Clinical trial NCT02224157
Conditions: Asthma
Sponsor: AstraZeneca
Start date: 2014-11-28; Completion date: 2017-08-16
Enrollment: 4215 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to test if Symbicort (budesonide/formoterol) Turbuhaler is effective in treating asthma when used 'as needed' in patients with milder asthma. The efficacy of Symbicort 'as needed' will be compared with Pulmicort (budesonide) Turbuhaler twice daily plus terbutaline Turbuhaler 'as needed'

Detailed description:
A 52-week, double-blind, randomised, multi-centre, phase III, parallel-group study in patients 12 years and older with asthma, evaluating the efficacy and safety of Symbicort (budesonide/formoterol) Turbuhaler 160/4.5 μg 'as needed' compared with Pulmicort (budesonide) Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg 'as needed'

Arms: arm 1: Symbicort (budesonide/formoterol) Turbuhaler 160/4.5 μg 'as needed' + Placebo Pulmicort Turbuhaler 200 μg bid arm 2: Pulmicort 200 μg Turbuhaler bid + terbutaline 0.4 mg Turbuhaler 'as needed'
Interventions: intervention 1: budesonide/formoterol 'as needed' + budesonide placebo bid intervention 2: budesonode bid + terbutaline 'as needed'
Intervention descriptions: intervention 1: Symbicort (budesonide/ formoterol) 160/4.5 μg powder for inhalation 'as needed' plus Pulmicort placebo 200 μg powder for inhalation, 1 inhalation twice daily (morning and evening), 52-week treatment intervention 2: Pulmicort (budesonide) 200 μg powder for inhalation, 1 inhalation twice daily (morning and evening) plus terbutaline 0.4 mg powder for inhalation 'as needed', 52-week treatment

Protocol documents:
Prot_001.pdf: 


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
2(70)
PROTOCOL SYNOPSIS
A 52-week, double-blind, randomised, multi-centre, phase III, parallel-
group study in patients 12 years and older with asthma, evaluating the 
efficacy and safety of Symbicort (budesonide/formoterol) Turbuhaler  
160/4.5 μg ‘as needed’ compared with Pulmicort (budesonide) Turbuhaler  
200 μg twice daily plus terbutaline Turbuhaler  0.4 mg ‘as needed’
International Co-ordinating Investigator
Eric D Bateman Prof, MB ChB, MD, FRCP, DCH
South Africa
Study site(s) and number of patients planned
This study will recruit patients worldwide at approximately 330 sites in about 25 countries.  
The target is to randomise 4114 male and female patients. The sample size will be re-
estimated based on blinded review during the study.  The number of patients might be 
increased up to a maximum of 6171 patients.
Study period
Phase of development
Estimated date of first patient enrolled
QIII 2014
III
Estimated date of last patient completed
QII 2017
Study design
This is a 52-week, double-blind, randomised, multi-centre, parallel-group, phase III study in 
patients 12 years and older with asthma, evaluating the efficacy and safety of Symbicort 
(budesonide/formoterol) Turbuhaler 160/4.5 μg ‘as needed’ compared with Pulmicort 
(budesonide) Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg ‘as needed’.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
3(70)
Objectives
Primary Objective:
Outcome Measure:
To demonstrate that Symbicort Turbuhaler 
160/4.5 μg ‘as needed’ is non-inferior to 
Pulmicort Turbuhaler 200 μg twice daily plus 
terbutaline Turbuhaler 0.4 mg ‘as needed’. 
Annual severe asthma exacerbation rate
Secondary Objective:
Outcome Measure :
To estimate the difference in efficacy between 
Symbicort Turbuhaler 160/4.5 μg ‘as needed’ 
and Pulmicort Turbuhaler 200 μg twice daily 
plus terbutaline Turbuhaler 0.4 mg ‘as needed’
Secondary variables
•Time to first severe asthma exacerbation
•Average change from baseline in pre-dose FEV1
•Time to study specific asthma related 
discontinuation
•Average change from baseline in ‘as needed’ use 
• Change from baseline in percent of ‘as needed’ free 
days
•Percentage of controller use days
•Average change from baseline in Asthma Control 
Questionnaire (5-item version) - ACQ-5 score
•Average change from baseline in Asthma Quality of 
Life Questionnaire Standardised Version - AQLQ(S) 
score
Safety Objective:
Outcome Measure :
To compare the safety of Symbicort 
Turbuhaler 160/4.5 μg ‘as needed’ with that of 
Pulmicort Turbuhaler 200 μg twice daily plus 
terbutaline Turbuhaler 0.4 mg ‘as needed’
Adverse events (nature, incidence and severity); 
pulse, blood pressure and physical examination
Target patient population
The target population includes male and female patients who are ≥12 years old and who have 
a documented clinical diagnosis of asthma for at least 6 months prior to Visit 1.  Patients who 
are either uncontrolled on an inhaled short acting bronchodilator(s) ‘as needed’ (short acting 
β2 agonist and/or short acting anticholinergic agent)  or who are controlled on mono-
maintenance therapy with either a low stable dose of an inhaled glucocorticosteroid or a 
leukotriene receptor antagonist in addition to 'as needed' use of inhaled short-acting 
bronchodilator (short acting β2 agonist and/or short acting anticholinergic agent) for the last 
30 days before Visit 2 will be eligible for the study.
The patients should have reversible airway obstruction.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
4(70)
Patients should have used the short acting β2 agonist on at least 3 separate days during the last 
week of the run-in period.
Duration of treatment
This study starts with an enrolment visit (Visit 1) where informed consent is obtained and 
inclusion and exclusion criteria are reviewed.  At Visit 2 patients will enter a 2-4 week run-in 
period during which all of them will be treated with a short acting β2 agonist (Bricanyl) ‘as 
needed’.  Eligible patients will be randomised at Visit 3 and enter a 52-week double-blind 
treatment period.  Two weeks after the completion of study treatment a follow-up telephone 
contact will be performed.  The total expected duration of the study for a patient will be 56-59 
weeks.
Investigational product, dosage and mode of administration
Symbicort Turbuhaler 160/4.5 μg (budesonide 160 μg and formoterol fumarate dihydrate 
4.5 μg per inhalation, powder for inhalation in a dry powder inhaler) used ‘as needed’ (to 
relieve asthma symptoms) in addition to Placebo for budesonide (powder for inhalation in a 
dry powder inhaler matching the Pulmicort Turbuhaler) administered two times daily.
Comparators, dosage and mode of administration
Terbutaline Turbuhaler 0.4 mg (terbutaline sulphate 0.4 mg per inhalation, powder for 
inhalation in a dry powder inhaler) used ‘as needed’ (to relieve asthma symptoms) in addition 
to Pulmicort Turbuhaler 200 μg (budesonide 200 μg per inhalation, powder for inhalation in a 
dry powder inhaler) administered two times daily.
Non-investigational medicinal product, dosage and mode of administration
Bricanyl Turbuhaler 0.5 mg (terbutaline sulphate 0.5 mg per inhalation, powder for inhalation 
in a dry powder inhaler) used ‘as needed’ during the run-in period and as a bronchodilator for 
the lung function measurements.
Statistical methods
Analysis of the primary variable:
The primary variable annual severe asthma exacerbation rate will be analysed by a negative 
binomial regression model.  The analysis will be based on the efficacy analysis set which 
includes all randomised patients receiving any investigational product, irrespective of their 
protocol adherence and continued participation in the study.  The planned treatment 
comparison will be Symbicort ‘as needed’ versus Pulmicort twice daily + terbutaline ‘as 
needed’ (non-inferiority, primary objective).
Formally, the null and alternative hypothesis is:
H0: rate-ratio (Symbicort vs Pulmicort) ≥1.2
HA: rate-ratio (Symbicort vs Pulmicort) < 1.2


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
5(70)
If the upper 95% 1-sided confidence limit of the relative risk ratio is < 1.2 then non-inferiority 
can be declared.
If the criteria for the alternative hypothesis is met then superiority of Symbicort vs Pulmicort 
in terms of annual severe asthma exacerbation will be assessed.
Formally, the null and alternative hypothesis for superiority testing is:
H0: rate-ratio (Symbicort vs Pulmicort) = 1
HA: rate-ratio (Symbicort vs Pulmicort) ≠1
Analysis of the secondary variables:
For all secondary variables stated below the treatment difference between Symbicort ‘as 
needed’ and Pulmicort twice daily + terbutaline ‘as needed’ will be estimated.
Time to first severe asthma exacerbation and time to discontinuation of investigational 
product due to asthma related events will be analysed by a Cox proportional hazards model.
Forced Expiratory Volume in one second, Asthma Control Questionnaire 5 item version and 
Asthma Quality of Life Questionnaire (Standardised Version) will be analysed by a mixed 
model repeated measures analysis model.
The change from baseline in the use of ‘as needed’ medication, and the percentage of ‘as 
needed’-free days will be analysed by analysis of covariance.
The percentage of controller use days will be analysed by analysis of covariance.
The total inhaled steroid load and the number of days with systemic glucocorticosteroids, 
respectively will be presented descriptively by treatment adjusted by the patients follow-up 
time.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
6(70)
TABLE OF CONTENTS
PAGE
TITLE PAGE...........................................................................................................1
PROTOCOL SYNOPSIS.........................................................................................2
TABLE OF CONTENTS.........................................................................................6
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS..........................11
1.
INTRODUCTION .................................................................................................13
1.1
Background and rationale for conducting this study .............................................13
1.2
Rationale for study design, doses and control groups............................................14
1.3
Benefit/risk and ethical assessment........................................................................15
1.4
Study Design..........................................................................................................16
2.
STUDY OBJECTIVES..........................................................................................16
2.1
Primary objective...................................................................................................16
2.2
Secondary objectives .............................................................................................17
2.3
Safety objectives ....................................................................................................17
2.4
Exploratory objectives ...........................................................................................17
3.
PATIENT SELECTION, ENROLMENT, RANDOMISATION, 
RESTRICTIONS, DISCONTINUATION AND WITHDRAWAL......................17
3.1
Inclusion criteria ....................................................................................................18
3.2
Exclusion criteria ...................................................................................................19
3.3
Patient enrolment and randomisation.....................................................................20
3.4
Procedures for handling incorrectly enrolled or randomised patients ...................21
3.5
Methods for assigning treatment groups................................................................21
3.6
Methods for ensuring blinding...............................................................................21
3.7
Methods for unblinding..........................................................................................22
3.8
Restrictions ............................................................................................................22
3.9
Discontinuation of investigational product............................................................22
3.9.1
Procedures for discontinuation of a patient from investigational product.............23
3.10
Criteria for withdrawal...........................................................................................23
3.10.1
Enrolment failures..................................................................................................23
3.10.2
Withdrawal of the informed consent......................................................................24


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
7(70)
3.11
Discontinuation of the study..................................................................................24
4.
STUDY PLAN AND TIMING OF PROCEDURES.............................................25
4.1
Enrolment and run-in periods ................................................................................31
4.1.1
Enrolment procedures at Visit 1 ............................................................................31
4.1.2
Run-in procedures at Visit 2 ..................................................................................31
4.2
Treatment period....................................................................................................32
4.3
Follow-up...............................................................................................................33
4.4
Follow-up in case of discontinuation of IP............................................................34
5.
STUDY ASSESSMENTS .....................................................................................34
5.1
Efficacy assessments..............................................................................................34
5.1.1
Severe asthma exacerbation...................................................................................34
5.1.2
Lung function measurement by spirometry (FEV1, FVC) at the study site...........35
5.1.2.1
Pre-bronchodilator and post-bronchodilator FEV1 and FVC including 
reversibility testing and calculation of predicted normal values (PN)...................36
5.1.2.2
Reversibility test ....................................................................................................37
5.1.3
Asthma Control Questionnaire (5-item Version)...................................................37
5.1.4
Asthma Quality of Life Questionnaire (Standardised Version).............................38
5.1.5
Administration of patient reported outcome questionnaires..................................38
5.1.6
Turbuhaler Usage Monitor (TUM) ........................................................................38
5.2
Safety assessments.................................................................................................39
5.2.1
Physical examination .............................................................................................39
5.2.2
Vital signs ..............................................................................................................39
5.2.2.1
Pulse and blood pressure........................................................................................39
5.3
Health Economics ..................................................................................................39
5.3.1
Health care resource utilisation..............................................................................40
5.3.1.1
Methods of assessment EQ-5D-5L ........................................................................40
5.3.1.2
Administration of EQ-5D-5L questionnaire ..........................................................40
5.4
Pharmacokinetics ...................................................................................................41
5.5
Pharmacodynamics ................................................................................................41
5.6
Pharmacogenetics ..................................................................................................41
5.7
Biomarker analysis.................................................................................................41
6.
SAFETY REPORTING AND MEDICAL MANAGEMENT ..............................41
6.1
Definition of adverse events ..................................................................................41
6.2
Definitions of serious adverse event......................................................................42
6.3
Recording of adverse events ..................................................................................42
6.3.1
Time period for collection of adverse events.........................................................42
6.3.2
Follow-up of unresolved adverse events................................................................42
6.3.3
Symptoms of the disease under study....................................................................42


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
8(70)
6.3.4
Variables ................................................................................................................43
6.3.5
Causality collection................................................................................................44
6.3.6
Adverse events based on signs and symptoms.......................................................44
6.3.7
Adverse events based on examinations and tests...................................................45
6.3.8
Hy’s Law................................................................................................................45
6.4
Reporting of serious adverse events.......................................................................45
6.5
Overdose ................................................................................................................46
6.6
Pregnancy...............................................................................................................47
6.6.1
Maternal exposure..................................................................................................47
6.6.2
Paternal exposure...................................................................................................48
6.7
Management of IP related toxicities ......................................................................48
6.8
Study governance and oversight ............................................................................48
6.8.1
Independent adjudication committee for fatal events ............................................48
7.
INVESTIGATIONAL PRODUCT AND OTHER TREATMENTS ....................49
7.1
Identity of investigational product(s).....................................................................49
7.1.1
Non-investigational product for run-in and for post-bronchodilator lung 
function measurements ..........................................................................................49
7.2
Dose and treatment regimens.................................................................................49
7.3
Labelling ................................................................................................................51
7.4
Storage ...................................................................................................................51
7.5
Compliance ............................................................................................................51
7.6
Accountability........................................................................................................51
7.7
Concomitant and other treatments .........................................................................51
7.7.1
Prohibited Medications ..........................................................................................51
7.7.2
Concomitant asthma treatment ..............................................................................53
7.7.3
Other concomitant treatment..................................................................................53
7.8
Post Study Access to Study Treatment ..................................................................53
8.
STATISTICAL ANALYSES BY ASTRAZENECA............................................53
8.1
Statistical considerations........................................................................................53
8.2
Sample size estimate..............................................................................................54
8.3
Definitions of analysis sets ....................................................................................55
8.3.1
Full analysis set......................................................................................................55
8.3.2
All patients analysis set..........................................................................................55
8.3.3
Safety analysis set..................................................................................................55
8.4
Outcome measures for analyses.............................................................................56
8.4.1
Derivation of efficacy variables.............................................................................56
8.4.1.1
Derivation of annual severe asthma exacerbation rate (primary variable) ............56


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
9(70)
8.4.1.2
Derivation of time to first severe asthma exacerbation .........................................56
8.4.1.3
Derivation of total inhaled steroid load and number of days with systemic 
GCS treatment........................................................................................................56
8.4.1.4
Derivation of ‘as-needed’ use ................................................................................56
8.4.1.5
Derivation of controller-use days...........................................................................57
8.4.1.6
Derivation of percent ‘as-needed’-free days..........................................................57
8.4.1.7
Derivation of time to asthma related discontinuation............................................58
8.4.1.8
Derivation of lung function variables ....................................................................58
8.4.2
Derivation of patient reported outcome variables..................................................58
8.4.2.1
Derivation of ACQ-5 .............................................................................................58
8.4.2.2
Standardised Asthma Quality of Life Questionnaire (AQLQ(S)) .........................59
8.4.3
Derivation of safety variables ................................................................................59
8.4.3.1
Vital signs ..............................................................................................................59
8.4.3.2
Other significant adverse events (OAE) ................................................................59
8.5
Methods for statistical analyses .............................................................................60
8.5.1
Analysis of the primary variable............................................................................60
8.5.2
Analysis of the secondary and other variables.......................................................60
8.5.3
Subgroup analysis ..................................................................................................62
8.5.4
Blinded sample size re-estimation .........................................................................62
8.5.5
Sensitivity analysis.................................................................................................62
8.5.6
Exploratory analysis...............................................................................................63
8.5.7
Analyses related to exploratory objective..............................................................63
9.
STUDY AND DATA MANAGEMENT BY ASTRAZENECA ..........................63
9.1
Training of study site personnel.............................................................................63
9.2
Monitoring of the study .........................................................................................63
9.2.1
Source data.............................................................................................................64
9.2.2
Study agreements...................................................................................................64
9.2.3
Archiving of study documents...............................................................................64
9.3
Study timetable and end of study...........................................................................64
9.4
Data management by Cognizant Data Management Centre..................................64
10.
ETHICAL AND REGULATORY REQUIREMENTS.........................................65
10.1
Ethical conduct of the study...................................................................................65
10.2
Patient data protection............................................................................................65
10.3
Ethics and regulatory review..................................................................................65
10.4
Informed consent ...................................................................................................66
10.5
Changes to the protocol and informed consent form.............................................67
10.6
Audits and inspections ...........................................................................................67
11.
LIST OF REFERENCES.......................................................................................67


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
10(70)
LIST OF TABLES
Table 1
Study Plan detailing the procedures .........................................................25
Table 2
Medications which may affect the reversibility test at Visit 2 
and/or at Visit 3 ........................................................................................52
Table 3
Medications Not allowed during the run-in period and while on IP ........52
LIST OF FIGURES
Figure 1
Study flow chart .......................................................................................16
LIST OF APPENDICES
Appendix A
Signatures
Appendix B
Additional Safety Information 
Appendix C
Asthma Control Questionnaire (5-item Version)
Appendix D
Asthma Quality of Life Questionnaire with Standardised Activities 
                  (AQLQ(S)) self administered ≥ 12 years of age (Standardised Version)
Appendix E
Inhaled Glucocorticosteroid Equivalence Table
Appendix F
EQ-5D-5L Health Questionnaire


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
11(70)
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS
The following abbreviations and special terms are used in this study Clinical Study Protocol.
Abbreviation or 
special term
Explanation
ACQ-5
Asthma Control Questionnaire (5-item Version)
AE
Adverse event
‘As-needed’
Administered as needed in response to symptoms; similar to reliever or
rescue medication
AQLQ(S)
Asthma Quality of Life Questionnaire (Standardised Version)
ATS/ERS
American Thoracic Society/European Respiratory Society
BID
Twice daily
(e)CRF
Case Report Form (electronic/paper)
CSA
Clinical Study Agreement
CSR
Clinical Study Report
DAE
Discontinuation of Investigational Product due to Adverse Event
DPI
Dry Powder Inhaler
EC
Ethics Committee, synonymous to Institutional Review Board (IRB) and 
Independent Ethics Committee (IEC)
EoT
End of Treatment
ePRO
Electronic Patient Reported Outcome
EQ-5D-5L
EuroQol Quality of Life Questionnaire
FEV1
Forced Expiratory Volume in one second
FVC
Forced Vital Capacity
GCP
Good Clinical Practice
GCS
Glucocorticosteroid
GINA
Global Initiative for Asthma (GINA). Strategy for Asthma Management
and Prevention 2012.
GMP
Good Manufacturing Practice
Grand
AstraZeneca Global Randomisation System
ICH
International Conference on Harmonisation
ICS
Inhaled glucocorticosteroid
ICU
Intensive Care Unit


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
12(70)
Abbreviation or 
special term
Explanation
International 
Coordinating 
investigator
If a study is conducted in several countries the International Coordinating 
Investigator is the Investigator coordinating the investigators and/or 
activities internationally. 
IP
Investigational Product 
ISF
Investigator Study File
IVRS
Interactive Voice Response System
IWRS
Interactive Web Response System
L
Litre
LABA
Long-acting β2 agonist
LTRA
Leukotriene Receptor Antagonist
mg
Milligramm
MID
Minimal important difference
ML
Millilitre
MMRM
Mixed Model Repeated Measures
OAE
Other Significant Adverse Event
PN
Predicted Normal
μg
Microgramm
SABA
Short-acting β2 agonist
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SMART
Symbicort Maintenance and Reliever Therapy
TUM
Turbuhaler Usage Monitor
ULN
Upper Limit of Normal
Vs
Versus
WBDC
Web Based Data Capture


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
13(70)
1.
INTRODUCTION
1.1
Background and rationale for conducting this study
Asthma is a respiratory disease characterized by chronic inflammation and largely reversible 
obstruction of the airways which vary over time.  The main aim of asthma management is to 
achieve and maintain asthma control.  For this purpose a stepwise treatment approach 
increasing in intensity is recommended (GINA 2012).  Using a rapid-acting β2-agonist, 
commonly salbutamol or terbutaline, on an ‘as needed’ basis in response to symptoms is the 
first treatment step (GINA step 1).  If asthma is not controlled on rapid-acting β2-agonists 
alone, a controller medication is added, usually a low dose inhaled glucocorticosteroid (ICS) 
taken regularly (GINA step 2).  Thus adding a controller medication that addresses the 
underlying inflammation is important to improve asthma control and decrease the risk of 
severe asthma exacerbations in patients with mild asthma (Pauwels et al 2003).
Despite the availability of these conventional treatment regimens, many patients with mild 
asthma are still uncontrolled and are at risk of severe exacerbations.  For example, severe 
exacerbations in mild asthma patients represent 30–40% of all asthma exacerbations requiring 
emergency consultation (Dusser et al 2007).  Furthermore, some patients over-rely on their 
rapid-acting β2-agonist for symptomatic improvement (Rabe et al 2004).  Overuse of rapid-
acting β2-agonists often leads to delayed introduction of ICS: even if ICS are prescribed 
adherence to ICS treatment is low (Horne et al 2006). The purpose of the current study is to 
test the hypothesis that in patients in need of low dose ICS (GINA step 2), asthma control can 
be achieved by ‘as needed’ administration of both the controller and the bronchodilator 
medications in response to symptoms. 
Symbicort is a fixed combination of the ICS budesonide and the rapid- and long-acting β2-
agonist (LABA) formoterol.  As formoterol has been shown to be as effective as short-acting 
β2-agonists (SABA) for symptom relief (Chuchalin et al 2005), (Pauwels et al 2003b), 
(Tattersfield et al 2001), Symbicort can also be used as a reliever medication in an acute 
asthma setting  (Palmqvist et al 2001).  Such use of Symbicort is approved for administration 
as Symbicort Maintenance and Reliever Therapy (SMART) in moderate-to-severe asthma.  
According to the SMART concept, Symbicort is taken as a regular maintenance treatment and 
‘as needed’ in response to symptoms.  Symbicort SMART has been shown to reduce 
exacerbations and improve asthma control (O'Byrne et al 2005), (Scicchitano et al 2004), 
(Rabe et al 2004), (Vogelmeier et al 2005), (Atienza et al 2013).
In mild asthma, initial studies where treatment was administered ‘as needed’ in response to 
symptoms, have shown promising results for Symbicort and similar combination products 
(Haahtela et al 2006, Papi et al 2007).  In patients with mild intermittent asthma and having 
signs of airway inflammation, Symbicort ‘as needed’ was more efficacious than Oxis (ie 
formoterol) ‘as needed’ in reducing fractional exhaled nitric oxide (FeNO) and improving 
lung function (Haahtela et al 2006).  Symptom-driven, ‘as needed’ use of a combination of a 
SABA (albuterol) and ICS (beclomethasone) in a single inhaler was equivalent to regular 


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
14(70)
treatment with inhaled ICS (beclomethasone) in controlling patients with mild persistent 
asthma (Papi et al 2007).
When administered on an ‘as needed’ basis without daily maintenance medication, Symbicort 
will provide both an anti-inflammatory medication and a reliever medication adapted to the 
patient’s current asthma symptoms.  Such an approach will address possible problems with 
timely administration and adherence to ICS in asthma patients in need of low dose ICS 
treatment.  In addition this will be a simplified and convenient treatment regimen as the 
patients will use one inhaler only instead of two (1 for controller medication and 1 for ‘as 
needed’ use).
1.2
Rationale for study design, doses and control groups
The design of the study incorporates features that are consistent with the Committee for 
Medicinal Products for Human Use Asthma guideline (CHMP 2013). A randomised, double-
blind, parallel-group design is standard in asthma clinical trials. Patients who are either 
uncontrolled on an inhaled short acting bronchodilator(s) ‘as needed’ (SABA and/or short 
acting anticholinergic agent) or controlled on mono-maintenance therapy with either a low 
dose ICS or a leukotriene receptor antagonist (LTRA) in addition to 'as needed' use of inhaled 
short-acting bronchodilator(s) (SABA and/or short acting anticholinergic agent) will be 
included in the study.  The study will begin with a 2 to 4 weeks run in period in order to 
collect patients’ baseline data and to ensure that the recruited patients are in need of GINA 
step 2 treatment.  A 12-month treatment period has been chosen as this study investigates a 
new treatment regimen with Symbicort Turbuhaler in a new patient population, which will 
include both adult and adolescent patients.
Asthma exacerbations are relatively rare events and more so in mild asthma and thus a 12 
month perspective is necessary owing to power considerations, and, secondly, as adherence to 
regular medications is an issue in mild asthma, a longer trial provides a longer period over 
which to observe patient behaviour which better approaches the intended long-term nature of 
the envisaged treatment, not achieved in a shorter controlled trial.
The efficacy and safety of Symbicort (budesonide/formoterol) Turbuhaler 160/4.5 μg ‘as 
needed’ will be compared with Pulmicort (budesonide) Turbuhaler 200 μg twice daily plus 
terbutaline Turbuhaler 0,4 mg ‘as needed’ which is one of the current standard treatments for 
patients at GINA step 2. Symbicort Turbuhaler 160/4.5 μg ‘as needed’ is the strength mostly 
used on an ‘as needed’ basis with the Symbicort SMART concept. This dose is considered 
adequate to provide an anti-inflammatory effect due to the budesonide component, and the 
formoterol component of Symbicort Turbuhaler provides rapid and effective symptom relief.  
Symbicort Turbuhaler is safe to use as evidenced by Symbicort SMART data.
During the study treatment terbutaline will be provided in a Turbuhaler (dry powder inhaler -
DPI) that is identical to the Symbicort Turbuhaler for blinding purposes.  Bricanyl Turbuhaler 
will be used during the run-in period.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
15(70)
Prevention of asthma exacerbations is a key goal of asthma management. It has been 
recognized that asthma exacerbations constitute the greatest risk to the patients, are a cause of 
anxiety to the patients and their families, and generate great cost for the society (Reddel et al 
2009). Therefore severe asthma exacerbations have been chosen as the primary variable in this 
study.  The study design includes clinic visits and additional phone contacts -or alternative 
method - to ensure that asthma exacerbation events are collected.  A blinded sample size re-
estimation will be done before the randomisation of the targeted 4114 patients.  The pooled 
blinded event rate will be monitored during the trial to allow for the possibility of an increase 
in sample size up to a maximum of 6171 randomised patients.
1.3
Benefit/risk and ethical assessment
Symbicort Turbuhaler, terbutaline Turbuhaler and  Pulmicort Turbuhaler are well known 
medications with efficacy and safety profiles established in numerous clinical studies and vast 
postmarketing experience.
Symbicort is effective as a reliever medication (Palmqvist et al 2001).  In the Symbicort 
SMART program the patients have been allowed to use up to 12 inhalations per day (10 ‘as 
needed’ inhalations in addition to their maintenance treatment) and the safety profile of 
Symbicort was no different from that of a fixed dose maintenance treatment.  Furthermore a 
study in which patients took 10 inhalations of Symbicort Turbuhaler 160/4.5 μg per inhalation 
as an addition to a daily Symbicort maintenance dose of 640/18 μg revealed no new safety 
concerns compared to what was already known for ICS and LABA (Ankerst et al 2003) 
demonstrating that occasional high doses of Symbicort Turbuhaler are safe and well tolerated.
Terbutaline Turbuhaler is a well-known and frequently used short acting β2 agonist (SABA).  
It is widely acknowledged that terbutaline has a rapid onset of action within minutes of 
inhalation and a favourable safety profile (Sears and Lötvall 2005).  The maximum dose to 
be allowed in the study is within the approved dose range in most countries.  
In this study patients will be instructed to contact the investigator for reassessment if using 
more than 12 inhalations per day with blinded ‘as needed’ investigational product - Symbicort 
Turbuhaler or terbutaline Turbuhaler - during the treatment period. 
Pulmicort which will be used as a maintenance treatment in the comparator arm is an effective 
and safe controller medication in asthma (GINA 2012).
All patients will be monitored during the course of the study with clinic visits at 17, 34 and 52 
weeks of treatment.  In addition patients will be contacted by phone call (or other methods if 
needed) between site visits at weeks 8, 25 and 42, and asked if they have used any additional 
asthma treatment other than the randomised treatment since the last visit.  The use of 
additional asthma treatment would be a trigger for the investigator to call the patient and ask 
for more information about the additional treatment and asthma worsening.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
16(70)
Patients who have discontinued Investigational Product (IP) prematurely will be followed up 
for severe asthma exacerbations and adverse events according to the original visit schedule 
(see Section 4.4).
Furthermore the patients will be instructed to contact the investigator at any time they feel a 
need for medical assistance.  Study specific treatment discontinuation criteria are applied for 
an individual patient in case of severe asthma exacerbations, see Section 3.9.  To conclude, the 
overall benefit/risk ratio is considered acceptable.
1.4
Study Design
Figure 1
Study flow chart
2.
STUDY OBJECTIVES
2.1
Primary objective
Primary Objective:
Outcome Measure:
To demonstrate that Symbicort Turbuhaler 
160/4.5 μg ‘as needed’ is non-inferior to 
Pulmicort Turbuhaler 200 μg twice daily plus 
terbutaline Turbuhaler 0.4 mg ‘as needed’
Annual severe asthma exacerbation rate


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
17(70)
2.2
Secondary objectives
Secondary Objective:
Outcome Measure :
To estimate the difference in efficacy between 
Symbicort Turbuhaler 160/4.5 μg ‘as needed’ 
and Pulmicort Turbuhaler 200 μg twice daily 
plus terbutaline  Turbuhaler 0.4 mg ‘as needed’
Secondary variables
•Time to first severe asthma exacerbation
•Average change from baseline in pre-dose FEV1
•Time to study specific asthma related 
discontinuation
•Average change from baseline in ‘as needed’ use 
• Change from baseline in percent of ‘as needed’ free 
days
•Percentage of controller use days
•Average change from baseline in Asthma Control
Questionnaire (5-item version) - ACQ-5 score
•Average change from baseline in Asthma Quality of 
Life Questionnaire Standardised Version - AQLQ(S) 
score
2.3
Safety objectives
Safety Objective:
Outcome Measure:
To compare the safety of Symbicort 
Turbuhaler 160/4.5 μg ‘as needed’ with that of 
Pulmicort Turbuhaler 200 μg twice daily plus 
terbutaline Turbuhaler 0.4 mg ‘as needed’
Adverse events (nature, incidence and severity); 
pulse, blood pressure and physical examination
2.4
Exploratory objectives  
Exploratory Objective:
Outcome Measure:
To compare health care resource utilization, 
indirect resource use and health related status  
associated with hospital admissions, health 
care visits and days lost from work/ school 
between treatment arms
•
EuroQol five dimensional 5-level 
questionnaire (EQ-5D-5L)
•
Health Economics Questionnaire for resource 
utilisation
3.
PATIENT SELECTION, ENROLMENT, RANDOMISATION, 
RESTRICTIONS, DISCONTINUATION AND WITHDRAWAL
Each patient should meet all of the inclusion criteria and none of the exclusion criteria for this 
study.  Under no circumstances can there be exceptions to this rule.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
18(70)
3.1
Inclusion criteria
For inclusion in the study patients should fulfil the following criteria:
1.
Provision of informed consent prior to any study specific procedures.  For patients 
under-age, signed informed consent from both the patient and the patient’s 
parent/legal guardian is required
2.
Outpatients of either gender aged ≥12 years at Visit 1
3.
Diagnosis of asthma according to GINA criteria based on symptoms with a 
documented history of at least 6 months prior to Visit 1. Lung function and 
reversibility tests performed as part of Visit 2 and 3 can be used as a confirmation 
of asthma diagnosis according to GINA criteria if there is no measure of lung 
function available before Visit 1
4.
Patients who are in need of GINA (2012) step 2 treatment:
!
uncontrolled on inhaled short-acting bronchodilator(s) ‘as needed’ (SABA 
and/or short acting anticholinergic agent) as judged by the investigator for the 
last 30 days before Visit 2, or
!
controlled on mono-maintenance therapy with low stable dose ICS (≤ 400 μg 
budesonide per day or corresponding dose of other ICS) (see Appendix E for 
conversion) or LTRA - in addition to 'as needed'  use of inhaled short-acting 
bronchodilator(s) (SABA and/or short acting anticholinergic agent) as judged 
by the investigator for the last 30 days prior to Visit 2
5.
Based on lung function tests (see Section 5.1.2) at Visit 2, patients pre-treated with
!
an inhaled short-acting bronchodilator(s) only should have pre-bronchodilator 
FEV1 ≥ 60 % of predicted normal (PN) and post-bronchodilator FEV1 ≥ 80 % 
of PN according to the European Respiratory Society (ERS) guidelines 
(Quanjer et al 2012)
!
low dose ICS or LTRA medication in addition to inhaled short-acting 
bronchodilator(s) should have pre-bronchodilator FEV1 ≥80 % PN according to 
the ERS guidelines
6.
Reversible airway obstruction according to a reversibility test (see Section 5.1.2.2) 
performed at Visit 2 defined as an increase in FEV1 ≥12% and ≥200 ml relative to 
baseline, after inhalation of 1 mg Bricanyl Turbuhaler. The test can be repeated at 
Visit 3 in case the patients fail at Visit 2. If patients fail at both occasions, they can 
still be included if they have a documented historical reversibility test within the 
last 12 months prior to Visit 3, with an increase in FEV1 ≥12% and ≥200 ml relative 
to baseline after administration of a rapid acting β2-agonist.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
19(70)
For randomisation at Visit 3, patients should fulfil the following criteria:
7.
Use of Bricanyl Turbuhaler ‘as needed’ due to asthma symptoms on at least 3 
separate days during the last week of the run-in period
8.
Ability to use Turbuhaler correctly.
3.2
Exclusion criteria
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1.
Involvement in the planning and/or conduct of the study (applies to both 
AstraZeneca staff and/or staff at the study site)
2.
Previous randomisation in the present study or in the study D589SC00001 
(SYGMA 1)
3.
Participation in another clinical study with a non-biologic investigational product or 
new formulation of a marketed non-biologic drug during the last 30 days prior to 
Visit 1
4.
Participation in another clinical trial with any marketed or investigational biologic 
drug within 4 months or 5 half-lives whichever is longer, prior to Visit 1
5.
Any asthma worsening requiring change in asthma treatment other than inhaled 
short- acting bronchodilator(s) (SABA and/or short acting anticholinergic agent) 
within 30 days prior to Visit 1
6.
Use of oral, rectal or parenteral GCS within 30 days and/or depot parenteral GCS 
within 12 weeks prior to Visit 1
7.
Use of any β-blocking agent including eye-drops
8.
Known or suspected hypersensitivity to study drugs or excipient
9.
Smoker (current or previous) with a smoking history of ≥ 10 pack years
10.
Medical history of life-threatening asthma including intubation and intensive care 
unit admission
11.
Any significant disease or disorder (e.g., cardiovascular, pulmonary other than 
asthma, gastrointestinal, hepatic, renal, neurological, musculoskeletal, endocrine, 
metabolic, malignant, psychiatric, major physical impairment) which, in the opinion 
of the investigator, may either put the patient at risk because of participation in the 
study, or may influence the results of the study, or the patient’s ability to participate 
in the study


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
20(70)
12.
Any clinically relevant abnormal findings in physical examination and/or vital signs 
at Visit 2, which, in the opinion of the investigator, may put the patient at risk if 
participating in the study
13.
Pregnancy, breast-feeding or planned pregnancy during the study.  Fertile women 
not using acceptable contraceptive measures, as judged by the investigator
14.
Planned hospitalisation during the study
15.
Suspected poor capability, as judged by the investigator, of following instructions 
of the study.
For randomisation at Visit 3, patients should not fulfil any of the following criteria:
16.
Use of ≥ 6 Bricanyl Turbuhaler ‘as needed’ inhalations per day, for a certain 
number of days depending on the actual length of run-in:  for ≥ 2 days out of 14 
days; for ≥ 3 days out of 15-21 days; for ≥ 4 days out of 22 or more days of run-in
17.
Any asthma worsening requiring change in asthma treatment other than inhaled 
short-acting bronchodilator(s) (SABA and/or short acting anticholinergic  agent) 
from Visit 1 until Visit 2 and / or requiring any asthma treatment other than run-in 
study medication from Visit 2 until randomisation.
See procedures for withdrawal of incorrectly enrolled patients in Section 3.4.
3.3
Patient enrolment and randomisation
Investigator(s) should keep a record, the patient screening log, of patients who entered pre-
study screening.
The Investigator(s) will:
1.
Obtain signed informed consent from the potential patient or their guardian/legal 
representative before any study specific procedures are performed
2.
Assign potential patient a unique enrolment number, beginning with ‘E#’
3.
Determine patient eligibility. See Section 3.1 and 3.2
4.
Assign eligible patient unique randomisation code.
If a patient withdraws from participation in the study, then his/her enrolment/randomisation 
code cannot be reused.
Randomisation codes will be assigned strictly sequentially as patients become eligible for 
randomisation.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
21(70)
3.4
Procedures for handling incorrectly enrolled or randomised 
patients
Patients who fail to meet the eligibility criteria should not, under any circumstances, be 
enrolled or receive study medication.  There can be no exceptions to this rule.  Patients who 
are enrolled, but subsequently found not to meet all the eligibility criteria must not be 
randomised or initiated on treatment, and must be withdrawn from the study.
Where a patient does not meet all the eligibility criteria but is randomised in error, or 
incorrectly started on treatment, the Investigator should inform the AstraZeneca study 
physician immediately, and a discussion should occur between the AstraZeneca study 
physician and the investigator regarding whether to continue or discontinue the patient from 
treatment.  The AstraZeneca study physician must ensure all decisions are appropriately 
documented.
3.5
Methods for assigning treatment groups
An Interactive Voice or Web Response System (IVRS/IWRS) will be utilized to assign 
enrolment and randomisation codes to the patients and to dispense run-in study drug at Visit 2 
and investigational product (IP) at Visit 3 and subsequent treatment visits.  Detailed 
instructions regarding the use of the IVRS/IWRS will be provided in a manual.
The randomisation codes will be computer generated by AstraZeneca R&D or delegate using 
GRand (AZ Global Randomisation system).  Randomisation will be made on site level.  The 
randomisation codes will be loaded into the IVRS/IWRS database.  As patients become 
eligible, they will be assigned to a treatment group in accordance with the randomisation 
scheme.  Randomisation codes will be assigned strictly sequentially as patients become 
eligible for randomisation.
The study will aim to achieve approximately 10% proportion of adolescents among the 
randomised patients.
3.6
Methods for ensuring blinding
This study will be double blind.  All packaging and labelling will be done in such a way as to 
ensure blinding.  Symbicort and terbutaline Turbuhalers will be identical, and the Pulmicort 
and placebo Turbuhalers will be identical.
The following personnel will have access to the randomisation list:
∀
Personnel carrying out the packaging and labelling of investigational product (IP)
∀
Personnel generating the randomisation list.
Personnel other than the above involved in the conduct of the study will not have access to the 
information in the randomisation list.  It will be kept in a secure location until the end of the 
study.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
22(70)
3.7
Methods for unblinding 
Individual treatment codes, indicating the treatment randomisation for each randomised 
patient, will be available to the Investigator(s) or pharmacists from the IVRS/IWRS.  Routines 
for this will be described in the IVRS/IWRS user manual that will be provided to each site.
The treatment code should not be broken except in medical emergencies when the appropriate 
management of the patient requires knowledge of the treatment randomisation.  The 
Investigator documents and reports the action to AstraZeneca, without revealing the treatment 
given to patient to the AstraZeneca staff.
AstraZeneca retains the right to break the code for Serious Adverse Events (SAEs) that are 
unexpected and are suspected to be causally related to an investigational product and that 
potentially require expedited reporting to regulatory authorities.  Treatment codes will not be 
broken for the planned analyses of data until all decisions on the evaluability of the data from 
each individual patient have been made and documented.
3.8
Restrictions
Patients should avoid strenuous exercise for at least 30 minutes, smoking for at least 1 hour 
and having a large meal for at least 2 hours before the planned visits to the study site.
Patients should if possible avoid intake of ‘as needed’ IP 6 hours prior to a study site visit. 
Restrictions regarding concomitant medication are described in Section 7.7.
3.9
Discontinuation of investigational product
Patients may be discontinued from IP in the following situations:
∀
Patients that are incorrectly randomised to the study
∀
Patient decision. The patient is at any time free to discontinue treatment, without 
prejudice to further treatment
∀
Adverse Event
∀
Severe non-compliance with the study protocol
∀
Safety reason as judged by the investigator and/or AstraZeneca
∀
Pregnancy. IP should be discontinued immediately if a patient becomes pregnant 
during the course of the study. See section 6.6.1
∀
Development of any of the following study specific discontinuation criteria will 
necessitate discontinuation of IP (for definition of severe asthma exacerbation, see 
Section 5.1.1):


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
23(70)
!
A severe asthma exacerbation with a duration of more than 3 weeks
!
Three severe asthma exacerbations within a period of 6 months
3.9.1
Procedures for discontinuation of a patient from investigational product 
At any time, patients are free to discontinue administration of investigational product or 
withdraw from the study (ie investigational product and assessments, see Section 3.10), 
without prejudice to further treatment.  A patient who decides to discontinue investigational 
product will always be asked about the reason(s) for this decision and the presence of any 
adverse events.
If possible, all patients who discontinue IP will be seen and Visit 6 / End of Treatment (EoT) 
assessments performed as soon as possible (see Table 1).
A follow-up phone contact will be performed 2 weeks +/-3 days after the last investigational 
product intake to follow adverse events.  If the patient discontinues IP more than 2 weeks +/-
3 days before a site visit, the information to be collected in the follow-up phone call can be 
collected at the visit instead (see Section 4.3).
After discontinuation of IP (ie before Visit 6) patients will be followed up for severe asthma
exacerbations, concomitant medications and adverse events according to the original visit 
schedule including site visits and phone contacts. If it is not possible for the patient to visit the 
study site, the visit(s) may be performed via phone (see Section 4.4 for details).
All Turbuhaler Usage Monitor (TUM) devices and all investigational products should be 
returned by the patient.  Discontinuation of the IP should be recorded in IVRS/IWRS.
If a patient discontinues IP due to a study specific discontinuation criteria this should always 
be recorded as ’Development of study specific discontinuation criteria’ on the IP 
discontinuation form in the eCRF and record asthma deterioration as an AE (see Section 
6.3.3).
If a patient is withdrawn from study, see Section 3.10.
3.10
Criteria for withdrawal 
3.10.1
Enrolment failures 
Enrolment failures are patients who do not fulfil the eligibility criteria for the study, and 
therefore must not be randomised.  These patients should have the reason for study withdrawal 
recorded as ‘Incorrect Enrolment’ (ie patient does not meet the required inclusion/exclusion 
criteria).  This reason for study withdrawal is only valid for enrolment failures (not 
randomised patients).


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
24(70)
The patient can be re-enrolled, due to the following reasons only: 
∀
Enrolment failure due to technical reason (e.g., study equipment not working 
properly), if agreed with AstraZeneca Study Physician 
∀
Enrolment failure due to inclusion criterion 5 not met at Visit 2 if according to 
investigator’s clinical judgment patient is likely to demonstrate FEV1 within the 
required ranges at a later occasion. Re-enrolment due to this reason can only be 
allowed once
∀
Enrolment failure due to inclusion criterion 6 not met for patients on inhaled short-
acting bronchodilator(s) as needed who were screen-failed prior to approval of CSP 
Amendment 2 and who have documented historical reversibility. Re-enrolment due 
to this reason can only be allowed once
Re-enrolled patient should re-sign informed consent, and assent where applicable, at the re-
enrolment Visit 1, and a new E-code will be assigned. All procedures for the enrolment/run-in 
period should be repeated.
Each re-enrolment must be documented in medical records at the study site and in the 
electronic Case Report Form (eCRF).
3.10.2
Withdrawal of the informed consent
Patients are free to withdraw from the study at any time (investigational product and 
assessments), without prejudice to further treatment.
A patient who withdraws consent will always be asked about the reason(s) for this decision 
and the presence of any adverse events (AE).  The Investigator will follow up AEs outside of 
the clinical study.  All TUMs and all investigational products should be returned by the 
patient.
If a patient withdraws from participation in the study, then his/her enrolment/randomisation 
code cannot be reused.  Withdrawn patients will not be replaced.
3.11
Discontinuation of the study
In case early study termination would occur for any unforeseen reason, the following steps 
have to be taken:
Regardless of the reason for early study termination, all data available for the patient at the 
time of termination must be recorded in the eCRF.
The Sponsor will ensure that adequate consideration is given to the protection of the patients' 
interests.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
25(70)
4.
STUDY PLAN AND TIMING OF PROCEDURES
Table 1
Study Plan detailing the procedures
Enrol
ment
Run-in
Rando
mi-
sation
Treatment
2 wks 
Follow
-up
For details 
see 
Protocol 
Section
Visit
1
2
3
Phone 
call
4
Phone 
call
5
Phone 
call
6/ 
EoTa,b
Phone 
call
Week
-2 to -4
0
8
17
25
34
42
52
54
Visit window 
(days)
0-7 
days 
before 
Visit 2
14-28 
days 
before 
Visit 3
±7
±7
±7
±7
±7
±7
±3
Written Informed 
consent 
X
3.3, 10.4
Allocation of 
enrolment code
X
4.1.1
Demography
X
4.1.1
Inclusion/exclusi
on criteria
X
X
X
3.1, 3.2
Medical/surgical 
history
X
4.1.1


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
26(70)
Enrol
ment
Run-in
Rando
mi-
sation
Treatment
2 wks 
Follow
-up
For details 
see 
Protocol 
Section
Visit
1
2
3
Phone 
call
4
Phone 
call
5
Phone 
call
6/ 
EoTa,b
Phone 
call
Week
-2 to -4
0
8
17
25
34
42
52
54
Visit window 
(days)
0-7 
days 
before 
Visit 2
14-28 
days 
before 
Visit 3
±7
±7
±7
±7
±7
±7
±3
Asthma history 
(including history 
of severe asthma 
exacerbations)
X
4.1.1
Smoking history
X
4.1.1
ACQ-5, 
AQLQ(S) 
X
X
X
X
X
5.1.3, 5.1.4, 
5.1.5
Health Care 
resource 
utilisation 
questionnaire, 
EQ-5D-5L
X
X
X
X
5.3.1
SAE/AEsc
Xc
Xc
X
X
X
X
X
6
Weight and 
height
X
Xd
4.1.2


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
27(70)
Enrol
ment
Run-in
Rando
mi-
sation
Treatment
2 wks 
Follow
-up
For details 
see 
Protocol 
Section
Visit
1
2
3
Phone 
call
4
Phone 
call
5
Phone 
call
6/ 
EoTa,b
Phone 
call
Week
-2 to -4
0
8
17
25
34
42
52
54
Visit window 
(days)
0-7 
days 
before 
Visit 2
14-28 
days 
before 
Visit 3
±7
±7
±7
±7
±7
±7
±3
Physical 
examination
X
X
5.2.1
Vital signs (pulse 
and blood 
pressure)
X
X
5.2.2.1
Pregnancy test (if 
applicable)
X
4.1.2
Adjustment of 
current asthma 
medication
X
4.1.2


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
28(70)
Enrol
ment
Run-in
Rando
mi-
sation
Treatment
2 wks 
Follow
-up
For details 
see 
Protocol 
Section
Visit
1
2
3
Phone 
call
4
Phone 
call
5
Phone 
call
6/ 
EoTa,b
Phone 
call
Week
-2 to -4
0
8
17
25
34
42
52
54
Visit window 
(days)
0-7 
days 
before 
Visit 2
14-28 
days 
before 
Visit 3
±7
±7
±7
±7
±7
±7
±3
Patient training in 
how to use 
Turbuhaler 
(inhalation 
technique) and 
TUM; checking 
inhalation 
technique and re-
training if needed
X
X
X
X
4.1.2
Bricanyl for run-
in 
(dispense/return)
d
r
4.1.2, 7.2
Randomisation 
X
3.3, 3.5
Lung function 
(FEV1, FVC pre-
and post-Bricanyl 
administration)
X
X
X
X
X
5.1.2, 7.2
for 
Bricanyl


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
29(70)
Enrol
ment
Run-in
Rando
mi-
sation
Treatment
2 wks 
Follow
-up
For details 
see 
Protocol 
Section
Visit
1
2
3
Phone 
call
4
Phone 
call
5
Phone 
call
6/ 
EoTa,b
Phone 
call
Week
-2 to -4
0
8
17
25
34
42
52
54
Visit window 
(days)
0-7 
days 
before 
Visit 2
14-28 
days 
before 
Visit 3
±7
±7
±7
±7
±7
±7
±3
Reversibility teste
X
Xe
5.1.2.2, 
Inclusion 
criterion 6
Collection of 
severe asthma 
exacerbations
Xf
Xf
Xf
Xf
Xf
Xf
4.2
Concomitant 
medications 
X
X
X
X
X
7.7
Investigational 
product 
(dispense/return/ 
check)
d
d/r/c
d/r/c
r/c
7
a
After discontinuation of IP (ie before visit 6) patients will be followed up according to the original visit schedule including site visits and phone contacts. 
Only Severe asthma exacerbations, AEs and concomitant medications will be collected.  If it is not possible for the patient to visit the study site, the 
visit(s) may be performed via phone. See section 4.4.
b
EoT is end of treatment visit.
c
Serious adverse events will be collected from time of signing Informed consent. Adverse events will be collected from visit 2.
d
Height only for adolescents.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
30(70)
e
Reversibility test will be performed at Visit 2.  The test can be repeated at Visit 3 in case the patients fail to meet inclusion criterion no. 6 at Visit 2.  See 
section 3.1 for inclusion criteria.
f
Severe asthma exacerbations will be collected from visit 3 through the entire study.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
31(70)
4.1
Enrolment and run-in periods
4.1.1
Enrolment procedures at Visit 1
Procedures will be performed according to the Study Plan, see Table 1.
Patients will obtain information regarding the study and sign informed consent for the study 
before any study related procedures are initiated.
Consented patients will be assessed to ensure that they meet eligibility criteria.  Patients who 
do not meet these criteria must not be enrolled in the study.
Eligible patients will receive an enrolment code, allocated by IVRS/IWRS.
Demography, medical, surgical and asthma history including previous asthma exacerbations 
and smoking history will be checked.
For the evaluation of smoking history, pack years will be calculated as follows:
10 pack years =
1 pack (20 cigarettes) per day for 10 years
or 2 pack (40 cigarettes) per day for 5 years
or ½ pack (10 cigarettes) per day for 20 years
1 cigar = 5 cigarettes
1 cigarillo = 2 cigarettes
50 g pipe tobacco = 65 cigarettes
Hand rolled cigarettes can be calculated as 
cigarettes or pipe tobacco.
All serious adverse events occurring after signing the informed consent will be reported. 
Patients will continue taking their prescribed medication until Visit 2 and will be informed 
about medication restrictions applicable before Visit 2 by the investigator (see section 7.7.1).
4.1.2
Run-in procedures at Visit 2
Visit 2 can be performed within 7 days after Visit 1.
Visit 1 and Visit 2 can be performed on the same day only in cases where the patient has not 
taken any medication which could affect the lung function measurements (see details in 
Section 7.7.1, Table 2).
Procedures will be performed according to the Study Plan, see Table 1.
Patients who fulfil the inclusion and none of the exclusion criteria (Visit 2) will enter a 2-4 
weeks run-in period.
From Visit 2 all adverse events will be collected (see Section 6 for details).


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
32(70)
Height will be measured in cm (without shoes) and weight in kg (light clothes and without 
shoes).  Physical examination will be performed and pulse and blood pressure will also be 
measured.
Pregnancy test by urine dipstick should be performed for female patients aged ≤60 years. 
Patients will be asked to stop their prescribed asthma medication (including maintenance 
treatment with ICS and LTRA) used at the time of study entry and during the enrolment 
period in accordance with Section 7.7.
At Visit 2 patients will complete ACQ-5 and AQLQ(S) questionnaires using the electronic 
Patient Reported Outcome (ePRO) device after receiving detailed information.
Instructions will be given to the patients on how to use the Turbuhaler (inhalation technique) 
and the TUM device.  Before taking the first dose of run-in medication the patient will be 
instructed by the study personnel how to take the medication.  In order to inhale properly 
according to instructions the patients will practice inhalation technique with a training device, 
as many times as judged necessary by the supervising study personnel.
All patients will receive Bricanyl Turbuhaler for ‘as needed’ use during the run-in period.
Spirometry – including reversibility test – will preferably be performed between 7 am and 11 
am to measure lung function and verify eligibility of the patient (see Section 5.1.2 for details).
Concomitant medications will be checked.
Patients will be instructed to contact their investigator immediately for reassessment if they 
need to take more than 12 inhalations per day from the run-in medication (white label with 
blue bar Turbuhaler).
4.2
Treatment period
At Visit 3 investigator should check eligibility of the patient before randomisation.
Length of run-in period is flexible from 2 to 4 weeks. Assessment of the Bricanyl ‘as needed’ 
use criterion is allowed more than once during run-in. If inclusion criterion 7 is not fulfilled 
after at least 2 weeks of run-in AND patient has not used Bricanyl Turbuhaler above the limits 
described in exclusion criterion 16, investigator can re-schedule Visit 3. Downloading the 
Turbuhaler Usage Monitor (TUM) data to check inclusion criterion 7 and exclusion criterion 
16 should be the first procedure during this visit. Patient can remain in run-in period for 
maximum 4 weeks.  
For timing of visits appointment for spirometry procedure (± 1 hour related to spirometry 
procedure at Visit 2) has to be taken into account (see Section 5.1.2 for details).
Treatment visits will take place at 17, 34 and 52 weeks of treatment after randomisation. 


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
33(70)
Description of the procedures for this period is included in the Study Plan, see Table 1. 
The patient should take the first dose of maintenance IP at the study site.
Patients should bring the study medication to site and take the morning dose of maintenance 
IP at the study site after study procedures are completed. Patient’s inhalation technique will be 
checked by the study personnel at each visit. Patient will be re-trained on how to use the 
Turbuhaler and TUM if needed.
Patients will be instructed to contact their investigator immediately for reassessment if they 
need to take more than 12 inhalations per day with blinded ‘as needed’ investigational product 
- Symbicort Turbuhaler or terbutaline Turbuhaler - during the treatment period.
At randomisation and each treatment visit, the patients will complete ACQ-5, AQLQ(S) and 
EQ-5D-5L questionnaires as the first activity.  Information on health care resource utilization 
will be collected.
Thereafter, spirometry will be performed within the requested time window (see Section 
5.1.2).
In addition patients will be contacted by phone call (or other methods if needed) preferably by 
the study nurse between site visits at weeks 8, 25 and 42 (Figure 1), and be asked if he/she 
since the last study visit
∀
has taken any additional asthma treatment other than the study medication and
∀
has had any asthma worsening that led to hospitalisation or emergency room visit or 
to a doctor’s consultation.
If the answer is “yes” the investigator will call the patient and ask for more detailed 
information in order to collect and document any additional asthma medication and/or severe 
asthma exacerbation events.
Investigators should make all efforts to collect severe asthma exacerbation data and verify the 
information given by the patient to the greatest possible extent using medical records and 
other source data.
4.3
Follow-up 
A follow-up telephone contact will be performed 2 weeks +/- 3 days after the last 
investigational product intake.  At the follow-up telephone call, the investigator will check for 
adverse events ongoing at the end of study treatment or occurred after last treatment visit.
In the event of discontinuation of IP, the procedure described in Section 3.9.1 will be 
followed.  Patients will be treated according to local medical practice.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
34(70)
4.4
Follow-up in case of discontinuation of IP
After discontinuation of IP (ie before Visit 6) patients will be followed up for severe asthma 
exacerbations, concomitant medications and adverse events according to the original visit 
schedule including site visits and phone contacts.  Patients will be treated according to local 
medical practice. Only Severe asthma exacerbations, AEs and concomitant medications will 
be documented and entered into the eCRF. No more study specific procedures will be required 
for the purpose of this study.
If it is not possible for the patient to visit the study site, the visit(s) may be performed via 
phone.
5.
STUDY ASSESSMENTS
The Rave Web Based Data Capture (WBDC) system will be used for data collection and 
query handling.  The investigator will ensure that data are recorded on the electronic Case 
Report Form (eCRF) as specified in the study protocol and in accordance with the instructions 
provided.
The investigator ensures the accuracy, completeness and timeliness of the data recorded and 
of the provision of answers to data queries according to the Clinical Study Agreement.  The 
investigator will sign the completed eCRFs.  A copy of the completed eCRFs will be archived 
at the study site.
5.1
Efficacy assessments
5.1.1
Severe asthma exacerbation
In this study severe asthma exacerbation is defined as deterioration of asthma that is 
associated with a medical intervention as described below.  Deterioration of asthma defined as 
worsening of asthma symptoms, increased use of ‘as needed’ medication, or deterioration of 
lung function which lasts for two or more days or which happens acutely (≤24 h) will be 
recorded in the eCRF by the investigator.
A severe exacerbation is defined as a deterioration of asthma requiring any of the following:
∀
Use of systemic glucocorticosteroids for at least 3 days1
∀
Inpatient hospitalization
∀
Emergency room visit2 due to asthma that required systemic glucocorticosteroids.
1 An injection of depot glucocorticosteroids due to asthma worsening is considered equivalent   
  to at least 3 days of systemic glucocorticosteroids 
2 Emergency room visit or other urgent unscheduled health care visit


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
35(70)
The start and end date of each severe asthma exacerbation will be recorded in the eCRF.  For 
severe exacerbations the start date is defined as the first day of hospitalisation / emergency 
room treatment or the first day of systemic (ie not inhaled) GCS treatment.  The end date is 
defined as the last day of hospitalisation/emergency room treatment or the last day of systemic 
GCS treatment.  If the same asthma exacerbation includes both hospitalisation/emergency 
room treatment and systemic GCS treatment, the start and end dates are the first and last day 
that either of the criteria was fulfilled.
Additional hospitalisations/emergency room treatments and systemic GCS treatments 
occurring during a severe asthma exacerbation should not be regarded as a new exacerbation.  
For severe asthma exacerbation to be counted as a separate event, it must be preceded by at 
least seven days in which no criteria for severe exacerbations are fulfilled.
If a patient has a severe asthma exacerbation with a duration of more than 3 weeks or 3 severe 
asthma exacerbations during 6 months, patient should discontinue IP and the reason should be 
recorded as ‘Development of study specific discontinuation criteria’ on the IP discontinuation 
form.
5.1.2
Lung function measurement by spirometry (FEV1, FVC) at the study site
Equipment and conditions
Spirometry will be performed by the Investigator or authorized delegate according to 
American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines (Miller et al 
2005).  The study site personnel who will be performing the testing should be properly 
certified / trained.
The spirometer must meet ATS/ERS recommendations (Miller et al 2005).  The 
monitor/vendor is responsible for checking that the spirometer in use meets these 
recommendations.  It should be serviced once a year or according to the manufacturer’s 
instruction at an authorised facility.  All service measures and repairs must be documented.
Due to diurnal variation of lung function it is important that all spirometry assessments at 
Visits 3, 4, 5 and 6 are performed ±1 hour in relation to the time of spirometry at Visit 2 and 
preferably after 7 am and no later than 11 am.
The spirometry should be conducted with the same spirometer within patients and for all 
patients at each site.  Preferably, the same study personnel should test the patient’s lung 
function throughout the study to reach optimal performance and to enhance reproducibility.  
The patient should rest at least 15 minutes prior to the test.  For repeated measurements e.g., to 
assess best of 3, a short pause (1 minute) between measurements is recommended.
The measurements are to be made with the patient seated in an upright position (preferably), 
or if not comfortable standing position is also acceptable.  The same position should be used 
for all spirometry measures during the entire study.  The head must not be tilted during 
measurements.  During the breathing manoeuvres, the thorax should be able to move freely; 
hence tight clothing should be loosened.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
36(70)
A nose-clip should be used for the manoeuvre.  Mouthpieces of the same dimension and shape 
should be used throughout the study.  Spirometry should be performed using a calibrated 
spirometer and values are expressed at Body Temperature and ambient Pressure Saturated 
with water vapour.
Calibration should be in accordance with each trademark specification.  If nothing else is 
specified, calibration should be performed every day when a patient visits the study site.  
Instead of using a 3 L syringe, a 1 L can be used 3 times.  The accuracy of the calibration must 
be within ± 3% of the reading or ± 0.05 L, whichever is greater.  All calibration reports should 
be signed, dated and filed in the ISF along with a signed and dated copy (if the calibration 
reports are not on archive-quality paper).  If a calibration report cannot be printed, the results 
should be documented in writing in the Investigator Study File (ISF).
FEV1 and FVC
The forced expiratory manoeuvre should start with a maximal inspiration and then be 
followed by a fast and forceful expiration that should last for at least 6 seconds.  It is 
important to encourage the patient to continue the expiration to be fast and forceful throughout 
the manoeuvre.  Check that none of the following has occurred; coughing during the first 
second, glottis closure, leak or obstruction of mouthpiece (by the tongue).
At least 3 technically satisfactory forced vital capacity (FVC) manoeuvres should be 
performed.  The difference between highest and second highest FVC and FEV1, respectively, 
should not be more than 150 mL.  A maximum of 8 manoeuvres should be performed in 
attempting to meet reproducibility criteria.  If the reproducibility criteria cannot be met within 
8 manoeuvres, the highest FEV1 value should be recorded, and a comment should be entered 
on the printout.
FEV1 values will be taken from the FVC curves.  After examining the data from all acceptable 
curves, the highest FEV1 value and the highest FVC value should be recorded, even if the 2 
values do not come from the same curve.
Signed and dated copies of the 3 best manoeuvres printouts must be kept in the ISF for source 
data verification.  The printouts must be marked with study code, enrolment code, date and 
time of measurements, visit number and patient initials.
5.1.2.1
Pre-bronchodilator and post-bronchodilator FEV1 and FVC including 
reversibility testing and calculation of predicted normal values (PN)
Pre-bronchodilator and post-bronchodilator FEV1 and FVC expressed in liters (L) will be 
performed at Visits 2 to 6.
The assessment will be performed as follows:
∀
Pre-bronchodilator FEV1 measurement
∀
Inhalation of Bricanyl Turbuhaler 2 x 0.5 mg


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
37(70)
∀
Wait 15 to 30 minutes
∀
Post-bronchodilator FEV1 measurement.
At Visit 2 these measurements are performed for inclusion verification and characterisation of 
the patient population.  Thus at this visit pre-bronchodilator and post-bronchodilator FEV1 PN 
will be calculated.  FEV1 PN value will be based on the reference values from European 
Respiratory Society (ERS) guidelines for adult and adolescent patients (Quanjer et al 2012).
At Visits 3 to 6 the purpose of the assessment is to get pre-bronchodilator and post-
bronchodilator values of FEV1 and FVC as part of the evaluation of lung function
5.1.2.2
Reversibility test
To fulfil the reversibility inclusion criterion at Visit 2 the increase in FEV1 relative to baseline 
must be ≥12% and ≥200 ml 15-30 minutes after inhalation of 2 x 0.5 mg Bricanyl Turbuhaler.
The reversibility is calculated as follows:
The investigator should record the pre- and post-bronchodilator FEV1 in the eCRF and the 
calculation will be performed by the eCRF.
If the reversibility inclusion criterion is not met at Visit 2, the reversibility test may be 
repeated at Visit 3.  If patients on low dose ICS or LTRA fail at both occasions, they can still 
be included if they have a documented historical reversibility within the last 12 months prior 
to Visit 3, see also inclusion criterion 6, Section 3.1.
5.1.3
Asthma Control Questionnaire (5-item Version)
The ACQ was developed by Juniper (Juniper et al 1999).  The ACQ includes 7 items 
covering all the criteria (symptoms, FEV1, and SABA used as rescue medication) deemed 
necessary by international guidelines committees for determining the adequacy of asthma 
control.  The ACQ has undergone rigorous validation and has been shown to have strong 
evaluative and discriminative measurement properties (Juniper et al 1999).  In this study, the 
FEV1 and SABA use questions will be excluded, and patients will be responding to the five 
symptom questions (ACQ-5).  It has been shown that exclusion of the questions for SABA use 
and/or the FEV1 does not alter the validity and the measurement properties of the 
questionnaire (Juniper et al 2001).  Linguistically validated translations of the ACQ-5 into 
the local languages will be used.  The original North American English version is included in 
Appendix C.
The ACQ-5 will be self-administered using ePRO device during site visits as indicated in 
Table 1.  The questions take approximately 2 to 3 minutes to complete.
100
)
(
1
)
(
1
)
(1
X
FEV
FEV
FEV
ity
Reversibil
before
before
after !
#


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
38(70)
Patients who are not fluent in the local language will not perform the ACQ-5 assessments, but 
they can still participate in the study.  The assessment of ACQ-5 will only be performed in 
countries where validated translations are available.
5.1.4
Asthma Quality of Life Questionnaire (Standardised Version)
The AQLQ has been developed by Juniper (Juniper et al 1992) and includes 32 questions in 
4 domains: activity limitation, symptoms, emotional function and exposure to environmental 
stimuli.  A feature of the AQLQ is that patients themselves select 5 of the 11 activity 
questions.  The standardised version of the AQLQ, the AQLQ(S), in which 5 generic activities 
replace the 5 patient-specific activities of the AQLQ (Juniper et al 1999) will be used in this 
study.  The AQLQ(S) is more appropriate than AQLQ for long-term clinical studies, when
patients’ activities and priorities may change over time.  The AQLQ(S) evaluates the impact 
of asthma on patients every day functioning and wellbeing.  The AQLQ(S) has been validated 
for use from the age of 12 years (Juniper et al 2005).  Linguistically validated translations of 
AQLQ(S) into the local languages will be used.  The North American English version is 
included in Appendix D.
The AQLQ(S) will be self-administered using ePRO device during site visits as indicated in 
Table 1.  The questionnaire takes approximately 15 minutes to complete.  The patient needs to 
be able to read and to be fluent in the local language to be able to answer the questions.  
Patients who are not fluent in the local language will not perform the AQLQ(S) assessments, 
but they can still participate in the study.  The assessment of AQLQ(S) will only be performed 
in countries where validated translations are available.
5.1.5
Administration of patient reported outcome questionnaires
The questionnaires (ACQ-5 and AQLQ[S]) should be completed using ePRO device at the 
scheduled visits before any other study-related procedures are performed to avoid biased 
responses. At Visit 2 only, the questionnaires can be completed following the lung function 
measurements. At Visit 2 instructions will be provided to each patient in the local language, 
how to complete the questionnaires.
The patient should be informed about the purpose and importance of completing the 
questionnaires and be given adequate time to complete all items.  It is important to administer 
the questionnaires according to the guidelines for standardised administration.  The questions 
should be completed in a quiet place without influence from family, friends, or study 
personnel.  Family, friends, or study personnel should never help the patient to choose an 
answer, interpret, or rephrase the questions for the patient.
5.1.6
Turbuhaler Usage Monitor (TUM)
The Turbuhaler Usage Monitor (TUM, a SmartTurbo™ version manufactured by Nexus6 Ltd, 
New Zealand) is a battery powered electronic data logger designed to be attached to a 
Turbuhaler (DPI).  The TUM contains an internal electronic clock and calendar that logs 


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
39(70)
through a microprocessor the date and time when the Turbuhaler base grip is rotated back and 
forth.
TUM devices will be used for the Turbuhalers containing ‘as needed’ and maintenance 
investigational product, and for Bricanyl Turbuhaler used during the run-in period as well (see 
also Section 7 for details).
The colour of the main body of all the TUMs will be white. The colour of the locking ring of 
the TUM will be:
!
white for the ‘as needed’ study medication and the Bricanyl Turbuhaler
!
brown for the maintenance study medication
Patients will be informed about the TUM at Visit 2 and will receive written user instructions 
(see Section 4.1.2).
5.2
Safety assessments 
5.2.1
Physical examination
A physical examination will be performed at Visit 2 and Visit 6 and include an assessment of 
the following: general appearance, respiratory, cardiovascular, abdomen, head and neck 
(including head, ears, eyes, nose and throat).  The examination at Visit 2 is regarded as 
baseline data.  Physical examination will also be performed in case of discontinuation of IP 
(see Section 3.9.1).  For reporting of AEs based on examinations, see Section 6.3.6.
5.2.2
Vital signs
For reporting of AEs based on vital signs, see Section 6.3.6.
5.2.2.1
Pulse and blood pressure
Blood pressure and pulse rate measurements will be performed at Visit 2 and Visit 6.  The 
measurements at Visit 2 are regarded as baseline data.  Blood pressure and pulse rate will also 
be measured in case of discontinuation of IP (see also Section 3.9.1).
Pulse rate (beats/min) will be measured over 30 seconds in a sitting position, after 5 minute 
rest.  Thereafter systolic and diastolic blood pressure (mmHg) will be measured using the 
same cuff size, appropriate for arm circumference, throughout the study
5.3
Health Economics
Information on health care resource utilization as well as health related quality of life (EQ-5D-
5L) will be collected at randomisation and at each treatment visits to enable health technology 
assessment, health economic analysis and health economic modelling.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
40(70)
5.3.1
Health care resource utilisation
At baseline (Visit 3, Randomisation) and at subsequent treatment visits until Visit 6 / EoT the 
patient will be asked questions about asthma-related health care resource use events since last 
visit as well as asthma-related sickness absence, time-off work or education.
The patient will be asked about health care resource use in terms of use of ambulance 
services; emergency room visits; hospital admissions to general or intensive care; ambulatory-
setting or home consultations with specialists, primary care physicians or other healthcare 
professionals; and telephone consultations with physicians or nurse.
For patients in paid employment, they will also be asked how much time they have taken as 
sickness absence due to their asthma.
For patients in education, they will also be asked how much time they have taken as sickness 
absence due to their asthma.
5.3.1.1
Methods of assessment EQ-5D-5L
The EQ-5D is a standardized measure of health status developed by the EuroQol Group in 
order to provide a simple, generic measure of health for clinical and economic appraisal (The 
EuroQol Group 1990).
The EQ-5D is applicable to a wide range of health conditions and treatment. It provides a 
simple descriptive profile and a single index value for health status that can be used in 
economic evaluation of health care.  There are two versions of EQ-5D – a three level version 
(EQ-5D-3L) and a five level version (EQ-5D-5L). The EQ-5D-5L will be used in this trial, see 
Appendix F.  The EQ-5D-5L consists of 2 pages - the EQ-5D descriptive system and the EQ 
Visual Analogue Scale (VAS). The descriptive system comprises five dimensions, mobility, 
self-care, usual activity, pain/discomfort and anxiety/depression.  Each dimension has five 
levels (response options): no problems, slight problems, moderate problems, severe problems 
and extreme problems. The EQ VAS records the respondent´s self-rated health on a 20 cm 
vertical visual analogue scale with endpoints labelled “the best health you can imagine” and 
“the worst health you can imagine”
This instrument is extensively validated and is available in several languages that facilitate its 
use in multinational studies.  The translations into local languages have been performed 
according to a linguistic validation process.
The EQ-5D-5L will be self-administered using the paper version.  The questions will be 
assessed at baseline (Randomisation Visit 3) and at subsequent treatment visits until Visit 6 / 
EoT.  The 5 questions will take approximately 5 minutes to answer.  The patients need to be 
able to read and to be fluent in the local language to be able to answer the questions.
5.3.1.2
Administration of EQ-5D-5L questionnaire
The EQ-5D-5L should be given to patients as detailed in the Study Plan (see Table 1), before 
assessments, prior to administration of study drug, and before imparting any news about the 


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
41(70)
status of their disease.  Patients should be allowed to complete the paper questionnaire in their 
own time, and without any help from relatives or clinic staff.  The patient can receive help 
from a study nurse in reading the instructions and questions. However, under no 
circumstances should help in interpreting the questions or in selecting responses be provided.
The appropriate module of eCRF will be completed by the clinic staff to detail if a 
questionnaire has been completed at each EQ-5D-5L visit, and if not, the reason will be 
recorded.  Each centre must allocate responsibility for the EQ-5D-5L questionnaire to a 
specific individual (ie a Research Nurse).  The AstraZeneca Study Team will provide training 
for relevant personnel in the administration of the EQ-5D-5L questionnaire.  Investigator or 
delegate will transfer the patient´s data from the paper copy to the eCRF.  It is also important 
that the significance and relevance of the data are explained carefully to participating patients 
so that they are motivated to comply with data collection (The EuroQol Group 1990).
Patients who are not fluent in the local language will not perform the EQ-5D-5L assessments, 
but they can still participate in the study.  The assessment of EQ-5D-5L will only be 
performed in countries where validated translations are available.
5.4
Pharmacokinetics
Pharmacokinetic samples will not be taken during the study.
5.5
Pharmacodynamics
Pharmacodynamic samples will not be taken during the study.
5.6
Pharmacogenetics
Pharmacogenetic samples will not be taken during the study.
5.7
Biomarker analysis 
Biological samples will not be taken during the study.
6.
SAFETY REPORTING AND MEDICAL MANAGEMENT
The Principal Investigator is responsible for ensuring that all staff involved in the study are 
familiar with the content of this section.
6.1
Definition of adverse events
An adverse event is the development of an undesirable medical condition or the deterioration 
of a pre-existing medical condition following or during exposure to a pharmaceutical product, 
whether or not considered causally related to the product.  An undesirable medical condition 
can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver) or the 
abnormal results of an investigation (e.g., laboratory findings, electrocardiogram).  In clinical 


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
42(70)
studies, an AE can include an undesirable medical condition occurring at any time, including 
run-in or washout periods, even if no study treatment has been administered.
The term AE is used to include both serious and non-serious AEs.
6.2
Definitions of serious adverse event
A serious adverse event is an AE occurring during any study phase (ie run-in, treatment, wash 
out, follow-up), that fulfils one or more of the following criteria:
∀
Results in death
∀
Is immediately life-threatening
∀
Requires in-patient hospitalisation or prolongation of existing hospitalisation 
∀
Results in persistent or significant disability/incapacity or substantial disruption of 
the ability to conduct normal life functions
∀
Is a congenital abnormality or birth defect
∀
Is an important medical event that may jeopardise the patient or may require 
medical intervention to prevent one of the outcomes listed above.
For further guidance on the definition of a SAE, see Appendix B to the Clinical Study 
Protocol.
6.3
Recording of adverse events
6.3.1
Time period for collection of adverse events
Adverse Events will be collected from Visit 2 throughout the entire treatment period and 
during the follow-up period until the last telephone follow-up, or the last contact.
SAEs will be recorded from the time of informed consent.
6.3.2
Follow-up of unresolved adverse events
Any AEs that are unresolved at the patient’s last AE assessment in the study are 
followed up by the Investigator for as long as medically indicated, but without 
further recording in the eCRF.  AstraZeneca retains the right to request additional 
information for any patient with ongoing AE(s)/SAE(s) at the end of the study, if 
judged necessary.
6.3.3
Symptoms of the disease under study
Asthma symptoms or signs, such as wheeze, cough, chest tightness, dyspnoea, breathlessness 
and phlegm, will be recorded as AEs only when:


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
43(70)
∀
The sign or symptom meets Serious Adverse Event criteria, see Section 6.2 for 
definition
∀
The patient discontinues IP due to the sign or symptom and/or
∀
The sign or symptom is new to the patient or not consistent with the patient’s pre-
existing asthma history (defined as within 1 year of Visit 1) as judged by the 
investigator.
If a patient discontinues IP due to a study specific discontinuation criterion this should always 
be recorded as ’Development of study specific discontinuation criteria’ on the IP 
discontinuation form in the eCRF.  In addition, the investigator has to report asthma 
deterioration as an AE leading to discontinuation with investigational product (DAE)/AE on 
the AE form.
6.3.4
Variables 
The following variables will be collected for each AE;
∀
AE (verbatim)
∀
The date when the AE started and stopped
∀
Maximum intensity
∀
Whether the AE is serious or not
∀
Investigator causality rating against the IP (yes or no)
∀
Action taken with regard to investigational product
∀
AE caused patient’s withdrawal from study (yes or no)
∀
Outcome.
In addition, the following variables will be collected for SAEs:
∀
Date AE met criteria for serious AE
∀
Date Investigator became aware of serious AE
∀
AE is serious due to
∀
Date of hospitalisation
∀
Date of discharge


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
44(70)
∀
Probable cause of death
∀
Date of death
∀
Autopsy performed
∀
Causality assessment in relation to Study procedure(s)
∀
Causality assessment in relation to Other medication
∀
Description of AE.
It is important to distinguish between serious and severe AEs.  Severity is a measure of 
intensity whereas seriousness is defined by the criteria in Section 6.2.  An AE of severe 
intensity need not necessarily be considered serious.  For example, nausea that persists for 
several hours may be considered severe nausea, but not a SAE unless it meets the criteria
shown in Section 6.2. On the other hand, a stroke that results in only a limited degree of 
disability may be considered a mild stroke but would be a SAE when it satisfies the criteria 
shown in Section 6.2.
Maximum intensity refers to the complete course of the AE.  The patient (parents/legal 
guardians) will be asked to assess the maximum intensity of the reported AEs according to the 
following scale:
∀
Mild (awareness of sign or symptom, but easily tolerated)
∀
Moderate (discomfort sufficient to cause interference with normal activities)
∀
Severe (incapacitating, with inability to perform normal activities).
6.3.5
Causality collection
The Investigator will assess causal relationship between Investigational Product and each 
Adverse Event, and answer ‘yes’ or ‘no’ to the question ‘Do you consider that there is a 
reasonable possibility that the event may have been caused by the investigational product?’
For SAEs causal relationship will also be assessed for other medication and study procedures.  
Note that for SAEs that could be associated with any study procedure the causal relationship is 
implied as ‘yes’.
A guide to the interpretation of the causality question is found in Appendix B to the Clinical 
Study Protocol.
6.3.6
Adverse events based on signs and symptoms
All AEs spontaneously reported by the patient or care provider or reported in response to the 
open question from the study personnel:  ‘Have you / your child had any health problems 
since the previous visit/you were last asked?’, or revealed by observation will be collected and 


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
45(70)
recorded in the eCRF.  The question will be put to each patient (or parent/legal guardian) in 
local language from Visit 2 to the last follow-up telephone contact.  When collecting AEs, the 
recording of diagnoses is preferred (when possible) to recording a list of signs and symptoms.  
However, if a diagnosis is known and there are other signs or symptoms that are not generally 
part of the diagnosis, the diagnosis and each sign or symptom will be recorded separately.
6.3.7
Adverse events based on examinations and tests
Vital signs data will be summarised in the clinical study report.  Deterioration as compared to 
baseline in protocol-mandated vital signs should therefore only be reported as AEs if they 
fulfil any of the SAE criteria or are the reason for discontinuation of treatment with the 
investigational product.
If deterioration in a vital sign is associated with clinical signs and symptoms, the sign or 
symptom will be reported as an AE and the associated vital sign will be considered as 
additional information.  In the absence of clinical signs or symptoms, clinically relevant 
deteriorations in non-mandated parameters should be reported as AE(s).
Any new or aggravated clinically relevant abnormal medical finding at a physical examination 
as compared with the baseline assessment will be reported as an AE.
6.3.8
Hy’s Law
Cases where any lab samples that are collected from a patient show an Aspartate 
Aminotransferase or Alanine Aminotransferase ≥3xUpper Limit of Normal (ULN) or total 
bilirubin ≥2xULN may need to be reported as SAEs according to handling of cases 
representing Hy’s Law.  In such case, the investigator should contact the AstraZeneca Study 
Physician.
6.4
Reporting of serious adverse events
All SAEs have to be reported, whether or not considered causally related to the investigational 
product, or to the study procedure(s). All SAEs will be recorded in the eCRF.
If any SAE occurs in the course of the study, then Investigators or other site personnel inform 
the appropriate AstraZeneca representatives within one day ie immediately but no later than 
24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative works with the Investigator to ensure that all the 
necessary information is provided to the AstraZeneca Patient Safety data entry site within 1 
calendar day of initial receipt for fatal and life threatening events and within 5 calendar 
days of initial receipt for all other SAEs.
For fatal or life-threatening adverse events where important or relevant information is missing, 
active follow-up is undertaken immediately.  Investigators or other site personnel inform 
AstraZeneca representatives of any follow-up information on a previously reported SAE 
within one calendar day ie immediately but no later than 24 hours of when he or she 
becomes aware of it.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
46(70)
Once the Investigators or other site personnel indicate an AE is serious in the WBDC system, 
an automated email alert is sent to the designated AstraZeneca representative.
If the WBDC system is not available, then the Investigator or other study site personnel 
reports a SAE to the appropriate AstraZeneca representative by telephone.
The AstraZeneca representative will advise the Investigator/study site personnel how to 
proceed. 
The reference document for definition of expectedness/listedness is the Investigator’s 
Brochure for the AstraZeneca drug and the EU Summary of Product Characteristics for the 
active comparator product (including AstraZeneca comparator).
6.5
Overdose
Background
The risks associated with overdosage of Symbicort are considered to be small, as the safety 
margins for inhaled budesonide and formoterol are substantial.  Administration of a Symbicort 
Turbuhaler dose of 1600/45 μg over one hour on top of maintenance treatment with daily 
doses of 640 μg budesonide and 18 μg formoterol in asthma patients raised no safety 
concerns, nor did a formoterol dose of 90 μg over three hours in adult patients with acute 
bronchoconstriction or a budesonide dose of 7200 μg in healthy volunteers.
In high-dose formoterol studies where terbutaline was given as an active comparator, a 
terbutaline dose up to 10 mg over three hours in adult patients with acute bronchoconstriction 
raised no safety concerns.
Symptoms
Inhaled glucocorticosteroids have a low toxicity, and are virtually without harmful effects 
after a single or a few doses, even if the doses are very high.  Thus, acute overdosage with 
budesonide - even in excessive doses - is not a clinical problem.  As with all GCSs, systemic 
glucocorticosteroid effects may appear if used chronically in excessive doses.
There is limited clinical experience regarding overdosage with inhaled formoterol.  An 
overdose would likely lead to effects that are typical of β2-agonists such as tremor, headache 
and palpitations.  Symptoms and signs reported with formoterol from isolated cases are 
tachycardia, hyperglycaemia, hypokalaemia, prolonged QTc-interval, arrhythmia, nausea and 
vomiting.
Experience with other β2-agonists has shown that overdoses may also cause restlessness, 
irritability, excitation, somnolence, convulsions and hyper- or hypotension.  Metabolic effects 
may include acidosis and in serious cases, possibly rhabdomyolysis and renal failure.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
47(70)
Treatment suggestions
Normally, an overdose with Symbicort or terbutaline should not require any special treatment.  
However if signs of adrenergic effects occur these should be counteracted by supportive and 
symptomatic treatment, according to local routines.
Procedures for reporting
For the purpose of this study, an accidental or deliberate intake of blinded treatment of more 
than 20 inhalations (> 3200/90 μg Symbicort or 8 mg terbutaline delivered dose) during one 
day is defined as an overdose and must be reported as such as described below:
An overdose with associated AEs is recorded as the AE diagnosis/symptoms on the relevant 
AE modules in the eCRF and on the Overdose eCRF module.  An overdose without associated 
symptoms is only reported on the Overdose eCRF module.
If an overdose on an AstraZeneca study drug occurs in the course of the study, then the 
Investigator or other site personnel inform appropriate AstraZeneca representatives 
immediately, or no later than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative works with the Investigator to ensure that all 
relevant information is provided to the AstraZeneca Patient Safety data entry site.
For overdoses associated with a SAE, the standard reporting timelines apply, see Section 6.4. 
For other overdoses, reporting must occur within 30 days.
6.6
Pregnancy
All pregnancies and outcomes of pregnancy should be reported to AstraZeneca.
6.6.1
Maternal exposure
If a patient becomes pregnant during the course of the study investigational product should be 
discontinued immediately.
Pregnant women, as well as those who are planning pregnancy or are breast-feeding, are 
excluded from the study.  In addition, fertile women not using acceptable contraceptive 
methods, as judged by the investigator, should not be included in the study.
Clinical experience with Symbicort in pregnant women is limited and patients that become 
pregnant must be discontinued from the investigational product.  However, reports from 
clinical studies and post-marketing surveillance do not indicate an increased risk when using 
Symbicort Turbuhaler during pregnancy.
Pregnancy itself is not regarded as an adverse event unless there is a suspicion that the 
investigational product under study may have interfered with the effectiveness of a 
contraceptive medication.  Congenital abnormalities/birth defects and spontaneous 
miscarriages should be reported and handled as SAEs.  Elective abortions without 


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
48(70)
complications should not be handled as AEs.  The outcome of all pregnancies (spontaneous 
miscarriage, elective termination, ectopic pregnancy, normal birth or congenital abnormality) 
should be followed up and documented even if the patient was discontinued from the study.
If any pregnancy occurs in the course of the study, then the Investigator or other site personnel 
informs the appropriate AstraZeneca representatives within 1day ie immediately but no later 
than 24 hours of when he or she becomes aware of it.
The designated AstraZeneca representative works with the Investigator to ensure that all 
relevant information is provided to the AstraZeneca Patient Safety data entry site within 1 or 5 
calendar days for SAEs (see Section 6.4) and within 30 days for all other pregnancies.
The same timelines apply when outcome information is available.
The PREGREP module in the eCRF is used to report the pregnancy and the PREGOUT paper 
form is used to report the outcome of the pregnancy.
6.6.2
Paternal exposure 
There is no restriction on fathering children or donating sperm during the study.
6.7
Management of IP related toxicities
Treatment related toxicity is not expected from budesonide/formoterol, when used as directed.  
For overdose, see Section 6.5.
6.8
Study governance and oversight
6.8.1
Independent adjudication committee for fatal events
An independent external adjudication committee will be constituted to provide an 
independent, external and unbiased assessment of fatal events reported during the study in 
order to determine whether the death may have been related to asthma. The committee will 
operate in accordance with an Adjudication Committee Charter, which will also provide detail 
on specific information the committee requires to enable the adjudication.
Following adjudication a notification will be sent to the AstraZeneca senior medical officer in 
order to decide whether a Data Safety Monitoring Board should be appointed for further 
review of safety data in the studies.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
49(70)
7.
INVESTIGATIONAL PRODUCT AND OTHER TREATMENTS
7.1
Identity of investigational product(s)
Investigational product
Dosage form and strength
Manufacturer
Symbicort Turbuhaler 160/4.5 μg
(Budesonide / formoterol fumarate 
dihydrate 160/4.5 μg)
Budesonide / formoterol fumarate dehydrate 
powder for inhalation, 160 μg budesonide and 
4.5 μg formoterol per inhalation, 120 doses
AstraZeneca
Terbutaline Turbuhaler 0.4 mg
(terbutaline sulphate 0.4mg)
Terbutaline sulphate powder for inhalation, 
0.4 mg terbutaline per inhalation, 120 doses
AstraZeneca
Pulmicort Turbuhaler 200 μg 
(budesonide 200 μg)
Budesonide powder for inhalation, 200 μg per 
inhalation, 200 doses
AstraZeneca
Placebo for budesonide (Placebo 
Turbuhaler) 
Placebo powder for inhalation, 200 doses
AstraZeneca
Budesonide/formoterol, terbutaline, budesonide and placebo for budesonide will all be 
dispensed as inhalers (Turbuhaler).  Budesonide/formoterol, terbutaline and placebo for 
budesonide inhalers contain lactose as part of the filling material whereas the budesonide 
inhaler and the Bricanyl Turbuhaler do not.
The terbutaline Turbuhaler 0.4 mg corresponds to Bricanyl Turbuhaler 0.5 mg with regards to 
the dose delivered.  The terbutaline Turbuhaler 0.4 mg dose is expressed as delivered dose 
whereas the Bricanyl Turbuhaler 0.5 mg dose is expressed as metered dose.  The terbutaline 
Turbuhaler 0.4 mg product is a clinical trial product that is blinded against the Symbicort 
Turbuhaler.
The budesonide dose in Pulmicort Turbuhaler, 200 μg expressed as metered dose, corresponds 
to the budesonide dose in Symbicort Turbuhaler, 160 μg expressed as delivered dose.
7.1.1
Non-investigational product for run-in and for post-bronchodilator lung 
function measurements
Additional study drug
Dosage form and strength
Manufacturer
Bricanyl Turbuhaler
0.5 mg 
Terbutaline sulphate powder for inhalation, 
0.5 mg terbutaline per inhalation, 100 doses
AstraZeneca
Bricanyl is a non-investigational medicinal product since it is used only ‘as needed’ during the 
run-in period and as a bronchodilator during the lung function measurements.
7.2
Dose and treatment regimens
Priming of the Turbuhaler
All Turbuhaler inhalers need to be primed before their initial use.  The priming should only be 
executed once per Turbuhaler (priming should not be repeated even if the inhaler is not used 
regularly).  The Investigator will prime the Bricanyl Turbuhaler at Visit 2 before attaching a 


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
50(70)
TUM and giving it to the patient.  At subsequent visits this procedure should be repeated for 
all Turbuhalers.  Instructions on how to use the Turbuhaler will be provided in local language 
to the patients.
The priming procedure:
Remove cover. Hold the inhaler in an upright position and turn the grip as far as possible in 
both directions. Perform this step twice.  The first dose can now be loaded.
Run-in period (Visit 2 to Visit 3)
At Visit 2 an empty Turbuhaler will be used for training purpose.  The training Turbuhaler 
should be kept at the study site and should not be taken home by the patients.  The training 
Turbuhaler will be labelled with an English label only.
Bricanyl Turbuhaler will be dispensed at Visit 2 and will be used as ‘as needed’ medication 
during the run-in period.  Bricanyl Turbuhaler will have blue grip and a white label with a 
blue bar.  Patients will be instructed to use Bricanyl Turbuhaler whenever needed to relieve 
asthma symptoms but not for prophylactic reasons.  In addition, those patients who are treated 
with low-dose ICS or LTRA at study entry will be asked to stop taking these medications at 
Visit 2.
Bricanyl Turbuhaler will also be used for the post-bronchodilator FEV1 and FVC 
measurements at Visits 2 to 6.
Treatment period (Visits 3 to 6)
At Visit 3 patients will be randomised to one of the 2 treatment groups with IP:
∀
Maintenance Placebo BID (twice daily) + Symbicort 160/4.5 μg ‘as needed’
∀
Maintenance Pulmicort 200 μg BID + terbutaline 0.4 mg ‘as needed’
At Visit 3 all randomised patients will receive maintenance study drug containing either 
Pulmicort or placebo as well as ‘as needed’ study drug, containing either Symbicort or 
terbutaline. 
To avoid confusion, the maintenance Turbuhalers and the Turbuhalers for ‘as needed’ 
treatment will have labels with different colours and the Turbuhaler grip will have different 
colours for the two different treatments.  The maintenance Turbuhaler will have brown grip 
and a white label with a yellow bar. During the treatment period the Turbuhaler for ’as 
needed’ treatment will have white grip and white label with a grey bar.  The patients will be 
instructed to take one inhalation from the inhaler with the brown grip every morning upon 
rising and every evening before going to bed.  Patients will further be instructed to take one 
inhalation from the inhaler with the white grip whenever needed to relieve asthma symptoms 
but not for prophylactic use.
The patient should take the first dose of maintenance IP (morning dose) at the study site.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
51(70)
During the treatment period, the patients are allowed to use up to 12 inhalations of the ‘as 
needed’ medication during one single day.  If a patient needs more than 12 inhalations of the 
‘as needed’ medication in one single day, the patient will be instructed to contact the 
investigator for reassessment of condition.
7.3
Labelling
Labels will be prepared in accordance with Good Manufacturing Practice (GMP) and local 
regulatory guidelines.  The labels will fulfil GMP Annex 13 requirements for labelling.  Label 
text will be translated into local language.
7.4
Storage
All study drugs should be kept in a secure place under appropriate storage conditions.  The 
investigational product label on the Turbuhaler specifies the appropriate storage.
7.5
Compliance
The administration of all study drugs (including investigational products) should be recorded 
in the appropriate sections of the eCRF.
Indication of study drug intake will be captured by TUM (see Section 5.1.6).
7.6
Accountability
The study drug provided for this study will be used only as directed in the study protocol.
The study site personnel will account for all study drugs dispensed to and returned from the 
patient.
Study site personnel will also account for all study drugs received at the site, unused study 
drugs and for appropriate destruction.  Certificates of delivery, destruction and return should 
be signed.
Study Drug is destroyed once there are satisfactory records of product accountability by the 
Monitor and the Study Leader has given authorisation.  The destruction of used and unused 
Study Drugs should preferably be done at the study site.  If destruction at the study site is not 
possible, the study site personnel should work with the Monitor to ensure Study Drugs are 
destroyed at a site approved by the local regulatory authority and in accordance with local 
regulations.  A Certificate of Destruction should be filed.
7.7
Concomitant and other treatments
7.7.1
Prohibited Medications
In order not to affect the reversibility test at Visit 2 and / or at Visit 3, patients should not have 
received the medications listed in Table 2 within the given time limits prior to the visit.
Asthma medication before study start is defined by inclusion criterion 4 not by Table 2.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
52(70)
Table 2
Medications which may affect the reversibility test at Visit 2 and/or at 
Visit 3
Not allowed before Visit 
Time limit prior to Visit
1.*
Inhaled disodium cromoglycate or inhaled nedocromil sodium
6 hours
2.* 
Inhaled short-acting anticholinergics
6 hours
3. 
Inhaled SABAs
6 hours
4.*
Inhaled long-acting β2-agonists (LABA)
formoterol
salmeterol
oladaterol
indacaterol
24 hours
24 hours
48 hours
72 hours
5.*
Oral β2-agonists as follows:
short-acting
depot
long-acting
6 hours
24 hours
48 hours
6.*
Transdermal β2-agonists
24 hours
7.*
Leukotriene receptor antagonist or 5-lipoxygenase inhibitors
48 hours
8.*
Xanthines:
once daily
twice daily
24 hours
12 hours
9.*
Inhaled anticholinergics:
acledinium
tiotropium
glycopyrrolate
24 hours
48 hours
48 hours
10.*
Medications containing ephedrine
24 hours
* Not allowed during run-in
Table 3
Medications Not allowed during the run-in period and while on IP
Not allowed during the run-in period and while on IP - For exceptions see section 7.7.2
1.
Oral, parenteral or rectal GCS
2.
Any ICS other than study medication
3.
Any β2-agonist other than the study medication
4.
Inhaled disodium cromoglycate or inhaled nedocromil sodium
5.
Leukotriene receptor antagonists or 5-lipoxygenase inhibitors
6.
Xanthines


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
53(70)
Not allowed during the run-in period and while on IP - For exceptions see section 7.7.2
7.
Inhaled anticholinergics
8.
Phosphodiesterase inhibitors
9.
Omalizumab or any other monoclonal or polyclonal therapy for any reason
10.
Beta-adrenergic blockers including eye-drops
11.
Systemic treatment with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazol and 
ritonavir)
7.7.2
Concomitant asthma treatment
Severe asthma exacerbation treatment: oral or parenteral GCS are allowed in case of a 
suspected severe asthma exacerbation. During a severe asthma exacerbation, treatment with 
the concomitant medications included in Number 2-7 (Table 3) is also allowed.
Other allowed asthma-related medications:
∀
Mucolytics and expectorants not containing bronchodilators
∀
Patients on allergen-specific immunotherapy (desensitization) must have been on a 
maintenance regimen for at least 4 weeks prior to Visit 2 and remain on a 
maintenance regimen during the study.  Patients should not begin allergen-specific 
immunotherapy during the course of the study
∀
Topical, nasal or ocular formulations of GCS, disodium chromoglycate and/or 
nedocromil sodium.
7.7.3
Other concomitant treatment
Medications other than that described above, which are considered necessary for the patient’s 
safety and well being, may be given at the discretion of the Investigator and recorded in the 
appropriate sections of the eCRF.
7.8
Post Study Access to Study Treatment
After discontinuation of IP patients will receive asthma medication prescribed according to 
the investigator’s judgment and local medical practice.
8.
STATISTICAL ANALYSES BY ASTRAZENECA
8.1
Statistical considerations
All personnel involved with the analysis of the study will remain blinded until database lock.
Analyses will be performed by AstraZeneca or its representatives.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
54(70)
A comprehensive Statistical Analysis Plan (SAP) will be prepared prior to first patient 
randomised and any subsequent amendments will be documented, with final amendments 
completed prior to unblinding of the data.
8.2
Sample size estimate
The study is powered to assess the primary objective of comparing Symbicort Turbuhaler ‘as-
needed’ versus Pulmicort Turbuhaler bid plus terbutaline Turbuhaler assuming that Symbicort 
Turbuhaler will be superior to Pulmicort Turbuhaler with regard to the annual severe asthma 
exacerbation rate.
Based on a subset of patients from the START study a retrospective estimation of severe 
exacerbation rate was 0.12 events per patient-year in the Pulmicort group (based on Poisson 
regression).  There was no sign of over-dispersion, hence the shape parameter is assumed to 
be 0.  The GOAL study (Bateman et al 2004) indicated a similar exacerbation rate in the 
steroid naïve sub-population 0.12 for patients treated with Fluticasone while for patients pre-
study treated with low-dose steroid the exacerbation rate was 0.17 for patients treated with 
Fluticasone.
The number of patients required for the analyses is estimated to be 4114 overall 
(2057/treatment group).  This was based on the following assumptions using a negative
binomial model (Keene ON et al 2007):
∀
alpha 5%
∀
power 90%
∀
exacerbation rate of 0.16 in the Pulmicort treatment group
∀
25% risk reduction in Symbicort vs Pulmicort
∀
no over-dispersion (shape parameter=0)
Based on these assumptions 3704 patients (1852 per arm) would be required.  Accounting for 
a 10% drop-out give a total sample size of 4114 patients (2057 per arm).
Sample size re-estimation:
Because of lacking phase II data on Symbicort ‘as-needed’ use in the target population there 
are uncertainties about the assumed exacerbation rates as well as the dispersion parameter.  To 
account for that uncertainty the overall exacerbation rate will be monitored during study in a 
blinded fashion and allow for an increase of the sample size by a maximum of 50% ie up to a 
total of 6171 patients.
The exacerbation rate and shape parameter will be estimated using the maximum likelihood 
approach as proposed by (Friede and Schmidli, 2010).  If results of the blinded reviews 
indicate that the projected power falls to below 85%, the sample size may be increased.  Since 


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
55(70)
this monitoring of the exacerbation rate will be performed in a blinded fashion, no adjustment 
for the type I error is needed.  The reviews will be based on pooled, blinded data and will not 
use any treatment information.  The blinding will be strictly maintained and not be affected by 
the reviews in any way.
Decision to change the primary objective from a superiority to non-inferiority hypothesis
In September 2016, the decision was made to change the primary objective to assess whether 
Symbicort Turbuhaler will be non-inferior to Pulmicort Turbuhaler with regard to the annual 
severe asthma exacerbation rate.  Assuming a 25% exacerbation risk reduction in Symbicort 
vs Pulmicort, 0.14 exacerbation rate and no overdispersion, a total sample size of 4114 will 
produce over 90% power to determine if Symbicort Turbuhaler is non-inferior to Pulmicort 
Turbuhaler with regard to the annual severe asthma exacerbation rate when the non-inferiority 
limit is set to 120% at the 5% (one-sided) significance level.
8.3
Definitions of analysis sets
8.3.1
Full analysis set
All patients randomised and receiving any investigational product will be included in the full 
analysis set, irrespective of their protocol adherence and continued participation in the study.  
Patients will be analysed according to their randomised treatment.
The efficacy analysis set will be based on the ‘full analysis set’ in line with the ICH E9 
guideline.
Analysis of primary and secondary variables will be based on data recorded up to the 
discontinuation of IP.  Sensitivity analyses will be provided including the data post 
discontinuation of IP.  Data for subjects who withdraw consent to participate in the study will 
be included up to the date of their study completion.
8.3.2
All patients analysis set
This analysis set comprises all patients screened for the study and will be used for reporting of 
disposition and enrolment failures.
8.3.3
Safety analysis set
All patients receiving any investigational product will be included in the safety analysis 
population.  Patients will be classified according to the treatment they actually received.  
Erroneously treated patients (e.g., those randomised to treatment A but actually given 
treatment B) will be accounted for in the actual treatment group.  The classification of patients 
will be finalised prior to database lock and documented in the Statistical Analysis Plan.  All 
safety summaries will be based on this analysis set.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
56(70)
8.4
Outcome measures for analyses
8.4.1
Derivation of efficacy variables
The primary analysis will include data from the randomisation visit until the subject 
terminates the use of IP.  Sensitivity analysis will include all data regardless of whether or not 
the subject terminated the use of IP.
8.4.1.1
Derivation of annual severe asthma exacerbation rate (primary variable)
The total number of severe asthma exacerbations will be calculated for each patient during the 
randomised treatment period according to the following principle:
For the production of summary statistics, the annual exacerbation rate per patient is calculated, 
and standardized using data from the double-blind treatment period according to the formula 
described below:
Annual Exacerbation Rate = Number of Exacerbations*365.25 / (Date of Visit6/EoT – Date of 
Randomisation (Visit 3) + 1)
8.4.1.2
Derivation of time to first severe asthma exacerbation
Time to first severe asthma exacerbation (see Section 8.5.2) will be calculated as the time 
from randomisation until the start date of the first severe asthma exacerbation ie:
Start Date of first severe asthma exacerbation – Date of Randomisation (Visit 3) +1
Patients not having any severe asthma exacerbation will be considered as censored at the date 
of their last visit or, for patients discontinuing IP, the day when it was decided that the patient 
should discontinue the IP.
Maximum follow-up time for a patient is approximately 52 weeks; defined as the time from 
randomisation to the date of Visit 6/EoT.  For a patient lost to follow-up, this will be defined 
as the time from randomisation to the time point after which an exacerbation could not be 
assessed.
8.4.1.3
Derivation of total inhaled steroid load and number of days with systemic GCS 
treatment
Total inhaled steroid load during the randomised treatment period will be calculated for each 
patient as the sum of the cumulative doses of maintenance ICS (budesonide), ‘as needed’ ICS 
as part of Symbicort (budesonide).  Data on IP will be recorded via the TUM.
The number of days with systemic GCS will be recorded via the appropriate CRF module.
8.4.1.4
Derivation of ‘as-needed’ use
‘As-needed’-use during the randomised treatment period will be calculated as the cumulative 
doses of ‘as-needed’ medication divided by the follow-up time (number of days).


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
57(70)
For Symbicort treatment arm ‘as needed’ will be Symbicort, while for the Pulmicort treatment 
arm ‘as needed’ will be terbutaline.
Change from baseline will be calculated for each patient, where baseline is defined as the ‘as-
needed’ use 10 days prior to randomisation during run-in.
‘As-needed’ use will be captured via the TUM device and measures the number of turns of the 
inhaler.
‘As-needed’ use (as recorded by the TUM) for the day- and night time period will be derived 
in the following way:
∀
Start of the daytime period is defined as the time when the patient takes their 
morning maintenance dose (between 04:00-11:59:59).  If the patient takes their 
morning maintenance dose before or after this time interval, or if there is no 
recorded morning maintenance dose the start of the daytime period will be set to the 
average of the recorded morning maintenance doses (between 04:00-11:59:59) 
across the trial for that patient.  The end of the daytime period will be set to the 
second prior to the start of the night-time period.
∀
Start of the night-time period is defined as the time when the patient takes their 
evening maintenance dose (between 18:00-23:59:59).  If the patient takes their 
evening maintenance dose before or after this time interval, or if there is no 
recorded evening maintenance dose the start of the night-time period will be set to 
the average of the recorded evening maintenance doses (between 18:00-23:59:59) 
across the trial for that patient.  The end of the night-time period will be set to the 
second prior to the start of the daytime period.
For analysis where full days are assessed they are a day followed by a night.
8.4.1.5
Derivation of controller-use days
‘Controller’-use during the randomised treatment period will be calculated as the cumulative 
days when any controller medication (containing ICS) was taken divided by the follow-up 
time (number of days).
For Symbicort treatment arm controller will be the ‘as needed’ use, while for the Pulmicort 
treatment arm this will be the maintenance use.  This will be derived from the TUM.
8.4.1.6
Derivation of percent ‘as-needed’-free days
An ‘as needed’-free day is defined as a day and night with no use of ‘as needed’ medication.  
Percent ‘as-needed’ free days will then be calculated as the number of days during the 
randomised treatment period with no record in the TUM device of ‘as-needed’ medication 
divided by the follow-up time (days).  Change from baseline will then be calculated for each 
patient, where baseline is defined as the ‘as-needed’ free days 10 days prior to randomisation 
during run-in.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
58(70)
8.4.1.7
Derivation of time to asthma related discontinuation
Study specific asthma related discontinuation criteria are given by:
∀
A severe asthma exacerbation with a duration for more than 3 weeks
∀
Three severe asthma exacerbations during 6 months
Time to discontinuation due to any of the specified asthma related events will be calculated as:
Date of discontinuation due to any of the specified asthma related events – Date of 
Randomisation (Visit 3) + 1
Patients not discontinuing the IP due to asthma related events will be considered as censored 
at the date of their last visit or, for patients discontinuing the IP, the day when it was decided 
that the patient should discontinue IP for whatever reason.
8.4.1.8
Derivation of lung function variables
Change from baseline (Visit 3) to Visits 4, 5 and 6 will be calculated for each patient for the 
following lung function variables:
∀
Pre- and post-bronchodilator FEV1 (L)
∀
Pre- and post-bronchodilator FEV1 % of predicted normal
∀
Pre- and post-bronchodilator FVC (L)
If the baseline measurement is missing, the last non-missing value before Visit 3 will be used 
as baseline instead.
Percent predicted of normal for pre- and post-bronchodilator FEV1 will be calculated 
according to Quanjer et al 2012.
8.4.2
Derivation of patient reported outcome variables
8.4.2.1
Derivation of ACQ-5
All 5 symptom questions are assessed on a 7-point scale from 0 to 6 where 0 represents good 
control and 6 represents poor control.  The overall score is the mean of the 5 items.  At least 4 
out of the 5 symptom items are needed to provide an ACQ score.
The minimal important difference (MID) has been defined as “the minimal change in score 
which clinicians consider to be clinically important and which would mandate, in the absence 
of troublesome side effects and undue cost, a change in the patient’s management”.  For the 
ACQ, it has been estimated to be a change in score of 0.5 (Juniper et al 2005 /2).
Baseline is defined as the ACQ-5 assessment at Visit 3.  In case of a missing value the Visit 2 
value will be used instead.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
59(70)
Based on MID the following variables will be derived:
∀
Patients improved (end of treatment – baseline) ≤-0.5
∀
Patients unchanged (end of treatment – baseline) within (-0.5; 0.5)
∀
Patients worsened (end of treatment – baseline) ≥0.5.
In addition, an asthma control variable based on ACQ-5 will be derived as:
∀
If the ACQ-5 value at the last visit (or last available value) is less than 0.75 the 
patient would be considered to be ‘in control’.  Otherwise ‘not in control’.
8.4.2.2
Standardised Asthma Quality of Life Questionnaire (AQLQ(S))
AQLQ(S) consists of 32 questions all assessed on a 7-point Likert scale from 1 to 7, with 
higher values indicating better health-related quality of life.  Domain scores as well as the 
overall scores are calculated from the unweighted arithmetic means of the individual question 
scores.  Differences between the follow-up visits and the baseline measure (Visit 3) for each 
of the domains and the overall scores will be calculated.  In addition the difference between 
the patients last measurements and baseline will be calculated.  For overall health-related 
quality of life and for each of the domains, the MID has been determined to be a change in 
score of 0.5 (Juniper et al 1994).
Baseline is defined as the assessment at Visit 3.  In case of a missing value the Visit 2 value 
will be used instead.
Based on MID the following variables will be derived:
∀
Patients improved (end of treatment – baseline) ≥0.5
∀
Patients unchanged (end of treatment – baseline) within (-0.5; 0.5)
∀
Patients worsened (end of treatment – baseline) ≤-0.5.
8.4.3
Derivation of safety variables
8.4.3.1
Vital signs
Change from baseline (Visit 2) to week 52 (Visit 6 / EoT) in pulse and blood pressure will be 
calculated for each patient.
8.4.3.2
Other significant adverse events (OAE)
During the evaluation of the AE data, an AstraZeneca medically qualified expert will review 
the list of AEs that were not reported as SAEs and DAEs.  Based on the expert’s judgement, 
significant adverse events of particular clinical importance may, after consultation with the 
Global Patient Safety Physician, be considered OAEs and reported as such in the Clinical 


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
60(70)
Study Report.  A similar review of vital signs data will be performed for identification of 
OAEs.
8.5
Methods for statistical analyses
All tests will be 2-sided and at 5% level of significance unless otherwise stated. No 
adjustment will be made for multiplicity.
For all repeated measures analyses, missing at random (MAR) will be assumed.
In addition the analyses described below, all variables will be summarised descriptively, as 
appropriate.
8.5.1
Analysis of the primary variable
The primary variable annual severe asthma exacerbation rate will be analysed by a negative 
binomial regression model.  The response variable in the model will be the number of severe 
asthma exacerbations over the treatment period.  The model will include treatment, pre-study 
treatment group and region as factors.  The logarithm of the follow-up time will be used as an 
offset variable.  From the negative binomial model the annual severe asthma exacerbation 
rates will be estimated and treatments effects will be expressed as the rate ratio along with its 
corresponding one-sided 95% non-inferiority interval (interval from point estimate to UCL) 
and two-sided 95% confidence interval.  The planned treatment comparison will be:
!
Symbicort vs Pulmicort (non-inferiority, primary objective)
Formally, the null and alternative hypothesis is:
H0: rate-ratio (Symbicort vs Pulmicort) ≥1.2
HA: rate-ratio (Symbicort vs Pulmicort) < 1.2
If the upper 95% 1-sided confidence limit of the relative risk ratio is < 1.2 then non-inferiority 
can be declared.
If the criteria for the alternative hypothesis is met then superiority of Symbicort vs Pulmicort 
in terms of annual severe asthma exacerbation will be assessed.
Formally, the null and alternative hypothesis for superiority testing is:
H0: rate-ratio (Symbicort vs Pulmicort) = 1
HA: rate-ratio (Symbicort vs Pulmicort) ≠1
8.5.2
Analysis of the secondary and other variables
For all secondary variables stated below Symbicort vs Pulmicort will be compared.  


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
61(70)
Exacerbations:  Time to first severe asthma exacerbation will be analysed by a Cox 
proportional hazards model with treatment, pre-study treatment group and region as factors.  
The hazard ratio and its corresponding 95% confidence interval will be estimated from the 
model.
Pre-dose FEV1:  The treatment effect for change from baseline (Visit 3) in pre-dose FEV1, 
will be estimated using a mixed model repeated measures (MMRM) analysis.  FEV1 data from 
visits 4, 5 and 6 will be included in the model, with terms for treatment, pre-study treatment 
group, region, visit and treatment*visit.  Baseline FEV1 (Visit 3) will be included as a 
covariate.  Visit will be fitted as a categorical variable, and the variance-covariance matrix 
will be assumed to be unstructured.  If the procedure does not converge then a compound 
symmetric variance-covariance matrix will be used instead.
This model will be used to give an overall assessment of the treatment effect as well as 95% 
confidence intervals.
Summary statistics will be presented for change from baseline across all the time points in the 
trial for pre- and post-dose FEV1 (L) and FVC, respectively by treatment.
Steroid load:  The total inhaled steroid load and the number of days with systemic GCS, 
respectively will be presented descriptively by treatment adjusted by the patients follow-up 
time.
‘As-needed’ use:  The change from baseline in ‘as-needed’ use will be analysed by analysis 
of covariance (ANCOVA) with treatment, pre-study treatment group and region as factors, 
and the ‘as-needed’ use value during run-in as a continuous covariate.  Least squared means 
by treatment and differences in least squared means (between treatments) along with 
corresponding 95% confidence intervals will be estimated.
More details of eg graphical presentations of pattern of use will be provided in the SAP.  It 
will include summaries of day time and night time use.
Percent ‘as needed’-free days:  The change from baseline in percent ‘as needed’-free days 
will all be analysed in the same way as ‘as-needed’ use described above.
Controller-use days: The percentage of controller use days will be analysed by analysis of 
covariance (ANCOVA) with treatment, pre-study treatment group and region as factors.  
Least squared means by treatment and differences in least squared means (between 
treatments) along with corresponding 95% confidence intervals will be estimated.
Discontinuation due to asthma related events:  Time to discontinuation due to asthma 
related events will be analysed by Cox proportional hazards model with treatment, pre-study 
treatment group and region as factors.  The hazard ratio and its corresponding 95% confidence 
interval will be estimated from the model.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
62(70)
PRO variables:  ACQ-5 and AQLQ(S) will be analysed in the same way as FEV1 using 
MMRM analysis.  In addition, change from baseline to the end of treatment will be analysed 
using analysis of covariance with treatment, pre-study treatment group and region as factors 
and baseline as a continuous variable.
Responder variables based on MID for ACQ-5 and AQLQ(S) will be analysed using a logistic 
regression model with treatment, region and pre-study treatment group as factors, and baseline 
as a covariate.  From the logistic regression model treatment effects will be estimated by odds-
ratio and its corresponding 95% confidence interval.
The responder variable ACQ-5 <0.75 at the end of treatment will be analyzed using a logistic 
regression model with treatment, region and pre-study treatment as factors, and baseline as a 
covariate.  From the logistic regression model treatment effects will be estimated by odds-
ratio and its corresponding 95% confidence interval.
Safety variables:  AEs will be summarized by means of count summaries.  AEs will be listed 
for each patient and summarized by System Organ Class and Preferred Term assigned to the 
event by MedDRA.  Other safety variables will be summarized as appropriate.  Further details 
will be provided in the SAP.
8.5.3
Subgroup analysis
The assessment of treatment effect will also be investigated in the 2 subgroups as defined by 
pre-study treatment to assess the consistency of the treatment effect.  This will be done for 
each of the primary and secondary variables by including a pre-study treatment*treatment 
interaction term in the models.  
8.5.4
Blinded sample size re-estimation
As described in Section 8.2, there will be a blinded analysis for the purpose of checking 
assumptions used in the estimation of sample size.  As such, no adjustment for Type I error is 
required.
8.5.5
Sensitivity analysis
Sensitivity analyses of the primary and key secondary variables will be carried out and will be 
specified in the SAP.
For the primary variable a sensitivity analysis will be performed including all data for patients 
who discontinue IP but remain in the study.
The primary analysis assumes that data are missing at random.  Different missing data 
assumptions will be explored if possible.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
63(70)
8.5.6
Exploratory analysis
8.5.7
Analyses related to exploratory objective
Descriptive reporting of the resource utilization data and health related quality of life data 
based on the EQ-5D-5L will be carried out in the CSR.  The data will be combined with 
economic data collected independently of the study to construct comparative health economic 
analyses between treatment groups.  The economic analyses and cost-effectiveness analyses 
that include data external to the study will be reported in a separate health economic report 
and will not be included in the CSR.
9.
STUDY AND DATA MANAGEMENT BY ASTRAZENECA
9.1
Training of study site personnel
Before the first patient is entered into the study, an AstraZeneca representative will review and 
discuss the requirements of the Clinical Study Protocol and related documents with the 
investigational staff and also train them in any study specific procedures and the WBDC, 
IVRS/IWRS and ePRO system(s) utilised.
The investigator and study site staff should preferably have prior experience in performing 
spirometry.
The Principal Investigator will ensure that appropriate training relevant to the study is given to 
all of these staff, and that any new information relevant to the performance of this study is 
forwarded to the staff involved.
The Principal Investigator will maintain a record of all individuals involved in the study 
(medical, nursing and other staff).
9.2
Monitoring of the study
During the study, an AstraZeneca representative will have regular contacts with the study site, 
including visits to:
∀
Provide information and support to the Investigator(s)
∀
Confirm that facilities remain acceptable
∀
Confirm that the investigational team is adhering to the protocol, that data are being 
accurately and timely recorded in the eCRFs and that study drug accountability 
checks are being performed
∀
Perform source data verification (a comparison of the data in the eCRFs with the 
patient’s medical records at the hospital or practice, and other records relevant to 
the study) including verification of informed consent of participating patients. This 
will require direct access to all original records for each patient (eg clinic charts).


