Real-World Outcome of Adalimumab on Rheumatoid Arthritis Patients in China (ROCKI Study)
Conditions: Rheumatoid Arthritis
Sponsor: AbbVie

Adalimumab 
Protocol P15-776
Version 7.0 dated 07 August 2017
1 
Title Page 
Title
Real-World Outcome of Adalimumab on Rheumatoid Arthritis 
Patients in China
Protocol Version Identifier
P15-776
Date of Last Version of 
Protocol
07 August 2017
EU PAS Register Number
Not registered (Non-PASS PMOS)
Active Substance
Not applicable (Non-PASS PMOS)
Medicinal Product
Not applicable (Non-PASS PMOS)
Product Reference
Not applicable (Non-PASS PMOS)
Procedure Number
Not applicable (Non-PASS PMOS)
Marketing Authorization 
Holder(s)
AbbVie Pharmaceutical Trading (Shanghai) Co. Ltd
17F, Chong Hing Finance Center 
288 West Nanjing Road, Shanghai 200003
Joint PASS
Not applicable (Non-PASS PMOS)
Research Question and 
Objectives
The overall strategic objective of this non-interventional, observational 
study is to assess the effect of Adalimumab on health-related quality of 
life and work productivity in patients with Rheumatoid Arthritis (RA) 
in China.
Country(ies) of Study
China
Author
This study will be conducted in compliance with this protocol. 
Confidential Information 
No use or disclosure outside AbbVie is permitted without prior written authorization from 
AbbVie. 
NCT02668640

 
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Protocol P15-776 
Version 7.0 dated 07 August 2017 
 
 
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Marketing Authorization Holder(s) 
Marketing Authorization Holder(s) 
AbbVie Pharmaceutical Trading (Shanghai) 
Co. Ltd  
17F, Chong Hing Finance Center  
288 West Nanjing Road, Shanghai 200003 
MAH Contact Person 
Not applicable (Non-PASS PMOS) 
 

 
Adalimumab  
Protocol P15-776 
Version 7.0 dated 07 August 2017 
 
 
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1.0 
Table of Contents 
1.0 
Table of Contents ..................................................................... 3 
2.0 
Abbreviations ........................................................................... 6 
3.0 
Responsible Parties .................................................................. 7 
4.0 
Abstract .................................................................................... 9 
5.0 
Amendments and Updates .................................................... 15 
6.0 
Milestones ............................................................................... 16 
7.0 
Rationale and Background ................................................... 16 
8.0 
Research Question and Objectives ...................................... 18 
9.0 
Research Methods ................................................................. 19 
9.1 
Study Design ............................................................................................ 19 
9.1.1 
Study Activities ........................................................................................ 21 
9.2 
Setting ...................................................................................................... 22 
9.2.1 
Inclusion Criteria: .................................................................................... 22 
9.2.2 
Exclusion Criteria: ................................................................................... 23 
9.2.3 Investigator Selection Criteria ................................................................................... 24 
9.2.4 Study Procedures ....................................................................................................... 24 
9.2.4.3 Investigator Recruitment ........................................................................................ 25 
9.2.4.4 Study site monitoring ............................................................................................. 25 
9.2.4.5 Patient Selection ..................................................................................................... 25 
9.2.4.6 Data Collection ....................................................................................................... 26 
9.2.4.7 Study Documents ................................................................................................... 26 
9.2.5 Adverse Events .......................................................................................................... 29 
9.3 
Variables .................................................................................................. 30 
9.4 
Data Sources ............................................................................................ 31 
9.5 
Study Size ................................................................................................ 31 
9.6 
Data Management and Storage Process ................................................... 31 
9.6.1 
Data Management .................................................................................... 31 
9.6.2 
Storage Process ........................................................................................ 32 
9.7 
Data Analysis ........................................................................................... 32 
9.7.1 
Statistical and Analytic plans ................................................................... 32 
9.7.2 
Analyzable population ............................................................................. 32 

