Defining Cut-off Values for Widely-used Composite Scores and Patient-reported Outcome Measures in Psoriatic Arthritis Corresponding to Remission and Flare Assessed by the Physician and the Patient
Conditions: Psoriatic Arthritis
Sponsor: Groupe Hospitalier Pitie-Salpetriere

1 
 
THE 
REMISSION 
AND 
FL ARE 
IN 
PSORIATIC 
ART HRITIS 
(REFLAP) STUDY 
DEFINING CUT-OFF VALUES FOR WIDEL Y-USED COMPOSITE 
SCORES AND PATIENT-REPORTED OUTCOME MEASURES IN 
PSORIATIC 
ARTHRITIS, 
CORRESPONDING 
TO 
MINIMAL 
DISEASE 
ACTIVITY, 
PATIENT-REPORTED 
ACCEPTABLE 
STATE/REMISSION, AND FLARE ASSESSED BY THE P HYSICIAN 
AND THE PATIENT  
A 
PROSPECTIVE 
6 -MONTH 
STUDY 
WITH 
A 
D OUBLE 
PERSPECTIVE 
Date of version  
April 21, 2017  
Principal 
investigator 
Laure GOSSEC, MD, PhD, France 
 
Contact:  
Laure Gossec                        
laure.gossec@aphp.fr 
Service de Rhumatologie, CHU Pitié Salpétrière       
47-83 Boulevard de l'Hôpital, 75013 Paris, France 
+33 1 42 17 84 21 
Steering 
committee  
Laura COATES, UK 
Maarten de WIT, Netherlands 
Ana-Maria ORBAI, USA  
Josef SMOLEN, Austria 
Promotor 
and 
sponsor 
Groupe 
d’Etudes 
et 
de 
Recherche 
de 
l’appareil 
locomoteur (GERPAL), a non-for-profit hospital-based 
research association, president Pr Pierre Bourgeois, 
Hopital Pitié-Salpétrière, 47-83 Bd Hopital, 75013 Paris 
France 
Principal investigator signature 
Laure Gossec, 21 April 2017 

2 
 
 
Contents 
 
Brief synopsis .................................................................................................................................................. 3 
Long Summary ................................................................................................................................................. 5 
Background...................................................................................................................................................... 7 
Objectives ...................................................................................................................................................... 10 
Patients and methods ................................................................................................................................... 11 
Study design .......................................................................................................................................... 11 
Patient research partner involvement .................................................................................................. 11 
Patients .................................................................................................................................................. 11 
Data collection ....................................................................................................................................... 13 
Outcomes and planned analyses........................................................................................................... 19 
Statistical analyses................................................................................................................................. 20 
Ethical and regulatory aspects ...................................................................................................................... 25 
Practical aspects ............................................................................................................................................ 27 
Coinvestigators ...................................................................................................................................... 27 
Proposed calendar ................................................................................................................................. 29 
Budget ................................................................................................................................................... 30 
Expected outcomes of the study ................................................................................................................... 32 
References ..................................................................................................................................................... 33 

3 
 
 
Brief synopsis 
Objective  
To define cutoffs of the most widely used composite scores and patient-reported 
outcomes (PROs), for levels corresponding to remission/low disease activity and for 
changes in levels corresponding to flares, in Psoriatic arthritis (PsA), from the patient 
and physician perspective.  
Methods 
Design: the ReFlaP (Remission/Flare in PsA) study is a prospective, multicentric 
international, longitudinal, observational study planned in 2017-18 in 28 centers 
across Europe, North and South America and Asia. We plan to include 450 patients 
over 6 months (20-30 patients per centre). Each patient is seen twice: once at 
baseline and once at 1-6 months (follow-up visit, either for usual follow-up or because 
of a flare) in the context of usual care. 
 
Patients: Consecutive adult patients with definite PsA (according to ClASsification of 
Psoriatic ARthritis (CASPAR) criteria and confirmation by a rheumatologist), and 
more than 2 years of disease duration.  
Data collection: During each visit, physicians will collect: 66-68 joint counts, tender 
entheseal points and body surface area of psoriasis. This will allow calculation of: 
Arithmetic Mean of Desirability Functions modified, Disease Activity in PSoriatic 
Arthritis (DAPSA), clinical DAPSA, Minimal Disease Activity and Psoriatic ArthritiS 
Disease Activity Score. PROs will include will include Patient Global Assessment, 
Pain, Health Assessment Questionnaire for Disability Index, PSoriatic Arthritis Impact 
of Disease, Psoriatic Arthritis Quality of Life, 36-Item Short Form Health Survey (SF-
36), PSoriatic Arthritis Impact of Disease, 12-Item Short Form Health Survey (SF-36), 
Patient Acceptable Symptom State (PASS), Minimal clinically important differences 
(MCID) and the recent Flare questionnaire. Assessment of disease activity status (i.e. 
remission or flare) will also be performed by both physician and patient using global 
questions. 
Planned analysis 
From the health professional perspective, ’remission’ will be defined as MDA and 
sensitivity analyses will use the other composite scores; flare will be defined as 
decision of treatment intensification and sensitivity analyses will be performed.  
From the patient perspective, ‘remission’ will be defined as PASS and as sensitivity 
analysis, patient-perceived remission/low disease single questions, and for flares, the 
flare questionnaire, and as sensitivity analyses, flare according to the patient (single 
question) and the assessment of worsening based on the validated MCID question.  

4 
 
We will assess what physician and patient-defined states correspond to both on 
composite scores and on PROs, using baseline data for remission/low disease 
activity and changes in scores between the 2 visits for flares. Cutoff values for each 
outcome or change corresponding to clinically important differences will be calculated 
using ROC curves and 75th percentile analyses.  
Planned outcomes 
The expected outcomes are a better knowledge of remission/low disease activity and 
flare in PsA in accordance to the perspectives of patients and physicians. We will 
define cutoff values for most widely-used scores in PsA, allowing easier interpretation 
of study results and in the clinic, helping a better communication with patients in a 
treat-to-target approach. 

