AutoDx-DR Prospective Clinical Validation Study Protocol

An Evaluation of the Accuracy of AutoDx-DR, a Software Algorithm That Detects Diabetic Retinopathy From Retinal Images of Individuals With Diabetes

In this study, we will prospectively evaluate the accuracy of a deep-learning based software algorithm in the detection of diabetic retinopathy from 60° wide single-field retinal fundus images.

Study Overview

• Status: Unknown
• Conditions: Diabetic Retinopathy
• Intervention / Treatment: Device: AutoDX-DR

Detailed Description

We will obtain 60° wide single-field retinal fundus images from subjects who are diabetic patients in primary care environments (i.e. non-eye care settings, such as internal medicine, family medicine, and endocrinology). The fundus images will be uploaded to the RetinaVue Network software using the AutoDx-DR with Over-read modality, where images are transmitted to both AutoDx-DR and a remote ophthalmologist. AutoDx-DR will generate an initial Refer or Not Refer recommendation and the remote ophthalmologist will provide a detailed diagnostic image interpretation which will be used for patient management and referral during the course of the study. AutoDx-DR can also generate a third output which is "Inadequate for Interpretation". In this case, the images will still be sent to the remote ophthalmologist for interpretation. If the ophthalmologist also cannot interpret the images, the patient will be recommended to have an in-person comprehensive ophthalmologic exam.

Subjects participating in this study will undergo further retinal fundus imaging: four mydriatic, stereoscopic 45° field of view (4W) retinal images and spectral domain optical coherence tomography (SD-OCT) captured with the Reference Standard Camera (i.e. Zeiss Cirrus 600 photo, or other appropriate FDA-cleared imaging device with stereo fundus photography and SD-OCT capability that meets the requirements of the certified fundus photography reading center such as Topcon, Optovue, and Heidelberg). The 4W and SD-OCT imaging will be performed by a certified technician located at or near the enrolling study site. The 4W and SD-OCT images will be interpreted by a certified fundus photography reading center (FPRC) for more than mild DR or any diabetic macular edema. The FPRC's Not Refer/Refer determination will be used as the "gold standard" interpretation in this study.

The AutoDx-DR interpretation of the 60° wide single-field images will be compared to the FPRC "gold standard" interpretation for the Not Refer/Refer recommendation. Accuracy metrics of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR), with 95% confidence intervals will be calculated. All diabetic patients who are attending routine primary care or endocrinology appointments and meet the enrollment criteria will be invited to participate in the study. All study procedures will be performed during a single study visit.

• Study Type: Interventional
• Enrollment (Anticipated): 1539
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

A documented diagnosis of diabetes mellitus in accordance with the criteria established by the American Diabetes Association (ADA)7 as indicated by at least one of the following:

• Hemoglobin A1c (HbA1c) > 6.5%
• Fasting Plasma Glucose (FPG; period of fasting must be at least 8 hours) > 126 mg/dL (7.0 mmol/L)

• Oral Glucose Tolerance Test (OGTT) with 2-hour plasma glucose >200 mg/dL (11.1 mmol/L), using the equivalent of an oral 75 g anhydrous glucose dose dissolved in water o Symptoms of hyperglycemia or hyperglycemic crisis with a random plasma glucose (RPG) ≥ 200 mg/dL (11.1 mmol/L)

  • 22 years of age or older
  • Ability to understand the study and sign the informed consent

Exclusion Criteria:

• A documented diagnosis of more than mild diabetic retinopathy in the patient record.

  o More than mild diabetic retinopathy shall be defined as moderate NPDR, severe NPDR, proliferative diabetic retinopathy (PDR) or any level of DME; or a documented diabetic eye exam report indicating more than microaneurysms [i.e. presence of intraretinal hemorrhages, venous beading, intraretinal microvascular abnormalities (IRMA,) neovascularization or DME.]

• They report having severe vision loss in both eyes.
• They report a history of laser treatment or surgery of the retina.
• They report that they are currently receiving treatment for DR or DME.
• They report a diagnosis of angle closure glaucoma.
• They report hypersensitivity to light which makes retinal imaging uncomfortable.
• They are currently pregnant or breastfeeding.
• They report that they have an iris supported intraocular lens or anterior chamber intraocular lens associated with a previous cataract surgery.
• They had a previous pupilloplasty surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: AutoDX and Gold Standard; A licensed clinician will obtain 60° wide single-field retinal fundus images from subjects who are diabetic patients in primary care environments (i.e. non-eye care settings, such as internal medicine, family medicine, and endocrinology). The fundus images will be uploaded to the RetinaVue Network software using the AutoDx-DR with Over-read modality, where images are transmitted to both AutoDx-DR and a remote ophthalmologist. Subjects participating in this study will undergo further retinal fundus imaging: four mydriatic, stereoscopic 45° field of view (4W) retinal images and spectral domain optical coherence tomography (SD-OCT) captured with the Reference Standard Camera

Device: AutoDX-DR; AutoDx-DR provides basic image interpretation for the detection of DR and diabetic macular edema (DME) and a Refer or Not Refer recommendation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity	The ability of AutoDX-DR to correctly identify those with the disease (true positive rate)	Each subject will only have one day study visit and will provide the AutoDX-DR and gold standard reading during their one visit.
Specificity	The ability of AutoDX-DR to correctly identify those without the disease (true negative rate)	Each subject will only have one day study visit and will provide the AutoDX-DR and gold standard reading during their one visit.

Collaborators and Investigators

• Sponsor: Hill-Rom
• Collaborators: Rho, Inc.; ClinEdge
• Investigators: Principal Investigator: Antonio Piñero-Piloña, MD, Diabetes Care Center; Principal Investigator: Joseph Woolley, MD, Southwest Internal Medicine; Principal Investigator: Keila Hoover, MD, Hoover Family Medicine; Principal Investigator: Quang Vo, MD, Dr. Steven Barag, DO; Principal Investigator: Peter Mattar, MD, Dr. Peter N. Mattar, MD; Principal Investigator: Efrain Soto, MD, Park Lakes Family Medicine; Principal Investigator: Harish Thakkar, MD, Southwest Medical Clinic; Principal Investigator: Luis Gonzalez-Orozco, MD, Clinic of Luis Gonzalez; Principal Investigator: Jennifer Bellucci-Jackson, MD, Family Medicine Specialists

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2020
• Primary Completion (Anticipated): July 31, 2021
• Study Completion (Anticipated): July 31, 2021

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 12, 2020
• First Posted (Actual): November 13, 2020

Study Record Updates

• Last Update Posted (Actual): November 13, 2020
• Last Update Submitted That Met QC Criteria: November 12, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Diabetic Retinopathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Diseases; Diabetic Retinopathy
• Other Study ID Numbers: 60095127

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes