Скачать или смотреть ASA BIOP Webinar: Cardiovascular Adverse Events in Oncology Trials

Cardiovascular Adverse Events in Oncology Trials: Understanding and Appreciating the Differences Between Clinical Trial Data and Real-World Reports

Jay Herson, PhD
Department of Biostatistics
Johns Hopkins Bloomberg School of Public Health
Baltimore, MD USA

Michael S. Ewer, MD, JD, PhD
Department of Cardiology, The University of Texas MD Anderson Cancer Center,
Houston, TX USA

Abstract
The oncology literature reports safety results from oncology randomized clinical trials [RCT]. However, reports are now appearing in the post market with adverse event estimates derived from sporadic report databases and insurance claims data. The cardiovascular adverse event rates for different therapies often vary between RCT data and this example of real-world data [RWD]. Rather than declare RCT estimates as gold standard and dismiss RWD we collaborated to study the origins, purpose, processing of each to discern some of the drivers of variation. We see RWD as the natural progression of the controlled and narrow populations seen in RCTs to broader patient populations found in RWD. The RWD were collected as part of an insurance claim or regulatory agency sporadic report. The RCT data were collected earlier under strict research requirements in order to obtain regulatory approval for new cancer therapies. We will present a taxonomy of cardiovascular adverse events, present the strengths and weaknesses of RCT and RWD in characterizing the frequency of cardio AEs. We consider methods that attempt to transform RWD, so they are more comparable to RCT data, as well as disproportionality analysis, methods of record linkage, natural language processing, new software to transform claims data to the format of electronic health records [EHR], machine learning and further analytic challenges of RWD as trialists specify new estimands. Utilization of RCT and RWD must respect the analytic needs of clinicians, biostatisticians, patients and regulators. In post market this entails consideration of both sources of data to guide clinical decisions while mindful of the distinctions.

JAY HERSON received the PhD in Biostatistics from Johns Hopkins. He has had a long career in oncology clinical trials which included faculty appointment at the University of Texas M.D. Anderson Cancer Center and, eventually, his own CRO, Applied Logic Associates, which became part of Westat in 2001. His primary interest is statistical applications in drug safety and is author of Data and Safety Monitoring Committees in Clinical Trials. Jay has served as Senior Associate in Biostatistics at the Johns Hopkins Bloomberg School of Public Health since 2004.

MICHAEL S. EWER received the M.D. from University of Basel, J.D. from University of Houston and PhD in Public Health from the University of Texas School of Public Health at Houston. Joining the M.D. Anderson Cancer Center faculty as a cardiologist in 1978 he pioneered in the study of cardiovascular adverse events in cancer treatments and is still a thought leader. Michael also teaches the health law course at the University of Houston Law Center.

Houston has been an important part of the co-authors’ careers but, as Jay will explain, they did not meet there.