 
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9.7.3 
Planned Methods of Statistical Analysis .................................................. 33 
9.7.4 
Primary Endpoint Analysis ...................................................................... 33 
9.7.5 
Secondary Endpoint Analysis .................................................................. 33 
9.7.6 
Additional Secondary Endpoint Analysis ................................................ 34 
9.7.7 
Exploratory Endpoint Analysis ................................................................ 34 
9.7.8 
Safety Analysis ........................................................................................ 35 
9.7.9 
Additional Analysis ................................................................................. 35 
9.7.10 
Missing Data ............................................................................................ 35 
9.8 
Quality Control ........................................................................................ 35 
9.8.1 
Ethics and Quality .................................................................................... 35 
9.8.2 
Quality Assurance .................................................................................... 36 
9.9 
Limitations of the Research Methods ...................................................... 37 
9.10 
Other Aspects ........................................................................................... 37 
9.10.1 
Note To File ............................................................................................. 37 
9.10.2 
Training Log ............................................................................................ 37 
9.10.3 
Visitor Log ............................................................................................... 37 
9.10.4 
Responsibilities of the Principal Investigator .......................................... 37 
9.10.5 
End of Trial .............................................................................................. 37 
10.0 
Protection of Human Subjects .............................................. 38 
11.0 
Management and Reporting of Adverse 
Events/Adverse Reactions ..................................................... 38 
11.1 
Adverse Event Definition and Serious Adverse Event Categories .......... 38 
11.2 
Severity .................................................................................................... 40 
11.3 
Relationship to Pharmaceutical Product .................................................. 40 
11.4 
Serious Adverse Event Collection Period ................................................ 41 
11.5 
Serious Adverse Event Reporting ............................................................ 41 
11.6 
Pregnancy Reporting ................................................................................ 41 
11.7 
Malignancy Reporting ............................................................................. 41 
11.8 
Product Complaint ................................................................................... 42 
12.0 
Plans for Disseminating and Communicating Study 
Results ..................................................................................... 43 
12.2 
Confidentiality ......................................................................................... 44 
12.2.1 
Patient confidentiality .............................................................................. 44 

 
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12.2.2 
Data confidentiality .................................................................................. 44 
12.3 
Study administration ................................................................................ 44 
12.4 
Investigators compliance ......................................................................... 44 
12.5 
Risks, Insurance, Indemnity and compensation ....................................... 45 
12.6 
Discontinuation or Drop-out .................................................................... 45 
12.7 
Quality control and audit ......................................................................... 45 
13.0 
References ............................................................................... 46 
 

 
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2.0 
Abbreviations 
 
ACR 
American College of Rheumatology 
AE 
Adverse Events 
ANOVA 
Analysis of Variance 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
CTCAE 
Common Terminology Criteria for Adverse Events 
DAS28 
Disease Activity Score in 28 Joints 
EQ-5D-3L 
EuroQol 5 dimension, 3 level quality of life questionnaire 
ESR 
Erythrocyte Sedimentation Rate 
EULAR 
The European League Against Rheumatism 
GP 
General Practitioner 
HAQ DI 
Health Assessment Questionnaire Disability Index 
HCRU 
Healthcare Resource Utilization 
ICF 
Informed Consent Form 
ICH-GCP 
International Conference on Harmonization of Good Clinical 
Practice 
NRS 
Numeric Rating Scale 
PGIC 
Patient Global Impression of Change  
PHI 
Protected Health Information 
PRO 
Patient-Reported Outcome 
QC 
Quality Check 
QoL 
Quality of Life  
RA 
Rheumatoid Arthritis 
SAP 
Statistical Analysis Plan 
SF-36 
Short Form 36-Item Health Survey 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
TNF 
Tumor Necrosis Factor 
VAS 
Visual Analogue Scale 
WPAI 
Work Productivity and Activity Impairment 
 
 
 
 
 

Adalimumab 
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3.0
Responsible Parties
Study-Designated 
Physician/
Sponsor: 
Affiliate Medical 
Director:
Statistics:
Principal Investigator:
Sponsor:
AbbVie Pharmaceutical Trading (Shanghai) Co. 
Ltd
17F, Chong Hing Finance Center 
288 West Nanjing Road, Shanghai 200003
Clinical Project Manager:
Product complaint
Emergency Contacts-
Safety Review Team

 
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PROTOCOL SIGNATURES 
 
 
 
Investigator Signature: 
I have read and agree to the Protocol Number P15-776, “Real-World Outcome of 
Adalimumab on Rheumatoid Arthritis Patients in China”. I am aware of my 
responsibilities as an investigator under the guidelines of Good Clinical Practices, local 
laws and regulations (as applicable) and the study protocol. I agree to conduct the study 
according to these laws and guidelines and to appropriately direct and assist the staff 
under my control, who will be involved in the study. 
 
Principal (Site) Investigator: 
 
Name (typed or printed): 
 
Institution and Address: 
 
 
 
 
 
 
 
Telephone Number: 
 
Signature: 
 
Date: 
 
 
 
 
(Day/ Month /Year) 
 
Full investigational site contact details, including telephone numbers, will be documented 
in the Study Master File. 
 
 
 

 
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4.0 
Abstract 
Title:  Real-World Outcome of Adalimumab on Rheumatoid Arthritis Patients in 
China 
Rationale and Background: Given the requirement to keep a balance between 
effectiveness and cost containment to ensure that the available health resources are 
used in a cost-effective manner, there is an increasing demand for real-world evidence 
(RWE) from policy makers, regulators, providers and payers in the region to optimize 
spending and patient outcomes. 
 
So far, there are no data available regarding adalimumab’s impact on patients’ quality 
of life (QoL) and healthcare resource utilization (HCRU) in a realistic study design, 
which provides greater generalization in China. 
 
The goal of this study is to determine the QoL, HCRU and costs of the patients care in 
subjects with RA who are treated with adalimumab in China. 
 
Results from study on the effect of adalimumab on Work Productivity and Activity 
Impairment (WPAI) scores and other Patient-Reported Outcomes (PROs) will be of 
interest to a variety of stakeholders in the healthcare system including patients, 
healthcare practitioners and payers in China. 
Research Question and Objectives: The objective of this non-interventional, 
observational study is to assess the effect of adalimumab on health-related QoL and 
work productivity in patients with Rheumatoid Arthritis (RA) in China. Specifically, to 
achieve the above objective the following concrete steps will be taken: 
1. Recruit investigators who are willing and able to recruit and follow new 
adalimumab users for 6 months follow-up 
2. Collect the patients’ clinical profile, patient-reported QoL, functioning, work 
productivity, treatment satisfaction and HCRU of RA patients at adalimumab 
initiation 
3. Follow the patients initiating adalimumab for 24 weeks and identify the 
changes in clinical, economic, and PROs associated with adalimumab 
Study Design: The study is designed as a prospective, observational study to assess the 
effect of adalimumab on health-related QoL and work productivity in patients with RA 
in China. 
 
RA patients, for whom adalimumab treatment has already been decided as per local 
label, will be recruited from within the clinical settings of each rheumatologist 
participating in the study. Approximately 52 patients diagnosed with RA that meet the 
inclusion and exclusion criteria will be enrolled at approximately 16 sites. 

 
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The Health Assessment Questionnaire Disability Index (HAQ DI) data will be 
collected at baseline, Week 12 and Week 24 after treatment initiation with 
adalimumab, as per standard daily clinical practice. In addition, when available, other 
PROs of work activity and well-being, including the WPAI, EuroQol 5 dimension 
(EQ-5D), and Short Form 36-Item Health Survey (SF-36), will also be collected. 
 
In addition, when available, the health care resource utilization will be collected. This 
includes surgical procedures, hospitalizations, bed days in hospital, physician 
consultations etc. Costs will be assigned based on the health care resource utilization 
using standardized costs for China. 
 
Note: This study is non-interventional and the subjects/investigators will follow the 
current clinical practice in each site and also the routine clinical follow up as determine 
by the treating physician.  
 
Population:  Subjects will be males and/or females who are attending a routine clinical 
visit and meet all of the inclusion criteria and none of the exclusion criteria. 
Approximately 52 patients diagnosed with RA will be recruited. 
 
