DeNovo Summary 180001

DE NOVO CLASSIFICATION REQUEST FOR

IDX-DR

EGULATORY INFORMATION

FDA identifies this generic type of device as:

Retinal diagnostic software device. A retinal diagnostic software device is a

prescription software device that incorporates an adaptive algorithm to evaluate

ophthalmic images for diagnostic screening to identify retinal diseases or conditions.

NEW REGULATION NUMBER: 21 CFR 886.1100

LASSIFICATION: Class II

RODUCT CODE: PIB

ACKGROUND

DEVICE NAME: IDx-DR

SUBMISSION NUMBER: DEN180001

DATE OF DE NOVO: January 12, 2018

CONTACT: IDx, LLC

2300 Oakdale Blvd

Coralville, IA 52241

INDICATIONS FOR USE

IDx-DR is indicated for use by health care providers to automatically detect more than

mild diabetic retinopathy (mtmDR) in adults diagnosed with diabetes who have not been

previously diagnosed with diabetic retinopathy. IDx-DR is indicated for use with the

Topcon NW400.

LIMITATIONS

Prescription Use only: Federal (USA) law restricts this device for sale by or on the order

of a physician.

Warnings

 IDx-DR is only designed to detect diabetic retinopathy. IDx-DR is not intended to detect

concomitant diseases. Patients should not rely on IDx-DR for detection of any other

disease.

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 People with diabetes may be at elevated risk of glaucoma and should be seen by an eye

care provider for glaucoma screening in accordance with recognized patient management

recommendations. IDx-DR does not screen for glaucoma.

 Patients should be informed that IDx-DR does not treat retinopathy and that their images

are analyzed to determine whether further examination is needed by an eye care provider.

Physicians should review IDx-DR results and advise patients of recommended referrals

to an eye care provider for evaluation and potential treatment.

 If IDx-DR is not able to generate a screening result on a patient who has been

pharmacologically dilated, the patient may have vision threatening diabetic retinopathy,

or other abnormalities including cataract. Such a patient should be seen by an eye care

provider for evaluation.

 Patients with an IDx-DR output indicating diabetic retinopathy should be immediately

referred to an eye-care provider for further screening and treatment. In cases where the

IDx-DR test provides no result, the patient should always be immediately retested or

referred to an eye care provider. In cases where the IDx-DR test does not detect the

presence of referable disease, the patient should be strongly encouraged to test again at an

appropriate point in the future.

 Do not use IDx-DR to screen for diabetes mellitus – IDx-DR is only for use in people

already diagnosed with diabetes mellitus.

 IDx-DR is designed to work with good quality, in-focus, digital retinal color images of

the fovea and disc. Do not submit retinal color images that are of poor quality, retinal

color images that were not made with a digital fundus camera, retinal images that are not

in color, images of other tissues or objects other than the retina, or color images that were

obtained by scanning images.

 IDx-DR is only intended to be used with images acquired with a Topcon TRC-NW400.

Refer to the FDA approved label of the Topcon TRC-NW400 for relevant

contraindications, warnings, and precautions.

PLEASE REFER TO THE LABELING FOR A COMPLETE LIST OF WARNINGS,

PRECAUTIONS AND CONTRAINDICATIONS.

EVICE DESCRIPTION

The IDx-DR consists of several components. A fundus camera is attached to a computer, where

the IDx-DR Client is installed. The Client allows the user to interact with the server-based

analysis software over a secure internet connection. Using the Client, users identify two fundus

images per eye to be dispatched to IDx-Service. IDx-Service is installed on a server hosted at a

secure datacenter. IDx-DR Analysis, which runs inside IDx-Service, processes the fundus images

and returns information on the image quality and the presence or absence of mtmDR to IDx-

Service. IDx- Service then returns the results to the IDx-DR Client.

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The component parts of IDx-DR illustrated above are summarized here and further described in

the following sections:

 IDx-DR Analysis: the analysis software that analyzes the patient’s images and determines

exam quality and the presence/absence of diabetic retinopathy. Additional information about

IDx-DR Analysis is provided below.

