Evaluation of the AudibleHealth Dx AI/ML-Based Dx SaMD Using FCV-SDS in the Diagnosis of COVID-19 Illness: Clinical Validation

Evaluation of the Artificial Intelligence/Machine Learning-Based Diagnostic Software as a Medical Device Using Forced Cough Vocalization Signal Data Signatures in the Diagnosis of COVID-19 Illness: A Prospective, Two-Arm Non-Inferiority Clinical Validation Trial of AudibleHealth Dx Software as a Medical Device (EUA-US)

The AudibleHealth Dx is a diagnostic software as a medical device (Dx SaMD) consisting of an ensemble of software subroutines that interacts with a proprietary database of Signal Data Signatures (SDS), using Artificial Intelligence/Machine Learning (AI/ML) to analyze forced cough vocalization signal data signatures (FCV-SDS) for diagnostic purposes.

This study will evaluate the performance of the AudibleHealth Dx in comparison to a standard of care Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test for the diagnosis of COVID-19.

A secondary purpose of the study will be usability testing of the device for participants and providers.

The study is a prospective, multi-site, non-inferiority trial comparing the AudibleHealth Dx to FDA approved COVID-19 RT-PCR testing to demonstrate non-inferiority of the PPA and NPA when using this device to diagnose COVID-19 illness. The AudibleHealth Dx test and the "BioFire Respiratory 2.1 (RP2.1)" (brand name) test will be performed for each participant during a single encounter. Participants and staff will be blinded to AudibleHealth Dx results and the RT-PCR status at the time of testing. No one will know both results in real-time except for the Site Coordinators and unblinded statistician specifically authorized to have these results for enrollment, audit, data tracking, and data compiling purposes. • Unblinding of the results will occur after the AudibleHealth Dx, RT-PCR, and the second RT-PCR results (if necessary for discordance) have been obtained. Results for the RT-PCR test will be received by the participant according to the clinical site's protocol.

Target enrollment for this trial will be 65 COVID-19 positive cases and 152 COVID-19 negative cases, presuming a prevalence of 0.30 for a total of 217 subjects meeting all inclusion criteria.

Inclusion Criteria:

• 18 years of age or older
• Present for elective, outpatient COVID-19 RT-PCR testing
• Meet the FDA EUA approved indications for use for RT-PCR nasal swab testing for COVID-19
• Stated willingness to comply with all trial procedures and availability for the duration of the trial
• Informed consent must be obtained prior to testing
• Ability to complete both the informed consent form and the screens on the medical device app in English (no translation to other languages is currently available)

Exclusion Criteria:

• Any individual who was a part of the AudibleHealth Dx Development, Training, and Usability trial (Training and test data sets are to be kept strictly separate.)
• Less than 18 years of age
• Unable to produce a voluntary forced cough vocalization (FCV)
• Recent acute traumatic injury to the head, neck, throat, chest, abdomen or trunk
• Patent tracheostomy stoma
• Recent chest / abdomen / trunk trauma or surgery, recent / persistent neurovascular injury or recent intracranial surgery
• Medical history of cribriform plate injury or cribriform plate surgery, diaphragmatic hernia, external beam neck / throat / maxillofacial radiation, phrenic nerve injury/palsy, radical neck / throat / maxillofacial surgery, vocal cord trauma or nodules
• Since persons with aphasia may have difficulty in producing an FCV-SDS in the time allotted by the app, this population also will be excluded from the current trial