Main Inclusion Criteria:  
Patients meeting all of the following inclusion criteria at baseline will be included: 
1. Subject has a diagnosis of RA as defined by the 1987 revised American College 
of Rheumatology (ACR) classification criteria and/or the ACR/the European 
League against Rheumatism (EULAR) 2010 classification criteria (any duration 
since diagnosis). 
2. Male or female subjects ≥18 years of age who is in compliance with eligibility 
for adalimumab based on the local label. 
3. Patients with moderate to severe RA defined as Disease Activity Score in 28 
Joints (DAS28) (ESR) or DAS28 (CRP) >3.2 
4. Biologically treatment naïve and initiated adalimumab at baseline visit, as per 
standard daily clinical practice. 
5. Availability of clinical data of the previous 12 weeks prior to baseline 
6. Ability to self-complete patient questionnaires 
7. Patients have signed the authorization (or informed consent where applicable) 
to disclose and use personal health information after been prescribed with 
adalimumab. 
 
Main Exclusion Criteria:  

 
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Patients meeting any of the following exclusion criteria at baseline will be excluded: 
1. Patients who are pregnant or breast feeding at enrolment or wish to become 
pregnant in the next 24 weeks.  
2. Participation in any RA-related clinical trial at the time of enrolment, at 
baseline or at any point during the past 24 weeks prior to baseline 
3. Patients, who in the clinician’s view, may not be able to accurately report their 
QoL or prior resource utilization 
4. Patients, who in the clinician’s view, may not be able to adhere to adalimumab 
therapy over 24 weeks. 
 

 
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Variables: 
Primary Variable 
x Change in HAQ DI score at week 24 from the baseline  
 
Secondary Variable 
x Change in HAQ DI score at week 12 from the baseline  
x Change in other PROs (SF-36 domain scales, EQ-5D Index, Work Productivity 
and Activity Impairment Questionnaire [WPAI])  from baseline to weeks 12 
and 24  
x Number and percent of patients achieving a clinically meaningful improvement 
on the HAQ DI, from baseline to weeks 12 and 24  
Additional Secondary Variable  
x Change in HAQ DI score from baseline to week 24  
x Changes in the disease severity and PROs from baseline to week 24  
x Healthcare Resource Utilization (HCRU) at baseline, weeks 12 and 24  
 
Exploratory Variable 
x Change in patient satisfaction questions from baseline to weeks 12 and 24 
x Patient’s impression of change at weeks 12 and 24 from baseline 
Data Sources:  Case Report Forms (CRFs) and patient questionnaires. Collection of 
data includes but not limited to subject demographics, clinical history, comorbidities, 
spontaneous 
adverse 
events, 
and 
concomitant 
medications. 
The 
following 
questionnaires will be utilized to collect data directly from participating subjects, when 
applicable: 
x EQ-5D 
x SF-36 
x HAQ DI 
x WPAI 
x HCRU 
x Patient Global Impression of Change (PGIC) 
x Patient Treatment Satisfaction Questions 
 
Study Size:  Approximately 52 patients diagnosed with RA that meet the inclusion and 
exclusion criteria will be enrolled at approximately 16 sites. The planned sample size 
provides 80% power for detecting a statistically significant improvement in HAQ-DI (Ѭ
HAQ-DI < 0) assuming a mean ѬHAQ-DI of -0.21 and a standard deviation of 0.5 

 
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(reference 11), at two-sided significance level of 0.05 and accounting for a 10% 
dropout rate. The sample size also provides 99% power for detecting a statistically 
significant clinically meaningful improvement in HAQ-DI (ѬHAQ-DI < -0.22) 
assuming a mean ѬHAQ-DI of -0.5 and a standard deviation of 0.7, at two-sided 
significance level of 0.05 and accounting for a 10% dropout rate.  
 
 
Data Analysis:   
All the following analysis will be based on the data as observed. 
 
Primary Endpoint Analysis 
Change in HAQ DI score at week 24 after the initiation of adalimumab, in those 
patients continuing on adalimumab. This change will be summarized as the mean and 
95% confidence interval and will be tested with a paired t-test.  
 
