The EarliPoint System is indicated for use in specialized developmental disabilities centers as a tool to aid clinicians in the diagnosis and assessment of Autism Spectrum Disorder (ASD) for patients ages 16 months through 30 months.

Device Description

The EarliPoint System is a medical device for diagnosis of Autism Spectrum Disorder (ASD) in children.

EarliPoint System consists of the following:

EarliPoint WebPortal to enter the patient information and for access to the patient evaluation results,
EarliPoint Device with eye-tracking capability captures the patient visual response to social information provided in the form of a series of age-appropriate videos
Artificial intelligence software analyzes the eye-tracking data and provides a diagnosis for ASD.
Eye-tracking data also outputs 3 indices (called EarliPoint Severity Indices) that proxy the ADOS-2 and Mullen validated ASD instruments
- Social Disability Index correlates and proxies ADOS-2
- Verbal Ability Index correlates and proxies the age equivalent Mullen Verbal Ability score
- Non-verbal Ability Index correlates and proxies the age equivalent non-verbal Mullen Ability score

AI/ML Overview

The EarliPoint System, a device for diagnosing Autism Spectrum Disorder (ASD), underwent a pivotal study to demonstrate its safety and effectiveness.

Here's a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of "acceptance criteria" but rather shows the device's performance (sensitivity and specificity) relative to a predicate device (CanvasDx) and a "gold standard" expert clinical diagnosis. The implication is that meeting or exceeding the predicate's performance, especially for certain populations, was a key aspect of acceptance.

Population/Metric	Sensitivity Mean (n/N) [95% CI]	Specificity Mean (n/N) [95% CI]
CanvasDx (mITD), N=425	51.6% (63/122) [42.8% - 60.5%]	18.5% (56/303) [14.3% - 23.3%]
EarliPoint (mITD), N=475	71% (157/221) [64.6% - 76.9%]	80.7% (205/254) [75.3% - 85.4%]
EarliPoint CertainDx (N=335)	78.0% (117/150) [70.5%, 84.3%]	85.4% (158/185) [79.5% - 90.2%]
EarliPoint UncertainDx (N=140)	56.3% (p=1.00)	68.1% (p=0.69)

Note: The document states: "When compared to the predicate. CanvasDx, the sensitivity and specificity of the EarliPoint device are higher than the CanvasDx and hence the two devices are substantially equivalent." This implies that outperforming the predicate was a key acceptance criterion.

2. Sample Size and Data Provenance

Test Set Sample Size: 475 evaluable patients for primary and secondary endpoint analysis (from an initial enrollment of 500).
Data Provenance: The study was "multi-center" with data collected from "six sites in the United States." The study was "prospective."

3. Number of Experts and Qualifications for Ground Truth

Number of Experts: Not explicitly stated, but the ground truth was established by "expert clinicians" at "six sites." The document refers to "expert clinician diagnosis" and "clinicians' reference diagnoses."
Qualifications of Experts: Described as "expert clinician diagnosis (current best practice for diagnosis of ASD)." Specific qualifications (e.g., years of experience, specialization) are not detailed.

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method for conflicting expert opinions. It refers to a "gold standard of the expert clinician diagnosis." It does, however, categorize the ground truth into "Certain Dx Population" (clinicians' certainty rating > 80%) and "Uncertain Dx Population" (clinicians' certainty rating ≤ 80%), indicating some level of consideration for diagnostic confidence.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was explicitly mentioned in the provided text, comparing human readers with AI assistance vs. without AI assistance. The study focuses on the device's performance compared to human expert diagnosis as the ground truth. The device is intended as an "aid clinicians," suggesting a human-in-the-loop scenario, but a specific MRMC study design is not detailed.

6. Standalone (Algorithm Only) Performance

The reported sensitivity and specificity values represent the standalone performance of the EarliPoint System's algorithm in diagnosing ASD, as it provides a "diagnosis for ASD" from analyzing eye-tracking data. The study "evaluated for ASD by both the EarliPoint system and by expert clinician diagnosis."

7. Type of Ground Truth Used

The primary ground truth used was "expert clinician diagnosis (current best practice for diagnosis of ASD)."
Additionally, the study correlated the three EarliPoint Severity Indices (Social Disability, Verbal Ability, Non-verbal Ability) against corresponding "expert clinical instruments of ADOS-2 and Mullen." This indicates a reliance on established clinical diagnostic tools as part of the expert ground truth.

