{"id":49314,"date":"2021-01-12T21:45:02","date_gmt":"2021-01-12T20:45:02","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=49314"},"modified":"2021-01-12T18:46:06","modified_gmt":"2021-01-12T17:46:06","slug":"covid-19-innova-testing-in-schools-dont-just-test-evaluate","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2021\/01\/12\/covid-19-innova-testing-in-schools-dont-just-test-evaluate\/","title":{"rendered":"Covid-19 INNOVA testing in schools: don\u2019t just test, evaluate"},"content":{"rendered":"<p class=\"standfirst\"><span style=\"font-weight: 400\">Using testing to manage classroom outbreaks, without isolating close contacts, risks increasing disease spread, say these authors<\/span><\/p>\n<p><!--more--><\/p>\n<p><span style=\"font-weight: 400\">Everybody wants schools to reopen when it is safe to do so, but for pupils, teachers, and their communities to remain safe they must stay close to covid free. Last term, schools limited pupil mixing and activities, and isolated pupil groups at home once a covid-19 case was identified, although many struggled with the lack of clear guidance. This term the government is planning to rely on INNOVA rapid lateral flow tests to mass screen staff and pupils, and serial test close school-contacts of covid cases. [1]\u00a0\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">The proposed strategies were announced to schools on the last day of term before the Christmas break, providing no time for schools to scrutinise and discuss their scientific basis, or to organise how the lateral flow test policy will be delivered. Lockdown now provides an opportunity to do this, albeit some schools have already started using tests in keyworkers\u2019 children who continue to attend.\u00a0\u00a0\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">There are two different components to the government\u2019s testing plan. The first, mass testing of staff and pupils on return and twice weekly thereafter, aims to detect individuals who have asymptomatic or pre-symptomatic infection. Using the test to identify infected individuals who successfully isolate and prevent onward transmission is a clearly good outcome. However, there are three questions to ask: first, whether other testing strategies could produce better outcomes; second, could the same or fewer resources be more effectively used in other ways to contain infection; and third, whether there are likely to be unintended consequences of testing which could counter any benefit.\u00a0\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Scientists have particular concerns that negative INNOVA results are too inaccurate to rule out covid. The Medicines and Healthcare products Regulatory Agency (MHRA) authorisation for INNOVA excludes using negative results to \u201cenable activity\u201d [2], and the Chief Medical Officer [3], World Health Organization [4], Royal College of Pathologists [5], SAGE [6], and others [7] have likewise advised caution. Mass testing could backfire and increase transmission if individuals receiving negative test results are falsely reassured that they cannot have covid infection, and consequently take risks and reduce preventative behaviours. In a Department of Education video from one school where mass testing was piloted, every student and one member of staff stated that the main benefit of testing to them was to feel safe, showing false reassurance and little understanding of this important limitation [8]. This misunderstanding is unsurprising since the version of the government\u2019s handbook for schools sent out in December stated: \u201cThese tests work \u2026 they were shown to be as accurate in identifying a case as a PCR test\u201d [1]. The strategy would have a chance if this were true, but this is incorrect. As the same wording was included in a template letter for schools to use, it has been widely shared with pupils and parents [9].\u00a0 The Department of Education has now removed the letter and updated guidance, but the update to the handbook is still misleading, starting with the statement \u201cThese tests are very accurate \u2026\u201d [10] and no correction has been issued to pupils and parents.<\/span><\/p>\n<p><span style=\"font-weight: 400\">There is an even greater risk that the second part of the strategy, serial-testing of close contacts, may increase rather than decrease covid cases in schools. Consider a pupil who shows symptoms, tests positive at a test-and-trace centre, and isolates at home. Their close school contacts continue to attend school and are tested for seven days, only sent home if INNOVA results are positive. The possibility that some close contacts who are infected will test negative and will spread the virus is not negligible. Any clinically vulnerable pupils or staff in the class will be put at particularly high risk.