The American Society of Clinical Oncology (ASCO) Annual Meeting (June 4-8), one of the largest scientific gatherings in cancer research, will feature several abstracts related to Project Data Sphere® research programs on External Control Arms and Immune-related Adverse Events.
External Control Arms
Of the 4,600 posters at ASCO this year, an emerging trend (more than 350 posters) is the use of real world data (RWD) and real world evidence (RWE). A landscape analysis by the FDA’s Donna Rivera and Paul Kluetz describes some of the more than 140 scenarios where RWD was presented in regulatory submissions over the past decade. (Abstract #18787: https://meetinglibrary.asco.org/record/199567/abstract)
One prominent use of RWD is as an external control or comparator arm to support claims of effectiveness where overall survival and response rate are used as primary outcomes. The primary conclusion from their analysis is the need to establish “metrics for robust data characterization and outcome validation” so that “RWD can be appropriately evaluated and provide the rigor necessary to be considered adequate RWE.”
Project Data Sphere’s External Control Arm program directly focuses on these two issues. Instead of using clinical data extracted from electronic health records, the PDS program is building external control populations from completed clinical trials and purpose-built registries. These data assets have quality components built in with clinical assessments and data entry performed under stringent protocols. We believe that this well-defined data environment will more rapidly clarify how external data assets should be developed and qualified for regulatory decision making.
Well-constructed, high quality external control arms can inform decision making throughout clinical development beginning well before regulatory engagement and be incorporated in complex innovative trial designs to: support a smaller control arm through hybrid approaches, accelerate interim analyses, and help optimize patient allocation in adaptive platform trials. [https://pubmed.ncbi.nlm.nih.gov/31155679/, https://pubmed.ncbi.nlm.nih.gov/31175098/]
PDS collaborators from Dana-Farber are presenting some of the initial findings from the GBM-INSIGhT trial, an adaptive platform trial in newly diagnosed glioblastoma.
- Abstract #2006: https://meetinglibrary.asco.org/record/195931/abstract
- Abstract #2014: https://meetinglibrary.asco.org/record/196561/abstract
Thirteen additional abstracts at the 2021 ASCO Annual Meeting demonstrate various uses of external control arms.
In addition, patient-level data from completed clinical trials made available through the data.projectdatasphere.org portal was used in at least three posters. These studies applied deep learning to these patient-level data assets to identify candidate predictors of outcome, phenotypes of super-responders to specific therapies, and illustrate the risk of introducing bias through patient censoring.
- Abstract #1549: https://meetinglibrary.asco.org/record/200166/abstract
- Abstract #1548: https://meetinglibrary.asco.org/record/200113/abstract
- Abstract #e13543: https://meetinglibrary.asco.org/record/200201/abstract
As more cancer patients are treated with immunotherapy, benefits have been observed as well as an increase in patients experiencing neurotoxicity. There is an urgent need to understand how and why these neurologic irAEs occur, and how to best manage them.
Comprehensive knowledge of neurologic irAEs is limited and treatment guidelines are based on consensus, not evidence.
PDS irAE Task Force Co-Chairs from Massachusetts General Hospital -- Dr. Amanda Guidon and Dr. Kerry Reynolds -- as well as PDS are among the authors of an abstract on consensus definitions that were achieved for seven core disorders. The authors believe the definitions now can be used broadly across clinical and research settings.
- Abstract #2647: https://meetinglibrary.asco.org/record/196134/abstract