Background Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. Methods We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. Results Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from − 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset. Conclusions RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias, so the positivity rates are probably overestimated.

Background Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA), using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. Methods We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. Findings Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from -6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 to 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset. Interpretation RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond ten days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias so the positivity rates are probably overestimated.

Bringing a diagnostic point of care test (POCT) to a healthcare market can be a painful experience as it requires the manufacturer to meet considerable technical, financial, managerial, and regulatory challenges. In this opinion article we propose a framework for developing the evidence needed to support product development, marketing, and adoption. We discuss each step in the evidence development pathway from the invention phase to the implementation of a new POCT in the healthcare system. We highlight the importance of articulating the value propositions and documenting the care pathway. We provide guidance on how to conduct care pathway analysis as little has been published on this. We summarize the clinical, economic and qualitative studies to be considered for developing evidence, and provide useful links to relevant software, on-line applications, websites, and give practical advice. We also provide advice on patient and public involvement and engagement (PPIE), and on product management. Our aim is to help device manufacturers to understand the concepts and terminology used in evaluation of in vitro diagnostics (IVDs) so that they can communicate effectively with evaluation methodologists, statisticians, and health economists. Manufacturers of medical tests and devices can use the proposed framework to plan their evidence development strategy in alignment with device development, applications for regulatory approval, and publication.

No routine laboratory biomarkers perform well enough in diagnosing COVID-19 in isolation for them to be used as a standalone diagnostic test or to help clinicians prioritize patients for treatment. Instead, other diagnostic tests are needed. The aim of this work was to statistically summarise routine laboratory biomarker measurements in COVID-19-positive and -negative patients to inform future work. A systematic literature review and meta-analysis were performed. The search included names of commonly used, routine laboratory tests in the UK NHS, and focused on research papers reporting laboratory results of patients diagnosed with COVID-19. A random effects meta-analysis of the standardized mean difference between COVID-19-positive and -negative groups was conducted for each biomarker. When comparing reported laboratory biomarker results, we identified decreased white blood cell, neutrophil, lymphocyte, eosinophil, and platelet counts; while lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase were elevated in COVID-19-positive compared to COVID-19-negative patients. Differences were identified across a number of routine laboratory biomarkers between COVID-19-positive and -negative patients. Further research is required to identify whether routine laboratory biomarkers can be used in the development of a clinical scoring system to aid with triage of patients.

Background Ventilator-associated pneumonia (VAP) is an important diagnosis in critical care. VAP research is complicated by the lack of agreed diagnostic criteria and reference standard test criteria. Our aim was to review which reference standard tests are used to evaluate novel index tests for suspected VAP. Methods We conducted a comprehensive search using electronic databases and hand reference checks. The Cochrane Library, MEDLINE, CINHAL, EMBASE, and web of science were searched from 2008 until November 2018. All terms related to VAP diagnostics in the intensive treatment unit were used to conduct the search. We adopted a checklist from the critical appraisal skills programme checklist for diagnostic studies to assess the quality of the included studies. Results We identified 2441 records, of which 178 were selected for full-text review. Following methodological examination and quality assessment, 44 studies were included in narrative data synthesis. Thirty-two (72.7%) studies utilised a sole microbiological reference standard; the remaining 12 studies utilised a composite reference standard, nine of which included a mandatory microbiological criterion. Histopathological criteria were optional in four studies but mandatory in none. Conclusions Nearly all reference standards for VAP used in diagnostic test research required some microbiological confirmation of infection, with BAL culture being the most common reference standard used.

There is an urgent requirement to identify which clinical settings are in most need of COVID-19 tests and the priority role(s) for tests in these settings to accelerate the development of tests fit for purpose in health and social care across the UK. This study sought to identify and prioritize unmet clinical needs for COVID-19 tests across different settings within the UK health and social care sector via an online survey of health and social care professionals and policymakers. Four hundred and forty-seven responses were received between 22nd May and 15th June 2020. Hospitals and care homes were recognized as the settings with the greatest unmet clinical need for COVID-19 diagnostics, despite reporting more access to laboratory molecular testing than other settings. Hospital staff identified a need for diagnostic tests for symptomatic workers and patients. In contrast, care home staff expressed an urgency for screening at the front door to protect high-risk residents and limit transmission. The length of time to test result was considered a widespread problem with current testing across all settings. Rapid tests for staff were regarded as an area of need across general practice and dental settings alongside tests to limit antibiotics use.

It is recommended that developers of Point Of Care Tests (POCTs) assess the care pathway of the patient population of interest in order to understand if the POCT fits within the pathway and has the potential to improve it. If the variation of the pathway across potential hospitals is large, then it is likely that the evaluation of effectiveness is harder and the route towards large-scale takes adoption longer. Evaluating care pathways can be a time-consuming activity when conducted through clinical audits or interviews with healthcare professionals. We have developed a more rapid methodology which extrapolates the care pathway from local hospital guidelines and assesses their variation. Sepsis kills 46,000 people per year in the UK with societal costs of up to £10 billion. Therefore, there is a clinical need for an optimized pathway. By applying our method in this field, we were able to assess the variation in current hospital guidelines for sepsis and infer the potential impact this may have on the evidence development on innovations in this applications. We obtained 15 local sepsis guidelines. Two independent reviewers extracted: use of the national early warning score (NEWS), signs and risk factors informing the decision to prescribe antibiotics, and the number of decisional steps up to this point. Considerable variation was observed in all the variables, which is likely to have an impact on future clinical and economic evaluations and adoption of POCT for the identification of patients with sepsis.

Objectives The second wave of the coronavirus pandemic is now established, occurring at a time of winter pressure on acute care in the NHS. This is likely to be more challenging then the first wave for the diagnosis of COVID-19 because of the similar symptomology with other respiratory conditions highly prevalent in winter. This study sought to understand the care pathways in place in UK NHS hospitals during the first wave (March–July 2020) for identification of patients with COVID-19 and to learn lessons to inform optimal testing strategies within the COVID-19 National Diagnostic Research and Evaluation Platform (CONDOR). Design, setting & participants Sixteen hospital-based clinicians from 12 UK NHS Trusts covering 10 different specialties were interviewed following a semi-structured topic guide. Data were coded soon after the interviews and analysed thematically. Results We developed a diagrammatic, high-level visualisation of the care pathway describing the main clinical decisions associated with the diagnosis and management of patients with suspected COVID-19. COVID-19 testing influenced infection control considerations more so than treatment decisions. Two main features of service provision influenced the patient management significantly: access to rapid laboratory testing and the number of single occupancy rooms. If time to return of result was greater than 24 h, patients with a presumptive diagnosis would often be cohorted based on clinical suspicion alone. Undetected COVID-19 during this time could therefore lead to an increased risk of viral transmission. Conclusions During the winter months, priority for provision of rapid testing at admission should be given to hospitals with limited access to laboratory services and single room availability. Access to rapid testing is essential for urgent decisions related to emergency surgery, maternity services and organ transplant. The pathway and prioritization of need will inform the economic modelling, clinical evaluations, and implementation of new clinical tests in UK.