Accuracy of package inserts of SARS-CoV-2 rapid antigen tests: a secondary analysis of manufacturer versus systematic review data.

BACKGROUND

Rapid antigen tests (RATs) were crucial during the COVID-19 pandemic. Information provided by the test manufacturer in product package inserts, also known as instructions for use (IFUs), is often the only data available to clinicians, public health professionals, and individuals on the diagnostic accuracy of these tests. We aimed to assess whether manufacturer IFU accuracy data aligned with evidence from independent research.

METHODS

We searched company websites for package inserts for RATs that were included in the July 2022 update of the Cochrane meta-analysis of SARS-CoV-2 RATs, which served as a benchmark for research evidence. We fitted bivariate hierarchical models to obtain absolute differences in sensitivity and specificity between IFU and Cochrane Review estimates for each test, as well as overall combined differences.

FINDINGS

We found 22 (100%) of 22 IFUs of the RATs included in the Cochrane Review. IFUs for 12 (55%) of 22 RATs reported statistically significantly higher sensitivity estimates than the Cochrane Review, and none reported lower estimates. The mean difference between IFU and Cochrane Review sensitivity estimates across tests was 12·0% (95% CI 7·5-16·6). IFUs in three (14%) of 22 diagnostic tests had significantly higher specificity estimates than the Cochrane Review and two (9%) of 22 had lower estimates. The mean difference between IFU and Cochrane Review specificity estimates across tests was 0·3% (95% CI 0·1-0·5). If 100 people with SARS-CoV-2 infection were tested with each of the tests in this study, on average 12 fewer people would be correctly diagnosed than is suggested by the package inserts.

INTERPRETATION

Health professionals and the public should be aware that package inserts for SARS-CoV-2 RATs might provide an overly optimistic picture of the sensitivity of a test. Regulatory bodies should strengthen their requirements for the reporting of diagnostic accuracy data in package inserts and policy makers should demand independent validation data for decision making.

FUNDING

None.

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests JB has received consulting fees from the New Diagnostics Working Group of the Stop TB Partnership. SB, JD, and JJD are supported by the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre. This Article presents independent research supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham National Health Services (NHS) Foundation Trust and the University of Birmingham. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. CMD has received research grants from the US National Institutes of Health, German Ministry of Education and Research, German Alliance for Global Health Research, United States Agency for International Development, FIND, German Center for Infection Research, UNAIDS, WHO, and Roche. CMD also declares a payment from Roche Diagnostics that she accepted as German law requires a manufacturer to pay for the use of data for regulatory purposes. Data was generated as part of an independent evaluation by CMD and team. CMD is an academic editor of PLoS Medicine and sits on the WHO technical advisory group on tuberculosis diagnostics. MP holds a Canada Research Chair Award from the Canadian Institutes of Health Research and serves as an adviser to the following non-profit agencies in global health: Bill & Melinda Gates Foundation; Foundation for Innovative New Diagnostics, WHO, and Stop TB Partnership. All other authors declare no competing interests.