(266 days)
The TytoCare Lung Sounds Analyzer is an over-the-counter decision support software system used in the evaluation of lung sounds in adults and children (2 years and older). It automatically analyzes the acoustic signal of the lung as recorded by the FDA cleared compatible Tyto Stethoscope and identifies recordings where a specific abnormal lung sound suggestive of "Wheeze" is suspected. It is not intended to detect other abnormal or normal lung sounds. A licensed health care professional's advice is required to understand the meaning of the TytoCare Lung Sounds Analyzer result. Healthcare provider should consider the device result in conjunction with recording and other relevant patient data.
The TytoCare Lung Sounds Analyzer is a web-based software system designed to aid in the clinical assessment of lungs auscultation sound data by analyzing recorded lung sounds to determine whether a Wheeze is detected within the recorded sound data.
The TytoCare Lung Sounds Analyzer Software is intended to process recordings from the FDA-cleared compatible Tyto Stethoscope (Tyto Stethoscope, K181612). The acquisition of the acoustic data (recordings) is carried out by a professional user in a clinical environment or by a lay- user in a non-medical environment, in compliance with the labeling of the Tyto Stethoscope.
The system is composed of the following sub-systems:
-
- The TytoCare Lung Sounds Analyzer Application Server (APS) communicates with the TytoCare Lung Sounds Analyzer Algorithm Server (ALS) and implements an application programming interface (API) for communication with the telehealth server.
-
- The TytoCare Lung Sounds Analyzer Algorithm Server (ALS) receives an audio file as input and returns an analysis result of positive or negative regarding whether a wheeze was detected as output.
-
- The TytoCare Lung Sounds Analyzer Web Server (WBS) provides a graphic indication whether a wheeze is detected in the recording. It can be utilized both in patient and clinician side.
All the software subsystems (servers and storage) are hosted in the cloud and communicate through IP network.
Here's a breakdown of the acceptance criteria and the study details for the TytoCare Lung Sounds Analyzer, based on the provided document:
Acceptance Criteria and Device Performance
| Parameter | Acceptance Criteria (Stated) | Reported Device Performance |
|---|---|---|
| Sensitivity (Se) | Not explicitly stated as a target | 0.69 (0.57–0.78) (95% CI) |
| Specificity (Sp) | Not explicitly stated as a target | 0.92 (0.88–0.95) (95% CI) |
| Overall Accuracy | Non-inferior to clinical readers | AUC = 0.91 (0.86-0.94) |
| Non-Inferiority | Non-inferiority margin of 5% (0.05) | Difference in AUC = 0.09 (0.04-0.13) which supports noninferiority (0.04 > -0.05) |
| Reproducibility | Not explicitly stated as a target | Kappa for device: 1.00 (1.00-1.00) vs. Clinical Readers: 0.6134 (0.5183-0.7016) |
Study Details
-
Sample size used for the test set and the data provenance:
- Sample Size: 371 recordings (86 Wheeze positive, 285 negative) from 359 patients.
- Data Provenance: Retrospective validation dataset of Tyto Stethoscope recordings sourced from real-world use of the Tyto Care FDA cleared Tyto Stethoscope. The dataset included recordings from patients with known pre-existing conditions (COPD or Asthma) (7.28%).
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Number of Experts: Three.
- Qualifications: Blinded experienced Pulmonologists. Specific years of experience are not mentioned.
-
Adjudication method for the test set:
- Adjudication Method: Majority vote of the three blinded Pulmonologists ("binary ground truth was determined by majority vote of these three Pulmonologists"). This is a 3-reader consensus method.
-
If a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done:
- Yes, a comparative study was done. The clinical performance section compares the device's AUC to that of "clinical readers (Physicians non-Pulmonologists)."
- Effect size of how much human readers improve with AI vs. without AI assistance: The study primarily focused on the device's accuracy being non-inferior to human readers, rather than human readers with AI assistance. The reported AUC for the device (0.91) was higher than the AUC for clinical readers (0.83), with a difference of 0.09. This suggests the device performs better than the un-assisted clinical readers. The study did not test human readers with AI assistance, so an effect size for human improvement with AI assistance cannot be determined from this document.