 IDx-DR Client: a software application component running on a computer, usually connected

to the fundus camera, at the customer site. Using this software, the customer can transfer

images to IDx-DR Analysis via IDx-Service and receive results back. IDx-DR Client does

not require installation and runs on all Windows computers locally. It requires an internet

connection to work. In a case where an exam could not be analyzed due to image quality or

an image acquisition protocol error, quality feedback is provided to help the operator acquire

high quality exams and successfully obtain a result after resubmission.

 IDx-Service: a general exam analysis service delivery software package, managed in a

separate software project with its own set of product and software requirements. IDx-Service

contains a webserver front-end that securely handles incoming requests, a database that

stores customer information, and a logging system that records information about each

transaction through IDx-Service. IDx-Service is also primarily responsible for device

cybersecurity.

UMMARY OF NONCLINICAL/BENCH STUDIES

OFTWARE

Software version IDx-DR 2.0.0 US was identified as having a major level of concern as

defined in the FDA guidance document “Guidance for the Content of Premarket

Submissions for Software Contained in Medical Devices.” The software documentation

included:

1. Software/Firmware Description

2. Device Hazard Analysis

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3. Software Requirement Specifications

4. Architecture Design Chart

5. Software Design Specifications

6. Traceability

7. Software Development Environment Description

8. Revision Level History

9. Unresolved Anomalies

10. Cybersecurity

A comprehensive risk analysis was provided for the software with detailed description of

the hazards, their causes and severity as well as acceptable methods for control of the

identified hazards. IDx provided a description, with test protocols including pass/fail

criteria and report of results, of acceptable verification and validation activities at the

unit, integration and system level. The expected impact of various hardware features on

performance was assessed and minimum specifications for acceptable images for analysis

were specified.

The cybersecurity considerations of data confidentiality, data integrity, data availability,

denial of service attacks and malware were adequately addressed using platform controls,

application controls and procedure controls and evidence was provided for the controls

performance as intended. Risks related to failure of various software components and

their potential impact on patient reports and operator failures were also adequately

addressed in the risk analysis. This software documentation information provided

sufficient evidence of safe and effective software performance.

IDx has provided a full characterization of the technical parameters of all the components

of the software, including a description of the algorithms that analyzes the patient’s

images, determines exam quality and the diagnostic screening of diabetic retinopathy.

IDx-DR requires one optic disc centered image and 1 macula centered image from a

fundus camera with at least 1000 by 1000 pixels per image. The impact of the applicable

image quality characteristics are described in the Image Quality and Human Factors

Validation Testing sections below.

The IDx-DR artificial intelligence device design has the ability to perform analysis on the

specific disease features that are important to a retina specialist for diagnostic screening

of DR. IDx will make future algorithm improvements under a consistent medically

relevant framework. A protocol was provided to mitigate the risk of algorithm changes

leading to changes in the device’s technical specifications, which would lead to changes

in false positive or false negative results. These changes could significantly affect clinical

functionality or performance specifications directly associated with the intended use of

the device. The protocol specifies the level of change in device specifications that could

significantly affect the safety or effectiveness of the device, triggering the requirement

for a 510(k) premarket notification submission before commercial introduction. This

protocol implements the recommendations provided in the FDA guidance document

“Deciding When to Submit a 510(k) for a Software Change to an Existing Device:

Guidance for Industry and FDA Staff.”

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SUMMARY OF CLINICAL INFORMATION

IDx conducted a pivotal clinical study with 900 patients who were enrolled at 10 primary

care sites. The target population was asymptomatic persons, ages 22 and older, who had

been diagnosed with diabetes and had not been previously diagnosed with diabetic

retinopathy (DR). The study population was enriched by targeting enrollment of subjects

with elevated Hemoglobin A1c (HbA1C) levels for a portion of the study in order to

increase the likelihood of enrolling patients with more serious DR. Before any participant

was recruited, IDx-DR operator trainees had to attest that they had not previously

performed ocular imaging. They then underwent a one-time standardized four hour

training program on how to acquire images, how to improve image quality if IDx-DR

gave an insufficient quality output, and how to submit images for analysis to IDx-DR. No

additional training was provided to any of the IDx-DR operators for the duration of the

study. A diagnosis of diabetes was defined as meeting the criteria established by either

the World Health Organization (WHO) or the American Diabetes Association (ADA);