\u00a0 This proposed strategy is, in effect, using negative INNOVA results to enable pupils to remain in school contrary to the MHRA restriction and scientific advice.<\/span><\/p>\n<p><span style=\"font-weight: 400\">In fact there are no evaluations of how well INNOVA detects cases in schools. Public Health England (PHE) and the University of Oxford used INNOVA in over 3,000 pupils in four schools, but crucially, did not evaluate to see if INNOVA testing had missed cases. [11] Other government-supported pilot school studies of INNOVA and of the saliva LAMP test [12] have the same design blind-spot.<\/span><\/p>\n<p><span style=\"font-weight: 400\">There are now six studies that provide evidence of how well INNOVA identifies cases compared with the \u201cgold standard\u201d PCR test done at the same time. Three are in people with symptoms: the manufacturer detected 96% (95% confidence interval: 89% to 99%) of cases in patients hospitalised with pneumonia [13]; PHE reported two studies in test-and-trace centres: one used experienced research nurses and laboratory scientists and detected 77% (72% to 81%) of cases, the other used test-and-trace centre staff and detected 58% (52% to 63%) [11]. These results show test performance declining when not done by experts, as will happen in schools.<\/span><\/p>\n<p><span style=\"font-weight: 400\">But pupils tested in schools will not have symptoms: three studies in symptomless people show the test as performing worse. In Liverpool, only 40% (29% to 52%) [14] and in University of Birmingham students only 3% (1% to 16%) of cases were detected. [15] Testing during an outbreak in a naval barracks by PHE detected only 28% (16% to 43%) of cases [11].\u00a0 Other lateral flow tests have also shown poorer performance in asymptomatics. [16]\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Lateral flow tests only detect cases when there are substantial quantities of virus on the swab.\u00a0 During an infection viral levels initially rise over several days as the virus proliferates, reach a peak (possibly coinciding with symptom onset), and fall once the individual\u2019s immune system successfully tackles the infection. Lateral flow tests only have a chance of detecting the infection around the peak but, even then, they miss cases (a third with the highest viral levels in Liverpool [14]).<\/span><\/p>\n<p><span style=\"font-weight: 400\">Cases are infectious before they are symptomatic: thus, there is a real risk \u2013 that the government strategy aims to address &#8211; that infected people transmit the virus before becoming symptomatic.\u00a0 But while mass testing with INNOVA will detect some of these cases, it will miss many, and falsely reassure those testing negative, if they are not properly informed of the test\u2019s limitations. Eight of every thousand testing negative in both Liverpool and Birmingham were positive on PCR [14,15] and two of every 1000 in Liverpool had high viral levels. Accordingly, the MHRA exceptional use approval restricts use of INNOVA to find positive cases, and explicitly <\/span><b>not<\/b><span style=\"font-weight: 400\"> to enable people to undertake activities based on a negative result [2].<\/span><\/p>\n<p><span style=\"font-weight: 400\">Quite apart from the practicality of implementing such a resource intensive approach, schools and pupils must be provided with accurate information to ensure that they do not inadvertently increase risk.\u00a0 Implementation should not happen without rigorous evaluations, which compare these strategies with other testing options, such as the use of PCR test-to-release after 5 days (as required for travellers [17]) for testing contacts, or pooled PCR testing (as successfully used at the University of Cambridge [18]) for identifying new cases.\u00a0 It is essential to check whether each strategy\u2019s benefits outweigh its harm, particularly with the increased transmission risk of the new variant. No testing strategy diminishes the need for the range of other interventions required to help make schools \u201csafer\u201d[19].<\/span><\/p>\n<p><span style=\"font-weight: 400\">Home isolation impacts hard on children, families, and teachers. But if INNOVA testing in schools risks spreading the disease more widely, it may lead to even more disruption to education and putting many more people at risk. Don\u2019t just test, evaluate.<\/span><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Jon Deeks<\/strong>*, Professor of Biostatistics University of Birmingham.<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Mike Gill<\/strong>, former Regional Director of Public Health, South East England.<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Sheila Bird<\/strong>*, Formerly Programme Leader, MRC Biostatistics Unit, University of Cambridge.<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Sylvia Richardson<\/strong>*, Director, MRC Biostatistics Unit, University of Cambridge, President of the Royal Statistical Society.