Validation of Handheld Ultrasound Devices for Point of Care Use in Rheumatology
Conditions: Psoriatic Arthritis
Sponsor: Ottawa Hospital Research Institute

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Validation of Handheld Ultrasound Devices for Point of Care Use in Rheumatology  
Protocol version 2.0 – 21Mar2023 
GRAPPA Ultrasound Working Group 
Principle Investigators 
: 
Sibel Zehra Aydin, MD  
Professor of Medicine, Rheumatology, 
Clinician Scientist in the Clinical 
Epidemiology Program at the OHRI, 
University of Ottawa, Ottawa, Ontario, 
Canada 
 
Lihi Eder, Associate Professor of Medicine, 
Rheumatology, University of Toronto, 
Toronto, ON, Canada 
 
Gurjit Kaeley, Professor of Medicine, 
Rheumatology, University of Florida, 
Jacksonville, FL, USA 
 
Investigator contact information: 
Dr. Aydin:1967 Riverside Dr., Ottawa, ON, Canada K1H 7W9 
GRAPPA Network: 3213 W. Wheeler st. #35, Seattle, WA, USA, 98199 
 
 
 

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Table of Contents 
1.0 BACKGROUND .......................................................................................................................... 3 
2.0 AIMS .......................................................................................................................................... 7 
3.0 STUDY OBJECTIVE .................................................................................................................... 7 
4.0 APPROACHES AND METHODS ................................................................................................... 8 
4.1 STUDY POPULATION ............................................................................................................ 9 
INCLUSION/EXCLUSION CRITERIA ......................................................................................... 9 
    4.2 CLINICAL DATA COLLECTION .............................................................................................. 9 
    4.3 ULTRASOUND PROTOCOL ................................................................................................. 10 
    4.4 STATISTICAL ANALYSIS ..................................................................................................... 17 
    4.5 SAMPLE SIZE CONSIDERATION ........................................................................................... 17 
5.0 IMPACT OF THE STUDY .......................................................................................................... 17 
6.0 TRANSLATION OF CRF ......................................................................................................... 18 
7.0 ETHICAL AND REGULATORY ASPECTS ................................................................................. 18 
    7.1 Participant consent…………………………………………………………………..….…18 
    7.2 Personal Information Management…………………………...…………………….……..18  
    7.3 Regulations and Review Board……………………………………………………………18 
8.0 DATA QUALITY ASSURANCE .................................................................................................. 19 
REFERENCES ................................................................................................................................ 21 
 
 
 

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1.0 Background 
Recently, ultrasonography (US) has experienced a rapid evolution in the field of rheumatology, an 
evolution certainly driven by the broad applicability of point-of-care (POC) US for the assessment 
of rheumatic diseases. Despite the use of US in many other medical fields, such as gynecology, 
emergency or gastroenterology for much longer, the uptake by the rheumatology community was 
only initiated in the last two decades. This is mostly due to the fact that most of the structures that 
are assessed in rheumatology are very superficial, and the technology to generate a high resolution 
view for these superficial structures, to a degree of being able to detect even mild inflammatory 
changes, have been developed relatively recently.  
US is made up of mechanical sound waves that can transmit through different materials like fluids, 
soft tissues and solids. Different tissues have different properties in terms of how much they 
transmit or reflect these waves and it makes them appear different on the screen. The Brightness 
mode (B mode) is the basic mode most commonly used and it is very helpful to determine if there 
is any inflammation in the investigated structure. In a much more sensitive manner than physical 
examination, B mode will detect structural changes associated with the presence of inflammation. 
In addition, it is possible to detect moving objects (such as erythrocytes) with US and convert such 
signal to an image, which is the principle of the Doppler view. Again, the Doppler has been used 
for a long time in other fields, such as cardiology, to detect the occlusion of carotid arteries, 
thrombosis of the deep veins or valvular insufficiencies of the heart. However, high erythrocyte 
velocities are characteristic of the latter pathologies and this is mostly not applicable to 
rheumatology practice. The neovascularisation within joints or tendons are at the capillary level 
and the flow is much slower. Power Doppler mode has been the recent breakthrough imaging 
technology in rheumatology as it allows the detection of active inflammation in a very sensitive 
manner. 
Nowadays, rheumatologists typically use US for guided injections and for the assessment of joint 
structures, connective and vascular tissues, and related pathologies.1 When it comes to the 
assessment of musculoskeletal (MSK) structures, the value of US lies upon a unifying principle 
for many arthritides: rapid detection of highly relevant and often times subclinical features of 
disease. For example, in a rapidly progressing disease like Rheumatoid Arthritis (RA), US allows 
faster detection of synovitis and bone erosion, resulting in earlier fulfillment of diagnostic criteria.2  

