in Digital Biomarkers

Webinar

Official Unveiling of Recommendations on Developing Novel Endpoints Generated by Mobile Technology for Use in Clinical Trials

PowerPoint Slide of Positive Impacts

Download the .pptx slide of “Positive Impacts of Developing Novel Endpoints for Use in Clinical Trials” to use in your presentations. (Note: The Positive Impacts are also included in the first page of the Recommendations above.)

Poster

Developing Novel Endpoints, Generated using Mobile Technology, for use in Clinical Trials: A Clinical Trials Transformation Initiative (CTTI) Project (Presented at SCT 2017 on May 8)

Expert Meeting Materials

Click to view materials, including presentations & summary, for the CTTI-hosted expert meeting, Developing Novel Endpoints Generated by Mobile Technology for Use in Clinical Trials

“By engaging with experts who have been early champions of mobile technology in trials and combining that with patient insights, CTTI has created practical recommendations and action-oriented tools that have the potential to really accelerate the use of mobile technology in clinical trials. In particular, the use cases provide a realistic pathway for incorporating novel endpoints through technology into clinical development programs. CTTI’s recommendations show we may be closer than previously believed to realizing the benefits of these novel endpoints, creating a sense of urgency to act.”

Craig Lipset Pfizer’s head of clinical innovation

“As we embark on a two-phase effort to develop a digital battery for use in Huntington Disease trials, we plan to use CTTI’s MCT Novel Endpoints recommendations to guide our work. In doing so, we feel strongly that we can reach our goal more quickly and more efficiently—ultimately, and most importantly, benefiting patients.”

Valentina Dilda, PhD Director, Experimental Medicine, CHDI Foundation

in detail icon In Detail

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

Project Team Members

Rolesort descending Name Affiliation Project
Executive Committee Champion John Alexander Duke University Novel Endpoints
Project Manager Lindsay Kehoe Clinical Trials Transformation Initiative Novel Endpoint Acceptance
Project Manager Jen Goldsack* Clinical Trials Transformation Initiative Novel Endpoints
Project Manager Lindsay Kehoe Clinical Trials Transformation Initiative Novel Endpoints
Social Science Lead Brian Perry Clinical Trials Transformation Initiative Novel Endpoint Acceptance
Social Science Lead Brian Perry Clinical Trials Transformation Initiative Novel Endpoints
Team Leader Rodrigo Garcia EMD Serono Novel Endpoint Acceptance
Team Leader Jörg Goldhahn ETH Zurich Novel Endpoint Acceptance
Team Leader Lauren Bataille The Michael J Fox Foundation for Parkinson's Research Novel Endpoints
Team Leader Rob DiCicco GlaxoSmithKline Novel Endpoints
Team Leader Cheryl Grandinetti Food and Drug Administration Novel Endpoints
Team Leader Will Herrington University of Oxford, CTSU Novel Endpoints
Team Leader Martin Landray University of Oxford, CTSU Novel Endpoints
Team Leader Kaveeta Vasisht Food and Drug Administration Novel Endpoints
Team Leader Elektra Papadopoulos Food and Drug Administration Novel Endpoint Acceptance
Team Leader Alicia Staley Medidata Solutions Novel Endpoint Acceptance
Team Member Sonja Cloosterman Orikami Novel Endpoint Acceptance
Team Member Andy Coravos Elektra Labs Novel Endpoint Acceptance
Team Member Matthew Diamond Food and Drug Administration Novel Endpoint Acceptance
Team Member Megan Doyle Amgen Inc Novel Endpoint Acceptance
Team Member Katy Eichinger University of Rochester Novel Endpoint Acceptance
Team Member Beatrix Friedeberg Amgen Inc Novel Endpoint Acceptance
Team Member Cynthia Geoghegan Individual Patient/Caregiver Novel Endpoint Acceptance
Team Member Martin Ho Food and Drug Administration Novel Endpoint Acceptance
Team Member Elizabeth Kunkoski Food and Drug Administration Novel Endpoint Acceptance
Team Member Kai Langel Johnson & Johnson/Janssen Novel Endpoint Acceptance
Team Member Adria Martig* Parkinson's Foundation Novel Endpoint Acceptance
Team Member Ingrid Oakley-Girvan Medable Novel Endpoint Acceptance
Team Member Lauren Oliva Biogen Novel Endpoint Acceptance
Team Member Ashish Narayan Feinstein Institute for Medical Research Novel Endpoints
Team Member Elektra Papodopoulos Food and Drug Administration Novel Endpoints
Team Member Daniel Rooks Novartis Novel Endpoint Acceptance
Team Member Nirav Sheth MC10 Novel Endpoints
Team Member Colleen Rouse Cleveland Clinic Coordinating Center for Clinical Research Novel Endpoint Acceptance
Team Member Ken Skodacek Food and Drug Administration Novel Endpoints
Team Member Komathi Stem monARC Bionetworks Novel Endpoints
Team Member Jeffrey Statland University of Kansas Medical Center Novel Endpoint Acceptance
Team Member Theresa Strong Foundation for Prader-Willi Research Novel Endpoints
Team Member Tom Switzer Genentech-a member of the Roche Group Novel Endpoint Acceptance
Team Member Marc Walton Johnson & Johnson Pharmaceutical Research and Development Novel Endpoints
Team Member Jeremy Wyatt ActiGraph Novel Endpoint Acceptance
Team Member Xinzhi Zhang National Institutes of Health Novel Endpoint Acceptance
Team Member Andrew Potter Food and Drug Administration Novel Endpoint Acceptance
Team Member Maria Ali The George Institute for Global Health Novel Endpoint Acceptance
Team Member Steven Berman Food and Drug Administration Novel Endpoint Acceptance
Team Member Joy Bhosai Duke University Novel Endpoint Acceptance
Team Member Emily Cerciello Crohn's & Colitis Foundation Novel Endpoint Acceptance
Team Member Timothy Chen Medidata Solutions Novel Endpoint Acceptance