Hemoglobin A1c (HbA1c ≥ 6.5% based on repeated assessments; Fasting Plasma

Glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L) based on repeated assessments; Oral Glucose

Tolerance Test (OGTT) with two-hour plasma glucose (2-hr PG) ≥ 200 mg/dL (11.1

mmol/L) using the equivalent of an oral 75g anhydrous glucose dose dissolved in water;

or symptoms of hyperglycemia or hyperglycemic crisis with a random plasma glucose

(RPG) ≥ 200 mg/dL (11.1 mmol/L). During the study, the IDx-DR operator made sure

that for every participant, a final IDx-DR output of more than mild DR (mtmDR)

detected (defined below), more than mild DR not detected, or insufficient quality, was

obtained. After the novice operator had generated an IDx-DR result, but during the same

visit, each participant underwent additional retinal imaging captured by a professional

ophthalmic photographer who had been certified by the Fundus Photography Reading

Center (FPRC). The professional ophthalmic photographer remained masked at all times

to the IDx-DR output and used a different, FDA-cleared camera system (Topcon 3D

OCT-1 Maestro) to obtain dilated four widefield stereo color fundus photography, lens

photography for media opacity assessment, and macular optical coherence tomography

(OCT) imaging.

Fundus Photography Reading Center – Reference Standard

These images were all sent to the FPRC, where the severity of retinopathy and diabetic

macular edema (DME) were determined according to the Early Treatment for Diabetic

Retinopathy Study severity (ETDRS) scale. These readings formed the reference standard

for the study. The FPRC grading protocol consisted of the following: the four widefield

stereo image pairs were read by three experienced and validated readers according to the

well-established ETDRS scale, using a majority voting paradigm. The macular OCT

images were read by the same readers for the presence of center involved DME according

to the Diabetic Retinopathy Clinical Research Network (DRCR) grading paradigm. Each

participant was categorized as mtmDR+ (ETDRS level 35 or higher and /or DME

present), or mtmDR- (ETDRS level 10-20 and DME absent). The worst of two eyes were

compared with the IDx-DR output at the participant level. Because DME can be

identified on the basis of retinal thickening on stereoscopic fundus photographs, as well

as on the basis of retinal thickening on OCT, performance using both definitions was

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analyzed. Stereoscopic fundus-based Clinically Significant DME (CSDME) was

identified if there was either retinal thickening or adjacent hard exudates < 600μm from

the foveal center, or a zone of retinal thickening > 1 disc area, part of which is less than 1

disc diameter from the foveal center, according to the FPRC, in any eye. OCT based

center involved DME was identified if a participant had central subfield (a 1.0mm circle

centered on the fovea) thickness that was >300μm according to the FPRC, in any eye.

Accordingly, the definition of mtmDR+: fundus mtmDR+ is defined as:

 ETDRS level ≥ 35 (determined from fundus photographs) and/or

 CSDME (determined from fundus photographs) and multimodal mtmDR+ is

defined as:

o ETDRS level ≥ 35 (determined from fundus photographs),

and / or

o CSDME (determined from fundus photographs)

and / or

o center-involved DME (determined from OCT).

FPRC readers were masked to the IDx-DR system outputs at all times, masked to the

fundus photograph reading when evaluating the OCT images, and masked to OCT

readings when evaluating fundus photographs. A total of 900 participants were enrolled

at 10 sites, of which 892 participants completed all procedures. A subset of 819 of these

participants could be fully analyzed, giving an analyzable fraction of 92% (95% CI, 90%-

93%). Median age was 59 years (range, 22-84 years); 47.5% of participants were male.

For the entire group of participants, 16.1% were Hispanic, 83.3% were not Hispanic, and

0.6% were unknown. Also, 63.4% were white, 28.6% African American, and 1.6%

Asian. 7.1% had type 1 diabetes and 92.9% had type 2 diabetes. Overall mean HbA1C ±

std was 9.4 ± 2.3mmol/l. Mean duration of diabetes was 12.7 ± 8.9 years, with a median

of 11.0 and a range of 0.0 - 57.0 years. The 819 participants whose results could be fully

evaluated and the 73 participants whose results could not be analyzed differed

significantly with respect to lens status, while mean age, ethnicity, race, and HbA1C level

were not significantly different.