<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Deborah Ashby<\/strong>*, Imperial College London, past-President of the Royal Statistical Society.<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\">* are members of the Royal Statistical Society Covid-19 Task Force or its Diagnostic Test Working Group.<\/span><\/em><\/p>\n<p><em><b>Conflicts of interest: <\/b><span style=\"font-weight: 400\">Jon Deeks leads the Cochrane covid-19 test evaluation reviews, is a member of the Royal Statistical Society covid-19 task force steering group, and <\/span><span style=\"font-weight: 400\">co-chair the RSS working group on diagnostic tests<\/span><span style=\"font-weight: 400\">.\u00a0 Mike Gill has no conflicts of interest. Sheila Bird is a member of the Royal Statistical Society\u2019s COVID-19 Taskforce and chairs its panel on test and trace. Sylvia Richardson is Director of the MRC Biostatistics Unit, President of the Royal Statistical Society and co-chair of the Royal Statistical Society Covid-19 Task Force. Deborah Ashby is Director of the School of Public Health, Imperial College London and Past President Royal Statistical Society. DA is investigator on the REACT study led by Imperial College, and co-chair of the RSS Diagnostic Test Working Group<\/span><\/em><\/p>\n<p><b>References:<\/b><\/p>\n<p><span style=\"font-weight: 400\">[1] NHS Test and Trace.\u00a0 Covid-19 National Testing Programme: Schools and College Handbook. 15 Dec 2020<\/span><\/p>\n<p><span style=\"font-weight: 400\">[2] Medicine and Healthcare products regulatory agency 23\/12\/2020\/\u00a0 MHRA issues exceptional use authorisation for NHS Test and Trace COVID-19 Self-Test device.\u00a0<\/span><span style=\"font-weight: 400\">https:\/\/www.gov.uk\/government\/news\/mhra-issues-exceptional-use-authorisation-for-nhs-test-and-trace-covid-19-self-test-device<\/span><\/p>\n<p><span style=\"font-weight: 400\">[3] House of Commons Science and Technology Committee Health and Social Care Committee.\u00a0 Oral evidence: Coronavirus: lessons learnt, HC 877.\u00a0 Wednesday 9<\/span><span style=\"font-weight: 400\">th<\/span><span style=\"font-weight: 400\"> December 2020.\u00a0 Q808.<\/span><\/p>\n<p><span style=\"font-weight: 400\">[4] World Health Organization. Antigen-detection in the diagnosis of SARS-CoV-2 infection using rapid immunoassays: interim guidance. 11 Sep 2020. <\/span><a href=\"https:\/\/www.who.int\/publications\/i\/item\/antigen-detection-in-the-diagnosis-of-sars-cov-2infection-using-rapid-immunoassays\"><span style=\"font-weight: 400\">https:\/\/www.who.int\/publications\/i\/item\/antigen-detection-in-the-diagnosis-of-sars-cov-2infection-using-rapid-immunoassays<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[5] The Royal College of Pathologists.\u00a0 Accuracy of lateral flow antigen tests for COVID-19.\u00a0 14<\/span><span style=\"font-weight: 400\">th<\/span><span style=\"font-weight: 400\"> December 2020.\u00a0 https:\/\/www.rcpath.org\/discover-pathology\/news\/accuracy-of-lateral-flow-antigen-tests-for-covid-19.html<\/span><\/p>\n<p><span style=\"font-weight: 400\">[6] SAGE 71 minutes: Coronavirus (COVID-19) response, Point 15.\u00a0 3 December 2020.\u00a0 <\/span><a href=\"https:\/\/www.gov.uk\/government\/publications\/sage-71-minutes-coronavirus-covid-19-response-3-december-2020\"><span style=\"font-weight: 400\">https:\/\/www.gov.uk\/government\/publications\/sage-71-minutes-coronavirus-covid-19-response-3-december-2020<\/span><\/a><span style=\"font-weight: 400\">.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">[7] Deeks JJ, Raffle AE. Lateral flow tests cannot rule out SARS-CoV-2 infection. BMJ 2020; 371:m4787.\u00a0 doi: <\/span><a href=\"https:\/\/doi.org\/10.1136\/bmj.m4787\"><span style=\"font-weight: 400\">https:\/\/doi.org\/10.1136\/bmj.m4787<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[8]<\/span> <a href=\"https:\/\/twitter.com\/educationgovuk\/status\/1345296310921007105\"><span style=\"font-weight: 400\">https:\/\/twitter.com\/educationgovuk\/status\/1345296310921007105<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[9] <\/span><span style=\"font-weight: 400\">https:\/\/schoolsweek.co.uk\/dfe-removes-highly-misleading-covid-testing-guidance\/<\/span><\/p>\n<p><span style=\"font-weight: 400\">[10] NHS Test and Trace.\u00a0 Covid-19 National Testing Programme: Schools and College Handbook. 4th January 2021. <\/span><a href=\"https:\/\/assets.publishing.service.gov.uk\/government\/uploads\/system\/uploads\/attachment_data\/file\/950515\/Schools_Colleges_Testing_Handbook_revised_04012021.pdf\"><span style=\"font-weight: 400\">https:\/\/assets.publishing.service.gov.uk\/government\/uploads\/system\/uploads\/attachment_data\/file\/950515\/Schools_Colleges_Testing_Handbook_revised_04012021.pdf<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[11] Preliminary report from the Joint PHE Porton Down &amp; University of Oxford SARS-CoV-2 test development and validation cell: Rapid evaluation of lateral flow viral antigen detection devices (LFDs) for mass community testing. 