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To learn more about Triangle CERSI, join our mailing list for future communications.

To learn more about Triangle CERSI, join our mailing list for future communications.

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Triangle 002: Utilizing the UNC Clinical Data Warehouse for Assessing Efficacy, Toxicity, and Dose-Response Relationships of Molecularly Targeted Therapies in Real-World Patients

Research

Utilizing the UNC Clinical Data Warehouse for Assessing Efficacy, Toxicity, and Dose-Response Relationships of Molecularly Targeted Therapies in Real-World Patients

CERSI P.I.s and Collaborators
Yanguang (Carter) Cao, PhD (UNC); Benyam Muluneh, PharmD (UNC)

FDA SMEs and Collaborators
Mirat Shah, MD; Elizabeth Duke, MD; Jonathon Vellejo, PhD; Kun Wang, PhD; Lori Ehrlich, MD, PhD; Donna Rivera PharmD, MS

The doses and schedules for molecularly targeted therapies are often not well-characterized prior to initiating trials with registrational intent for marketing approval. This can lead to the selection of dosages that have increased toxicity without additional efficacy. 

Therapies may be poorly tolerated at approved dosages, leading patients or providers to prematurely modify the dosage or discontinue an otherwise efficacious treatment. FDA launched 'Project Optimus' to emphasize the need for dosage optimization prior to drug approval. An understanding of how the toxicities and dosage modifications for approved targeted therapies affect outcomes for patients in the real world setting will enhance Project Optimus efforts, in collaboration with the Oncology Real World Evidence program, to advance potential patient-centric uses of real-world data. To bridge this knowledge gap, we will investigate the prevalence of dosage modifications in patients and the resulting safety and effectiveness profiles of targeted therapies commonly prescribed for patients with Chronic Lymphocytic Leukemia (CLL) and Chronic Myeloid Leukemia (CML). 

We will primarily use real-world data (RWD) sourced from the Clinical Data Warehouse at the University of North Carolina at Chapel Hill to address three key questions. Firstly, we will assess the frequency of dosage modifications in patients in the real-world setting using pharmacy refill records and electronic medical record information. Secondly, we will aim to determine whether modifications in treatment doses, made in response to tolerability, have any negative impact on clinical outcomes including survival. Lastly, we will explore whether the toxicity associated with treatment directly affects clinical outcomes including survival among patients in the real-world setting. 

We will primarily utilize the clinical data warehouse at UNC Health Care System for this project, and we are also considering other sources of real-world data, such as medical claims data and randomized clinical trials, where appropriate to support the analyses. Recognizing the potential challenges and biases that can be associated with RWD studies, we will harness the capabilities of statistical modeling and advanced data mining and causal inference approaches to explore methodological approaches to provide valid answers to these questions.

How does this project fit into the FDA's Regulatory Science Framework?

This projects aims to modernize development and evaluation of FDA-regulated products using methods to assess real-world data to serve as real-world evidence, strengthening post-market surveillance and labeling of FDA regulated products, and supporting regulatory decision-making.

PI profile: Dr. Yanguang Cao

Learn how Triangle CERSI's Dr. Yanguang Cao is making an impact through regulatory science.