Study Endpoint Results

A total of 900 participants were enrolled at 10 sites, of which 892 participants completed

all procedures. Of the 892 participants completing all procedures, 40 had exams that

could not be analyzed by the FPRC and 33 received an IDx-DR insufficient quality result

or had a missing IDx-DR output. Thus, a subset of 819 of participants could be fully

analyzed by the IDx-DR device to produce an IDx-DR disease output, giving an

analyzable fraction of 92% (95% CI, 90%-93%). The primary outcomes were the

sensitivity and specificity of IDx-DR. Performance thresholds were defined at 85.0% for

sensitivity and 82.5% for specificity, reflecting anticipated enrollment numbers and pre-

specified regulatory requirements. In addition to observed sensitivity and specificity,

enrichment corrected sensitivity and specificity were calculated using logistic regression

to evaluate whether performance would have been different if the study population had

not been enriched with subjects with higher HbA1C levels. Analyses were based on the

data from all participants who had valid results on both IDx-DR and the FPRC imaging

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and reading protocol, except where indicated; reported subgroup analyses were

prespecified. A total of 198 mtmDR+ participants were fully analyzable according to the

FPRC reading protocol, thus prevalence was 23.8% (198/819). Of these, 29 had CSDME

according to fundus photography; 19 participants had center-involved DME according to

OCT; and 42 participants had either CSDME and/or center involved DME, with

corresponding prevalence of 3.5% for CSDME, 2.3% for center-involved DME, and

5.1% for any DME according to both of these assessments. Average centerfield thickness

was 239μm (+-0.05 μm) in the participants with CSDME (from fundus photographs

only), and 304μm (+-0.06 μm) in the participants with center-involved OCT DME. IDx-

DR correctly identified 173 of the 198 fully analyzable participants with fundus

mtmDR+, thus observed sensitivity was at 87.4% (95%CI, 81.9% - 92.9%). Sensitivity

corrected for enrichment was also high, at 87.2% (95% CI, 81.8% - 91.2%) to fundus

mtmDR+, and 85.9% (95% CI, 82.5%-88.7%) to multimodal mtmDR+, i.e. including

participants with either CSDME or center involved DME. There were no significant

effects for age, sex, race, ethnicity, HbA1C, lens status or site, on sensitivity. The

retrospective power was 93%. IDx-DR correctly identified, with an mtmDR positive

output, 28 of 29 (96%; 95% CI, 83%-99%) participants with CSDME (fundus

photographs only), 16 of 19 participants (84%; 95% CI, 62% - 94%) with center-involved

DME (OCT only), and identified all participants with ETDRS level 43 or higher. Among

the 621 fully analyzable participants who did not have fundus mtmDR according to

FPRC grading, there were 556 participants with an mtmDR not detected output, thus

observed specificity was 89.5% (95% CI, 86.9%-93.1%). Specificity corrected for

enrichment was also high at 90.7% (95% CI, 88.3% - 92.7%) for fundus mtmDR-

participants, and 90.7% (95% CI, 86.8%-93.5%) for multimodal mtmDR- participants.

There were no significant effects of sex, ethnicity, race, HbA1C, lens status, or site, on

specificity, while increased specificity was observed in subjects over 65 years of age (p =

0.030). The retrospective power was 87%. Positive predictive value was 72.7% (173/238)

and negative predictive value was 95.7% (556/581). In the 38 participants with AI system

insufficient image quality, the prevalence of mtmDR was 10/38 (26%), comparable to the

mtmDR prevalence in the fully analyzable dataset. Among the 73/892 non-analyzable

participants, 35 (4%) lacked a completed FPRC grading. In the worst case scenario,

assuming all of these 35 participants had mtmDR, the sensitivity and specificity would

have been 80.7% (two-sided 95% CI, 76.7%-84.2%) and 89.8% (two-sided 95% CI,

85.9% - 92.7%) respectively.

