Home Testing of Respiratory Illness

Background and Rationale

Acute respiratory infections (ARI) cause considerable disease burden globally and can affect both the upper and lower respiratory tract. A majority of ARI are caused by viruses, like the influenza virus, while bacteria are only implicated in approximately 10% of cases . The symptomology across various viral ARI are broadly similar, but two viruses, namely influenza and respiratory syncytial virus (RSV) are associated with considerable morbidity and mortality among adults and children. More immediate virus identification would improve patient health management by triaging appropriate and timely treatment and infection-control measures to mitigate health costs, additional health complications, and total days of symptom expression.

Despite viral infections causing the majority of ARIs, 61% of those with acute respiratory symptoms receive an antibiotic treatment. Due to the rise of antibiotic resistance, the inappropriate and over-prescription of antibiotics has become a severe health risk and is contributing to greater health complications and increased mortality rates. As a result, the correct diagnosis of the various infections associated with ARIs has become even more imperative to not cause undue harm. The abundance, accessibility, and rapidly advancing technology in wearable devices contributes to the progress some studies have demonstrated in using the devices as a potential mechanism to more rapidly identify various diseases. Though limited research has explored this new perspective specifically in illnesses associated with ARI, recent findings were able to demonstrate influenza signals at a population level using step, sleep, and heart rate data collected from consumer wearable devices.

Influenza virus is important to diagnose correctly because, despite annual vaccinations, it has been associated with higher morbidity and mortality than most other ARI viruses and has been associated with greater individual symptom severity. During the 2017-2018 flu season in the United States, it was estimated that 48.8 million people became sick with influenza, 959,000 were hospitalized, and there were 79,400 deaths recorded due to influenza. Additionally, more vulnerable populations, like young children, those experiencing chronic illness, and older adults, disproportionately represent the hospitalization and death totals reported. Older adults represented 70% of influenza related hospitalizations in the 2017-2018 flu season and 90% of influenza related deaths.

The rapid diagnosis of influenza is also of particular importance due to the effectiveness of influenza antiviral medication that is largely limited to initiation within 48 hours of symptom onset. Additionally, rapid diagnosis also has the potential to enact infection control measures to attenuate viral spread, particularly among vulnerable populations, using behavioral interventions or other non-pharmaceutical approaches. Diagnosis of influenza infection in centralized laboratories has largely progressed from traditional viral culture to the use of reverse transcription-polymerase chain reaction (RT-PCR) methods . Alternatively, influenza infection can be detected within a medical office or pharmacy using commercially-available rapid diagnostic tests (RDTs) of varying complexity, cost and accuracy.

There is now interest to expand RDTs to self-conducted tests that individuals can complete at home to further reduce the period between the onset of illness and effective treatment. Audere, a digital health non-profit, developed a mobile device app, the flu@home app, to guide individuals to perform an influenza RDT themselves without being in a clinical setting. The flu@home test uses a mixture of images and written directions prompted through the flu@home app to walk individuals through an influenza RDT process. The flu@home test also includes modified influenza RDT test material from an FDA 510(k) cleared RDT and includes an optional in-app automated influenza RDT test result interpretation system to eventually help inform health decisions and behaviors. Though no research has been published on the efficacy of the flu@home system, it has been implemented, and is being investigated, in two large prospective observational clinical studies during the 2019-2020 flu season, with collaborators at the University of Washington, Seattle and University of Adelaide, Australia.

Expanding on the previous research and development that has been done, the aim of this study is to develop a methodology to better classify and detect RVI cases, including influenza, through the use of behavioral data and patient-reported outcomes, using RVI confirmation through laboratory testing as a reference. This study also aims to assess the accuracy of the flu@home RDT self-test, the in-app automated RDT test result interpretation, and a data enhanced RDT test interpretation, compared to the interpretation provided by a trained professional RDT reader, the PCR test result, and a reference influenza test interpretations/analysis.

Device Description

The flu@home test kit is an at-home self-administered modified influenza RDT that is completed with the assistance of a mobile device app. The flu@home app feature was developed by Audere, a digital health non-profit based in Seattle. The flu@home test consists of the instructional app experience that guides participants through the influenza RDT procedure and the physical material of the RDT influenza test kit modified from the Quidel QuickVue Influenza A+B test. The flu@home app will solely be utilized as an instructional guide and research data collection tool for this study.

The flu@home test kit's instructional app features are available on iOS and Android platforms. The instructional app features include multiple pages of text and imagery content guiding participants through the entirety of the influenza RDT process, from completing a nasal swab to adding solution into a test tube to run a lateral flow immunoassay. The instructional app also includes an in-app questionnaire for participants to complete during a 10-minute participant wait period while their immunoassay processes. The flu@home test kit also guides participants through the viral collection and appropriate transport procedure of study samples for additional RVI analysis to be completed at an accredited laboratory.

The physical material of the flu@home test kit consists of components from an existing commercial influenza RDT, with additional material to collect and return a reference sample for laboratory testing. The complete flu@home test kit includes two foam-tipped nasal swabs, a small tube with dried reagent, a saline vial, a lateral-flow immunoassay test strip, and a tube with liquid reagent for the PCR test. RDT testing material is utilized from the CLIA-waived Quidel QuickVue Influenza A+B Test. All physical testing material will be assembled and mailed to participants through a 3rd party vendor, Molecular Testing Lab (MTL). The flu@home test kit also includes mailing material for participants to return the RDT test remnant and strip to be discarded by MTL and the reference nasal swab for laboratory testing through PCR procedures at MTL's accredited facility.

The flu@home test kit's interpretation features will not be shared with participants within the parameters of this study.

Regulatory Status

The flu@home test kit is considered a non-significant investigational device that is being used for data collection purposes and will be labeled as an investigational device. The test kit contains foam-tipped nasal swabs, a small tube with dried reagent, a saline vial and test strip from the CLIA-waived Quidel QuickVue Influenza A+B Test, and a tube with liquid reagent for the PCR test.

Explanation of choice comparator

PCR (RT-PCR for RNA viruses including influenza) is a reliable reference test for influenza and other respiratory viruses. RT-PCR was identified as the comparator for the modified at-home self-administered influenza RDT. Though RDTs can produce results in a much shorter period of time than RT-PCRs, RT-PCRs have been found to have more sensitivity to the influenza viruses than do RDTs. PCR or RT-PCR is often used as the reference test in research studies and studies designed for FDA submission (e.g., influenza RT-PCR was used as a reference test in the FDA 510(k) submission for the Quidel QuickVue Influenza A+B Test; Quidel, 2018).