Clinical Epidemiology (Oct 2022)
Oncology Drug Effectiveness from Electronic Health Record Data Calibrated Against RCT Evidence: The PARSIFAL Trial Emulation
Abstract
David Merola,1,2 Jessica Young,2,3 Deborah Schrag,4 Kueiyu Joshua Lin,1,2,5 Nicholas Robert,6 Sebastian Schneeweiss1,2 1Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 2Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA; 3Department of Population Medicine, Harvard Medical School & Harvard Pilgrim Healthcare Institute, Boston, MA, USA; 4Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical School New York, New York, NY, USA; 5Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 6Ontada, Irving, TX, USACorrespondence: David Merola, Email [email protected]: The use of electronic health records (EHR) data to assess drug effectiveness in clinical oncology practice is of great interest to regulators, clinicians, and payers. However, the utility of EHR data in clinical effectiveness studies may be limited by missing data, unmeasured confounding, and imperfect outcome surveillance. This study sought to emulate and compare the results of a randomized controlled trial investigating the efficacy of palbociclib with fulvestrant vs letrozole in advanced breast cancer.Methods: This was a cohort study using longitudinal EHR data derived from outpatient oncology practices in the United States. Eligibility criteria from the PARSIFAL trial were emulated as closely as possible. Patients were included if they had hormone-positive, human epidermal growth factor receptor – 2 (HER-2) negative metastatic breast cancer and had no record of prior treatment for metastatic disease. Patients initiating first-line treatment with palbociclib and fulvestrant following their first record of metastasis were compared to those initiating palbociclib and letrozole on the same day. Treatments were ascertained by oncology medication ordering records in the data source. The primary outcome was death as recorded in the oncologists’ EHR systems.Results: There were 1886 eligible women in the study cohort. Although the 3-year survival was meaningfully lower in clinical practice (59%) compared to the randomized trial (78%), the relative effect size was a hazard ratio (HR) of 1.07 (95% CI: 0.86– 1.35), similar to the randomized trial (HR = 1.00; 95% CI: 0.68– 1.48).Conclusion: Despite common challenges encountered in EHR-based studies, it is possible to achieve similar conclusions to emulated randomized trials with the application of analytic approaches that address missing data, confounding, and selection bias. This is a promising finding in light of other emulations and ongoing efforts to improve data from clinical practice and causal analytics.Keywords: real-world evidence, comparative effectiveness research, oncology, pharmacoepidemiology, healthcare databases