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
64(70)
The AstraZeneca representative will be available between visits if the Investigator(s) or other 
staff at the site needs information and advice about the study conduct.
9.2.1
Source data
Refer to the Clinical Study Agreement for location of source data.
9.2.2
Study agreements
The Principal Investigator at each site should comply with all the terms, conditions, and 
obligations of the Clinical Study Agreement, or equivalent, for this study.  In the event of any 
inconsistency between this Clinical Study Protocol and the Clinical Study Agreement, the 
terms of Clinical Study Protocol shall prevail with respect to the conduct of the study and the 
treatment of patients and in all other respects, not relating to study conduct or treatment of 
patients, the terms of the Clinical Study Agreement shall prevail.
Agreements between AstraZeneca and the Principal Investigator should be in place before any 
study-related procedures can take place, or patients are enrolled.
9.2.3
Archiving of study documents
The Investigator follows the principles outlined in the Clinical Study Agreement (CSA).
9.3
Study timetable and end of study
The end of the study is defined as ‘the last visit of the last patient undergoing the study’.
The study is expected to start in Quarter 3 in 2014 and to end by Quarter 2 in 2017.
The study may be terminated at individual sites if the study procedures are not being 
performed according to GCP, or if recruitment is slow.  AstraZeneca may also terminate the 
entire study prematurely if concerns for safety arise within this study or in any other study 
with budesonide/formoterol/terbutaline.
9.4
Data management by Cognizant Data Management Centre 
Data management will be performed by Cognizant Data Management Centre staff according 
to the Data Management Plan.  Adverse events and medical/surgical history will be classified 
according to the terminology of the latest version of the Medical Dictionary for Regulatory 
Activities (MedDRA).  Medications will be classified according to the AstraZeneca Drug 
Dictionary.  Classification coding will be performed by the Medical Coding Team at the 
AstraZeneca Data Management Centre.
The data collected through third party sources will be obtained and reconciled against study 
data.
Data queries will be raised for inconsistent, impossible or missing data.  All entries to the 
study database will be available in an audit trail.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
65(70)
The data will be validated as defined in the Data Management Plan.  Quality control 
procedures will be applied to each stage of data handling to ensure that all data are reliable 
and have been processed correctly.  The Data Management Plan will also clarify the roles and 
responsibilities of the various functions and personnel involved in the data management 
process.
When all data have been coded, validated, signed and locked, clean file will be declared.  Any 
treatment revealing data may thereafter be added and the final database will be locked.
Serious Adverse Event (SAE) Reconciliation
SAE reconciliation reports are produced and reconciled with the Patient Safety database.
Management of external data
Data Management determines the format of the data to be received from external vendors and 
coordinates the flow of data to the clinical database.  Data Management will ensure that the 
data collection tool (e.g., ePRO, TUM and IVRS etc) will be tested and validated.  External 
data reconciliation will be done with the clinical database as applicable.
10.
ETHICAL AND REGULATORY REQUIREMENTS
10.1
Ethical conduct of the study
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH/Good Clinical Practice, applicable 
regulatory requirements and the AstraZeneca policy on Bioethics and Human Biological 
Samples.
10.2
Patient data protection
The Informed Consent Form will incorporate (or, in some cases, be accompanied by a 
separate document incorporating) wording that complies with relevant data protection and 
privacy legislation.
10.3
Ethics and regulatory review
An Ethics Committee should approve the final study protocol, including the final version of 
the Informed Consent Form and any other written information and/or materials to be provided 
to the patients.  The Investigator will ensure the distribution of these documents to the 
applicable Ethics Committee, and to the study site staff.
The opinion of the Ethics Committee should be given in writing. The Investigator should 
submit the written approval to AstraZeneca before enrolment of any patient into the study. 
The Ethics Committee should approve all advertising used to recruit patients for the study.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
66(70)
AstraZeneca should approve any modifications to the Informed Consent Form that are needed 
to meet local requirements.
If required by local regulations, the protocol should be re-approved by the Ethics Committee 
annually.
Before enrolment of any patient into the study, the final study protocol, including the final 
version of the Informed Consent Form, is approved by the national regulatory authority or a 
notification to the national regulatory authority is done, according to local regulations.
AstraZeneca will handle the distribution of any of these documents to the national regulatory 
authorities.
AstraZeneca will provide Regulatory Authorities, Ethics Committees and Principal 
Investigators with safety updates/reports according to local requirements.
In countries where applicable:  Each Principal Investigator is responsible for providing the 
Ethics Committees/IRB with reports of any serious and unexpected adverse drug reactions 
from any other study conducted with the investigational product.  AstraZeneca will provide 
this information to the Principal Investigator so that he/she can meet these reporting 
requirements.
10.4
Informed consent
The Principal Investigator(s) at each site will:
∀
Ensure each patient is given full and adequate oral and written information about 
the nature, purpose, possible risk and benefit of the study
∀
Ensure each patient is notified that they are free to discontinue from the study at any 
time
∀
Ensure that each patient is given the opportunity to ask questions and allowed time 
to consider the information provided
∀
Ensure each patient provides signed and dated informed consent before conducting 
any procedure specifically for the study
∀
Ensure the original, signed Informed Consent Form(s) is/are stored in the 
Investigator’s Study File
∀
Ensure a copy of the signed Informed Consent Form is given to the patient
∀
Ensure that any incentives for patients who participate in the study as well as any 
provisions for patients harmed as a consequence of study participation are described 
in the informed consent form that is approved by an Ethics Committee.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
67(70)
10.5
Changes to the protocol and informed consent form
Study procedures will not be changed without the mutual agreement of the International co-
ordinating Investigator and AstraZeneca.
If there are any substantial changes to the study protocol, then these changes will be 
documented in a study protocol amendment and where required in a new version of the study 
protocol (Revised Clinical Study Protocol).
The amendment is to be approved by the relevant Ethics Committee and if applicable, also the 
national regulatory authority approval, before implementation.  Local requirements are to be 
followed for revised protocols.
AstraZeneca will distribute any subsequent amendments and new versions of the protocol to 
each Principal Investigator(s). For distribution to Ethics Committee see Section 10.3.
If a protocol amendment requires a change to a site’s Informed Consent Form, AstraZeneca 
and the site’s Ethics Committee are to approve the revised Informed Consent Form before the 
revised form is used. 
If local regulations require, any administrative change will be communicated to or approved 
by each Ethics Committee.
10.6
Audits and inspections
Authorised representatives of AstraZeneca, a regulatory authority, or an Ethics Committee 
may perform audits or inspections at the site, including source data verification.  The purpose 
of an audit or inspection is to systematically and independently examine all study-related 
activities and documents, to determine whether these activities were conducted, and data were 
recorded, analysed, and accurately reported according to the protocol, Good Clinical Practice 
(GCP), guidelines of the International Conference on Harmonisation (ICH), and any 
applicable regulatory requirements.  The Investigator will contact AstraZeneca immediately if 
contacted by a regulatory agency about an inspection at the site.
11.
LIST OF REFERENCES
Ankerst et al 2003
Ankerst J, Persson G, Weibull E. Tolerability of high dose of budesonide/formoterol in a 
single inhaler in patients with asthma. Pulm Pharmacol Ther 2003;13(3):147-51.
Atienza et al 2013
Atienza T, Aquino T, Fernández M, Boonsawat W, Kawai M, Kudo T et al. 
Budesonide/formoterol maintenance and reliever therapy via Turbuhaler versus fixed-dose 
budesonide/formoterol plus terbutaline in patients with asthma: phase III study results. 
Respirology 2013 Feb;18(2):354-63.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
68(70)
Bateman et al 2004
Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels R, et al (2004) Can 
guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL 
(GOAL) Study. Am J Respir Crit Care Med, 170:836-44.
Chuchalin et al 2005
Chuchalin A, Kasl M, Bengtsson T, Nihlen U, Rosenborg J. Formoterol used as needed in 
patients with intermittent or mild persistent asthma. Respir Med 2005;99:461-70.
CHMP 2013
The European Agency for the Evaluation of Medicinal Products. Note for guidance on the 
clinical investigation of medicinal products in the treatment of asthma. CHMP/EWP/2922/01, 
Rev.1, June 2013.
Dusser et al 2007
Dusser D, Montani D, Chanez P, de Blic J, Delacourt C, Deschildre A et al. Mild asthma: an 
expert review on epidemiology, clinical characteristics and treatment recommendations. 
Allergy 2007;62:591-604.
Friede and Schmidli, 2010
Friede T and Schmidli H. Blinded sample size reestimation with negative binomial counts in 
superiority and non-inferiority trials. Methods Inf Med. 2010;49(6):618-24. doi: 
10.3414/ME09-02-0060. Epub 2010 Aug 5.
GINA 2012
Global Initiative for Asthma (GINA). Strategy for Asthma Management and Prevention 2012.
Haahtela et al 2006
Haahtela T, Tamminen K, Malmberg LP, Zetterstrom O, Karjalainen J, Yla-Outinen H, et al. 
Formoterol as needed with or without budesonide in patients with intermittent asthma and 
raised NO levels in exhaled air: A SOMA study. Eur Respir J 2006;28(4):748-55.
Horne et al 2006
Horne R. Compliance, adherence and concordance: Implications for asthma treatment. Chest 
2006;130(1 suppl):65-72.
Juniper et al 1992
Juniper EF, Guyatt GH, Epstein RS, Ferrie PJ, Jaeschke R, Hiller TK. Evaluation of 
impairment of health-related quality of life in asthma: development of a questionnaire for use 
in clinical trials. Thorax 1992;47:76-83. 
Juniper et al 1994
Juniper EF, Guyatt GH, Willan A, Griffith LE. Determining a minimal important change in a 
disease-specific quality of life questionnaire. J Clin Epidemiol 1994;47:81-7.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
69(70)
Juniper et al 1999
Juniper EF, Buist AS, Cox FM, Ferrie PJ, King DR. Validation of a standardized version of 
the Asthma Quality of Life Questionnaire. Chest 1999;115:1265-70. 
Juniper et al 2001
Juniper EF, O’Byrne PM, Roberts JN. Measuring asthma control in group studies: do we need 
airway calibre and rescue β2-agonist use? Respir Med 2001;95:319-23. 
Juniper et al 2005
Juniper EF, Svensson K, Mörk AC, Ståhl E. Modification of the asthma quality of life 
questionnaire (standardised) for patients 12 years and older. Health Qual Life Outcomes 
2005;3:58.
Juniper et al 2005 /2
Juniper EF, Svensson K, Mörk A-C, Ståhl E. Measurement properties and interpretation of 
three shortened versions of the asthma control questionnaire. Respiratory Medicine 2005; 
99:553-558.
Keene ON et al 2007
Keene ON, Jones MRK, Lane PW, Anderson J. Analysis of exacerbation rates in asthma and 
chronic obstructive pulmonary disease: example from the TRISTAN study. Pharmaceutical 
Statistics 2007;6:89–97.
Miller et al 2005
Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A et al. Standardisation 
of Spirometry. Eur Respir J 2005;26:319-38.
O'Byrne et al 2005
O'Byrne PM, Bisgaard H, Godard PP, Pistolesi M, Palmqvist M, Zhu Y et al. 
Budesonide/formoterol combination therapy as both maintenance and reliever medication in 
asthma. Am J Respir Crit Care Med. 2005;171:129-36.
Palmqvist et al 2001
Palmqvist M, Arvidsson P, Beckman O, Peterson S, Lötvall J. Onset of bronchodilation of 
budesonide/formoterol vs. salmeterol/fluticasone in single inhalers. Pulm Pharm Ther 
2001;14:29-34.
Papi et al 2007
Papi A, Canonica GW, Maestrelli P, Paggiaro P, Olivieri D, Pozzi E, et al; BEST Study 
Group. Rescue Use of Beclomethasone and Albuterol in a Single Inhaler for Mild Asthma. N 
Engl J Med 2007; 356:2040-2052.
Pauwels et al 2003
Pauwels RA, Pedersen S, Busse WW, Tan WC, ChenYZ, Ohlsson SV et al, on behalf of the 
START Investigators Group. Early intervention with budesonide in mild persistent asthma: a 
randomised, double-blind trial. Lancet 2003;361:1071-6.


Revised Clinical Study Protocol
Drug Substance Budesonide/formoterol  
Study Code D589SC00003
Edition Number 4
Date 12 October 2016
70(70)
Pauwels et al 2003b
Pauwels RA, Sears M, Campell M, Villasante C, Huang S, Lindh A. Formoterol as relief 
medication in asthma: a worldwide safety and effectiveness trial. Eur Resp J 2003;22:787-94.
Quanjer et al 2012
Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, et al. Multi-ethnic reference 
values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur 
Respir J 2012;40(6):1324-43.
Rabe et al 2004
Rabe KF, Adachi M, Lai CK, Soriano JB, Vermeire PA, Weiss KB et al. Worldwide severity 
and control of asthma in children and adults: the global asthma insights and reality surveys. J 
Allergy Clin Immunol 2004;114(1):40-7.
Rabe et al 2006
Rabe KF, Atienza T, Magyar P, Larsson P, Jorup C, Lalloo UG. Effect of budesonide in 
combination with formoterol for reliever therapy in asthma exacerbations: a randomised 
controlled, double-blind study. Lancet 2006;368:744-53.
Reddel et al 2009
Reddel HK, Taylor DR, Bateman ED et al. An Official American Thoracic Society/European 
Respiratory Society Statement: Asthma Control and Exacerbations. Am J Respir Crit Care 
2009; 180: 59–99.
Scicchitano et al 2004
Scicchitano R, Aalbers R, Ukena D, Manjra A, Fouquert L, Centanni S et al. Efficacy and 
safety of budesonide/formoterol single inhaler therapy vs a higher dose of budesonide in 
moderate to severe asthma. Curr Med Res Opin 2004;20:1403-18.
Sears and Lötvall 2005
Sears MR, Lötvall J. Past, present and future - β2 adrenoceptor agonists in asthma 
management. Resp Med 2005;99(2):152-70.
Tattersfield et al 2001
Tattersfield AE, Löfdahl CG, Postma DS, Eivindson A, Schreurs AG, Rasidakis A, et al. 
Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised 
trial. Lancet 2001;357:257-61.
The EuroQol Group 1990
EuroQol Group. EuroQol – a new facility for the measurement of health related quality of life.  
Health Policy 1990;16:199-208
Vogelmeier et al 2005
Vogelmeier C, D'Urzo A, Pauwels R, Merino JM, Jaspal M, Boutet S et al. 
Budesonide/formoterol maintenance and reliever therapy: an effective asthma treatment 
option? Eur Respir J 2005;26:819-28.


Clinical Study Protocol Appendix B
Drug Substance
budesonide/formoterol
Study Code
D589SC00003
Edition Number
1
Date
17 June 2014
Appendix B
Additional Safety Information


Clinical Study Protocol Appendix B
Drug Substance budesonide/formoterol
Study Code D589SC00003
Edition Number 1
Date 17 June 2014
2(3)
FURTHER GUIDANCE ON THE DEFINITION OF A SERIOUS 
ADVERSE EVENT (SAE)
Life threatening
‘Life-threatening’ means that the subject was at immediate risk of death from the AE as it 
occurred or it is suspected that use or continued use of the product would result in the 
subject’s death.  ‘Life-threatening’ does not mean that had an AE occurred in a more severe 
form it might have caused death (eg, hepatitis that resolved without hepatic failure).
Hospitalisation
Outpatient treatment in an emergency room is not in itself a serious AE, although the reasons 
for it may be (eg, bronchospasm, laryngeal oedema).  Hospital admissions and/or surgical 
operations planned before or during a study are not considered AEs if the illness or disease 
existed before the subject was enrolled in the study, provided that it did not deteriorate in an 
unexpected way during the study.
Important medical event or medical intervention
Medical and scientific judgement should be exercised in deciding whether a case is serious in 
situations where important medical events may not be immediately life threatening or result in 
death, hospitalisation, disability or incapacity but may jeopardize the subject or may require 
medical intervention to prevent one or more outcomes listed in the definition of serious.  
These should usually be considered as serious.
Simply stopping the suspect drug does not mean that it is an important medical event; medical 
judgement must be used.
Examples of such events are:
!
Angioedema not severe enough to require intubation but requiring iv hydrocortisone 
treatment
!
Hepatotoxicity caused by paracetamol (acetaminophen) overdose requiring 
treatment with N-acetylcysteine
!
Intensive treatment in an emergency room or at home for allergic bronchospasm
!
Blood dyscrasias (eg, neutropenia or anaemia requiring blood transfusion, etc) or 
convulsions that do not result in hospitalisation
!
Development of drug dependency or drug abuse.


Clinical Study Protocol Appendix B
Drug Substance budesonide/formoterol
Study Code D589SC00003
Edition Number 1
Date 17 June 2014
3(3)
A GUIDE TO INTERPRETING THE CAUSALITY QUESTION
The following factors should be considered when deciding if there is a “reasonable 
possibility” that an AE may have been caused by the drug.
!
Time Course.  Exposure to suspect drug.  Has the subject actually received the 
suspect drug?  Did the AE occur in a reasonable temporal relationship to the 
administration of the suspect drug?
!
Consistency with known drug profile.  Was the AE consistent with the previous 
knowledge of the suspect drug (pharmacology and toxicology) or drugs of the same 
pharmacological class? OR could the AE be anticipated from its pharmacological 
properties?
!
Dechallenge experience.  Did the AE resolve or improve on stopping or reducing 
the dose of the suspect drug?
!
No alternative cause.  The AE cannot be reasonably explained by another aetiology 
such as the underlying disease, other drugs, other host or environmental factors.
!
Rechallenge experience.  Did the AE reoccur if the suspected drug was reintroduced 
after having been stopped? AstraZeneca would not normally recommend or support 
a rechallenge.
!
Laboratory tests.  A specific laboratory investigation (if performed) has confirmed 
the relationship?
A “reasonable possibility” could be considered to exist for an AE where one or more of these 
factors exist.
In contrast, there would not be a “reasonable possibility” of causality if none of the above 
criteria apply or where there is evidence of exposure and a reasonable time course but any 
dechallenge (if performed) is negative or ambiguous or there is another more likely cause of 
the AE.
In difficult cases, other factors could be considered such as:
!
Is this a recognised feature of overdose of the drug?
!
Is there a known mechanism?
Ambiguous cases should be considered as being a “reasonable possibility” of a causal 
relationship unless further evidence becomes available to refute this.  Causal relationship in 
cases where the disease under study has deteriorated due to lack of effect should be classified 
as no reasonable possibility.


Clinical Study Protocol Appendix C
Drug Substance
budesonide/formoterol
Study Code
D589SC00003
Edition Number
1
Date
17 June 2014
Appendix C
Asthma Control Questionnaire (5-item version)



6<03720621/<02',),('-81(

1257+$0(5,&$1(1*/,6+

$67+0$&21752/
48(67,211$,5($&4
6<03720621/<









42/7(&+12/2*,(6/7'







)RUIXUWKHULQIRUPDWLRQ

(OL]DEHWK-XQLSHU0&6306F
3URIHVVRU
0DUFXVH)LHOGV
%RVKDP:HVW6XVVH[
321$(QJODQG
7HOHSKRQH
)D[
(PDLOMXQLSHU#TROWHFKFRXN
:HEKWWSZZZTROWHFKFRXN



7KH$VWKPD&RQWURO4XHVWLRQQDLUH$&4LVFRS\ULJKWHGDQGDOOULJKWVDUH
UHVHUYHG1RSDUWRIWKLVTXHVWLRQQDLUHPD\EHVROGPRGLILHGRU
UHSURGXFHGLQDQ\IRUPZLWKRXWWKHH[SUHVVSHUPLVVLRQRI(OL]DEHWK
-XQLSHURQEHKDOIRI42/7HFKQRORJLHV/LPLWHG

'(&(0%(5





6<03720621/<02',),('-81(

1257+$0(5,&$1(1*/,6+
$67+0$&21752/48(67,211$,5(




3DJHRI


3OHDVHDQVZHUTXHVWLRQV

&LUFOHWKHQXPEHURIWKHUHVSRQVHWKDWEHVWGHVFULEHVKRZ\RXKDYHEHHQGXULQJWKHSDVWZHHN


2QDYHUDJHGXULQJWKHSDVWZHHN
KRZRIWHQZHUH\RXZRNHQE\\RXU
DVWKPDGXULQJWKHQLJKW"

1HYHU

+DUGO\HYHU

$IHZWLPHV

6HYHUDOWLPHV

0DQ\WLPHV

$JUHDWPDQ\WLPHV

8QDEOHWRVOHHSEHFDXVHRIDVWKPD



2QDYHUDJHGXULQJWKHSDVWZHHN
KRZEDGZHUH\RXUDVWKPDV\PSWRPV
ZKHQ\RXZRNHXSLQWKHPRUQLQJ"

1RV\PSWRPV

9HU\PLOGV\PSWRPV

0LOGV\PSWRPV

0RGHUDWHV\PSWRPV

4XLWHVHYHUHV\PSWRPV

6HYHUHV\PSWRPV

9HU\VHYHUHV\PSWRPV



,QJHQHUDOGXULQJWKHSDVWZHHNKRZ
OLPLWHGZHUH\RXLQ\RXUDFWLYLWLHV
EHFDXVHRI\RXUDVWKPD"

1RWOLPLWHGDWDOO

9HU\VOLJKWO\OLPLWHG

6OLJKWO\OLPLWHG

0RGHUDWHO\OLPLWHG

9HU\OLPLWHG

([WUHPHO\OLPLWHG

7RWDOO\OLPLWHG



,QJHQHUDOGXULQJWKHSDVWZHHNKRZ
PXFKVKRUWQHVVRIEUHDWKGLG\RX
H[SHULHQFHEHFDXVHRI\RXUDVWKPD"

1RQH

$YHU\OLWWOH

$OLWWOH

$PRGHUDWHDPRXQW

4XLWHDORW

$JUHDWGHDO

$YHU\JUHDWGHDO


,QJHQHUDOGXULQJWKHSDVWZHHNKRZ
PXFKRIWKHWLPHGLG\RXZKHH]H"


1RWDWDOO

+DUGO\DQ\RIWKHWLPH

$OLWWOHRIWKHWLPH

$PRGHUDWHDPRXQWRIWKHWLPH

$ORWRIWKHWLPH

0RVWRIWKHWLPH

$OOWKHWLPH





Clinical Study Protocol Appendix D
Drug Substance
budesonide/formoterol
Study Code
D589SC00003
Edition Number
1
Date
17 June 2014
Appendix D
Asthma Quality of Life Questionnaire with Standardised Activities 
(AQLQ(S)) self administered ≥ 12 years of age




















Clinical Study Protocol Appendix E
Drug Substance
Budesonide/formoterol
Study Code
D589SC00003
Edition Number
2
Date
17 August 2015
Appendix E
Inhaled Glucocorticosteroids Equivalence Table


Clinical Study Protocol Appendix E
Drug Substance Budesonide/formoterol
Study Code D589SC00003
Edition Number 2
Date 17 August 2015
2(2)
INHALED GLUCOCORTICOSTEROIDS EQUIVALENCE TABLE
Asthma Therapy
Total Daily Dose (μg/day)
Inhaled Glucocorticosteroid
Low
Beclomethasone dipropionate (non HFA propellant)
200 to 500
Beclomethasone HFA*
100 to 250 
Ciclesonide 
80 to 160
Triamcinolone acetonide 
400 to 1000
Flunisolide 
500 to 1000
Fluticasone propionate 
100 to 250
Budesonide 
200 to 400
Mometasone furoate 
200 
* For some HFA beclomethasone products dose ranges related to non-HFA beclomethasone 
may apply depending on formulation.  Formulations with smaller particles size have greater 
lung disposition.  The manufacturer’s information should be reviewed in order to determine 
patient’s eligibility with regard to ICS daily dose.


Clinical Study Protocol Appendix F
Drug Substance
budesonide/formoterol
Study Code
D589SC00003
Edition Number
1
Date
17 June 2014
Appendix F
EQ-5D-5L Health Questionnaire



8.(QJOLVKY(XUR4RO*URXS(4'LVDWUDGHPDUNRIWKH(XUR4RO*URXS














+HDOWK4XHVWLRQQDLUH


(QJOLVKYHUVLRQIRUWKH8.








8.(QJOLVKY(XUR4RO*URXS(4'LVDWUDGHPDUNRIWKH(XUR4RO*URXS


8QGHUHDFKKHDGLQJSOHDVHWLFNWKH21(ER[WKDWEHVWGHVFULEHV\RXUKHDOWK72'$<

02%,/,7<
,KDYHQRSUREOHPVLQZDONLQJDERXW




,KDYHVOLJKWSUREOHPVLQZDONLQJDERXW




,KDYHPRGHUDWHSUREOHPVLQZDONLQJDERXW



,KDYHVHYHUHSUREOHPVLQZDONLQJDERXW




,DPXQDEOHWRZDONDERXW







6(/)&$5(
,KDYHQRSUREOHPVZDVKLQJRUGUHVVLQJP\VHOI



,KDYHVOLJKWSUREOHPVZDVKLQJRUGUHVVLQJP\VHOI 


,KDYHPRGHUDWHSUREOHPVZDVKLQJRUGUHVVLQJP\VHOI


,KDYHVHYHUHSUREOHPVZDVKLQJRUGUHVVLQJP\VHOI


,DPXQDEOHWRZDVKRUGUHVVP\VHOI





868$/$&7,9,7,(6HJZRUNVWXG\KRXVHZRUN
IDPLO\RUOHLVXUHDFWLYLWLHV
,KDYHQRSUREOHPVGRLQJP\XVXDODFWLYLWLHV



,KDYHVOLJKWSUREOHPVGRLQJP\XVXDODFWLYLWLHV



,KDYHPRGHUDWHSUREOHPVGRLQJP\XVXDODFWLYLWLHV


,KDYHVHYHUHSUREOHPVGRLQJP\XVXDODFWLYLWLHV



,DPXQDEOHWRGRP\XVXDODFWLYLWLHV





3$,1',6&20)257
,KDYHQRSDLQRUGLVFRPIRUW 





,KDYHVOLJKWSDLQRUGLVFRPIRUW





,KDYHPRGHUDWHSDLQRUGLVFRPIRUW 




,KDYHVHYHUHSDLQRUGLVFRPIRUW





,KDYHH[WUHPHSDLQRUGLVFRPIRUW






$1;,(7<'(35(66,21
,DPQRWDQ[LRXVRUGHSUHVVHG





,DPVOLJKWO\DQ[LRXVRUGHSUHVVHG 




,DPPRGHUDWHO\DQ[LRXVRUGHSUHVVHG




,DPVHYHUHO\DQ[LRXVRUGHSUHVVHG




,DPH[WUHPHO\DQ[LRXVRUGHSUHVVHG








8.(QJOLVKY(XUR4RO*URXS(4'LVDWUDGHPDUNRIWKH(XUR4RO*URXS



x :HZRXOGOLNHWRNQRZKRZJRRGRUEDG\RXUKHDOWKLV
72'$<
x 7KLVVFDOHLVQXPEHUHGIURPWR
x PHDQVWKHEHVWKHDOWK\RXFDQLPDJLQH
PHDQVWKHZRUVWKHDOWK\RXFDQLPDJLQH
x 0DUNDQ;RQWKHVFDOHWRLQGLFDWHKRZ\RXUKHDOWKLV72'$<
x 1RZSOHDVHZULWHWKHQXPEHU\RXPDUNHGRQWKHVFDOHLQWKH
ER[EHORZ




<285+($/7+72'$< 
































7KHEHVWKHDOWK
\RXFDQLPDJLQH
7KHZRUVWKHDOWK
\RXFDQLPDJLQH

SAP_000.pdf: 
Statistical Analysis Plan
Study Code
D589SC00003
Edition Number
2
Date 
06 September 2017
A 52-week, double-blind, randomised, multi-centre, phase III, parallel-
group study in patients 12 years and older with asthma, evaluating the 
efficacy and safety of Symbicort (budesonide/formoterol) Turbuhaler
160/4.5 μg ‘as needed’ compared with Pulmicort (budesonide) Turbuhaler
  200 μg twice daily plus terbutaline Turbuhaler 0.4 mg ‘as needed’






Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
4
TABLE OF CONTENTS
PAGE
TITLE PAGE.......................................................................................................1
SIGNATURE OF STUDY STATISTICIAN........................................................2
SIGNATURE OF GLOBAL PRODUCT STATISTICIAN ..................................3
TABLE OF CONTENTS.....................................................................................4
1.
STUDY DETAILS.............................................................................................10
1.1
Study objectives................................................................................................. 10
1.1.1
Primary objective...............................................................................................10
1.1.2
Secondary objectives..........................................................................................10
1.1.3
Safety objective..................................................................................................11
1.1.4
Exploratory objectives .......................................................................................11
1.2
Study design ...................................................................................................... 11
1.3
Number of patients.............................................................................................16
2.
ANALYSIS SETS .............................................................................................17
2.1
Definition of analysis sets .................................................................................. 17
2.1.1
All patients analysis set......................................................................................17
2.1.2
Full analysis set..................................................................................................17
2.1.3
Safety analysis set..............................................................................................17
2.2
Violations and deviations ................................................................................... 18
3.
PRIMARY AND SECONDARY VARIABLES.................................................20
3.1
General considerations for outcome variables..................................................... 20
3.1.1
Definition of baseline.........................................................................................20
3.1.2
Definition of end of treatment ............................................................................21
3.1.3
Valid maintenance and ‘as needed’ medication turns..........................................21
3.1.4
Timing of maintenance and ‘as needed’ medication and allocation to 
day/night period.................................................................................................22
3.1.5
Visit windowing.................................................................................................23
3.1.6
Definition of completing treatment, completing study, randomised 
treatment period and study period ......................................................................23
3.1.7
Definition of last dose of IP................................................................................ 23
3.2
Primary variable.................................................................................................23
3.3
Demography and patient characteristics .............................................................23
3.3.1
Demography, weight and height.........................................................................23
3.3.2
Medical, asthma and smoking history.................................................................24
3.4
Efficacy variables............................................................................................... 24


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
5
3.4.1
Severe asthma exacerbation ...............................................................................24
3.4.1.1
Definition of severe asthma exacerbation ...........................................................24
3.4.1.2
Number of severe asthma exacerbations, and annual severe exacerbation 
rate.....................................................................................................................25
3.4.1.3
Time to first severe asthma exacerbation............................................................25
3.4.2
Medication-based outcomes ............................................................................... 26
3.4.2.1
‘As needed’ medication use................................................................................26
3.4.2.2
Daily end-points.................................................................................................26
3.4.3
Total inhaled steroid load...................................................................................27
3.4.4
Number of days with systemic GCS treatment due to asthma .............................28
3.4.5
Time to study specific asthma-related discontinuation........................................ 28
3.4.6
Lung function variables......................................................................................28
3.4.7
Patient reported outcomes ..................................................................................29
3.4.7.1
Asthma Control Questionnaire – 5-item Version (ACQ-5) .................................29
3.4.7.2
Asthma Quality of Life Questionnaire – Standardised version (AQLQ(S)).........29
3.5
Safety variables..................................................................................................30
3.5.1
Vital signs.......................................................................................................... 30
3.5.2
Physical examination .........................................................................................31
3.5.3
Adverse events (including Serious Adverse Events)...........................................31
3.5.3.1
Collection of AEs and SAEs .............................................................................. 31
3.5.3.2
Definition of adverse event leading to discontinuation of investigational 
product (DAE) ...................................................................................................32
3.5.3.3
AEs representing potential β2 agonist effects and AEs representing 
potential ICS effects...........................................................................................32
3.5.3.4
Other significant adverse events (OAEs)............................................................32
3.5.3.5
Adverse events data handling.............................................................................32
3.6
Other variables................................................................................................... 33
3.6.1
Concomitant medications...................................................................................33
3.6.2
Discontinuation of investigational product .........................................................33
3.6.3
Compliance of study maintenance medication....................................................34
4.
ANALYSIS METHODS....................................................................................35
4.1
General principles.............................................................................................. 35
4.2
Analysis methods...............................................................................................36
4.2.1
Patient disposition..............................................................................................36
4.2.2
Demography data and patient characteristics ...................................................... 36
4.2.3
Concomitant medication ....................................................................................36
4.2.4
Exposure to study treatment ............................................................................... 37
4.2.5
Primary efficacy analysis ...................................................................................37
4.2.5.1
Annual severe asthma exacerbation rate.............................................................37
4.2.6
Secondary efficacy analyses...............................................................................38
4.2.6.1
Severe asthma exacerbation variables.................................................................38
4.2.6.2
Discontinuation of IP due to study specific asthma related events....................... 39
4.2.6.3
Discontinuation of IP and study withdrawal .......................................................39


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
6
4.2.6.4
Steroid load........................................................................................................39
4.2.6.5
Lung function measurements..............................................................................39
4.2.6.6
Patient reported outcomes ..................................................................................40
4.2.6.7
‘As needed’ use, Percent ‘as needed’ free days, and Percent controller use 
days ...................................................................................................................41
4.2.6.8
Maintenance medication compliance..................................................................42
4.2.7
Safety analysis ...................................................................................................42
4.2.8
Supportive, subgroup, and sensitivity analyses...................................................43
4.2.8.1
Supportive analysis ............................................................................................43
4.2.8.2
Subgroup analysis..............................................................................................43
4.2.8.3
Sensitivity analysis.............................................................................................46
4.2.9
Exploratory analysis...........................................................................................47
4.2.9.1
Health care resource utilization and work and school absence ............................48
4.2.9.2
EQ-5D-5L..........................................................................................................49
5.
CHANGES OF ANALYSIS FROM PROTOCOL .............................................50
6.
REFERENCES ..................................................................................................51
7.
APPENDIX 1: METHOD FOR CALCULATING PREDICTED 
NORMAL FEV1................................................................................................ 53
7.1
Equation for calculating predicted multi-ethnic predicted normal FEV1.............53
7.2
Lookup table for final term.................................................................................54
8.
APPENDIX 2: IDENTIFCATION OF ADDITIONAL STEROID 
MEDICATIONS FOR ANALYSES ..................................................................58
9.
APPENDIX 3: POTENTIAL CLASS EFFECTS Β2-AGONISTS AND 
POTENTIAL ICS EFFECTS ............................................................................. 60
10.
APPENDIX 4: VISIT WINDOWING................................................................63
11.
APPENDIX 5: COMPUTING EQ-5D-5L CROSSWALK INDEX 
VALUES WITH SAS USING THE UNITED KINGDOM (UK) VALUE 
SET.................................................................................................................... 67
LIST OF TABLES
Table 1 Study assessments .................................................................................................13
Table 2 Subgroups .............................................................................................................45
Table 3 Acceptable timing range for each visit...................................................................63
LIST OF FIGURES
Figure 1 Study flow chart...................................................................................................12


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
7
LIST OF ABBREVIATIONS
Abbreviation or 
special term
Explanation
ACQ-5
Asthma Control Questionnaire 5-item version
AE
Adverse event
ANCOVA
Analysis of covariance
AQLQ(S)
Asthma Quality of Life Questionnaire (Standardised version)
ATC
Anatomical therapeutic chemical
BID
Twice daily
CI
Confidence Interval
CSR 
Clinical study report
DAE
Adverse event leading to discontinuation
DBL
Database lock
(e)CRF
(Electronic) Case report form
EoT
End of Treatment
ERS
European Respiratory Society
EU
European Union
EQ-5D-5L
EuroQol Quality of Life Questionnaire
FAS
Full analysis set
FCS
Fully conditional specification
FDA
(United States) Food and Drug Administration
FEV1
Forced expiratory volume in one second
FVC
Forced vital capacity
GCS
Glucocorticosteroid
GINA
Global Initiative for Asthma
GLI
Global Lung Function Initiative
HRU
Healthcare resource use
ICH 
International Conference on Harmonisation (of Technical Requirements for 
Registration of Pharmaceuticals for Human Use)
ICS
Inhaled (gluco)corticosteroid
IP
Investigational product
IVRS/IWRS
Interactive voice/web response system
J2R
Jump to reference
LTRA
Leukotriene antagonist


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
8
Abbreviation or 
special term
Explanation
MAR 
Missing at random
NICE
National institute of clinical excellence
MID
Minimal important difference
MMRM
Mixed model repeated measures
MNAR
Missing not at random
OAE
Other significant adverse event
PN
Predicted normal
PT
Preferred Term
QA
Quality Assurance
SABA
Short-acting β-agonist
SAE
Serious adverse event
SAP 
Statistical analysis plan
SC
Subject characteristics
SOC
System Organ Class
TUM
Turbuhaler usage monitor
VAS
Visual Analogue Scale
vs
versus


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
9
AMENDMENT HISTORY
Date
Brief description of change
6 February 2017
AstraZeneca comments incorporated. The primary objective revised from 
demonstrating superiority to demonstrating non-inferiority (to be consistent 
with revised primary objective per study protocol Amendment 4)
8 March 2017 
Decision to exclude 12 randomised patients from SYGMA2 study site 5702 
(Poland) will be excluded from the Full Analysis set and the Safety analysis set
due to significant deviations. The deviations were mainly relating to 
unavailability, discrepancies and poor quality of source data which question the 
validity and integrity of the trial data generated from this site. 
8 March 2017
Decision to exclude all randomised patients in France in the non-inferiority test 
due to Ethic Committee rejection of CSP amendment 4 in France.
24th March 2017
Version 1.2 
Updated by Phastar pre-BDR1
13th April 2017
Decision to exclude 1 randomised patient from study site 2612 (Germany) that 
was randomised in error from Full Analysis Set and Safety Analysis Set. Due 
to the subject age, local ethics committee decided data of this patient cannot be 
used for the analysis. 
1st June 2017
Version 1.3
Updated by Phastar after BDR1 CRM
21st June 2017
Version 1.4
Updated by Phastar after AZ review
18th August 2017
Version 1.5
Updated by Phastar post BDR2 for AZ review
6th September 2017
Version 2
Updated by Phastar after AZ review.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
10
1.
STUDY DETAILS 
1.1
Study objectives 
1.1.1
Primary objective 
Primary Objective:
Outcome Measure:
To demonstrate that Symbicort Turbuhaler
160/4.5 μg ‘as needed’ is non-inferior to 
Pulmicort Turbuhaler 200 μg twice daily plus 
terbutaline Turbuhaler 0.4 mg ‘as needed’.
Annual severe asthma exacerbation rate
1.1.2
Secondary objectives 
Secondary Objective:
Outcome Measure:
To estimate the difference in efficacy
between Symbicort Turbuhaler 160/4.5 μg
‘as needed’ and Pulmicort Turbuhaler 200 μg 
twice daily plus terbutaline Turbuhaler 0.4
mg ‘as needed’
Secondary variables
•Time to first severe asthma exacerbation
• Change from baseline in pre-dose forced 
expiratory volume in one second (FEV1)
•Time to study specific asthma related 
discontinuation
• Change from baseline in ‘as needed’
use
• Change from baseline in percent of 
‘as needed’-free days
•Percentage of controller use days
• Change from baseline in Asthma Control 
Questionnaire—5-item version (ACQ-5)
score
• Change from baseline in Asthma Quality
of Life Questionnaire Standardised Version 
(AQLQ(S)) score


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
11
1.1.3
Safety objective 
Safety Objective:
Outcome Measure:
To compare the safety of Symbicort
Turbuhaler 160/4.5 μg ‘as needed’
with that of Pulmicort Turbuhaler 200 μg
twice daily plus terbutaline Turbuhaler 0.4 mg
‘as needed’
Adverse events (nature, incidence and
severity); pulse, blood pressure and 
physical examination
1.1.4
Exploratory objectives 
Exploratory Objective:
Outcome Measure:
To compare health care resource utilization,
indirect resource use and health related status 
associated with hospital admissions, health 
care visits and days lost from work/ school 
between treatment arms
• EuroQol five dimensional 5-level
questionnaire (EQ-5D-5L)
• Health Economics Questionnaire for 
resource utilisation
1.2
Study design 
This is a 52-week, double-blind, randomised, multi-centre, parallel-group, phase III study in 
patients 12 years and older with asthma, evaluating the efficacy and safety of Symbicort 
(budesonide/formoterol) Turbuhaler 160/4.5 μg ‘as needed’ compared with Pulmicort 
(budesonide) Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg ‘as needed’.
Figure 1 illustrates the flow of patients through the study from enrolment to study end. 
Patients will begin with a 2 to 4 week run-in period to collect baseline data and to ensure that 
they are in need of Global Initiative for Asthma (GINA) step 2 treatment. Patients will then be 
randomised to one of the two treatment groups described above and continue on the study for
52 weeks. Patients will receive a final follow-up telephone call to check for adverse events
(AE).
Table 1 describes the assessments to be performed at each of the scheduled study visits.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
12
Figure 1 Study flow chart 


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
13
Table 1 Study assessments
Enrolment
Run-in
Rando-
misation
Treatment
2 wks
Follow-up
Visit
1
2
3
Phone call
4
Phone call
5
Phone call
6/ EoTa,b
Phone call
Week
-2 to -4
0
8
17
25
34
42
52
54
Visit window
(days)
0-7 days 
before Visit 2
14-28 days 
before Visit 3
±7
±7
±7
±7
±7
±7
±3
Written Informed 
consent
X
Allocation of 
enrolment code
X
Demography
X
Inclusion/exclusion 
criteria
X
X
X
Medical/surgical 
history
X
Asthma history 
(including 
exacerbation 
history)
X
Smoking history
X
ACQ-5, AQLQ(S)
X
X
X
X
X
Health Care 
resource utilisation 
questionnaire, EQ-
5D-5L
X
X
X
X
SAE/AEsc
Xc
Xc
X
X
X
X
X
Weight and height
X
Xd
Physical 
examination
X
X


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
14
Enrolment
Run-in
Rando-
misation
Treatment
2 wks
Follow-up
Visit
1
2
3
Phone call
4
Phone call
5
Phone call
6/ EoTa,b
Phone call
Week
-2 to -4
0
8
17
25
34
42
52
54
Visit window
(days)
0-7 days 
before Visit 2
14-28 days 
before Visit 3
±7
±7
±7
±7
±7
±7
±3
Vital signs (pulse 
and blood pressure)
X
X
Pregnancy test (if 
applicable)
X
Adjustment of 
current asthma 
medication
X
Patient training in 
how to use 
Turbuhaler 
(inhalation 
technique) and 
TUM
X
Bricanyl for run-in
(dispense/return)
d
r
Randomisation
X
Lung function 
(FEV1, FVC pre-
and post-Bricanyl 
administration)
X
X
X
X
X
Reversibility teste
X
Xe
Collection of severe 
asthma 
b i
Xf
Xf
Xf
Xf
Xf
Xf
Concomitant 
medications
X
X
X
X
X


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
15
Enrolment
Run-in
Rando-
misation
Treatment
2 wks
Follow-up
Visit
1
2
3
Phone call
4
Phone call
5
Phone call
6/ EoTa,b
Phone call
Week
-2 to -4
0
8
17
25
34
42
52
54
Visit window
(days)
0-7 days 
before Visit 2
14-28 days 
before Visit 3
±7
±7
±7
±7
±7
±7
±3
Investigational 
product 
(dispense/return/ 
check)
d
d/r/c
d/r/c
r/c
a
After discontinuation of IP (ie before Visit 6) patients will be followed up according to the original visit schedule including site
visits and phone contacts. Only Severe asthma exacerbations, AEs and concomitant medications will be collected. If it is not
possible for the patient to visit the study site, the visit(s) may be performed via phone. See CSP Section 4.4.
b
EoT is end of treatment visit.
c
Serious adverse events will be collected from time of signing Informed consent. Adverse events will be collected from Visit 2.
d
Height only for adolescents.
e
Reversibility test will be performed at Visit 2. The test can be repeated at Visit 3 in case the patients fail to meet inclusion criterion
no. 6 at Visit 2. See CSP Section 3.1 for inclusion criteria.
f
Severe asthma exacerbations will be collected from Visit 3 through the entire study.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
16
1.3
Number of patients
The study was originally powered to assess the primary objective of comparing Symbicort 
Turbuhaler ‘as needed’ versus Pulmicort Turbuhaler bid plus terbutaline Turbuhaler assuming that 
Symbicort Turbuhaler will be superior to Pulmicort Turbuhaler with regard to the annual severe 
asthma exacerbation rate. The change in the primary objective to non-inferiority did not lead to a
sample size increase as Symbicort was assumed to be more efficacious (25%) than maintenance 
Pulmicort (in the same way that in the sample size calculation for the superiority test).
The severe exacerbation rate in the Pulmicort treatment group was estimated based on a 
retrospective Poisson regression on data from a subset of patients (in the Pulmicort group) from the 
START study (Pauwels et al 2003), as well as patients from the GOAL study treated with 
Fluticasone (Bateman et al 2004). The exacerbation rate in the START study was estimated to be 
0.12 events per patient-year in the Pulmicort group. In the GOAL study, where patients were 
treated with Fluticasone, the exacerbation rate for the steroid naïve sub- population was also 0.12 
events per patient-year, while for patients who had previously received low-dose steroid treatment, 
the exacerbation rate was 0.17 events per patient-year. Based on this information, the exacerbation 
rate for patients in the present study was estimated to be 0.16 events per patient-year. There was no 
evidence of over-dispersion in either study, so the shape parameter was assumed to be 0.
Calculations for estimating sample size were based on the following assumptions using a negative 
binomial model (Keene et al 2007):
!
alpha 5%
!
power 90%
!
exacerbation rate of 0.16 in the Pulmicort treatment group
!
25% risk reduction in Symbicort vs Pulmicort
!
no over-dispersion (shape parameter=0)
Based on these assumptions 3704 patients (1852 per arm) would be required. Accounting for a 
10% drop-out gives a total sample size of 4114 patients (2057 per arm).
Sample size re-estimation: The relative lack of phase II data on Symbicort ‘as needed’ use in the 
target population means that there is a high degree of uncertainty about the assumed exacerbation 
rates and the dispersion parameter. To account for that uncertainty, the overall exacerbation rate 
will be monitored during the study. The maximum likelihood approach as proposed by Friede and 
Schmidli, 2010 will be used to estimate the exacerbation rate and shape parameter. The reviews 
will be based on pooled, blinded data and will not use any treatment information. If the results of 
the blinded reviews indicate that the projected power falls to below 85%, the sample size may be 
increased. An allowance will be made for an increase in the sample size by a maximum of 50% i.e. 
up to a total of 6171 patients. Since this monitoring of the exacerbation rate will be performed in a 
blinded fashion, no adjustment for the type I error is needed.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
17
Decision to change the primary objective from a superiority to non-inferiority hypothesis
In protocol amendment 4, the decision was made to change the primary objective to assess whether
Symbicort Turbuhaler will be non-inferior to Pulmicort Turbuhaler with regard to the annual
severe asthma exacerbation rate. Assuming a 25% exacerbation risk reduction in Symbicort vs 
Pulmicort, 0.14 overall exacerbation rate and no overdispersion, a total sample size of 4114 will
provide at least 90% power to determine if Symbicort Turbuhaler is non-inferior to Pulmicort
Turbuhaler with regard to the annual severe asthma exacerbation rate when the non-inferiority
limit is set to 20% at the 5% (one-sided) significance level.
2.
ANALYSIS SETS 
2.1
Definition of analysis sets 
2.1.1
All patients analysis set
This analysis set comprises all patients screened for the study and will be used for reporting of 
disposition and enrolment failures.
2.1.2
Full analysis set
All patients randomised and receiving any investigational product will be included in the full 
analysis set, irrespective of their protocol adherence and continued participation in the study. 
Patients will be analysed according to their randomised treatment.
Twelve randomised patients from study site 5702 (Poland) will be excluded from the Full analysis 
set due to significant deviations. The deviations were mainly relating to unavailability, 
discrepancies and poor quality of source data which question the validity and integrity of the trial 
data generated from this site. Data listings for these 12 patients will be provided in Appendix 12.2 
in the Clinical Study Report (CSR).
One randomised patient from study site 2612 (Germany) was randomised in error. Due to the 
subject age, local ethics committee decided data of this patient cannot be used for the analysis. 
Data listings for this 1 patient will be provided in Appendix 12.2 in the CSR.   
The efficacy analysis will be based on the full analysis set (FAS) in line with the ICH E9 guideline.
Analysis of primary and secondary efficacy variables will be based on data recorded up to the 
discontinuation of investigational product (IP). Sensitivity analysis will be provided including the 
data post discontinuation of IP for the primary efficacy variable. Data for patients who withdraw 
consent to participate in the study will be included up to the date of their study discontinuation.
2.1.3
Safety analysis set
All patients receiving any investigational product will be included in the safety analysis 
population. 


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
18
The following exclusions from the Safety Analysis Set will be made:
!
12 randomised patients from study site 5702 (Poland) will be excluded from the Safety 
analysis set due to significant deviations. The deviations were mainly relating to 
unavailability, discrepancies and poor quality of source data which question the validity 
and integrity of the trial data generated from this site. Data listings for these 12 patients 
will be provided in Appendix 12.2 in the CSR.
!
1 randomised patient from study site 2612 (Germany) was randomised in error. Due to 
the subject age, local ethics committee decided data of this patient cannot be used for the 
analysis. Data listings for this 1 patient will be provided in Appendix 12.2 in the CSR. 
Patients will be classified according to the treatment they actually received. If a patient has a 
wrong kit id, then the treatment they actually received will be determined based on which 
treatment was used the most. All patients should be allocated to the safety analysis set prior to 
Database Lock (DBL), however the classification of treatment received, will not be determined 
until after unblinding, and will be documented. All safety summaries will be based on this analysis 
set.
2.2
Violations and deviations 
Important protocol deviations will be listed and summarised by randomised treatment group and 
discussed in the CSR. None of the deviations will lead to any patients being excluded from any of 
the analysis sets described in Section 2.1. A per-protocol analysis excluding patients with 
important protocol deviation is not planned.
The following violations of inclusion criteria will be considered important protocol deviations 
when the study physician or principle investigator make a decision to discontinue the patient from 
the study due to one or more of these criteria. They will be identified using the CRIT and TERM 
Electronic Case Report Form (eCRF) modules.  
!
Diagnosis of asthma according to GINA criteria based on symptoms with a documented 
history of at least 6 months prior to Visit 1.
!
Patients who are in need of GINA (2012) step 2 treatment:
∀
uncontrolled on inhaled short-acting bronchodilator(s) ‘as needed’ (SABA and/or 
short acting anticholinergic agent) as judged by the investigator for the last 30 days 
before Visit 2, or
∀
controlled on mono-maintenance therapy - with low stable dose Inhaled (gluco) 
coriticosteroid (ICS) (≤ 400 μg budesonide per day or corresponding dose of other 
ICS) (see Appendix E for conversion) or LTRA - in addition to 'as needed' use of 
inhaled short-acting bronchodilator(s) (SABA and/or short acting anticholinergic 
agent), as judged by the investigator for the last 30 days prior to Visit 2


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
19
Based on lung function tests (see Section 5.1.2 of CSP) at Visit 2, patients pre-treated with
∀
an inhaled short acting bronchodilator only should have pre-bronchodilator FEV1 
≥60 % of predicted normal (PN) and post-bronchodilator FEV1 ≥ 80 % PN 
according to the European Respiratory Society (ERS) guidelines (Quanjer et al 
2012)
∀
low dose ICS or LTRA medication in addition to inhaled short-acting
∀
bronchodilator(s) should have pre-bronchodilator FEV1 ≥80 % PN according to the 
ERS guidelines
!
Reversible airway obstruction according to a reversibility test (see Section 5.1.2.2 of 
CSP) performed at Visit 2 defined as an increase in FEV1 ≥12% and ≥200 ml relative 
to baseline, after inhalation of 1 mg Bricanyl Turbuhaler. 
The following violations of exclusion criteria will be considered important protocol deviations. 
They will be identified using the CRIT eCRF module only  
!
Medical history of life- threatening asthma including intubation and intensive care unit 
admission
!
Any significant disease or disorder which, in the opinion of the investigator, may either 
put the patient at risk because of participation in the study, or may influence the results 
of the study, or the patient’s ability to participate in the study
See the CSP Sections 3.1 and 3.2 for full definitions of the inclusion and exclusion criteria.
In addition to the programmatic determination of the deviations above, monitoring notes or 
summaries will be reviewed to determine any important post entry protocol deviations that are not 
identifiable via programming, and to check that those identified via programming are correctly 
classified. The final classification will be made prior to database lock. There are two types of 
non-programmable important protocol deviation:
!
Cases with severe noncompliance with study protocol potentially affecting primary 
endpoint as identified by study team physician during medical monitoring
!
Wrong allocation of Kit I.D – Patient received IP from different treatment arm than 
assigned via Interactive Voice Response System (IVRS)
Due to treatment blinding, it will not be possible to identify if the wrong kit is different from the 
randomised treatment until after DBL. 
All randomised patients who failed any inclusion/exclusion criteria will be listed along with details 
of the failed criteria. This information will also be summarised in terms of the number (%) of 
patient failing any of the inclusion/exclusion criteria and will be based on the FAS.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
20
3.
PRIMARY AND SECONDARY VARIABLES
3.1
General considerations for outcome variables 
3.1.1
Definition of baseline 
Unless otherwise specified, the following general principles apply for determining the baseline for 
variables collected during scheduled visits.
Efficacy data collected at scheduled visits
The baseline value for variables collected during scheduled visits will be defined in two separate 
ways depending on how the data for that variable was collected. 
Baseline for variables that included visit information will be defined as the last measured value 
prior to first dose of IP on Visit 3 only. I.e., no data from earlier visits will be used if Visit 3 data 
are missing. Baseline will be calculated using this method for the following variables:
!
Lung function variables:
∀
FEV1 (L), pre- and post-bronchodilator*
∀
FEV1 % of predicted normal, pre- and post-bronchodilator*
∀
Forced vital capacity (FVC) (L), pre- and post-bronchodilator*
!
Exploratory variables:
∀
EQ-5D-5L index score
∀
EQ-5D-5L Visual analogue scale (VAS) score
*Note baseline post-bronchodilator values are calculated post-bricanyl, but before first dose of IP
Efficacy data with no visit information
Baseline for variables that did not include visit information will be defined as the last measured 
value prior to first dose of IP. Baseline will be calculated using this method for the following
variables:
!
Patient-reported outcomes:
∀
ACQ-5 score
∀
AQLQ(S) score


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
21
‘As needed’medication
‘As needed’ medication at baseline is Bricanyl Turbuhaler 0.5 mg. Its baseline value is defined as 
average number of uses per day in the 10 days prior to randomisation during the run-in period. 
Each day for baseline will begin at 07:00 and end at 06:59:59 on the following day. It includes the 
last measurement taken on the morning of randomisation (prior to the first dose of maintenance 
medication, or 06:59:59, whichever is earlier).
‘As needed’-freedays
‘As needed’-free days at baseline is defined as number of days with no ‘as needed’ medication use 
(a day and a night) in the 10 days prior to randomisation during the run-in period. Percent 
‘as needed’-free days at baseline will then be calculated as the number of ‘as needed’-free days at 
baseline divided by 10 multiplied by 100. Each day is calculated in the same way as the day 
calculation for ‘as needed’ medication in the previous section.
Safety data(vitalsigns and physical examination) and height
The baseline for vital signs (pulse rate and blood pressure), physical examination measurements
and height is defined as the value recorded at Visit 2. If the Visit 2 record is missing, then baseline 
will be left as missing.
3.1.2
Definition of end of treatment
Patient-reported outcomes and exploratory variables
For patient reported outcomes end of treatment is defined as Visit 6, or the last visit for which the
score of interest was calculated being the patient on study drug.
Safety data(vitalsigns and physical examination)
End of Treatment is the last scheduled visit prior to or on the day of last dose of IP.
3.1.3
Valid maintenance and ‘as needed’ medication turns 
The use of maintenance and ‘as needed’ medication will be captured via the Turbuhaler Usage 
Monitor (TUM). This device is fitted to the Turbuhaler and records the timing of each turn of the 
inhaler.
A two-stage approach will be applied to exclude turns from the TUM which are considered 
impossible. 
(i)
Turns taking place within ≤1 second of the previous turn will be excluded from analysis. 
(ii)
The number of turns per day per inhaler will be limited to the number of available doses 
in each inhaler (120 as needed, 200 maintenance).