5 
 
Long Summary 
 
Introduction  
Psoriatic arthritis (PsA) is a heterogeneous chronic disease with a significant 
patient-perceived impact leading to pain, fatigue, impaired function and quality of life 
and psychological distress. Remission is the announced treatment target in PsA. 
Several definitions of remission have been proposed including definitions on 
composite scores such as the Disease Activity in Psoriatic Arthritis (DAPSA) and 
Minimal Disease Activity (MDA), however their translation into the patient’s 
perspective is lacking. Flares are frequent in PsA and are important for patients but 
are not well-defined from the physician’s perspective. Although some work is ongoing 
regarding remission and flare from the patient’s perspective, currently no information 
allows to cross-tabulate and compare the patient and physician perspectives 
regarding remission and flare in PsA . 
The objective is to define cutoffs of the most widely used composite scores and 
patient-reported outcomes (PROs), for levels corresponding to remission/low disease 
activity and for changes in levels corresponding to flares, in PsA, when remission/low 
disease activity and flare are defined from the patient and physician perspective.  
Methods 
Design: the ReFlaP (Remission/Flare in PsA) study is a prospective, multicentric 
international, longitudinal, observational study. It will take place in 2017-18 in 28 
centers across Europe, North and South America and Asia. We plan to include a total 
of 450 patients. The inclusion period will last 6 months; each center will include 
around 20 patients. Each patient is seen twice - once at baseline and once at 1-6 
months (follow-up visit either for usual follow up or due to a flare) in the context of 
usual care. 
Patients: Consecutive adult patients with definite PsA (according to ClASsification of 
Psoriatic ARthritis (CASPAR) criteria and confirmation by a rheumatologist), more 
than 2 years of disease duration, and will be included after signed informed consent.  
Data collection: During each visit, physicians will collect data on the disease and on 
disease activity: 66 swollen joint counts, 68 tender joint counts, tender entheseal 
points (Leeds Enthesitis Index) and body surface area of psoriasis. This will allow 
calculation of most of the usual composite scores of PsA: Arithmetic Mean of 
Desirability Functions modified (AMDF modified), Disease Activity in PSoriatic 
Arthritis (DAPSA), clinical DAPSA (c-DAPSA), Minimal Disease Activity (MDA) and 
Psoriatic Arthritis Disease Activity Score (PASDAS). Well-validated patient-reported 
outcomes will be collected from patients: Patient Global Assessment (PGA), Pain,, 
Health Assessment Quality (HAQ-DI), PSoriatic Arthritis Impact of Disease (PSAID) 
which includes a fatigue question, 12-Item Short Form Health Survey (SF-12), Patient 
Acceptable Symptom State (PASS) and the validated question for Minimal clinically 

6 
 
important differences (MCID) as well as a recent Flare questionnaire. Assessment of 
disease activity status (i.e. remission/low disease activity or flare) will be performed 
by both physician and patient using global questions. 
Planned analysis 
To define cutoffs of the most widely used composite scores and PROs, for levels 
corresponding to remission/low disease activity and for changes in levels 
corresponding to flares, in PsA: 
From the health professional perspective, the gold standard for ’remission’ will be 
MDA and sensitivity analyses will use physician-perceived remission/low disease 
activity (single questions) and remission in composite scores (DAPSA, c-DAPSA, 
modified AMDF, PASDAS); for flare the gold standard will be decision of treatment 
intensification and sensitivity analyses will use: global assessment of flare and 
increase in category of disease activity in the composite scores.  
From the perspective of the patient, the gold standard will be for ‘remission’, PASS 
and as sensitivity analysis, patient-perceived remission/low disease single questions 
yes/no, and for flares, the GRAPPA flare questionnaire, and as sensitivity analyses, 
flare according to the patient (single question) and the assessment of worsening in 
MCID.  
We will assess what physician-defined remission/low disease activity/flare and 
patient-defined remission/low disease activity/flare correspond to both on composite 
‘physician’ scores and on all the collected PRO scores. We will use data collected at 
baseline cross sectionally for remission/low disease activity and changes in scores 
between the 2 visits for flares. 
Cutoff values for each outcome and for each change corresponding to clinically 
important differences in outcome will be calculated using ROC curves and 75th 
percentile analyses. Sensitivity analyses will explore cutoff values found according to 
patient demographic characteristics and country. We will compare attainment of 
remission or flare according to the different definitions, using kappa analyses. Rasch 
analyses will be used as necessary. 
 
Planned outcomes 
The expected outcomes of this study are a better knowledge of remission/low 
disease activity and flare in PsA in accordance to the perspectives of patients and 
physicians. We will define cutoff values for most widely-used scores in PsA, allowing 
easier interpretation of study results and in the clinic, helping a better communication 
with patients. 
Better knowledge of the important aspects of disease fluctuation and of patient 
relevant disease targets in PsA should enhance patient care and management in a 
treat-to-target approach. 

7 
 
Background 
 
Psoriatic arthritis (PsA) is a complex disease with inflammation that spans a 
wide spectrum to include peripheral joints, skin, entheses, spine, and other adjacent 
tissues. (Kleinert2007) PsA is an erosive and proliferative deforming arthritis usually 
accompanied by skin lesions as well as in some cases other manifestations.  
Recent management recommendations state that remission is the treatment 
goal in PsA. (Gossec2016a, Coates2016a, Coates2016b) However, experts also 
recognize that remission is sometimes difficult to achieve and maintain and that, in 
some patients, some residual or mild disease activity may be acceptable. 
(Gossec2016a, Coates2016a) Thus, ‘‘near-remission’’ or ‘‘minimal/ low disease 
activity’’ could be an appropriate goal for treatment in some individual patients. 
(Kavanaugh2006, Gossec2016b)  
There are several definitions of remission and acceptable residual 
disease activity levels in PsA. (Kavanaugh2006, Acosta2014) The Group for 
Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) suggested that remission 
in PsA should be characterized by ‘‘a complete absence of disease activity, with no 
signs or symptoms of active disease’’. (Kavanaugh2006) In parallel, the European 
League Against Rheumatism (EULAR) defined remission in PsA as “the absence of 
clinical and laboratory evidence of significant inflammatory disease activity.” 
(Gossec2016a) Contrary to the situation in rheumatoid arthritis where a specific 
definition of remission has been proposed by a European League Against 
Rheumatism (EULAR)/American College of Rheumatology (ACR) consensus 
(Aletaha2010a, Bykerk2012), in PsA a specific and quantifiable definition of 
remission is lacking. However some approaches have been proposed recently based 
on physician consensus exercises and using composite disease activity scores. 
Remission and low disease activity definitions have been defined using the Disease 
Activity index for Psoriatic Arthritis (DAPSA) (Aletaha2016b) The DAPSA is 
composed of five untransformed, unweighted variables, including two patient-
centered items (patient global assessment and pain on an 11-point numeric rating 
scale), one physician centered item (swollen joint count using 66 joints, 66-SJC), one 
item dependent on patient and physician (tender joint count using 68 joints, 68-TJC), 
and a laboratory variable (C Reactive Protein (CRP) in mg/dL). (Aletaha2016b) The 
DAPSA-based remission status (i.e., a score <4 points) is associated with no or 
minimal residual ultrasound signals in the joints. (Schoels2016) A clinical DAPSA 
score (c-DAPSA) is also available and is calculated using the same variables as 
DAPSA, without CRP.  Other measures with validated definitions of remission include 
the Composite Psoriatic Disease Activity Index (CPDAI), the GRAPPA-developed 
PsA Disease Activity Score (PASDAS) and Arythmetic Mean of Desirability Functions 
(AMDF). (Mumtaz2011, Helliwell2014) 
An alternative treatment target is Minimal Disease Activity (MDA). Minimal 
disease activity (MDA), agreed at the Outcome Measures in Rheumatology Clinical 

8 
 
Trials (OMERACT) 6 conference is defined as “that state of disease activity deemed 
a useful target of treatment by both the patient and the physician, given current 
treatment possibilities and limitations”. (Wells2005). Patients are classified as 
achieving MDA if they fulfill 5 of 7 outcome measures: tender joint count ≤1; swollen 
joint count ≤1; psoriasis activity and severity index ≤1 or body surface area ≤3; 
patient pain visual analog scale (VAS) score of ≤15; patient global disease activity 
VAS score of ≤20; Health Assessment Questionnaire (HAQ) score ≤0.5; and tender 
entheseal points ≤1. (Coates2010b) The recently published Tight control in PsA 
(TICOPA) trial now provides evidence for treating to target using the MDA criteria. In 
this trial, patients with active PsA randomised to the tight control arm had a treatment 
escalation starting with conventional synthetic DMARDs up to biologics, if the pre-
defined target of MDA was not reached: the group with tight control had more 
favorable clinical and patient reported outcomes. (Coates2013c)  
 
Remission from the patient perspective has not been defined. The only 
data available are issued from qualitative studies and have not been further 
quantified or even graded for importance. These qualitative studies bring information 
on the patient experience of remission and other aspects of PsA (this work is 
underway as part of a GRAPPA/OMERACT initiative). PsA has a significant impact 
on patients’ lives, as seen not only in qualitative studies but also through PRO 
(patient-reported outcome) assessments. The impact of PsA includes pain, fatigue, 
altered quality of life and impaired physical functioning as well as psychological 
impact. (Gossec2014, Strand2012). The wide-reaching impact of PsA has been 
recognized by OMERACT in the new updated Core Set for PsA (Orbai2016a). The 
Patient Acceptable Symptom State (PASS) is a well-validated single question which 
may approximate ‘remission’ for the patient since at least, it defines an acceptable 
state (Tubach2012, Heiberg2008). 
PROs are an important component to assessing disease impact and therapy 
response in patients with PsA. (Strand 2016, Kirkham2015, Gniadecki2012) Many 
questionnaires and PROs are used in rheumatology. (OML) Some of these 
questionnaires assess a single aspect of disease impact: e.g., pain or patient global 
assessment (usually assessed using a numeric or visual rating scale) and physical 
functioning (usually assessed through the Health Assessment Questionnaire (HAQ) 
whereas others assess global impact of disease or quality of life. (Chandra2007, 
Pincus2007) These include generic questionnaires such as 36-Item Short Form 
Health Survey (SF-36), and disease specific questionnaires such as the EULAR-
developed PsA Impact of Disease (PsAID) questionnaire or the PsA Quality of Life 
Scale (PsAQoL). (McKenna2004; SF36; Gossec2014c) 
Knowledge of meaningful cutoffs for both patients and physicians for 
PROs and PsA composite scores, corresponding to both physician-defined 
targets (such as MDA) and patient-defined acceptable states, will improve PsA 
disease activity targeting, management and long term patient outcomes. It is 

9 
 
important to note that given the culture-dependent nature of PROs, an international 
study would be preferred to ensure generalizability of our findings. (Putrik2016) 
 
Another important concept in disease activity is flares. Most studies 
describe flare as an absence of remission or absence of minimal disease activity 
though the notion of a change in status is important when defining 
flares.(Dougados2016) From the physician perspective, a change in therapy 
(intensification) could also be used as a surrogate marker of flare. (Alten2011); a flare 
can also be defined as a worsening of disease activity using composite scores. 
From the patient perspective, flares are a complex notion. Recently, 
GRAPPA has developed a preliminary flare PRO. (Moverly2016a, Moverly2015b) in 
this work, 20 items were agreed on as important by patients and 23 by physicians to 
define a flare, 8 items were accepted by both with the notion of a recent 
change/increase in the number or combination of symptoms. The concept of flare 
covers articular, skin, emotional, participation and fatigue domains. These qualitative 
studies bring information on the patient perspective on what it means to be in flare. 
(Orbai2016, Moverley2016a, Moverley2015b)  
To our knowledge, this flare questionnaire has not yet been validated and in 
particular it is unknown how flares assessed using this questionnaire relate to 
changes both in composite scores (i.e. mixing physician assessment and PROs) and 
in other PROs. Quantification is needed to define cutoff values for change in 
usual composite scores and PROs, which would correspond to a flare from the 
patient and physician perspectives in PsA. 
 
Overall, there are no validated cut-off values of PROs and composite scores 
corresponding to different states of disease activity in PsA (namely, remission and 
flare).  
Such innovative data would be very useful in a ‘treat to target’ approach 
to allow mutual interpretation of patient and physician treatment objectives. 

10 
 
Objectives 
 
- 
To define cutoffs of the most widely used composite scores (mixing physician 
assessment and PROs) and PROs, for disease activity levels corresponding to 
PsA remission/low disease activity and for change in level of disease activity 
corresponding to PsA flare, when remission/low disease activity and flare are 
defined from the patients’ and physicians’ perspectives.  
- 
From the physicians’ perspective, ’remission’ will be defined by MDA and 
sensitivity analyses will use physician-perceived remission/low disease (single 
questions) and remission in composite scores (DAPSA, modified AMDF, 
PASDAS); flare will be defined as decision of treatment intensification and 
sensitivity analyses will use: global assessment of flare and increase in 
category of disease activity in the composite scores.  
- 
From the patients’ perspective, ‘remission’ will be defined as PASS attained 
and as sensitivity analysis, patient-perceived remission or low disease single 
questions yes/no, and flares will be defined using the GRAPPA flare 
questionnaire, and as sensitivity analyses, flare according to the patient (single 
question) and the assessment of worsening in MCID.  
We will assess what ‘physician-defined’ remission/low disease/flare and patient-
defined remission/low disease/flare correspond to both on composite ‘physician’ 
scores and on all the collected PRO scores.  We will use cross-sectional data 
collected at baseline for remission and low disease activity; and changes in 
scores between the 2 visits for flares. 

