Creation of an ustekinumab external control arm for Crohn's disease using electronic health records data: A pilot study.

BACKGROUND: Randomized trials are the gold-standard for clinical evidence generation, but they can sometimes be limited by infeasibility and unclear generalizability to real-world practice. External control arm (ECA) studies may help address this evidence gaps by constructing retrospective cohorts that closely emulate prospective ones. Experience in constructing these outside the context of rare diseases or cancer is limited. We piloted an approach for developing an ECA in Crohn's disease using electronic health records (EHR) data. METHODS: We queried EHR databases and manually screened records at the University of California, San Francisco to identify patients meeting the eligibility criteria of TRIDENT, a recently completed interventional trial involving an ustekinumab reference arm. We defined timepoints to balance missing data and bias. We compared imputation models by their impacts on cohort membership and outcomes. We assessed the accuracy of algorithmic data curation against manual review. Lastly, we assessed disease activity following treatment with ustekinumab. RESULTS: Screening identified 183 patients. 30% of the cohort had missing baseline data. Nonetheless, cohort membership and outcomes were robust to the method of imputation. Algorithms for ascertaining non-symptom-based elements of disease activity using structured data were accurate against manual review. The cohort consisted of 56 patients, exceeding planned enrollment in TRIDENT. 34% of the cohort was in steroid-free remission at week 24. CONCLUSION: We piloted an approach for creating an ECA in Crohn's disease from EHR data by using a combination of informatics and manual methods. However, our study reveals significant missing data when standard-of-care clinical data are repurposed. More work will be needed to improve the alignment of trial design with typical patterns of clinical practice, and thereby enable a future of more robust ECAs in chronic diseases like Crohn's disease.

Rapid testing for coronavirus disease 2019 (COVID-19).

Rapid testing, generally refers to the paper-based diagnostic platform known as "lateral flow assay" (LFA), has emerged as a critical asset to the containment of coronavirus disease 2019 (COVID-19) around the world. LFA technology stands out amongst peer platforms due to its cost-effective design, user-friendly interface, and low sample-to-readout times. This article aims to introduce its design, use, and practicality for the purpose of diagnosing SARS-CoV-2 infection. A connection is made from the normal COVID-19 immune response to the design and efficacy of rapid testing. Interference in test results is a challenge shared by most diagnostic platforms and can be rooted in various underlying issues. The current knowledge and situation about interference in rapid COVID-19 tests due to variant strains as well as vaccination are discussed. The cost and societal impact are reviewed as they play important roles in determining how to properly implement public testing practices. Perspectives on improving the performance, especially detection sensitivity, of LFA for COVID-19 are provided.