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Early disease detection with US perhaps takes its most relevant sense in psoriatic arthritis (PsA), 
where efforts are currently being deployed to intercept disease in its transition from psoriasis 
(PsO).  
Three clinically quiet disease stages have recently been proposed between PsO and clinically 
detected PsA (see illustration 1)3 : 
• A preclinical phase (aberrant activation of the immune system) 
• A subclinical PsA phase (soluble biomarkers and imaging findings with no clinical 
symptoms) 
• A prodromal PsA arthralgia and fatigue with no synovitis and or enthesitis on physical 
exam yet 
 
US is the imaging technique at the core of disease characterization during the latter 2 quiet stages. 
In the sub-clinical phase, several studies report more entheseal inflammation and synovitis on 
ultrasonography in PsO patients vs. healthy controls (HC). During the prodromal phase, a clinical 
and sonographic study on PsO patients with arthralgia revealed that sonographically determined 
tenosynovitis was the most significant contributor to symptoms and that sonographically 
determined enthesitis was linked to the future evolution of PsA. The identification of specific 
imaging lesions, associated with overt clinical PsA development, will be the challenge for the 
coming years, in order to correctly identify PsO patients at risk for PsA development.3  
The DUET (Diagnostic Ultrasound Enthesitis Tool) study, headed by our group, the GRAPPA US 
working group, is working towards deriving a sonographic enthesitis scoring system accurately 

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distinguishing early PsA from non-PsA patients (including osteoarthritis (OA) patients with PsO), 
over the coming year.4 Prior to diagnosis, there is great value attributed to PsA screening within 
the PsO population in the dermatology setting. As such, US was proven to be a great complement 
to the Early Arthritis for Psoriatic Patients (EARP) screening questionnaires and Psoriasis 
Epidemiology Screening Tool (PEST), increasing the specificity of referrals from 9% to 77% 
without compromising sensitivity.5 
The use of US is not limited to RA and PsA in rheumatology. US detection of subclinical synovitis, 
seen in a large proportion of systemic lupus erythematosus (SLE) patients, could also reveal to be 
a great asset for early SLE patient management.6 Overuse tendinopathies are group of MSK 
pathologies without a systemic component frequently seen by rheumatologists. Shoulder pain, for 
example, is second to low back pain as the most frequent MSK complaint leading to referral for 
rheumatological assessment.7 Tendinopathies of the rotator cuff are diagnosed with greatest cost-
efficiency, sensitivity and specificity using MSK US. The same imaging technique is also used for 
the guided peritendinous administration of several therapeutic agents, including corticosteroids, 
Hyaluronic Acid (HA) and sclerosis agents, to avoid intratendinous injections.8 Combining these 
two US applications has already shown to improve therapeutic efficiency.9 OA, the most common 
form of arthritis (affecting 25–50% of US adults by age 85) and frequent contributor to disability, 
is another rheumatic disease for which recent advances brought US frontstage.10 There is growing 
support for the utility of US in OA assessment, as it is more sensitive than conventional 
radiography which may allow earlier disease identification. Additionally, US provides detailed 
imaging of soft tissues and inflammation, allowing detection of a variety of features relevant to 
OA, including osteophytes, effusions, synovitis, enthesitis, bursitis, and cartilage pathology, in a 
more cost-effective manner than MRI. 10 The OMERACT group recently released updated 
definitions of US-detected pathologies with pertinence in OA. The most relevant were synovitis, 
erosion and enthesitis.11 One caveat remains in the assessment of OA enthesopathy with US: it is 
a feature shared with PsA, and thus creates the need for differentiation between early PsA and OA 
patients suffering from comorbid PsO. Concluding on the broad applicability of POC US in 
rheumatology, giant cell arteritis (GCA) and Sjögren Syndrome are examples of  inflammatory 
diseases of vascular and connective tissue respectively, for which US plays a role in diagnosis. In 
GCA, US could contribute to reducing the risk of permanent sight loss associated with diagnostic 

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delay.12 In Sjögren, US assessment of salivary glands is an important non-invasive measure 
supporting the diagnostic process.13 
Moving on to the subject of ultrasonography scanners as medical devices; more specifically the 
high quality US scanners and high-resolution transducers required for the practice of 
rheumatology. A number of barriers persist and stand in the way of a wider use of POC US for the 
detection, diagnosis and management of rheumatic diseases.  A significant one is the acquisition 
and maintenance costs of high quality instruments, limiting accessibility for community 
practitioners. There are recent technical and technological advances in the field of handheld 
ultrasonography that are set to overcome the access barrier. Typically, the cost of acquisition of 
scanners with a greyscale frequency of at least 13 MHz and a Doppler frequency of at least 8 MHz 
ranges from 25 000CAD to 90 000CAD. Hand-held US technology promises to take this cost down 
to a price tag under 10,000CADwith the introduction of affordable high-definition scanners 
possessing the specifications/requirements for use in the rheumatology practice (Greyscale 
frequency: 12 - 20 MHz and Doppler frequency: 8 - 12 MHz).  Clarius Mobile Health Inc., an 
innovative company based out of Vancouver B.C., produces such devices. Clarius US scanner 
have regulatory approval by the FDA and Health Canada. However, before they can be specifically 
used for the practice of rheumatology, their performance needs to be validated against gold-
standard devices for key interventions. 
 
US holds significant promise as an imaging tool in rheumatology and in the future, handheld US 
could be used at the bedside to provide diagnostic and prognostic information, as well as guide 
both systemic and local treatment decisions and applications. Through the accurate assessment of 
disease extension and activity (e.g. presence of enthesitis in a PsA patient presenting with primarily 
as synovial disease), the bedside application of US in standard assessment of the PsA patients will 
enable the understanding of which domains are involved and would require treatment/and which 
treatment based on the domain involved. There are numerous advantages of the hand-held US 
devices over the existing gold standard devices for being accessible by more physicians, therefore 
by more patients. The ability to carry the device in their pocket will allow the physicians to be able 
to use in multiple settings, e.g. in different offices or inpatient vs outpatient clinics. Making the 
bedside US a part of the clinical assessment will avoid any delays in diagnosis and lead to earlier 
treatments. In addition, it increases the patients adherence to therapy adjustments. 14 As such, the 

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goal of this trial will be to validate two affordable handheld MSK US scanner against gold-standard 
devices through an assessment of their accuracy for: 
• visualizing anatomical structures and pathologies 
• detecting vascular flow 
2.0 Aim 
Our aim to test the concurrent validity of the Clarius handheld US devices versus gold-standard device 
to detect characteristic features of healthy and rheumatic joints (i.e. anatomical structures and vascular 
flow). 
3.0 Study Objectives 
Primary objective: 
To determine whether handheld US devices (Clarius HD3 L20 and L15 scanners) B mode are as 
accurate as gold standard device (GE Logic E9/S8) at visualizing intraarticular synovitis 
Secondary objectives: 
1. To determine whether handheld US devices (Clarius HD3 L20 and L15 scanners) power 
Doppler mode are as accurate as gold standard device (GE Logic E9/S8) at detecting 
intrasynovial signals  
2. To determine whether handheld US devices (Clarius HD3 L20 and L15 scanners) B mode are 
as accurate as gold standard device (GE Logic E9/S8) at visualizing tenosynovitis  
3. To determine whether handheld US devices (Clarius HD3 L20 and L15 scanners) power 
Doppler mode are as accurate as gold standard device (GE Logic E9/S8) at detecting 
intratendineous signals  
4. To determine whether handheld US devices (Clarius HD3 L20 and L15 scanners) B mode are 
as accurate as gold standard device (GE Logic E9/S8) at visualizing bone erosions  
5. To determine whether handheld US devices (Clarius HD3 L20 and L15 scanners) B mode are 
as accurate as gold standard device (GE Logic E9/S8) at grading intraarticular synovitis   

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6. To determine whether handheld US devices (Clarius HD3 L20 and L15 scanners) power 
Doppler mode are as accurate as gold standard device (GE Logic E9/S8) at grading intrasynovial 
signals  
7. To determine whether handheld US devices (Clarius HD3 L20 and L15 scanners) B mode are 
as accurate as gold standard device (GE Logic E9/S8) at grading bone erosions  
8. To determine whether handheld US devices (Clarius HD3 L20 and L15 scanners) power 
Doppler mode are as accurate as gold standard device (GE Logic E9/S8) at visualizing 
elementary lesions of enthesitis   
9.  To determine whether handheld US devices (Clarius HD3 L20 and L15 scanners) power 
Doppler mode are as accurate as gold standard device (GE Logic E9/S8) at detecting entheseal 
signals   
10. To determine whether handheld US devices (Clarius HD3 L20 and L15 scanners) B-mode 
are as accurate as gold standard device (GE Logic E9/S8) at detecting trilaminar appearance of 
the nail plate abnormalities 
4.0 Approaches and Methods 
Number of arms:  single arm (repeating an image collection protocol with hand held US and the 
gold standard devices for each patient) 
Blinding:  The scoring of the US images will be done in a blinded fashion. The de-identified 
images from different patients and different scanners will be pooled to ensure the principle 
investigators (PIs) blindness to both the patients’ clinical findings and the scores of other imaging 
modality. 
 
 
 
 
 
 
 
 

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4.1 Study Population  
Adult patients with peripheral PsA that is not in minimal disease activity (MDA) and presenting 
at least one tender and swollen joint. 
Inclusion Criteria 
• Age ≥18  
• Meets the classification for psoriatic arthritis (CASPAR) criteria 
• Able to provide an informed consent 
• Having peripheral disease phenotype of PsA 
• At least one tender and swollen join on the day of US 
Exclusion Criteria 
• Having isolated axial PsA 
• Being in MDA with no tender and swollen joints 
4.2 Clinical Data Collection  
There will only be one study visit. The consent, clinical data collection and US assessments will 
be done with the same study visit. 
Clinical Assessment: This will be performed by an experienced rheumatologist on each site. The 
following information will be collected: 
Patient’s age, gender, Body Mass Index (BMI), physical activity, smoking, treatments and disease 
activity, based on 66/68 joint count for tender and swollen joints, Spondyloarthritis Research 
Consortium of Canada (SPARCC) enthesitis index, number of dactylitic digits, body surface area 
for skin disease and presence of nail disease. 
For the Patient-Reported Outcomes (PROs), pain Visual Analogy Scale (VAS), patient global and 
Health Assessment Questionnaire Disability Index (HAQ-DI) will be collected.  

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Medical device incident collection and documentation: Both US machines are approved by Health 
Canada and FDA. If any incident occurs, this will be reported to the manufacturer and applicable 
Health Authorities as per medical device regulations and will also be included in the final report 
that will be provided to the REB.  
4.3 Ultrasound Protocol (Assessment of Joints and Enthesis)  
Each patient will have consecutive (same day) US examinations using the Clarius handheld and 
GE gold-standard devices. All scans will be performed in a darkened room. Power Doppler settings 
will be standardized with a pulse repetition frequency of 500 Hz and low wall filters. The colour 
gain will be increased to the highest value where power Doppler signals under the bony cortex are 
not generated. There will be no further training for this step as the 3 investigators have done 
multiple research projects together and separately, with reproducibility being tested and 
presented.15 However, there will be a investigators meeting prior to data collection to review all 
anatomical sites, positioning and standard views and agree on labelling. All images will be labeled 
to identify anatomical site and laterality. A glossary will be provided for labelling, to ensure 
blinding in the later stages.  At least one B mode and one power Doppler image will be saved for 
each site and lesion. The standard will be saving the images in longitudinal views. Transverse 
views will be saved if there is an abnormality noted on the long axis. 
Representative images will be collected and saved for all of the following structures bilaterally: 
Joints (24 total): 2nd-3rd metacarpophalangeal (MCP), 2nd-3rd proximal interphalangeal (PIP), 2nd-
3rd distal interphalangeal (DIP), wrist, elbow, shoulder, knee, ankle and 5th metatarsophalangeal 
(MTP) joints of the foot, bilaterally. For the MCP, PIP and DIP joints, if joints other than the 2nd 
or 3rd present with swelling (e.g. 4th or 5th) they will be scanned instead. This approach is to ensure 
a maximum number of swollen joints will be assessed. 
Entheses (20 total): 
Large entheses: Supraspinatus, triceps, common extensor tendon, quadriceps, patellar ligament 
(origin and insertion), Achilles tendon, Plantar fascia insertions;  
Small entheses: extensor digitorum tendon insertion at the DIP and PIP level  
Tendons (4 total): Extensor digitorum tendon of the second digits, tibialis posterior tendon in the 
ankles 

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Nail: In case of having a nail PsO, the most involved nail and contralateral side will be assessed. 
If there is no nail PsO, procedure will be performed on the nail of the 2nd digit of the hands. 
 
All study procedures and that will take place in one study visit, as summarize in Table-1. 
 
Table-1: Assessment schedule 
 
Procedures 
Visit 1 
Obtain informed Consent 
x 
Inclusion/ Exclusion criteria 
x 
Demographics 
x 
Relevant medical history 
x 
Current Psoriatic Arthritis treatment 
x 
Pain VAS 
x 
Patient global assessment 
x 
HAQ-DI 
x 
Disease activity (66/68 joint count) 
x 
SPARCC enthesitis index 
x 
Dactylitis count 
x 
BSA 
x 
Presence of nail disease 
x 
Ultrasound protocol using both machines 
x 
Documentation of the ESR and CRP (if already done as standard of care) 
x 
Adverse event collection 
x 
VAS: Visual Analogue Scale; HAQ-DI: Health Assessment Questionnaire Disability Index; SPARCC: 
Spondloarthritis Research Consortium of Canada; BSA: Body Surface Area; ESR: Erythrocyte Sedimentation Rate; 
CRP: C-reactive protein 
 
 
 

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Scanners/probes that will be used for each anatomical site is summarized in Table-2. 
Table-2: Probes/scanners, views and anatomical sites 
Anatomical site 
Views 
GE Logic E9/S8 
Clarius L15 
Clarius L20 
2nd MCP joints  
dorsal and lateral 
X 
X 
X 
3rd MCP joints 
dorsal 
X 
 
X 
2nd-3rd PIP, 2nd-3rd DIP 
dorsal 
X 
 
X 
Wrist 
dorsal 
X 
X 
X 
5th MTP joints 
dorsal and lateral 
X 
 
X 
Elbow joints 
posterior 
X 
X 
 
Shoulder joints 
posterior 
X 
X 
 
Knee joints 
anterosuperior 
X 
X 
 
Ankle joints 
anterior 
X 
X 
 
Nails 
 
dorsal 
X 
 
X 
Achilles 
tendon 
insertions 
posterior 
X 
X 
X 
Supraspinatus tendon 
insertions 
lateral 
X 
X 
 
Triceps 
tendon 
insertions 
posterior 
X 
X 
 
Common 
extensor 
tendon origins 
lateral 
X 
X 
 
Quadriceps 
tendon 
insertions 
anterior 
X 
X 
 
Patellar 
ligament 
(origin and insertion) 
anterior 
X 
X 
 

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Plantar 
fascia 
insertions 
plantar 
X 
X 
 
Extensor 
digitorum 
tendon insertions at 
DIP and PIP 
dorsal 
X 
 
X 
Extensor 
digitorum 
tendon of the second 
digits 
dorsal 
X 
 
X 
Tibialis 
posterior 
tendon  
medial 
X 
X 
 
MCP: metacarpophalangeal; PIP: proximal interphalangeal; DIP: distal interphalangeal (DIP): MTP:  
metatarsophalangeal 
Subject ID: Every study subject will be given unique study ID. This will consist of site ID and 
patient number respectively (Site IDs will be 01 for OHRI, 02 for Women College and 03 for 
University of Florida).  
Labelling: During the ultrasound scan every image that is saved will be given a label by the local 
research assistant.  
Exporting: After each scan, all the images of each study subject will be exported in JPEG format. 
The images will be saved in a file with the subject ID, which will be unique. This file will be send 
to the central site (OHRI) using Sharepoint by the local research assistant. 
Blinding: At the central site (OHRI), the research assistant will give a unique identifier number to 
each image, for a random quality control and for cross referencing whenever needed. The cropped 
images, as detailed below, will not have the subject ID visible to the PI at the time of reading but 
will be accessible for the quality control. (read-only access). The research assistant at OHRI is the 
only site personnel who has the capacity to uncrop the images in the PowerPoint file (password 
protected files).  
For interim analysis, image reading will be performed after the first 10 patients. Final reading will 
be done after all patients are recruited. Images will be scored by the principal investigator at OHRI. 
Images will not contain any identifiable information such as Date of Birth (DOB) or initials. The 
US images will be transferred to a PowerPoint file by the research assistant at OHRI in JPEG 

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format. The research assistant will generate an unblinded master list, inaccessible to other site 
personnel, to link the slide numbers with the patients and scanned anatomical sites and the slide 
will have no other information on the patient number or ID. For scoring the images by the PI, a 
random order slide show will be conducted, irrespective of the machine used or the anatomical site 
or patient assessed, to ensure blindness to data related to the patient identifiers (The PI will not be 
blinded to the machine that the image was taken with as the JPEG format that is achieved from 
different machines are identifiable, but due to the random order scoring, images that belong to the 
same joint by the different machines are not to be scored consecutively). There will be nine 
separate powerpoint files, for images of joints, tendons, entheses, nail including power Doppler 
and gray scale findings; and grey scale file for erosions. Scoring will be done using previously 
validated methods as detailed below.  
During the data collection, there will be interim analysis: Interim analysis will be done after 10 
patients being recruited. The readings and scorings will be done by the principal investigator at 
OHRI center, following the exact methodology as above. 
 The grading of greyscale intraarticular synovitis and power Doppler intrasynovial signals will be 
done based on the OMERACT definitions (scales of 0-3) as follows16, 17 : 
Greyscale inflammatory (hypoechoic) synovial hyperplasia: 
• 
Grade 0: no hypoechoic synovial hyperplasia 
• 
Grade 1: minimal hypoechoic synovial hyperplasia (filling the angle between the 
periarticular bones, without bulging over the line linking tops of the bones) 
• 
Grade 2: hypoechoic synovial hyperplasia bulging over the line linking tops of the 
periarticular bones but without extension along the bone diaphysis 
• 
Grade 3: hypoechoic synovial hyperplasia bulging over the line linking tops of the 
periarticular bones and with extension to at least one of the bone diaphyses 
Power Doppler signal: 
• 
Grade 0: no flow in the hypoechoic synovial hyperplasia 
• 
Grade 1: up to three single spots signals or up to two confluent spots or one confluent spot 
plus up to two single spots 

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• 
Grade 2: vessel signals in less than half of the area of the synovium (≤50%) 
• 
Grade 3: vessel signals in more than half of the area of the synovium (>50%) 
Elementary lesions of enthesitis will be defined and scored as per the GRAPPA US working 
group’s definitions, as used in the multicenter DUET study co-supported by Novartis18 : 
Hypoechogenicity: Distinct loss of homogenous fibrillar pattern with relative hypoechogenicity 
compared to the rest of the enthesis after correcting for anisotropy.   
• 
Grade 0:  
Absent 
• 
Grade 1: 
Present 
Thickening: Increased thickness of the tendon/ligament at the enthesis compared to its body. 
Thickness may be difficult to judge and should be suspected when accompanied by other 
entheseal lesions.  
• Grade 0: 
Absent 
• Grade 1: 
Present 
Bone Erosion: A cortical defect confirmed with a step-down contour defect detected in two 
planes at the insertion of the tendon/ligament to the bone. 
• Grade 0: 
Absent 
• Grade 1: 
Present 
Enthesophyte: A step-up bony prominence at the normal bone contour. Grade the severity of 
the enthesophyte based on its length. Although the readers are not expected to measure the 
length of the enthesis we provided suggested cut off points to guide the grading of the 
enthesophytes  
• Grade 0 :  
No enthesophytes 
• Grade 1 :  
Small enthesophyte  
• Grade 2:  
Medium enthesophyte  
• Grade 3:  
Large enthesophyte 
Calcification: Hyperechoic linear structures detected within the tendon/ligament at the insertion 
to the bone but with no congruency with the bone.  