11 
 
Patients and methods 
 
Study design 
 
This study is a pragmatic, prospective, multicentric and international, 
longitudinal observational study performed in usual care. It is planned to take place in 
2017-18 in 5 participating centres in France, 15 other European tertiary rheumatology 
centers (Germany, Hungary, Ireland, Italy, Norway, Romania, Spain, Turkey and the 
UK), 4 centers in the USA, 2 centers in Canada, 1 in Brazil, and 2 in Asia (Singapore 
and Russia). The international aspect is important firstly to reflect the potential 
diversity of patient views across countries and cultures, and secondly to facilitate 
rapid patient inclusion. 
 
Patient research partner involvement 
 
Rules proposed by EULAR and OMERACT are followed to facilitate patient 
involvement. (deWit2011, Cheung2014) 
At the highest level: one patient partner (MdW) is part of the steering committee.  
Three other patient research partners helped to finalize the study design and data 
collection including the remission/low disease and flare global questions, and will give 
feedback on the results of the study. The 3 patients are Laurence Carton (France), 
Heidi Bertheussen (Norway) and Jim Walker (Scotland). 
A first teleconference and email exchanges with the 4 patient research partners with 
PsA was organized in March 2017 to elaborate the remission and flare gestalt 
questions; and a second teleconference with the same partners will allow to present, 
discuss and interpret findings from a patient perspective.  
Of note, we will not perform qualitative work on remission and flares with patients to 
avoid duplicating ongoing efforts in this area. (Moverley2015b, Orbai unpublished) 
 
Patients 
 
Patients’ recruitment 
 
Over the 6 months recruitment period, all patients with definite PsA who satisfy 
the inclusion criteria, seen in outpatient visits in the participating centers by one of the 
investigators, will be asked to participate.  
We expect a total of 700 patients will be contacted, to include 500 patients.  

12 
 
It is planned that in each center, 15-30 patients will be included. The first 15-30 
consecutive patients will be selected in each center to reduce bias selection.   
Each patient will be assessed, the first time, at the time of a scheduled visit in one of 
the participating centers according to local practice; and the second time, 1-6 months 
later, at the next consecutive assessment of his/her status according to usual 
practice. The choice of this second time point is important because as this is a ‘non-
interventional’ study, there is no consensus about the period of follow-up between 
countries we are in a usual practice setting when leaving the choice open to the 
physician between 1 and 6 months. 
 
Furthermore, the open timeframe will increase the probability to detect a flare since in 
many cases, patients will consult the physician in case of flare but this visit would be 
missed using a fixed time point.  
We will encourage physicians to see patients if they are reporting a flare, as is 
recommended in a treat-to-target approach. 
The follow-up for each patient will be of 1 to 6 months (last date allowed: 7 months).   
 
Inclusion criteria 
      - Age>18 years 
- Definite PsA according to the ClASsification of Psoriatic ARthritis (CASPAR) 
criteria and diagnosis confirmed by a rheumatologist. (Taylor2006)  
- Willingness to participate and signed informed consent. 
- There are no inclusion criteria based on disease activity or treatment. Given the 
international study with countries with varied levels of health and of access to care 
and treatments, the study should include patients with a wide range of disease 
severity and activity at baseline.  
   - Patients with more than 2 years of disease duration will be included in the study 
for more homogeneity.  
  
Patient will be included consecutively. A registry will be kept locally to note the age 
and gender of patients who have been proposed the study but refused to participate. 
 
 
Exclusion criteria 
- 
No definite PsA or less than 2 years of disease duration 

13 
 
- 
Patients who don’t speak or read the local language or are not comfortable 
filling in a paper CRF in the local language. 
 
 
 
Data collection 
 
Each patient is assessed twice, at both assessments the same data are collected 
except for data which do not change such as demographic data (Table 1). 
To avoid circularity, physician questionnaires will be filled after the patient 
questionnaire (which is done alone by the patient) and physicians will fill it without 
looking at the patient questionnaire (however they can collect PROs according to 
their usual practice).  
 
 
Physician CRF (Table 1) 
Characteristics of the patients will be collected by the health professionals, 
physicians or research nurses in the physician CRF: sex, age, year of PsA diagnosis, 
work status, treatments (including biological therapy), CASPAR criteria. (Taylor2006) 
The predominant type of PsA (peripheral, axial or entheseal) will be collected and 
current types of involvement will be collected.  
A validated comorbidity index will be collected. (Groll2005) 
 
Elaboration of the physician questions for remission/ flare  
 
Global questions for remission/low disease and flare were elaborated for the purpose 
of this study since none exist. There global questions were developed by the steering 
committee.  
 
Physician data regarding disease activity including physical examination  
Physicians will fill in all the information necessary to calculate the following composite 
scores: DAPSA remission, DAPSA Low Disease Activity (using both DAPSA and c-
DAPSA), PASDAS remission, AMDF modified remission, MDA and its several 
versions including MDA where both joint measures are mandated, MDA where the 
skin measure is mandated, MDA where these three are mandated and Very Low 
Disease Activity (VLDA) corresponding to all MDA criteria fulfilled. (Schoels 2015, 
Smolen2015, Mumtaz2011, Helliwell2014, Coates2010, Coates2016a, Coates2016d) 

14 
 
This includes a physical assessment with 66 swollen joint counts, 68 tender joint 
counts, tender entheseal points (Leeds Enthesitis Index), body surface area of 
psoriasis and physician global assessment. Weight and height will also be collected. 
 
Physicians will also answer general questions on their gestalt on the disease status 
(remission/low disease activity or flare, please see above). To better understand the 
reasoning of the physician, specific questions related to the perceived cause of 
current symptom levels will also be asked: causality of patient symptoms between 
disease activity, sequels of disease or comorbidities. (as was the case in a recently-
completed study in spondyloarthritis, Dougados 2017) 
Here we are using a modified AMDF with no PASI replaced with skin global 
assessment and body surface area, to facilitate feasibility of data collection in 
rheumatology clinics. Furthermore the PsA Quality of Life score which is part of 
AMDF will not be collected: thus this is a modified AMDF. (McKenna2004, 
Mease2016) 
We are aware we will not be collecting the data needed to calculate the Composite 
Psoriatic Disease Activity Index (CPDAI) for feasibility reasons. However a modified 
CPDAI may be calculated based on available data. 
We will avoid circularity by not calculating the composite scores in the CRF.  
 
