Implementation of the COVID-19 Vulnerability Index Across an International Network of Health Care Data Sets: Collaborative External Validation Study
Authors: Reps Jenna M , Kim Chungsoo , Williams Ross D , Markus Aniek F , Yang Cynthia , Duarte-Salles Talita , Falconer Thomas , Jonnagaddala Jitendra , Williams Andrew , Fernández-Bertolín Sergio , DuVall Scott L , Kostka Kristin , Rao Gowtham , Shoaibi Azza , Ostropolets Anna , Spotnitz Matthew E , Zhang Lin , Casajust Paula , Steyerberg Ewout W , Nyberg Fredrik , Kaas-Hansen Benjamin Skov , Choi Young Hwa , Morales Daniel , Liaw Siaw-Teng , Abrahão Maria Tereza Fernandes , Areia Carlos , Matheny Michael E , Lynch Kristine E , Aragón María , Park Rae Woong , Hripcsak George , Reich Christian G , Suchard Marc A , You Seng Chan , Ryan Patrick B , Prieto-Alhambra Daniel , Rijnbeek Peter R 
Published: February 2021

Background
SARS-CoV-2 is straining health care systems globally. The burden on hospitals during the pandemic could be reduced by implementing prediction models that can discriminate patients who require hospitalization from those who do not. The COVID-19 vulnerability (C-19) index, a model that predicts which patients will be admitted to hospital for treatment of pneumonia or pneumonia proxies, has been developed and proposed as a valuable tool for decision-making during the pandemic. However, the model is at high risk of bias according to the “prediction model risk of bias assessment” criteria, and it has not been externally validated.

Objective
The aim of this study was to externally validate the C-19 index across a range of health care settings to determine how well it broadly predicts hospitalization due to pneumonia in COVID-19 cases.

Methods
We followed the Observational Health Data Sciences and Informatics (OHDSI) framework for external validation to assess the reliability of the C-19 index. We evaluated the model on two different target populations, 41,381 patients who presented with SARS-CoV-2 at an outpatient or emergency department visit and 9,429,285 patients who presented with influenza or related symptoms during an outpatient or emergency department visit, to predict their risk of hospitalization with pneumonia during the following 0-30 days. In total, we validated the model across a network of 14 databases spanning the United States, Europe, Australia, and Asia.

Results
The internal validation performance of the C-19 index had a C statistic of 0.73, and the calibration was not reported by the authors. When we externally validated it by transporting it to SARS-CoV-2 data, the model obtained C statistics of 0.36, 0.53 (0.473-0.584) and 0.56 (0.488-0.636) on Spanish, US, and South Korean data sets, respectively. The calibration was poor, with the model underestimating risk. When validated on 12 data sets containing influenza patients across the OHDSI network, the C statistics ranged between 0.40 and 0.68.

Conclusions
Our results show that the discriminative performance of the C-19 index model is low for influenza cohorts and even worse among patients with COVID-19 in the United States, Spain, and South Korea. These results suggest that C-19 should not be used to aid decision-making during the COVID-19 pandemic. Our findings highlight the importance of performing external validation across a range of settings, especially when a prediction model is being extrapolated to a different population. In the field of prediction, extensive validation is required to create appropriate trust in a model.