-
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, a standalone accuracy assessment was performed. Table 3 explicitly presents "The stand-alone accuracy of the TytoCare Lung Sounds Analyzer" with sensitivity and specificity results.
-
The type of ground truth used:
- Type of Ground Truth: Expert consensus. Specifically, a majority vote of three blinded experienced Pulmonologists.
-
The sample size for the training set:
- The document does not provide the sample size for the training set. It only mentions the validation dataset.
-
How the ground truth for the training set was established:
- The document does not provide information on how the ground truth for the training set was established. It only describes the ground truth establishment for the validation dataset.
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February 24, 2023
Tyto Care Ltd. Stella Perry RA&QA Director 14 Beni Gaon Street Netanya, 4250803 Israel
Re: K221614
Trade/Device Name: TytoCare Lung Sounds Analyzer Regulation Number: 21 CFR 868.1900 Regulation Name: Diagnostic Pulmonary-Function Interpretation Calculator Regulatory Class: Class II Product Code: PHZ Dated: January 26, 2023 Received: January 26, 2023
Dear Stella Perry:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Rachana Visaria -S
Rachana Visaria, Ph.D. Assistant Director DHT1C: Division of Sleep Disordered Breathing, Respiratory and Anesthesia Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K221614
Device Name
TytoCare Lung Sounds Analyzer
Indications for Use (Describe)
The TytoCare Lung Sounds Analyzer is an over-the-counter decision support software system used in the evaluation of lung sounds in adults and children (2 years and older). It automatically analyzes the acoustic signal of the lung as recorded by the FDA cleared compatible Tyto Stethoscope and identifies recordings where a specific abnormal lung sound suggestive of "Wheeze" is suspected. It is not intended to detect other abnormal or normal lung sounds. A licensed health care professional's advice is required to understand the meaning of the TytoCare Lung Sounds Analyzer result. Healthcare provider should consider the device result in conjunction with recording and other relevant patient data.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) Summary
| Submitter Nameand Address: | Tyto Care Ltd.14 Beni Gaon StreetNetanya, Israel, 4250803 |
|---|---|
| Contact Person: | Stella Raizelman PerryRA & QA DirectorEmail: stellar@tytocare.comPhone Number: +972 72-2210750Fax Number: +972 72-2210752 |
| EstablishmentRegistrationNumber: | 3012678246 |
| Date Prepared: | February 24, 2023 |
| Device TradeName(s): | TytoCare Lung Sounds Analyzer |
| Device CommonName: | TytoCare Lung Sounds Analyzer |
| Classification: | Name: Diagnostic pulmonary-function interpretationcalculatorProduct code: PHZSecondary product code: DQDRegulation No: 21 CFR 868.1900Class: IIPanel: Anesthesiology |
Predicate Device(s):
Device name wheezo WheezeRate Detector (by Respiri Limited) 510(k) No. K202062
Date of Clearance March 11, 2021
Reference Device(s):
| Device name | 510(k) No. | Date of Clearance |
|---|---|---|
| Tyto Stethoscope | K181612 | December 17, 2018 |
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Intended use / indication for use statement
The TytoCare Lung Sounds Analyzer is an over-the-counter decision support software system used in the evaluation of lung sounds in adults and children (2 years and older). It automatically analyzes the acoustic signal of the lung as recorded by the FDA cleared compatible Tyto Stethoscope and identifies recordings where a specific abnormal lung sound suggestive of "Wheeze" is suspected. It is not intended to detect other abnormal or normal lung sounds. A licensed health care professional's advice is required to understand the meaning of the TytoCare Lung Sounds Analyzer result. Healthcare provider should consider the device result in conjunction with recording and other relevant patient data.
Device description
The TytoCare Lung Sounds Analyzer is a web-based software system designed to aid in the clinical assessment of lungs auscultation sound data by analyzing recorded lung sounds to determine whether a Wheeze is detected within the recorded sound data.
The TytoCare Lung Sounds Analyzer Software is intended to process recordings from the FDA-cleared compatible Tyto Stethoscope (Tyto Stethoscope, K181612). The acquisition of the acoustic data (recordings) is carried out by a professional user in a clinical environment or by a lay- user in a non-medical environment, in compliance with the labeling of the Tyto Stethoscope.
The system is composed of the following sub-systems:
-
- The TytoCare Lung Sounds Analyzer Application Server (APS) communicates with the TytoCare Lung Sounds Analyzer Algorithm Server (ALS) and implements an application programming interface (API) for communication with the telehealth server.
-
- The TytoCare Lung Sounds Analyzer Algorithm Server (ALS) receives an audio file as input and returns an analysis result of positive or negative regarding whether a wheeze was detected as output.
-
- The TytoCare Lung Sounds Analyzer Web Server (WBS) provides a graphic indication whether a wheeze is detected in the recording. It can be utilized both in patient and clinician side.
All the software subsystems (servers and storage) are hosted in the cloud and communicate through IP network.
Substantial Equivalence to Predicate Devices
The following table compares the TytoCare Lung Sounds Analyzer to the predicate
and reference device devices:
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| Device | Predicate | Reference device | Summary | |
|---|---|---|---|---|
| Device Name | TytoCare Lungs SoundsAnalyzer | wheezo WheezeRateDetector | Tyto Stethoscope (OTC) | NA |
| DeviceManufacturer | Tyto Care Ltd. | Respiri Limited | Tyto Care Ltd. | NA |
| 510(k) Number | K221614 | K202062 | K181612 | NA |
| Device Class | Class II | Class II | Class II | Same |
| Review Panel | Anesthesiology | Anesthesiology | Cardiovascular | Same |
| Product code | PHZDQD | PHZ | DQD | Same |
| Regulation number | 21 CFR 868.1900 | 21 CFR 868.1900 | 21 CFR 870.1875 | Same |
| Classification Name | Diagnostic pulmonary-function interpretationcalculator | Diagnostic pulmonary-function interpretationcalculator | Stethoscope | Same |
| Intended use andindication for use | The TytoCare Lung SoundsAnalyzer is an over-the-counter decision supportsoftware system used in theevaluation of lung sounds inadults and children (2 yearsand older). It automaticallyanalyzes the acoustic signal | Wheezo is intended todetect and recordabnormal breath sounds(continuous adventitiousbreath sounds/CABS) atthe windpipe (trachea),reported as WheezeRatein adults and children (2 | The Tyto Stethoscope is anelectronic stethoscope thatenables transmission ofauscultation sound data,whereby a clinician at onelocation on an IP networkcan listen to the auscultationsounds of a patient on site or | SameBoth the predicate device and thesubject device have the sameintended use and indication foruse in that both are intended todetect specific and abnormalbreath sounds in the same |
| Device | Predicate | Reference device | Summary | |
| of the lung as recorded bythe FDA cleared compatibleTyto Stethoscope andidentifies recordings wherea specific abnormal lungsound suggestive of"Wheeze", is suspected. Itis not intended to detectother abnormal or normallung sounds. A licensedhealth care professional'sadvice is required tounderstand the meaning ofthe TytoCare Lung SoundsAnalyzer result. Healthcareprovider should considerthe device result inconjunction with recordingand other relevant patientdata. | years and older). Alicensed health careprofessional's advice isrequired to understand themeaning and importanceof the wheezo readings. | at a different location on theIP network with the signalcarried on an IP connectionbetween the two locations.The Tyto Stethoscope isintended to be used byprofessional users in aclinical environment or bylay users in a nonclinicalenvironment. The device isfor medical diagnosticspurposes only. The device isnot intended for self-diagnosis. | intended patient population (adultand pediatric) by the same user[Health Care Professional (HCP)]when self-administered by patientand/or the HCPs.Both devices are only intended tobe interpreted by HCP and HCPadvice is required for the patientto understand their result. Bothare labeled OTC. | |
| Type of use | Over-The-Counter Use | Over-The-Counter Use | Over-The-Counter Use | Same |
| Intended users | Intended to be used byprofessional users and layusers. | Intended to be used by layusers | Intended to be used byprofessional users and layusers | Similar, the TytoCare LungSounds Analyzer is intended forclinicians and lay users. |