Blood test results 
No specific blood tests will be performed for this study. 
The last available results (<4 weeks) for C Reactive Protein will be collected in the 
CRF and when answering the CASPAR criteria questions, the physician will be asked 
for Rheumatoid Factor test results (in the patient’s lifetime).  
 
Radiographic assessment 
The last available X-Rays of hands and feet will be assessed locally by the health 
professional to answer the CASPAR question on the presence or not of specific 
radiographic changes. 
 
Treatment changes 
Physicians will collect patient treatments for PsA and will answer if the treatment is 
changed or not and in which way (i.e., intensification, yes/no) at each visit.  
 

15 
 
Patient CRF (Table 1)   
 
General questions 
 
Question regarding demographic data and smoking status as well as current levels of 
physical exercise will be asked. 
 
Elaboration of the patient questions for remission/ flare  
 
For these questions, flare and remission/low disease activity questions were 
developed for the purpose of this study. Patients will answer a specific targeted 
question on their assessment of remission yes/no and low disease activity yes/no. 
These unique and binary questions were refined with our 4 patient research partners 
because none exist in PsA. For flares also, we developed a binary question with the 
patient partners: using as basis the GRAPPA Flare pivotal question as well as 
previous work in the field of rheumatoid arthritis (Moverley 2016, Alten2011, 
Bykerk2016)  
The questions were elaborated in a teleconference in March 2017 with the 4 patient 
research partners with PsA. The goal was to elaborate a global question for 
remission, and for low disease activity, and a global question for flare. A translation of 
the flare/ remission/low disease activity questions will be performed by 2 persons. 
Patient generated data regarding disease activity     
PROs will be collected for PsA patients, at baseline and 1-6 months later at the 
second visit. Given difficulties with international authorizations for online data 
collection, the data will be collected anonymously in paper format. 
 
Remission assessment    
The Patient Acceptable Symptom State (PASS) will be assessed: this corresponds to 
the clinically relevant cut-off from the patient’s perspective allowing classification of 
patients as being in « an acceptable state » or not with one question (“If you were to 
remain for the rest of your life as you were during the last 48 hours, would this be 
acceptable or unacceptable for you?”). (Tubach2012, Wariaghli2012) The PASS will 
be collected at baseline and at the second visit. (Heiberg2008, Tubach2012) 
Patients will also answer a specific targeted question on their assessment of 
remission yes/no and of low disease activity (please see above).  
Flare  
Only flares at the time of assessment are targeted (and not recall of previous flares). 
To assess flares from the patient perspective, the preliminary GRAPPA flare 
instrument will be evaluated: 1.A recent change in joint pain.2.A recent change in 
location of symptoms (i.e., sudden increase in pain or swelling in hands/feet).3.A 
recent change in the number of tender and/or sore joints. 4. A recent change in the 

16 
 
number of aching joints. 5. The presence or degree of pressure-sensitive joints.6.A 
recent change/increase in the number of swollen joints. 7. A recent change/increase 
in night pain. 8. A recent change/increase in the number or combination of symptoms 
(Table 1). (Moverly2016a) 
Patient will also answer a specific targeted question on their assessment of flare 
yes/no (see above). 
The Minimum Clinically Important Difference (MCID) question gives information on 
change in disease status. The question is: “How would you describe your overall 
status since your last visit: much better, better, the same, worse, much worse?” Here, 
worse or much worse will be used to define a flare. (Curtis2015)  
 
Composite PROs 
The PsAID is a questionnaire that can be used to calculate a score reflecting the 
impact of psoriatic arthritis (PsA) from the patients’ perspective. (Gossec2014e) 
 
The 12-Item Short Form Health Survey (SF12) is a multi-purpose, generic health 
survey. (SF36 online) It yields an 8-scale profile of functional health and well-being 
scores as well as psychometrically-based physical and mental health summary 
measures and a preference-based health utility index. A physical summary score 
(physical composite score: PCS) and a mental summary (mental composite score: 
MCS) are calculated according to an established algorithm. PCS includes physical 
function, physical role, bodily pain and general health and MCS includes mental 
health, emotional role, social function and vitality. The SF-12 is copyrighted. It can be 
used instead of SF-36 in composite scores, as recently proposed. 
 
Unidimensional PROs 
 
Patient Global Assessment (PGA) (on a 0–10 scale) asks the patient to give an 
overall assessment of how the arthritis is doing, thereby integrating a number of 
dimensions related to disease activity or to other aspects. The wording of questions 
and anchors are usually as follows: for the PGA, ‘Considering all of the ways your 
arthritis affects you, mark “X” on the scale for how well you are doing’ (‘very well’ to 
‘very poor’).  
 
Patient global for skin and for joints will also be evaluated on a numeric scale from 0 
to 10 since part of the AMDF. (Helliwell2013) This will also give some indication on 
patient-perceived skin involvement. 
Pain will be evaluated on a numeric scale from 0 to 10. 

17 
 
Fatigue will be analysed also (it is included in the PsAID). 
The HAQ-Disability index is a disability questionnaire which includes 8 domains 
scored on a 0-3 scale (0 = without any difficulty, 1 = with some difficulty, 2 = with 
much difficulty, 3 = unable to do). (Pincus2007) 
 
The validated single questions to define Minimal Clinically Important Difference 
(MCID) and PASS will be assessed as explained above. 
 
 
CRF translations 
The physician CRF does not need to be translated. In the patient CRF, existing 
validated translations of the tools integrated in the CRF will be used. The rest of 
the CRF (i.e., demographic data etc) will only have a simple translation (by one 
person). 
For the global remission and flare questions as well as for the Leeds Flare 
questionnaire, we need to perform translations since some of these questions 
were developed for this study (remission/flare questions) and the Leeds Flare 
questionnaire is not translated. 
We will follow a simplified but validated translation and cross cultural adaptation 
process (Guillemin1993, Beaton2000).  
Step 1: Two persons (at least 1 rheumatologist, at least one bilingual person, 
and wherever possible also a patient research partner) translate independently 
the English version into the target language. 
Step 2 : consensus between the translators leads to a final version. Please keep 
in mind that the final wording needs to be understood by lay people including 
low-education people (“the aim is for a 9-yr old child to understand the 
wording”).  
Step 3: Backward translation of the new-language version into English is 
performed by an independent bilingual native English speaker, blinded to the 
English original version. 
Step 4: consensus meeting between the translators to check the meaning has 
not been changed or lost. The group will compare the initial version and the 
back-translation and will discuss the phrasing of the target-language version, 
and by consensus will produce a final version. The committee has to ensure that 
the translation is fully comprehensive and to verify cross-cultural equivalence of 
the source and final versions. Please keep in mind again at this phase that the 
final wording needs to be understood by lay people including low-education 
people.  
 