8 Nov 2020. <\/span><a href=\"https:\/\/www.ox.ac.uk\/news\/2020-11-11-oxford-university-and-phe-confirm-lateral-flow-tests-show-high-specificity-and-are\"><span style=\"font-weight: 400\">https:\/\/www.ox.ac.uk\/news\/2020-11-11-oxford-university-and-phe-confirm-lateral-flow-tests-show-high-specificity-and-are<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[12] <\/span><span style=\"font-weight: 400\">Godfrey, Keith\u00a0,\u00a0Southampton COVID-19 Testing Pilot Programme\u00a0(2020)\u00a0<\/span><i><span style=\"font-weight: 400\">Evaluation of the expanded Southampton pilot study (Phase 2) for use of saliva-based lamp testing in asymptomatic populations: Final report, 16th November 2020<\/span><\/i><span style=\"font-weight: 400\">\u00a0Southampton.\u00a0University of Southampton\u00a0120pp.\u00a0(<\/span><a href=\"http:\/\/dx.doi.org\/10.5258\/SOTON\/P0045\"><span style=\"font-weight: 400\">doi:10.5258\/SOTON\/P0045<\/span><\/a><span style=\"font-weight: 400\">).\u00a0 <\/span><a href=\"https:\/\/eprints.soton.ac.uk\/445622\/\"><span style=\"font-weight: 400\">https:\/\/eprints.soton.ac.uk\/445622\/<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[13] Innova Medical Group. SARS-CoV-2 antigen<\/span><span style=\"font-weight: 400\"> rapid qualitative test. Instructions for use. Version A\/02 2020-07-01. <\/span><a href=\"https:\/\/cdn.website-editor.net\/6f54caea7c6f4adfba8399428f3c0b0c\/files\/uploaded\/Innova-SARS-Cov-2-Antigen-test-IFU.pdf\"><span style=\"font-weight: 400\">https:\/\/cdn.website-editor.net\/6f54caea7c6f4adfba8399428f3c0b0c\/files\/uploaded\/Innova-SARS-Cov-2-Antigen-test-IFU.pdf<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[14] Liverpool Covid-19 Community Testing Pilot.\u00a0 Interim Evaluation Report.\u00a0 23<\/span><span style=\"font-weight: 400\">rd<\/span><span style=\"font-weight: 400\"> December. <\/span><a href=\"https:\/\/www.liverpool.ac.uk\/media\/livacuk\/coronavirus\/Liverpool,Community,Testing,Pilot,Interim,Evaluation.pdf\"><span style=\"font-weight: 400\">https:\/\/www.liverpool.ac.uk\/media\/livacuk\/coronavirus\/Liverpool,Community,Testing,Pilot,Interim,Evaluation.pdf<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[15] Ferguson J, Dunn S, Best A, Mirza J, Percival B, Mayhew M, Megram O, Ashford F, White T, Moles-Garcia O, Crawford L, Plant T, Bosworth A, Kidd M, Richter A, Deeks J, McNally A. Validation testing to determine the effectiveness of lateral flow testing for asymptomatic SARS-CoV-2 detection in low prevalence settings.\u00a0 medRxiv 2020.12.01.20237784; doi: <\/span><a href=\"https:\/\/doi.org\/10.1101\/2020\/12\/01\/20237784\"><span style=\"font-weight: 400\">https:\/\/doi.org\/10.1101\/2020\/12\/01\/20237784<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[16] Pray IW, Ford L, Cole D, et al. Performance of an Antigen-Based Test for Asymptomatic and Symptomatic SARS-CoV-2 Testing at Two University Campuses \u2014 Wisconsin, September\u2013October 2020. MMWR Morb Mortal Wkly Rep 2021;69:1642\u20131647. DOI: <\/span><a href=\"http:\/\/dx.doi.org\/10.15585\/mmwr.mm695152a3\"><span style=\"font-weight: 400\">http:\/\/dx.doi.org\/10.15585\/mmwr.mm695152a3<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[17] Guidance: Coronavirus (COVID-19): Test to Release for international travel. 27<\/span><span style=\"font-weight: 400\">th<\/span><span style=\"font-weight: 400\"> November 2020. <\/span><a href=\"https:\/\/www.gov.uk\/guidance\/coronavirus-covid-19-test-to-release-for-international-travel\"><span style=\"font-weight: 400\">https:\/\/www.gov.uk\/guidance\/coronavirus-covid-19-test-to-release-for-international-travel<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[18] <\/span><span style=\"font-weight: 400\">https:\/\/www.cam.ac.uk\/coronavirus\/stay-safe-cambridge-uni\/asymptomatic-covid-19-screening-programme<\/span><\/p>\n<p><span style=\"font-weight: 400\">[19] Independent Sage An urgent plan for safer schools\u00a0 <\/span><span style=\"font-weight: 400\">https:\/\/www.independentsage.org\/wp-content\/uploads\/2020\/11\/Safe-schools-v4b1.pdf<\/span><\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Using testing to manage classroom outbreaks, without isolating close contacts, risks increasing disease spread, say these authors [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/bmj\/2021\/01\/12\/covid-19-innova-testing-in-schools-dont-just-test-evaluate\/\">More&#8230;<\/a><\/p>\n","protected":false},"author":66,"featured_media":49389,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[223],"tags":[],"class_list":["post-49314","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-guest-bloggers"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - 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