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Trial registered on ANZCTR


Registration number
ACTRN12620000304932
Ethics application status
Approved
Date submitted
21/02/2020
Date registered
5/03/2020
Date last updated
5/03/2020
Date data sharing statement initially provided
5/03/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Diabetic Retinopathy Screening at Point Of Care (DR SPOC)
Scientific title
Diabetic Retinopathy Screening at Point Of Care amongst high-risk diabetic clinic patients using portable non-mydriatic fundus photography and combined pupillometry/electroretinography to determine diagnostic accuracy and the prevalence of undiagnosed or vision-threatening diabetic retinopathy.
Secondary ID [1] 298041 0
None
Universal Trial Number (UTN)
U1111-1232-1773
Trial acronym
DR SPOC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic retinopathy 312514 0
Condition category
Condition code
Eye 311053 311053 0 0
Diseases / disorders of the eye
Metabolic and Endocrine 311054 311054 0 0
Diabetes
Public Health 311055 311055 0 0
Epidemiology

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants received three interventions in a fixed order at one clinic visit:
(1) Two-field bilateral Non-mydriatic fundus photography (NMFP);
(2) Combined electroretinography & pupillometry (ERG);
(3) Two-field bilateral mydriadic fundus photography (MFP) - the control intervention.
There was no pre-specified washout time between interventions.

Intervention Name: (1) Two-field bilateral Non-mydriatic fundus photography (NMFP)
*RetinaVUE 100 registered trade mark (Welch Allyn, Macquarie Park, Australia): portable camera provided to enrolled patients in the clinic
*performed a research assistant with prior computer-based and face-to-face NMFP training
*administered once clinic admission, taking approximately 2-10 minutes for complete examination of both eyes
*digital fundus images are then interpreted by an ophthalmologist

Intervention Name: (2) combined electroretinography & pupillometry (ERG)
*RETeval registered trade mark (Welch Allyn, Macquarie Park, Australia): full-field electroreintography and pupillometry device
*performed by a research assistant with prior training
*administered once clinic admission, taking approximately 2-10 minutes for complete examination of both eyes
*the automatically generated report is then interpreted by an ophthalmologist
Intervention code [1] 314274 0
Early detection / Screening
Comparator / control treatment
Comparator Intervention Name: (3) Two-field bilateral mydriadic fundus photography (MFP)
*RetinaVUE 100 registered trade mark (Welch Allyn, Macquarie Park, Australia): portable camera provided to enrolled patients in the clinic
*performed by a research assistant with prior computer-based and face-to-face NMFP training\
* after informed consent, topical mydriasis with tropicamide 0.5% or 1% was administered and further two-field dilated fundus photographs were taken from each eye
*administered once clinic admission, taking approximately 2-10 minutes for complete examination of both eyes
*digital fundus images are then interpreted by an ophthalmologist
Control group
Active

Outcomes
Primary outcome [1] 322492 0
Diabetic retinopathy as assessed by ophthalmology review of two-field, mydriatic fundus photographs.
* Measured using international clinical diabetic retinopathy disease severity scale (ICDRSS) grading
Timepoint [1] 322492 0
Assessed once at cross-sectional visit
Primary outcome [2] 323094 0
Diabetic retinopathy as assessed by ophthalmology review of two-field, non-mydriatic fundus photographs.
* Measured using ICDRSS grading
Timepoint [2] 323094 0
Assessed once at cross-sectional visit
Primary outcome [3] 323095 0
Diabetic retinopathy as assessed by combined pupillometry and electroretinography.
* Measured using ICDRSS grading
Timepoint [3] 323095 0
Assessed once at cross-sectional visit
Secondary outcome [1] 378700 0
Undiagnosed diabetic retinopathy as assessed by study specific questionnaire to participants.
Timepoint [1] 378700 0
Assessed once at cross-sectional visit
Secondary outcome [2] 378701 0
Diabetic retinopathy grading as assessed by automated image processing of fundus photographs
*Assessed using the following modified ICDRSS criteria:
*UNGRADABLE - >30% of the image was obscured or if vessels in the macular region could not be distinguished as maculopathy,
*NON-REFERABLE - mild or less diabetic retinopathy, and no maculopathy
*REFERABLE - moderate or worse diabetic retinopathy, or MACULOPATHY (a modified definition of diabetic macular oedema: the presence of exudates, retinal thickening (if visible on nonstereo photographs), or microaneurysms, all within 1 disc diameter of the fovea)
Timepoint [2] 378701 0
Assessed once at cross-sectional visit.
Secondary outcome [3] 380769 0
Time to acquire screening interventions.
*Measured by digital timer and recorded in the study specific questionnaire.
Timepoint [3] 380769 0
At the time of fundus image acquisition
Secondary outcome [4] 380770 0
Proportions of fundus images which are gradable
*As determined by two masked investigators, with a third medical retina subspecialist ophthalmologist arbiter in case of disagreement
*Using the definition; UNGRADABLE = >30% of the image was obscured or if vessels in the macular region could not be distinguished as maculopathy,
Timepoint [4] 380770 0
After grading

Eligibility
Key inclusion criteria
Participation was offered to diabetic patients over 18 years of age, who attended the Foot Ulcer or Integrated Diabetes Clinics at these hospitals by the treating endocrinologist.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients with photosensitive epilepsy were excluded from participation,
* Patients with a family history of angle-closure glaucoma were not offered pupil dilation

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
non-randomised, standard order of investigations/interventions: 1) NMC, 2) ERG, 3) MC
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Statistical and inferential analyses will be performed using SAS software, Version 9.4 (Cary, NC: SAS Institute). The prevalence of DR, vision-threatening DR and undiagnosed DR will be estimated with 95% confidence intervals and age-adjusted comparisons will be made between the study population and community and clinical populations. McNemar’s test will be used to compare the rate of successful administration of the diagnostic tests. Point estimates with 95% confidence intervals for sensitivity, specificity, of NMC and ERG will be estimated in comparison to MC. The same methods will be used to compare automated image screening with human image grading results. Costs of administration of will be compared using linear regression to model the different methods, adjusting for repeated measures on the same patient, demographic and clinical characteristics.
Known population screening study rates of vision threatening diabetic retinopathy suggest 1-7% (4.5% in the most recent Australian study), and of any diabetic retinopathy being between 25-33%. When the prevalence of vision threatening diabetic retinopathy is estimated to be 5%, the minimum sample size required for a screening study is 400 participants (including 20 participants having the disease). This will be required to achieve a minimum power of 80% (actual power = 80.4%) in order to detect a change in the percentage value of sensitivity from 0.50 to 0.80, based on a target significance level of 0.05 (actual p = 0.041). This sample size would also be enough for a screening study for the estimated prevalence of any diabetic retinopathy being 25-33%.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 15943 0
Westmead Hospital - Westmead
Recruitment hospital [2] 15944 0
Blacktown Hospital - Blacktown
Recruitment postcode(s) [1] 29427 0
2145 - Westmead
Recruitment postcode(s) [2] 29428 0
2148 - Blacktown

Funding & Sponsors
Funding source category [1] 302571 0
University
Name [1] 302571 0
Discipline of Clinical Ophthalmology & Eye Health, Faculty of Medicine & Health, University of Sydney
Address [1] 302571 0
Save Sight Institute
South Block, Sydney Eye Hospital
8 Macquarie Street
Sydney NSW 2000
Country [1] 302571 0
Australia
Funding source category [2] 305042 0
Hospital
Name [2] 305042 0
Research and Education Network, Western Sydney Local Health District
Address [2] 305042 0
WSLHD Research and Education Network,
Westmead Hospital,
Hawkesbury Road,
Westmead NSW 2145
Country [2] 305042 0
Australia
Primary sponsor type
Hospital
Name
Westmead Hospital, Dept of Ophthalmology
Address
B4a, Westmead Hospital,
Hawkesbury Road,
Westmead NSW 2145
Country
Australia
Secondary sponsor category [1] 302479 0
University
Name [1] 302479 0
University of NSW, Rural Clinical School
Address [1] 302479 0
26 Highfields Circuit
Port Macquarie,
NSW, 2444
Country [1] 302479 0
Australia
Secondary sponsor category [2] 305405 0
Commercial sector/Industry
Name [2] 305405 0
Hill-Rom Australia
Address [2] 305405 0
Suite 4.01, 2-4 Lyonpark Rd
Macquarie Park, NSW 2113
Country [2] 305405 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303214 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 303214 0
Research Office, Level 2, REN Building
Westmead Hospital, Hawkesbury & Darcy Roads, Westmead NSW 2145
Ethics committee country [1] 303214 0
Australia
Date submitted for ethics approval [1] 303214 0
25/10/2017
Approval date [1] 303214 0
14/02/2018
Ethics approval number [1] 303214 0
AU RED SSA/17/WMEAD/

Summary
Brief summary
This study is attempting to address shortcomings with the current DR screening process by implementing novel portable devices at point of care for high-risk patients.

Non mydriatic camera (NMC) fundus photography has been approved by the NHMRC as a screening tool for DR. Combined pupillometry/electroretinography (ERG) has been proven sensitive and specific for DR screening. We will build on these promising novel screening tools through implementation in new clinical settings: point of care in hospital. Opportunistic diabetes case-finding by HbA1c screening of patients presenting to Blacktown ED identified 66% of patients had diabetes or pre-diabetes. Synchronising our DR screening protocol with established successful systems for identification of high-risk patients, using the WSLHD Diabetes Detection and Management Strategy & Western Sydney Diabetes Initiative will amplify the clinical impact of these initiatives by reducing the burden of blindness.

The goals of this study align with the WSLHD Better West Strategic Priorities which identified the priority for “Healthy people- Overcome diabetes through screening and early management”.

Our aim is to investigate whether NMC and ERG screening at the point of care in patients with high risk for DR, results in improved detection of new and vision threatening DR compared to current screening practices.

This study aims to establish:
*The proportion of patients with undiagnosed and/or vision threatening DR in patients presenting to hospital emergency departments with raised blood sugar level (BSL) and/or HbA1c, or high-risk foot clinics. The rate of undiagnosed DR will be compared to population based estimates from the 2016 National Eye Health Survey and ophthalmology clinic populations.
*The various methods (NMC, ERG, MC and computer-automated DR screening) will be compared with respect to:
*Rate of successful administration eg. proportion of retinal images that are readable.
*The relative diagnostic accuracy in this novel setting
*Cost of the procedure from health care provider perspective (time, personnel, equipment).
*The value of ERG in addition to NMC in screening this population.
*The validity of portable NMC and ERG compared with dilated 2-field MC.
*Fundus DR grading by an automated image screening program will be compared to human graders with a cost-benefit analysis.
*The value of this screening protocol compared with community screening.

In combination, these aims will provide an evidence base for clinically appropriate HbA1c and BSL screening criteria.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92874 0
A/Prof Andrew White
Address 92874 0
Westmead Eye Clinic
B4a, Westmead Hospital
Hawkesbury Road,
Westmead NSW 2145
Country 92874 0
Australia
Phone 92874 0
+61 2 86273647
Fax 92874 0
Email 92874 0
andrew.white@sydney.edu.au
Contact person for public queries
Name 92875 0
Dr Hamish Dunn
Address 92875 0
Port Macquarie Eye Centre
35 Ackroyd St,
Port Macquarie, NSW 2444
Country 92875 0
Australia
Phone 92875 0
+61 2 6584 5554
Fax 92875 0
Email 92875 0
hamish.dunn@sydney.edu.au
Contact person for scientific queries
Name 92876 0
Dr Hamish Dunn
Address 92876 0
Port Macquarie Eye Centre
35 Ackroyd St,
Port Macquarie, NSW 2444
Country 92876 0
Australia
Phone 92876 0
+61 2 6584 5554
Fax 92876 0
Email 92876 0
hamish.dunn@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual, de-identified data underlying published results.
When will data be available (start and end dates)?
Beginning 6 months after and ending 3 years after publication of main results.
Available to whom?
Researchers who provide a methodologically sound proposal, on a case-by-case basis at the discretion of Primary Sponsor.
Available for what types of analyses?
Any analysis justified in the research proposal
How or where can data be obtained?
Access subject to approvals by Principal Investigator (by email to hamish.dunn@sydney.edu.au), with a requirement to sign data access agreement and approval by the Sydney Local Health District HREC.
What supporting documents are/will be available?
No other documents available
Summary results
No Results