18 
 
Table 1: data collection  
Type 
of 
data 
Collected data 
Baseline 
1-6 months 
 
Patient 
CRF 
Identifying initials and patient number 
X 
X 
Gender 
X 
 
Smoking status, height and weight 
X 
 
Exercise levels 
X 
 
Patient Pain Visual Analogue Score  
X 
X 
Patient VAS for skin 
X 
X 
Patient VAS for joints 
X 
X 
Patient’s Global Assessment of Disease Activity  
X 
X 
Health Assessment Questionnaire  
X 
X 
SF-12 
X 
X 
PsAID-12  
X 
X 
Disease status: remission yes/no, low disease 
activity yes/no, flare yes/no, and number of recent 
flares 
X 
X 
MCID 
X 
X 
GRAPPA flare instrument 
X 
X 
PASS 
X 
X 
Physician 
CRF 
Year of birth of the patient 
X 
 
CASPAR criteria (individual criteria) 
X 
 
Confirmation of PsA by the physician 
X 
 
Year of PsA diagnosis 
X 
 
Treatments  
X 
X 
Level of studies 
X 
 
Physician Global Assessment  
X 
X 
Predominant type 
of 
PsA: 
axial, 
peripheral, 
enthesitic  
X 
 
Tender joint count (68) 
X 
X 
Swollen joint count (66) and deformed joints 
X 
X 
Body surface area of Psoriasis (%) 
X 
X 
Tender entheseal points (Leeds Enthesitis Index) 
X 
X 
CRP  
X 
X 
Comorbidity index (Groll2005) 
X 
 
Disease status: remission yes/no, low disease 
activity yes/no, flare yes/no, qualitative questions 
regarding cause of symptoms 
X 
X 
Treatment intensification (yes/no) 
X 
X 
 

20 
 
-and sensitivity analyses will use the treating physician-perceived remission or low 
disease (single questions), other definitions of MDA as recently proposed, and 
remission in composite scores (cutoffs have been defined for DAPSA, modified 
AMDF, PASDAS); 
- for flare the gold standard will be decision of treatment intensification  
-and sensitivity analyses will use: global assessment of flare and increase in category 
of disease activity in the composite scores.  
From the patients’ perspective 
-the main definition will be for ‘remission’, PASS  
-and as sensitivity analysis, patient-perceived remission or low disease single 
questions yes/no,  
-and for flares, the GRAPPA flare questionnaire,  
-and as sensitivity analyses, flare according to the patient (single question) and the 
assessment of worsening in MCID.  
 
 
Obtaining cutoffs 
We will assess what physician-defined remission/low disease activity/flare and 
patient-defined remission/low disease activity/flare correspond to both on composite 
‘physician’ scores and on all the collected PRO scores (Figure and Table 2).  We will 
use data collected at baseline cross sectionally for remission and low disease activity 
and changes in scores between the 2 visits for flares. 
We will use data collected at baseline and at 1-6 months since flare is usually 
referred to as a change in disease status and indeed we are planning to define cutoff 
values for change in each outcome, corresponding to a flare.(Gossec2016)  
Although we are aware the cutoff values obtained may differ between physicians and 
patients, we are not planning a reconciliation exercise. 
 
 
  
Statistical analyses 
 
Sample size 
 
The sample size is calculated to be able to determine the cutoff value of PsAID 
corresponding to remission or flare with a certain precision. 

21 
 
With a standard deviation of 2.30 as observed in the PsAID development study on 
107 and 475 patients, with a confidence level of 0.95 and a precision of 0.05, it is 
necessary to analyse 82 patients in ‘remission’ (whatever the remission definition) or 
in flare. Since we expect around 20% of patients to be in remission in this usual 
practice cohort (given percentages of MDA are around 40-50% in randomised clinical 
trials of biological), and around 20% of patients to be in flare, we need to analyse a 
total of 410 patients for remission, thus we need to include 450 patients (taking into 
account uninterpretable CRFs due to missing data). (SAMPLE, Möttönen1999). For 
flares we are aware the sample size will be slightly smaller (taking into account 
patients having had a treatment intensification will not be assessed the second time), 
however for this exploratory analysis the sample size is considered sufficient for 
flares. 
 
Planned analyses 
 
Population: Analyses will be performed on all included patients with data available 
regarding the remission and flare status questions. 
For remission, all included patients with data available regarding remission will be 
assessed. The primary analysis is on baseline data. The data from the second visit 
will be seen as confirmatory and will be analysed as longitudinal data accounting for 
multiple visits. 
For flare, only patients with both visits completed will be used. Change in outcomes 
between the 2 visits will be assessed. 
Similarly to what has been done in axial spondyloarthritis (and differently to what has 
been done in rheumatoid arthritis), it is decided that flare will be defined as a change 
in status between the 2 time points, i.e., a flare is an absolute or relative change 
between 2 values: the observed value of the outcome at the time of the flare, minus 
the referral value (previous status before the flare). (Gossec2016, Bykerk2016) 
The patient’s initial status (referral value of the outcomes at the first visit) may vary 
from no symptoms to moderate/high disease activity but we will analyse separately 
patients with very high initial values, since it is considered that definitions of flares are 
only relevant for patients initially not in very high disease activity.  
 
Planned analyses:  
Cutoff values for each outcome and for each change in outcome will be calculated 
using ROC curves and 75th percentile analyses (Table 2 and 3). For ROC curves, 
different cutoffs will be calculated, both using Youden’s statistic (maximizing both 
sensitivity and specificity) but also using a fixed specificity number (80%) since 
specificity is more important than sensitivity in this case (to avoid overdiagnosing 

22 
 
flares). The 75th percentile technique is a classical technique which finds the value 
above which, 75% of patients reporting an outcome or a change in outcome, are 
placed. Rasch analysis will be used as appropriate. (Tubach2005, Machado2016) 
These techniques are widely used to determine cutoff values for continuous scores 
and are recommended by COSMIN (Mokkink2016/ website.cosmin) 
Sensitivity analyses will explore cutoff values found according to patient demographic 
characteristics and country. 
We will compare attainment of remission/low disease activity or flare according to the 
different definitions, using kappa analyses and logistic regression analyses will 
explore characteristics of patients who are in ‘discordance’ or not for flare/remission 
with the physician-defined definition, and physicians who are in ‘discordance’ with 
patients as well. 
 
Missing data: All data will be analysed. To minimize missing data, the order of 
questions will also be studied to motivate respondents to finish the entire 
questionnaire. 
 