8. Sample Size for the Training Set

The document does not provide the sample size used for the training set. It only describes the design and results of the pivotal clinical study (test set).

9. 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 focuses solely on the test set's ground truth.

Summary

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June 8, 2022

Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, with the word "ADMINISTRATION" underneath.

EarliTec Diagnostics, Inc. % Sew-Wah Tay, Ph.D. Regulatory Consultant Libra Medical, Inc. 8401 73rd Ave N. Suite 63 Brooklyn Park, Minnesota 55428

Re: K213882

Trade/Device Name: EarliPoint System Regulation Number: 21 CFR 882.1491 Regulation Name: Pediatric Autism Spectrum Disorder Diagnosis Aid Regulatory Class: Class II Product Code: QPF Dated: December 28, 2021 Received: December 29, 2021

Dear Dr. Sew-Wah Tay:

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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part

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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 (QS) 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,

Jay Gupta Assistant Director DHT5A: Division of Neurosurgical, Neurointerventional and Neurodiagnostic Devices OHT5: Office of Neurological and Physical Medicine 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) K213882

Device Name EarliPoint System

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
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X Prescription Use (Part 21 CFR 801 Subpart D)

| Over-The-Counter Use (21 CFR 801 Subpart C)

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510(K) SUMMARY

1 SUBMITTER

Sponsor/Manufacturer

EarliTec Diagnostics, Inc. 755 Commerce Drive, Suite 700 Decatur, GA 30030

Correspondent

Sew-Wah Tay, PhD Regulatory Consultant, Libra Medical Inc. Phone: 612-801-6782 Email: swtay@libramed.com

Date prepared: March 17, 2022

2 DEVICE

Name of Device:	EarliPoint System
Common or Usual Name:	Pediatric Autism Spectrum Disorder diagnostic tool
Regulation Number:	21 CFR 882.1491
Regulatory Class:	II
Product Code:	OPF

PREDICATE DEVICE 3

Predicate Device: Cognoa ASD Diagnosis Aid (DEN200069)

Technological Reference: 2D VOG - Video-Oculography (K972243)

DEVICE DESCRIPTION 4

The EarliPoint System is a medical device for diagnosis of Autism Spectrum Disorder (ASD) in children.

EarliPoint System consists of the following:

EarliPoint WebPortal to enter the patient information and for access to the patient -

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evaluation results,

-EarliPoint Device with eye-tracking capability captures the patient visual response to social information provided in the form of a series of age-appropriate videos
-Artificial intelligence software analyzes the eye-tracking data and provides a diagnosis for ASD.
-Eye-tracking data also outputs 3 indices (called EarliPoint Severity Indices) that proxy the ADOS-2 and Mullen validated ASD instruments
- o Social Disability Index correlates and proxies ADOS-2
- Verbal Ability Index correlates and proxies the age equivalent Mullen Verbal o Ability score
- o Non-verbal Ability Index correlates and proxies the age equivalent non-verbal Mullen Ability score

The eye-tracker used in the EarliPoint device has similar capability and specifications to the 2D VOG (K972243 - technological reference). The technical specifications of the 2D VOG are compared to the eye tracking component of EarliPoint.

Description	2D VOG(K972243)	EarliPoint Eye Tracking Sub-system
Wavelength	Near-InfraredSpectrum	Near-Infrared Spectrum
Intensity	Undefined but likelymeets IEC/EN62471	Conforms to safety limit for continue use perIEC/EN 62471(Photobiological safety of lamps/lampsystem)
Light source	IR LED	IR LED
Duration ofUse/Exposure	~15 minutes	~15 minutes
Accuracy/Precisionfor intended use(gaze position)	Unknown	0.5°
RecordingMeasurement	2D Eye Movements	2D Eye Movements
Video Hardware	Video Camera	Video Camera
Mounting Hardware	Mobile eye tracking(Face Mask)	Remote eye-tracking system(Display Screen)

Table 1. Eye Tracking Technical Specifications

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Description	2D VOG(K972243)	EarliPoint Eye Tracking Sub-system
Processor Hardware	Personal computer	Personal computer
Sampling Rate	Undefined	120 Hz

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റ INDICATIONS FOR USE

The EarliPoint System is indicated for use in specialized developmental disabilities centers as a tool to aid clinicians in the diagnosis and assessment of ASD patients ages 16 months through 30 months.

6 PERFORMANCE DATA

The following performance data were provided in support of the substantial equivalence determination.

6.1 Mechanical/electrical safety and electromagnetic compatibility (EMC)

Mechanical/electrical safety and EMC testing were conducted on the EarliPoint device consisting of the patient console and the operator console for patient behavioral tracking. The EarliPoint device is classified as Class I for protection against electric shock with Type B applied part and is intended for continuous mode of operation. Compliance testing shows that the EarliPoint device complies with all the applicable tests of IEC 60601-1 standard for mechanical/electrical safety and the IEC 60601-1-2 standard for EMC.

6.2 Software Verification and Validation Testing

Software verification and validation testing were conducted and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices." The software for this device was considered as a "minor" level of concern as a failure or latent flaw in the software is unlikely to result in injury.

6.3 Clinical Studies

The safety and effectiveness of the EarliPoint System in diagnosing the presence ASD was evaluated in a pivotal study where patients were diagnosed by the device as well and expert clinicians (reference standard).

In addition, a repeatability and reproducibility study showed that the EarliPoint diagnosis is reliable and consistent. The pivotal study showed that the device is safe and effective as a tool to assist clinician in diagnosing young children for ASD.

6.3.1 Pivotal Study Design

The pivotal study was a prospective, double-blind, multi-center, within-subject comparison where 500 patients from six sites in the United States were enrolled, of which 475 were evaluable for primary and secondary endpoint analysis and 25 patients had missing data of the device or the control diagnosis (standard of care).

All patients were evaluated for ASD by both the EarliPoint system and by expert clinician diagnosis (current best practice for diagnosis of ASD) to evaluate the sensitivity and specificity of the EarliPoint System diagnosis relative to the expert clinical diagnosis. The study also correlated the three EarliPoint Severity Indices of social disability, verbal ability and nonverbal ability against the corresponding expert clinical instruments of ADOS-2 and Mullen.

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The pivotal study showed that the EarliPoint device was safe and effective in the diagnosis of ASD in children. There was no reported serious adverse event related to the use of the EarliPoint system and, like the CanvasDx device study, there was evidence of EarliPoint device performance differences across subjects based on sex, race/ethnicity.

When compared to the predicate. CanvasDx, the sensitivity and specificity of the EarliPoint device are higher than the CanvasDx and hence the two devices are substantially equivalent.

Population	SensitivityMean (n/N)95% CI	SpecificityMean (n/N)95% CI
CanvasDx (mITD)N=425	51.6% (63/122)42.8% - 60.5%	18.5% (56/303)14.3% - 23.3%
EarliPoint (mITD)N=475	71% (157/221)64.6% - 76.9%	80.7% (205/254)75.3% - 85.4%
EarliPoint CertainDx(Clinicians are Certain ofDiagnosis only)N=335	78.0% (117/150)70.5%, 84.3%	85.4% (158/185)79.5% - 90.2%

The primary effectiveness endpoint was compared to the gold standard of the expert clinician diagnosis. Three populations were evaluated for the primary endpoint: mITD (n=475, all patients with evaluable data), Certain Dx Population (n=335, patients with expert clinician diagnosis with certainty rating > 80%), and Uncertain Dx Population (n=140, patients with expert clinician diagnosis with certainty rating ≤ 80%). As expected, the best results were obtained when the ground truth (clinicians' reference diagnoses) were more certain.

For the subgroup of Uncertain Dx population, given the uncertain nature of the expert diagnosis, the EarliPoint system showed low specificity and sensitivity with mean specificity of 68.1% (p=0.69) and mean sensitivity of 56.3% (p=1.00).

6.3.2 Repeatability and Reproducibility Study

In the EarliPoint repeatability and reproducibility study, the variance attributable to the device is 6.18 % repeatability and 0% for reproducibility assuming no subject and device interaction. Majority of the variance is a result of subject-to-subject variability.

7 PREDICATE COMPARISON

7.1 Intended Use Comparison

The EarliPoint system has the same intended use as the Cognoa ASD Diagnosis Aid (DEN200069). Both are intended for non-invasive objective evaluation of the ASD status of a child by using software to analyze the child's behavior in response to external stimuli. Both are intended for use in to evaluate young children.

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While the indication for use of the devices differs slightly, the intended use is the same. The EarliPoint system diagnostic tool outputs definite diagnosis of positive ASD or negative ASD for each and every patient while the CanvasDx device outputs an actual diagnosis of ASD or non-ASD in only 32% of the time. In 68% of the time, the CanvasDx output an indeterminate diagnosis. Hence the CanvasDx is indicated as a screening aid for diagnosis of ASD. Results from both devices are intended to be presented to the patient's family by a trained clinician.

