Reply to the Comment: Research Design Concerns in a TriNetX Analysis of Venous Thromboembolism in Pediatric Cystic Fibrosis Patients

Thank you for the opportunity to reply to the correspondence from Drs Lee and Wang.[ 1 ] We thank the authors for their interest in our recent article.[ 2 ] We appreciate this opportunity to promote scientific discourse and critically appraise research methodologies. Defining patient age In our investigation, we included patients aged 21 years or younger at the time of query who had an encounter with the ICD-10-CM code for cystic fibrosis (CF) between January 1, 2010, and January 1, 2020. We agree that, in some instances, selecting patients based on their age at disease diagnosis is preferable to using their current age at the time of the study. Using age at diagnosis can ensure that historical patients are included in the cohort. However, given the rapid evolution that has occurred in the fields of both pediatric venous thromboembolism (VTE) and CF over the past decade regarding both preventative and therapeutic strategies, an alternative approach of selecting patients by their current age at the time of conducting the analysis is not only reasonable, but also affords the most up-to-date findings. Specifically, we would like to highlight that while CF is a congenital disease, universal neonatal screening was not recommended by the Centers for Disease Control and Prevention until 2004, despite the discovery of the immunoreactive trypsin (IRT) neonatal screening test in 1979.[ 3 ] [ 4 ] Universal screening increased from 7 states in 2003 to all 50 states by 2010.[ 5 ] [ 6 ] Universal screening based on IRT led to a younger age of diagnosis and improved nutritional outcomes in patients with CF.[ 7 ] Furthermore, despite the discovery of the CFTR gene in 1989, the Food and Drug Administration approval of the first CFTR modulator was only recently attained in 2012.[ 8 ] Early diagnosis, specialized multidisciplinary care centers, aggressive nutritional management, advanced antibiotic therapies, and the development of CFTR modulators have collectively improved patient outcomes, quality of life, and life expectancy in the last three decades.[ 8 ] Yet, a longer life with CF could also lead to the possibility of increased risks of complications such as VTE. In our study, using the age-at-event (age at diagnosis) filter would include a patient with CF (pwCF) who was born in 1990 and had a hospital visit in 2010 at age 20. This patient may not have received early diagnosis and specialized multidisciplinary CF care as would a patient born in 2000. This partly explains the higher mean age at CF diagnosis in the authors' correspondence when historical patients were included using an age-at-event filter (mean [range]: 8.5 years [0–21]), compared with when a current-age filter was used (mean [range]: 3.7 years [0–15]). Publication History Article published online: 10 March 2026 © 2026. Thieme. All rights reserved. Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA