2 Rapid health technology assessment of xxxxx Health Information and Quality Authority Rapid health technology assessment (HTA) of alternatives to laboratory- based real-time RT-PCR to diagnose current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Submitted to NPHET: 7 October 2020 Published: 21 October 2020 Rapid HTA of alternatives to laboratory-based real-time RT-PCR to diagnose current infection with SARS-CoV-2 Health Information and Quality Authority Version history Version Date Specific updates V1.0 2 October 2020 First draft of the rapid health technology assessment (HTA) circulated to the Expert Advisory Group (EAG) for review. V2.0 7 October 2020 Rapid HTA submitted as advice to the National Public Health Emergency Team (NPHET). V3.0 20 October 2020 Updated the rapid review of international guidance and use of tests and testing methods for the detection of SARS-CoV-2. Included minor wording amendments to the rapid HTA. ii Rapid HTA of alternatives to laboratory-based real-time RT-PCR to diagnose current infection with SARS-CoV-2 Health Information and Quality Authority About the Health Information and Quality Authority The Health Information and Quality Authority (HIQA) is an independent statutory authority established to promote safety and quality in the provision of health and social care services for the benefit of the health and welfare of the public. HIQA’s mandate to date extends across a wide range of public, private and voluntary sector services. Reporting to the Minister for Health and engaging with the Minister for Children and Youth Affairs, HIQA has responsibility for the following: . Setting standards for health and social care services — Developing person-centred standards and guidance, based on evidence and international best practice, for health and social care services in Ireland. Regulating social care services — The Chief Inspector within HIQA is responsible for registering and inspecting residential services for older people and people with a disability, and children’s special care units. Regulating health services — Regulating medical exposure to ionising radiation. Monitoring services — Monitoring the safety and quality of health services and children’s social services, and investigating as necessary serious concerns about the health and welfare of people who use these services. Health technology assessment — Evaluating the clinical and cost- effectiveness of health programmes, policies, medicines, medical equipment, diagnostic and surgical techniques, health promotion and protection activities, and providing advice to enable the best use of resources and the best outcomes for people who use our health service. Health information — Advising on the efficient and secure collection and sharing of health information, setting standards, evaluating information resources and publishing information on the delivery and performance of Ireland’s health and social care services. National Care Experience Programme — Carrying out national service- user experience surveys across a range of health services, in conjunction with the Department of Health and the HSE. iii Rapid HTA of alternatives to laboratory-based real-time RT-PCR to diagnose current infection with SARS-CoV-2 Health Information and Quality Authority CONTENTS Version history ............................................................................................................... ii About the Health Information and Quality Authority ......................................................... iii Foreword.................................................................................................................... viii Acknowledgements ........................................................................................................x The membership of the EAG was as follows: .................................................................x Members of HIQA’s Evidence Synthesis Team: ............................................................ xii Conflicts of interest .................................................................................................. xiii List of abbreviations used in this report ......................................................................... xiv Advice to the National Public Health Emergency Team .................................................. xvii 1 Background ............................................................................................................ 1 2 Description of technology ........................................................................................ 3 Key points ................................................................................................................ 3 2.1 Background ..................................................................................................... 5 2.1.1 Aims of testing .......................................................................................... 6 2.1.2 Testing processes ...................................................................................... 8 2.1.3 Technologies for detection of SARS-CoV-2 ................................................... 9 2.1.4 Viral RNA detection ................................................................................... 10 2.1.5 Virus antigen detection ............................................................................. 10 2.1.6 Antibody detection ................................................................................... 11 2.2 Consideration of alternatives to standard technology.......................................... 12 2.2.1 Rapid testing ............................................................................................ 16 2.2.2 Viral RNA detection ................................................................................... 17 2.2.3 Current laboratory-based methods ............................................................. 19 2.2.4 Commercially available near-patient isothermal amplification methods .......... 20 2.2.5 Near-patient methods currently in development .......................................... 21 2.2.6 Other laboratory methods ......................................................................... 22 2.3 Antigen detection tests .................................................................................... 24 2.3.1 Immunoassays ......................................................................................... 25 2.3.2 Protein microarrays .................................................................................. 27 2.4 Biosensors ...................................................................................................... 28 2.5 Microfluidic technology .................................................................................... 28 2.6 Testing approaches ......................................................................................... 29 2.6.1 Sample collection and processing methods ................................................. 29 iv Rapid HTA of alternatives to laboratory-based real-time RT-PCR to diagnose current infection with SARS-CoV-2 Health Information and Quality Authority 2.6.2 Sample pooling approaches ....................................................................... 29 2.6.3 Record linkage ......................................................................................... 31 2.7 Considerations for use ..................................................................................... 32 3 Rapid review of international testing methods .......................................................... 37 Key points ............................................................................................................... 37 3.1 Background .................................................................................................... 38 3.2 Methods ......................................................................................................... 38 3.3 Results ........................................................................................................... 39 3.3.1 Primary test for the detection of SARS-CoV-2 .............................................. 40 3.3.2 Sample / specimen ................................................................................... 52 3.3.3 Additional tests for the detection of SARS-CoV-2 ......................................... 52 3.3.4 Use of alternative approaches to testing ..................................................... 54 3.3.5 Use of rapid or near-patient (point-of-care) testing ..................................... 55 3.3.6 International guidance on rapid antigen tests ............................................. 62 3.4 Discussion ...................................................................................................... 70 4 Diagnostic accuracy of alternatives to laboratory-based rRT-PCR ............................... 72 Key points ............................................................................................................... 72 4.1 Background .................................................................................................... 75 4.1.1 The need for alternatives .......................................................................... 75 4.1.2 Contextual factors relating to test performance ........................................... 75 4.2 Assessing the accuracy of diagnostic tests for the detection of SARS-CoV-2 ......... 77 4.2.1 Determination of diagnostic test accuracy ..................................................