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
22
3.1.4
Timing of maintenance and ‘as needed’ medication and allocation to day/night 
period
‘As needed’ use (as recorded by the TUM) will be allocated to daytime and night-time periods in 
the following way:
!
Start of the daytime period is defined as the time when the patient takes their morning 
maintenance dose (between 04:00-11:59:59). If the patient takes their morning 
maintenance dose before or after this time interval, or if there is no recorded morning 
maintenance dose the start of the daytime period will be set to the average of the 
recorded morning maintenance doses (between 04:00-11:59:59) across the trial for that 
patient. The end of the daytime period will be set one second prior to the start of the 
night-time period.
!
Start of the night-time period is defined as the time when the patient takes their evening 
maintenance dose (between 18:00-23:59:59). If the patient takes their evening 
maintenance dose before or after this time interval, or if there is no recorded evening 
maintenance dose the start of the night-time period will be set to the average of the 
recorded evening maintenance doses (between 18:00-23:59:59) across the trial for that 
patient. The end of the night-time period will be set one second prior to the start of the 
daytime period. The final night-time period will occur on the day prior to last dose of IP, 
as no evening maintenance dose is expected on the final day.
For analyses where full days are assessed they are defined as a day followed by a night, with the 
start of each day defined by the start of the daytime period described above.
On the treatment start day, only those ‘as needed’ medications taken after the first maintenance 
medication will be considered to be in the randomised treatment period. Any ‘as needed’ 
medication taken prior to the first maintenance will be considered ‘run-in’ medication.  If there is 
no maintenance medication on the treatment start day, then 12pm will be considered the end of 
run-in and start of the randomised treatment period.  However, only those run-in ‘as needed’ 
medications recorded up to 06:59:59 will be included in baseline calculations.
On the treatment end day, only medications up to 18:59:59 will be included in the randomised
treatment period.  
For the purpose of calculating steroid load, maintenance medication will be assigned to each study 
day using the same windows as defined for the ‘as needed’ medication above.  
For the purpose of study treatment compliance, and exposure, maintenance medication will be 
assigned to each study day if it occurs anytime from 4am on that study day until 3:59:59am on the 
following day (or 18:59:59 for the treatment end day). On treatment start day the start of the 
window will be 00:00:00 instead of 04:00:00.
A low proportion of data collected via the TUM were found to have a timestamp outside of the
run-in period or the randomised treatment period. These records are excluded from all analysis.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
23
3.1.5
Visit windowing
Details of the method for programming visit windowing is shown in Appendix 4: Visit windowing.
3.1.6
Definition of completing treatment, completing study, randomised treatment 
period and study period
A patient will be considered as completing treatment if they have not discontinued IP prematurely 
according to the DOSDISC (dose discontinuation) module. If a patient does not have a record in 
DOSDISC, then a patient will be considered as completing treatment if they received treatment for 
>=51 weeks. A patient will be considered as completing the study if they have not discontinued the 
study prematurely according to the TERM (Termination) module. The randomised treatment 
period is defined as the time from first dose of IP until the last dose of IP inclusive. The study 
period is the period from Visit 3 (Randomisation visit) up to Visit 6 (Week 52). A patients’
follow-up time on randomised treatment is defined as the time from first dose of IP until the last 
dose of IP inclusive. A patients’ follow-up time on study period is defined as the time from first 
dose of IP until the patient completes or pre-maturely withdraws from the study.
3.1.7
Definition of last dose of IP
The last dose of IP is defined as the date of discontinuation of IP if available, otherwise end date of 
dosing if available, otherwise date of termination if available.
3.2
Primary variable 
The primary efficacy variable is the annual severe asthma exacerbation rate.
The definition of the event “a severe asthma exacerbation” and method for deriving the primary
variable is given in Section 3.4.1 below.
3.3
Demography and patient characteristics
3.3.1
Demography, weight and height 
The following demographic data will be collected at enrolment (Visit 1):
!
Date of birth
!
Gender
!
Race/ethnicity population 
Race and ethnicity information will be collected as per AstraZeneca standards using the standard 
race and ethnicity categories stipulated in FDA guidance. However, for the purposes of calculating 
multi-ethnic predicted normal values of FEV1 (Quanjer et al 2012), a different categorisation of 
ethnicity is required. This variable is collected as “ethnic population” in the subject characteristics
(SC) module of the eCRF. See Section 3.4.6 for further details on the calculation of predicted 
normal FEV1.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
24
Weight in kilogram and height in cm will be measured at Visit 2. For adolescents (i.e. patients 
aged less than 18 years at the date of informed consent), height will additionally be measured at 
Visit 6. Body mass index [weight in kg / (height in m)2] will be categorised as (<25, ≥25 and <30 
and ≥ 30).
Age at date of informed consent (in terms of whole years lived) will be derived using date of birth 
and date of Visit 1. It will be categorised (≥12 and <18, ≥18 and <50, ≥50 and <65, ≥65 and <85 
and ≥ 85 years of age).
Region will be defined as follows:
!
Latin America: Argentina, Brazil, Chile, Colombia, Mexico, Peru
!
EU: Bulgaria, Czech Republic, France, Germany, Hungary, Romania, Slovakia, Spain, 
Sweden
!
East Asia: Philippines, South Korea, Thailand, Vietnam
!
Rest of World: Australia, New Zealand, Russia, Saudi Arabia, South Africa, Ukraine
For the purpose of calculating predicted normal lung function variables (FEV1, and FVC), age at
the day the test is conducted will be calculated to the nearest 0.01 years. Height for adults will be 
assumed to be constant throughout the course of the study. Further details on the use of 
demographic variables for calculating predicted normal FEV1 is given in Section 3.4.6.
3.3.2
Medical, asthma and smoking history 
Medical (incl. surgical), asthma (incl. exacerbations) and smoking history (smoking status and the 
number of pack years consumption) are recorded during the enrolment visit (Visit 1).
3.4
Efficacy variables
3.4.1
Severe asthma exacerbation
3.4.1.1
Definition of severe asthma exacerbation 
A severe exacerbation is defined as a deterioration of asthma requiring any of the following:
!
use of systemic glucocorticosteroids (GCS) for at least 3 days1,
!
inpatient hospitalization, or
!
emergency room visit2 due to asthma that required systemic steroids3. 
1 An injection of depot corticosteroids due to asthma worsening is considered equivalent 
to at least 3 days of systemic corticosteroids. If duration of GCS is missing, a 
conservative approach is taken and duration is assumed >= 3 days.
2 Emergency room visit or other urgent unscheduled health care visit


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
25
3 Systemic steroids used for any length of time. 
For severe exacerbations, the start date is defined as the first day of hospitalisation/emergency 
room treatment or the first day of systemic (i.e. not inhaled) GCS treatment.  The end date is 
defined as the last day of hospitalisation/emergency room treatment or the last day of systemic 
GCS treatment (according to prescription). If the same asthma exacerbation includes both 
hospitalisation/emergency room treatment and systemic GCS treatment, the start and end dates are 
the first and last day that either of the criteria was fulfilled. No date imputation is done for severe 
exacerbations with missing end dates.
Additional hospitalisations/emergency room treatments and systemic GCS treatments occurring 
during a severe asthma exacerbation should not be regarded as a new exacerbation. 
For a severe asthma exacerbation to be counted as a separate event, it must be preceded by at least 
seven days in which no criteria for severe exacerbations are fulfilled.
3.4.1.2
Number of severe asthma exacerbations, and annual severe exacerbation rate
The total number of severe asthma exacerbations during the 52-week double-blind randomised 
treatment period will be calculated for each patient, following the method set out in Section 
3.4.1.1.
In order to account for varying lengths of follow-up time (due to early study drug discontinuation, 
early study withdrawal, patient lost to follow-up, or minor differences of the timing of Visit 6), the
annual severe exacerbation rate will be presented for the purposes of summary statistics. This will 
be calculated on a study level as follows:
Study level: Annual severe exacerbation rate = ∑Number of severe exacerbations * 365.25/
∑ (Date of last dose of IP – date of first dose of IP +1)
For patients who discontinue randomised study drug pre-maturely but remain in the study, severe 
asthma exacerbation data will continue to be collected according to the original visit schedule for 
sensitivity analysis described in Section 4.2.8.3. Number of severe asthma exacerbations will also 
include those data collected after discontinuation of randomised study drug, and up to last visit 
(Visit 6). The annual severe exacerbation rate for the purpose of sensitivity analysis will be 
calculated on a study level as follows:
Study level: Annual severe exacerbation rate (SA) = ∑Number of exacerbations captured during 
study period * 365.25/ ∑(Date of latest follow-up prior to or on Visit 6 – date of first dose of IP + 
1)
3.4.1.3
Time to first severe asthma exacerbation 
The start and end dates of each severe exacerbation will be recorded in the eCRF at the site visits. 
From the start date and the date of first dose of IP, the time to first severe asthma exacerbation will 
be calculated as below:


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
26
Time to first severe asthma exacerbation = Start date of first severe asthma exacerbation – Date of 
first dose of IP + 1
Patients not having any severe asthma exacerbation will be considered censored at their latest 
follow-up date whilst in the randomised treatment period. The latest follow-up date is defined as 
the last dose of IP as defined in Section 3.1.7.
Time to censoring in days is then calculated as follows:
Time to censoring = Date of latest follow-up date on IP – Date of first dose of IP + 1
3.4.2
Medication-based outcomes 
3.4.2.1
‘As needed’ medication use 
‘As needed’ use during the randomised treatment period will be calculated as the cumulative doses 
of ‘as needed’ medication divided by the number of days in the randomised treatment period 
(Date last dose of IP – date of first dose of IP +1).
For Symbicort treatment arm ‘as needed’ will be Symbicort, while for the Pulmicort treatment arm
‘as needed’ will be terbutaline.
Measurement of ‘as needed’ use is defined as the number of turns of the inhaler captured via the
TUM device. Change from baseline will be calculated for each patient, where baseline is defined 
as in Section 3.1.1. As TUM device is capturing the number of turns by day and by night, 
‘as needed’ medication use will be defined by day, by night and by total as defined in 
Section 3.1.4. 
For total and night mean number of ‘as needed’ medication uses, the final day of treatment will not 
be included as part of the randomised treatment period.  This is due to the patients returning their 
TUM prior to the final evening.
3.4.2.2
Daily end-points 
‘As needed’-freedays
An ‘as needed’-free day is defined as a day and night with no use of ‘as needed’ medication. 
Percent ‘as needed’-free days will then be calculated as the number of days during the randomised 
treatment period with no record in the TUM device of ‘as needed’ medication divided by the 
number of days in the randomised treatment period multiplied by 100. Change from baseline will 
then be calculated for each patient, where baseline is defined as in Section 3.1.1.
ICS controller use days
A controller use day is defined as a day and night with any use of controller medication.
Controller use during the randomised treatment period will be calculated as the cumulative days
when any controller medication (containing ICS) was taken divided by the number of days in the 
randomised treatment period (date of last dose of IP – date of first dose of IP + 1).


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
27
For the Symbicort treatment arm, the controller will be the ‘as needed’ medication. For the 
Pulmicort treatment arm, the controller will be the maintenance medication. Plus, any additional 
prescribed inhaled corticosteroid for asthma exacerbations which is applicable for all treatment 
arms. Controller use will be derived using data collected from the TUM device, additional 
prescribed inhaled corticosteroids are collected via the MED and EXACASI modules of the eCRF
and defined in Appendix 2.
The denominator for percentage of ‘as needed’ free-days and controller use days will be 10 days 
for the baseline period (‘as needed’-free days only), and (date of last dose of IP – date of first dose 
of IP + 1) for the randomised treatment period.
3.4.3
Total inhaled steroid load
Data on additional inhaled and systemic steroids prescribed for exacerbations will be collected via 
the EXACASI eCRF module. Additional ICS and systemic GCS prescribed on the day of IP 
discontinuation for an asthma exacerbation will be considered as during the randomised treatment 
period, otherwise they will be considered as during the follow-up period (See Appendix 2).
Total inhaled steroid load (total ICS dose) during the randomised treatment period will be 
calculated for each patient as the sum of the cumulative doses of maintenance ICS (budesonide), 
‘as needed’ ICS as part of Symbicort (budesonide), and additional prescribed inhaled 
corticosteroids of any type. 
For calculation purposes, the dose for ‘as needed’ ICS part of the Symbicort arm will be the 
delivered dose, 160μg.  The maintenance ICS part of the Pulmicort arm will be converted from the 
metered dose, 200μg to 160μg, the delivered dose. For additional ICS, the dose, as recorded by the 
investigators in the eCRF will be used. 
Doses which are not in μg should be converted to μg before being summed. For additional 
prescribed inhaled corticosteroids, 100% compliance will be assumed. Data on IP usage will be 
recorded via the TUM, while additional prescribed inhaled corticosteroids will be collected via the 
appropriate CRF module, and can be identified as per the table in Appendix 2.
To account for differences in the length of follow-up, a time-standardised variable, mean daily ICS 
dose, will be estimated. This will be calculated separately for each patient, and then averaged over 
all patients:
Total ICS: Mean daily ICS dose = Total ICS dose / (Date of last dose of IP – Date of first dose of 
IP + 1)
The mean daily ICS dose will also be calculated separately for IP [maintenance ICS (budesonide), 
‘as needed’ ICS as part of Symbicort (budesonide)] and additionally prescribed ICS. Also, 
additionally prescribed ICS will be separated by individual ICS medications. 
IP: Mean daily ICS dose = Total ICS dose (IP only) / (Date of last dose of IP – Date of first dose 
of IP + 1)


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
28
Additional ICS: Mean daily ICS dose = Total ICS dose (Additional only) / (Date of last dose of IP
– Date of first dose of IP + 1)
If there is no available end date for additional ICS, then it will be assumed that it continues until IP 
discontinuation.
3.4.4
Number of days with systemic GCS treatment due to asthma
The number of days with systemic GCS due to asthma will be recorded via the eCRF MED 
module (identified as per the table in Appendix 2) at each visit. The total number of days recorded 
during the randomised treatment period will then be calculated for each patient.
3.4.5
Time to study specific asthma-related discontinuation
The following criteria should lead to discontinuation from the IP due to asthma related events:
!
A severe asthma exacerbation with duration for more than 3 weeks
!
Three severe asthma exacerbations during 6 months
For patients who experience one of these events, time to discontinuation of IP due to any of the 
specified asthma related events will be calculated as:
Time to discontinuation of IP due to any asthma-related event = Date of study drug termination 
due to any asthma-related event – Date of first dose of IP+ 1
Time to censoring will be defined as for censoring for asthma exacerbations (see Section 3.4.1.3), 
with the exception that only patients who discontinued the study for any reason other than one of 
the pre-defined asthma-related events will be censored as of their discontinuation date.
3.4.6
Lung function variables 
The following lung function measurements will be calculated at Visits 2, 3 (baseline), 4, 5 and 6, at 
two time-points per visit (pre- and post-bronchodilator):
!
FEV1 (L)
!
FEV1 % of predicted normal (PN)
!
FVC (L)
In addition, a treatment average will be calculated within subject as the average of Visits 4 to 6
(one value per visit).  Change from baseline for each of these three variables, for both time-points 
will also be calculated for Visits 4, 5, 6 and treatment average. Please refer to Section 3.1.1 for the 
baseline definition.
FEV1 predicted normal will be derived using the patient’s age (to the nearest 0.01 years, at the time 
of the visit), height (for adults, measured at screening; for adolescents, interpolated between 
measurements taken at Visits 2 and 6) and ethnic population, following the Global Lung Initiative 


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
29
(GLI) 2012 lung function regression equations (Quanjer et al 2012). Full details of how this 
method is applied can be found in Appendix 1: Method for calculating predicted normal FEV1.
Percentage of predicted normal FEV1 is then calculated as follows:
FEV1 (% of PN) = 100 × (FEV1 (actual) / FEV1 (predicted))
3.4.7
Patient reported outcomes
3.4.7.1
Asthma Control Questionnaire – 5-item Version (ACQ-5)
The 5-item version of the ACQ questionnaire contains five questions on patients’ symptoms, 
which are assessed on a 7-point scale from 0 (representing good control) to 6 (representing poor 
control). The ACQ score is the mean score of all questions for which responses are provided. A 
minimum of 4 out of 5 questions must be answered for a valid ACQ-5 score.
The ACQ is conducted at Visits 2, 3, 4, 5 and 6, with the score evaluated at each visit. Change 
from baseline for Visits 4, 5 and 6 (individual visits, end of treatment and average across Visits 4 
to 6) will also be calculated (baseline calculated as described in Section 3.1.1).
End of treatment is defined in Section 3.1.2. The following categorical outcome variables will be 
calculated based on ACQ-5 score at the end of treatment:
!
Asthma control at end of study: ACQ-5 score at end of treatment < 0.75, ≥0.75
!
Patient improved: ΔBL (ACQ-5 score) at end of treatment ≤ –0.5
!
Patient unchanged: ΔBL (ACQ-5 score) at end of treatment ϵ (–0.5, 0.5)
!
Patient worsened: ΔBL (ACQ-5 score) at end of treatment ≥ 0.5 where ΔBL(x) denotes 
“Change from baseline in x”.
Note: Patient improved/unchanged/worsened responses are based on a minimal important 
difference (MID) of 0.5.
If more than one ACQ-5 is completed on any day, the questionnaire with the worst score (highest 
mean value) will be used in the analysis. This applies to both baseline and post-baseline 
assessments.
3.4.7.2
Asthma Quality of Life Questionnaire – Standardised version (AQLQ(S))
The AQLQ(S) includes 32 questions relating to 4 distinct domains:
!
activity limitation (11 questions; minimum 7 questions required for a valid score)
!
symptoms (12 questions; minimum 8)
!
emotional function (5 questions; minimum 3)


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
30
!
exposure to environmental stimuli (4 questions; minimum 3)
Each question is answered on a 7-point scale ranging from 1 to 7 with lower values representing 
more severe impairment.
For each of the four domains, a domain score is calculated as the mean score of all its constituent 
items (this is defined as missing if the minimum number of questions required for a valid score is 
not met). An overall score across the whole questionnaire is calculated as the mean score of all 32 
items. In case of any missing answers, the overall score is calculated as a weighted mean of the 
domain scores, with the nominal fraction of items in each domain as weights. If one or more 
domains are missing, the overall score is also missing. (Note: when there are no missing answers, 
this method is equivalent to the average response of all 32 questions taken individually.)
The four domain scores and an overall score will be calculated for Visits 2, 3, 4, 5 and 6. Change 
from baseline for all four domain scores and the overall score will be calculated for Visits 4, 5 and 
6 (individual visits, end of treatment and average across Visits 4 to 6) will also be calculated 
(baseline calculated as described in Section 3.1.1).
End of treatment is defined in Section 3.1.2. The following categorical outcome variable will be 
calculated based on overall AQLQ(S) score at the end of treatment:
!
Patient improved: ΔBL(AQLQ(S) score) at end of treatment ≥ 0.5
!
Patient unchanged: ΔBL(AQLQ(S) score) at end of treatment ϵ (–0.5, 0.5)
!
Patient worsened: ΔBL(AQLQ(S) score) at end of treatment ≤ –0.5 where ΔBL(x) denotes
“Change from baseline in x”.
Note: Patient improved/unchanged/worsened responses are based on a MID of 0.5.
If more than one AQLQ(S) is completed on any day, the questionnaire with the worst overall score 
(lowest mean value) will be used for the analysis. This applies to both baseline and post-baseline 
assessments.
3.5
Safety variables 
3.5.1
Vital signs
The following vital signs measurements will be conducted at Visits 2 and 6 (or discontinuation of 
IP):
!
Pulse rate
!
Systolic blood pressure
!
Diastolic blood pressure


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
31
Vital signs measurements will continue to be collected in patients who discontinue IP prematurely. 
Change from baseline for all three variables will be defined as the difference between 
measurements at Visit 6 (or discontinuation of IP) and Visit 2 (as per Section 3.1.1 above).
3.5.2
Physical examination 
The following physical examination assessments will be made at Visits 2 and 6 (or discontinuation 
of IP):
!
General appearance
!
Respiratory
!
Cardiovascular
!
Abdomen
!
Head and neck (including head, ears, eyes, nose and throat)
3.5.3
Adverse events (including Serious Adverse Events)
3.5.3.1
Collection of AEs and SAEs
Adverse Events (AEs) will be collected from Visit 2 throughout the treatment period and including 
the follow-up period until the last telephone follow-up, or the last contact.
Serious Adverse Events (SAEs) will be recorded from the time of informed consent (Visit 1). 
The following assessments will be collected for each AE:
!
AE (verbatim)
!
The date when the AE started and stopped
!
Maximum intensity (mild/moderate/severe)
!
Whether the AE is serious or not
!
Investigator causality rating against the IP (yes or no)
!
Action taken with regard to investigational product
!
AE caused patient’s withdrawal from study (yes or no)
!
Outcome
In addition, the following variables will be collected for SAEs:
!
Date AE met criteria for serious AE


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
32
!
Date Investigator became aware of serious AE
!
AE is serious due to
!
Date of hospitalisation
!
Date of discharge
!
Probable cause of death
!
Date of death
!
Autopsy performed
!
Causality assessment in relation to study procedure(s)
!
Causality assessment in relation to other medication
!
Description of AE
3.5.3.2
Definition of adverse event leading to discontinuation of investigational product 
(DAE) 
Adverse events where “Action taken with regard to investigational product” is answered 
“discontinued” will be defined as DAEs and reported separately (in addition to being reported as 
general AEs).
3.5.3.3
AEs representing potential β2 agonist effects and AEs representing potential ICS 
effects
Summary tables of AEs representing potential β2 agonist effects and AEs representing potential
ICS effects will be produced (See Appendix 3: Potential class effects β2-agonists and Potential 
ICS effects). 
3.5.3.4
Other significant adverse events (OAEs)
During the evaluation of the AE data, an AstraZeneca medically qualified expert will review the 
list of AEs that were not reported as SAEs and DAEs.  Based on the expert’s judgement, 
significant adverse events of particular clinical importance may, after consultation with the Global 
Patient Safety Physician, be considered OAEs and reported as such in the Clinical Study Report.  
A similar review of vital signs data will be performed for identification of OAEs.
OAEs will be reported in a separate table (in addition to being reported as general AEs).
3.5.3.5
Adverse events data handling
Adverse events will be reported as occurring during the run-in period if the start date is on or after 
the first date of run-in medication, and prior to the first dose of randomised medication.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
33
Adverse events will be considered as occurring during the randomised period if the onset date is on 
or after the date of first dose of randomised study medication and onset is not later than one day 
after the last day of randomised treatment.
Adverse events that start during the run-in period but continue and become serious adverse events 
during the randomised period will be reported in both run-in and also in the randomised treatment 
period.
Adverse events will be considered as occurring during the follow-up period if the onset date is 
later than one day after the last day of randomised treatment.
Adverse events will be considered as occurring during the follow-up period if the onset date is 
later than one day after the last day of randomised treatment.
If an AE has a missing onset date, then, unless the stop date of the AE indicates otherwise, this will 
be considered as occurring during the randomised treatment period. Similarly, if an AE has a 
partial onset date, then unless the partial onset date or the stop date indicates otherwise, this will be 
considered as occurring during the randomised treatment period.
3.6
Other variables 
3.6.1
Concomitant medications
Concomitant inhaled and systemic asthma treatment as prescribed in response to severe 
exacerbations will be recorded in the EXACASI eCRF module with medication specified in the 
MED module.
Other concomitant medication, which is considered necessary for the patient’s safety and well-
being, may be given at the discretion of the investigator and recorded in the appropriate sections of 
the eCRF.
Additional ICS and systemic GCS prescribed on the day of IP discontinuation for an asthma 
exacerbation will be considered as during the randomised treatment period, otherwise they will be 
considered as during the follow-up period (See Appendix 2). All other concomitant medication 
prescribed on the day of IP discontinuation will be counted as during the randomised treatment 
period unless the reason is ‘disease under study’ where it will be considered as follow-up. 
3.6.2
Discontinuation of investigational product
Patients may be discontinued from IP in the following situations:
!
Patients that are incorrectly enrolled and/or randomised to study
!
Patient decision. The patient is at any time free to discontinue treatment, without 
prejudice to further treatment
!
Adverse Event
!
Severe non-compliance with the study protocol


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
34
!
Safety reason as judged by the investigator and/or AstraZeneca
!
Pregnancy
!
Development of any of the following study specific criteria for discontinuation:
∀
A severe asthma exacerbation with duration of more than 3 weeks
∀
Three severe asthma exacerbations within a period of 6 months
In these cases, the reason for withdrawal from the study will be “Discontinuation of investigational 
product” and the reason for discontinuation will also be recorded.
Time to discontinuation from IP due to any of the specified reasons will be calculated as:
Time to discontinuation of IP = Date of study drug termination – Date of first dose of IP+ 1
Time to censoring will be calculated using same methodology as described for asthma 
exacerbations (see Section 3.4.1.3).
3.6.3
Compliance of study maintenance medication
Summary statistics about maintenance medication compliance will be produced. For expected 
maintenance inhalations, only one maintenance dose is expected on the final day of treatment.
Compliance for maintenance medication (%) will be calculated for each patient as: 
(Total actual maintenance inhalations/Total expected maintenance inhalations)*100.
Total expected maintenance inhalations = number of days in randomised treatment period * 2 - 1
Other compliance metrics includes the proportion of study days where patients used no doses, 1-2 
doses only, 2 doses only, and more than 2 doses.  
For the purpose of graphical representation, the proportion of study days where patients used ≥1 
inhalation will also be calculated per week as follows:
!
Derive the percentage per day as number of patients who took at least 1 inhalation 
divided by the number of patients still in the randomised treatment period on the 
respective study day.
!
For each week take a mean of the percentages for the 7 days of the week. 


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
35
4.
ANALYSIS METHODS 
4.1
General principles 
All tests will be 2-sided and at 5% level of significance unless otherwise stated. No adjustment will 
be made for multiplicity, except for the primary variable annual severe exacerbation rate, which is 
described in Section 4.2.5.1.
For all statistical analyses, missing at random (MAR) will be assumed. Missing not at random 
(MNAR) mechanism will be explored as a sensitivity analysis of the primary variable annual 
severe exacerbation rate, further described in Section 4.2.8.3. 
In addition to the analyses described below, all variables will be summarised descriptively, as 
appropriate.
For efficacy analysis, the following general principles guide the statistical hypotheses to be tested:
!
The two treatment groups in the study (with short names defined for clarity) are as 
follows: 
∀
Symbicort Turbuhaler 160/4.5μg ‘as needed’ with no maintenance treatment
(Symbicort ‘as needed’)
∀
Pulmicort Turbuhaler 200μg twice daily ‘maintenance’ plus terbutaline Turbuhaler 
0.4mg ‘as needed’ (Pulmicort bid)
!
For the purpose of this statistical analysis plan (SAP), the treatment that a patient has 
been randomised to for the duration of the study will be referred to simply as 
‘treatment’; treatment prescribed to a patient prior to the study will be referred to as 
‘pre-study treatment’.
The two pre-study treatment groups are defined as follows:
!
Uncontrolled on an inhaled short-acting BD 'as needed' (SABA and/or short-acting 
anticholinergic agent)
!
Controlled on ICS or LTRA: Controlled on mono-maintenance therapy with either a low 
dose ICS or a LTRA in addition to 'as needed' use of inhaled short-acting BD (SABA 
and/or short-acting anticholinergic agent).
Unless otherwise stated all efficacy and safety analyses will be conducted using the “randomised 
treatment period” which begins at date of first dose of investigational product (maintenance or ‘as 
needed’ study medication). It ends at the end date of dosing if available, otherwise date of 
termination if available, otherwise last visit date
Any AE starting or worsening during the randomised treatment period up to 1 day after IP 
discontinuation is considered treatment emergent..


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
36
4.2
Analysis methods
4.2.1
Patient disposition 
Patient disposition will be summarised using the All Patients analysis set. The number of patients 
who were enrolled, run-in and not run-in will be summarised. The number and percentage of 
patients within each treatment group will be presented by the following categories; randomised,
not randomised (and reasons), randomised who received study treatment, randomised who did not 
receive study treatment (and reasons), completed randomised treatment, pre-maturely discontinued 
randomised treatment (and reasons), and completed the study and patients withdrawn from study 
(and reasons).
A separate table will present the number and percentage of patients randomised to each treatment
group by region and country. This table will be based on the FAS. 
4.2.2
Demography data and patient characteristics
Age, gender, race, ethnic group and region will be summarised by treatment group and by 
treatment and pre-treatment group for the full analysis set. Baseline characteristics will be 
summarised by treatment for the full analysis set. These include previous disease-related 
treatments, medical and surgical histories. Weight, height, body mass index, smoking status, and 
ACQ and AQLQ questionnaires will be summarised by treatment, and by treatment and pre-study 
treatment group.  FEV1 (pre- and post-bronchodilator) and reversibility (ml and %) will be 
summarised during run-in and at baseline by treatment, and by treatment and pre-study treatment. 
Asthma duration (defined by Time in years since asthma diagnosis, and Time in years since 
asthma symptoms started), a binary variable capturing if the most recent severe exacerbation was 
in last 12 months (Yes/No), and the number of severe exacerbations in the previous 12 months will 
be summarised by randomised treatment group, for all patients and by pre-study treatment 
subgroup at the enrolment visit. 
FEV1 % predicted normal (pre-bronchodilator and post-bronchodilator) as assessed at study entry 
and baseline will also be categorised into the following four categories for pre-bronchodilator 
measurements: < 60%, ≥60% to < 80% , ≥80% to <100%, ≥100%, and for post-bronchodilator 
measurements the categories are: <80%, ≥80% to <100%, ≥100%. The number of patients and 
percentage of patients falling into each of these categories and treatment group will be presented 
both in total, and by each pre-treatment subgroup.  
Medical and surgical histories will be summarised by MedDRA preferred term (PT) within 
MedDRA system organ class (SOC). 
4.2.3
Concomitant medication 
The number and percentage of patients who take allowed concomitant medications, and those who 
take disallowed concomitant medications during the study, will be presented by treatment group. 
Concomitant medications will be classified according to the AstraZeneca Drug Dictionary 
(AZDD). The summary tables will present data by generic term within (Anatomical Therapeutic 
Chemical) ATC code for the full analysis set.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
37
4.2.4
Exposure to study treatment
Exposure to study treatment during randomised treatment period will be summarised for the Safety 
Population. It will be calculated as the date of last dose – date of first dose + 1. Descriptive 
statistics will be presented by treatment group, and by treatment group and pre-study treatment 
group. Cumulative exposure will also be presented by treatment group, and by treatment group and 
pre-study treatment group and also summarised by the following categories: ≥1 day, >4 weeks, 
>8 weeks, >16 weeks, >24 weeks, >32 weeks, >40 weeks, >48 weeks and >52 weeks of study
treatment exposure. 
4.2.5
Primary efficacy analysis
4.2.5.1
Annual severe asthma exacerbation rate
The primary variable, annual severe asthma exacerbation rate, will be analysed by a negative 
binomial regression model. The response variable in the model will be the number of severe 
asthma exacerbations over the randomised treatment period. The model will include randomised 
treatment, pre-study treatment group and region as factors. The logarithm of the follow-up time 
will be used as an offset variable to adjust for patients having different exposure time of 
randomised study treatment. Where the follow-up time is defined as the time the patient was on 
randomised study drug. 
The evaluation of the treatment effect will take place in a step-wise order:
Step 1: The Negative binomial regression model will be fitted to the FAS, including patient data 
up to study drug discontinuation, but for this particular analysis excluding patient data from France 
(9 randomised patients in total). From this model, the annual severe asthma exacerbation rates will 
be estimated using least square means, and the treatment effect will be expressed as the rate ratio 
along with its corresponding 1-sided 95% confidence interval (CI). Output from this analysis will 
be used to evaluate the non-inferiority hypothesis as stated below:   
Symbicort vs Pulmicort (non-inferiority, primary objective)
Formally, the null and alternative hypothesis are:
  H0: rate-ratio (Symbicort vs Pulmicort) ≥1.2
  H1: rate-ratio (Symbicort vs Pulmicort) < 1.2
If the upper 1-sided 95% confidence limit of the rate-ratio is < 1.2 then non-inferiority can be 
declared. If the criteria for the alternative hypothesis is met, then superiority of Symbicort vs 
Pulmicort in terms of annual severe asthma exacerbation will be assessed (Step 2 below).
Step 2: The same Negative binomial regression model will be fitted to the FAS, including all 
patient data up to study drug discontinuation. From this model, the annual severe asthma 
exacerbation rates will be estimated using least square means, and the treatment effect will be 
expressed as the rate ratio along with its corresponding 2-sided 95% CI and p-value. Output from 
this analysis will be used to evaluate the superiority hypothesis as stated below:   


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
38
Formally, the null and alternative hypothesis for superiority testing is:
    H0: rate-ratio (Symbicort vs Pulmicort) = 1
    H1: rate-ratio (Symbicort vs Pulmicort) ≠1
The 95% 2-sided CI will be evaluated for the superiority hypothesis. 
The Negative Binomial regression model will be coded using the PROC GENMOD procedure in 
SAS®, using the following code as a guide:
proc genmod data=indata;
  class trtcd pst region;
  model nexac = trtcd pst region / dist=negbin offset=logfup;
run;
The rate ratio estimates together with the corresponding 1-sided and two-sided 95% CI will be 
shown in a Forest plot. 
4.2.6
Secondary efficacy analyses
4.2.6.1
Severe asthma exacerbation variables
Time to first severe asthma exacerbation will be analysed by Cox proportional hazards model with 
randomised treatment, pre-study treatment group and region as factors. The hazard ratio and its 
corresponding 95% CI will be estimated from the model. A Kaplan-Meier plot for time to first 
severe exacerbation will be generated.
The Cox proportional hazards model will be coded using PROC PHREG in SAS®, using the 
following code as a guide:
proc phreg data=indata;
  class trtcd pst region;
  model texac*censor(0) = trtcd pst region;
run;
All severe exacerbations, severe exacerbations requiring hospitalisation, severe exacerbations 
requiring systemic steroid use for at least 3 days, and severe exacerbations requiring emergency 
room visit and systemic steroids (total number, patients with at least one and annual rate) will be 
summarised using descriptive statistics and will be presented by treatment group. Further, number 
of severe exacerbations per patient (continuous and categorical), total days of exacerbation, 
average duration of exacerbation in days for the all severe exacerbations and the three components 
described above. Additionally, a time-event plot displaying each severe exacerbation by patient 
will be generated.
A table presenting the total number of severe exacerbations, and the total number and percentage 
of these events that were preceded by a worsening of asthma symptoms within 24 hours, including 
type of symptom, will be presented by each randomised treatment group. A graphical display 


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
39
showing the average of ‘as needed’ inhalations by day from 14 days before to 14 days after the 
onset of a severe asthma exacerbation by treatment will be produced. 
4.2.6.2
Discontinuation of IP due to study specific asthma related events
Time to study specific discontinuation of IP due to asthma related events will be analysed by Cox 
proportional hazards model with treatment, pre-study treatment group and region as factors. The 
hazard ratio and its corresponding 95% CI will be estimated from the model (as with time to first 
severe asthma exacerbations in Section 3.4.1.3).
Summary statistics alone will be presented if the number of study-specific asthma related 
discontinuations is considered to be too small to enable a meaningful statistical analysis.
In addition, the number of patients and the percentage of patients meeting a study specific asthma 
related discontinuation criterion, will be presented by randomised treatment group for the FAS. 
The table will include both the total and also each of the two discontinuation criteria: Severe 
asthma exacerbation with duration for more than 3 weeks, and Three severe asthma exacerbations
during 6 months. 
4.2.6.3
Discontinuation of IP and study withdrawal
Kaplan-Meier plots will be produced showing Time to discontinuation of IP and Time to study 
withdrawal in unit weeks by treatment group for the FAS.  Time to discontinuation of IP will be 
the time from first dose of IP to time of IP discontinuation or completion (whatever occurs first). 
Time to study withdrawal will be the time from first dose of IP to time of study withdrawal or 
completion (whatever occurs first).
4.2.6.4
Steroid load
The mean daily ICS (IP only, additional ICS and total, in μg) and the number of days with 
systemic GCS due to asthma will be presented descriptively by randomised treatment. A line graph 
will examine the change in mean daily inhaled steroid load over the randomised treatment period, 
by study week. In addition, a box and whisker plot presenting the mean daily ICS dose during the 
randomised treatment period, by each randomised treatment group will be produced. Within each 
treatment group there will be three different boxes presented: first box representing the total ICS, 
second box presenting the IP only ICS and the third box presenting additional ICS use.    
4.2.6.5
Lung function measurements
The treatment effect for change from baseline in FEV1 (measured in litres) will be estimated using 
a mixed model repeated measures (MMRM) analysis. Pre- and post-bronchodilator FEV1 will be 
analysed in separate models, using the same modelling method.
For each model (pre- and post-bronchodilator) measurements of the outcome variable will be taken 
at Visits 4, 5, and 6. Terms for randomised treatment, pre-study treatment, region, visit and 
(randomised treatment*visit) will be included as fixed effects. Patient will be included as a random 
effect. Baseline FEV1 will be included as a continuous covariate. Visit will be fitted as an 
unordered categorical variable, and the variance-covariance matrix will be assumed to be 


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
40
unstructured. The model will be coded using the PROC MIXED procedure in SAS® using the 
following code as a guide:
proc mixed data=indata;
class trtcd pst region visit;
model chg = trtcd pst region visit trtcd*visit base/ddfm=kr;
repeated visit / subject=usubjid type=un;
run;
If the procedure does not converge then a compound symmetric variance-covariance matrix will be 
used instead (replacing type=un with type=cs in the above code).
Kenward-Roger denominator degrees of freedom will be used (Kenward and Roger 1997).
This model will be used to give an overall assessment of the treatment effect as well as 95% CIs. 
Separate treatment effects per visit will be presented. Graphical plots of the treatment effect for 
pre- and post- bronchodilator FEV1 (Least Squares Means and 95% CI) over time will also be 
presented.
Summary statistics will be presented by treatment for pre- and post-bronchodilator FEV1 (L), 
FEV1 (% of predicted normal) and FVC (L) (including change from baseline in those variables) 
across all the visits in the trial. Graphical plots of the FEV1 variables above over time will also be 
presented using model estimates.
4.2.6.6
Patient reported outcomes
ACQ-5 and AQLQ will be analysed in the same way as FEV1 using MMRM analysis using the 
corresponding baseline values. Figures showing the treatment effect for ACQ-5 and AQLQ overall 
scores (LSMeans ad 95% CI) over time will also be presented.
Responder variables based on a clinical improvement in ACQ-5 and AQLQ(S) of MID at end of 
treatment compared to baseline and the responder variable ACQ-5 < 0.75 at the end of treatment 
will be analysed using logistic regression models. For each outcome variable, the model will 
include randomised treatment, pre-study treatment and region as factors, and baseline ACQ-5 or 
AQLQ(S) score (whichever matches the outcome variable in question) as a continuous covariate. 
From the logistic regression model treatment effects will be estimated by odds-ratio and its 
corresponding 95% CI. 
The model will be coded using the PROC LOGISTIC procedure in SAS® using the following 
code as a guide:


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
41
proc logistic data=indata;
  class trtcd pst region;
  model resp = trtcd pst region base;
run;
In addition, the proportion of patients who had a clinical worsening or no clinically meaningful 
difference in ACQ-5 and AQLQ(S) based on MID at end of treatment compared to baseline will be 
reported. 
Translation issues were identified in some versions of the ACQ-5/AQLQ questionnaires in some 
countries. Any patient who completed an ACQ-5 questionnaire with a translation issue will be 
excluded from all ACQ-5 analysis. Any patient who completed an AQLQ questionnaire with a 
translation issue will be excluded from all AQLQ analysis 
Descriptive statistics for absolute and change from baseline values in ACQ-5 and AQLQ (total and 
domain scores) will be presented by treatment across visits, treatment average and end of 
treatment.     
Graphical plots of change from baseline ACQ and AQLQ over time will also be presented using 
model estimates.
4.2.6.7
‘As needed’ use, Percent ‘as needed’ free days, and Percent controller use days
Summary statistics about ‘as needed’ medication use and change from baseline in ‘as needed’ 
medication use will be produced for day, night and total respectively by treatment. The average 
number of ‘as needed’ inhalations and days with no inhalations, with 1 to 2, with 3 to 5, with 6 to 
8, with 9 to 12 and more than 12 inhalations will be analysed using descriptive statistics.
Summary statistics about high use of ‘as needed’ medication (>8 and >12 inhalations on one day) 
will also be produced. A line graph will examine the mean ‘as needed’ medication use over the 
randomised treatment period for daytime, nighttime and total.
Change from baseline in ‘as needed’ medication use will be analysed using analysis of covariance 
(ANCOVA) models. Day, night and total ‘as needed’ use will be analysed using separate models, 
following the same modelling method. Change from baseline will be calculated as the difference 
between the mean of all days during the randomised treatment period and the mean of all days 
during the last 10 days of the run-in period.
The ANCOVA models will include randomised treatment, pre-study treatment and region as 
categorical factors and baseline ‘as needed’ medication use as a continuous covariate. Baseline
‘as needed’ medication use definition is specified in Section 3.1.1. Least squared means by 
randomised treatment group and differences in least squared means (between randomised 
treatment groups) along with corresponding 95% CIs will be estimated.
The percentage of controller use days will be analysed using descriptive statistics by treatment, and 
modelled through an ANCOVA model with randomised treatment, pre-study treatment and region 
as factors.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
42
Summary statistics for ‘as needed’ free days (%) and change from baseline in ‘as needed’ free days 
(%) will be produced by treatment. The change from baseline in ‘as needed’ free days (%) will be 
analysing using an ANCOVA model with randomised treatment, pre-study treatment and region as 
categorical factors and baseline ‘as needed’ free days (%) as a continuous covariate. Baseline ‘as 
needed’ free days (%) definition is specified in Section 3.1.1.
4.2.6.8
Maintenance medication compliance
Summary statistics about maintenance medication compliance will be produced. See Section 3.6.3
for metrics. To examine changes in compliance over time the proportion of days where patients 
used ≥1 inhalation will be plotted over the randomised treatment period by week. Mean 
maintenance medication use per day will be depicted graphically by week and treatment.
4.2.7
Safety analysis 
Safety variables will be presented descriptively by actual given treatment and pre-study treatment; 
no formal statistical hypothesis testing will be conducted.
The following safety variables will be summarised by treatment:
!
Vital signs (pulse rate, systolic blood pressure, diastolic blood pressure)
∀
Raw measurements (Visits 2, 6 and end of treatment)
∀
Change from baseline (Visit 2 to end of treatment)
!
Physical examination (general appearance, respiratory, cardiovascular, abdomen, 
head/neck)
∀
Shift tables from baseline to the end of treatment
A summary overview table of patients with adverse events, with fatal adverse events, SAEs, DAEs 
and OAEs during the randomised treatment period will be presented by treatment, and by 
treatment and pre-study treatment.
The number and percentage of patients who experience one or more AE during run-in, and follow-
up will be tabulated by SOC and PT and by treatment. The incidence rate of AEs will also be 
presented in the tables. The incidence rate is defined as the number of patients who have 
experienced the event per 100 patient treatment years.
The number and percentage of patients who experience one or more AE/SAE/DAE over the 
randomised treatment will be tabulated by SOC and PT by treatment and by treatment and pre-
study treatment. The incidence rate of AEs will also be presented in the tables. The number of 
percentage of patients who experience common AEs (frequency of >=2%) common SAEs 
(frequency of >=0.2%), and common DAE (frequency of >=0.2%) will be summarised by 
preferred term and treatment. In addition, summary tables of AEs representing potential β2 agonist 
effects and AEs representing potential ICS effects will be produced by medical concept and 
preferred term and by treatment.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
43
The number of events and event rates for AEs and SAEs will also be presented by SOC and PT by 
treatment.  Event rates are defined as the total number of events across all patients in the treatment 
group per 100 patient treatment years. 
The number and percentage of patients who experience a fatal AE during the randomised treatment 
will be tabulated by SOC and PT by treatment.
Patient information will be listed for those patients with SAEs, with DAE and with fatal AEs over 
the entire study period. 
The number and percentage of patients experiencing other significant adverse events during the 
randomised treatment will be summarised by SOC and PT by treatment.
4.2.8
Supportive, subgroup, and sensitivity analyses
4.2.8.1
Supportive analysis
A supportive analysis will be carried out for the primary variable; annual severe exacerbation rate, 
to evaluate the non-inferiority hypothesis test by using a 97.5% 1 sided upper CI for the rate ratio. 
The annual exacerbation rates, the rate ratio and the corresponding 1-sided upper 97.5% CI for the 
rate ratio will be presented from the primary analysis model, excluding patients from France. 
4.2.8.2
Subgroup analysis 
For all subgroup analysis, if the model does not converge, then just summary statistics will be 
presented. 
Pre-study treatment:
The treatment effect will be investigated in the 2 subgroups as defined by pre-study treatment to 
assess the consistency of the treatment effect across subgroups. An interaction effect will be 
evaluated for the following efficacy variables: severe exacerbation rate, time-to first severe 
exacerbation, ACQ, and FEV1 pre- bronchodilator. For total inhaled steroid load, and time to 
asthma related discontinuation, descriptive statistics by treatment group will be presented by 
pre-study treatment category.
The treatment-by-pre-study treatment interaction term will be used to explore the consistency of 
the treatment effect across pre-study treatment subgroup categories in the below models. The 
interaction p-value from the Type III sums of squares test will be presented.
For severe exacerbation rate, and time-to first severe exacerbation, similar models to the overall 
population will be carried out but adding treatment-by-pre-study treatment interaction as factor 
into the model. 
For ACQ, FEV1 pre- bronchodilator, similar models to the overall population will be carried out 
but adding treatment-by-pre-study treatment, pre-study treatment-by-visit, and treatment-by-visit-
by- pre-study treatment. The 3-way interaction will be used to estimate the least squares mean of 
the treatment effect and its corresponding 95% CI by visit. Forest plots presenting the overall and 


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
44
pre-study treatment subgroup categories treatment effects and their associated 95% CI will be 
generated.
Severe asthma exacerbations: 
For severe exacerbations rate, the consistency of treatment effect across subgroups will also be 
examined with regard to: sex, age, pre-study treatment, severe exacerbations 12 months prior to 
enrolment, baseline ACQ, asthma onset, smoking, region, baseline pre-bronchodilator FEV1 PN, 
and average use of SABA during run-in period. This will be done by including a 
(subgroup*randomised treatment) interaction term in the models.
Forest plots presenting the rate ratios estimates and their associated 95% CI by subgroup:
pre-study treatment category will be provided.
Subgroup analysis on exacerbations will not be conducted on an individual subgroup if less than 
20 exacerbations were experienced in the respective subgroup.
Subgroups are described in Table 2 below.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
45
Table 2 Subgroups
Group
Subgroup
Pre-study treatmenta
Uncontrolled on BD
Controlled on ICS or LTRA
Sex
Male
Female
Age 
Adolescents: 12-<18 years
Adults: 18 - <65 years
Elderly: ≥65 years
Severe exacerbations 12 months prior to enrolmentb
0
≥1
Baseline ACQ
≤0.75
>0.75 - ≤1.5
>1.5
Asthma onset 
New diagnosis: Asthma diagnosed in the last 2 
years.
Not new diagnosis: Asthma diagnosed over 2 
years ago.
Smoking
Never
Current/Former
Regionc
Latin America
EU
East Asia
Rest of World
FEV1 %PN Pre bronchodilator (run-in)
<80
≥80 to <100
≥ 100
Average use of SABA per day during run-in period 
(puffs)
0 to < 1
1 to 2
> 2
a Uncontrolled on BD: Uncontrolled on an inhaled short-acting BD ‘as needed’ (SABA and/or short-acting 
anticholinergic agent); Controlled on ICS or LTRA: Controlled on mono-maintenance therapy with either a low 
dose ICS or a LTRA in addition to 'as needed' use of inhaled short-acting BD (SABA and/or short-acting 
anticholinergic agent).
b Severe exacerbation definition at baseline is different to the study definition.
c See Section 3.1 for a list of countries in each region. 


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
46
4.2.8.3
Sensitivity analysis 
Sensitivity analyses of the primary variable will be carried out to assess the robustness of the 
treatment effect under different underlying assumptions for missingness.
Severe asthma exacerbations will be analysed by the same Negative binomial regression model as 
described in Section 4.2.5.1, with only difference that any exacerbations occurring after 
discontinuation of randomised study drug will be accounted for in the analysis, and offset for 
adjustment of a patient’s follow-up time will be accounted for as the time from first dose of IP and 
up to study discontinuation, regardless of whether patient pre-maturely discontinued randomised 
study drug or not, see Section 3.4.1.2. 
Similarly, to the primary analysis described in Section 4.2.5.1, the Negative Binomial regression 
will be fitted twice to the data: 
The first analysis will evaluate the non-inferiority hypothesis test by including data also after IP 
discontinuation, but excluding patients from France. From this analysis the annual exacerbation 
rates, the rate ratio and the corresponding 1-sided upper 95% CI for the rate ratio will be presented. 
The second analysis will evaluate the superiority hypothesis by including all data, regardless of 
pre-maturely IP discontinuation. From this analysis the annual exacerbation rates, the rate ratio and 
the corresponding 2-sided 95% CI for the rate ratio and p-value will be presented.  
In addition, a sensitivity analysis assuming MNAR will be carried out. 
The same approach will be used for this sensitivity analysis, that is, the Negative binomial 
regression model will be fitted twice to data, where: 
The first analysis will evaluate the consistency in the primary endpoint and the non-inferiority 
hypothesis test by assuming data after IP discontinuation to be MNAR, but excluding patients from 
France. From this analysis the annual exacerbation rates, the rate ratio and the corresponding 
1-sided upper 95% CI for the rate ratio will be presented. 
The second analysis will evaluate the consistency in the primary endpoint and the superiority 
hypothesis by assuming data after IP discontinuation to be MNAR. From this analysis the annual 
exacerbation rates, the rate ratio and the corresponding 2-sided 95% CI for the rate ratio and 
p-value will be presented
For MNAR (both analyses), a ‘Jump to Reference’ (J2R) approach will be used, where post-IP 
discontinuation data will be imputed for both treatment arms based on the estimated rate observed 
in the control arm before IP-discontinuation.
The controlled imputation method was introduced by Keene et al, 2014 and further developed at 
AstraZeneca [Wan et al, 2015, Gottlow et al, 2015], and allows for different underlying
assumptions to be used. As with the primary analysis this sensitivity analysis includes all data until 
patients discontinue IP.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
47
For this method, an underlying negative binomial stochastic process for the rate of exacerbations is 
assumed and post-IP discontinuation counts will be imputed conditional upon the observed number 
of events prior to IP discontinuation.
The method involves first fitting the primary analysis i.e. negative binomial regression model to 
the observed data and then imputing post-IP discontinuation counts by sampling from the
conditional negative binomial probability relating post-IP discontinuation counts and observed
prior-IP discontinuation counts.
	, = |	, =  =
( +  + )
( + 1)( + ) 	
1 −	

(1)
Here  is number of counts before IP discontinuation,  is number of counts after IP
discontinuation,  is the dispersion parameter and which is assumed to be the same for different 
treatment arms, j denotes the treatment arm and i denotes the subject identifier.
Furthermore
	 = 	, −	,	,
1 −	,	,
(2)
where 	, is the estimated negative binomial distribution rate parameter before IP discontinuation 
from the study, and 	, is the rate parameter after IP discontinuation. For J2R, 	,will be equal to 
, (with adjustment of duration of time) where ,is the estimated rate parameter for the 
Pulmicort bid group up to IP discontinuation.
The imputed number of exacerbations that would have been seen is then combined with the
observed exacerbations and data are analysed using the primary analysis method, i.e. by the same 
Negative binomial regression model as described in Section 4.2.5.1.
This analysis is repeated multiple times and the results combined using Rubin’s formulae [Rubin, 
1987]. For those patients who discontinue IP during study period, the total time at risk of an 
exacerbation (observed + imputed) will be 365 days. A seed of 784088 will be used and 100 
imputations will be carried out.
4.2.9
Exploratory analysis 
Descriptive reporting of the resource utilization data and health related quality of life data based on
the EQ-5D-5L will be presented in the CSR. The data will be combined with economic data 
collected independently of the study to construct comparative health economic analyses between 
treatment groups. The economic analyses and cost-effectiveness analyses that include data external 
to the study will be reported in a separate health economic report and will not be included in the 
CSR.
Baseline is calculated as described in Section 3.1.1. End of treatment is calculated as described in 
Section 3.1.2.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
48
4.2.9.1
Health care resource utilization and work and school absence
Descriptive statistics by treatment will be presented for asthma related health care utilisation 
variables.
At baseline and at subsequent treatment visits until EoT, the patient will be asked questions about 
asthma-related health care resource use (HRU) events since last visit as well as asthma-related 
sickness and absence from work or education. 
The patient will be asked about health care resource use in terms of:
!
Hospitalizations (Number of days) 
∀
Hospitalization intensive care unit (ICU) 
∀
Hospitalization general ward (GW) 
!
ER visits
!
An emergency room or urgent care visit (defined as evaluation and treatment for <24 
hours in an emergency department or urgent care centre) due to asthma that required 
systemic corticosteroids. 
!
Ambulance transport (number)
!
Specialist visit
!
Primary health care physician visit
!
Other health care visit
!
Home visits physician
!
Home visits other health care
!
Telephone calls physician
!
Telephone calls nurse
HRU will be asthma-related only.  Descriptive statistics will be presented for each health care 
resource item, by treatment group. Summary measures to be included are total number of each 
HRU event (visits) and/or days of events, number and percentage of patients experiencing at least 
one HRU event, and the total number of each HRU event or days of event divided by patient 
treatment years (annual rate). 
The patient will be asked about work and school productivity loss in terms of:
!
Work absence due to your asthma (days)


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
49
!
School absence due to asthma (days)
Descriptive statistics will be presented for work and school absence, by treatment group. Summary 
measures to be included are total number of days, number and percentage of patients experiencing 
at least one absence day, and mean number of days absent per patient per year.
4.2.9.2
EQ-5D-5L
Summary statistics by treatment will be provided for absolute and change from baseline values in 
EQ-5D-5L (VAS and index) by treatment and visit. Boxplots will be produced to show the 
absolute values at baseline and each visit. Further, EQ-5D-5L domains will be described by 
treatment and visit.  
The EQ-5D-5L consists of 2 pages - the EQ-5D descriptive system and the VAS. The descriptive 
system comprises five dimensions, mobility, self-care, usual activity, pain/discomfort and 
anxiety/depression. Each dimension has five levels (response options): no problems, slight 
problems, moderate problems, severe problems and extreme problems. The VAS records the 
respondent´s self-rated health on a 20cm vertical visual analogue scale with endpoints labelled “the 
best health you can imagine” and “the worst health you can imagine”.
The questions will be assessed at baseline and at subsequent treatment visits until EoT. 
EQ-5D will be presented in three different ways: 
1) Presenting results from the EQ-5D-5L descriptive system as a health profile at baseline, all 
post-baseline visits and EoT (%, n) by domain
2) Presenting results of the VAS as a measure of overall self-rated health status - baseline 
scores, scores at each visit, changes from baseline at each visit and boxplots of VAS score 
over the randomised treatment period
3) Presenting results from the EQ-5D-5L crosswalk index value (using UK value set, see 
below) baseline utility, each visit, changes from baseline at each visit and boxplots of
utility over the randomised treatment period 
The National Institute of Health and Care Excellence (NICE) in England has made an 
interim position statement (August 2017) about the use of the 5 level version of the EQ-5D for 
companies, academic groups, and others preparing evidence submissions for NICE.
The main recommendations are:
If the 5 level is used (EQ-5D-5L), then apply the mapping function developed by Van 
Hout et al, 2012
to convert it to the EQ-5D-3L for the reference-case analyses
SAS syntax for computing EQ-5D-5L crosswalk index values with SAS using the United Kingdom 
(UK) value set can be found in Appendix 5: .


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
50
No imputation will be made for missing data in either the EQ-5D-5L or VAS responses.
5.
CHANGES OF ANALYSIS FROM PROTOCOL
Decision to exclude 12 randomised patients from study site 5702 (Poland) will be excluded from 
the Full Analysis set and the Safety analysis set due to significant deviations. The deviations were 
mainly relating to unavailability, discrepancies and poor quality of source data which question the 
validity and integrity of the trial data generated from this site. Data listings for these 12 patients 
will be provided in Appendix 12.2 in CSR.
Decision made to exclude all randomised patients in France in the non-inferiority test due to Ethic 
Committee rejection of CSP amendment 4 in France.
Decision to exclude 1 randomised patient from study site 2612 (Germany) that was randomised in 
error from Full Analysis Set and Safety Analysis Set. Due to the subject age, local ethics 
committee decided data of this patient cannot be used for the analysis. As patient signed informed 
consent, data listings will be provided for this patient in Appendix 12.2 in CSR.  


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
51
6.
REFERENCES 
Bateman et al 2004
Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels R, et al (2004) Can
guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL (GOAL) 
study. Am J Respir Crit Care Med, 170:836-44.
Friede and Schmidli, 2010
Friede T and Schmidli H. Blinded sample size reestimation with negative binomial counts in
superiority and non-inferiority trials. Methods Inf Med. 2010;49(6):618-24. doi: 10.3414/ME09-
02-0060. Epub 2010 Aug 5.
Gottlow et al, 2015
Gottlow M, Hollis S, Wan R, Hirsch I, Darilay A, Weissfeld L, France L. A Simulation study of a 
controlled imputation approach for analyzing missing data in recurrent events due to early
discontinuations. PSI Annual Conference 2015.
Van Hout et al, 2012
Van Hout B, Janssen M.F, Feng Y.S, Kohlmann T,  Busschbach J, Golicki D, Lloyd A, Scalone L,  
Kind P, Pickard A.S. Interim Scoring for the EQ-5D-5L: Mapping the EQ-5D-5L to EQ-5D-3L 
Value Sets: VALUE IN HEALTH 15.  2012;  708 –715
Keene et al 2007
Keene ON, Jones MRK, Lane PW, Anderson J. Analysis of exacerbation rates in asthma and
chronic obstructive pulmonary disease: example from the TRISTAN study. Pharmaceutical
Statistics 2007;6:89–97.
Keene et al, 2014
Keene, O. N., Roger, J. H., Hartley, B. F. and Kenward, M. G. (2014), Missing data sensitivity 
analysis for recurrent event data using controlled imputation. Pharmaceut. Statist., 13: 258–264.
Kenward and Roger 1997
Kenward MG and Roger JH. Small sample inference for fixed effects from restricted maximum 
likelihood. Biometrics 1997; 53: 983–997.
Pauwels et al 2003
Pauwels RA, Pedersen S, Busse WW, Tan WC, Chen YZ, Ohlsson SV et al, on behalf of the 
START Investigators Group. Early intervention with budesonide in mild persistent asthma: a 
randomised, double-blind trial. Lancet 2003;361:1071-6.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
52
Quanjer et al 2012
Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, et al. Multi-ethnic reference 
values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur 
Respir J 2012;40(6):1324-43.
Rubin, 1987
Rubin DB. Multiple imputation for nonresponse in surveys. New York: John Wiley & Sons, Inc. 
1987.
Wan et al, 2015
Wan R, Hirsch I, Gottlow M, Hollis S, Darilay A, Weissfeld L, France L. Controlled imputation 
approach for analyzing missing data in recurrent events due to early discontinuations. DIA/FDA 
Statistics Forum 2015.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
53
7.
APPENDIX 1: METHOD FOR CALCULATING PREDICTED 
NORMAL FEV1
7.1
Equation for calculating predicted multi-ethnic predicted normal 
FEV1
The equation for calculating predicted normal FEV1 is of the form:
PN FEV1 = exp(a0 + a1·ln(Height) + a2·ln(Age) + a3·AfrAm + a4·NEAsia + a5·SEAsia +
a6·Other + Mspline)
The following input variables are used in the predicted normal FEV1 equation:
!
Height is the patient’s height in cm (to the nearest 0.1 cm)
!
Age is the patient’s age in years (to the nearest 0.1 years) – this should be recalculated 
based on the visit date and patient’s date of birth
!
AfrAm is equal to 1 if the patient’s ethnic population is African American, 0 otherwise
!
NEAsia is equal to 1 if the patient’s ethnic population is North East Asian, 0 otherwise
!
SEAsia is equal to 1 if the patient’s ethnic population is South East Asian, 0 otherwise
!
Other is equal to 1 if the patient’s ethnic population is Other/Mixed, 0 otherwise
The constants a0, a1, a2, a3, a4 and a5 depend on the patient’s sex, as outlined in the table below:
Constant
Males
Females
a0
-10.3420
-9.6987
a1
2.2196
2.1211
a2
0.0574
-0.0270
a3
-0.1589
-0.1484
a4
-0.0351
-0.0149
a5
-0.0881
-0.1208
a6
-0.0708
-0.0708
The final term in the predicted normal FEV1 equation, Mspline, is obtained a lookup table (see
Section 7.2), based on the patient’s age and sex.
For patients aged 25 or over, the following equation may be used to approximate Mspline in place of 
the lookup tables:
Mspline = b0 + b1·(Age/100) + b2·(Age/100)2 + b3·(Age/100)3 + b4·(Age/100)4 + b5·(Age/100)5


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
54
where b0, b1, b2, b3, b4 and b5 are constants that depend on the patient’s sex, as outlined in the table 
below:
Constant
Males
Females
b0
0.3901
0.0552
b1
-1.0579
1.6029
b2
1.4743
-6.4845
b3
-2.1077
10.2723
b4
-0.1215
-9.8630
b5
0.8873
3.8802
7.2
Lookup table for final term 
The following lookup table is used for determining the value of Mspline in the equation for 
calculating predicted normal FEV1 (see Section 3.4.6). For ages other than those listed here, the 
value is derived using linear interpolation of the two nearest ages (i.e. those ages either side of the 
patient’s actual age).


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
55
The lookup table is available from the Global Lung Function Initiative website (URL at the time of 
writing: http://www.lungfunction.org/files/lookuptables7April2013.xls).
Age
Male
Female
Age
Male
Female
Age
Male
Female
12
-0.0176
0.0274
20.5
0.2090
0.1842
29
0.1574
0.1625
12.25
-0.0101
0.0386
20.75
0.2092
0.1842
29.25
0.1554
0.1617
12.5
-0.0019
0.0496
21
0.2091
0.1841
29.5
0.1534
0.1608
12.75
0.0071
0.0604
21.25
0.2089
0.1840
29.75
0.1514
0.1599
13
0.0169
0.0709
21.5
0.2084
0.1838
30
0.1495
0.1590
13.25
0.0274
0.0810
21.75
0.2079
0.1835
30.25
0.1475
0.1581
13.5
0.0384
0.0907
22
0.2071
0.1832
30.5
0.1455
0.1572
13.75
0.0497
0.0999
22.25
0.2063
0.1828
30.75
0.1436
0.1562
14
0.0612
0.1086
22.5
0.2053
0.1823
31
0.1417
0.1553
14.25
0.0728
0.1168
22.75
0.2042
0.1818
31.25
0.1397
0.1543
14.5
0.0844
0.1244
23
0.2030
0.1812
31.5
0.1378
0.1533
14.75
0.0958
0.1315
23.25
0.2016
0.1806
31.75
0.1359
0.1523
15
0.1068
0.1379
23.5
0.2002
0.1799
32
0.1340
0.1512
15.25
0.1175
0.1438
23.75
0.1987
0.1792
32.25
0.1321
0.1501
15.5
0.1276
0.1492
24
0.1970
0.1785
32.5
0.1302
0.1490
15.75
0.1371
0.1540
24.25
0.1954
0.1777
32.75
0.1283
0.1479
16
0.1460
0.1583
24.5
0.1936
0.1769
33
0.1265
0.1467
16.25
0.1542
0.1621
24.75
0.1918
0.1761
33.25
0.1246
0.1456
16.5
0.1616
0.1655
25
0.1899
0.1753
33.5
0.1227
0.1444
16.75
0.1684
0.1684
25.25
0.1880
0.1745
33.75
0.1209
0.1431
17
0.1744
0.1711
25.5
0.1861
0.1737
34
0.1190
0.1418
17.25
0.1798
0.1733
25.75
0.1841
0.1729
34.25
0.1172
0.1406
17.5
0.1845
0.1753
26
0.1821
0.1721
34.5
0.1153
0.1392
17.75
0.1887
0.1770
26.25
0.1801
0.1713
34.75
0.1135
0.1379
18
0.1924
0.1785
26.5
0.1781
0.1705
35
0.1116
0.1365
18.25
0.1956
0.1797
26.75
0.1760
0.1697
35.25
0.1097
0.1351
18.5
0.1984
0.1808
27
0.1739
0.1690
35.5
0.1078
0.1337
18.75
0.2008
0.1816
27.25
0.1718
0.1682
35.75
0.1059
0.1322
19
0.2029
0.1823
27.5
0.1697
0.1674
36
0.1040
0.1308
19.25
0.2046
0.1829
27.75
0.1677
0.1666
36.25
0.1021
0.1292
19.5
0.2060
0.1833
28
0.1656
0.1658
36.5
0.1001
0.1277
19.75
0.2072
0.1837
28.25
0.1635
0.1650
36.75
0.0982
0.1262
20
0.2081
0.1839
28.5
0.1615
0.1642
37
0.0962
0.1246
20.25
0.2087
0.1841
28.75
0.1594
0.1634
37.25
0.0943
0.1230


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
57
Age
Male
Female
Age
Male
Female
Age
Male
Female
37.5
0.0923
0.1214
47
0.0135
0.0486
56.5
-0.0759
-0.0375
37.75
0.0903
0.1197
47.25
0.0114
0.0465
56.75
-0.0785
-0.0401
38
0.0883
0.1180
47.5
0.0093
0.0445
57
-0.0812
-0.0426
38.25
0.0863
0.1164
47.75
0.0072
0.0424
57.25
-0.0839
-0.0451
38.5
0.0843
0.1147
48
0.0050
0.0403
57.5
-0.0866
-0.0477
38.75
0.0823
0.1129
48.25
0.0029
0.0382
57.75
-0.0893
-0.0503
39
0.0803
0.1112
48.5
0.0007
0.0361
58
-0.0920
-0.0529
39.25
0.0782
0.1094
48.75
-0.0015
0.0339
58.25
-0.0947
-0.0555
39.5
0.0762
0.1076
49
-0.0036
0.0318
58.5
-0.0975
-0.0581
39.75
0.0742
0.1058
49.25
-0.0058
0.0297
58.75
-0.1002
-0.0607
40
0.0721
0.1040
49.5
-0.0080
0.0275
59
-0.1030
-0.0634
40.25
0.0700
0.1022
49.75
-0.0103
0.0254
59.25
-0.1058
-0.0660
40.5
0.0680
0.1003
50
-0.0125
0.0232
59.5
-0.1086
-0.0687
40.75
0.0659
0.0985
50.25
-0.0147
0.0210
59.75
-0.1114
-0.0714
41
0.0638
0.0966
50.5
-0.0170
0.0188
60
-0.1143
-0.0741
41.25
0.0617
0.0947
50.75
-0.0193
0.0166
60.25
-0.1171
-0.0768
41.5
0.0596
0.0928
51
-0.0216
0.0144
60.5
-0.1199
-0.0795
41.75
0.0575
0.0909
51.25
-0.0239
0.0122
60.75
-0.1228
-0.0822
42
0.0554
0.0889
51.5
-0.0262
0.0099
61
-0.1257
-0.0850
42.25
0.0533
0.0870
51.75
-0.0285
0.0077
61.25
-0.1286
-0.0878
42.5
0.0511
0.0850
52
-0.0309
0.0054
61.5
-0.1315
-0.0905
42.75
0.0490
0.0830
52.25
-0.0332
0.0032
61.75
-0.1344
-0.0933
43
0.0469
0.0811
52.5
-0.0356
0.0009
62
-0.1373
-0.0961
43.25
0.0448
0.0791
52.75
-0.0380
-0.0014
62.25
-0.1402
-0.0989
43.5
0.0427
0.0771
53
-0.0404
-0.0037
62.5
-0.1431
-0.1018
43.75
0.0406
0.0751
53.25
-0.0428
-0.0061
62.75
-0.1461
-0.1046
44
0.0386
0.0731
53.5
-0.0453
-0.0084
63
-0.1490
-0.1075
44.25
0.0365
0.0710
53.75
-0.0478
-0.0108
63.25
-0.1519
-0.1103
44.5
0.0344
0.0690
54
-0.0502
-0.0131
63.5
-0.1549
-0.1132
44.75
0.0323
0.0670
54.25
-0.0527
-0.0155
63.75
-0.1578
-0.1161
45
0.0302
0.0650
54.5
-0.0552
-0.0179
64
-0.1608
-0.1190
45.25
0.0281
0.0630
54.75
-0.0578
-0.0203
64.25
-0.1638
-0.1219
45.5
0.0261
0.0609
55
-0.0603
-0.0227
64.5
-0.1667
-0.1249
45.75
0.0240
0.0589
55.25
-0.0629
-0.0252
64.75
-0.1697
-0.1278
46
0.0219
0.0568
55.5
-0.0654
-0.0276
65
-0.1727
-0.1308
46.25
0.0198
0.0548
55.75
-0.0680
-0.0301
65.25
-0.1757
-0.1338
46.5
0.0177
0.0527
56
-0.0706
-0.0326
65.5
-0.1786
-0.1368


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
58
8.
APPENDIX 2: IDENTIFCATION OF ADDITIONAL STEROID 
66.25
-0.1876
-0.1458
75.75
-0.3018
-0.2674
85.25
-0.4092
-0.3883
66.5
-0.1906
-0.1488
76
-0.3048
-0.2707
85.5
-0.4119
-0.3913
66.75
-0.1936
-0.1519
76.25
-0.3077
-0.2740
85.75
-0.4145
-0.3944
67
-0.1966
-0.1550
76.5
-0.3107
-0.2773
86
-0.4172
-0.3974
67.25
-0.1996
-0.1580
76.75
-0.3136
-0.2805
86.25
-0.4198
-0.4004
67.5
-0.2026
-0.1611
77
-0.3166
-0.2838
86.5
-0.4225
-0.4034
67.75
-0.2056
-0.1642
77.25
-0.3195
-0.2871
86.75
-0.4251
-0.4064
68
-0.2086
-0.1674
77.5
-0.3224
-0.2903
87
-0.4277
-0.4094
68.25
-0.2116
-0.1705
77.75
-0.3253
-0.2936
87.25
-0.4303
-0.4124
68.5
-0.2147
-0.1736
78
-0.3282
-0.2968
87.5
-0.4329
-0.4153
68.75
-0.2177
-0.1768
78.25
-0.3311
-0.3001
87.75
-0.4355
-0.4183
69
-0.2207
-0.1799
78.5
-0.3340
-0.3033
88
-0.4381
-0.4213
69.25
-0.2237
-0.1831
78.75
-0.3369
-0.3065
88.25
-0.4407
-0.4242
69.5
-0.2267
-0.1863
79
-0.3398
-0.3098
88.5
-0.4433
-0.4272
69.75
-0.2298
-0.1895
79.25
-0.3427
-0.3130
88.75
-0.4459
-0.4301
70
-0.2328
-0.1926
79.5
-0.3455
-0.3162
89
-0.4484
-0.4330
70.25
-0.2358
-0.1958
79.75
-0.3484
-0.3194
89.25
-0.4510
-0.4359
70.5
-0.2388
-0.1991
80
-0.3512
-0.3226
89.5
-0.4536
-0.4389
70.75
-0.2418
-0.2023
80.25
-0.3541
-0.3258
89.75
-0.4561
-0.4418
71
-0.2449
-0.2055
80.5
-0.3569
-0.3290
90
-0.4586
-0.4446
71.25
-0.2479
-0.2087
80.75
-0.3597
-0.3322
90.25
-0.4612
-0.4475
71.5
-0.2509
-0.2120
81
-0.3625
-0.3354
90.5
-0.4637
-0.4504
71.75
-0.2539
-0.2152
81.25
-0.3654
-0.3386
90.75
-0.4662
-0.4533
72
-0.2569
-0.2184
81.5
-0.3682
-0.3417
91
-0.4687
-0.4561
72.25
-0.2599
-0.2217
81.75
-0.3709
-0.3449
91.25
-0.4712
-0.4590
72.5
-0.2630
-0.2249
82
-0.3737
-0.3480
91.5
-0.4737
-0.4618
72.75
-0.2660
-0.2282
82.25
-0.3765
-0.3512
91.75
-0.4762
-0.4647
73
-0.2690
-0.2315
82.5
-0.3793
-0.3543
92
-0.4787
-0.4675
73.25
-0.2720
-0.2347
82.75
-0.3820
-0.3574
92.25
-0.4811
-0.4703
73.5
-0.2750
-0.2380
83
-0.3848
-0.3606
92.5
-0.4836
-0.4732
73.75
-0.2780
-0.2413
83.25
-0.3875
-0.3637
92.75
-0.4861
-0.4760
74
-0.2810
-0.2445
83.5
-0.3903
-0.3668
93
-0.4885
-0.4788
74.25
-0.2840
-0.2478
83.75
-0.3930
-0.3699
93.25
-0.4910
-0.4816
74.5
-0.2869
-0.2511
84
-0.3957
-0.3730
93.5
-0.4934
-0.4844
74.75
-0.2899
-0.2543
84.25
-0.3984
-0.3760
93.75
-0.4959
-0.4871
75
-0.2929
-0.2576
84.5
-0.4011
-0.3791
94
-0.4983
-0.4899
75.25
-0.2959
-0.2609
84.75
-0.4038
-0.3822
94.25
-0.5007
-0.4927


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
59
MEDICATIONS FOR ANALYSES
Relevant SAP section
Parameter
Source of data
3.4.3
Additional steroids for 
asthma*
1a.  Inhaled corticosteroids as recorded on the EXACASI 
module
1b. MED module with ATC codes R03BA or R03AK and 
reason is either ‘Disease under study’ or ‘Protocol defined 
exacerbation of disease under study’.
1c. MED module with ATC codes R03BA or R03AK and 
Therapy reason is ’Adverse event’ and Reason for therapy 
text in the MED module contains the word ’asthma’ or 
’astma’. (Note each letter in asthma/astma should be allowed 
to be in upper/lower case)
1d. MED module with ATC codes R03BA or R03AK and 
Therapy reason is ’Other’ and Reason for therapy contains
the word ’asthma’ or ’astma’ (Note each letter in 
asthma/astma should be allowed to be in upper/lower case)
2. Systemic corticosteroids given for an exacerbation as per 
the EXACASI module
3a. Systemic corticosteroids recorded on the MED module 
where ATC code is H02AB and Therapy reason is ‘Disease 
under study’ or ‘Protocol defined exacerbation of disease 
under study’
3b. Systemic corticosteroids recorded on the MED module 
where ATC code is H02AB and Therapy reason is ’Adverse 
event’ and Reason for therapy text in the MED module 
contains the word ’asthma’ or ’astma'. (Note each letter in 
asthma/astma should be allowed to be in upper/lower case)
3c. Systemic corticosteroids recorded on the MED module 
where ATC code is H02AB and Therapy reason is ’Other’ 
and Reason for therapy text  contains the word ’asthma’ 
(Note each letter in asthma/astma should be allowed to be in 
upper/lower case)
3.4.3
Total inhaled steroid 
load**
1a and any medication in the MED module with ATC code 
either R03BA or R03AK (all reasons) plus investigational 
product.  The exception is on the treatment end date, when 
only those steroids prescribed for asthma (1a above) are used.
3.4.4
Number of days of 
systemic GCS use due 
to asthma***
2, 3a, 3b, or 3c above 
* For medications starting on the day of IP discontinuation, the only sources of data are 1a, 2 and 3a
** For medications starting on the day of IP discontinuation, the only source of data is 1a
*** For medications starting on the day of IP discontinuation, the only sources of data are 2 and 3a.  


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
60
9.
APPENDIX 3: POTENTIAL CLASS EFFECTS Β2-AGONISTS 
AND POTENTIAL ICS EFFECTS
The following is a list of preferred terms, in MedDRA version 20.0, representing potential β2-
agonist effects, presented by medical concept (group of terms describing the same medical 
phenomenon). The preferred terms and the medical concepts have been defined by 
AstraZeneca and is applicable for the Symbicort development program as needed. 
Potential class effects β2- agonists
Medical concept
MedDRA (version 20.0) Preferred Term
Agitation
Agitation
Aggression
Anxiety
Anxiety
Feeling jittery
Nervousness
Restlessness
Tension
Hyperglycaemia  
Blood glucose increased
Hyperglycaemia
Headache
Headache
Muscle cramp
Muscle spasms
Hypokalaemia
Blood Potassium decreased
Hypokalaemia
Sleep effects
Initial insomnia
Insomnia
Sleep disorder
Tremor
Tremor
Cardiac events
Acute myocardial infarction
Adams-Stokes syndrome
Angina pectoris
Angina unstable
Arrhythmia
Arrhythmia supraventricular
Atrial fibrillation
Atrial flutter
Atrial tachycardia
Blood pressure ambulatory increased
Blood pressure increased


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
61
Blood pressure systolic increased
Extrasystoles
Heart rate increased
Hypertension
Palpitations
Sinus tachycardia
Supraventricular extrasystoles
Supraventricular tachyarrhythmia
Supraventricular tachycardia
Tachyarrhythmia
Tachycardia
Ventricular extrasystoles
Choice of terms agreed between Symbicort’s GSP Ulrika Larsdotter, SP Fredrik Randers, SSAMT leader Svante 
Joelson and PS Ulrika Emerath on 28 April 2017. 
The following list is of preferred terms, in MedDRA version 20.0, representing potential ICS
effects, presented by location and medical concept (group of terms describing the same 
medical phenomenon). The preferred terms and the medical concepts have been defined by 
AstraZeneca and is applicable for the Symbicort development program as needed. 
Potential Class effects
Inhaled corticosteroids
Location
Medical concept
MedDRA (version 20.0) Preferred Term
Local steroid effects
Candidiasis
Candida infection
Oral candidiasis
Oropharyngeal candidiasis
Voice effects
Aphonia
Dysphonia
Systemic steroid effects
Adrenal suppression
Addison´s disease
Adrenal insufficiency
Adrenal suppression
Adrenocortical insufficiency acute
Blood cortisol decreased
Cortisol free urine decreased
Secondary adrenocortical insufficiency
Urine cortisol/creatinine ratio decreased
Diabetes control
Diabetes mellitus
Diabetes mellitus inadequate control
Metabolic bone 
All Pts in MedDRA Standardised 


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
62
effects and fractures
MedDRA query (SMQ): 
Osteoporosis/osteopenia, version 20.0 
broad
Growth retardation
Growth retardation
Body height below normal
Body height decreased
Ocular effects
Cataract
Cataract cortical
Cataract diabetic
Cataract nuclear
Cataract subcapsular
Glaucoma
Angle closure glaucoma
Open angle glaucoma
Intraocular pressure increased
Lenticular opacities
Ocular hypertension
Glaucomatous optic disc atrophy
Intraocular pressure test abnormal
Psychiatric effects
Depressed mood
Depressive symptom
Dysphoria
Euphoric mood
Insomnia
Psychotic disorder
Restlessness
Skin effects
Contusion
Ecchymosis
Increased tendency to bruise
Petechiae
Purpura
Skin atrophy
Taste effects
Dysgeusia
Choice of terms agreed between Symbicort’s GSP Ulrika Larsdotter, SP Fredrik Randers, SSAMT leader Svante 
Joelson and PS Ulrika Emerath on 28 April 2017. 
Updated to MedDRA 20.0 by Ulrika Emerath on 4 May 2017.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
63
10.
APPENDIX 4: VISIT WINDOWING
Visit windowing for run-in, on-treatment and end of treatment measurements will be 
conducted for FEV1, FVC, ACQ, AQLQ, EQ5D, vital signs, height, weight and physical 
examination. For each measurement, the available data will be used to determine which 
analysis visit number the measurement belongs to. Raw visit numbers will not be used in 
analysis. For each analysis visit the acceptable timing range describes the earliest and latest 
date a measurement can occur to be considered as the value for that analysis visit. For 
instance, the acceptable timing range for analysis visit 4 is >13 to 21 weeks, so measurements 
occurring on or before 13 weeks and after 21 weeks cannot be considered as an analysis Visit
4 measurement. 
Table 3 Acceptable timing range for each visit
Stage
Analysis Visit 
number
Timepoint
Endpoints 
collected
Acceptable time range in relation to 
first dose of IP
Run-in
Visit 2
-
FEV1, FVC, 
ACQ, AQLQ
FEV1, FVC, ACQ, AQLQ: Visit 2 
measurement from date of Visit 2 until 
the day of first run-in medication. 
Vital signs, height weight and physical 
examination: Visit 2
Baseline visit
Visit 3
0 weeks
FEV1, FVC, 
ACQ, 
AQLQ, 
EQ5D
See Section 3.1.1 for definitions of 
baseline.
On treatment*
Visit 4
17 weeks
FEV1, FVC, 
ACQ, 
AQLQ, 
EQ5D
>13 to 21 weeks
On treatment*
Visit 5
34 weeks
FEV1, FVC, 
ACQ, 
AQLQ, 
EQ5D
>30 to 38 weeks


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
64
On treatment
Visit 6
52 weeks
All, apart 
from height 
which is 
collected for 
adolescents 
only. 
≥48 weeks 
Acceptable upper range for 
measurements:
FEV1, FVC: date of analysis Visit 6 and 
no later than the day after IP
discontinuation.
ACQ, AQLQ, EQ5D, vital signs, height 
(adolescents only), weight and physical 
examination: no later than 7 days after 
IP discontinuation.
End of treatment
Visit 7
-
All, apart 
from height 
which is 
collected for 
adolescents 
only.
End of treatment can occur anytime 
between Visit 3 and one day after IP 
discontinuation for all patients who took 
at least one dose of IP. 
Acceptable upper range for 
measurements:
FEV1, FVC: date of analysis Visit 6 and 
no later than the day after IP 
discontinuation.
ACQ, AQLQ, EQ5D, vital signs, height 
(adolescents only), weight and physical 
examination: no later than 7 days after 
IP discontinuation.
*If a patient discontinues IP early, all measurements up to and including the day after IP discontinuation can be 
considered for on-treatment values. 
Rules for FEV1, FVC, EQ5D, vital signs, height, weight and physical examination:
1. Measurements from unscheduled visits (visit number with decimals of format X.0X or 
with a module occurrence number>1000) will not be used in the analysis. The rational 
for this is that normally an unscheduled visit is made in connection to an asthma 
exacerbation or AE, and assessments at such visits will not be representative of 
scheduled visits. There are cases when a measurement cannot be completed at the 
scheduled visits. In these cases, the patient returns on another timepoint to complete 
the assessment. In these cases, the scheduled visit number is used in combination with 
a recording of the actual assessment date. Such an assessment will not be considered 
unscheduled and can be included in the analysis. 
2. The order of selecting measurements for each visit is specified below. Visit timepoint 
is the CSP specified timepoint, as in CSP Table 1, i.e. Visit 4 timepoint is 4 weeks. 
Note that a scheduled visit inside another scheduled visit’s timing window will be 
considered for analysis, e.g. a Visit 4 occurring in Visit 5 window (>30 - 38 weeks). 
Also note that if there is more than one non-missing observation at same date, the one 


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
65
with the lowest module occurrence number should be used as that should be the 
original measurement. Refer to Table 3 for acceptable timing range.  
Rules for ACQ and AQLQ:
1. Unlike the other parameters, ACQ and AQLQ should not be measured on unscheduled 
visits in connection to for example an AE or exacerbation. Therefore, as visit numbers 
were not collected for ACQ and AQLQ, we only look at the assessment date in 
relation to the date of first dose of IP according to the acceptable timing range in Table 
3.
2. If there is more than one non-missing observation of ACQ and AQLQ at the same date 
the worse assessment should be used. Which assessment is worse is based on the total 
score. For ACQ a higher total score is worse, and for AQLQ a lower total score is 
worse.
Run-in analysis visit:
1. Use scheduled Visit 2 if available and within acceptable Visit 2 timing range. Include 
assessments recorded as Visit 2 even if before Visit 2 date and or after until day of 
run-in medication
2. If more than one scheduled Visit 2 in acceptable Visit 2 timing range use earliest 
scheduled visit.  
Randomisation visit
1. If more than one scheduled Visit 3 in acceptable Visit 3 timing range use earliest
scheduled visit.  
On-treatment analysis Visits 4 and 5 
1. Use closest scheduled visit to visit timepoint if within visit acceptable timing range 
and at most one day after IP discontinuation if patient is a non-completer. If 2 or more 
scheduled visits from visit timepoint are equidistant (and not more than 1 day after IP 
discontinuation if patient is a non-completer) use earlier visit.
2. Use closest other scheduled visit if within visit acceptable range and at most one day 
after IP discontinuation if patient is a non-completer. If 2 or more scheduled visits 
from visit timepoint are equidistant (and not more than 1 day after IP discontinuation if 
patient is a non-completer) use earlier visit.
End of treatment analysis visit for FEV1 and FVC 
If a Visit 6 measurement according to visit windows is missing, use last available non-missing 
measurement made at a scheduled visit but no later than one day after IP discontinuation.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
66
End of treatment analysis visit for other variables 
Other variables include ACQ, AQLQ, EQ5D, vital signs, height (adolescents only), weight 
and physical examination.
If a Visit 6 measurement according to visit windows is missing, use last available non-missing 
measurement made at a scheduled visit but no later than 7 days after IP discontinuation.
On-treatment analysis Visit 6 
Patients must have completed at least 48 weeks on IP to have a Visit 6 measurement. For 
these patients, their Visit 6 measurements will be the same as their end of treatment 
measurements.