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• Grade 0 :  
No calcifications 
• Grade 1 :  
Punctate hyperechoic area 
• Grade 2:  
Linear calcification without acoustic shadow 
• Grade 3:  
Egg-shell calcification with posterior acoustic 
shadow 
Doppler Signal: The presence of positive Doppler signal at the enthesis, confirmed in two 
perpendicular planes and distinguished from reflection of surface artifacts and nutritional vessel 
signal.  
The intensity of the Doppler signal at the enthesis will be graded using a semi-quantitative score. 
Note: we will consider any Doppler signal at the enthesis area including signals appearing 
beyond 2 mm of the bony cortex, however, not including Doppler signals at the bursa which 
will be scored separately.  
We will score the intensity of the Doppler signal on a semi quantitative grading system: 
• Grade 0:  
No Doppler signal 
• Grade 1:  
A single confluent Doppler signal or up to 3 discrete 
Doppler spots  
• Grade 2:  
Doppler signal affecting less than half of the 
enthesis 
• Grade 3:  
Doppler signal covering more than half of the 
enthesis 
In addition, the location of each Doppler signal will be recorded: 
• Zone 1:              ≤2mm from the bone cortex – Zone 1 
• Zone 2:              >2mm from the bone cortex – Zone 2 
 
 
 
 
4.4 Statistical Analysis: 

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The primary endpoint analysis will be the interrater agreement of detecting any synovitis in B 
mode with the Clarius and gold standard machine. The kappa coefficients will be evaluated using 
the guideline outlined by Landis and Koch, where the strength of the kappa coefficients are: 0.01-
0.20 slight; 0.21-0.40 fair; 0.41-0.60 moderate; 0.61-0.80 substantial; 0.81-1.00 almost perfect.19 
For secondary outcomes, the interrater agreement for the presence of Doppler signals within the 
joints, tenosynovitis, erosions, nail, as well as features of enthesitis (hypoechogenicity, thickening, 
erosions, enthesophytes, calcifications) will also be evaluated using the same method. The 
agreement of the semiquantitative grading of the intraarticular findings’ severity (synovitis in B 
mode, Doppler signals, erosions, each being on a scale between 0-3) will be done using weighted 
kappa analysis.20 
An interim analysis will be done after 10 patients. A moderate level of interrater agreement within 
that sample size (primary outcome) will allow parallel initiation of subsequent studies proposed in 
the research framework. 
4.5 Sample Size Consideration  
Study agreement analyses will be done per joint. To give a kappa ≥ 0.61 (from substantial interrater 
agreement to almost perfect agreement) with a confidence interval width of 0.15 and the 
expectation of approximately 20 % of joints assessed having any synovitis in B mode (based on a 
previous study by our group), 683 joints would be required.18 This corresponds to 30 patients if 24 
joints per patient are assessed. Non-inferiority margin will be κ≥ 0.61. 
5.0 Impact of the study  
The relatively low cost of the hand-held US devices makes them affordable for the everyday 
rheumatology practices, including the community and academic centers. Although the study is 
focused on PsA patients, the wide range of lesions that will be investigated in this study will help 
to prove the validity of the hand-held US in comparison to the high-end machines for other uses 
of US in the field of rheumatology. We hope that our results will increase the uptake up MSK US 
in daily practice that will allow earlier diagnosis and more accurate assessment of disease activity 
on a large scale. US itself has been characterized as more sensitive than either X-ray or Magnetic 
Resonance Imaging (MRI) at detecting joint involvement in PsA.21 Adding to this increased 
sensitivity, handheld POC US also has the potential to accelerate the patient journey to diagnosis 

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and optimized therapy by circumventing the long waiting lists associated to MRI  imaging that 
plague the Canadian healthcare system. In fact, the Conference Board of Canada estimates that, 
by 2022, the average wait will be 133 days for MRI, greatly exceeding the acceptable target of 30 
days22. This is concerning when it has been shown that, for PsA, a diagnostic delay of more than 
6 months (180 days) is associated to irreversible joint damage and poor functional outcomes. 
 