23 
 
Table 2. Planned analyses: defining cutoff values according to different definitions of remission/low disease activity (LDA)  
Gold standards 
are below 
MDA 
Modified 
versions of 
MDA 
Physician Gobal 
Assessment 
 
DAPSA/c-DAPSA 
 
PASDAS  
Modified 
AMDF 
PsAID 
 
HAQ 
 
Pain 
 
Fatigue 
PGA 
 
SF12 
 
MDA 
 
 
 
 
 
 
 
 
 
 
 
 
modified versions 
MDA 
 
 
 
 
 
 
 
 
 
 
 
 
Physician 
remission/LDA 
single questions 
 
 
 
 
 
 
 
 
 
 
 
 
Physician Global 
Assessment<4/10 
 
 
 
 
 
 
 
 
 
 
 
 
Composite score 
DAPSA 
 
 
 
 
 
 
 
 
 
 
 
 
Composite score 
PASDAS 
 
 
 
 
 
 
 
 
 
 
 
 
PASS 
 
 
 
 
 
 
 
 
 
 
 
 
Patient 
remission/LDA 
single questions 
 
 
 
 
 
 
 
 
 
 
 
 

24 
 
 
Table 3. Planned analyses: defining cutoff values for change of outcomes according to different definitions of flare  
Gold 
standards 
are 
below 
MDA 
Physician 
global ass. 
DAPSA/c-
DAPSA 
 
PASDAS  Modified 
AMDF 
GRAPPA 
flare 
questionnaire  
PsAID 
 
HAQ 
 
Pain 
 
Fatigue 
PGA 
 
SF12 
 
Treatment intensification 
 
 
 
 
 
 
 
 
 
 
 
 
Physician flare single 
question 
 
 
 
 
 
 
 
 
 
 
 
 
Composite 
score 
DAPSA 
change 
in 
category 
 
 
 
 
 
 
 
 
 
 
 
 
Composite score 
PASDAS change in 
category 
 
 
 
 
 
 
 
 
 
 
 
 
GRAPPA flare 
questionnaire 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient flare single 
question 
 
 
 
 
 
 
 
 
 
 
 
 
Worsening MCID 
 
 
 
 
 
 
 
 
 
 
 
 

25 
 
 
Ethical and regulatory aspects 
 
The promoter and sponsor of this observational study is a non-for-profit hospital-
based research association, the Groupe d’Etudes et de Recherche de l’appareil 
locomoteur (GERPAL), president Pr Pierre Bourgeois, Hopital Pitié-Salpétrière, 47-83 
Bd Hopital, 75013 Paris : Association Loi 1901 – SIRET number : 404 828 527 00014 
- Code APE : 731 Z, telephone +33142177801. 
The Principal Investigator is Laure Gossec MD PhD. 
 
Participation request 
 
Around 600 consecutive patients with PsA will be contacted during outpatient 
visits and will be asked to participate to the study. They will be given full information 
on the study. 
Patients who are willing to participate are asked for a signed informed consent. 
All patients will receive at inclusion full information. On this document will be clearly 
indicated how to un-register from the trial. 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 or deleted. The participants can 
have access to their data and correct them if requested. 
 
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. 
 
Regulations and Review Boards 
The study will be conducted in accordance with the protocol, ICH Good Clinical 
Practice, ethical principles that have their origin in the Declaration of Helsinki 
and all applicable local regulations.   
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. The details will be 
determined in each clinical setting that participates in this study. 
This study is considered as ‘non-interventional’. It will be presented to approval 
of an ethical committee for France. Ethical committees in each country will be 

26 
 
solicited by the principal investigators. A notice to the CCTIR and a request for 
authorization to the CNIL will be submitted for France and necessary 
authorisations will be obtained prior to the study in each participating country. 
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.   
 
 
Protocol registration 
The protocol will be registered in clinicaltrials.gov. 
 
Data Quality Assurance 
Data treatment.  
Patients will be identified by a local number at each investigator site, which will 
have a 3-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.    
All results will be forwarded anonymously (without identifying number, see 
above) to the data center in Paris, France to be entered (double data entry) into 
a pooled database. Data will be stored and analysed anonymously. 
 
Quality control 
 
There are several levels for quality control. 
A. Locally for each CRF. 
Last question of the CRF for the investigator: “Have you checked that the 
patient has filled in all the questions of his/her CRF, and have you filled in 
all the questions of your questionnaire?” 
 
B. Central quality control. 
CRFs will be sent by the national PI to the statistical center, Paris, every 
10 CRFs, to be checked centrally for quality control. 
 
 
  
 
  

27 
 
 
Practical aspects 
 
Coinvestigators 
 
This project is a collaborative effort of 23 centres from 16 countries, which 
contribute medical data collected on their patients for central data analysis. 
In order to analyse the data and in the interest of all participants, the study 
coordinators (i.e. each investigator in the list below) are responsible for correct 
data procurement, delivery of analysis results to the participants and 
development of agreed publication strategies. 
Table 4 shows the list of investigators. Each center will include between 15 and 
30 patients. 
Investigator engagement is formalized by an investigator contract and includes: 
A- 
Translation of the CRF as needed, following the procedures for correct 
translation as outlined in the Study Protocol. 
B- 
Obtainment of all necessary authorizations to perform the study in 
accordance with all applicable regulations.  
C- 
Inclusion of consecutive patients with PsA who fulfill the inclusion criteria 
and who accept to participate.  
The objective is to include 15-30 patients per centre. This contract will not 
influence your management procedures or therapy choices for the patient 
(observational study). 
D- 
Upkeep of a patient log with patient identification (to be kept locally) 
E- 
Collection at baseline of the CRF data from patient and physician on the 
paper CRF, and collection again of data at the next consecutive visit (planned 
according to usual care). 
F- 
Transmission 
of 
the 
CRFs 
without 
any 
identifying 
information 
(anonymised data) to the principal investigator for central data entry in France. 
Coauthorship in the final scientific publication(s) will be proposed to 
investigators who have contributed at least 15 full patients and who satisfy 
international authorship criteria. Of note, only one investigator per centre can be 
coauthor. 