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
67
11.
APPENDIX 5: COMPUTING EQ-5D-5L CROSSWALK INDEX 
VALUES WITH SAS USING THE UNITED KINGDOM (UK) 
VALUE SET
The variables for the 5 dimensions of the EQ-5D-5L descriptive system should be named 'mobility', 
'selfcare', 'activity', 'pain', and 'anxiety'. If they are given different names the syntax code below will not 
work properly. The 5 variables should contain the values for the different dimensions in the EQ-5D 
health profile (i.e. 1, 2, 3, 4 or 5). The variable 'EQindex' contains the values of the EQ-5D-5L 
crosswalk index values on the basis of the UK set of weights. 
You can copy and paste the syntax below directly into a SAS syntax window.
******************************************************************
*SAS syntax code for the computation of index*
*values with the UK TTO value set*
******************************************************************;
data Euroqol.UK_tto;
set Euroqol.EQ5D_states;
EQindex = .;
if (mobility=1 and selfcare=1 and activity=1 and pain=1 and anxiety=1) then EQindex = 1.000;
if (mobility=1 and selfcare=1 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.879;
if (mobility=1 and selfcare=1 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.848;
if (mobility=1 and selfcare=1 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.635;
if (mobility=1 and selfcare=1 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.414;
if (mobility=1 and selfcare=1 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.837;
if (mobility=1 and selfcare=1 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.768;
if (mobility=1 and selfcare=1 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.750;
if (mobility=1 and selfcare=1 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.537;
if (mobility=1 and selfcare=1 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.316;
if (mobility=1 and selfcare=1 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.796;
if (mobility=1 and selfcare=1 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.740;
if (mobility=1 and selfcare=1 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.725;
if (mobility=1 and selfcare=1 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.512;
if (mobility=1 and selfcare=1 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.291;
if (mobility=1 and selfcare=1 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.584;
if (mobility=1 and selfcare=1 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.527;
if (mobility=1 and selfcare=1 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.513;
if (mobility=1 and selfcare=1 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.352;
if (mobility=1 and selfcare=1 and activity=1 and pain=4 and anxiety=5) then EQindex = 0.186;
if (mobility=1 and selfcare=1 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.264;
if (mobility=1 and selfcare=1 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.208;
if (mobility=1 and selfcare=1 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.193;
if (mobility=1 and selfcare=1 and activity=1 and pain=5 and anxiety=4) then EQindex = 0.112;
if (mobility=1 and selfcare=1 and activity=1 and pain=5 and anxiety=5) then EQindex = 0.028;
if (mobility=1 and selfcare=1 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.906;
if (mobility=1 and selfcare=1 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.837;
if (mobility=1 and selfcare=1 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.819;
if (mobility=1 and selfcare=1 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.606;
if (mobility=1 and selfcare=1 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.385;
if (mobility=1 and selfcare=1 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.795;
if (mobility=1 and selfcare=1 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.736;
if (mobility=1 and selfcare=1 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.721;
if (mobility=1 and selfcare=1 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.508;
if (mobility=1 and selfcare=1 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.287;
if (mobility=1 and selfcare=1 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.767;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
68
if (mobility=1 and selfcare=1 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.711;
if (mobility=1 and selfcare=1 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.696;
if (mobility=1 and selfcare=1 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.483;
if (mobility=1 and selfcare=1 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.262;
if (mobility=1 and selfcare=1 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.555;
if (mobility=1 and selfcare=1 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.498;
if (mobility=1 and selfcare=1 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.484;
if (mobility=1 and selfcare=1 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.323;
if (mobility=1 and selfcare=1 and activity=2 and pain=4 and anxiety=5) then EQindex = 0.157;
if (mobility=1 and selfcare=1 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.235;
if (mobility=1 and selfcare=1 and activity=2 and pain=5 and anxiety=2) then EQindex = 0.179;
if (mobility=1 and selfcare=1 and activity=2 and pain=5 and anxiety=3) then EQindex = 0.164;
if (mobility=1 and selfcare=1 and activity=2 and pain=5 and anxiety=4) then EQindex = 0.083;
if (mobility=1 and selfcare=1 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.001;
if (mobility=1 and selfcare=1 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.883;
if (mobility=1 and selfcare=1 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.827;
if (mobility=1 and selfcare=1 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.812;
if (mobility=1 and selfcare=1 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.599;
if (mobility=1 and selfcare=1 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.378;
if (mobility=1 and selfcare=1 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.785;
if (mobility=1 and selfcare=1 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.728;
if (mobility=1 and selfcare=1 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.714;
if (mobility=1 and selfcare=1 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.501;
if (mobility=1 and selfcare=1 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.280;
if (mobility=1 and selfcare=1 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.760;
if (mobility=1 and selfcare=1 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.704;
if (mobility=1 and selfcare=1 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.689;
if (mobility=1 and selfcare=1 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.476;
if (mobility=1 and selfcare=1 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.255;
if (mobility=1 and selfcare=1 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.548;
if (mobility=1 and selfcare=1 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.491;
if (mobility=1 and selfcare=1 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.477;
if (mobility=1 and selfcare=1 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.316;
if (mobility=1 and selfcare=1 and activity=3 and pain=4 and anxiety=5) then EQindex = 0.150;
if (mobility=1 and selfcare=1 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.228;
if (mobility=1 and selfcare=1 and activity=3 and pain=5 and anxiety=2) then EQindex = 0.172;
if (mobility=1 and selfcare=1 and activity=3 and pain=5 and anxiety=3) then EQindex = 0.157;
if (mobility=1 and selfcare=1 and activity=3 and pain=5 and anxiety=4) then EQindex = 0.076;
if (mobility=1 and selfcare=1 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.008;
if (mobility=1 and selfcare=1 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.776;
if (mobility=1 and selfcare=1 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.719;
if (mobility=1 and selfcare=1 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.705;
if (mobility=1 and selfcare=1 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.535;
if (mobility=1 and selfcare=1 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.359;
if (mobility=1 and selfcare=1 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.677;
if (mobility=1 and selfcare=1 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.621;
if (mobility=1 and selfcare=1 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.606;
if (mobility=1 and selfcare=1 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.437;
if (mobility=1 and selfcare=1 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.260;
if (mobility=1 and selfcare=1 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.653;
if (mobility=1 and selfcare=1 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.596;
if (mobility=1 and selfcare=1 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.582;
if (mobility=1 and selfcare=1 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.412;
if (mobility=1 and selfcare=1 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.236;
if (mobility=1 and selfcare=1 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.475;
if (mobility=1 and selfcare=1 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.419;
if (mobility=1 and selfcare=1 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.404;
if (mobility=1 and selfcare=1 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.270;
if (mobility=1 and selfcare=1 and activity=4 and pain=4 and anxiety=5) then EQindex = 0.131;
if (mobility=1 and selfcare=1 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.209;
if (mobility=1 and selfcare=1 and activity=4 and pain=5 and anxiety=2) then EQindex = 0.153;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
69
if (mobility=1 and selfcare=1 and activity=4 and pain=5 and anxiety=3) then EQindex = 0.138;
if (mobility=1 and selfcare=1 and activity=4 and pain=5 and anxiety=4) then EQindex = 0.057;
if (mobility=1 and selfcare=1 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.027;
if (mobility=1 and selfcare=1 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.556;
if (mobility=1 and selfcare=1 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.500;
if (mobility=1 and selfcare=1 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.485;
if (mobility=1 and selfcare=1 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.404;
if (mobility=1 and selfcare=1 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.320;
if (mobility=1 and selfcare=1 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.458;
if (mobility=1 and selfcare=1 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.401;
if (mobility=1 and selfcare=1 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.387;
if (mobility=1 and selfcare=1 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.306;
if (mobility=1 and selfcare=1 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.222;
if (mobility=1 and selfcare=1 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.433;
if (mobility=1 and selfcare=1 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.377;
if (mobility=1 and selfcare=1 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.362;
if (mobility=1 and selfcare=1 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.281;
if (mobility=1 and selfcare=1 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.197;
if (mobility=1 and selfcare=1 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.328;
if (mobility=1 and selfcare=1 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.272;
if (mobility=1 and selfcare=1 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.257;
if (mobility=1 and selfcare=1 and activity=5 and pain=4 and anxiety=4) then EQindex = 0.176;
if (mobility=1 and selfcare=1 and activity=5 and pain=4 and anxiety=5) then EQindex = 0.092;
if (mobility=1 and selfcare=1 and activity=5 and pain=5 and anxiety=1) then EQindex = 0.170;
if (mobility=1 and selfcare=1 and activity=5 and pain=5 and anxiety=2) then EQindex = 0.114;
if (mobility=1 and selfcare=1 and activity=5 and pain=5 and anxiety=3) then EQindex = 0.099;
if (mobility=1 and selfcare=1 and activity=5 and pain=5 and anxiety=4) then EQindex = 0.018;
if (mobility=1 and selfcare=1 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.066;
if (mobility=1 and selfcare=2 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.846;
if (mobility=1 and selfcare=2 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.779;
if (mobility=1 and selfcare=2 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.761;
if (mobility=1 and selfcare=2 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.548;
if (mobility=1 and selfcare=2 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.327;
if (mobility=1 and selfcare=2 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.737;
if (mobility=1 and selfcare=2 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.678;
if (mobility=1 and selfcare=2 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.663;
if (mobility=1 and selfcare=2 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.450;
if (mobility=1 and selfcare=2 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.229;
if (mobility=1 and selfcare=2 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.709;
if (mobility=1 and selfcare=2 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.653;
if (mobility=1 and selfcare=2 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.638;
if (mobility=1 and selfcare=2 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.425;
if (mobility=1 and selfcare=2 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.204;
if (mobility=1 and selfcare=2 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.497;
if (mobility=1 and selfcare=2 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.441;
if (mobility=1 and selfcare=2 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.426;
if (mobility=1 and selfcare=2 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.266;
if (mobility=1 and selfcare=2 and activity=1 and pain=4 and anxiety=5) then EQindex = 0.099;
if (mobility=1 and selfcare=2 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.177;
if (mobility=1 and selfcare=2 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.121;
if (mobility=1 and selfcare=2 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.106;
if (mobility=1 and selfcare=2 and activity=1 and pain=5 and anxiety=4) then EQindex = 0.025;
if (mobility=1 and selfcare=2 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.059;
if (mobility=1 and selfcare=2 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.806;
if (mobility=1 and selfcare=2 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.748;
if (mobility=1 and selfcare=2 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.733;
if (mobility=1 and selfcare=2 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.520;
if (mobility=1 and selfcare=2 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.299;
if (mobility=1 and selfcare=2 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.706;
if (mobility=1 and selfcare=2 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.649;
if (mobility=1 and selfcare=2 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.634;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
70
if (mobility=1 and selfcare=2 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.421;
if (mobility=1 and selfcare=2 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.200;
if (mobility=1 and selfcare=2 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.681;
if (mobility=1 and selfcare=2 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.624;
if (mobility=1 and selfcare=2 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.610;
if (mobility=1 and selfcare=2 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.397;
if (mobility=1 and selfcare=2 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.176;
if (mobility=1 and selfcare=2 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.468;
if (mobility=1 and selfcare=2 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.412;
if (mobility=1 and selfcare=2 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.397;
if (mobility=1 and selfcare=2 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.237;
if (mobility=1 and selfcare=2 and activity=2 and pain=4 and anxiety=5) then EQindex = 0.071;
if (mobility=1 and selfcare=2 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.149;
if (mobility=1 and selfcare=2 and activity=2 and pain=5 and anxiety=2) then EQindex = 0.092;
if (mobility=1 and selfcare=2 and activity=2 and pain=5 and anxiety=3) then EQindex = 0.078;
if (mobility=1 and selfcare=2 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.003;
if (mobility=1 and selfcare=2 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.088;
if (mobility=1 and selfcare=2 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.796;
if (mobility=1 and selfcare=2 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.740;
if (mobility=1 and selfcare=2 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.725;
if (mobility=1 and selfcare=2 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.512;
if (mobility=1 and selfcare=2 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.291;
if (mobility=1 and selfcare=2 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.698;
if (mobility=1 and selfcare=2 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.642;
if (mobility=1 and selfcare=2 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.627;
if (mobility=1 and selfcare=2 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.414;
if (mobility=1 and selfcare=2 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.193;
if (mobility=1 and selfcare=2 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.673;
if (mobility=1 and selfcare=2 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.617;
if (mobility=1 and selfcare=2 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.602;
if (mobility=1 and selfcare=2 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.389;
if (mobility=1 and selfcare=2 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.168;
if (mobility=1 and selfcare=2 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.461;
if (mobility=1 and selfcare=2 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.405;
if (mobility=1 and selfcare=2 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.390;
if (mobility=1 and selfcare=2 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.230;
if (mobility=1 and selfcare=2 and activity=3 and pain=4 and anxiety=5) then EQindex = 0.063;
if (mobility=1 and selfcare=2 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.141;
if (mobility=1 and selfcare=2 and activity=3 and pain=5 and anxiety=2) then EQindex = 0.085;
if (mobility=1 and selfcare=2 and activity=3 and pain=5 and anxiety=3) then EQindex = 0.070;
if (mobility=1 and selfcare=2 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.011;
if (mobility=1 and selfcare=2 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.095;
if (mobility=1 and selfcare=2 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.689;
if (mobility=1 and selfcare=2 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.633;
if (mobility=1 and selfcare=2 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.618;
if (mobility=1 and selfcare=2 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.448;
if (mobility=1 and selfcare=2 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.272;
if (mobility=1 and selfcare=2 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.591;
if (mobility=1 and selfcare=2 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.534;
if (mobility=1 and selfcare=2 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.520;
if (mobility=1 and selfcare=2 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.350;
if (mobility=1 and selfcare=2 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.174;
if (mobility=1 and selfcare=2 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.566;
if (mobility=1 and selfcare=2 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.510;
if (mobility=1 and selfcare=2 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.495;
if (mobility=1 and selfcare=2 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.325;
if (mobility=1 and selfcare=2 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.149;
if (mobility=1 and selfcare=2 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.389;
if (mobility=1 and selfcare=2 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.332;
if (mobility=1 and selfcare=2 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.318;
if (mobility=1 and selfcare=2 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.184;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
71
if (mobility=1 and selfcare=2 and activity=4 and pain=4 and anxiety=5) then EQindex = 0.044;
if (mobility=1 and selfcare=2 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.122;
if (mobility=1 and selfcare=2 and activity=4 and pain=5 and anxiety=2) then EQindex = 0.066;
if (mobility=1 and selfcare=2 and activity=4 and pain=5 and anxiety=3) then EQindex = 0.051;
if (mobility=1 and selfcare=2 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.030;
if (mobility=1 and selfcare=2 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.114;
if (mobility=1 and selfcare=2 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.469;
if (mobility=1 and selfcare=2 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.413;
if (mobility=1 and selfcare=2 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.398;
if (mobility=1 and selfcare=2 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.317;
if (mobility=1 and selfcare=2 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.233;
if (mobility=1 and selfcare=2 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.371;
if (mobility=1 and selfcare=2 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.315;
if (mobility=1 and selfcare=2 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.300;
if (mobility=1 and selfcare=2 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.219;
if (mobility=1 and selfcare=2 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.135;
if (mobility=1 and selfcare=2 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.346;
if (mobility=1 and selfcare=2 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.290;
if (mobility=1 and selfcare=2 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.275;
if (mobility=1 and selfcare=2 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.194;
if (mobility=1 and selfcare=2 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.110;
if (mobility=1 and selfcare=2 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.241;
if (mobility=1 and selfcare=2 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.185;
if (mobility=1 and selfcare=2 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.170;
if (mobility=1 and selfcare=2 and activity=5 and pain=4 and anxiety=4) then EQindex = 0.089;
if (mobility=1 and selfcare=2 and activity=5 and pain=4 and anxiety=5) then EQindex = 0.005;
if (mobility=1 and selfcare=2 and activity=5 and pain=5 and anxiety=1) then EQindex = 0.083;
if (mobility=1 and selfcare=2 and activity=5 and pain=5 and anxiety=2) then EQindex = 0.027;
if (mobility=1 and selfcare=2 and activity=5 and pain=5 and anxiety=3) then EQindex = 0.012;
if (mobility=1 and selfcare=2 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.069;
if (mobility=1 and selfcare=2 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.153;
if (mobility=1 and selfcare=3 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.815;
if (mobility=1 and selfcare=3 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.759;
if (mobility=1 and selfcare=3 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.744;
if (mobility=1 and selfcare=3 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.531;
if (mobility=1 and selfcare=3 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.310;
if (mobility=1 and selfcare=3 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.717;
if (mobility=1 and selfcare=3 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.660;
if (mobility=1 and selfcare=3 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.646;
if (mobility=1 and selfcare=3 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.433;
if (mobility=1 and selfcare=3 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.212;
if (mobility=1 and selfcare=3 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.692;
if (mobility=1 and selfcare=3 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.636;
if (mobility=1 and selfcare=3 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.621;
if (mobility=1 and selfcare=3 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.408;
if (mobility=1 and selfcare=3 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.187;
if (mobility=1 and selfcare=3 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.480;
if (mobility=1 and selfcare=3 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.423;
if (mobility=1 and selfcare=3 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.409;
if (mobility=1 and selfcare=3 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.248;
if (mobility=1 and selfcare=3 and activity=1 and pain=4 and anxiety=5) then EQindex = 0.082;
if (mobility=1 and selfcare=3 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.160;
if (mobility=1 and selfcare=3 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.104;
if (mobility=1 and selfcare=3 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.089;
if (mobility=1 and selfcare=3 and activity=1 and pain=5 and anxiety=4) then EQindex = 0.008;
if (mobility=1 and selfcare=3 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.076;
if (mobility=1 and selfcare=3 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.786;
if (mobility=1 and selfcare=3 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.730;
if (mobility=1 and selfcare=3 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.715;
if (mobility=1 and selfcare=3 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.502;
if (mobility=1 and selfcare=3 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.281;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
72
if (mobility=1 and selfcare=3 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.688;
if (mobility=1 and selfcare=3 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.631;
if (mobility=1 and selfcare=3 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.617;
if (mobility=1 and selfcare=3 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.404;
if (mobility=1 and selfcare=3 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.183;
if (mobility=1 and selfcare=3 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.663;
if (mobility=1 and selfcare=3 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.607;
if (mobility=1 and selfcare=3 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.592;
if (mobility=1 and selfcare=3 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.379;
if (mobility=1 and selfcare=3 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.158;
if (mobility=1 and selfcare=3 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.451;
if (mobility=1 and selfcare=3 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.394;
if (mobility=1 and selfcare=3 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.380;
if (mobility=1 and selfcare=3 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.219;
if (mobility=1 and selfcare=3 and activity=2 and pain=4 and anxiety=5) then EQindex = 0.053;
if (mobility=1 and selfcare=3 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.131;
if (mobility=1 and selfcare=3 and activity=2 and pain=5 and anxiety=2) then EQindex = 0.075;
if (mobility=1 and selfcare=3 and activity=2 and pain=5 and anxiety=3) then EQindex = 0.060;
if (mobility=1 and selfcare=3 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.021;
if (mobility=1 and selfcare=3 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.105;
if (mobility=1 and selfcare=3 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.779;
if (mobility=1 and selfcare=3 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.723;
if (mobility=1 and selfcare=3 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.708;
if (mobility=1 and selfcare=3 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.495;
if (mobility=1 and selfcare=3 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.274;
if (mobility=1 and selfcare=3 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.681;
if (mobility=1 and selfcare=3 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.624;
if (mobility=1 and selfcare=3 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.610;
if (mobility=1 and selfcare=3 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.397;
if (mobility=1 and selfcare=3 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.176;
if (mobility=1 and selfcare=3 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.656;
if (mobility=1 and selfcare=3 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.600;
if (mobility=1 and selfcare=3 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.585;
if (mobility=1 and selfcare=3 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.372;
if (mobility=1 and selfcare=3 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.151;
if (mobility=1 and selfcare=3 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.444;
if (mobility=1 and selfcare=3 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.387;
if (mobility=1 and selfcare=3 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.373;
if (mobility=1 and selfcare=3 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.212;
if (mobility=1 and selfcare=3 and activity=3 and pain=4 and anxiety=5) then EQindex = 0.046;
if (mobility=1 and selfcare=3 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.124;
if (mobility=1 and selfcare=3 and activity=3 and pain=5 and anxiety=2) then EQindex = 0.068;
if (mobility=1 and selfcare=3 and activity=3 and pain=5 and anxiety=3) then EQindex = 0.053;
if (mobility=1 and selfcare=3 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.028;
if (mobility=1 and selfcare=3 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.112;
if (mobility=1 and selfcare=3 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.672;
if (mobility=1 and selfcare=3 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.615;
if (mobility=1 and selfcare=3 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.601;
if (mobility=1 and selfcare=3 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.431;
if (mobility=1 and selfcare=3 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.255;
if (mobility=1 and selfcare=3 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.573;
if (mobility=1 and selfcare=3 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.517;
if (mobility=1 and selfcare=3 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.502;
if (mobility=1 and selfcare=3 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.333;
if (mobility=1 and selfcare=3 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.156;
if (mobility=1 and selfcare=3 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.549;
if (mobility=1 and selfcare=3 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.492;
if (mobility=1 and selfcare=3 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.478;
if (mobility=1 and selfcare=3 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.308;
if (mobility=1 and selfcare=3 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.132;
if (mobility=1 and selfcare=3 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.371;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
73
if (mobility=1 and selfcare=3 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.315;
if (mobility=1 and selfcare=3 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.300;
if (mobility=1 and selfcare=3 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.166;
if (mobility=1 and selfcare=3 and activity=4 and pain=4 and anxiety=5) then EQindex = 0.027;
if (mobility=1 and selfcare=3 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.105;
if (mobility=1 and selfcare=3 and activity=4 and pain=5 and anxiety=2) then EQindex = 0.049;
if (mobility=1 and selfcare=3 and activity=4 and pain=5 and anxiety=3) then EQindex = 0.034;
if (mobility=1 and selfcare=3 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.047;
if (mobility=1 and selfcare=3 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.131;
if (mobility=1 and selfcare=3 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.452;
if (mobility=1 and selfcare=3 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.396;
if (mobility=1 and selfcare=3 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.381;
if (mobility=1 and selfcare=3 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.300;
if (mobility=1 and selfcare=3 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.216;
if (mobility=1 and selfcare=3 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.354;
if (mobility=1 and selfcare=3 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.297;
if (mobility=1 and selfcare=3 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.283;
if (mobility=1 and selfcare=3 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.202;
if (mobility=1 and selfcare=3 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.118;
if (mobility=1 and selfcare=3 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.329;
if (mobility=1 and selfcare=3 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.273;
if (mobility=1 and selfcare=3 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.258;
if (mobility=1 and selfcare=3 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.177;
if (mobility=1 and selfcare=3 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.093;
if (mobility=1 and selfcare=3 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.224;
if (mobility=1 and selfcare=3 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.168;
if (mobility=1 and selfcare=3 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.153;
if (mobility=1 and selfcare=3 and activity=5 and pain=4 and anxiety=4) then EQindex = 0.072;
if (mobility=1 and selfcare=3 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.012;
if (mobility=1 and selfcare=3 and activity=5 and pain=5 and anxiety=1) then EQindex = 0.066;
if (mobility=1 and selfcare=3 and activity=5 and pain=5 and anxiety=2) then EQindex = 0.010;
if (mobility=1 and selfcare=3 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.005;
if (mobility=1 and selfcare=3 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.086;
if (mobility=1 and selfcare=3 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.170;
if (mobility=1 and selfcare=4 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.723;
if (mobility=1 and selfcare=4 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.667;
if (mobility=1 and selfcare=4 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.652;
if (mobility=1 and selfcare=4 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.471;
if (mobility=1 and selfcare=4 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.283;
if (mobility=1 and selfcare=4 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.624;
if (mobility=1 and selfcare=4 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.568;
if (mobility=1 and selfcare=4 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.553;
if (mobility=1 and selfcare=4 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.373;
if (mobility=1 and selfcare=4 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.185;
if (mobility=1 and selfcare=4 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.600;
if (mobility=1 and selfcare=4 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.544;
if (mobility=1 and selfcare=4 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.529;
if (mobility=1 and selfcare=4 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.348;
if (mobility=1 and selfcare=4 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.160;
if (mobility=1 and selfcare=4 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.414;
if (mobility=1 and selfcare=4 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.357;
if (mobility=1 and selfcare=4 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.343;
if (mobility=1 and selfcare=4 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.202;
if (mobility=1 and selfcare=4 and activity=1 and pain=4 and anxiety=5) then EQindex = 0.055;
if (mobility=1 and selfcare=4 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.133;
if (mobility=1 and selfcare=4 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.077;
if (mobility=1 and selfcare=4 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.062;
if (mobility=1 and selfcare=4 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.019;
if (mobility=1 and selfcare=4 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.103;
if (mobility=1 and selfcare=4 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.694;
if (mobility=1 and selfcare=4 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.638;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
74
if (mobility=1 and selfcare=4 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.623;
if (mobility=1 and selfcare=4 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.442;
if (mobility=1 and selfcare=4 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.254;
if (mobility=1 and selfcare=4 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.596;
if (mobility=1 and selfcare=4 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.539;
if (mobility=1 and selfcare=4 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.525;
if (mobility=1 and selfcare=4 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.344;
if (mobility=1 and selfcare=4 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.156;
if (mobility=1 and selfcare=4 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.571;
if (mobility=1 and selfcare=4 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.515;
if (mobility=1 and selfcare=4 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.500;
if (mobility=1 and selfcare=4 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.319;
if (mobility=1 and selfcare=4 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.131;
if (mobility=1 and selfcare=4 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.385;
if (mobility=1 and selfcare=4 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.328;
if (mobility=1 and selfcare=4 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.314;
if (mobility=1 and selfcare=4 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.173;
if (mobility=1 and selfcare=4 and activity=2 and pain=4 and anxiety=5) then EQindex = 0.026;
if (mobility=1 and selfcare=4 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.104;
if (mobility=1 and selfcare=4 and activity=2 and pain=5 and anxiety=2) then EQindex = 0.048;
if (mobility=1 and selfcare=4 and activity=2 and pain=5 and anxiety=3) then EQindex = 0.033;
if (mobility=1 and selfcare=4 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.048;
if (mobility=1 and selfcare=4 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.132;
if (mobility=1 and selfcare=4 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.687;
if (mobility=1 and selfcare=4 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.631;
if (mobility=1 and selfcare=4 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.616;
if (mobility=1 and selfcare=4 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.435;
if (mobility=1 and selfcare=4 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.247;
if (mobility=1 and selfcare=4 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.588;
if (mobility=1 and selfcare=4 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.532;
if (mobility=1 and selfcare=4 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.517;
if (mobility=1 and selfcare=4 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.337;
if (mobility=1 and selfcare=4 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.149;
if (mobility=1 and selfcare=4 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.564;
if (mobility=1 and selfcare=4 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.508;
if (mobility=1 and selfcare=4 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.493;
if (mobility=1 and selfcare=4 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.312;
if (mobility=1 and selfcare=4 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.124;
if (mobility=1 and selfcare=4 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.378;
if (mobility=1 and selfcare=4 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.321;
if (mobility=1 and selfcare=4 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.307;
if (mobility=1 and selfcare=4 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.166;
if (mobility=1 and selfcare=4 and activity=3 and pain=4 and anxiety=5) then EQindex = 0.019;
if (mobility=1 and selfcare=4 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.097;
if (mobility=1 and selfcare=4 and activity=3 and pain=5 and anxiety=2) then EQindex = 0.041;
if (mobility=1 and selfcare=4 and activity=3 and pain=5 and anxiety=3) then EQindex = 0.026;
if (mobility=1 and selfcare=4 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.055;
if (mobility=1 and selfcare=4 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.139;
if (mobility=1 and selfcare=4 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.601;
if (mobility=1 and selfcare=4 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.545;
if (mobility=1 and selfcare=4 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.530;
if (mobility=1 and selfcare=4 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.382;
if (mobility=1 and selfcare=4 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.228;
if (mobility=1 and selfcare=4 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.502;
if (mobility=1 and selfcare=4 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.446;
if (mobility=1 and selfcare=4 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.431;
if (mobility=1 and selfcare=4 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.283;
if (mobility=1 and selfcare=4 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.130;
if (mobility=1 and selfcare=4 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.478;
if (mobility=1 and selfcare=4 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.422;
if (mobility=1 and selfcare=4 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.407;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
75
if (mobility=1 and selfcare=4 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.259;
if (mobility=1 and selfcare=4 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.105;
if (mobility=1 and selfcare=4 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.318;
if (mobility=1 and selfcare=4 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.262;
if (mobility=1 and selfcare=4 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.247;
if (mobility=1 and selfcare=4 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.126;
if (mobility=1 and selfcare=4 and activity=4 and pain=4 and anxiety=5) then EQindex = 0.000;
if (mobility=1 and selfcare=4 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.078;
if (mobility=1 and selfcare=4 and activity=4 and pain=5 and anxiety=2) then EQindex = 0.022;
if (mobility=1 and selfcare=4 and activity=4 and pain=5 and anxiety=3) then EQindex = 0.007;
if (mobility=1 and selfcare=4 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.074;
if (mobility=1 and selfcare=4 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.158;
if (mobility=1 and selfcare=4 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.425;
if (mobility=1 and selfcare=4 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.369;
if (mobility=1 and selfcare=4 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.354;
if (mobility=1 and selfcare=4 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.273;
if (mobility=1 and selfcare=4 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.189;
if (mobility=1 and selfcare=4 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.327;
if (mobility=1 and selfcare=4 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.270;
if (mobility=1 and selfcare=4 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.256;
if (mobility=1 and selfcare=4 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.175;
if (mobility=1 and selfcare=4 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.091;
if (mobility=1 and selfcare=4 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.302;
if (mobility=1 and selfcare=4 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.246;
if (mobility=1 and selfcare=4 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.231;
if (mobility=1 and selfcare=4 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.150;
if (mobility=1 and selfcare=4 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.066;
if (mobility=1 and selfcare=4 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.197;
if (mobility=1 and selfcare=4 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.141;
if (mobility=1 and selfcare=4 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.126;
if (mobility=1 and selfcare=4 and activity=5 and pain=4 and anxiety=4) then EQindex = 0.045;
if (mobility=1 and selfcare=4 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.039;
if (mobility=1 and selfcare=4 and activity=5 and pain=5 and anxiety=1) then EQindex = 0.039;
if (mobility=1 and selfcare=4 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.017;
if (mobility=1 and selfcare=4 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.032;
if (mobility=1 and selfcare=4 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.113;
if (mobility=1 and selfcare=4 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.197;
if (mobility=1 and selfcare=5 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.436;
if (mobility=1 and selfcare=5 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.380;
if (mobility=1 and selfcare=5 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.365;
if (mobility=1 and selfcare=5 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.284;
if (mobility=1 and selfcare=5 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.200;
if (mobility=1 and selfcare=5 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.338;
if (mobility=1 and selfcare=5 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.281;
if (mobility=1 and selfcare=5 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.267;
if (mobility=1 and selfcare=5 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.186;
if (mobility=1 and selfcare=5 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.102;
if (mobility=1 and selfcare=5 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.313;
if (mobility=1 and selfcare=5 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.257;
if (mobility=1 and selfcare=5 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.242;
if (mobility=1 and selfcare=5 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.161;
if (mobility=1 and selfcare=5 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.077;
if (mobility=1 and selfcare=5 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.208;
if (mobility=1 and selfcare=5 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.152;
if (mobility=1 and selfcare=5 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.137;
if (mobility=1 and selfcare=5 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.056;
if (mobility=1 and selfcare=5 and activity=1 and pain=4 and anxiety=5) then EQindex = -0.028;
if (mobility=1 and selfcare=5 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.050;
if (mobility=1 and selfcare=5 and activity=1 and pain=5 and anxiety=2) then EQindex = -0.006;
if (mobility=1 and selfcare=5 and activity=1 and pain=5 and anxiety=3) then EQindex = -0.021;
if (mobility=1 and selfcare=5 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.102;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
76
if (mobility=1 and selfcare=5 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.186;
if (mobility=1 and selfcare=5 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.407;
if (mobility=1 and selfcare=5 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.351;
if (mobility=1 and selfcare=5 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.336;
if (mobility=1 and selfcare=5 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.255;
if (mobility=1 and selfcare=5 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.171;
if (mobility=1 and selfcare=5 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.309;
if (mobility=1 and selfcare=5 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.252;
if (mobility=1 and selfcare=5 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.238;
if (mobility=1 and selfcare=5 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.157;
if (mobility=1 and selfcare=5 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.073;
if (mobility=1 and selfcare=5 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.284;
if (mobility=1 and selfcare=5 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.228;
if (mobility=1 and selfcare=5 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.213;
if (mobility=1 and selfcare=5 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.132;
if (mobility=1 and selfcare=5 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.048;
if (mobility=1 and selfcare=5 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.179;
if (mobility=1 and selfcare=5 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.123;
if (mobility=1 and selfcare=5 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.108;
if (mobility=1 and selfcare=5 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.027;
if (mobility=1 and selfcare=5 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.057;
if (mobility=1 and selfcare=5 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.021;
if (mobility=1 and selfcare=5 and activity=2 and pain=5 and anxiety=2) then EQindex = -0.035;
if (mobility=1 and selfcare=5 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.050;
if (mobility=1 and selfcare=5 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.131;
if (mobility=1 and selfcare=5 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.215;
if (mobility=1 and selfcare=5 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.400;
if (mobility=1 and selfcare=5 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.344;
if (mobility=1 and selfcare=5 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.329;
if (mobility=1 and selfcare=5 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.248;
if (mobility=1 and selfcare=5 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.164;
if (mobility=1 and selfcare=5 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.302;
if (mobility=1 and selfcare=5 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.245;
if (mobility=1 and selfcare=5 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.231;
if (mobility=1 and selfcare=5 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.150;
if (mobility=1 and selfcare=5 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.066;
if (mobility=1 and selfcare=5 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.277;
if (mobility=1 and selfcare=5 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.221;
if (mobility=1 and selfcare=5 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.206;
if (mobility=1 and selfcare=5 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.125;
if (mobility=1 and selfcare=5 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.041;
if (mobility=1 and selfcare=5 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.172;
if (mobility=1 and selfcare=5 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.116;
if (mobility=1 and selfcare=5 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.101;
if (mobility=1 and selfcare=5 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.020;
if (mobility=1 and selfcare=5 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.064;
if (mobility=1 and selfcare=5 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.014;
if (mobility=1 and selfcare=5 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.042;
if (mobility=1 and selfcare=5 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.057;
if (mobility=1 and selfcare=5 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.138;
if (mobility=1 and selfcare=5 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.222;
if (mobility=1 and selfcare=5 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.381;
if (mobility=1 and selfcare=5 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.325;
if (mobility=1 and selfcare=5 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.310;
if (mobility=1 and selfcare=5 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.229;
if (mobility=1 and selfcare=5 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.145;
if (mobility=1 and selfcare=5 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.282;
if (mobility=1 and selfcare=5 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.226;
if (mobility=1 and selfcare=5 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.211;
if (mobility=1 and selfcare=5 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.130;
if (mobility=1 and selfcare=5 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.046;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
77
if (mobility=1 and selfcare=5 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.258;
if (mobility=1 and selfcare=5 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.202;
if (mobility=1 and selfcare=5 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.187;
if (mobility=1 and selfcare=5 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.106;
if (mobility=1 and selfcare=5 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.022;
if (mobility=1 and selfcare=5 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.153;
if (mobility=1 and selfcare=5 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.097;
if (mobility=1 and selfcare=5 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.082;
if (mobility=1 and selfcare=5 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.001;
if (mobility=1 and selfcare=5 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.083;
if (mobility=1 and selfcare=5 and activity=4 and pain=5 and anxiety=1) then EQindex = -0.005;
if (mobility=1 and selfcare=5 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.061;
if (mobility=1 and selfcare=5 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.076;
if (mobility=1 and selfcare=5 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.157;
if (mobility=1 and selfcare=5 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.241;
if (mobility=1 and selfcare=5 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.342;
if (mobility=1 and selfcare=5 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.286;
if (mobility=1 and selfcare=5 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.271;
if (mobility=1 and selfcare=5 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.190;
if (mobility=1 and selfcare=5 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.106;
if (mobility=1 and selfcare=5 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.244;
if (mobility=1 and selfcare=5 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.187;
if (mobility=1 and selfcare=5 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.173;
if (mobility=1 and selfcare=5 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.092;
if (mobility=1 and selfcare=5 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.008;
if (mobility=1 and selfcare=5 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.219;
if (mobility=1 and selfcare=5 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.163;
if (mobility=1 and selfcare=5 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.148;
if (mobility=1 and selfcare=5 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.067;
if (mobility=1 and selfcare=5 and activity=5 and pain=3 and anxiety=5) then EQindex = -0.017;
if (mobility=1 and selfcare=5 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.114;
if (mobility=1 and selfcare=5 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.058;
if (mobility=1 and selfcare=5 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.043;
if (mobility=1 and selfcare=5 and activity=5 and pain=4 and anxiety=4) then EQindex = -0.038;
if (mobility=1 and selfcare=5 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.122;
if (mobility=1 and selfcare=5 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.044;
if (mobility=1 and selfcare=5 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.100;
if (mobility=1 and selfcare=5 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.115;
if (mobility=1 and selfcare=5 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.196;
if (mobility=1 and selfcare=5 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.280;
if (mobility=2 and selfcare=1 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.877;
if (mobility=2 and selfcare=1 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.809;
if (mobility=2 and selfcare=1 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.791;
if (mobility=2 and selfcare=1 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.578;
if (mobility=2 and selfcare=1 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.357;
if (mobility=2 and selfcare=1 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.767;
if (mobility=2 and selfcare=1 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.708;
if (mobility=2 and selfcare=1 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.693;
if (mobility=2 and selfcare=1 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.480;
if (mobility=2 and selfcare=1 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.259;
if (mobility=2 and selfcare=1 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.739;
if (mobility=2 and selfcare=1 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.683;
if (mobility=2 and selfcare=1 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.668;
if (mobility=2 and selfcare=1 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.455;
if (mobility=2 and selfcare=1 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.234;
if (mobility=2 and selfcare=1 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.527;
if (mobility=2 and selfcare=1 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.470;
if (mobility=2 and selfcare=1 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.456;
if (mobility=2 and selfcare=1 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.296;
if (mobility=2 and selfcare=1 and activity=1 and pain=4 and anxiety=5) then EQindex = 0.129;
if (mobility=2 and selfcare=1 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.207;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
78
if (mobility=2 and selfcare=1 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.151;
if (mobility=2 and selfcare=1 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.136;
if (mobility=2 and selfcare=1 and activity=1 and pain=5 and anxiety=4) then EQindex = 0.055;
if (mobility=2 and selfcare=1 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.029;
if (mobility=2 and selfcare=1 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.836;
if (mobility=2 and selfcare=1 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.778;
if (mobility=2 and selfcare=1 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.762;
if (mobility=2 and selfcare=1 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.549;
if (mobility=2 and selfcare=1 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.328;
if (mobility=2 and selfcare=1 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.735;
if (mobility=2 and selfcare=1 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.679;
if (mobility=2 and selfcare=1 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.664;
if (mobility=2 and selfcare=1 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.451;
if (mobility=2 and selfcare=1 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.230;
if (mobility=2 and selfcare=1 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.710;
if (mobility=2 and selfcare=1 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.654;
if (mobility=2 and selfcare=1 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.639;
if (mobility=2 and selfcare=1 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.426;
if (mobility=2 and selfcare=1 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.205;
if (mobility=2 and selfcare=1 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.498;
if (mobility=2 and selfcare=1 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.442;
if (mobility=2 and selfcare=1 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.427;
if (mobility=2 and selfcare=1 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.267;
if (mobility=2 and selfcare=1 and activity=2 and pain=4 and anxiety=5) then EQindex = 0.100;
if (mobility=2 and selfcare=1 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.178;
if (mobility=2 and selfcare=1 and activity=2 and pain=5 and anxiety=2) then EQindex = 0.122;
if (mobility=2 and selfcare=1 and activity=2 and pain=5 and anxiety=3) then EQindex = 0.107;
if (mobility=2 and selfcare=1 and activity=2 and pain=5 and anxiety=4) then EQindex = 0.026;
if (mobility=2 and selfcare=1 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.058;
if (mobility=2 and selfcare=1 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.826;
if (mobility=2 and selfcare=1 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.770;
if (mobility=2 and selfcare=1 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.755;
if (mobility=2 and selfcare=1 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.542;
if (mobility=2 and selfcare=1 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.321;
if (mobility=2 and selfcare=1 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.728;
if (mobility=2 and selfcare=1 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.671;
if (mobility=2 and selfcare=1 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.657;
if (mobility=2 and selfcare=1 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.444;
if (mobility=2 and selfcare=1 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.223;
if (mobility=2 and selfcare=1 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.703;
if (mobility=2 and selfcare=1 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.647;
if (mobility=2 and selfcare=1 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.632;
if (mobility=2 and selfcare=1 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.419;
if (mobility=2 and selfcare=1 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.198;
if (mobility=2 and selfcare=1 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.491;
if (mobility=2 and selfcare=1 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.434;
if (mobility=2 and selfcare=1 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.420;
if (mobility=2 and selfcare=1 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.260;
if (mobility=2 and selfcare=1 and activity=3 and pain=4 and anxiety=5) then EQindex = 0.093;
if (mobility=2 and selfcare=1 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.171;
if (mobility=2 and selfcare=1 and activity=3 and pain=5 and anxiety=2) then EQindex = 0.115;
if (mobility=2 and selfcare=1 and activity=3 and pain=5 and anxiety=3) then EQindex = 0.100;
if (mobility=2 and selfcare=1 and activity=3 and pain=5 and anxiety=4) then EQindex = 0.019;
if (mobility=2 and selfcare=1 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.065;
if (mobility=2 and selfcare=1 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.719;
if (mobility=2 and selfcare=1 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.663;
if (mobility=2 and selfcare=1 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.648;
if (mobility=2 and selfcare=1 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.478;
if (mobility=2 and selfcare=1 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.302;
if (mobility=2 and selfcare=1 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.620;
if (mobility=2 and selfcare=1 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.564;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
79
if (mobility=2 and selfcare=1 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.549;
if (mobility=2 and selfcare=1 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.380;
if (mobility=2 and selfcare=1 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.204;
if (mobility=2 and selfcare=1 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.596;
if (mobility=2 and selfcare=1 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.540;
if (mobility=2 and selfcare=1 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.525;
if (mobility=2 and selfcare=1 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.355;
if (mobility=2 and selfcare=1 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.179;
if (mobility=2 and selfcare=1 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.419;
if (mobility=2 and selfcare=1 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.362;
if (mobility=2 and selfcare=1 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.348;
if (mobility=2 and selfcare=1 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.213;
if (mobility=2 and selfcare=1 and activity=4 and pain=4 and anxiety=5) then EQindex = 0.074;
if (mobility=2 and selfcare=1 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.152;
if (mobility=2 and selfcare=1 and activity=4 and pain=5 and anxiety=2) then EQindex = 0.096;
if (mobility=2 and selfcare=1 and activity=4 and pain=5 and anxiety=3) then EQindex = 0.081;
if (mobility=2 and selfcare=1 and activity=4 and pain=5 and anxiety=4) then EQindex = 0.000;
if (mobility=2 and selfcare=1 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.084;
if (mobility=2 and selfcare=1 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.499;
if (mobility=2 and selfcare=1 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.443;
if (mobility=2 and selfcare=1 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.428;
if (mobility=2 and selfcare=1 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.347;
if (mobility=2 and selfcare=1 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.263;
if (mobility=2 and selfcare=1 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.401;
if (mobility=2 and selfcare=1 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.344;
if (mobility=2 and selfcare=1 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.330;
if (mobility=2 and selfcare=1 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.249;
if (mobility=2 and selfcare=1 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.165;
if (mobility=2 and selfcare=1 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.376;
if (mobility=2 and selfcare=1 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.320;
if (mobility=2 and selfcare=1 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.305;
if (mobility=2 and selfcare=1 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.224;
if (mobility=2 and selfcare=1 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.140;
if (mobility=2 and selfcare=1 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.271;
if (mobility=2 and selfcare=1 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.215;
if (mobility=2 and selfcare=1 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.200;
if (mobility=2 and selfcare=1 and activity=5 and pain=4 and anxiety=4) then EQindex = 0.119;
if (mobility=2 and selfcare=1 and activity=5 and pain=4 and anxiety=5) then EQindex = 0.035;
if (mobility=2 and selfcare=1 and activity=5 and pain=5 and anxiety=1) then EQindex = 0.113;
if (mobility=2 and selfcare=1 and activity=5 and pain=5 and anxiety=2) then EQindex = 0.057;
if (mobility=2 and selfcare=1 and activity=5 and pain=5 and anxiety=3) then EQindex = 0.042;
if (mobility=2 and selfcare=1 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.039;
if (mobility=2 and selfcare=1 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.123;
if (mobility=2 and selfcare=2 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.778;
if (mobility=2 and selfcare=2 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.720;
if (mobility=2 and selfcare=2 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.705;
if (mobility=2 and selfcare=2 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.492;
if (mobility=2 and selfcare=2 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.271;
if (mobility=2 and selfcare=2 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.678;
if (mobility=2 and selfcare=2 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.621;
if (mobility=2 and selfcare=2 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.606;
if (mobility=2 and selfcare=2 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.393;
if (mobility=2 and selfcare=2 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.172;
if (mobility=2 and selfcare=2 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.653;
if (mobility=2 and selfcare=2 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.596;
if (mobility=2 and selfcare=2 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.582;
if (mobility=2 and selfcare=2 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.369;
if (mobility=2 and selfcare=2 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.148;
if (mobility=2 and selfcare=2 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.440;
if (mobility=2 and selfcare=2 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.384;
if (mobility=2 and selfcare=2 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.369;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
80
if (mobility=2 and selfcare=2 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.209;
if (mobility=2 and selfcare=2 and activity=1 and pain=4 and anxiety=5) then EQindex = 0.043;
if (mobility=2 and selfcare=2 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.121;
if (mobility=2 and selfcare=2 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.064;
if (mobility=2 and selfcare=2 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.050;
if (mobility=2 and selfcare=2 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.031;
if (mobility=2 and selfcare=2 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.115;
if (mobility=2 and selfcare=2 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.747;
if (mobility=2 and selfcare=2 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.691;
if (mobility=2 and selfcare=2 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.676;
if (mobility=2 and selfcare=2 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.463;
if (mobility=2 and selfcare=2 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.242;
if (mobility=2 and selfcare=2 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.648;
if (mobility=2 and selfcare=2 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.592;
if (mobility=2 and selfcare=2 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.577;
if (mobility=2 and selfcare=2 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.364;
if (mobility=2 and selfcare=2 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.143;
if (mobility=2 and selfcare=2 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.624;
if (mobility=2 and selfcare=2 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.567;
if (mobility=2 and selfcare=2 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.553;
if (mobility=2 and selfcare=2 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.340;
if (mobility=2 and selfcare=2 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.119;
if (mobility=2 and selfcare=2 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.411;
if (mobility=2 and selfcare=2 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.355;
if (mobility=2 and selfcare=2 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.340;
if (mobility=2 and selfcare=2 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.180;
if (mobility=2 and selfcare=2 and activity=2 and pain=4 and anxiety=5) then EQindex = 0.014;
if (mobility=2 and selfcare=2 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.092;
if (mobility=2 and selfcare=2 and activity=2 and pain=5 and anxiety=2) then EQindex = 0.035;
if (mobility=2 and selfcare=2 and activity=2 and pain=5 and anxiety=3) then EQindex = 0.021;
if (mobility=2 and selfcare=2 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.060;
if (mobility=2 and selfcare=2 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.144;
if (mobility=2 and selfcare=2 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.740;
if (mobility=2 and selfcare=2 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.683;
if (mobility=2 and selfcare=2 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.669;
if (mobility=2 and selfcare=2 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.456;
if (mobility=2 and selfcare=2 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.235;
if (mobility=2 and selfcare=2 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.641;
if (mobility=2 and selfcare=2 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.585;
if (mobility=2 and selfcare=2 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.570;
if (mobility=2 and selfcare=2 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.357;
if (mobility=2 and selfcare=2 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.136;
if (mobility=2 and selfcare=2 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.617;
if (mobility=2 and selfcare=2 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.560;
if (mobility=2 and selfcare=2 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.546;
if (mobility=2 and selfcare=2 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.333;
if (mobility=2 and selfcare=2 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.112;
if (mobility=2 and selfcare=2 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.404;
if (mobility=2 and selfcare=2 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.348;
if (mobility=2 and selfcare=2 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.333;
if (mobility=2 and selfcare=2 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.173;
if (mobility=2 and selfcare=2 and activity=3 and pain=4 and anxiety=5) then EQindex = 0.007;
if (mobility=2 and selfcare=2 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.085;
if (mobility=2 and selfcare=2 and activity=3 and pain=5 and anxiety=2) then EQindex = 0.028;
if (mobility=2 and selfcare=2 and activity=3 and pain=5 and anxiety=3) then EQindex = 0.014;
if (mobility=2 and selfcare=2 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.067;
if (mobility=2 and selfcare=2 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.151;
if (mobility=2 and selfcare=2 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.632;
if (mobility=2 and selfcare=2 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.576;
if (mobility=2 and selfcare=2 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.561;
if (mobility=2 and selfcare=2 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.392;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
81
if (mobility=2 and selfcare=2 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.216;
if (mobility=2 and selfcare=2 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.534;
if (mobility=2 and selfcare=2 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.477;
if (mobility=2 and selfcare=2 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.463;
if (mobility=2 and selfcare=2 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.293;
if (mobility=2 and selfcare=2 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.117;
if (mobility=2 and selfcare=2 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.509;
if (mobility=2 and selfcare=2 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.453;
if (mobility=2 and selfcare=2 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.438;
if (mobility=2 and selfcare=2 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.269;
if (mobility=2 and selfcare=2 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.093;
if (mobility=2 and selfcare=2 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.332;
if (mobility=2 and selfcare=2 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.276;
if (mobility=2 and selfcare=2 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.261;
if (mobility=2 and selfcare=2 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.127;
if (mobility=2 and selfcare=2 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.013;
if (mobility=2 and selfcare=2 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.066;
if (mobility=2 and selfcare=2 and activity=4 and pain=5 and anxiety=2) then EQindex = 0.009;
if (mobility=2 and selfcare=2 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.005;
if (mobility=2 and selfcare=2 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.086;
if (mobility=2 and selfcare=2 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.170;
if (mobility=2 and selfcare=2 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.413;
if (mobility=2 and selfcare=2 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.356;
if (mobility=2 and selfcare=2 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.342;
if (mobility=2 and selfcare=2 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.261;
if (mobility=2 and selfcare=2 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.177;
if (mobility=2 and selfcare=2 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.314;
if (mobility=2 and selfcare=2 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.258;
if (mobility=2 and selfcare=2 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.243;
if (mobility=2 and selfcare=2 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.162;
if (mobility=2 and selfcare=2 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.078;
if (mobility=2 and selfcare=2 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.290;
if (mobility=2 and selfcare=2 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.233;
if (mobility=2 and selfcare=2 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.219;
if (mobility=2 and selfcare=2 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.138;
if (mobility=2 and selfcare=2 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.054;
if (mobility=2 and selfcare=2 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.185;
if (mobility=2 and selfcare=2 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.128;
if (mobility=2 and selfcare=2 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.114;
if (mobility=2 and selfcare=2 and activity=5 and pain=4 and anxiety=4) then EQindex = 0.033;
if (mobility=2 and selfcare=2 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.051;
if (mobility=2 and selfcare=2 and activity=5 and pain=5 and anxiety=1) then EQindex = 0.027;
if (mobility=2 and selfcare=2 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.030;
if (mobility=2 and selfcare=2 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.044;
if (mobility=2 and selfcare=2 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.125;
if (mobility=2 and selfcare=2 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.209;
if (mobility=2 and selfcare=3 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.758;
if (mobility=2 and selfcare=3 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.702;
if (mobility=2 and selfcare=3 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.687;
if (mobility=2 and selfcare=3 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.474;
if (mobility=2 and selfcare=3 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.253;
if (mobility=2 and selfcare=3 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.660;
if (mobility=2 and selfcare=3 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.603;
if (mobility=2 and selfcare=3 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.589;
if (mobility=2 and selfcare=3 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.376;
if (mobility=2 and selfcare=3 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.155;
if (mobility=2 and selfcare=3 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.635;
if (mobility=2 and selfcare=3 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.579;
if (mobility=2 and selfcare=3 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.564;
if (mobility=2 and selfcare=3 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.351;
if (mobility=2 and selfcare=3 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.130;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
82
if (mobility=2 and selfcare=3 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.423;
if (mobility=2 and selfcare=3 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.366;
if (mobility=2 and selfcare=3 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.352;
if (mobility=2 and selfcare=3 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.192;
if (mobility=2 and selfcare=3 and activity=1 and pain=4 and anxiety=5) then EQindex = 0.025;
if (mobility=2 and selfcare=3 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.103;
if (mobility=2 and selfcare=3 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.047;
if (mobility=2 and selfcare=3 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.032;
if (mobility=2 and selfcare=3 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.049;
if (mobility=2 and selfcare=3 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.133;
if (mobility=2 and selfcare=3 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.729;
if (mobility=2 and selfcare=3 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.673;
if (mobility=2 and selfcare=3 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.658;
if (mobility=2 and selfcare=3 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.445;
if (mobility=2 and selfcare=3 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.224;
if (mobility=2 and selfcare=3 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.631;
if (mobility=2 and selfcare=3 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.575;
if (mobility=2 and selfcare=3 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.560;
if (mobility=2 and selfcare=3 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.347;
if (mobility=2 and selfcare=3 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.126;
if (mobility=2 and selfcare=3 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.606;
if (mobility=2 and selfcare=3 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.550;
if (mobility=2 and selfcare=3 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.535;
if (mobility=2 and selfcare=3 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.322;
if (mobility=2 and selfcare=3 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.101;
if (mobility=2 and selfcare=3 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.394;
if (mobility=2 and selfcare=3 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.338;
if (mobility=2 and selfcare=3 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.323;
if (mobility=2 and selfcare=3 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.163;
if (mobility=2 and selfcare=3 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.004;
if (mobility=2 and selfcare=3 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.074;
if (mobility=2 and selfcare=3 and activity=2 and pain=5 and anxiety=2) then EQindex = 0.018;
if (mobility=2 and selfcare=3 and activity=2 and pain=5 and anxiety=3) then EQindex = 0.003;
if (mobility=2 and selfcare=3 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.078;
if (mobility=2 and selfcare=3 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.162;
if (mobility=2 and selfcare=3 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.722;
if (mobility=2 and selfcare=3 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.666;
if (mobility=2 and selfcare=3 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.651;
if (mobility=2 and selfcare=3 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.438;
if (mobility=2 and selfcare=3 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.217;
if (mobility=2 and selfcare=3 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.624;
if (mobility=2 and selfcare=3 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.567;
if (mobility=2 and selfcare=3 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.553;
if (mobility=2 and selfcare=3 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.340;
if (mobility=2 and selfcare=3 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.119;
if (mobility=2 and selfcare=3 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.599;
if (mobility=2 and selfcare=3 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.543;
if (mobility=2 and selfcare=3 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.528;
if (mobility=2 and selfcare=3 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.315;
if (mobility=2 and selfcare=3 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.094;
if (mobility=2 and selfcare=3 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.387;
if (mobility=2 and selfcare=3 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.330;
if (mobility=2 and selfcare=3 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.316;
if (mobility=2 and selfcare=3 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.156;
if (mobility=2 and selfcare=3 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.011;
if (mobility=2 and selfcare=3 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.067;
if (mobility=2 and selfcare=3 and activity=3 and pain=5 and anxiety=2) then EQindex = 0.011;
if (mobility=2 and selfcare=3 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.004;
if (mobility=2 and selfcare=3 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.085;
if (mobility=2 and selfcare=3 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.169;
if (mobility=2 and selfcare=3 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.615;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
83
if (mobility=2 and selfcare=3 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.559;
if (mobility=2 and selfcare=3 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.544;
if (mobility=2 and selfcare=3 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.374;
if (mobility=2 and selfcare=3 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.198;
if (mobility=2 and selfcare=3 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.516;
if (mobility=2 and selfcare=3 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.460;
if (mobility=2 and selfcare=3 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.445;
if (mobility=2 and selfcare=3 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.276;
if (mobility=2 and selfcare=3 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.100;
if (mobility=2 and selfcare=3 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.492;
if (mobility=2 and selfcare=3 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.436;
if (mobility=2 and selfcare=3 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.421;
if (mobility=2 and selfcare=3 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.251;
if (mobility=2 and selfcare=3 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.075;
if (mobility=2 and selfcare=3 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.315;
if (mobility=2 and selfcare=3 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.258;
if (mobility=2 and selfcare=3 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.244;
if (mobility=2 and selfcare=3 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.109;
if (mobility=2 and selfcare=3 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.030;
if (mobility=2 and selfcare=3 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.048;
if (mobility=2 and selfcare=3 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.008;
if (mobility=2 and selfcare=3 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.023;
if (mobility=2 and selfcare=3 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.104;
if (mobility=2 and selfcare=3 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.188;
if (mobility=2 and selfcare=3 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.395;
if (mobility=2 and selfcare=3 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.339;
if (mobility=2 and selfcare=3 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.324;
if (mobility=2 and selfcare=3 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.243;
if (mobility=2 and selfcare=3 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.159;
if (mobility=2 and selfcare=3 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.297;
if (mobility=2 and selfcare=3 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.240;
if (mobility=2 and selfcare=3 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.226;
if (mobility=2 and selfcare=3 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.145;
if (mobility=2 and selfcare=3 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.061;
if (mobility=2 and selfcare=3 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.272;
if (mobility=2 and selfcare=3 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.216;
if (mobility=2 and selfcare=3 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.201;
if (mobility=2 and selfcare=3 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.120;
if (mobility=2 and selfcare=3 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.036;
if (mobility=2 and selfcare=3 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.167;
if (mobility=2 and selfcare=3 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.111;
if (mobility=2 and selfcare=3 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.096;
if (mobility=2 and selfcare=3 and activity=5 and pain=4 and anxiety=4) then EQindex = 0.015;
if (mobility=2 and selfcare=3 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.069;
if (mobility=2 and selfcare=3 and activity=5 and pain=5 and anxiety=1) then EQindex = 0.009;
if (mobility=2 and selfcare=3 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.047;
if (mobility=2 and selfcare=3 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.062;
if (mobility=2 and selfcare=3 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.143;
if (mobility=2 and selfcare=3 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.227;
if (mobility=2 and selfcare=4 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.666;
if (mobility=2 and selfcare=4 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.610;
if (mobility=2 and selfcare=4 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.595;
if (mobility=2 and selfcare=4 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.414;
if (mobility=2 and selfcare=4 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.227;
if (mobility=2 and selfcare=4 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.568;
if (mobility=2 and selfcare=4 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.511;
if (mobility=2 and selfcare=4 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.497;
if (mobility=2 and selfcare=4 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.316;
if (mobility=2 and selfcare=4 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.128;
if (mobility=2 and selfcare=4 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.543;
if (mobility=2 and selfcare=4 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.487;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
84
if (mobility=2 and selfcare=4 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.472;
if (mobility=2 and selfcare=4 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.291;
if (mobility=2 and selfcare=4 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.104;
if (mobility=2 and selfcare=4 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.357;
if (mobility=2 and selfcare=4 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.300;
if (mobility=2 and selfcare=4 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.286;
if (mobility=2 and selfcare=4 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.145;
if (mobility=2 and selfcare=4 and activity=1 and pain=4 and anxiety=5) then EQindex = -0.002;
if (mobility=2 and selfcare=4 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.077;
if (mobility=2 and selfcare=4 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.020;
if (mobility=2 and selfcare=4 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.006;
if (mobility=2 and selfcare=4 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.076;
if (mobility=2 and selfcare=4 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.160;
if (mobility=2 and selfcare=4 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.637;
if (mobility=2 and selfcare=4 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.581;
if (mobility=2 and selfcare=4 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.566;
if (mobility=2 and selfcare=4 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.385;
if (mobility=2 and selfcare=4 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.198;
if (mobility=2 and selfcare=4 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.539;
if (mobility=2 and selfcare=4 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.482;
if (mobility=2 and selfcare=4 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.468;
if (mobility=2 and selfcare=4 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.287;
if (mobility=2 and selfcare=4 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.099;
if (mobility=2 and selfcare=4 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.514;
if (mobility=2 and selfcare=4 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.458;
if (mobility=2 and selfcare=4 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.443;
if (mobility=2 and selfcare=4 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.262;
if (mobility=2 and selfcare=4 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.075;
if (mobility=2 and selfcare=4 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.328;
if (mobility=2 and selfcare=4 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.272;
if (mobility=2 and selfcare=4 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.257;
if (mobility=2 and selfcare=4 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.116;
if (mobility=2 and selfcare=4 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.030;
if (mobility=2 and selfcare=4 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.048;
if (mobility=2 and selfcare=4 and activity=2 and pain=5 and anxiety=2) then EQindex = -0.009;
if (mobility=2 and selfcare=4 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.023;
if (mobility=2 and selfcare=4 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.104;
if (mobility=2 and selfcare=4 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.188;
if (mobility=2 and selfcare=4 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.630;
if (mobility=2 and selfcare=4 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.574;
if (mobility=2 and selfcare=4 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.559;
if (mobility=2 and selfcare=4 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.378;
if (mobility=2 and selfcare=4 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.191;
if (mobility=2 and selfcare=4 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.532;
if (mobility=2 and selfcare=4 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.475;
if (mobility=2 and selfcare=4 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.461;
if (mobility=2 and selfcare=4 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.280;
if (mobility=2 and selfcare=4 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.092;
if (mobility=2 and selfcare=4 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.507;
if (mobility=2 and selfcare=4 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.451;
if (mobility=2 and selfcare=4 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.436;
if (mobility=2 and selfcare=4 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.255;
if (mobility=2 and selfcare=4 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.068;
if (mobility=2 and selfcare=4 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.321;
if (mobility=2 and selfcare=4 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.264;
if (mobility=2 and selfcare=4 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.250;
if (mobility=2 and selfcare=4 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.109;
if (mobility=2 and selfcare=4 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.038;
if (mobility=2 and selfcare=4 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.041;
if (mobility=2 and selfcare=4 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.016;
if (mobility=2 and selfcare=4 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.031;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
85
if (mobility=2 and selfcare=4 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.112;
if (mobility=2 and selfcare=4 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.196;
if (mobility=2 and selfcare=4 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.544;
if (mobility=2 and selfcare=4 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.488;
if (mobility=2 and selfcare=4 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.473;
if (mobility=2 and selfcare=4 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.325;
if (mobility=2 and selfcare=4 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.172;
if (mobility=2 and selfcare=4 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.446;
if (mobility=2 and selfcare=4 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.389;
if (mobility=2 and selfcare=4 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.375;
if (mobility=2 and selfcare=4 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.227;
if (mobility=2 and selfcare=4 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.073;
if (mobility=2 and selfcare=4 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.421;
if (mobility=2 and selfcare=4 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.365;
if (mobility=2 and selfcare=4 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.350;
if (mobility=2 and selfcare=4 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.202;
if (mobility=2 and selfcare=4 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.049;
if (mobility=2 and selfcare=4 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.262;
if (mobility=2 and selfcare=4 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.205;
if (mobility=2 and selfcare=4 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.191;
if (mobility=2 and selfcare=4 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.069;
if (mobility=2 and selfcare=4 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.057;
if (mobility=2 and selfcare=4 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.022;
if (mobility=2 and selfcare=4 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.035;
if (mobility=2 and selfcare=4 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.050;
if (mobility=2 and selfcare=4 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.131;
if (mobility=2 and selfcare=4 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.215;
if (mobility=2 and selfcare=4 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.369;
if (mobility=2 and selfcare=4 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.312;
if (mobility=2 and selfcare=4 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.298;
if (mobility=2 and selfcare=4 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.217;
if (mobility=2 and selfcare=4 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.133;
if (mobility=2 and selfcare=4 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.270;
if (mobility=2 and selfcare=4 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.214;
if (mobility=2 and selfcare=4 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.199;
if (mobility=2 and selfcare=4 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.118;
if (mobility=2 and selfcare=4 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.034;
if (mobility=2 and selfcare=4 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.246;
if (mobility=2 and selfcare=4 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.189;
if (mobility=2 and selfcare=4 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.175;
if (mobility=2 and selfcare=4 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.094;
if (mobility=2 and selfcare=4 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.010;
if (mobility=2 and selfcare=4 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.140;
if (mobility=2 and selfcare=4 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.084;
if (mobility=2 and selfcare=4 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.069;
if (mobility=2 and selfcare=4 and activity=5 and pain=4 and anxiety=4) then EQindex = -0.012;
if (mobility=2 and selfcare=4 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.096;
if (mobility=2 and selfcare=4 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.018;
if (mobility=2 and selfcare=4 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.074;
if (mobility=2 and selfcare=4 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.089;
if (mobility=2 and selfcare=4 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.170;
if (mobility=2 and selfcare=4 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.254;
if (mobility=2 and selfcare=5 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.379;
if (mobility=2 and selfcare=5 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.323;
if (mobility=2 and selfcare=5 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.308;
if (mobility=2 and selfcare=5 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.227;
if (mobility=2 and selfcare=5 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.143;
if (mobility=2 and selfcare=5 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.281;
if (mobility=2 and selfcare=5 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.224;
if (mobility=2 and selfcare=5 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.210;
if (mobility=2 and selfcare=5 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.129;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
86
if (mobility=2 and selfcare=5 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.045;
if (mobility=2 and selfcare=5 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.256;
if (mobility=2 and selfcare=5 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.200;
if (mobility=2 and selfcare=5 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.185;
if (mobility=2 and selfcare=5 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.104;
if (mobility=2 and selfcare=5 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.020;
if (mobility=2 and selfcare=5 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.151;
if (mobility=2 and selfcare=5 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.095;
if (mobility=2 and selfcare=5 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.080;
if (mobility=2 and selfcare=5 and activity=1 and pain=4 and anxiety=4) then EQindex = -0.001;
if (mobility=2 and selfcare=5 and activity=1 and pain=4 and anxiety=5) then EQindex = -0.085;
if (mobility=2 and selfcare=5 and activity=1 and pain=5 and anxiety=1) then EQindex = -0.007;
if (mobility=2 and selfcare=5 and activity=1 and pain=5 and anxiety=2) then EQindex = -0.063;
if (mobility=2 and selfcare=5 and activity=1 and pain=5 and anxiety=3) then EQindex = -0.078;
if (mobility=2 and selfcare=5 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.159;
if (mobility=2 and selfcare=5 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.243;
if (mobility=2 and selfcare=5 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.350;
if (mobility=2 and selfcare=5 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.294;
if (mobility=2 and selfcare=5 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.279;
if (mobility=2 and selfcare=5 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.198;
if (mobility=2 and selfcare=5 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.114;
if (mobility=2 and selfcare=5 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.252;
if (mobility=2 and selfcare=5 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.196;
if (mobility=2 and selfcare=5 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.181;
if (mobility=2 and selfcare=5 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.100;
if (mobility=2 and selfcare=5 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.016;
if (mobility=2 and selfcare=5 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.227;
if (mobility=2 and selfcare=5 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.171;
if (mobility=2 and selfcare=5 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.156;
if (mobility=2 and selfcare=5 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.075;
if (mobility=2 and selfcare=5 and activity=2 and pain=3 and anxiety=5) then EQindex = -0.009;
if (mobility=2 and selfcare=5 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.122;
if (mobility=2 and selfcare=5 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.066;
if (mobility=2 and selfcare=5 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.051;
if (mobility=2 and selfcare=5 and activity=2 and pain=4 and anxiety=4) then EQindex = -0.030;
if (mobility=2 and selfcare=5 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.114;
if (mobility=2 and selfcare=5 and activity=2 and pain=5 and anxiety=1) then EQindex = -0.036;
if (mobility=2 and selfcare=5 and activity=2 and pain=5 and anxiety=2) then EQindex = -0.092;
if (mobility=2 and selfcare=5 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.107;
if (mobility=2 and selfcare=5 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.188;
if (mobility=2 and selfcare=5 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.272;
if (mobility=2 and selfcare=5 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.343;
if (mobility=2 and selfcare=5 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.287;
if (mobility=2 and selfcare=5 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.272;
if (mobility=2 and selfcare=5 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.191;
if (mobility=2 and selfcare=5 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.107;
if (mobility=2 and selfcare=5 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.245;
if (mobility=2 and selfcare=5 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.188;
if (mobility=2 and selfcare=5 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.174;
if (mobility=2 and selfcare=5 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.093;
if (mobility=2 and selfcare=5 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.009;
if (mobility=2 and selfcare=5 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.220;
if (mobility=2 and selfcare=5 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.164;
if (mobility=2 and selfcare=5 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.149;
if (mobility=2 and selfcare=5 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.068;
if (mobility=2 and selfcare=5 and activity=3 and pain=3 and anxiety=5) then EQindex = -0.016;
if (mobility=2 and selfcare=5 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.115;
if (mobility=2 and selfcare=5 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.059;
if (mobility=2 and selfcare=5 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.044;
if (mobility=2 and selfcare=5 and activity=3 and pain=4 and anxiety=4) then EQindex = -0.037;
if (mobility=2 and selfcare=5 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.121;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
87
if (mobility=2 and selfcare=5 and activity=3 and pain=5 and anxiety=1) then EQindex = -0.043;
if (mobility=2 and selfcare=5 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.099;
if (mobility=2 and selfcare=5 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.114;
if (mobility=2 and selfcare=5 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.195;
if (mobility=2 and selfcare=5 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.279;
if (mobility=2 and selfcare=5 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.324;
if (mobility=2 and selfcare=5 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.268;
if (mobility=2 and selfcare=5 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.253;
if (mobility=2 and selfcare=5 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.172;
if (mobility=2 and selfcare=5 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.088;
if (mobility=2 and selfcare=5 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.226;
if (mobility=2 and selfcare=5 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.169;
if (mobility=2 and selfcare=5 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.155;
if (mobility=2 and selfcare=5 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.074;
if (mobility=2 and selfcare=5 and activity=4 and pain=2 and anxiety=5) then EQindex = -0.010;
if (mobility=2 and selfcare=5 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.201;
if (mobility=2 and selfcare=5 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.145;
if (mobility=2 and selfcare=5 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.130;
if (mobility=2 and selfcare=5 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.049;
if (mobility=2 and selfcare=5 and activity=4 and pain=3 and anxiety=5) then EQindex = -0.035;
if (mobility=2 and selfcare=5 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.096;
if (mobility=2 and selfcare=5 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.040;
if (mobility=2 and selfcare=5 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.025;
if (mobility=2 and selfcare=5 and activity=4 and pain=4 and anxiety=4) then EQindex = -0.056;
if (mobility=2 and selfcare=5 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.140;
if (mobility=2 and selfcare=5 and activity=4 and pain=5 and anxiety=1) then EQindex = -0.062;
if (mobility=2 and selfcare=5 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.118;
if (mobility=2 and selfcare=5 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.133;
if (mobility=2 and selfcare=5 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.214;
if (mobility=2 and selfcare=5 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.298;
if (mobility=2 and selfcare=5 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.285;
if (mobility=2 and selfcare=5 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.229;
if (mobility=2 and selfcare=5 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.214;
if (mobility=2 and selfcare=5 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.133;
if (mobility=2 and selfcare=5 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.049;
if (mobility=2 and selfcare=5 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.187;
if (mobility=2 and selfcare=5 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.130;
if (mobility=2 and selfcare=5 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.116;
if (mobility=2 and selfcare=5 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.035;
if (mobility=2 and selfcare=5 and activity=5 and pain=2 and anxiety=5) then EQindex = -0.049;
if (mobility=2 and selfcare=5 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.162;
if (mobility=2 and selfcare=5 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.106;
if (mobility=2 and selfcare=5 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.091;
if (mobility=2 and selfcare=5 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.010;
if (mobility=2 and selfcare=5 and activity=5 and pain=3 and anxiety=5) then EQindex = -0.074;
if (mobility=2 and selfcare=5 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.057;
if (mobility=2 and selfcare=5 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.001;
if (mobility=2 and selfcare=5 and activity=5 and pain=4 and anxiety=3) then EQindex = -0.014;
if (mobility=2 and selfcare=5 and activity=5 and pain=4 and anxiety=4) then EQindex = -0.095;
if (mobility=2 and selfcare=5 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.179;
if (mobility=2 and selfcare=5 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.101;
if (mobility=2 and selfcare=5 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.157;
if (mobility=2 and selfcare=5 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.172;
if (mobility=2 and selfcare=5 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.253;
if (mobility=2 and selfcare=5 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.337;
if (mobility=3 and selfcare=1 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.850;
if (mobility=3 and selfcare=1 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.794;
if (mobility=3 and selfcare=1 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.779;
if (mobility=3 and selfcare=1 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.566;
if (mobility=3 and selfcare=1 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.345;
if (mobility=3 and selfcare=1 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.752;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
88
if (mobility=3 and selfcare=1 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.695;
if (mobility=3 and selfcare=1 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.681;
if (mobility=3 and selfcare=1 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.468;
if (mobility=3 and selfcare=1 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.247;
if (mobility=3 and selfcare=1 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.727;
if (mobility=3 and selfcare=1 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.671;
if (mobility=3 and selfcare=1 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.656;
if (mobility=3 and selfcare=1 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.443;
if (mobility=3 and selfcare=1 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.222;
if (mobility=3 and selfcare=1 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.515;
if (mobility=3 and selfcare=1 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.458;
if (mobility=3 and selfcare=1 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.444;
if (mobility=3 and selfcare=1 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.283;
if (mobility=3 and selfcare=1 and activity=1 and pain=4 and anxiety=5) then EQindex = 0.117;
if (mobility=3 and selfcare=1 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.195;
if (mobility=3 and selfcare=1 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.139;
if (mobility=3 and selfcare=1 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.124;
if (mobility=3 and selfcare=1 and activity=1 and pain=5 and anxiety=4) then EQindex = 0.043;
if (mobility=3 and selfcare=1 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.041;
if (mobility=3 and selfcare=1 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.821;
if (mobility=3 and selfcare=1 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.765;
if (mobility=3 and selfcare=1 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.750;
if (mobility=3 and selfcare=1 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.537;
if (mobility=3 and selfcare=1 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.316;
if (mobility=3 and selfcare=1 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.723;
if (mobility=3 and selfcare=1 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.666;
if (mobility=3 and selfcare=1 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.652;
if (mobility=3 and selfcare=1 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.439;
if (mobility=3 and selfcare=1 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.218;
if (mobility=3 and selfcare=1 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.698;
if (mobility=3 and selfcare=1 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.642;
if (mobility=3 and selfcare=1 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.627;
if (mobility=3 and selfcare=1 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.414;
if (mobility=3 and selfcare=1 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.193;
if (mobility=3 and selfcare=1 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.486;
if (mobility=3 and selfcare=1 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.429;
if (mobility=3 and selfcare=1 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.415;
if (mobility=3 and selfcare=1 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.254;
if (mobility=3 and selfcare=1 and activity=2 and pain=4 and anxiety=5) then EQindex = 0.088;
if (mobility=3 and selfcare=1 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.166;
if (mobility=3 and selfcare=1 and activity=2 and pain=5 and anxiety=2) then EQindex = 0.110;
if (mobility=3 and selfcare=1 and activity=2 and pain=5 and anxiety=3) then EQindex = 0.095;
if (mobility=3 and selfcare=1 and activity=2 and pain=5 and anxiety=4) then EQindex = 0.014;
if (mobility=3 and selfcare=1 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.070;
if (mobility=3 and selfcare=1 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.814;
if (mobility=3 and selfcare=1 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.758;
if (mobility=3 and selfcare=1 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.743;
if (mobility=3 and selfcare=1 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.530;
if (mobility=3 and selfcare=1 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.309;
if (mobility=3 and selfcare=1 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.716;
if (mobility=3 and selfcare=1 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.659;
if (mobility=3 and selfcare=1 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.645;
if (mobility=3 and selfcare=1 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.432;
if (mobility=3 and selfcare=1 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.211;
if (mobility=3 and selfcare=1 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.691;
if (mobility=3 and selfcare=1 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.635;
if (mobility=3 and selfcare=1 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.620;
if (mobility=3 and selfcare=1 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.407;
if (mobility=3 and selfcare=1 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.186;
if (mobility=3 and selfcare=1 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.479;
if (mobility=3 and selfcare=1 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.422;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
89
if (mobility=3 and selfcare=1 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.408;
if (mobility=3 and selfcare=1 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.247;
if (mobility=3 and selfcare=1 and activity=3 and pain=4 and anxiety=5) then EQindex = 0.081;
if (mobility=3 and selfcare=1 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.159;
if (mobility=3 and selfcare=1 and activity=3 and pain=5 and anxiety=2) then EQindex = 0.103;
if (mobility=3 and selfcare=1 and activity=3 and pain=5 and anxiety=3) then EQindex = 0.088;
if (mobility=3 and selfcare=1 and activity=3 and pain=5 and anxiety=4) then EQindex = 0.007;
if (mobility=3 and selfcare=1 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.077;
if (mobility=3 and selfcare=1 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.707;
if (mobility=3 and selfcare=1 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.650;
if (mobility=3 and selfcare=1 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.636;
if (mobility=3 and selfcare=1 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.466;
if (mobility=3 and selfcare=1 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.290;
if (mobility=3 and selfcare=1 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.608;
if (mobility=3 and selfcare=1 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.552;
if (mobility=3 and selfcare=1 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.537;
if (mobility=3 and selfcare=1 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.368;
if (mobility=3 and selfcare=1 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.191;
if (mobility=3 and selfcare=1 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.584;
if (mobility=3 and selfcare=1 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.527;
if (mobility=3 and selfcare=1 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.513;
if (mobility=3 and selfcare=1 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.343;
if (mobility=3 and selfcare=1 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.167;
if (mobility=3 and selfcare=1 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.406;
if (mobility=3 and selfcare=1 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.350;
if (mobility=3 and selfcare=1 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.335;
if (mobility=3 and selfcare=1 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.201;
if (mobility=3 and selfcare=1 and activity=4 and pain=4 and anxiety=5) then EQindex = 0.062;
if (mobility=3 and selfcare=1 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.140;
if (mobility=3 and selfcare=1 and activity=4 and pain=5 and anxiety=2) then EQindex = 0.084;
if (mobility=3 and selfcare=1 and activity=4 and pain=5 and anxiety=3) then EQindex = 0.069;
if (mobility=3 and selfcare=1 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.012;
if (mobility=3 and selfcare=1 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.096;
if (mobility=3 and selfcare=1 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.487;
if (mobility=3 and selfcare=1 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.431;
if (mobility=3 and selfcare=1 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.416;
if (mobility=3 and selfcare=1 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.335;
if (mobility=3 and selfcare=1 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.251;
if (mobility=3 and selfcare=1 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.389;
if (mobility=3 and selfcare=1 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.332;
if (mobility=3 and selfcare=1 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.318;
if (mobility=3 and selfcare=1 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.237;
if (mobility=3 and selfcare=1 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.153;
if (mobility=3 and selfcare=1 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.364;
if (mobility=3 and selfcare=1 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.308;
if (mobility=3 and selfcare=1 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.293;
if (mobility=3 and selfcare=1 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.212;
if (mobility=3 and selfcare=1 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.128;
if (mobility=3 and selfcare=1 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.259;
if (mobility=3 and selfcare=1 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.203;
if (mobility=3 and selfcare=1 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.188;
if (mobility=3 and selfcare=1 and activity=5 and pain=4 and anxiety=4) then EQindex = 0.107;
if (mobility=3 and selfcare=1 and activity=5 and pain=4 and anxiety=5) then EQindex = 0.023;
if (mobility=3 and selfcare=1 and activity=5 and pain=5 and anxiety=1) then EQindex = 0.101;
if (mobility=3 and selfcare=1 and activity=5 and pain=5 and anxiety=2) then EQindex = 0.045;
if (mobility=3 and selfcare=1 and activity=5 and pain=5 and anxiety=3) then EQindex = 0.030;
if (mobility=3 and selfcare=1 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.051;
if (mobility=3 and selfcare=1 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.135;
if (mobility=3 and selfcare=2 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.763;
if (mobility=3 and selfcare=2 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.707;
if (mobility=3 and selfcare=2 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.692;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
90
if (mobility=3 and selfcare=2 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.479;
if (mobility=3 and selfcare=2 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.258;
if (mobility=3 and selfcare=2 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.665;
if (mobility=3 and selfcare=2 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.609;
if (mobility=3 and selfcare=2 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.594;
if (mobility=3 and selfcare=2 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.381;
if (mobility=3 and selfcare=2 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.160;
if (mobility=3 and selfcare=2 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.640;
if (mobility=3 and selfcare=2 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.584;
if (mobility=3 and selfcare=2 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.569;
if (mobility=3 and selfcare=2 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.356;
if (mobility=3 and selfcare=2 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.135;
if (mobility=3 and selfcare=2 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.428;
if (mobility=3 and selfcare=2 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.372;
if (mobility=3 and selfcare=2 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.357;
if (mobility=3 and selfcare=2 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.197;
if (mobility=3 and selfcare=2 and activity=1 and pain=4 and anxiety=5) then EQindex = 0.030;
if (mobility=3 and selfcare=2 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.108;
if (mobility=3 and selfcare=2 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.052;
if (mobility=3 and selfcare=2 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.037;
if (mobility=3 and selfcare=2 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.044;
if (mobility=3 and selfcare=2 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.128;
if (mobility=3 and selfcare=2 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.735;
if (mobility=3 and selfcare=2 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.678;
if (mobility=3 and selfcare=2 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.664;
if (mobility=3 and selfcare=2 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.451;
if (mobility=3 and selfcare=2 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.230;
if (mobility=3 and selfcare=2 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.636;
if (mobility=3 and selfcare=2 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.580;
if (mobility=3 and selfcare=2 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.565;
if (mobility=3 and selfcare=2 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.352;
if (mobility=3 and selfcare=2 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.131;
if (mobility=3 and selfcare=2 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.612;
if (mobility=3 and selfcare=2 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.555;
if (mobility=3 and selfcare=2 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.541;
if (mobility=3 and selfcare=2 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.328;
if (mobility=3 and selfcare=2 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.107;
if (mobility=3 and selfcare=2 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.399;
if (mobility=3 and selfcare=2 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.343;
if (mobility=3 and selfcare=2 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.328;
if (mobility=3 and selfcare=2 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.168;
if (mobility=3 and selfcare=2 and activity=2 and pain=4 and anxiety=5) then EQindex = 0.002;
if (mobility=3 and selfcare=2 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.080;
if (mobility=3 and selfcare=2 and activity=2 and pain=5 and anxiety=2) then EQindex = 0.023;
if (mobility=3 and selfcare=2 and activity=2 and pain=5 and anxiety=3) then EQindex = 0.009;
if (mobility=3 and selfcare=2 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.072;
if (mobility=3 and selfcare=2 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.157;
if (mobility=3 and selfcare=2 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.727;
if (mobility=3 and selfcare=2 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.671;
if (mobility=3 and selfcare=2 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.656;
if (mobility=3 and selfcare=2 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.443;
if (mobility=3 and selfcare=2 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.222;
if (mobility=3 and selfcare=2 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.629;
if (mobility=3 and selfcare=2 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.573;
if (mobility=3 and selfcare=2 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.558;
if (mobility=3 and selfcare=2 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.345;
if (mobility=3 and selfcare=2 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.124;
if (mobility=3 and selfcare=2 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.604;
if (mobility=3 and selfcare=2 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.548;
if (mobility=3 and selfcare=2 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.533;
if (mobility=3 and selfcare=2 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.320;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
91
if (mobility=3 and selfcare=2 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.099;
if (mobility=3 and selfcare=2 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.392;
if (mobility=3 and selfcare=2 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.336;
if (mobility=3 and selfcare=2 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.321;
if (mobility=3 and selfcare=2 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.161;
if (mobility=3 and selfcare=2 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.006;
if (mobility=3 and selfcare=2 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.072;
if (mobility=3 and selfcare=2 and activity=3 and pain=5 and anxiety=2) then EQindex = 0.016;
if (mobility=3 and selfcare=2 and activity=3 and pain=5 and anxiety=3) then EQindex = 0.001;
if (mobility=3 and selfcare=2 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.080;
if (mobility=3 and selfcare=2 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.164;
if (mobility=3 and selfcare=2 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.620;
if (mobility=3 and selfcare=2 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.564;
if (mobility=3 and selfcare=2 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.549;
if (mobility=3 and selfcare=2 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.379;
if (mobility=3 and selfcare=2 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.203;
if (mobility=3 and selfcare=2 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.522;
if (mobility=3 and selfcare=2 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.465;
if (mobility=3 and selfcare=2 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.451;
if (mobility=3 and selfcare=2 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.281;
if (mobility=3 and selfcare=2 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.105;
if (mobility=3 and selfcare=2 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.497;
if (mobility=3 and selfcare=2 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.441;
if (mobility=3 and selfcare=2 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.426;
if (mobility=3 and selfcare=2 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.256;
if (mobility=3 and selfcare=2 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.080;
if (mobility=3 and selfcare=2 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.320;
if (mobility=3 and selfcare=2 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.263;
if (mobility=3 and selfcare=2 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.249;
if (mobility=3 and selfcare=2 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.115;
if (mobility=3 and selfcare=2 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.025;
if (mobility=3 and selfcare=2 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.053;
if (mobility=3 and selfcare=2 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.003;
if (mobility=3 and selfcare=2 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.018;
if (mobility=3 and selfcare=2 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.099;
if (mobility=3 and selfcare=2 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.183;
if (mobility=3 and selfcare=2 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.400;
if (mobility=3 and selfcare=2 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.344;
if (mobility=3 and selfcare=2 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.329;
if (mobility=3 and selfcare=2 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.248;
if (mobility=3 and selfcare=2 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.164;
if (mobility=3 and selfcare=2 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.302;
if (mobility=3 and selfcare=2 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.246;
if (mobility=3 and selfcare=2 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.231;
if (mobility=3 and selfcare=2 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.150;
if (mobility=3 and selfcare=2 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.066;
if (mobility=3 and selfcare=2 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.277;
if (mobility=3 and selfcare=2 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.221;
if (mobility=3 and selfcare=2 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.206;
if (mobility=3 and selfcare=2 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.125;
if (mobility=3 and selfcare=2 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.041;
if (mobility=3 and selfcare=2 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.172;
if (mobility=3 and selfcare=2 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.116;
if (mobility=3 and selfcare=2 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.101;
if (mobility=3 and selfcare=2 and activity=5 and pain=4 and anxiety=4) then EQindex = 0.020;
if (mobility=3 and selfcare=2 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.064;
if (mobility=3 and selfcare=2 and activity=5 and pain=5 and anxiety=1) then EQindex = 0.014;
if (mobility=3 and selfcare=2 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.042;
if (mobility=3 and selfcare=2 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.057;
if (mobility=3 and selfcare=2 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.138;
if (mobility=3 and selfcare=2 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.222;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
92
if (mobility=3 and selfcare=3 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.746;
if (mobility=3 and selfcare=3 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.690;
if (mobility=3 and selfcare=3 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.675;
if (mobility=3 and selfcare=3 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.462;
if (mobility=3 and selfcare=3 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.241;
if (mobility=3 and selfcare=3 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.648;
if (mobility=3 and selfcare=3 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.591;
if (mobility=3 and selfcare=3 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.577;
if (mobility=3 and selfcare=3 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.364;
if (mobility=3 and selfcare=3 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.143;
if (mobility=3 and selfcare=3 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.623;
if (mobility=3 and selfcare=3 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.567;
if (mobility=3 and selfcare=3 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.552;
if (mobility=3 and selfcare=3 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.339;
if (mobility=3 and selfcare=3 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.118;
if (mobility=3 and selfcare=3 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.411;
if (mobility=3 and selfcare=3 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.354;
if (mobility=3 and selfcare=3 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.340;
if (mobility=3 and selfcare=3 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.179;
if (mobility=3 and selfcare=3 and activity=1 and pain=4 and anxiety=5) then EQindex = 0.013;
if (mobility=3 and selfcare=3 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.091;
if (mobility=3 and selfcare=3 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.035;
if (mobility=3 and selfcare=3 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.020;
if (mobility=3 and selfcare=3 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.061;
if (mobility=3 and selfcare=3 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.145;
if (mobility=3 and selfcare=3 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.717;
if (mobility=3 and selfcare=3 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.661;
if (mobility=3 and selfcare=3 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.646;
if (mobility=3 and selfcare=3 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.433;
if (mobility=3 and selfcare=3 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.212;
if (mobility=3 and selfcare=3 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.619;
if (mobility=3 and selfcare=3 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.562;
if (mobility=3 and selfcare=3 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.548;
if (mobility=3 and selfcare=3 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.335;
if (mobility=3 and selfcare=3 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.114;
if (mobility=3 and selfcare=3 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.594;
if (mobility=3 and selfcare=3 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.538;
if (mobility=3 and selfcare=3 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.523;
if (mobility=3 and selfcare=3 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.310;
if (mobility=3 and selfcare=3 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.089;
if (mobility=3 and selfcare=3 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.382;
if (mobility=3 and selfcare=3 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.325;
if (mobility=3 and selfcare=3 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.311;
if (mobility=3 and selfcare=3 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.150;
if (mobility=3 and selfcare=3 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.016;
if (mobility=3 and selfcare=3 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.062;
