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:
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.
Craig Lipset Pfizer’s head of clinical innovation
“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.”
Valentina Dilda, PhD Director, Experimental Medicine, CHDI Foundation
“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.”
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:
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:
The Novel Endpoint Acceptance project team will engage in the following actions to support the project objectives:
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:
The second section provides recommendations on practical approaches to developing novel endpoints, including:
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:
|Team Leader||Elektra Papadopoulos||Food and Drug Administration||Novel Endpoint Acceptance|
|Social Science Lead||Brian Perry||Clinical Trials Transformation Initiative||Novel Endpoint Acceptance|
|Team Member||Daniel Rooks||Novartis||Novel Endpoint Acceptance|
|Team Member||Colleen Rouse||Cleveland Clinic Coordinating Center for Clinical Research||Novel Endpoint Acceptance|
|Team Leader||Alicia Staley||Medidata Solutions||Novel Endpoint Acceptance|
|Team Member||Jeffrey Statland||University of Kansas Medical Center||Novel Endpoint Acceptance|
|Team Member||Tom Switzer||Genentech-a member of the Roche Group||Novel Endpoint Acceptance|
|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||Sue Jane Wang||Food and Drug Administration/CDER||Novel Endpoint Acceptance|
|Team Member||Shelly Barnes||UCB||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|
|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 Leader||Rodrigo Garcia||EMD Serono||Novel Endpoint Acceptance|
|Team Member||Cynthia Geoghegan||Individual Patient/Caregiver||Novel Endpoint Acceptance|
|Team Leader||Jörg Goldhahn||ETH Zurich||Novel Endpoint Acceptance|
|Team Member||Martin Ho||Food and Drug Administration||Novel Endpoint Acceptance|
|Project Manager||Lindsay Kehoe||Clinical Trials Transformation Initiative||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||Nirav Sheth||MC10||Novel Endpoints|
|Team Member||Ken Skodacek||Food and Drug Administration||Novel Endpoints|
|Team Member||Komathi Stem||monARC Bionetworks||Novel Endpoints|
|Team Member||Theresa Strong||Foundation for Prader-Willi Research||Novel Endpoints|
|Team Member||Marc Walton||Johnson & Johnson Pharmaceutical Research and Development||Novel Endpoints|
|Project Manager||Jen Goldsack*||Clinical Trials Transformation Initiative||Novel Endpoints|
|Executive Committee Champion||John Alexander||Duke University||Novel Endpoints|
|Social Science Lead||Brian Perry||Clinical Trials Transformation Initiative||Novel Endpoints|
|Project Manager||Lindsay Kehoe||Clinical Trials Transformation Initiative||Novel Endpoints|
|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|