While the indications for use statements are not identical, we believe that the intended use is substantially equivalent for the purpose of the device classification of the EarliPoint system as a Class II device. Hence the EarliPoint System met the first criteria for substantial equivalence

Description	Subject Device:EarliPoint System	Predicate Device:Cognoa ASD Diagnosis Aid(DEN200069)	TechnologicalReferenceSensomotoric EyeTracker(K972243)
Data collection	Patient console with eye-tracking technology for datacollection and softwareanalysis for diagnosis of ASD.	Data collected using normalcommercially available camerato videotaped behavior	Similar eye-trackingtechnology for datacollection
ASD diagnosis	Use software algorithm toanalyze the eye tracking dataand compare it to data modelof normative data for diagnosis	Software analysis of video,behavior assessmentsquestionnaires (parent, video-based expert, and healthcareprofessional) to generateassessment of ASD.	NA
Electrical safetytesting	Meets electrical safetystandards per IEC 60601-12005:2012	Not applicable as this issoftware as a medical device	Met all electrical andLED safety testing
Software	Compliant to ISO 62304	Compliant to ISO 62304	NA
Clinical performancedata for ASD	Pivotal data available to showsafety and effectiveness	Pivotal data available to showsafety and effectiveness	NA
Risk level of thedevice	Low risk device, non-invasive	Low risk device	Low risk device

7.2 Technological Characteristics Comparison With The Predicate CanvasDx Device

The principle technological characteristic for both the subject and predicate device (CanvasDx) is digitizing the patient's reaction to social stimuli in the form of video and using software to analyze the child's reaction for the evaluation of ASD. Both devices are non-invasive and are of low risk. The eye-tracker is technological similar to the 2D VOG eye-tracker which have

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decades of safe use so there are no new safety questions.

The EarliPoint device analyzes the patient reaction to social stimuli by tracking the patient's eye movement when stimulated by a series of videos of social scenes while the predicate analyzes the videos of the patient's reaction when placed in a socially stimulating setting. The CanvasDx device analyzes the patient reaction to social stimuli by taking a video of the patient's and analyzing the video in combination with assessments from the caregiver and primary care giver after digitizing the responses.

Both devices use artificial intelligence software to analyze the patient's reaction to provide an ASD diagnosis or assist in the diagnosis for ASD.

At a high level. the subject and predicate devices are based on the following same technological elements:

. Collection of digital information of patient's reaction when stimulated socially.
Software analysis of patient physical reactions for evaluation of ASD. ●

Scientific data in the form of clinical performances of the device show that any technological differences between the subject and predicate devices do not raise new or different concerns of safety and efficacy.

7.3 Substantial Equivalence Conclusion

Based on the same intended use, technological characteristics, and the summary of data submitted, the EarliPoint device is found to be substantially equivalent to the predicated device. Safety and performance test data including bench testing to IEC 60601-1 (2012) and comprehensive assessment including clinical data, demonstrated the device safety and effectiveness as intended without raising new and different questions of safety and effectiveness.

Regulation Number and Section

§ 882.1491 Pediatric Autism Spectrum Disorder diagnosis aid.

(a)
Identification. A pediatric Autism Spectrum Disorder diagnosis aid is a prescription device that is intended for use as an aid in the diagnosis of Autism Spectrum Disorder in pediatric patients.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use, including an evaluation of sensitivity, specificity, positive predictive value, and negative predictive value using a reference method of diagnosis and assessment of patient behavioral symptomology.
(2) Software verification, validation, and hazard analysis must be provided. Software documentation must include a detailed, technical description of the algorithm(s) used to generate device output(s), and a cybersecurity assessment of the impact of threats and vulnerabilities on device functionality and user(s).
(3) Usability assessment must demonstrate that the intended user(s) can safely and correctly use the device.
(4) Labeling must include:
(i) Instructions for use, including a detailed description of the device, compatibility information, and information to facilitate clinical interpretation of all device outputs; and
(ii) A summary of any clinical testing conducted to demonstrate how the device functions as an interpretation of patient behavioral symptomology associated with Autism Spectrum Disorder. The summary must include the following:
(A) A description of each device output and clinical interpretation;
(B) Any performance measures, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV);
(C) A description of how the cutoff values used for categorical classification of diagnoses were determined; and
(D) Any expected or observed adverse events and complications.
(iii) A statement that the device is not intended for use as a stand-alone diagnostic.