if (mobility=3 and selfcare=3 and activity=2 and pain=5 and anxiety=2) then EQindex = 0.006;
if (mobility=3 and selfcare=3 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.009;
if (mobility=3 and selfcare=3 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.090;
if (mobility=3 and selfcare=3 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.174;
if (mobility=3 and selfcare=3 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.710;
if (mobility=3 and selfcare=3 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.654;
if (mobility=3 and selfcare=3 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.639;
if (mobility=3 and selfcare=3 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.426;
if (mobility=3 and selfcare=3 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.205;
if (mobility=3 and selfcare=3 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.612;
if (mobility=3 and selfcare=3 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.555;
if (mobility=3 and selfcare=3 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.541;
if (mobility=3 and selfcare=3 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.328;
if (mobility=3 and selfcare=3 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.107;
if (mobility=3 and selfcare=3 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.587;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
93
if (mobility=3 and selfcare=3 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.531;
if (mobility=3 and selfcare=3 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.516;
if (mobility=3 and selfcare=3 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.303;
if (mobility=3 and selfcare=3 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.082;
if (mobility=3 and selfcare=3 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.375;
if (mobility=3 and selfcare=3 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.318;
if (mobility=3 and selfcare=3 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.304;
if (mobility=3 and selfcare=3 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.143;
if (mobility=3 and selfcare=3 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.023;
if (mobility=3 and selfcare=3 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.055;
if (mobility=3 and selfcare=3 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.001;
if (mobility=3 and selfcare=3 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.016;
if (mobility=3 and selfcare=3 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.097;
if (mobility=3 and selfcare=3 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.181;
if (mobility=3 and selfcare=3 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.603;
if (mobility=3 and selfcare=3 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.546;
if (mobility=3 and selfcare=3 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.532;
if (mobility=3 and selfcare=3 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.362;
if (mobility=3 and selfcare=3 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.186;
if (mobility=3 and selfcare=3 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.504;
if (mobility=3 and selfcare=3 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.448;
if (mobility=3 and selfcare=3 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.433;
if (mobility=3 and selfcare=3 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.264;
if (mobility=3 and selfcare=3 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.087;
if (mobility=3 and selfcare=3 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.480;
if (mobility=3 and selfcare=3 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.423;
if (mobility=3 and selfcare=3 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.409;
if (mobility=3 and selfcare=3 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.239;
if (mobility=3 and selfcare=3 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.063;
if (mobility=3 and selfcare=3 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.302;
if (mobility=3 and selfcare=3 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.246;
if (mobility=3 and selfcare=3 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.231;
if (mobility=3 and selfcare=3 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.097;
if (mobility=3 and selfcare=3 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.042;
if (mobility=3 and selfcare=3 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.036;
if (mobility=3 and selfcare=3 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.020;
if (mobility=3 and selfcare=3 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.035;
if (mobility=3 and selfcare=3 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.116;
if (mobility=3 and selfcare=3 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.200;
if (mobility=3 and selfcare=3 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.383;
if (mobility=3 and selfcare=3 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.327;
if (mobility=3 and selfcare=3 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.312;
if (mobility=3 and selfcare=3 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.231;
if (mobility=3 and selfcare=3 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.147;
if (mobility=3 and selfcare=3 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.285;
if (mobility=3 and selfcare=3 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.228;
if (mobility=3 and selfcare=3 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.214;
if (mobility=3 and selfcare=3 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.133;
if (mobility=3 and selfcare=3 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.049;
if (mobility=3 and selfcare=3 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.260;
if (mobility=3 and selfcare=3 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.204;
if (mobility=3 and selfcare=3 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.189;
if (mobility=3 and selfcare=3 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.108;
if (mobility=3 and selfcare=3 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.024;
if (mobility=3 and selfcare=3 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.155;
if (mobility=3 and selfcare=3 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.099;
if (mobility=3 and selfcare=3 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.084;
if (mobility=3 and selfcare=3 and activity=5 and pain=4 and anxiety=4) then EQindex = 0.003;
if (mobility=3 and selfcare=3 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.081;
if (mobility=3 and selfcare=3 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.003;
if (mobility=3 and selfcare=3 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.059;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
94
if (mobility=3 and selfcare=3 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.074;
if (mobility=3 and selfcare=3 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.155;
if (mobility=3 and selfcare=3 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.239;
if (mobility=3 and selfcare=4 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.654;
if (mobility=3 and selfcare=4 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.598;
if (mobility=3 and selfcare=4 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.583;
if (mobility=3 and selfcare=4 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.402;
if (mobility=3 and selfcare=4 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.214;
if (mobility=3 and selfcare=4 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.555;
if (mobility=3 and selfcare=4 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.499;
if (mobility=3 and selfcare=4 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.484;
if (mobility=3 and selfcare=4 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.304;
if (mobility=3 and selfcare=4 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.116;
if (mobility=3 and selfcare=4 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.531;
if (mobility=3 and selfcare=4 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.475;
if (mobility=3 and selfcare=4 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.460;
if (mobility=3 and selfcare=4 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.279;
if (mobility=3 and selfcare=4 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.091;
if (mobility=3 and selfcare=4 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.345;
if (mobility=3 and selfcare=4 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.288;
if (mobility=3 and selfcare=4 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.274;
if (mobility=3 and selfcare=4 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.133;
if (mobility=3 and selfcare=4 and activity=1 and pain=4 and anxiety=5) then EQindex = -0.014;
if (mobility=3 and selfcare=4 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.064;
if (mobility=3 and selfcare=4 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.008;
if (mobility=3 and selfcare=4 and activity=1 and pain=5 and anxiety=3) then EQindex = -0.007;
if (mobility=3 and selfcare=4 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.088;
if (mobility=3 and selfcare=4 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.172;
if (mobility=3 and selfcare=4 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.625;
if (mobility=3 and selfcare=4 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.569;
if (mobility=3 and selfcare=4 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.554;
if (mobility=3 and selfcare=4 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.373;
if (mobility=3 and selfcare=4 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.185;
if (mobility=3 and selfcare=4 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.527;
if (mobility=3 and selfcare=4 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.470;
if (mobility=3 and selfcare=4 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.456;
if (mobility=3 and selfcare=4 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.275;
if (mobility=3 and selfcare=4 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.087;
if (mobility=3 and selfcare=4 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.502;
if (mobility=3 and selfcare=4 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.446;
if (mobility=3 and selfcare=4 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.431;
if (mobility=3 and selfcare=4 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.250;
if (mobility=3 and selfcare=4 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.062;
if (mobility=3 and selfcare=4 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.316;
if (mobility=3 and selfcare=4 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.259;
if (mobility=3 and selfcare=4 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.245;
if (mobility=3 and selfcare=4 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.104;
if (mobility=3 and selfcare=4 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.043;
if (mobility=3 and selfcare=4 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.035;
if (mobility=3 and selfcare=4 and activity=2 and pain=5 and anxiety=2) then EQindex = -0.021;
if (mobility=3 and selfcare=4 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.036;
if (mobility=3 and selfcare=4 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.117;
if (mobility=3 and selfcare=4 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.201;
if (mobility=3 and selfcare=4 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.618;
if (mobility=3 and selfcare=4 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.562;
if (mobility=3 and selfcare=4 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.547;
if (mobility=3 and selfcare=4 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.366;
if (mobility=3 and selfcare=4 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.178;
if (mobility=3 and selfcare=4 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.519;
if (mobility=3 and selfcare=4 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.463;
if (mobility=3 and selfcare=4 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.448;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
95
if (mobility=3 and selfcare=4 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.268;
if (mobility=3 and selfcare=4 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.080;
if (mobility=3 and selfcare=4 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.495;
if (mobility=3 and selfcare=4 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.439;
if (mobility=3 and selfcare=4 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.424;
if (mobility=3 and selfcare=4 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.243;
if (mobility=3 and selfcare=4 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.055;
if (mobility=3 and selfcare=4 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.309;
if (mobility=3 and selfcare=4 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.252;
if (mobility=3 and selfcare=4 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.238;
if (mobility=3 and selfcare=4 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.097;
if (mobility=3 and selfcare=4 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.050;
if (mobility=3 and selfcare=4 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.028;
if (mobility=3 and selfcare=4 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.028;
if (mobility=3 and selfcare=4 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.043;
if (mobility=3 and selfcare=4 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.124;
if (mobility=3 and selfcare=4 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.208;
if (mobility=3 and selfcare=4 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.532;
if (mobility=3 and selfcare=4 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.476;
if (mobility=3 and selfcare=4 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.461;
if (mobility=3 and selfcare=4 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.313;
if (mobility=3 and selfcare=4 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.159;
if (mobility=3 and selfcare=4 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.433;
if (mobility=3 and selfcare=4 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.377;
if (mobility=3 and selfcare=4 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.362;
if (mobility=3 and selfcare=4 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.214;
if (mobility=3 and selfcare=4 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.061;
if (mobility=3 and selfcare=4 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.409;
if (mobility=3 and selfcare=4 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.353;
if (mobility=3 and selfcare=4 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.338;
if (mobility=3 and selfcare=4 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.190;
if (mobility=3 and selfcare=4 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.036;
if (mobility=3 and selfcare=4 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.249;
if (mobility=3 and selfcare=4 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.193;
if (mobility=3 and selfcare=4 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.178;
if (mobility=3 and selfcare=4 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.057;
if (mobility=3 and selfcare=4 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.069;
if (mobility=3 and selfcare=4 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.009;
if (mobility=3 and selfcare=4 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.047;
if (mobility=3 and selfcare=4 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.062;
if (mobility=3 and selfcare=4 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.143;
if (mobility=3 and selfcare=4 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.227;
if (mobility=3 and selfcare=4 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.356;
if (mobility=3 and selfcare=4 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.300;
if (mobility=3 and selfcare=4 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.285;
if (mobility=3 and selfcare=4 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.204;
if (mobility=3 and selfcare=4 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.120;
if (mobility=3 and selfcare=4 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.258;
if (mobility=3 and selfcare=4 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.201;
if (mobility=3 and selfcare=4 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.187;
if (mobility=3 and selfcare=4 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.106;
if (mobility=3 and selfcare=4 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.022;
if (mobility=3 and selfcare=4 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.233;
if (mobility=3 and selfcare=4 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.177;
if (mobility=3 and selfcare=4 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.162;
if (mobility=3 and selfcare=4 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.081;
if (mobility=3 and selfcare=4 and activity=5 and pain=3 and anxiety=5) then EQindex = -0.003;
if (mobility=3 and selfcare=4 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.128;
if (mobility=3 and selfcare=4 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.072;
if (mobility=3 and selfcare=4 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.057;
if (mobility=3 and selfcare=4 and activity=5 and pain=4 and anxiety=4) then EQindex = -0.024;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
96
if (mobility=3 and selfcare=4 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.108;
if (mobility=3 and selfcare=4 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.030;
if (mobility=3 and selfcare=4 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.086;
if (mobility=3 and selfcare=4 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.101;
if (mobility=3 and selfcare=4 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.182;
if (mobility=3 and selfcare=4 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.266;
if (mobility=3 and selfcare=5 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.367;
if (mobility=3 and selfcare=5 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.311;
if (mobility=3 and selfcare=5 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.296;
if (mobility=3 and selfcare=5 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.215;
if (mobility=3 and selfcare=5 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.131;
if (mobility=3 and selfcare=5 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.269;
if (mobility=3 and selfcare=5 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.212;
if (mobility=3 and selfcare=5 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.198;
if (mobility=3 and selfcare=5 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.117;
if (mobility=3 and selfcare=5 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.033;
if (mobility=3 and selfcare=5 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.244;
if (mobility=3 and selfcare=5 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.188;
if (mobility=3 and selfcare=5 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.173;
if (mobility=3 and selfcare=5 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.092;
if (mobility=3 and selfcare=5 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.008;
if (mobility=3 and selfcare=5 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.139;
if (mobility=3 and selfcare=5 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.083;
if (mobility=3 and selfcare=5 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.068;
if (mobility=3 and selfcare=5 and activity=1 and pain=4 and anxiety=4) then EQindex = -0.013;
if (mobility=3 and selfcare=5 and activity=1 and pain=4 and anxiety=5) then EQindex = -0.097;
if (mobility=3 and selfcare=5 and activity=1 and pain=5 and anxiety=1) then EQindex = -0.019;
if (mobility=3 and selfcare=5 and activity=1 and pain=5 and anxiety=2) then EQindex = -0.075;
if (mobility=3 and selfcare=5 and activity=1 and pain=5 and anxiety=3) then EQindex = -0.090;
if (mobility=3 and selfcare=5 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.171;
if (mobility=3 and selfcare=5 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.255;
if (mobility=3 and selfcare=5 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.338;
if (mobility=3 and selfcare=5 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.282;
if (mobility=3 and selfcare=5 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.267;
if (mobility=3 and selfcare=5 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.186;
if (mobility=3 and selfcare=5 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.102;
if (mobility=3 and selfcare=5 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.240;
if (mobility=3 and selfcare=5 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.183;
if (mobility=3 and selfcare=5 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.169;
if (mobility=3 and selfcare=5 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.088;
if (mobility=3 and selfcare=5 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.004;
if (mobility=3 and selfcare=5 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.215;
if (mobility=3 and selfcare=5 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.159;
if (mobility=3 and selfcare=5 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.144;
if (mobility=3 and selfcare=5 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.063;
if (mobility=3 and selfcare=5 and activity=2 and pain=3 and anxiety=5) then EQindex = -0.021;
if (mobility=3 and selfcare=5 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.110;
if (mobility=3 and selfcare=5 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.054;
if (mobility=3 and selfcare=5 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.039;
if (mobility=3 and selfcare=5 and activity=2 and pain=4 and anxiety=4) then EQindex = -0.042;
if (mobility=3 and selfcare=5 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.126;
if (mobility=3 and selfcare=5 and activity=2 and pain=5 and anxiety=1) then EQindex = -0.048;
if (mobility=3 and selfcare=5 and activity=2 and pain=5 and anxiety=2) then EQindex = -0.104;
if (mobility=3 and selfcare=5 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.119;
if (mobility=3 and selfcare=5 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.200;
if (mobility=3 and selfcare=5 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.284;
if (mobility=3 and selfcare=5 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.331;
if (mobility=3 and selfcare=5 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.275;
if (mobility=3 and selfcare=5 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.260;
if (mobility=3 and selfcare=5 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.179;
if (mobility=3 and selfcare=5 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.095;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
97
if (mobility=3 and selfcare=5 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.233;
if (mobility=3 and selfcare=5 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.176;
if (mobility=3 and selfcare=5 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.162;
if (mobility=3 and selfcare=5 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.081;
if (mobility=3 and selfcare=5 and activity=3 and pain=2 and anxiety=5) then EQindex = -0.004;
if (mobility=3 and selfcare=5 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.208;
if (mobility=3 and selfcare=5 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.152;
if (mobility=3 and selfcare=5 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.137;
if (mobility=3 and selfcare=5 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.056;
if (mobility=3 and selfcare=5 and activity=3 and pain=3 and anxiety=5) then EQindex = -0.028;
if (mobility=3 and selfcare=5 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.103;
if (mobility=3 and selfcare=5 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.047;
if (mobility=3 and selfcare=5 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.032;
if (mobility=3 and selfcare=5 and activity=3 and pain=4 and anxiety=4) then EQindex = -0.049;
if (mobility=3 and selfcare=5 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.133;
if (mobility=3 and selfcare=5 and activity=3 and pain=5 and anxiety=1) then EQindex = -0.055;
if (mobility=3 and selfcare=5 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.111;
if (mobility=3 and selfcare=5 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.126;
if (mobility=3 and selfcare=5 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.207;
if (mobility=3 and selfcare=5 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.291;
if (mobility=3 and selfcare=5 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.312;
if (mobility=3 and selfcare=5 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.256;
if (mobility=3 and selfcare=5 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.241;
if (mobility=3 and selfcare=5 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.160;
if (mobility=3 and selfcare=5 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.076;
if (mobility=3 and selfcare=5 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.213;
if (mobility=3 and selfcare=5 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.157;
if (mobility=3 and selfcare=5 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.142;
if (mobility=3 and selfcare=5 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.061;
if (mobility=3 and selfcare=5 and activity=4 and pain=2 and anxiety=5) then EQindex = -0.023;
if (mobility=3 and selfcare=5 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.189;
if (mobility=3 and selfcare=5 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.133;
if (mobility=3 and selfcare=5 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.118;
if (mobility=3 and selfcare=5 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.037;
if (mobility=3 and selfcare=5 and activity=4 and pain=3 and anxiety=5) then EQindex = -0.047;
if (mobility=3 and selfcare=5 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.084;
if (mobility=3 and selfcare=5 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.028;
if (mobility=3 and selfcare=5 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.013;
if (mobility=3 and selfcare=5 and activity=4 and pain=4 and anxiety=4) then EQindex = -0.068;
if (mobility=3 and selfcare=5 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.152;
if (mobility=3 and selfcare=5 and activity=4 and pain=5 and anxiety=1) then EQindex = -0.074;
if (mobility=3 and selfcare=5 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.130;
if (mobility=3 and selfcare=5 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.145;
if (mobility=3 and selfcare=5 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.226;
if (mobility=3 and selfcare=5 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.310;
if (mobility=3 and selfcare=5 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.273;
if (mobility=3 and selfcare=5 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.217;
if (mobility=3 and selfcare=5 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.202;
if (mobility=3 and selfcare=5 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.121;
if (mobility=3 and selfcare=5 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.037;
if (mobility=3 and selfcare=5 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.175;
if (mobility=3 and selfcare=5 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.118;
if (mobility=3 and selfcare=5 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.104;
if (mobility=3 and selfcare=5 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.023;
if (mobility=3 and selfcare=5 and activity=5 and pain=2 and anxiety=5) then EQindex = -0.062;
if (mobility=3 and selfcare=5 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.150;
if (mobility=3 and selfcare=5 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.094;
if (mobility=3 and selfcare=5 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.079;
if (mobility=3 and selfcare=5 and activity=5 and pain=3 and anxiety=4) then EQindex = -0.002;
if (mobility=3 and selfcare=5 and activity=5 and pain=3 and anxiety=5) then EQindex = -0.086;
if (mobility=3 and selfcare=5 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.045;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
98
if (mobility=3 and selfcare=5 and activity=5 and pain=4 and anxiety=2) then EQindex = -0.011;
if (mobility=3 and selfcare=5 and activity=5 and pain=4 and anxiety=3) then EQindex = -0.026;
if (mobility=3 and selfcare=5 and activity=5 and pain=4 and anxiety=4) then EQindex = -0.107;
if (mobility=3 and selfcare=5 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.191;
if (mobility=3 and selfcare=5 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.113;
if (mobility=3 and selfcare=5 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.169;
if (mobility=3 and selfcare=5 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.184;
if (mobility=3 and selfcare=5 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.265;
if (mobility=3 and selfcare=5 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.349;
if (mobility=4 and selfcare=1 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.813;
if (mobility=4 and selfcare=1 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.757;
if (mobility=4 and selfcare=1 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.742;
if (mobility=4 and selfcare=1 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.539;
if (mobility=4 and selfcare=1 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.327;
if (mobility=4 and selfcare=1 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.714;
if (mobility=4 and selfcare=1 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.658;
if (mobility=4 and selfcare=1 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.643;
if (mobility=4 and selfcare=1 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.440;
if (mobility=4 and selfcare=1 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.229;
if (mobility=4 and selfcare=1 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.690;
if (mobility=4 and selfcare=1 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.634;
if (mobility=4 and selfcare=1 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.619;
if (mobility=4 and selfcare=1 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.416;
if (mobility=4 and selfcare=1 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.204;
if (mobility=4 and selfcare=1 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.485;
if (mobility=4 and selfcare=1 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.429;
if (mobility=4 and selfcare=1 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.414;
if (mobility=4 and selfcare=1 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.260;
if (mobility=4 and selfcare=1 and activity=1 and pain=4 and anxiety=5) then EQindex = 0.099;
if (mobility=4 and selfcare=1 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.177;
if (mobility=4 and selfcare=1 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.121;
if (mobility=4 and selfcare=1 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.106;
if (mobility=4 and selfcare=1 and activity=1 and pain=5 and anxiety=4) then EQindex = 0.025;
if (mobility=4 and selfcare=1 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.059;
if (mobility=4 and selfcare=1 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.784;
if (mobility=4 and selfcare=1 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.728;
if (mobility=4 and selfcare=1 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.713;
if (mobility=4 and selfcare=1 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.510;
if (mobility=4 and selfcare=1 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.299;
if (mobility=4 and selfcare=1 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.686;
if (mobility=4 and selfcare=1 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.629;
if (mobility=4 and selfcare=1 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.615;
if (mobility=4 and selfcare=1 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.411;
if (mobility=4 and selfcare=1 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.200;
if (mobility=4 and selfcare=1 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.661;
if (mobility=4 and selfcare=1 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.605;
if (mobility=4 and selfcare=1 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.590;
if (mobility=4 and selfcare=1 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.387;
if (mobility=4 and selfcare=1 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.176;
if (mobility=4 and selfcare=1 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.456;
if (mobility=4 and selfcare=1 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.400;
if (mobility=4 and selfcare=1 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.385;
if (mobility=4 and selfcare=1 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.231;
if (mobility=4 and selfcare=1 and activity=2 and pain=4 and anxiety=5) then EQindex = 0.070;
if (mobility=4 and selfcare=1 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.149;
if (mobility=4 and selfcare=1 and activity=2 and pain=5 and anxiety=2) then EQindex = 0.092;
if (mobility=4 and selfcare=1 and activity=2 and pain=5 and anxiety=3) then EQindex = 0.078;
if (mobility=4 and selfcare=1 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.004;
if (mobility=4 and selfcare=1 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.088;
if (mobility=4 and selfcare=1 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.777;
if (mobility=4 and selfcare=1 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.721;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
99
if (mobility=4 and selfcare=1 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.706;
if (mobility=4 and selfcare=1 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.503;
if (mobility=4 and selfcare=1 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.291;
if (mobility=4 and selfcare=1 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.678;
if (mobility=4 and selfcare=1 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.622;
if (mobility=4 and selfcare=1 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.607;
if (mobility=4 and selfcare=1 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.404;
if (mobility=4 and selfcare=1 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.193;
if (mobility=4 and selfcare=1 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.654;
if (mobility=4 and selfcare=1 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.598;
if (mobility=4 and selfcare=1 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.583;
if (mobility=4 and selfcare=1 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.380;
if (mobility=4 and selfcare=1 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.168;
if (mobility=4 and selfcare=1 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.449;
if (mobility=4 and selfcare=1 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.393;
if (mobility=4 and selfcare=1 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.378;
if (mobility=4 and selfcare=1 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.224;
if (mobility=4 and selfcare=1 and activity=3 and pain=4 and anxiety=5) then EQindex = 0.063;
if (mobility=4 and selfcare=1 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.141;
if (mobility=4 and selfcare=1 and activity=3 and pain=5 and anxiety=2) then EQindex = 0.085;
if (mobility=4 and selfcare=1 and activity=3 and pain=5 and anxiety=3) then EQindex = 0.070;
if (mobility=4 and selfcare=1 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.011;
if (mobility=4 and selfcare=1 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.095;
if (mobility=4 and selfcare=1 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.676;
if (mobility=4 and selfcare=1 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.620;
if (mobility=4 and selfcare=1 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.605;
if (mobility=4 and selfcare=1 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.442;
if (mobility=4 and selfcare=1 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.272;
if (mobility=4 and selfcare=1 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.577;
if (mobility=4 and selfcare=1 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.521;
if (mobility=4 and selfcare=1 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.506;
if (mobility=4 and selfcare=1 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.343;
if (mobility=4 and selfcare=1 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.174;
if (mobility=4 and selfcare=1 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.553;
if (mobility=4 and selfcare=1 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.497;
if (mobility=4 and selfcare=1 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.482;
if (mobility=4 and selfcare=1 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.319;
if (mobility=4 and selfcare=1 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.149;
if (mobility=4 and selfcare=1 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.381;
if (mobility=4 and selfcare=1 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.325;
if (mobility=4 and selfcare=1 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.310;
if (mobility=4 and selfcare=1 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.180;
if (mobility=4 and selfcare=1 and activity=4 and pain=4 and anxiety=5) then EQindex = 0.044;
if (mobility=4 and selfcare=1 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.122;
if (mobility=4 and selfcare=1 and activity=4 and pain=5 and anxiety=2) then EQindex = 0.066;
if (mobility=4 and selfcare=1 and activity=4 and pain=5 and anxiety=3) then EQindex = 0.051;
if (mobility=4 and selfcare=1 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.030;
if (mobility=4 and selfcare=1 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.114;
if (mobility=4 and selfcare=1 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.469;
if (mobility=4 and selfcare=1 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.413;
if (mobility=4 and selfcare=1 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.398;
if (mobility=4 and selfcare=1 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.317;
if (mobility=4 and selfcare=1 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.233;
if (mobility=4 and selfcare=1 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.371;
if (mobility=4 and selfcare=1 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.315;
if (mobility=4 and selfcare=1 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.300;
if (mobility=4 and selfcare=1 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.219;
if (mobility=4 and selfcare=1 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.135;
if (mobility=4 and selfcare=1 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.346;
if (mobility=4 and selfcare=1 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.290;
if (mobility=4 and selfcare=1 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.275;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
100
if (mobility=4 and selfcare=1 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.194;
if (mobility=4 and selfcare=1 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.110;
if (mobility=4 and selfcare=1 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.241;
if (mobility=4 and selfcare=1 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.185;
if (mobility=4 and selfcare=1 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.170;
if (mobility=4 and selfcare=1 and activity=5 and pain=4 and anxiety=4) then EQindex = 0.089;
if (mobility=4 and selfcare=1 and activity=5 and pain=4 and anxiety=5) then EQindex = 0.005;
if (mobility=4 and selfcare=1 and activity=5 and pain=5 and anxiety=1) then EQindex = 0.083;
if (mobility=4 and selfcare=1 and activity=5 and pain=5 and anxiety=2) then EQindex = 0.027;
if (mobility=4 and selfcare=1 and activity=5 and pain=5 and anxiety=3) then EQindex = 0.012;
if (mobility=4 and selfcare=1 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.069;
if (mobility=4 and selfcare=1 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.153;
if (mobility=4 and selfcare=2 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.726;
if (mobility=4 and selfcare=2 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.670;
if (mobility=4 and selfcare=2 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.655;
if (mobility=4 and selfcare=2 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.452;
if (mobility=4 and selfcare=2 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.241;
if (mobility=4 and selfcare=2 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.628;
if (mobility=4 and selfcare=2 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.572;
if (mobility=4 and selfcare=2 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.557;
if (mobility=4 and selfcare=2 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.353;
if (mobility=4 and selfcare=2 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.142;
if (mobility=4 and selfcare=2 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.603;
if (mobility=4 and selfcare=2 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.547;
if (mobility=4 and selfcare=2 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.532;
if (mobility=4 and selfcare=2 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.329;
if (mobility=4 and selfcare=2 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.118;
if (mobility=4 and selfcare=2 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.399;
if (mobility=4 and selfcare=2 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.342;
if (mobility=4 and selfcare=2 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.328;
if (mobility=4 and selfcare=2 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.173;
if (mobility=4 and selfcare=2 and activity=1 and pain=4 and anxiety=5) then EQindex = 0.013;
if (mobility=4 and selfcare=2 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.091;
if (mobility=4 and selfcare=2 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.034;
if (mobility=4 and selfcare=2 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.020;
if (mobility=4 and selfcare=2 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.061;
if (mobility=4 and selfcare=2 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.145;
if (mobility=4 and selfcare=2 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.698;
if (mobility=4 and selfcare=2 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.641;
if (mobility=4 and selfcare=2 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.627;
if (mobility=4 and selfcare=2 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.423;
if (mobility=4 and selfcare=2 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.212;
if (mobility=4 and selfcare=2 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.599;
if (mobility=4 and selfcare=2 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.543;
if (mobility=4 and selfcare=2 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.528;
if (mobility=4 and selfcare=2 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.325;
if (mobility=4 and selfcare=2 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.113;
if (mobility=4 and selfcare=2 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.575;
if (mobility=4 and selfcare=2 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.518;
if (mobility=4 and selfcare=2 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.504;
if (mobility=4 and selfcare=2 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.300;
if (mobility=4 and selfcare=2 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.089;
if (mobility=4 and selfcare=2 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.370;
if (mobility=4 and selfcare=2 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.313;
if (mobility=4 and selfcare=2 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.299;
if (mobility=4 and selfcare=2 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.144;
if (mobility=4 and selfcare=2 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.016;
if (mobility=4 and selfcare=2 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.062;
if (mobility=4 and selfcare=2 and activity=2 and pain=5 and anxiety=2) then EQindex = 0.006;
if (mobility=4 and selfcare=2 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.009;
if (mobility=4 and selfcare=2 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.090;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
101
if (mobility=4 and selfcare=2 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.174;
if (mobility=4 and selfcare=2 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.690;
if (mobility=4 and selfcare=2 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.634;
if (mobility=4 and selfcare=2 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.619;
if (mobility=4 and selfcare=2 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.416;
if (mobility=4 and selfcare=2 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.205;
if (mobility=4 and selfcare=2 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.592;
if (mobility=4 and selfcare=2 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.536;
if (mobility=4 and selfcare=2 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.521;
if (mobility=4 and selfcare=2 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.317;
if (mobility=4 and selfcare=2 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.106;
if (mobility=4 and selfcare=2 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.567;
if (mobility=4 and selfcare=2 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.511;
if (mobility=4 and selfcare=2 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.496;
if (mobility=4 and selfcare=2 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.293;
if (mobility=4 and selfcare=2 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.082;
if (mobility=4 and selfcare=2 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.363;
if (mobility=4 and selfcare=2 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.306;
if (mobility=4 and selfcare=2 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.292;
if (mobility=4 and selfcare=2 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.137;
if (mobility=4 and selfcare=2 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.023;
if (mobility=4 and selfcare=2 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.055;
if (mobility=4 and selfcare=2 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.002;
if (mobility=4 and selfcare=2 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.016;
if (mobility=4 and selfcare=2 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.097;
if (mobility=4 and selfcare=2 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.181;
if (mobility=4 and selfcare=2 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.589;
if (mobility=4 and selfcare=2 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.533;
if (mobility=4 and selfcare=2 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.518;
if (mobility=4 and selfcare=2 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.355;
if (mobility=4 and selfcare=2 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.186;
if (mobility=4 and selfcare=2 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.491;
if (mobility=4 and selfcare=2 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.434;
if (mobility=4 and selfcare=2 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.420;
if (mobility=4 and selfcare=2 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.257;
if (mobility=4 and selfcare=2 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.087;
if (mobility=4 and selfcare=2 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.466;
if (mobility=4 and selfcare=2 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.410;
if (mobility=4 and selfcare=2 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.395;
if (mobility=4 and selfcare=2 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.232;
if (mobility=4 and selfcare=2 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.063;
if (mobility=4 and selfcare=2 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.294;
if (mobility=4 and selfcare=2 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.238;
if (mobility=4 and selfcare=2 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.223;
if (mobility=4 and selfcare=2 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.093;
if (mobility=4 and selfcare=2 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.042;
if (mobility=4 and selfcare=2 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.036;
if (mobility=4 and selfcare=2 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.021;
if (mobility=4 and selfcare=2 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.035;
if (mobility=4 and selfcare=2 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.116;
if (mobility=4 and selfcare=2 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.200;
if (mobility=4 and selfcare=2 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.383;
if (mobility=4 and selfcare=2 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.326;
if (mobility=4 and selfcare=2 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.312;
if (mobility=4 and selfcare=2 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.231;
if (mobility=4 and selfcare=2 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.147;
if (mobility=4 and selfcare=2 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.284;
if (mobility=4 and selfcare=2 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.228;
if (mobility=4 and selfcare=2 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.213;
if (mobility=4 and selfcare=2 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.132;
if (mobility=4 and selfcare=2 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.048;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
102
if (mobility=4 and selfcare=2 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.260;
if (mobility=4 and selfcare=2 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.203;
if (mobility=4 and selfcare=2 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.189;
if (mobility=4 and selfcare=2 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.108;
if (mobility=4 and selfcare=2 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.024;
if (mobility=4 and selfcare=2 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.155;
if (mobility=4 and selfcare=2 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.098;
if (mobility=4 and selfcare=2 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.084;
if (mobility=4 and selfcare=2 and activity=5 and pain=4 and anxiety=4) then EQindex = 0.003;
if (mobility=4 and selfcare=2 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.081;
if (mobility=4 and selfcare=2 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.003;
if (mobility=4 and selfcare=2 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.060;
if (mobility=4 and selfcare=2 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.074;
if (mobility=4 and selfcare=2 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.155;
if (mobility=4 and selfcare=2 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.239;
if (mobility=4 and selfcare=3 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.709;
if (mobility=4 and selfcare=3 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.653;
if (mobility=4 and selfcare=3 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.638;
if (mobility=4 and selfcare=3 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.435;
if (mobility=4 and selfcare=3 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.223;
if (mobility=4 and selfcare=3 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.610;
if (mobility=4 and selfcare=3 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.554;
if (mobility=4 and selfcare=3 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.539;
if (mobility=4 and selfcare=3 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.336;
if (mobility=4 and selfcare=3 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.125;
if (mobility=4 and selfcare=3 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.586;
if (mobility=4 and selfcare=3 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.530;
if (mobility=4 and selfcare=3 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.515;
if (mobility=4 and selfcare=3 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.312;
if (mobility=4 and selfcare=3 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.100;
if (mobility=4 and selfcare=3 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.381;
if (mobility=4 and selfcare=3 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.325;
if (mobility=4 and selfcare=3 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.310;
if (mobility=4 and selfcare=3 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.156;
if (mobility=4 and selfcare=3 and activity=1 and pain=4 and anxiety=5) then EQindex = -0.005;
if (mobility=4 and selfcare=3 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.073;
if (mobility=4 and selfcare=3 and activity=1 and pain=5 and anxiety=2) then EQindex = 0.017;
if (mobility=4 and selfcare=3 and activity=1 and pain=5 and anxiety=3) then EQindex = 0.002;
if (mobility=4 and selfcare=3 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.079;
if (mobility=4 and selfcare=3 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.163;
if (mobility=4 and selfcare=3 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.680;
if (mobility=4 and selfcare=3 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.624;
if (mobility=4 and selfcare=3 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.609;
if (mobility=4 and selfcare=3 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.406;
if (mobility=4 and selfcare=3 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.195;
if (mobility=4 and selfcare=3 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.582;
if (mobility=4 and selfcare=3 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.525;
if (mobility=4 and selfcare=3 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.511;
if (mobility=4 and selfcare=3 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.307;
if (mobility=4 and selfcare=3 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.096;
if (mobility=4 and selfcare=3 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.557;
if (mobility=4 and selfcare=3 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.501;
if (mobility=4 and selfcare=3 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.486;
if (mobility=4 and selfcare=3 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.283;
if (mobility=4 and selfcare=3 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.072;
if (mobility=4 and selfcare=3 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.352;
if (mobility=4 and selfcare=3 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.296;
if (mobility=4 and selfcare=3 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.281;
if (mobility=4 and selfcare=3 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.127;
if (mobility=4 and selfcare=3 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.034;
if (mobility=4 and selfcare=3 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.045;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
103
if (mobility=4 and selfcare=3 and activity=2 and pain=5 and anxiety=2) then EQindex = -0.012;
if (mobility=4 and selfcare=3 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.027;
if (mobility=4 and selfcare=3 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.108;
if (mobility=4 and selfcare=3 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.192;
if (mobility=4 and selfcare=3 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.673;
if (mobility=4 and selfcare=3 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.617;
if (mobility=4 and selfcare=3 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.602;
if (mobility=4 and selfcare=3 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.399;
if (mobility=4 and selfcare=3 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.187;
if (mobility=4 and selfcare=3 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.574;
if (mobility=4 and selfcare=3 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.518;
if (mobility=4 and selfcare=3 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.503;
if (mobility=4 and selfcare=3 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.300;
if (mobility=4 and selfcare=3 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.089;
if (mobility=4 and selfcare=3 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.550;
if (mobility=4 and selfcare=3 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.494;
if (mobility=4 and selfcare=3 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.479;
if (mobility=4 and selfcare=3 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.276;
if (mobility=4 and selfcare=3 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.064;
if (mobility=4 and selfcare=3 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.345;
if (mobility=4 and selfcare=3 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.289;
if (mobility=4 and selfcare=3 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.274;
if (mobility=4 and selfcare=3 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.120;
if (mobility=4 and selfcare=3 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.041;
if (mobility=4 and selfcare=3 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.037;
if (mobility=4 and selfcare=3 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.019;
if (mobility=4 and selfcare=3 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.034;
if (mobility=4 and selfcare=3 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.115;
if (mobility=4 and selfcare=3 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.199;
if (mobility=4 and selfcare=3 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.572;
if (mobility=4 and selfcare=3 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.516;
if (mobility=4 and selfcare=3 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.501;
if (mobility=4 and selfcare=3 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.338;
if (mobility=4 and selfcare=3 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.168;
if (mobility=4 and selfcare=3 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.473;
if (mobility=4 and selfcare=3 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.417;
if (mobility=4 and selfcare=3 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.402;
if (mobility=4 and selfcare=3 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.239;
if (mobility=4 and selfcare=3 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.070;
if (mobility=4 and selfcare=3 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.449;
if (mobility=4 and selfcare=3 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.393;
if (mobility=4 and selfcare=3 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.378;
if (mobility=4 and selfcare=3 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.215;
if (mobility=4 and selfcare=3 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.045;
if (mobility=4 and selfcare=3 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.277;
if (mobility=4 and selfcare=3 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.221;
if (mobility=4 and selfcare=3 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.206;
if (mobility=4 and selfcare=3 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.076;
if (mobility=4 and selfcare=3 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.060;
if (mobility=4 and selfcare=3 and activity=4 and pain=5 and anxiety=1) then EQindex = 0.018;
if (mobility=4 and selfcare=3 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.038;
if (mobility=4 and selfcare=3 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.053;
if (mobility=4 and selfcare=3 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.134;
if (mobility=4 and selfcare=3 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.218;
if (mobility=4 and selfcare=3 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.365;
if (mobility=4 and selfcare=3 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.309;
if (mobility=4 and selfcare=3 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.294;
if (mobility=4 and selfcare=3 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.213;
if (mobility=4 and selfcare=3 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.129;
if (mobility=4 and selfcare=3 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.267;
if (mobility=4 and selfcare=3 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.211;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
104
if (mobility=4 and selfcare=3 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.196;
if (mobility=4 and selfcare=3 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.115;
if (mobility=4 and selfcare=3 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.031;
if (mobility=4 and selfcare=3 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.242;
if (mobility=4 and selfcare=3 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.186;
if (mobility=4 and selfcare=3 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.171;
if (mobility=4 and selfcare=3 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.090;
if (mobility=4 and selfcare=3 and activity=5 and pain=3 and anxiety=5) then EQindex = 0.006;
if (mobility=4 and selfcare=3 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.137;
if (mobility=4 and selfcare=3 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.081;
if (mobility=4 and selfcare=3 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.066;
if (mobility=4 and selfcare=3 and activity=5 and pain=4 and anxiety=4) then EQindex = -0.015;
if (mobility=4 and selfcare=3 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.099;
if (mobility=4 and selfcare=3 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.021;
if (mobility=4 and selfcare=3 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.077;
if (mobility=4 and selfcare=3 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.092;
if (mobility=4 and selfcare=3 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.173;
if (mobility=4 and selfcare=3 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.257;
if (mobility=4 and selfcare=4 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.622;
if (mobility=4 and selfcare=4 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.565;
if (mobility=4 and selfcare=4 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.551;
if (mobility=4 and selfcare=4 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.377;
if (mobility=4 and selfcare=4 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.197;
if (mobility=4 and selfcare=4 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.523;
if (mobility=4 and selfcare=4 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.467;
if (mobility=4 and selfcare=4 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.452;
if (mobility=4 and selfcare=4 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.278;
if (mobility=4 and selfcare=4 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.098;
if (mobility=4 and selfcare=4 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.499;
if (mobility=4 and selfcare=4 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.442;
if (mobility=4 and selfcare=4 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.428;
if (mobility=4 and selfcare=4 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.254;
if (mobility=4 and selfcare=4 and activity=1 and pain=3 and anxiety=5) then EQindex = 0.074;
if (mobility=4 and selfcare=4 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.318;
if (mobility=4 and selfcare=4 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.262;
if (mobility=4 and selfcare=4 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.247;
if (mobility=4 and selfcare=4 and activity=1 and pain=4 and anxiety=4) then EQindex = 0.110;
if (mobility=4 and selfcare=4 and activity=1 and pain=4 and anxiety=5) then EQindex = -0.032;
if (mobility=4 and selfcare=4 and activity=1 and pain=5 and anxiety=1) then EQindex = 0.047;
if (mobility=4 and selfcare=4 and activity=1 and pain=5 and anxiety=2) then EQindex = -0.010;
if (mobility=4 and selfcare=4 and activity=1 and pain=5 and anxiety=3) then EQindex = -0.024;
if (mobility=4 and selfcare=4 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.105;
if (mobility=4 and selfcare=4 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.189;
if (mobility=4 and selfcare=4 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.593;
if (mobility=4 and selfcare=4 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.536;
if (mobility=4 and selfcare=4 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.522;
if (mobility=4 and selfcare=4 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.348;
if (mobility=4 and selfcare=4 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.168;
if (mobility=4 and selfcare=4 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.494;
if (mobility=4 and selfcare=4 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.438;
if (mobility=4 and selfcare=4 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.423;
if (mobility=4 and selfcare=4 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.249;
if (mobility=4 and selfcare=4 and activity=2 and pain=2 and anxiety=5) then EQindex = 0.069;
if (mobility=4 and selfcare=4 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.470;
if (mobility=4 and selfcare=4 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.413;
if (mobility=4 and selfcare=4 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.399;
if (mobility=4 and selfcare=4 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.225;
if (mobility=4 and selfcare=4 and activity=2 and pain=3 and anxiety=5) then EQindex = 0.045;
if (mobility=4 and selfcare=4 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.289;
if (mobility=4 and selfcare=4 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.233;
if (mobility=4 and selfcare=4 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.218;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
105
if (mobility=4 and selfcare=4 and activity=2 and pain=4 and anxiety=4) then EQindex = 0.082;
if (mobility=4 and selfcare=4 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.060;
if (mobility=4 and selfcare=4 and activity=2 and pain=5 and anxiety=1) then EQindex = 0.018;
if (mobility=4 and selfcare=4 and activity=2 and pain=5 and anxiety=2) then EQindex = -0.039;
if (mobility=4 and selfcare=4 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.053;
if (mobility=4 and selfcare=4 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.134;
if (mobility=4 and selfcare=4 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.218;
if (mobility=4 and selfcare=4 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.586;
if (mobility=4 and selfcare=4 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.529;
if (mobility=4 and selfcare=4 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.515;
if (mobility=4 and selfcare=4 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.341;
if (mobility=4 and selfcare=4 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.161;
if (mobility=4 and selfcare=4 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.487;
if (mobility=4 and selfcare=4 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.431;
if (mobility=4 and selfcare=4 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.416;
if (mobility=4 and selfcare=4 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.242;
if (mobility=4 and selfcare=4 and activity=3 and pain=2 and anxiety=5) then EQindex = 0.062;
if (mobility=4 and selfcare=4 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.463;
if (mobility=4 and selfcare=4 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.406;
if (mobility=4 and selfcare=4 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.392;
if (mobility=4 and selfcare=4 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.218;
if (mobility=4 and selfcare=4 and activity=3 and pain=3 and anxiety=5) then EQindex = 0.038;
if (mobility=4 and selfcare=4 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.282;
if (mobility=4 and selfcare=4 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.226;
if (mobility=4 and selfcare=4 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.211;
if (mobility=4 and selfcare=4 and activity=3 and pain=4 and anxiety=4) then EQindex = 0.074;
if (mobility=4 and selfcare=4 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.068;
if (mobility=4 and selfcare=4 and activity=3 and pain=5 and anxiety=1) then EQindex = 0.011;
if (mobility=4 and selfcare=4 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.046;
if (mobility=4 and selfcare=4 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.060;
if (mobility=4 and selfcare=4 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.141;
if (mobility=4 and selfcare=4 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.225;
if (mobility=4 and selfcare=4 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.504;
if (mobility=4 and selfcare=4 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.448;
if (mobility=4 and selfcare=4 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.433;
if (mobility=4 and selfcare=4 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.290;
if (mobility=4 and selfcare=4 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.142;
if (mobility=4 and selfcare=4 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.406;
if (mobility=4 and selfcare=4 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.350;
if (mobility=4 and selfcare=4 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.335;
if (mobility=4 and selfcare=4 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.192;
if (mobility=4 and selfcare=4 and activity=4 and pain=2 and anxiety=5) then EQindex = 0.043;
if (mobility=4 and selfcare=4 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.381;
if (mobility=4 and selfcare=4 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.325;
if (mobility=4 and selfcare=4 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.310;
if (mobility=4 and selfcare=4 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.167;
if (mobility=4 and selfcare=4 and activity=4 and pain=3 and anxiety=5) then EQindex = 0.019;
if (mobility=4 and selfcare=4 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.226;
if (mobility=4 and selfcare=4 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.169;
if (mobility=4 and selfcare=4 and activity=4 and pain=4 and anxiety=3) then EQindex = 0.155;
if (mobility=4 and selfcare=4 and activity=4 and pain=4 and anxiety=4) then EQindex = 0.036;
if (mobility=4 and selfcare=4 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.087;
if (mobility=4 and selfcare=4 and activity=4 and pain=5 and anxiety=1) then EQindex = -0.009;
if (mobility=4 and selfcare=4 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.065;
if (mobility=4 and selfcare=4 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.080;
if (mobility=4 and selfcare=4 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.160;
if (mobility=4 and selfcare=4 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.245;
if (mobility=4 and selfcare=4 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.339;
if (mobility=4 and selfcare=4 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.282;
if (mobility=4 and selfcare=4 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.268;
if (mobility=4 and selfcare=4 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.187;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
106
if (mobility=4 and selfcare=4 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.103;
if (mobility=4 and selfcare=4 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.240;
if (mobility=4 and selfcare=4 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.184;
if (mobility=4 and selfcare=4 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.169;
if (mobility=4 and selfcare=4 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.088;
if (mobility=4 and selfcare=4 and activity=5 and pain=2 and anxiety=5) then EQindex = 0.004;
if (mobility=4 and selfcare=4 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.216;
if (mobility=4 and selfcare=4 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.159;
if (mobility=4 and selfcare=4 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.145;
if (mobility=4 and selfcare=4 and activity=5 and pain=3 and anxiety=4) then EQindex = 0.064;
if (mobility=4 and selfcare=4 and activity=5 and pain=3 and anxiety=5) then EQindex = -0.020;
if (mobility=4 and selfcare=4 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.111;
if (mobility=4 and selfcare=4 and activity=5 and pain=4 and anxiety=2) then EQindex = 0.054;
if (mobility=4 and selfcare=4 and activity=5 and pain=4 and anxiety=3) then EQindex = 0.040;
if (mobility=4 and selfcare=4 and activity=5 and pain=4 and anxiety=4) then EQindex = -0.041;
if (mobility=4 and selfcare=4 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.126;
if (mobility=4 and selfcare=4 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.047;
if (mobility=4 and selfcare=4 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.104;
if (mobility=4 and selfcare=4 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.118;
if (mobility=4 and selfcare=4 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.199;
if (mobility=4 and selfcare=4 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.283;
if (mobility=4 and selfcare=5 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.349;
if (mobility=4 and selfcare=5 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.293;
if (mobility=4 and selfcare=5 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.278;
if (mobility=4 and selfcare=5 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.197;
if (mobility=4 and selfcare=5 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.113;
if (mobility=4 and selfcare=5 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.251;
if (mobility=4 and selfcare=5 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.195;
if (mobility=4 and selfcare=5 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.180;
if (mobility=4 and selfcare=5 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.099;
if (mobility=4 and selfcare=5 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.015;
if (mobility=4 and selfcare=5 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.226;
if (mobility=4 and selfcare=5 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.170;
if (mobility=4 and selfcare=5 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.155;
if (mobility=4 and selfcare=5 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.074;
if (mobility=4 and selfcare=5 and activity=1 and pain=3 and anxiety=5) then EQindex = -0.010;
if (mobility=4 and selfcare=5 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.121;
if (mobility=4 and selfcare=5 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.065;
if (mobility=4 and selfcare=5 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.050;
if (mobility=4 and selfcare=5 and activity=1 and pain=4 and anxiety=4) then EQindex = -0.031;
if (mobility=4 and selfcare=5 and activity=1 and pain=4 and anxiety=5) then EQindex = -0.115;
if (mobility=4 and selfcare=5 and activity=1 and pain=5 and anxiety=1) then EQindex = -0.037;
if (mobility=4 and selfcare=5 and activity=1 and pain=5 and anxiety=2) then EQindex = -0.093;
if (mobility=4 and selfcare=5 and activity=1 and pain=5 and anxiety=3) then EQindex = -0.108;
if (mobility=4 and selfcare=5 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.189;
if (mobility=4 and selfcare=5 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.273;
if (mobility=4 and selfcare=5 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.321;
if (mobility=4 and selfcare=5 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.264;
if (mobility=4 and selfcare=5 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.250;
if (mobility=4 and selfcare=5 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.169;
if (mobility=4 and selfcare=5 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.085;
if (mobility=4 and selfcare=5 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.222;
if (mobility=4 and selfcare=5 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.166;
if (mobility=4 and selfcare=5 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.151;
if (mobility=4 and selfcare=5 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.070;
if (mobility=4 and selfcare=5 and activity=2 and pain=2 and anxiety=5) then EQindex = -0.014;
if (mobility=4 and selfcare=5 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.198;
if (mobility=4 and selfcare=5 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.141;
if (mobility=4 and selfcare=5 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.127;
if (mobility=4 and selfcare=5 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.046;
if (mobility=4 and selfcare=5 and activity=2 and pain=3 and anxiety=5) then EQindex = -0.039;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
107
if (mobility=4 and selfcare=5 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.092;
if (mobility=4 and selfcare=5 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.036;
if (mobility=4 and selfcare=5 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.021;
if (mobility=4 and selfcare=5 and activity=2 and pain=4 and anxiety=4) then EQindex = -0.060;
if (mobility=4 and selfcare=5 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.144;
if (mobility=4 and selfcare=5 and activity=2 and pain=5 and anxiety=1) then EQindex = -0.066;
if (mobility=4 and selfcare=5 and activity=2 and pain=5 and anxiety=2) then EQindex = -0.122;
if (mobility=4 and selfcare=5 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.137;
if (mobility=4 and selfcare=5 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.218;
if (mobility=4 and selfcare=5 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.302;
if (mobility=4 and selfcare=5 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.313;
if (mobility=4 and selfcare=5 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.257;
if (mobility=4 and selfcare=5 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.242;
if (mobility=4 and selfcare=5 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.161;
if (mobility=4 and selfcare=5 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.077;
if (mobility=4 and selfcare=5 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.215;
if (mobility=4 and selfcare=5 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.159;
if (mobility=4 and selfcare=5 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.144;
if (mobility=4 and selfcare=5 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.063;
if (mobility=4 and selfcare=5 and activity=3 and pain=2 and anxiety=5) then EQindex = -0.021;
if (mobility=4 and selfcare=5 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.190;
if (mobility=4 and selfcare=5 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.134;
if (mobility=4 and selfcare=5 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.119;
if (mobility=4 and selfcare=5 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.038;
if (mobility=4 and selfcare=5 and activity=3 and pain=3 and anxiety=5) then EQindex = -0.046;
if (mobility=4 and selfcare=5 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.085;
if (mobility=4 and selfcare=5 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.029;
if (mobility=4 and selfcare=5 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.014;
if (mobility=4 and selfcare=5 and activity=3 and pain=4 and anxiety=4) then EQindex = -0.067;
if (mobility=4 and selfcare=5 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.151;
if (mobility=4 and selfcare=5 and activity=3 and pain=5 and anxiety=1) then EQindex = -0.073;
if (mobility=4 and selfcare=5 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.129;
if (mobility=4 and selfcare=5 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.144;
if (mobility=4 and selfcare=5 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.225;
if (mobility=4 and selfcare=5 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.309;
if (mobility=4 and selfcare=5 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.294;
if (mobility=4 and selfcare=5 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.238;
if (mobility=4 and selfcare=5 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.223;
if (mobility=4 and selfcare=5 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.142;
if (mobility=4 and selfcare=5 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.058;
if (mobility=4 and selfcare=5 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.196;
if (mobility=4 and selfcare=5 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.139;
if (mobility=4 and selfcare=5 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.125;
if (mobility=4 and selfcare=5 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.044;
if (mobility=4 and selfcare=5 and activity=4 and pain=2 and anxiety=5) then EQindex = -0.040;
if (mobility=4 and selfcare=5 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.171;
if (mobility=4 and selfcare=5 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.115;
if (mobility=4 and selfcare=5 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.100;
if (mobility=4 and selfcare=5 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.019;
if (mobility=4 and selfcare=5 and activity=4 and pain=3 and anxiety=5) then EQindex = -0.065;
if (mobility=4 and selfcare=5 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.066;
if (mobility=4 and selfcare=5 and activity=4 and pain=4 and anxiety=2) then EQindex = 0.010;
if (mobility=4 and selfcare=5 and activity=4 and pain=4 and anxiety=3) then EQindex = -0.005;
if (mobility=4 and selfcare=5 and activity=4 and pain=4 and anxiety=4) then EQindex = -0.086;
if (mobility=4 and selfcare=5 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.170;
if (mobility=4 and selfcare=5 and activity=4 and pain=5 and anxiety=1) then EQindex = -0.092;
if (mobility=4 and selfcare=5 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.148;
if (mobility=4 and selfcare=5 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.163;
if (mobility=4 and selfcare=5 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.244;
if (mobility=4 and selfcare=5 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.328;
if (mobility=4 and selfcare=5 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.255;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
108
if (mobility=4 and selfcare=5 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.199;
if (mobility=4 and selfcare=5 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.184;
if (mobility=4 and selfcare=5 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.103;
if (mobility=4 and selfcare=5 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.019;
if (mobility=4 and selfcare=5 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.157;
if (mobility=4 and selfcare=5 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.101;
if (mobility=4 and selfcare=5 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.086;
if (mobility=4 and selfcare=5 and activity=5 and pain=2 and anxiety=4) then EQindex = 0.005;
if (mobility=4 and selfcare=5 and activity=5 and pain=2 and anxiety=5) then EQindex = -0.079;
if (mobility=4 and selfcare=5 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.132;
if (mobility=4 and selfcare=5 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.076;
if (mobility=4 and selfcare=5 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.061;
if (mobility=4 and selfcare=5 and activity=5 and pain=3 and anxiety=4) then EQindex = -0.020;
if (mobility=4 and selfcare=5 and activity=5 and pain=3 and anxiety=5) then EQindex = -0.104;
if (mobility=4 and selfcare=5 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.027;
if (mobility=4 and selfcare=5 and activity=5 and pain=4 and anxiety=2) then EQindex = -0.029;
if (mobility=4 and selfcare=5 and activity=5 and pain=4 and anxiety=3) then EQindex = -0.044;
if (mobility=4 and selfcare=5 and activity=5 and pain=4 and anxiety=4) then EQindex = -0.125;
if (mobility=4 and selfcare=5 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.209;
if (mobility=4 and selfcare=5 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.131;
if (mobility=4 and selfcare=5 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.187;
if (mobility=4 and selfcare=5 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.202;
if (mobility=4 and selfcare=5 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.283;
if (mobility=4 and selfcare=5 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.367;
if (mobility=5 and selfcare=1 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.336;
if (mobility=5 and selfcare=1 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.280;
if (mobility=5 and selfcare=1 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.265;
if (mobility=5 and selfcare=1 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.184;
if (mobility=5 and selfcare=1 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.100;
if (mobility=5 and selfcare=1 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.238;
if (mobility=5 and selfcare=1 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.181;
if (mobility=5 and selfcare=1 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.167;
if (mobility=5 and selfcare=1 and activity=1 and pain=2 and anxiety=4) then EQindex = 0.086;
if (mobility=5 and selfcare=1 and activity=1 and pain=2 and anxiety=5) then EQindex = 0.002;
if (mobility=5 and selfcare=1 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.213;
if (mobility=5 and selfcare=1 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.157;
if (mobility=5 and selfcare=1 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.142;
if (mobility=5 and selfcare=1 and activity=1 and pain=3 and anxiety=4) then EQindex = 0.061;
if (mobility=5 and selfcare=1 and activity=1 and pain=3 and anxiety=5) then EQindex = -0.023;
if (mobility=5 and selfcare=1 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.108;
if (mobility=5 and selfcare=1 and activity=1 and pain=4 and anxiety=2) then EQindex = 0.052;
if (mobility=5 and selfcare=1 and activity=1 and pain=4 and anxiety=3) then EQindex = 0.037;
if (mobility=5 and selfcare=1 and activity=1 and pain=4 and anxiety=4) then EQindex = -0.044;
if (mobility=5 and selfcare=1 and activity=1 and pain=4 and anxiety=5) then EQindex = -0.128;
if (mobility=5 and selfcare=1 and activity=1 and pain=5 and anxiety=1) then EQindex = -0.050;
if (mobility=5 and selfcare=1 and activity=1 and pain=5 and anxiety=2) then EQindex = -0.106;
if (mobility=5 and selfcare=1 and activity=1 and pain=5 and anxiety=3) then EQindex = -0.121;
if (mobility=5 and selfcare=1 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.202;
if (mobility=5 and selfcare=1 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.286;
if (mobility=5 and selfcare=1 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.307;
if (mobility=5 and selfcare=1 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.251;
if (mobility=5 and selfcare=1 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.236;
if (mobility=5 and selfcare=1 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.155;
if (mobility=5 and selfcare=1 and activity=2 and pain=1 and anxiety=5) then EQindex = 0.071;
if (mobility=5 and selfcare=1 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.209;
if (mobility=5 and selfcare=1 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.152;
if (mobility=5 and selfcare=1 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.138;
if (mobility=5 and selfcare=1 and activity=2 and pain=2 and anxiety=4) then EQindex = 0.057;
if (mobility=5 and selfcare=1 and activity=2 and pain=2 and anxiety=5) then EQindex = -0.027;
if (mobility=5 and selfcare=1 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.184;
if (mobility=5 and selfcare=1 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.128;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
109
if (mobility=5 and selfcare=1 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.113;
if (mobility=5 and selfcare=1 and activity=2 and pain=3 and anxiety=4) then EQindex = 0.032;
if (mobility=5 and selfcare=1 and activity=2 and pain=3 and anxiety=5) then EQindex = -0.052;
if (mobility=5 and selfcare=1 and activity=2 and pain=4 and anxiety=1) then EQindex = 0.079;
if (mobility=5 and selfcare=1 and activity=2 and pain=4 and anxiety=2) then EQindex = 0.023;
if (mobility=5 and selfcare=1 and activity=2 and pain=4 and anxiety=3) then EQindex = 0.008;
if (mobility=5 and selfcare=1 and activity=2 and pain=4 and anxiety=4) then EQindex = -0.073;
if (mobility=5 and selfcare=1 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.157;
if (mobility=5 and selfcare=1 and activity=2 and pain=5 and anxiety=1) then EQindex = -0.079;
if (mobility=5 and selfcare=1 and activity=2 and pain=5 and anxiety=2) then EQindex = -0.135;
if (mobility=5 and selfcare=1 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.150;
if (mobility=5 and selfcare=1 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.231;
if (mobility=5 and selfcare=1 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.315;
if (mobility=5 and selfcare=1 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.300;
if (mobility=5 and selfcare=1 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.244;
if (mobility=5 and selfcare=1 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.229;
if (mobility=5 and selfcare=1 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.148;
if (mobility=5 and selfcare=1 and activity=3 and pain=1 and anxiety=5) then EQindex = 0.064;
if (mobility=5 and selfcare=1 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.202;
if (mobility=5 and selfcare=1 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.145;
if (mobility=5 and selfcare=1 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.131;
if (mobility=5 and selfcare=1 and activity=3 and pain=2 and anxiety=4) then EQindex = 0.050;
if (mobility=5 and selfcare=1 and activity=3 and pain=2 and anxiety=5) then EQindex = -0.035;
if (mobility=5 and selfcare=1 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.177;
if (mobility=5 and selfcare=1 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.121;
if (mobility=5 and selfcare=1 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.106;
if (mobility=5 and selfcare=1 and activity=3 and pain=3 and anxiety=4) then EQindex = 0.025;
if (mobility=5 and selfcare=1 and activity=3 and pain=3 and anxiety=5) then EQindex = -0.059;
if (mobility=5 and selfcare=1 and activity=3 and pain=4 and anxiety=1) then EQindex = 0.072;
if (mobility=5 and selfcare=1 and activity=3 and pain=4 and anxiety=2) then EQindex = 0.016;
if (mobility=5 and selfcare=1 and activity=3 and pain=4 and anxiety=3) then EQindex = 0.001;
if (mobility=5 and selfcare=1 and activity=3 and pain=4 and anxiety=4) then EQindex = -0.080;
if (mobility=5 and selfcare=1 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.164;
if (mobility=5 and selfcare=1 and activity=3 and pain=5 and anxiety=1) then EQindex = -0.086;
if (mobility=5 and selfcare=1 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.142;
if (mobility=5 and selfcare=1 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.157;
if (mobility=5 and selfcare=1 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.238;
if (mobility=5 and selfcare=1 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.322;
if (mobility=5 and selfcare=1 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.281;
if (mobility=5 and selfcare=1 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.225;
if (mobility=5 and selfcare=1 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.210;
if (mobility=5 and selfcare=1 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.129;
if (mobility=5 and selfcare=1 and activity=4 and pain=1 and anxiety=5) then EQindex = 0.045;
if (mobility=5 and selfcare=1 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.182;
if (mobility=5 and selfcare=1 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.126;
if (mobility=5 and selfcare=1 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.111;
if (mobility=5 and selfcare=1 and activity=4 and pain=2 and anxiety=4) then EQindex = 0.030;
if (mobility=5 and selfcare=1 and activity=4 and pain=2 and anxiety=5) then EQindex = -0.054;
if (mobility=5 and selfcare=1 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.158;
if (mobility=5 and selfcare=1 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.102;
if (mobility=5 and selfcare=1 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.087;
if (mobility=5 and selfcare=1 and activity=4 and pain=3 and anxiety=4) then EQindex = 0.006;
if (mobility=5 and selfcare=1 and activity=4 and pain=3 and anxiety=5) then EQindex = -0.078;
if (mobility=5 and selfcare=1 and activity=4 and pain=4 and anxiety=1) then EQindex = 0.053;
if (mobility=5 and selfcare=1 and activity=4 and pain=4 and anxiety=2) then EQindex = -0.003;
if (mobility=5 and selfcare=1 and activity=4 and pain=4 and anxiety=3) then EQindex = -0.018;
if (mobility=5 and selfcare=1 and activity=4 and pain=4 and anxiety=4) then EQindex = -0.099;
if (mobility=5 and selfcare=1 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.183;
if (mobility=5 and selfcare=1 and activity=4 and pain=5 and anxiety=1) then EQindex = -0.105;
if (mobility=5 and selfcare=1 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.161;
if (mobility=5 and selfcare=1 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.176;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
110
if (mobility=5 and selfcare=1 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.257;
if (mobility=5 and selfcare=1 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.341;
if (mobility=5 and selfcare=1 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.242;
if (mobility=5 and selfcare=1 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.186;
if (mobility=5 and selfcare=1 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.171;
if (mobility=5 and selfcare=1 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.090;
if (mobility=5 and selfcare=1 and activity=5 and pain=1 and anxiety=5) then EQindex = 0.006;
if (mobility=5 and selfcare=1 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.144;
if (mobility=5 and selfcare=1 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.087;
if (mobility=5 and selfcare=1 and activity=5 and pain=2 and anxiety=3) then EQindex = 0.073;
if (mobility=5 and selfcare=1 and activity=5 and pain=2 and anxiety=4) then EQindex = -0.009;
if (mobility=5 and selfcare=1 and activity=5 and pain=2 and anxiety=5) then EQindex = -0.093;
if (mobility=5 and selfcare=1 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.119;
if (mobility=5 and selfcare=1 and activity=5 and pain=3 and anxiety=2) then EQindex = 0.063;
if (mobility=5 and selfcare=1 and activity=5 and pain=3 and anxiety=3) then EQindex = 0.048;
if (mobility=5 and selfcare=1 and activity=5 and pain=3 and anxiety=4) then EQindex = -0.033;
if (mobility=5 and selfcare=1 and activity=5 and pain=3 and anxiety=5) then EQindex = -0.117;
if (mobility=5 and selfcare=1 and activity=5 and pain=4 and anxiety=1) then EQindex = 0.014;
if (mobility=5 and selfcare=1 and activity=5 and pain=4 and anxiety=2) then EQindex = -0.042;
if (mobility=5 and selfcare=1 and activity=5 and pain=4 and anxiety=3) then EQindex = -0.057;
if (mobility=5 and selfcare=1 and activity=5 and pain=4 and anxiety=4) then EQindex = -0.138;
if (mobility=5 and selfcare=1 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.222;
if (mobility=5 and selfcare=1 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.144;
if (mobility=5 and selfcare=1 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.200;
if (mobility=5 and selfcare=1 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.215;
if (mobility=5 and selfcare=1 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.296;
if (mobility=5 and selfcare=1 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.380;
if (mobility=5 and selfcare=2 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.249;
if (mobility=5 and selfcare=2 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.193;
if (mobility=5 and selfcare=2 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.178;
if (mobility=5 and selfcare=2 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.097;
if (mobility=5 and selfcare=2 and activity=1 and pain=1 and anxiety=5) then EQindex = 0.013;
if (mobility=5 and selfcare=2 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.151;
if (mobility=5 and selfcare=2 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.095;
if (mobility=5 and selfcare=2 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.080;
if (mobility=5 and selfcare=2 and activity=1 and pain=2 and anxiety=4) then EQindex = -0.001;
if (mobility=5 and selfcare=2 and activity=1 and pain=2 and anxiety=5) then EQindex = -0.085;
if (mobility=5 and selfcare=2 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.126;
if (mobility=5 and selfcare=2 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.070;
if (mobility=5 and selfcare=2 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.055;
if (mobility=5 and selfcare=2 and activity=1 and pain=3 and anxiety=4) then EQindex = -0.026;
if (mobility=5 and selfcare=2 and activity=1 and pain=3 and anxiety=5) then EQindex = -0.110;
if (mobility=5 and selfcare=2 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.021;
if (mobility=5 and selfcare=2 and activity=1 and pain=4 and anxiety=2) then EQindex = -0.035;
if (mobility=5 and selfcare=2 and activity=1 and pain=4 and anxiety=3) then EQindex = -0.050;
if (mobility=5 and selfcare=2 and activity=1 and pain=4 and anxiety=4) then EQindex = -0.131;
if (mobility=5 and selfcare=2 and activity=1 and pain=4 and anxiety=5) then EQindex = -0.215;
if (mobility=5 and selfcare=2 and activity=1 and pain=5 and anxiety=1) then EQindex = -0.137;
if (mobility=5 and selfcare=2 and activity=1 and pain=5 and anxiety=2) then EQindex = -0.193;
if (mobility=5 and selfcare=2 and activity=1 and pain=5 and anxiety=3) then EQindex = -0.208;
if (mobility=5 and selfcare=2 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.289;
if (mobility=5 and selfcare=2 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.373;
if (mobility=5 and selfcare=2 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.221;
if (mobility=5 and selfcare=2 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.164;
if (mobility=5 and selfcare=2 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.150;
if (mobility=5 and selfcare=2 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.069;
if (mobility=5 and selfcare=2 and activity=2 and pain=1 and anxiety=5) then EQindex = -0.016;
if (mobility=5 and selfcare=2 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.122;
if (mobility=5 and selfcare=2 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.066;
if (mobility=5 and selfcare=2 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.051;
if (mobility=5 and selfcare=2 and activity=2 and pain=2 and anxiety=4) then EQindex = -0.030;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
111
if (mobility=5 and selfcare=2 and activity=2 and pain=2 and anxiety=5) then EQindex = -0.114;
if (mobility=5 and selfcare=2 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.098;
if (mobility=5 and selfcare=2 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.041;
if (mobility=5 and selfcare=2 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.027;
if (mobility=5 and selfcare=2 and activity=2 and pain=3 and anxiety=4) then EQindex = -0.054;
if (mobility=5 and selfcare=2 and activity=2 and pain=3 and anxiety=5) then EQindex = -0.139;
if (mobility=5 and selfcare=2 and activity=2 and pain=4 and anxiety=1) then EQindex = -0.008;
if (mobility=5 and selfcare=2 and activity=2 and pain=4 and anxiety=2) then EQindex = -0.064;
if (mobility=5 and selfcare=2 and activity=2 and pain=4 and anxiety=3) then EQindex = -0.079;
if (mobility=5 and selfcare=2 and activity=2 and pain=4 and anxiety=4) then EQindex = -0.160;
if (mobility=5 and selfcare=2 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.244;
if (mobility=5 and selfcare=2 and activity=2 and pain=5 and anxiety=1) then EQindex = -0.166;
if (mobility=5 and selfcare=2 and activity=2 and pain=5 and anxiety=2) then EQindex = -0.222;
if (mobility=5 and selfcare=2 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.237;
if (mobility=5 and selfcare=2 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.317;
if (mobility=5 and selfcare=2 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.402;
if (mobility=5 and selfcare=2 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.213;
if (mobility=5 and selfcare=2 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.157;
if (mobility=5 and selfcare=2 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.142;
if (mobility=5 and selfcare=2 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.061;
if (mobility=5 and selfcare=2 and activity=3 and pain=1 and anxiety=5) then EQindex = -0.023;
if (mobility=5 and selfcare=2 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.115;
if (mobility=5 and selfcare=2 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.059;
if (mobility=5 and selfcare=2 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.044;
if (mobility=5 and selfcare=2 and activity=3 and pain=2 and anxiety=4) then EQindex = -0.037;
if (mobility=5 and selfcare=2 and activity=3 and pain=2 and anxiety=5) then EQindex = -0.121;
if (mobility=5 and selfcare=2 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.090;
if (mobility=5 and selfcare=2 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.034;
if (mobility=5 and selfcare=2 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.019;
if (mobility=5 and selfcare=2 and activity=3 and pain=3 and anxiety=4) then EQindex = -0.062;
if (mobility=5 and selfcare=2 and activity=3 and pain=3 and anxiety=5) then EQindex = -0.146;
if (mobility=5 and selfcare=2 and activity=3 and pain=4 and anxiety=1) then EQindex = -0.015;
if (mobility=5 and selfcare=2 and activity=3 and pain=4 and anxiety=2) then EQindex = -0.071;
if (mobility=5 and selfcare=2 and activity=3 and pain=4 and anxiety=3) then EQindex = -0.086;
if (mobility=5 and selfcare=2 and activity=3 and pain=4 and anxiety=4) then EQindex = -0.167;
if (mobility=5 and selfcare=2 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.251;
if (mobility=5 and selfcare=2 and activity=3 and pain=5 and anxiety=1) then EQindex = -0.173;
if (mobility=5 and selfcare=2 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.229;
if (mobility=5 and selfcare=2 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.244;
if (mobility=5 and selfcare=2 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.325;
if (mobility=5 and selfcare=2 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.409;
if (mobility=5 and selfcare=2 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.194;
if (mobility=5 and selfcare=2 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.138;
if (mobility=5 and selfcare=2 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.123;
if (mobility=5 and selfcare=2 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.042;
if (mobility=5 and selfcare=2 and activity=4 and pain=1 and anxiety=5) then EQindex = -0.042;
if (mobility=5 and selfcare=2 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.096;
if (mobility=5 and selfcare=2 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.040;
if (mobility=5 and selfcare=2 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.025;
if (mobility=5 and selfcare=2 and activity=4 and pain=2 and anxiety=4) then EQindex = -0.056;
if (mobility=5 and selfcare=2 and activity=4 and pain=2 and anxiety=5) then EQindex = -0.140;
if (mobility=5 and selfcare=2 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.071;
if (mobility=5 and selfcare=2 and activity=4 and pain=3 and anxiety=2) then EQindex = 0.015;
if (mobility=5 and selfcare=2 and activity=4 and pain=3 and anxiety=3) then EQindex = 0.000;
if (mobility=5 and selfcare=2 and activity=4 and pain=3 and anxiety=4) then EQindex = -0.081;
if (mobility=5 and selfcare=2 and activity=4 and pain=3 and anxiety=5) then EQindex = -0.165;
if (mobility=5 and selfcare=2 and activity=4 and pain=4 and anxiety=1) then EQindex = -0.034;
if (mobility=5 and selfcare=2 and activity=4 and pain=4 and anxiety=2) then EQindex = -0.090;
if (mobility=5 and selfcare=2 and activity=4 and pain=4 and anxiety=3) then EQindex = -0.105;
if (mobility=5 and selfcare=2 and activity=4 and pain=4 and anxiety=4) then EQindex = -0.186;
if (mobility=5 and selfcare=2 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.270;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
112
if (mobility=5 and selfcare=2 and activity=4 and pain=5 and anxiety=1) then EQindex = -0.192;
if (mobility=5 and selfcare=2 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.248;
if (mobility=5 and selfcare=2 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.263;
if (mobility=5 and selfcare=2 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.344;
if (mobility=5 and selfcare=2 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.428;
if (mobility=5 and selfcare=2 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.155;
if (mobility=5 and selfcare=2 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.099;
if (mobility=5 and selfcare=2 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.084;
if (mobility=5 and selfcare=2 and activity=5 and pain=1 and anxiety=4) then EQindex = 0.003;
if (mobility=5 and selfcare=2 and activity=5 and pain=1 and anxiety=5) then EQindex = -0.081;
if (mobility=5 and selfcare=2 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.057;
if (mobility=5 and selfcare=2 and activity=5 and pain=2 and anxiety=2) then EQindex = 0.001;
if (mobility=5 and selfcare=2 and activity=5 and pain=2 and anxiety=3) then EQindex = -0.014;
if (mobility=5 and selfcare=2 and activity=5 and pain=2 and anxiety=4) then EQindex = -0.095;
if (mobility=5 and selfcare=2 and activity=5 and pain=2 and anxiety=5) then EQindex = -0.179;
if (mobility=5 and selfcare=2 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.032;
if (mobility=5 and selfcare=2 and activity=5 and pain=3 and anxiety=2) then EQindex = -0.024;
if (mobility=5 and selfcare=2 and activity=5 and pain=3 and anxiety=3) then EQindex = -0.039;
if (mobility=5 and selfcare=2 and activity=5 and pain=3 and anxiety=4) then EQindex = -0.120;
if (mobility=5 and selfcare=2 and activity=5 and pain=3 and anxiety=5) then EQindex = -0.204;
if (mobility=5 and selfcare=2 and activity=5 and pain=4 and anxiety=1) then EQindex = -0.073;
if (mobility=5 and selfcare=2 and activity=5 and pain=4 and anxiety=2) then EQindex = -0.129;
if (mobility=5 and selfcare=2 and activity=5 and pain=4 and anxiety=3) then EQindex = -0.144;
if (mobility=5 and selfcare=2 and activity=5 and pain=4 and anxiety=4) then EQindex = -0.225;
if (mobility=5 and selfcare=2 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.309;
if (mobility=5 and selfcare=2 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.231;
if (mobility=5 and selfcare=2 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.287;
if (mobility=5 and selfcare=2 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.302;
if (mobility=5 and selfcare=2 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.383;
if (mobility=5 and selfcare=2 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.467;
if (mobility=5 and selfcare=3 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.232;
if (mobility=5 and selfcare=3 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.176;
if (mobility=5 and selfcare=3 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.161;
if (mobility=5 and selfcare=3 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.080;
if (mobility=5 and selfcare=3 and activity=1 and pain=1 and anxiety=5) then EQindex = -0.004;
if (mobility=5 and selfcare=3 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.134;
if (mobility=5 and selfcare=3 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.077;
if (mobility=5 and selfcare=3 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.063;
if (mobility=5 and selfcare=3 and activity=1 and pain=2 and anxiety=4) then EQindex = -0.019;
if (mobility=5 and selfcare=3 and activity=1 and pain=2 and anxiety=5) then EQindex = -0.103;
if (mobility=5 and selfcare=3 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.109;
if (mobility=5 and selfcare=3 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.053;
if (mobility=5 and selfcare=3 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.038;
if (mobility=5 and selfcare=3 and activity=1 and pain=3 and anxiety=4) then EQindex = -0.043;
if (mobility=5 and selfcare=3 and activity=1 and pain=3 and anxiety=5) then EQindex = -0.127;
if (mobility=5 and selfcare=3 and activity=1 and pain=4 and anxiety=1) then EQindex = 0.004;
if (mobility=5 and selfcare=3 and activity=1 and pain=4 and anxiety=2) then EQindex = -0.052;
if (mobility=5 and selfcare=3 and activity=1 and pain=4 and anxiety=3) then EQindex = -0.067;
if (mobility=5 and selfcare=3 and activity=1 and pain=4 and anxiety=4) then EQindex = -0.148;
if (mobility=5 and selfcare=3 and activity=1 and pain=4 and anxiety=5) then EQindex = -0.232;
if (mobility=5 and selfcare=3 and activity=1 and pain=5 and anxiety=1) then EQindex = -0.154;
if (mobility=5 and selfcare=3 and activity=1 and pain=5 and anxiety=2) then EQindex = -0.210;
if (mobility=5 and selfcare=3 and activity=1 and pain=5 and anxiety=3) then EQindex = -0.225;
if (mobility=5 and selfcare=3 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.306;
if (mobility=5 and selfcare=3 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.390;
if (mobility=5 and selfcare=3 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.203;
if (mobility=5 and selfcare=3 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.147;
if (mobility=5 and selfcare=3 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.132;
if (mobility=5 and selfcare=3 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.051;
if (mobility=5 and selfcare=3 and activity=2 and pain=1 and anxiety=5) then EQindex = -0.033;
if (mobility=5 and selfcare=3 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.105;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
113
if (mobility=5 and selfcare=3 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.048;
if (mobility=5 and selfcare=3 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.034;
if (mobility=5 and selfcare=3 and activity=2 and pain=2 and anxiety=4) then EQindex = -0.047;
if (mobility=5 and selfcare=3 and activity=2 and pain=2 and anxiety=5) then EQindex = -0.131;
if (mobility=5 and selfcare=3 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.080;
if (mobility=5 and selfcare=3 and activity=2 and pain=3 and anxiety=2) then EQindex = 0.024;
if (mobility=5 and selfcare=3 and activity=2 and pain=3 and anxiety=3) then EQindex = 0.009;
if (mobility=5 and selfcare=3 and activity=2 and pain=3 and anxiety=4) then EQindex = -0.072;
if (mobility=5 and selfcare=3 and activity=2 and pain=3 and anxiety=5) then EQindex = -0.156;
if (mobility=5 and selfcare=3 and activity=2 and pain=4 and anxiety=1) then EQindex = -0.025;
if (mobility=5 and selfcare=3 and activity=2 and pain=4 and anxiety=2) then EQindex = -0.081;
if (mobility=5 and selfcare=3 and activity=2 and pain=4 and anxiety=3) then EQindex = -0.096;
if (mobility=5 and selfcare=3 and activity=2 and pain=4 and anxiety=4) then EQindex = -0.177;
if (mobility=5 and selfcare=3 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.261;
if (mobility=5 and selfcare=3 and activity=2 and pain=5 and anxiety=1) then EQindex = -0.183;
if (mobility=5 and selfcare=3 and activity=2 and pain=5 and anxiety=2) then EQindex = -0.239;
if (mobility=5 and selfcare=3 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.254;
if (mobility=5 and selfcare=3 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.335;
if (mobility=5 and selfcare=3 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.419;
if (mobility=5 and selfcare=3 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.196;
if (mobility=5 and selfcare=3 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.140;
if (mobility=5 and selfcare=3 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.125;
if (mobility=5 and selfcare=3 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.044;
if (mobility=5 and selfcare=3 and activity=3 and pain=1 and anxiety=5) then EQindex = -0.040;
if (mobility=5 and selfcare=3 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.098;
if (mobility=5 and selfcare=3 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.041;
if (mobility=5 and selfcare=3 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.027;
if (mobility=5 and selfcare=3 and activity=3 and pain=2 and anxiety=4) then EQindex = -0.055;
if (mobility=5 and selfcare=3 and activity=3 and pain=2 and anxiety=5) then EQindex = -0.139;
if (mobility=5 and selfcare=3 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.073;
if (mobility=5 and selfcare=3 and activity=3 and pain=3 and anxiety=2) then EQindex = 0.017;
if (mobility=5 and selfcare=3 and activity=3 and pain=3 and anxiety=3) then EQindex = 0.002;
if (mobility=5 and selfcare=3 and activity=3 and pain=3 and anxiety=4) then EQindex = -0.079;
if (mobility=5 and selfcare=3 and activity=3 and pain=3 and anxiety=5) then EQindex = -0.163;
if (mobility=5 and selfcare=3 and activity=3 and pain=4 and anxiety=1) then EQindex = -0.032;
if (mobility=5 and selfcare=3 and activity=3 and pain=4 and anxiety=2) then EQindex = -0.088;
if (mobility=5 and selfcare=3 and activity=3 and pain=4 and anxiety=3) then EQindex = -0.103;
if (mobility=5 and selfcare=3 and activity=3 and pain=4 and anxiety=4) then EQindex = -0.184;
if (mobility=5 and selfcare=3 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.268;
if (mobility=5 and selfcare=3 and activity=3 and pain=5 and anxiety=1) then EQindex = -0.190;
if (mobility=5 and selfcare=3 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.246;
if (mobility=5 and selfcare=3 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.261;
if (mobility=5 and selfcare=3 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.342;
if (mobility=5 and selfcare=3 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.426;
if (mobility=5 and selfcare=3 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.177;
if (mobility=5 and selfcare=3 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.121;
if (mobility=5 and selfcare=3 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.106;
if (mobility=5 and selfcare=3 and activity=4 and pain=1 and anxiety=4) then EQindex = 0.025;
if (mobility=5 and selfcare=3 and activity=4 and pain=1 and anxiety=5) then EQindex = -0.059;
if (mobility=5 and selfcare=3 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.078;
if (mobility=5 and selfcare=3 and activity=4 and pain=2 and anxiety=2) then EQindex = 0.022;
if (mobility=5 and selfcare=3 and activity=4 and pain=2 and anxiety=3) then EQindex = 0.007;
if (mobility=5 and selfcare=3 and activity=4 and pain=2 and anxiety=4) then EQindex = -0.074;
if (mobility=5 and selfcare=3 and activity=4 and pain=2 and anxiety=5) then EQindex = -0.158;
if (mobility=5 and selfcare=3 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.054;
if (mobility=5 and selfcare=3 and activity=4 and pain=3 and anxiety=2) then EQindex = -0.002;
if (mobility=5 and selfcare=3 and activity=4 and pain=3 and anxiety=3) then EQindex = -0.017;
if (mobility=5 and selfcare=3 and activity=4 and pain=3 and anxiety=4) then EQindex = -0.098;
if (mobility=5 and selfcare=3 and activity=4 and pain=3 and anxiety=5) then EQindex = -0.182;
if (mobility=5 and selfcare=3 and activity=4 and pain=4 and anxiety=1) then EQindex = -0.051;
if (mobility=5 and selfcare=3 and activity=4 and pain=4 and anxiety=2) then EQindex = -0.107;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
114
if (mobility=5 and selfcare=3 and activity=4 and pain=4 and anxiety=3) then EQindex = -0.122;
if (mobility=5 and selfcare=3 and activity=4 and pain=4 and anxiety=4) then EQindex = -0.203;
if (mobility=5 and selfcare=3 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.287;
if (mobility=5 and selfcare=3 and activity=4 and pain=5 and anxiety=1) then EQindex = -0.209;
if (mobility=5 and selfcare=3 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.265;
if (mobility=5 and selfcare=3 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.280;
if (mobility=5 and selfcare=3 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.361;
if (mobility=5 and selfcare=3 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.445;
if (mobility=5 and selfcare=3 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.138;
if (mobility=5 and selfcare=3 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.082;
if (mobility=5 and selfcare=3 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.067;
if (mobility=5 and selfcare=3 and activity=5 and pain=1 and anxiety=4) then EQindex = -0.014;
if (mobility=5 and selfcare=3 and activity=5 and pain=1 and anxiety=5) then EQindex = -0.098;
if (mobility=5 and selfcare=3 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.040;
if (mobility=5 and selfcare=3 and activity=5 and pain=2 and anxiety=2) then EQindex = -0.017;
if (mobility=5 and selfcare=3 and activity=5 and pain=2 and anxiety=3) then EQindex = -0.032;
if (mobility=5 and selfcare=3 and activity=5 and pain=2 and anxiety=4) then EQindex = -0.113;
if (mobility=5 and selfcare=3 and activity=5 and pain=2 and anxiety=5) then EQindex = -0.197;
if (mobility=5 and selfcare=3 and activity=5 and pain=3 and anxiety=1) then EQindex = 0.015;
if (mobility=5 and selfcare=3 and activity=5 and pain=3 and anxiety=2) then EQindex = -0.041;
if (mobility=5 and selfcare=3 and activity=5 and pain=3 and anxiety=3) then EQindex = -0.056;
if (mobility=5 and selfcare=3 and activity=5 and pain=3 and anxiety=4) then EQindex = -0.137;
if (mobility=5 and selfcare=3 and activity=5 and pain=3 and anxiety=5) then EQindex = -0.221;
if (mobility=5 and selfcare=3 and activity=5 and pain=4 and anxiety=1) then EQindex = -0.090;
if (mobility=5 and selfcare=3 and activity=5 and pain=4 and anxiety=2) then EQindex = -0.146;
if (mobility=5 and selfcare=3 and activity=5 and pain=4 and anxiety=3) then EQindex = -0.161;
if (mobility=5 and selfcare=3 and activity=5 and pain=4 and anxiety=4) then EQindex = -0.242;
if (mobility=5 and selfcare=3 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.326;
if (mobility=5 and selfcare=3 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.248;
if (mobility=5 and selfcare=3 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.304;
if (mobility=5 and selfcare=3 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.319;
if (mobility=5 and selfcare=3 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.400;
if (mobility=5 and selfcare=3 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.484;
if (mobility=5 and selfcare=4 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.205;
if (mobility=5 and selfcare=4 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.149;
if (mobility=5 and selfcare=4 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.134;
if (mobility=5 and selfcare=4 and activity=1 and pain=1 and anxiety=4) then EQindex = 0.053;
if (mobility=5 and selfcare=4 and activity=1 and pain=1 and anxiety=5) then EQindex = -0.031;
if (mobility=5 and selfcare=4 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.107;
if (mobility=5 and selfcare=4 and activity=1 and pain=2 and anxiety=2) then EQindex = 0.050;
if (mobility=5 and selfcare=4 and activity=1 and pain=2 and anxiety=3) then EQindex = 0.036;
if (mobility=5 and selfcare=4 and activity=1 and pain=2 and anxiety=4) then EQindex = -0.045;
if (mobility=5 and selfcare=4 and activity=1 and pain=2 and anxiety=5) then EQindex = -0.129;
if (mobility=5 and selfcare=4 and activity=1 and pain=3 and anxiety=1) then EQindex = 0.082;
if (mobility=5 and selfcare=4 and activity=1 and pain=3 and anxiety=2) then EQindex = 0.026;
if (mobility=5 and selfcare=4 and activity=1 and pain=3 and anxiety=3) then EQindex = 0.011;
if (mobility=5 and selfcare=4 and activity=1 and pain=3 and anxiety=4) then EQindex = -0.070;
if (mobility=5 and selfcare=4 and activity=1 and pain=3 and anxiety=5) then EQindex = -0.154;
if (mobility=5 and selfcare=4 and activity=1 and pain=4 and anxiety=1) then EQindex = -0.023;
if (mobility=5 and selfcare=4 and activity=1 and pain=4 and anxiety=2) then EQindex = -0.079;
if (mobility=5 and selfcare=4 and activity=1 and pain=4 and anxiety=3) then EQindex = -0.094;
if (mobility=5 and selfcare=4 and activity=1 and pain=4 and anxiety=4) then EQindex = -0.175;
if (mobility=5 and selfcare=4 and activity=1 and pain=4 and anxiety=5) then EQindex = -0.259;
if (mobility=5 and selfcare=4 and activity=1 and pain=5 and anxiety=1) then EQindex = -0.181;
if (mobility=5 and selfcare=4 and activity=1 and pain=5 and anxiety=2) then EQindex = -0.237;
if (mobility=5 and selfcare=4 and activity=1 and pain=5 and anxiety=3) then EQindex = -0.252;
if (mobility=5 and selfcare=4 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.333;
if (mobility=5 and selfcare=4 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.417;
if (mobility=5 and selfcare=4 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.176;
if (mobility=5 and selfcare=4 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.120;
if (mobility=5 and selfcare=4 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.105;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
115
if (mobility=5 and selfcare=4 and activity=2 and pain=1 and anxiety=4) then EQindex = 0.024;
if (mobility=5 and selfcare=4 and activity=2 and pain=1 and anxiety=5) then EQindex = -0.060;
if (mobility=5 and selfcare=4 and activity=2 and pain=2 and anxiety=1) then EQindex = 0.078;
if (mobility=5 and selfcare=4 and activity=2 and pain=2 and anxiety=2) then EQindex = 0.022;
if (mobility=5 and selfcare=4 and activity=2 and pain=2 and anxiety=3) then EQindex = 0.007;
if (mobility=5 and selfcare=4 and activity=2 and pain=2 and anxiety=4) then EQindex = -0.074;
if (mobility=5 and selfcare=4 and activity=2 and pain=2 and anxiety=5) then EQindex = -0.158;
if (mobility=5 and selfcare=4 and activity=2 and pain=3 and anxiety=1) then EQindex = 0.053;
if (mobility=5 and selfcare=4 and activity=2 and pain=3 and anxiety=2) then EQindex = -0.003;
if (mobility=5 and selfcare=4 and activity=2 and pain=3 and anxiety=3) then EQindex = -0.018;
if (mobility=5 and selfcare=4 and activity=2 and pain=3 and anxiety=4) then EQindex = -0.099;
if (mobility=5 and selfcare=4 and activity=2 and pain=3 and anxiety=5) then EQindex = -0.183;
if (mobility=5 and selfcare=4 and activity=2 and pain=4 and anxiety=1) then EQindex = -0.052;
if (mobility=5 and selfcare=4 and activity=2 and pain=4 and anxiety=2) then EQindex = -0.108;
if (mobility=5 and selfcare=4 and activity=2 and pain=4 and anxiety=3) then EQindex = -0.123;
if (mobility=5 and selfcare=4 and activity=2 and pain=4 and anxiety=4) then EQindex = -0.204;
if (mobility=5 and selfcare=4 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.288;
if (mobility=5 and selfcare=4 and activity=2 and pain=5 and anxiety=1) then EQindex = -0.210;
if (mobility=5 and selfcare=4 and activity=2 and pain=5 and anxiety=2) then EQindex = -0.266;
if (mobility=5 and selfcare=4 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.281;
if (mobility=5 and selfcare=4 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.362;
if (mobility=5 and selfcare=4 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.446;
if (mobility=5 and selfcare=4 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.169;
if (mobility=5 and selfcare=4 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.113;
if (mobility=5 and selfcare=4 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.098;
if (mobility=5 and selfcare=4 and activity=3 and pain=1 and anxiety=4) then EQindex = 0.017;
if (mobility=5 and selfcare=4 and activity=3 and pain=1 and anxiety=5) then EQindex = -0.067;
if (mobility=5 and selfcare=4 and activity=3 and pain=2 and anxiety=1) then EQindex = 0.071;
if (mobility=5 and selfcare=4 and activity=3 and pain=2 and anxiety=2) then EQindex = 0.014;
if (mobility=5 and selfcare=4 and activity=3 and pain=2 and anxiety=3) then EQindex = 0.000;
if (mobility=5 and selfcare=4 and activity=3 and pain=2 and anxiety=4) then EQindex = -0.081;
if (mobility=5 and selfcare=4 and activity=3 and pain=2 and anxiety=5) then EQindex = -0.165;
if (mobility=5 and selfcare=4 and activity=3 and pain=3 and anxiety=1) then EQindex = 0.046;
if (mobility=5 and selfcare=4 and activity=3 and pain=3 and anxiety=2) then EQindex = -0.010;
if (mobility=5 and selfcare=4 and activity=3 and pain=3 and anxiety=3) then EQindex = -0.025;
if (mobility=5 and selfcare=4 and activity=3 and pain=3 and anxiety=4) then EQindex = -0.106;
if (mobility=5 and selfcare=4 and activity=3 and pain=3 and anxiety=5) then EQindex = -0.190;
if (mobility=5 and selfcare=4 and activity=3 and pain=4 and anxiety=1) then EQindex = -0.059;
if (mobility=5 and selfcare=4 and activity=3 and pain=4 and anxiety=2) then EQindex = -0.115;
if (mobility=5 and selfcare=4 and activity=3 and pain=4 and anxiety=3) then EQindex = -0.130;
if (mobility=5 and selfcare=4 and activity=3 and pain=4 and anxiety=4) then EQindex = -0.211;
if (mobility=5 and selfcare=4 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.295;
if (mobility=5 and selfcare=4 and activity=3 and pain=5 and anxiety=1) then EQindex = -0.217;
if (mobility=5 and selfcare=4 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.273;
if (mobility=5 and selfcare=4 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.288;
if (mobility=5 and selfcare=4 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.369;
if (mobility=5 and selfcare=4 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.453;
if (mobility=5 and selfcare=4 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.150;
if (mobility=5 and selfcare=4 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.094;
if (mobility=5 and selfcare=4 and activity=4 and pain=1 and anxiety=3) then EQindex = 0.079;
if (mobility=5 and selfcare=4 and activity=4 and pain=1 and anxiety=4) then EQindex = -0.002;
if (mobility=5 and selfcare=4 and activity=4 and pain=1 and anxiety=5) then EQindex = -0.086;
if (mobility=5 and selfcare=4 and activity=4 and pain=2 and anxiety=1) then EQindex = 0.052;
if (mobility=5 and selfcare=4 and activity=4 and pain=2 and anxiety=2) then EQindex = -0.005;
if (mobility=5 and selfcare=4 and activity=4 and pain=2 and anxiety=3) then EQindex = -0.019;
if (mobility=5 and selfcare=4 and activity=4 and pain=2 and anxiety=4) then EQindex = -0.100;
if (mobility=5 and selfcare=4 and activity=4 and pain=2 and anxiety=5) then EQindex = -0.184;
if (mobility=5 and selfcare=4 and activity=4 and pain=3 and anxiety=1) then EQindex = 0.027;
if (mobility=5 and selfcare=4 and activity=4 and pain=3 and anxiety=2) then EQindex = -0.029;
if (mobility=5 and selfcare=4 and activity=4 and pain=3 and anxiety=3) then EQindex = -0.044;
if (mobility=5 and selfcare=4 and activity=4 and pain=3 and anxiety=4) then EQindex = -0.125;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
116
if (mobility=5 and selfcare=4 and activity=4 and pain=3 and anxiety=5) then EQindex = -0.209;
if (mobility=5 and selfcare=4 and activity=4 and pain=4 and anxiety=1) then EQindex = -0.078;
if (mobility=5 and selfcare=4 and activity=4 and pain=4 and anxiety=2) then EQindex = -0.134;
if (mobility=5 and selfcare=4 and activity=4 and pain=4 and anxiety=3) then EQindex = -0.149;
if (mobility=5 and selfcare=4 and activity=4 and pain=4 and anxiety=4) then EQindex = -0.230;
if (mobility=5 and selfcare=4 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.314;
if (mobility=5 and selfcare=4 and activity=4 and pain=5 and anxiety=1) then EQindex = -0.236;
if (mobility=5 and selfcare=4 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.292;
if (mobility=5 and selfcare=4 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.307;
if (mobility=5 and selfcare=4 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.388;
if (mobility=5 and selfcare=4 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.472;
if (mobility=5 and selfcare=4 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.111;
if (mobility=5 and selfcare=4 and activity=5 and pain=1 and anxiety=2) then EQindex = 0.055;
if (mobility=5 and selfcare=4 and activity=5 and pain=1 and anxiety=3) then EQindex = 0.040;
if (mobility=5 and selfcare=4 and activity=5 and pain=1 and anxiety=4) then EQindex = -0.041;
if (mobility=5 and selfcare=4 and activity=5 and pain=1 and anxiety=5) then EQindex = -0.125;
if (mobility=5 and selfcare=4 and activity=5 and pain=2 and anxiety=1) then EQindex = 0.013;
if (mobility=5 and selfcare=4 and activity=5 and pain=2 and anxiety=2) then EQindex = -0.044;
if (mobility=5 and selfcare=4 and activity=5 and pain=2 and anxiety=3) then EQindex = -0.058;
if (mobility=5 and selfcare=4 and activity=5 and pain=2 and anxiety=4) then EQindex = -0.139;
if (mobility=5 and selfcare=4 and activity=5 and pain=2 and anxiety=5) then EQindex = -0.223;
if (mobility=5 and selfcare=4 and activity=5 and pain=3 and anxiety=1) then EQindex = -0.012;
if (mobility=5 and selfcare=4 and activity=5 and pain=3 and anxiety=2) then EQindex = -0.068;
if (mobility=5 and selfcare=4 and activity=5 and pain=3 and anxiety=3) then EQindex = -0.083;
if (mobility=5 and selfcare=4 and activity=5 and pain=3 and anxiety=4) then EQindex = -0.164;
if (mobility=5 and selfcare=4 and activity=5 and pain=3 and anxiety=5) then EQindex = -0.248;
if (mobility=5 and selfcare=4 and activity=5 and pain=4 and anxiety=1) then EQindex = -0.117;
if (mobility=5 and selfcare=4 and activity=5 and pain=4 and anxiety=2) then EQindex = -0.173;
if (mobility=5 and selfcare=4 and activity=5 and pain=4 and anxiety=3) then EQindex = -0.188;
if (mobility=5 and selfcare=4 and activity=5 and pain=4 and anxiety=4) then EQindex = -0.269;
if (mobility=5 and selfcare=4 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.353;
if (mobility=5 and selfcare=4 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.275;
if (mobility=5 and selfcare=4 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.331;
if (mobility=5 and selfcare=4 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.346;
if (mobility=5 and selfcare=4 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.427;
if (mobility=5 and selfcare=4 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.511;
if (mobility=5 and selfcare=5 and activity=1 and pain=1 and anxiety=1) then EQindex = 0.122;
if (mobility=5 and selfcare=5 and activity=1 and pain=1 and anxiety=2) then EQindex = 0.066;
if (mobility=5 and selfcare=5 and activity=1 and pain=1 and anxiety=3) then EQindex = 0.051;
if (mobility=5 and selfcare=5 and activity=1 and pain=1 and anxiety=4) then EQindex = -0.030;
if (mobility=5 and selfcare=5 and activity=1 and pain=1 and anxiety=5) then EQindex = -0.114;
if (mobility=5 and selfcare=5 and activity=1 and pain=2 and anxiety=1) then EQindex = 0.024;
if (mobility=5 and selfcare=5 and activity=1 and pain=2 and anxiety=2) then EQindex = -0.033;
if (mobility=5 and selfcare=5 and activity=1 and pain=2 and anxiety=3) then EQindex = -0.048;
if (mobility=5 and selfcare=5 and activity=1 and pain=2 and anxiety=4) then EQindex = -0.129;
if (mobility=5 and selfcare=5 and activity=1 and pain=2 and anxiety=5) then EQindex = -0.213;
if (mobility=5 and selfcare=5 and activity=1 and pain=3 and anxiety=1) then EQindex = -0.001;
if (mobility=5 and selfcare=5 and activity=1 and pain=3 and anxiety=2) then EQindex = -0.057;
if (mobility=5 and selfcare=5 and activity=1 and pain=3 and anxiety=3) then EQindex = -0.072;
if (mobility=5 and selfcare=5 and activity=1 and pain=3 and anxiety=4) then EQindex = -0.153;
if (mobility=5 and selfcare=5 and activity=1 and pain=3 and anxiety=5) then EQindex = -0.237;
if (mobility=5 and selfcare=5 and activity=1 and pain=4 and anxiety=1) then EQindex = -0.106;
if (mobility=5 and selfcare=5 and activity=1 and pain=4 and anxiety=2) then EQindex = -0.162;
if (mobility=5 and selfcare=5 and activity=1 and pain=4 and anxiety=3) then EQindex = -0.177;
if (mobility=5 and selfcare=5 and activity=1 and pain=4 and anxiety=4) then EQindex = -0.258;
if (mobility=5 and selfcare=5 and activity=1 and pain=4 and anxiety=5) then EQindex = -0.342;
if (mobility=5 and selfcare=5 and activity=1 and pain=5 and anxiety=1) then EQindex = -0.264;
if (mobility=5 and selfcare=5 and activity=1 and pain=5 and anxiety=2) then EQindex = -0.320;
if (mobility=5 and selfcare=5 and activity=1 and pain=5 and anxiety=3) then EQindex = -0.335;
if (mobility=5 and selfcare=5 and activity=1 and pain=5 and anxiety=4) then EQindex = -0.416;
if (mobility=5 and selfcare=5 and activity=1 and pain=5 and anxiety=5) then EQindex = -0.500;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
117
if (mobility=5 and selfcare=5 and activity=2 and pain=1 and anxiety=1) then EQindex = 0.093;
if (mobility=5 and selfcare=5 and activity=2 and pain=1 and anxiety=2) then EQindex = 0.037;
if (mobility=5 and selfcare=5 and activity=2 and pain=1 and anxiety=3) then EQindex = 0.022;
if (mobility=5 and selfcare=5 and activity=2 and pain=1 and anxiety=4) then EQindex = -0.059;
if (mobility=5 and selfcare=5 and activity=2 and pain=1 and anxiety=5) then EQindex = -0.143;
if (mobility=5 and selfcare=5 and activity=2 and pain=2 and anxiety=1) then EQindex = -0.005;
if (mobility=5 and selfcare=5 and activity=2 and pain=2 and anxiety=2) then EQindex = -0.062;
if (mobility=5 and selfcare=5 and activity=2 and pain=2 and anxiety=3) then EQindex = -0.076;
if (mobility=5 and selfcare=5 and activity=2 and pain=2 and anxiety=4) then EQindex = -0.157;
if (mobility=5 and selfcare=5 and activity=2 and pain=2 and anxiety=5) then EQindex = -0.241;
if (mobility=5 and selfcare=5 and activity=2 and pain=3 and anxiety=1) then EQindex = -0.030;
if (mobility=5 and selfcare=5 and activity=2 and pain=3 and anxiety=2) then EQindex = -0.086;
if (mobility=5 and selfcare=5 and activity=2 and pain=3 and anxiety=3) then EQindex = -0.101;
if (mobility=5 and selfcare=5 and activity=2 and pain=3 and anxiety=4) then EQindex = -0.182;
if (mobility=5 and selfcare=5 and activity=2 and pain=3 and anxiety=5) then EQindex = -0.266;
if (mobility=5 and selfcare=5 and activity=2 and pain=4 and anxiety=1) then EQindex = -0.135;
if (mobility=5 and selfcare=5 and activity=2 and pain=4 and anxiety=2) then EQindex = -0.191;
if (mobility=5 and selfcare=5 and activity=2 and pain=4 and anxiety=3) then EQindex = -0.206;
if (mobility=5 and selfcare=5 and activity=2 and pain=4 and anxiety=4) then EQindex = -0.287;
if (mobility=5 and selfcare=5 and activity=2 and pain=4 and anxiety=5) then EQindex = -0.371;
if (mobility=5 and selfcare=5 and activity=2 and pain=5 and anxiety=1) then EQindex = -0.293;
if (mobility=5 and selfcare=5 and activity=2 and pain=5 and anxiety=2) then EQindex = -0.349;
if (mobility=5 and selfcare=5 and activity=2 and pain=5 and anxiety=3) then EQindex = -0.364;
if (mobility=5 and selfcare=5 and activity=2 and pain=5 and anxiety=4) then EQindex = -0.445;
if (mobility=5 and selfcare=5 and activity=2 and pain=5 and anxiety=5) then EQindex = -0.529;
if (mobility=5 and selfcare=5 and activity=3 and pain=1 and anxiety=1) then EQindex = 0.086;
if (mobility=5 and selfcare=5 and activity=3 and pain=1 and anxiety=2) then EQindex = 0.030;
if (mobility=5 and selfcare=5 and activity=3 and pain=1 and anxiety=3) then EQindex = 0.015;
if (mobility=5 and selfcare=5 and activity=3 and pain=1 and anxiety=4) then EQindex = -0.066;
if (mobility=5 and selfcare=5 and activity=3 and pain=1 and anxiety=5) then EQindex = -0.150;
if (mobility=5 and selfcare=5 and activity=3 and pain=2 and anxiety=1) then EQindex = -0.013;
if (mobility=5 and selfcare=5 and activity=3 and pain=2 and anxiety=2) then EQindex = -0.069;
if (mobility=5 and selfcare=5 and activity=3 and pain=2 and anxiety=3) then EQindex = -0.084;
if (mobility=5 and selfcare=5 and activity=3 and pain=2 and anxiety=4) then EQindex = -0.165;
if (mobility=5 and selfcare=5 and activity=3 and pain=2 and anxiety=5) then EQindex = -0.249;
if (mobility=5 and selfcare=5 and activity=3 and pain=3 and anxiety=1) then EQindex = -0.037;
if (mobility=5 and selfcare=5 and activity=3 and pain=3 and anxiety=2) then EQindex = -0.093;
if (mobility=5 and selfcare=5 and activity=3 and pain=3 and anxiety=3) then EQindex = -0.108;
if (mobility=5 and selfcare=5 and activity=3 and pain=3 and anxiety=4) then EQindex = -0.189;
if (mobility=5 and selfcare=5 and activity=3 and pain=3 and anxiety=5) then EQindex = -0.273;
if (mobility=5 and selfcare=5 and activity=3 and pain=4 and anxiety=1) then EQindex = -0.142;
if (mobility=5 and selfcare=5 and activity=3 and pain=4 and anxiety=2) then EQindex = -0.198;
if (mobility=5 and selfcare=5 and activity=3 and pain=4 and anxiety=3) then EQindex = -0.213;
if (mobility=5 and selfcare=5 and activity=3 and pain=4 and anxiety=4) then EQindex = -0.294;
if (mobility=5 and selfcare=5 and activity=3 and pain=4 and anxiety=5) then EQindex = -0.378;
if (mobility=5 and selfcare=5 and activity=3 and pain=5 and anxiety=1) then EQindex = -0.300;
if (mobility=5 and selfcare=5 and activity=3 and pain=5 and anxiety=2) then EQindex = -0.356;
if (mobility=5 and selfcare=5 and activity=3 and pain=5 and anxiety=3) then EQindex = -0.371;
if (mobility=5 and selfcare=5 and activity=3 and pain=5 and anxiety=4) then EQindex = -0.452;
if (mobility=5 and selfcare=5 and activity=3 and pain=5 and anxiety=5) then EQindex = -0.536;
if (mobility=5 and selfcare=5 and activity=4 and pain=1 and anxiety=1) then EQindex = 0.067;
if (mobility=5 and selfcare=5 and activity=4 and pain=1 and anxiety=2) then EQindex = 0.011;
if (mobility=5 and selfcare=5 and activity=4 and pain=1 and anxiety=3) then EQindex = -0.004;
if (mobility=5 and selfcare=5 and activity=4 and pain=1 and anxiety=4) then EQindex = -0.085;
if (mobility=5 and selfcare=5 and activity=4 and pain=1 and anxiety=5) then EQindex = -0.169;
if (mobility=5 and selfcare=5 and activity=4 and pain=2 and anxiety=1) then EQindex = -0.032;
if (mobility=5 and selfcare=5 and activity=4 and pain=2 and anxiety=2) then EQindex = -0.088;
if (mobility=5 and selfcare=5 and activity=4 and pain=2 and anxiety=3) then EQindex = -0.103;
if (mobility=5 and selfcare=5 and activity=4 and pain=2 and anxiety=4) then EQindex = -0.184;
if (mobility=5 and selfcare=5 and activity=4 and pain=2 and anxiety=5) then EQindex = -0.268;
if (mobility=5 and selfcare=5 and activity=4 and pain=3 and anxiety=1) then EQindex = -0.056;