The following summarizes the key performance results of the IDx-DR study:

Sensitivity – 87%

Specificity – 90%

Imageability – 96%

PPV (Positive Predictive Value) – 73%

NPV (Negative Predictive Value) – 96%

Image Quality Results

Of the 857 participants that received a completed FPRC grading, 38 participants (4%)

received an insufficient image quality output from IDx-DR after completion of IDx-DR

imaging protocol. Thus image-ability, defined as the percentage of participants with a

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completed FPRC grading and a disease level output was high (819/852) or 96.1% (95.0%

CI, 94.0-96.8%). For the IDx-DR imaging protocol, 76.4% of participants did not require

pharmacologic dilation, while 23.6% did require dilation to obtain an IDx-DR disease

level output. The majority of participants, 64.7%, completed the IDx-DR imaging

protocol of four photographs the first time; 8.5% were able to complete the protocol after

a single retry; 3.2% needed two retries; 19.7% needed three, 3.4% needed four; and 0.5%

needed five retries. In this clinical study, the IDx-DR System was able to achieve

sufficient performance when compared to the highest quality reference standard as

determined by the FPRC, met predetermined sensitivity and specificity standards for the

autonomous detection of more than mild DR or DME in people with diabetes but no

history of DR in primary care settings.

Precision Study

A separate reproducibility and repeatability (precision) study was conducted involving 24

participants. Participants in the substudy had already participated in the IDx-DR protocol:

12 participants had mtmDR- based on the original FPRC grading and 12 had mtmDR+.

Each participant in the sub-study completed the entire IDx-DR imaging protocol 10

times, imaged by three different NW400 Operators on two different Topcon NW400

fundus cameras. NW400 operators were instructed to give participants at least 15 minutes

between exams. Each subject underwent the entire IDx-DR imaging protocol 10 times,

i.e., 10 image sets per subject, 240 image sets in total. Five images from a single subject

were determined to be of insufficient quality according to the IDx-DR and thus were

omitted from analysis, the remaining 235 (97.9%) image sets were used for analysis. The

binary output of IDx-DR was used to assess repeatability and reproducibility. For 23 out

of 24 participants, the IDx-DR outputs were identical on all 10 imaging protocols for

each of them, irrespective of camera, operator, or repeat. For one of the 24 subjects, 9 out

of 10 IDx-DR outputs were identical as mild or more DR not detected, while 1 out of

these 10 outputs was mild or more DR detected. Thus, there is almost complete

agreement (99.6%) of IDx-DR outputs across repeats, operators and cameras.

Human Factors Validation Testing Study

Human Factors Validation Testing Study was performed to assess the user interface (IDx-

DR Client). IDx’s human factors testing validated the setting in which the device is

intended to be used. The IDx-DR workflow, training materials, and instructions were

developed through a series pre-trial human factors testing. The standardized workflow,

training program, and operator materials developed by this process were then

implemented and tested during the IDx-DR clinical trial, which took place in the primary

care setting. Final human factors validation results were successful in the IDx-DR clinical

trial, as reflected by the data on subject imageability. This IDx-DR Human Factors

Validation Test Plan empirically tested, improved upon, and validated the IDx-DR

System (i.e. the camera, camera operation, the IDx-DR imaging protocol, and the

standardized training and operational materials) in a real-world environment in order to

mitigate the residual usability.

The Human Factors Validation Test Plan occurred across two stages. The empirical

testing first collected feedback in three “Phases” to improve usability of the IDx-DR

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Client, derive standardized training materials, and develop the validation test plan. Final

testing was carried out as a part of the IDx-DX clinical trial, which validated the camera

use, the imaging protocol, and the standardized system materials that enable the capture

of four medical-grade retinal images by previously untrained camera operators for at least

80% of the subjects imaged. The three Phases of initial empirical testing were carried out

as follows: the camera and imaging protocol were tested and improved in Phase I and II.