28 
 
Table 4. Coinvestigators  
Country 
Identity 
Centre 
Role 
Austria 
Smolen 
Josef 
S. 
Medical University of Vienna, 
Vienna, Austria 
Co-investigator 
and steering 
Brazil 
Palominos 
Penelope 
Hospital de Clinicas de Porto 
Alegre, Porto Alegre, Brazil 
Co-investigator 
Canada 
Aydin Sibel 
Ottawa 
University 
School 
of 
Medicine, Ottawa, Canada 
Co-investigator 
Canada 
Eder Lihi 
University of Toronto, Toronto, 
Canada 
Co-investigator 
Estonia 
Talli Sandra 
Tallinn Central Hospital, Tallinn, 
Estonia 
Co-investigator 
France 
Dernis 
Emmanuelle 
Le Mans Central Hospital, Le 
Mans, France 
Co-investigator 
France 
Gossec Laure 
CHU 
Pitié 
Salpétrière, 
Paris, 
France       
Co-investigator 
and steering 
France 
Richette Pascal  Lariboisiere 
Hospital, 
Paris 
France 
Co-investigator 
France 
Ruyssen-
Witrand Adeline 
Pierre-Paul 
Riquet 
Hospital, 
Toulouse, France 
Co-investigator 
France 
Soubrier Martin 
Gabriel 
Montpied 
Hospital, 
Clermont Ferrand, France 
Co-investigator 
Germany 
Kiltz Uta 
Herne 
and 
Ruhr-Universität 
Bochum, Herne, Germany 
Co-investigator 
Ireland 
Veale Douglas 
St Vincent’s University Hospital, 
Dublin, Ireland 
Co-investigator 
Italy 
Scrivo Rossana Sapienza Università di Roma, 
Rome, Italy 
Co-investigator 
Italy 
Lubrano Ennio 
Universita degli Studi del Molise, 
Campobasso, Italy 
Co-investigator 
Netherlands Vis Marijn 
Erasmus University Rotterdam, Co-investigator 

29 
 
Netherlands 
Romania 
Balanescu 
Andra 
Sf Maria Hospital, University of 
Medicine and Pharmacy Carol 
Davila, Bucharest, Romania 
Co-investigator 
Russia 
Gaydukova 
Inna  
Saratov State Medical University, 
Saratovskaya oblast', Saratov, 
Russia 
Co-investigator 
Singapore 
Leung Katy 
Singapore 
General 
Hospital, 
Singapore 
Co-investigator 
Spain 
Canete Juan D 
Hospital Clínic and IDIBAPS, 
Barcelona, Spain 
Co-investigator 
Turkey 
Kalyoncu Umut 
Hacettepe 
University, 
Ankara, 
Turkey 
Co-investigator 
UK 
Coates Laura  
University 
of 
Oxford 
Medical 
School, Oxford, UK 
Co-investigator 
and steering 
USA 
Orbai 
Ana- 
Maria 
Johns 
Hopkins 
University, 
Baltimore, USA 
Co-investigator 
USA 
Husni Elaine 
Cleveland Clinic Main Campus, 
Cleveland, USA 
Co-investigator 
 
Proposed calendar  
 
1. 1st Jan 2017- 30th June 2017: Study protocol and CRF finalisation, 
translations and regulatory authorisations 
2. 1st May 2017 to 30th December 2017: Patient inclusion and data collection 
(baseline). 
3. 1st June 2017 to 31th July 2018: Second assessment / second patient visit  
4. September 2018: Statistical analysis. 
5. September-December 2018: Manuscript(s) preparation. 
The study initiation will necessitate a 2-hour investigator webconference, then follow-
up investigator meetings will be performed during international congresses and by 
regular web conferences. 

30 
 
The project progress will be monitored by two-month-reports prepared by the 
investigators and forwarded to the study coordinators. 
 The results will be presented primarily at international meetings but also at national 
meetings by the individual investigators. The final manuscript(s) will be submitted to 
international rheumatology journals. All national investigators who have included at 
least 15 patients (one representative per center) and the steering committee will be 
coauthors. 
 
 
Budget 
 
The total budget for this study is calculated at 160 000 euros. The detailed budget is 
below in Table 3. 
 
This budget includes central funds for study coordination and analyses, and local 
funds for each investigator’s center for translations, ethical submissions and patient 
inclusions. It is expected 450 baseline visits and 400 second visits. 
 
Financial support is sought from Pfizer through an unrestricted research grants 
(investigator initiative research grant) and acceptance is obtained on April 20,2017.                          
 
Financial compensation for investigators 
The compensation is planned as follows: 
- 
CRF translation (300 euros per language) 
- 
Ethical consent obtainment (400 euros per country, to be paid to the 
centre which performed the process in case of several centres per country) 
- 
Remuneration for each patient included (100 euros per first visit and 75 
per second patient visit) 
Thus for a centre including 20 patients, the total sum payable will be 4200 
euros. 
Payment shall be made within 30 days of receipt and approval of invoices. The 
investigator is responsible for the payment of any applicable taxes associated 
with the receipt of the compensation. 

31 
 
Table 3 Budget 
 
 Expenses 
Total 
Budget 
(Euros) 
Budget 
for 
first 
year 
(2017) 
Budget 
for 
second 
year 
(2018) 
Project management 
10 000 
5 000 
5 000 
Study organisation and follow up 
16 000 
8 000 
8 000 
Patient research partner contribution 
4 000 
2 000 
2 000 
Steering committee honoraria (1000 per person) 
5 000 
2 500 
2 500 
CRF translation (300 per language, 10 languages) 3 000 
3 000 
0 
Ethical submission (400 per country, 15 countries) 6 000 
6 000 
0 
CRF printing and mailing 
3 000 
2 000 
1 000 
Remuneration for each patient included (100 per 
first visit and 75 per second patient visit) 
75 000 
45 000 
30 000 
Double data entry 
6 000 
3 000 
3 000 
Statistical analyses 
15 000 
2 000 
13 000 
Copyrighted questionnaire fees (SF-12) 
2 000 
1 000 
1 000 
Accounts and taxes (10%) 
15 000 
8 700 
6 300 
TOTAL 
160 000 
88 200 
71 800 
 
 
 

32 
 
Expected outcomes of the study 
 
The expected outcomes of this study are a better knowledge of remission and flare in 
PsA with a cross-tabulation of the perspectives of patients and physicians. The 
quantitative data will allow to calculate cutoff values for scores used in PsA which will 
facilitate shared decision making in a ‘treat to target’ approach and the interpretation 
of future studies and clinical trials in the field of PsA. 
The international nature of the study will enhance external validity of the results given 
the subjective nature of patient assessments of flare and remission (Putrik2016) 
Better knowledge of the important aspects of disease fluctuation and of patient 
relevant disease targets in PsA should enhance patient care and management. 
The present study is in line with recent EULAR recommendations for future research 
in PsA, i.e., the research agenda developed by the EULAR management taskforce. 
(Gossec2016a) 
 
 

33 
 
 
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