6.0 Translation of CRF 
The physician Case Report Form (CRF) does not need to be translated. The patient CRFs and 
consent forms will be available in English and in French. The PROs have already been validated 
in French.  
7.0 Ethical and regulatory aspects 
The primary site for ethics submission will be the Ottawa Hospital/the Ottawa Hospital Research 
Institute; 1967 Riverside Dr., Ottawa, ON, Canada K1H 7W9. The Principal Investigator is Sibel 
Aydin, MD. 
7.1 Participant consent 
Eligible patients will be approached for study recruitment during their visits in rheumatology. 
Patients who are willing to participate will be asked for a signed informed consent. All patients 
will receive detailed information about the study at the time of enrollment. The participants will 
have the opportunity to leave the study at any time. According to the participant’s will data 
previously recorded could be kept in the database for analysis, in case they withdraw consent.  
7.2 Personal information management 
The local investigators will keep a confidential correspondence list of patient identifiers and of 
patient numbers. The centralized information will consist entirely of de-identified data. 
7.3 Regulations and Review Board 
The study will be conducted in accordance with the protocol, Good Clinical Practice (GCP), ethical 
principles that have their origin in the Declaration of Helsinki and all applicable local regulations.   

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Independent Ethics Committee or Institutional Review Board approval of the protocol will be 
obtained prior to commencing the study at each site, through the principal investigator and 
designated investigators.  
An Institutional Review Board approved, study-specific informed consent will be reviewed, signed 
and dated by the subject (and the investigator) prior to the performance of any study-related 
procedures.   
 
8.0 Data Quality Assurance 
Data management 
Patients will be identified by a local number at each investigator site, which will have a 2-letter 
code for a site and a number for each patient.  Each site will keep a confidential subject 
identification code list, so that if there are missing data this information will be available locally 
to clarify the information.    
Two paper CRFs, patient and physician CRFs, will be filled for each patient during the visit and 
these will be the source documents. The CRFs will be scanned and uploaded to the SharePoint at 
each center, within 3 day after the visit. In addition, US images of each patient will be uploaded to 
the SharePoint. US images and CRFs uploaded from each center will be reviewed by the research 
assistant at Ottawa Hospital Research Institute (OHRI) center. If there are any missing or erroneous 
data, it will be ensured that the errors and deficiencies are corrected by contacting the center. Any 
queries will be confirmed with the site within a week of the data entry. Center will then correct 
and update the physician CRF as per Good Documentation Practices and re-scan the CRF to the 
sharepoint. Then the analyzed CRFs data will be transferred to Research Electronic Data Capture 
(REDCap) ( version 12.4.18 - © 2023 Vanderbilt University) by the research assistant at OHRI. 
After all the data is transferred to REDCap, the data in Sharepoint will be deleted. The data in 
REDCap will also be deleted when the data is exported and the analysis is completed.  The 
exported data will be locked and stored in a secure and password protected computer at The Ottawa 
Hospital, according to the requirements by the Research Ethics Board (REB) at The Ottawa 
Hospital. The paper CRFs, which are the source documents, will also be maintained on site for 10 

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years . The electronic data will be stored for 15 years.  For both devices already being Health 
Canada and FDA approved, a Data Monitoring Committee is not deemed to be needed by the PIs. 
Publication, Study Results and Authorship Criteria 
The study will be registered on clinicaltrials.gov including a study report at the end of the study. 
The results will be presented in EULAR 2023 congress and subsequent national and international 
rheumatology congresses. A manuscript will be generated to be published in a peer reviewed 
rheumatology journal with the possibility of subsequent publications on post-hoc analysis.  To be 
eligible to be included in publications, investigators will be required to have a significant 
contribution to one of the following aspects of the study, in compliance with the ICMJE 
(International Committee of Medical Journal Editors) recommendations and criteria: 
1) Conception of the study and development of the methodology. This will include members of the 
steering and advisory committee. 
2) Data collection. Each investigator will be required to recruit 10 cases. 
3) Data analysis 
4)  Contribute to the publication by reviewing and approving the final abstract/manuscript. 
Timetable: 
Action 
Timeframe 
Ethics application- approval 
September-October 2022 
Contracts 
November-December 2022 
Recruitment  
January -April 2023 
Analysis and Abstract submission for 
ACR 2023 congress and subsequent 
national and international rheumatology 
congresses 
May 2023 
Writing the manuscript 
May-July 2023 
 

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