Training content and product image feedback controls were tested and improved in Phase

III. To create consistent, scalable training, the training and operational materials were

standardized prior to the IDx-DR1 clinical trial. The development of standardized

training materials was tested by bringing in previously untrained photographers and

training them under the Phase III consent and protocol. The critical task for the IDx-DR

system is the ability to capture 4 images of sufficient quality. The purpose of the system

validation test plan was to demonstrate that IDx’s intended image capture workflow and

training methodology can successfully be used by previously untrained camera operators

to capture four medical-grade retinal images from 80% or more of subjects who complete

the full imaging protocol on a camera intended for use with IDx-DR IDx-DR System.

The Human Factors Validation Plan was designed to validate the camera, imaging

protocol, and standardized materials developed from empirical data gathered during

Phases I, II, and III. Operators underwent training prior to the clinical trial as described

below. As a part of training prior to the IDx-DR clinical trial, operators completed a

trainee self-certification form, which includes documentation that they have successfully

imaged 10 subjects.

Clinical trial results indicating that previously untrained camera operators can capture

four medical grade retinal images from the vast majority of subjects who complete the

protocol using the IDx-DR System valid Camera, IDx-DR Imaging Protocol, and

Standardized training and operational materials. Finally, the IDx-DR validation testing

results show an image quality sufficient rate of 96%.

Pediatric Extrapolation

In this De Novo request, existing clinical data were not leveraged to support the use of the device

in a pediatric patient population.

LABELING

The device labeling is for primary care clinics and stable visually asymptomatic patients

diagnosed with diabetes that have not been previously diagnosed with diabetic retinopathy.

Several product warnings are included in the labeling that carefully specify the intended patient

population, image acquisition factors that may impact IDx-DR results, and provide guidance for

patient referral based on the IDx-DR screening result. These warnings were found to be

appropriate. The labeling also provided a complete summary of the clinical trial procedures,

patient population, and results. This summary includes prominent instructions regarding

interpretation of the output as well as a representation of average variability observed in the

device performance for various device outputs. Labeling intended for internal consideration was

also provided which adequately described detailed steps and features that could affect accuracy

of results.

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RISKS TO HEALTH

The table below identifies the risks to health that may be associated with use of a retinal diagnostic

software device and the measures necessary to mitigate these risks.

Identified Risk Mitigation Measures

False positive results leading to

additional unnecessary medical

procedures

 Diagnostic algorithm failure

 Software failure

Clinical performance testing;

Software verification, validation, and hazard analysis;

and

Protocol for technical specification changes

False negative results leading to delay

of further evaluation or treatment

 Diagnostic algorithm failure

 Software failure

Clinical performance testing;

Software verification, validation, and hazard analysis;

Protocol for technical specification changes; and

Labeling

Operator failure to provide images that

meet input quality specifications

Labeling,

Training, and

Human factors validation testing

PECIAL CONTROLS:

In combination with the general controls of the FD&C Act, the retinal diagnostic software device

is subject to the following special controls:

1. Software verification and validation documentation, based on a comprehensive hazard

analysis, must fulfill the following:

a. Software documentation must provide a full characterization of technical parameters of

the software, including algorithm(s).

b. Software documentation must describe the expected impact of applicable image

acquisition hardware characteristics on performance and associated minimum

specifications.

c. Software documentation must include a cybersecurity vulnerability and management

process to assure software functionality.

d. Software documentation must include mitigation measures to manage failure of any

subsystem components with respect to incorrect patient reports and operator failures.

2. Clinical performance data supporting the indications for use must be provided, including the

following:

a. Clinical performance testing must evaluate sensitivity, specificity, positive predictive

value, and negative predictive value for each endpoint reported for the indicated disease

or condition across the range of available device outcomes.

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b. Clinical performance testing must evaluate performance under anticipated conditions of

use.

c. Statistical methods must include the following:

i. Where multiple samples from the same patient are used, statistical analysis must not

assume statistical independence without adequate justification.

ii. Statistical analysis must provide confidence intervals for each performance metric.

d. Clinical data must evaluate the variability in output performance due to both the user and

the image acquisition device used.

3. A training program with instructions on how to acquire and process quality images must be

provided.

4. Human factors validation testing that evaluates the effect of the training program on user

performance must be provided.