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| Device | Predicate | Reference device | Summary | |
|---|---|---|---|---|
| Intended patient population | Intended for patients of 2 years and older | Intended for patients of 2 years and older | Intended for patients of all ages | Same |
| Intended environment | Non-clinical (home) and clinical | Non-clinical (home) | Non-clinical (home) and clinical | Similar.the TytoCare Lung Sounds Analyzer is intended for both home and clinical environment |
| Form | Stand-alone software system | Hardware and Software, hand-held stand-alone device used with smartphone | Hardware and Software, hand-held stand-alone device used with smartphone | Different.The acquisition of lung sounds of both devices is conducted by FDA cleared device, therefore there is no new question of effectiveness. |
| Device | Predicate | Reference device | Summary | |
| Device composition | The following modulescompose the TytoCareLung Sounds Analyzer:• The TytoCare LungSounds AnalyzerApplication Server (APS)• The TytoCare LungSounds AnalyzerAlgorithm Server (ALS)• The TytoCare LungSounds Analyzer WebServer (WBS) provides agraphic indicationwhether a wheeze isdetected in the recordingIt can be utilized both inpatient and clinician side. | The wheezo WheezeRateDetector consists of:• Wheezo SensingDevice• Wheezo App• Cloud server | Hardware:• A stethoscope ChestPiece:o Stethoscope Adaptoro TytoCare DeviceSoftware:• TytoCare DeviceApplication[runs on TytoCare Device]• TytoCareApplication[runs on the mobiledevice]• ClinicianApplication[runs on the clinicianplatform]• Server software[runs on the Tyto Server] | DifferentThe TytoCare Lung SoundsAnalyzer is a Stand-alonesoftware system used withcompatible Tyto Stethoscope torecord lung sounds. The Wheezois Hardware and Software, hand-held device used with smartphone.Both devices acquire lung soundsand provide indication on thepresence of wheeze to the user.The difference doesn't raise newquestions of safety oreffectiveness. |
| Input | Lung sounds recorded bycompatible TytoStethoscope | Lung sounds recorded bythe wheezo device | Lung sounds recorded bythe Tyto Stethoscope | DifferentBoth devices acquire lung soundswith device cleared by the FDAfor that purpose |
| Device | Predicate | Reference device | Summary | |
| The difference doesn't raise newquestions of safety oreffectiveness | ||||
| Device technologyand operatingprinciple | The recordings are createdby the compatible TytoStethoscope (K181612) andare sent by the third-partypoint of care app to theclinician app through thetelehealth server.The telehealth server sendsthe set of the lung soundrecordings to the TytoCareLung Sounds Analyzer webserver using its dedicatedAPI.The telehealth serversubsequently sends the linkto results and the relevantUI web view to the point ofcare app and clinician app.The algorithm runsautomatically and returns aresponse for each audio filewith the indication ofwheezes to the telehealthserver, which sends aresponse to both the | User places sensor ontheir neck for 30 secondsto perform a passivemanoeuvre. The devicerecords, analyses the lungsounds and quantifies thepresence of wheezing.The wheezo transfers auser's breath sound data tothe App using a SmartDevice. The sound data isanalyzed in the algorithm,which is integrated insidethe App and runs on theSmart Device. | User place the TytoStethoscope's adaptor in fullcontact with the patient'sbody, data is recorded andtransmitted from the chestpiece (i.e., the The TytoCaredevice mounted withadaptor) to the user end unit(i.e., a mobile device suchas smartphone), via Wi-Fi,and then over the internet tothe clinician end unit (i.e., aclinician platform such asPC or laptop. | Same.Both devices acquire lungsounds with device cleared by theFDA for that purpose, analyze thelung sounds and provideindication on the presence ofwheeze. |
| Device | Predicate | Reference device | Summary | |
| clinician side and thepatient side. | ||||
| Sensor type andtechnology | NA, software only | Microphone sensor (madeof silicon) acquires, filtersand digitizes the breathsounds. | Embedded acousticpiezoelectric contact sensorcaptures analog auscultationsound data, amplifies it,filters, digitizes and store it. | Different but the differencedoesn't raise new questions ofsafety or effectiveness. Thesubject device is intended to beused with compatible TytoStethoscope (reference device) torecord lung sounds.The predicate and the referencedevices both use a handheld piecewith embedded sensor in the chestpiece to acquire lung sounds. Thesafety and performance of thereference device sensor's type andtechnology has been establishedpreviously for acquiring lungsounds by means of FDAclearance. |
| Sensor location | NA, software only | Trachea | Top part of the chest and thetop part of patient's back(Left Upper Lobe, LeftLower Lobe, Right UpperLobe, Right Lower Lobe). | Different but the differencedoesn't raise new questions ofsafety or effectiveness. Thesubject device is intended to beused with compatible TytoStethoscope (reference device) torecord lung sounds.The safety and performance of thereference device sensor's locationfor acquiring lung sounds hasbeen established before by meansof FDA clearance. |
| Signal length | The length of the signal is dictated by the recording process of the compatible Stethoscope. The subject device processes the recordings in segments of up to 12 seconds while signals shorter than 6 seconds will not be processed. | 30 seconds | Variable | Different but the difference doesn't raise new questions of safety or effectiveness. The safety and performance of the different signal length that is used in the process of lung sound acquisition by numerous FDA cleared electronic stethoscopes including the reference device as well as Diagnostic Pulmonary-Function Interpretation Calculators including the predicate device was established. Thus, the impact of different signal length on performance does not raise a new question of safety or performance. |
| Data transfer and storage | The telehealth server sends the list of the recordings (identified by a unique identifier and time stamp) to the TytoCare Lung Sound Analyzer web server using its dedicated API. The server executes the TytoCare Lung Sounds Analyzer which runs the algorithm and provides the results. Then the TytoCare Lung Sound Analyzer web | Every recording is automatically uploaded to the cloud. However, if an Internet connection is not available, up to 20 most recent recordings will be stored locally on the smartphone. | The stethoscope recordings are transferred to the server using the software of the Tyto Stethoscope. However, if an Internet connection is not available, most recent recordings will be stored locally on the Tyto Stethoscope. | Different medical device data system but the difference doesn't raise new questions of safety or effectiveness. |
| Device | Predicate | Reference device | Summary | |
| server initiates the web userinterface.All the software subsystems(server and storage) arehosted in the cloud andcommunicate through IPnetwork. | ||||
| Output | • Positive (wheezesuspected),• Negative (Wheeze notsuspected),• The TytoCare lungssounds analyzer was notable to analyze therecording | Detection andquantification of wheezepresence, expressed as"wheeze rate". | NA | Different but no new questions ofsafety and effectiveness as boththe device and the predicate usesoftware algorithm to detectabnormal breath sound (wheeze)in lung recordings. |
| Accuracy | Non-inferior to clinicalreaders | Non-inferior to clinicalreaders | NA | Same |
| User interface forpoint of care andclinician apps | Web view | Mobile App | • TytoCare Device LCDscreen• TytoCare mobile App | SameBoth predicate and referencedevice use a proprietary mobileApp for recordings acquisitionand management.Different UI of the device usingweb-view doesn't raise newquestions of safety oreffectiveness. |
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Image /page/11/Picture/0 description: The image shows the logo for TytoCare. The logo features a stylized owl icon to the left of the word "tytocare" in a lowercase, rounded sans-serif font. A small trademark symbol is positioned to the upper right of the word "tytocare".
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Image /page/12/Picture/0 description: The image shows the logo for TytoCare. The logo is in a light blue color. The logo features an owl icon to the left of the word "tytocare", with the "TM" symbol in the upper right corner.
Table 1. Substantial Equivalence Summary
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The TytoCare Lung Sounds Analyzer and the predicate device have the same intended use and indication for use in that both are intended to detect specific and abnormal breath sounds in the same intended patient population (adult and children's) by the same user [Health Care Professional (HCP)] when administered by patient and/or the HCPs. Both devices are only intended to be interpreted by HCP advice is required for the patient to understand their result. Both are labeled OTC.
