The proportion of COVID-19 infections missed by the Innova lateral flow test (LFT) are “substantial enough to be of clinical importance” according to an analysis published in The BMJ.
The study by Professor Jonathan Deeks and colleagues used empirical data from three UK test settings to show that previous models underpinning government policy overestimate the efficacy of LFTs, particularly in people with no symptoms.
"Claims that LFTs can identify 'the vast majority who are infectious' are likely overstated," say the authors, and risk "providing false reassurance to those seeking to rule out infection".
"Using an analysis linking six sources of empirical evidence, we have shown that the current Innova LFT is predicted to miss substantial proportions of infectious individuals."
In an opinion piece accompanying the article, Dr Angela Raffle and Dr Mike Gill, former regional director of public health, go further: "The clear implication is that any positive impact from the detection of asymptomatic people may be outweighed by the effects of infectious people being falsely reassured and therefore mixing with others, perhaps even ignoring their symptoms."
Professor Deeks and colleagues acknowledge that LFTs remain an important tool in managing the COVID-19 pandemic. The tests are convenient, relatively cheap, and provide results quickly, which limits delays to self-isolation, something that is known to reduce transmission. But they emphasise that "clinicians and policy makers must be aware of the limitations".
"Until new generation LFTs are available that meet the regulatory performance requirements, negative test results from LFTs cannot be relied on to exclude current infection."
Real World Test Settings
The UK has spent more than £7 billion on lateral flow devices since mid-2020, but empirical evidence for the efficacy of screening for SARs-CoV-2 remains lacking.
The widespread use of LFTs for detecting infection has been recommended based on the predictions of largely mathematical models. However, these models make key assumptions about the viral loads required to transmit disease and subsequently the sensitivity needed for LFTs to detect infectious disease.
The new analysis seeks to check these predictions using data from three real world test settings: symptomatic testing at an NHS Test-and-Trace centre, mass testing of asymptomatic residents in Liverpool, and screening of asymptomatic students at the University of Birmingham.
A linked data analysis was used to identify the joint probability that people were infectious (with a positive viral culture or as a secondary case) but would test negative on Innova.
The study estimates for the number of positive cases missed by testing were much higher than those derived from the key mathematical models used previously to inform policy decisions in the UK.
The study predicts that Innova LFTs would miss 20% of positive cases in people attending an NHS Test-and Trace centre, 29% of cases in people without symptoms attending municipal mass testing, and 81% of cases in people without symptoms attending university screen testing.
In comparison, both of the mathematical models analysed in the study estimated much lower numbers of missed infections (8%, 10%, and 32% in these settings in one of the models).
Viral Loads and Asymptomatic Screening
The percentage of positive cases that were missed varied between settings because of different viral load distributions. The analysis showed that people were most at risk of having false negative LFT results when viral loads were lower.
This is significant because current UK recommendations encourage use of LFTs as a screening tool in people without symptoms, who are likely to have lower viral loads even in the event of infection.
In the opinion piece accompanying the analysis, Dr Raffle and Dr Gill point out: "Both the Innova (Biotime) test and the more recently issued Flowflex test are being used outside of their original manufacturers’ recommendations. Neither test has been thoroughly evaluated for self-testing or for use in asymptomatic people."
Dr Gill explained to Medscape UK: "The analysis confirms the real possibility that at least some of the rapid antigen tests in widespread use are just not fit for some of the purposes to which they’ve been put, a possibility already pointed to by our growing experience of their inadequacies in everyday use."
"It should occasion a serious reassessment by the MHRA of the rational basis for its exceptional use authorisations, specifically of rapid antigen tests in asymptomatic people who are not known contacts of a case."
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