Statistical Analysis Plan
Study code D589SC00003
Edition Number 2
Date 06 September 2017
118
if (mobility=5 and selfcare=5 and activity=4 and pain=3 and anxiety=2) then EQindex = -0.112;
if (mobility=5 and selfcare=5 and activity=4 and pain=3 and anxiety=3) then EQindex = -0.127;
if (mobility=5 and selfcare=5 and activity=4 and pain=3 and anxiety=4) then EQindex = -0.208;
if (mobility=5 and selfcare=5 and activity=4 and pain=3 and anxiety=5) then EQindex = -0.292;
if (mobility=5 and selfcare=5 and activity=4 and pain=4 and anxiety=1) then EQindex = -0.161;
if (mobility=5 and selfcare=5 and activity=4 and pain=4 and anxiety=2) then EQindex = -0.217;
if (mobility=5 and selfcare=5 and activity=4 and pain=4 and anxiety=3) then EQindex = -0.232;
if (mobility=5 and selfcare=5 and activity=4 and pain=4 and anxiety=4) then EQindex = -0.313;
if (mobility=5 and selfcare=5 and activity=4 and pain=4 and anxiety=5) then EQindex = -0.397;
if (mobility=5 and selfcare=5 and activity=4 and pain=5 and anxiety=1) then EQindex = -0.319;
if (mobility=5 and selfcare=5 and activity=4 and pain=5 and anxiety=2) then EQindex = -0.375;
if (mobility=5 and selfcare=5 and activity=4 and pain=5 and anxiety=3) then EQindex = -0.390;
if (mobility=5 and selfcare=5 and activity=4 and pain=5 and anxiety=4) then EQindex = -0.471;
if (mobility=5 and selfcare=5 and activity=4 and pain=5 and anxiety=5) then EQindex = -0.555;
if (mobility=5 and selfcare=5 and activity=5 and pain=1 and anxiety=1) then EQindex = 0.028;
if (mobility=5 and selfcare=5 and activity=5 and pain=1 and anxiety=2) then EQindex = -0.028;
if (mobility=5 and selfcare=5 and activity=5 and pain=1 and anxiety=3) then EQindex = -0.043;
if (mobility=5 and selfcare=5 and activity=5 and pain=1 and anxiety=4) then EQindex = -0.124;
if (mobility=5 and selfcare=5 and activity=5 and pain=1 and anxiety=5) then EQindex = -0.208;
if (mobility=5 and selfcare=5 and activity=5 and pain=2 and anxiety=1) then EQindex = -0.071;
if (mobility=5 and selfcare=5 and activity=5 and pain=2 and anxiety=2) then EQindex = -0.127;
if (mobility=5 and selfcare=5 and activity=5 and pain=2 and anxiety=3) then EQindex = -0.142;
if (mobility=5 and selfcare=5 and activity=5 and pain=2 and anxiety=4) then EQindex = -0.223;
if (mobility=5 and selfcare=5 and activity=5 and pain=2 and anxiety=5) then EQindex = -0.307;
if (mobility=5 and selfcare=5 and activity=5 and pain=3 and anxiety=1) then EQindex = -0.095;
if (mobility=5 and selfcare=5 and activity=5 and pain=3 and anxiety=2) then EQindex = -0.151;
if (mobility=5 and selfcare=5 and activity=5 and pain=3 and anxiety=3) then EQindex = -0.166;
if (mobility=5 and selfcare=5 and activity=5 and pain=3 and anxiety=4) then EQindex = -0.247;
if (mobility=5 and selfcare=5 and activity=5 and pain=3 and anxiety=5) then EQindex = -0.331;
if (mobility=5 and selfcare=5 and activity=5 and pain=4 and anxiety=1) then EQindex = -0.200;
if (mobility=5 and selfcare=5 and activity=5 and pain=4 and anxiety=2) then EQindex = -0.256;
if (mobility=5 and selfcare=5 and activity=5 and pain=4 and anxiety=3) then EQindex = -0.271;
if (mobility=5 and selfcare=5 and activity=5 and pain=4 and anxiety=4) then EQindex = -0.352;
if (mobility=5 and selfcare=5 and activity=5 and pain=4 and anxiety=5) then EQindex = -0.436;
if (mobility=5 and selfcare=5 and activity=5 and pain=5 and anxiety=1) then EQindex = -0.358;
if (mobility=5 and selfcare=5 and activity=5 and pain=5 and anxiety=2) then EQindex = -0.414;
if (mobility=5 and selfcare=5 and activity=5 and pain=5 and anxiety=3) then EQindex = -0.429;
if (mobility=5 and selfcare=5 and activity=5 and pain=5 and anxiety=4) then EQindex = -0.510;
if (mobility=5 and selfcare=5 and activity=5 and pain=5 and anxiety=5) then EQindex = -0.594;
if (mobility = .) or (selfcare = .) or (activity = .) or (pain = .) or (anxiety = .) then EQindex = . ;
output;
run;