5. A protocol must be developed that describes the level of change in device technical

specifications that could significantly affect the safety or effectiveness of the device.

6. Labeling must include:

a. Instructions for use, including a description of how to obtain quality images and how

device performance is affected by user interaction and user training.

b. The type of imaging data used, what the device outputs to the user, and whether the

output is qualitative or quantitative.

c. Warnings regarding image acquisition factors that affect image quality.

d. Warnings regarding interpretation of the provided outcomes, including:

i. A warning that the device is not to be used to screen for the presence of diseases or

conditions beyond its indicated uses.

ii. A warning that the device provides a screening diagnosis only and that it is critical

that the patient be advised to receive follow-up care.

iii. A warning that the device does not treat the screened disease.

e. A summary of the clinical performance of the device for each output, with confidence

intervals.

f. A summary of the clinical performance testing conducted with the device, including a

description of the patient population and clinical environment under which it was

evaluated.

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BENEFIT/RISK DETERMINATION

The substantial benefits of early detection of mtmDR, including potential prevention of

significant vision loss with the potential timely treatment of DR, are highly valuable to the

intended population. Moreover, the high accuracy of the IDx-DR makes the potential risk of

false negatives low. Accordingly, the probable benefits of the IDx-DR outweigh the probable

risks.

Summary of Benefits

IDx-DR offers the important benefits of potential increased access to diabetic retinopathy

screening for people with diabetes in a primary care setting. Earlier detection of mtmDR among

these patients can help to enable the timely delivery of potentially sight saving interventions. The

pivotal clinical study, which enrolled a total of 900 participants, demonstrated observed

sensitivity for mtmDR 87.4%, with observed specificity of 89.5%. The device performed well

across the range of study participant characteristics enrolled in the study. The vast majority of

study participants had a screening diagnosis result. Among study participants who also had

fundus photo reading center results (needed for study analysis), 96.1% (819/852) produced an

IDx-DR output of mtmDR or negative for mtmDR. Thus, the clinical study successfully and

robustly demonstrated safe and effective clinical performance of IDx-DR when used to

automatically (without physician assistance) detect mtmDR.

Summary of Risks

The IDx-DR system, which makes use of a standard fundus camera, presents minimal physical

harm risks to patients. As with most diagnostic tools, the principal risks are those of false

negative results. A false negative result for mtmDR may result in delayed diagnosis and

treatment if the patient is not referred to an eye care professional by the health care provider.

This risk is mitigated by the health care provider’s recommendation for follow-up screenings.

DR is understood to progress slowly and, thus, repeat screenings would provide additional

opportunities to correctly identify the existence of mtmDR. In addition, all patients are

recommended to see their eye care professional as usual to evaluate for other ophthalmic

conditions not addressed by IDx-DR. Thus, some percentage of false negative subjects will be

additionally screened for DR during their annual eye care exam. Other risks associated with the

device are expected to be rare. A false positive result, for example, would mean an indication of

disease in a patient who does not have clinical signs of diabetic retinopathy. This would result in

a referral for further examination by an eye care professional which might lead to alarm fatigue.

Given that examination by an eye care professional once per year is the recommended standard

of care, this would not introduce any significant risk for the patient.

Summary of Other Factors

Device errors can arise from failure to operate the instrument correctly, or more broadly, failure

to correctly interpret test results. These are mitigated by appropriate end user device training and

a comprehensive user manual. Device labeling, which has been developed in accordance with 21

CFR 809.10(b)(9), provides a detailed explanation of the interpretation of results.

Patient Perspectives

This submission did not include specific information on patient perspectives for this device.

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Benefit/Risk Conclusion

In conclusion, given the available information above, the data support that for the screening of

diabetic retinopathy in patients with diabetes, the probable benefits outweigh the probable risks for

the IDx-DR. The device provides substantial benefits and the risks can be mitigated by the use of

general controls and the identified special controls.

CONCLUSION

The De Novo request for the IDx-DR is granted and the device is classified under the following:

Product Code: PIB

Device Type: Retinal diagnostic software device

Class: II

Regulation: 21 CFR 886.1100

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