The TytoCare Lung Sounds Analyzer is a stand-alone software system that has the same intended use as the predicate (automatically detect wheezes) but at the absence of the sensor technology that is built into the predicate device. The Tyto Stethoscope (K181612) that is source of the lung recordings for the TytoCare Lung Sounds Analyzer was added as reference device to this premarket notification to account for these technological differences. The compatible Tyto Stethoscope is FDA cleared thus the technical differences as far as the different input to the device and its predicate do not raise new or different questions of safety and effectiveness.
Both devices are intended to detect wheezes and the output conveys this information to the user. The question concerning the ability of a software (in both cases the recording is analyzed by proprietary software) to accurately detect abnormal breath sound is not new. The predicate utilizes software for the analysis thus it raised similar questions before. The different software algorithm does require that its accuracy will be substantiated with valid performance data (accuracy testing).
Both devices display the result to the user interface is different but the difference does not raise new questions of safety and effectiveness as the predicate already introduced the questions concerning the impact of displaying the results to the same lay user. The different user interface does require that the substantial equivalence be based on performance evaluation (human factor testing).
Performance evaluation:
The TytoCare Lung Sounds Analyzer was subject to performance evaluation following methodology similar to the ones used to test the predicate device. A testing plan was developed and performed to verify that the TytoCare Lung Sounds Analyzer meets its specifications. The main aspects of the testing plan included:
- · SW verification and validation The software including both custom developed software and OTS software, have been verified and validated. The software is a Moderate Level of Concern (LOC) per FDA guidance.
- · Cybersecurity- The cybersecurity assessment including cybersecurity risk analysis was performed per FDA guidance for Content of Premarket Submissions for Management of Cybersecurity in Medical Devices.
- · Human factors validation testing was conducted, human factors data supports that individuals are able to successfully self-select themselves for the device and the risk of self-diagnosis is effectively mitigated similar to the predicate device.
- · Performance evaluation the Technical (Analytical) accuracy has been characterized and the Clinical preference has been validated including reproducibility:
The performance of the TytoCare Lung Sounds Analyzer device in detecting wheeze in recordings acquired by the compatible Tyto Stethoscope has been evaluated on a retrospective validation dataset of Tyto Stethoscope recordings sourced from real world use of the Tyto Care FDA cleared Tyto Stethoscope. 371 recordings (86 recordings
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Image /page/14/Picture/0 description: The image shows the logo for TytoCare. The logo is in blue and features a stylized owl icon to the left of the word "tytocare". The "TM" symbol is located in the upper right corner of the word "tytocare".
were Wheeze positive and 285 negative, from a total of 359 patients) corresponded to the intended patient population of the TytoCare Lung Sounds Analyzer Software (Age >2 years). The validation data-set included recordings with known pre-existing conditions (COPD or Asthma) (7.28%). The demographics of the validation dataset are presented hereunder:
Table 2: Validation data-set demographics
| N=359patients | |||
|---|---|---|---|
| Age Group (Years) | Wheeze Positive | Wheeze Negative | Total |
| 2-18 | 63 (24.3%) | 196 (75.7%) | 259 (72.1%) |
| >=18 | 17 (17%) | 83 (83%) | 100 (27.9%) |
| Gender | Positive | Negative | Total |
| Male | 49 (25.9%) | 140 (74.1%) | 189 (52.6%) |
| Female | 31(18.2%) | 139 (81.8%) | 170 (47.3%) |
To establish the ground truth, all of the recordings were read by three blinded experienced Pulmonologists at random, the binary ground truth was determined by majority vote of these three Pulmonologists.
