FebriDx point-of-care test in patients with suspected COVID-19: a systematic review and individual patient data meta-analysis of diagnostic test accuracy studies
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Abstract
Background
We conducted a systematic review and individual patient data (IPD) meta-analysis to evaluate the diagnostic accuracy of a commercial point-of-care test, the FebriDx lateral flow device (LFD), in adult patients with suspected COVID-19. The FebriDx LFD is designed to distinguish between viral and bacterial respiratory infection.
Methods
We searched MEDLINE, EMBASE, PubMed, Google Scholar, LitCovid, ClinicalTrials.gov and preprint servers on the 13 th of January 2021 to identify studies reporting diagnostic accuracy of FebriDx (myxovirus resistance protein A component) versus real time reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 in adult patients suspected of COVID-19. IPD were sought from studies meeting the eligibility criteria. Studies were screened for risk of bias using the QUADAS-2 tool. A bivariate linear mixed model was fitted to the data to obtain a pooled estimate of sensitivity and specificity with 95% confidence intervals (95% CIs). A summary receiver operating characteristic (SROC) curve of the model was constructed. A sub-group analysis was performed by meta-regression using the same modelling approach to compare pooled estimates of sensitivity and specificity between patients with a symptom duration of 0 to 7 days and >7 days, and patients aged between 16 to 73 years and >73 years.
Results
Ten studies were screened, and three studies with a total of 1481 patients receiving hospital care were included. FebriDx produced an estimated pooled sensitivity of 0.911 (95% CI: 0.855-0.946) and specificity of 0.868 (95% CI: 0.802-0.915) compared to RT-PCR. There were no significant differences between the sub-groups of 0 to 7 days and >7 days in estimated pooled sensitivity (p = 0.473) or specificity (p = 0.853). There were also no significant differences between the sub-groups of 16 to 73 years of age and >73 years of age in estimated pooled sensitivity (p = 0.946) or specificity (p = 0.486).
Conclusions
Based on the results of three studies, the FebriDx LFD had high diagnostic accuracy for COVID-19 in a hospital setting, however, the pooled estimates of sensitivity and specificity should be interpreted with caution due to the small number of studies included, risk of bias, and inconsistent reference standards. Further research is required to confirm these findings, and determine how FebriDx would perform in different healthcare settings and patient populations.
Trial registration
This study was conducted at pace as part of the COVID-19 National Diagnostic Research and Evaluation Platform (CONDOR) national test evaluation programme ( https://www.condor-platform.org ), and as a result, no protocol was developed, and the study was not registered.
Lay summary
Tests to diagnose COVID-19 are crucial to help control the spread of the disease and to guide treatment. Over the last few months, tests have been developed to diagnose COVID-19 either by detecting the presence of the virus or by detecting specific markers linked to the virus being active in the body. These tests use complex machines in laboratories accepting samples from large geographical areas. Sometimes it takes days for test results to come back. So, to reduce the wait for results, new portable tests are being developed. These ‘point-of-care (POC)’ tests are designed to work close to where patients require assessment and care such as hospital emergency departments, GP surgeries or care homes. For these new POC tests to be useful, they should ideally be as good as standard laboratory tests.
In this study we looked at published research into a new test called FebriDx. FebriDx is a POC test that detects the body’s response to infection, and is claimed to be able to detect the presence of any viral infection, including infections due to the SARS-CoV-2 virus which causes COVID-19, as well as bacterial infections which can have similar symptoms. The FebriDx result was compared with standard laboratory tests for COVID-19 performed on the same patient’s throat and nose swab sample. We were able to analyse data from three studies with a total of 1481 adult patients who were receiving hospital care with symptoms of COVID-19 during the UK pandemic. Approximately one fifth of the patients were diagnosed as positive for SARS-CoV-2 virus using standard laboratory tests for COVID-19.
Our analysis demonstrated that FebriDx correctly identified 91 out of 100 patients who had COVID-19 according to the standard laboratory test. FebriDx also correctly identified 87 out of 100 patients who did not have COVID-19 according to the standard laboratory test. These results have important implications for how these tests could be used. As there were slightly fewer FebriDx false results when the results of the standard laboratory test were positive (9 out of 100) than when the results of the standard laboratory test were negative (13 out of 100), we can have slightly more confidence in a positive test result using FebriDx than a negative FebriDx result.
Overall, we have shown that the FebriDx POC test performed well during the UK COVID-19 pandemic when compared with laboratory tests, especially when COVID-19 was indicated. For the future, this means that the FebriDx POC test might be helpful in making a quick clinical decision on whether to isolate a patient with COVID-19-like symptoms arriving in a busy emergency department. However, our results indicate it would not completely replace the need to conduct a laboratory test in certain cases to confirm COVID-19.
There are limitations to our findings. For example, we do not know if FebriDx will work in a similar way with patients in different settings such as in the community or care homes. Similarly, we do not know whether other viral and bacterial infections which cause similar COVID-19 symptoms, and are more common in the autumn and winter months, could influence the FebriDx test accuracy. Our findings are also only based on three studies.
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SciScore for 10.1101/2020.10.15.20213108: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources This study was conducted at pace as part of the CONDOR national test evaluation programme (18), and as a result, no protocol was developed, and the study was not registered. CONDORsuggested: (Condor, RRID:SCR_017664)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the …SciScore for 10.1101/2020.10.15.20213108: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources This study was conducted at pace as part of the CONDOR national test evaluation programme (18), and as a result, no protocol was developed, and the study was not registered. CONDORsuggested: (Condor, RRID:SCR_017664)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations: The reference standard of RT-PCR on nose and throat swab samples is imperfect, and while commonly used as a reference test, it is not a gold standard (26). RT-PCR has shown limited diagnostic performance characteristics, particularly with the production of false negative results in patients presenting in an emergency with suspected COVID-19 (27-29). An imperfect reference standard in this case, which most likely produced false negative results, would be likely to produce an underestimate of both sensitivity and specificity. If additional clinical and diagnostic data were available for both studies, this analysis would have benefitted from the use of a composite reference standard (30) or latent class analyses with instrumental variables to minimise the probability of such error or bias (31-33). Although both studies used RT-PCR as the reference standard, different RT-PCR tests were used across the studies. The accuracy of the different RT-PCR tests used will vary between methods, and as these methods were further developed during the pandemic, this leads to an inconsistent reference standard. This suggests that the pooled diagnostic accuracy estimates should be treated with caution. Both studies were conducted during the first peak of the SARS-CoV-2 pandemic in the UK (March/April 2020), where the prevalence of COVID-19 was high. The pooled diagnostic accuracy results (particularly PPV and NPV) should only be interpreted within this specific phase of the pandemic...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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