For the characterization of the stand-alone accuracy, the automated binary result of the software has been compared to ground truth and specificity and sensitivity were calculated. This stand-alone accuracy is presented hereunder in table 3:
Table 3: The stand-alone accuracy of the TytoCare Lung Sounds Analyzer
| Parameter | Estimate (two-sided 95% CI) |
|---|---|
| Sensitivity (Se) | 0.69 (0.57–0.78) |
| Specificity (Sp) | 0.92 (0.88–0.95) |
For the characterization of the clinical performance the Area under the Receiver Operating Curve (AUC) for Wheeze detection by the device was compared to the clinical readers (Physicians non-Pulmonologists). To calculate the AUC the probability score was extracted from the device and compared to a 5-point likelihood score that was recorded by the clinical readers independently for every recording.
The primary endpoint was to establish that the clinical accuracy of the TytoCare Lung Sounds Analyzer software's is non- inferior to the clinical readers provided with a 5% non-inferiority margin. The secondary endpoint was the reproducibility of the software as compared to the readers.
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Image /page/15/Picture/0 description: The image shows the TytoCare logo. The logo features a stylized owl icon on the left, followed by the word "tytocare" in a lowercase, sans-serif font. A trademark symbol is located to the upper right of the word "tytocare".
Table 4: The clinical accuracy of the TytoCare Lung Sounds Analyzer as compared to Clinical readers.
| Parameter | Estimate 95% two sides CI |
|---|---|
| AUC TytoCare Lung Sound Analyzer | 0.91 (0.86-0.94) |
| AUC Clinical readers | 0.83 (0.78-0.86) |
The AUC of the device was 0.91 (0.86-0.94) compared to the reader's AUC of 0.83 (0.78-0.86). The difference in AUC was 0.09 (0.04-0.13) which supports the noninferiority (0.04 > margin of -0.05) of the device compared to the reader. Noninferiority was established also when confounders such as age groups (<2, 2-6, >6 yo) and the relevant pre-existing conditions (Asthma or COPD) were accounted for in subgroup analysis.
Table 5: Reproducibility of device compared to the clinical readers in the detection of wheezes.
| Parameter | Kappa | LCI | UCI |
|---|---|---|---|
| Clinical Readers | 0.6134 | 0.5183 | 0.7016 |
| TytoCare Lung sounds analyzer | 1.0000 | 1.0000 | 1.0000 |
| TytoCare Lung sounds analyzer– Clinical Readers | 0.3866 | 0.2984 | 0.4817 |
LCI – lower bound of two-sided 95% confidence interval; UCI – upper bound of two-sided 95% confidence interval
Standards applied
- . ANSI AAMI ISO 14971:2019, Medical devices - Application of risk management to medical devices
- ANSI AAMI IEC 62304:2006/A1:2016, Medical device software - Software life cycle processes
- . ISO 15223-1 Fourth edition 2021-07, Medical devices - Symbols to be used with information to be supplied by the manufacturer - Part 1: General requirements
- IEC 62366-1 Edition 1.1 2020-06, Medical devices Part 1: Application of ● usability engineering to medical devices
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Conclusion
The TytoCare Lung Sounds Analyzer Software has the same intended use and similar indication for use as the predicate. The TytoCare Lung Sounds Analyzer is only compatible with the reference FDA cleared TytoCare Stethoscope that provides the input stethoscope recording. Therefore, the technological differences in sensor technology, anatomical recording site, signal length and user interface as compared to the predicate do not raise new/different questions of safety and effectiveness relative to the reference device. The differences in the user interface and software algorithm do not raise new/different questions of safety and effectiveness. These differences were evaluated for their effect on safety and performance using a performance evaluation for device accuracy that followed the same method used to substantiate the predicate device and the results demonstrated that similarly the TytoCare Lung Sounds Analyzer is as safe and as effective as the predicate in that its accuracy in detecting wheeze is non inferior to that of the physician. Human factors data supports that the TytoCare Lung Sounds Analyzer has been found to be as safe and as effective for the intended users, uses and use environments. Thus, we conclude that the TytoCare Lung Sounds Analyzer is substantially equivalent. i.e. as safe and as effective as the predicate device.
§ 868.1900 Diagnostic pulmonary-function interpretation calculator.
(a)
Identification. A diagnostic pulmonary-function interpretation calculator is a device that interprets pulmonary study data to determine clinical significance of pulmonary-function values.(b)
Classification. Class II (performance standards).