Secondary Endpoint Analysis 
x Change in HAQ DI score at week 12 after the initiation of adalimumab, in those 
patients continuing on adalimumab. This change will be summarized as the 
mean and 95% confidence interval and will be tested with a paired t-test.  
x Change in other PROs (SF-36 domain scales, EQ-5D Index, WPAI total lost 
productivity) at weeks 12 and 24 after the initiation of adalimumab, in those 
patients continuing on adalimumab. These changes will be summarized as the 
means and 95% confidence intervals and will be tested with paired t-tests. 
x Number and percent of patients achieving a clinically meaningful improvement 
on the HAQ DI, as defined by a -0.22 point improvement or greater, at weeks 
12 and 24 after the initiation of adalimumab, in those patients continuing on 
adalimumab. 
Additional Secondary Endpoint Analysis 
x Change in HAQ DI score at week 24 after the initiation of adalimumab, in those 
patients continuing on adalimumab, compared with those patients not 
continuing on adalimumab. The mean changes in these two groups will be 
compared using an independent t-test. 
x HCRU will be described using number and percentage within each category 
(number of consultations, number of procedures received, number of surgeries, 
number of hospitalizations and length of stay, number of concomitant 
medications) 
x Associations between disease severity and PROs 
x Associations between change in disease severity and change in PROs  

 
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Exploratory Endpoint Analysis 
x Change in patient satisfaction questions at weeks 12 and 24 after the initiation 
of adalimumab, in those patients continuing on adalimumab. These changes 
will be summarized as number and percentage of each response and compared 
with Kruskal–Wallis test. Satisfaction will also be dichotomized and analyzed 
over time with Cochrane-Armitage test for trends.  
x Patient’s impression of change at weeks 12 and 24 after the initiation of 
adalimumab, in those patients continuing on adalimumab (as observed 
population). These changes will be summarized as number and percentage of 
each response and compared with Kruskal–Wallis test. 
 
 

 
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5.0 
Amendments and Updates 
Number 
Date 
Section of Study 
Protocol 
Amendment or 
Update 
Reason 
P15-776 
05/06/2015 
n/a 
Initial Protocol 
n/a 
P15-776 
20/08/2015 
Management and 
Reporting of 
Adverse 
Events/Adverse 
Reactions 
Pediatric & 
Malignancy 
As per the 
Protocol 
Guidance  
P15-776 
01/09/2015 
 
 
Change from 
area study to 
affiliate study 
P15-776 
01/10/2015 
 
 
Revise based on 
GMA-RC’s 
comments 
P15-776 
02/23/2016 
 
 
Revise based on 
new standard 
language, legal 
and 
investigators’ 
comments  
P15-776 
08/07/2017 
3.0 Responsible 
parties 
Staff revised 
Revised based 
on changes 
P15-776 
08/07/2017 
6.0 Milestones 
Timeline change 
Revise based on 
enrollment 
progress 
P15-776 
08/07/2017 
9.1 Study design 
Sample size from 
200 to 52 
Revise based on 
enrollment 
progress 
P15-776 
08/07/2017 
9.2 Setting 
Sample size from 
200 to 52 
Revise based on 
enrollment 
progress 
P15-776 
08/07/2017 
9.5 Study Size 
Sample size 
reduced from 200 to 
52 with power 
reduced to 80%; 
dropout rate 
reduced to 10%; 
remove WPAI as 
key factor for 
Revise based on 
enrollment 
progress 

 
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sample size   
P15-776 
08/07/2017 
9.2.3~12.7 
Remove “IMS” or 
change “IMS” to 
“AbbVie” at 
appropriate places. 
AbbVie is in 
charge of study 
operation. 
P15-776 
08/07/2017 
12.5 Risks 
Combine 12.5 and 
12.6 and add 
subject insurance 
language. 
Affiliate 
provides product 
liability 
insurance for 
PMOS. 
P15-776 
08/07/2017 
Annexure 
Remove all 
annexures and CRF. 
Annexures not 
applicable for 
China. 
CRF is in a 
separate 
document. 
 
6.0 
Milestones 
Major study milestones and their planned dates are as follows: 
Start of Data Collection (FPFV): 
15 April 2016 
End of Data Collection: 
30 June 2018 
Study Progress Report: 
Not Applicable  
Registration in the EU PAS register: 
Not Applicable  
Final Report of Study Results: 
31 December 2018  
 
7.0 
Rationale and Background 
Disability has been defined as impairments, activity limitations and participation 
restrictions due to personal and environmental factors (1). The concept of disability is one 
where a physical health condition or disease is evaluated in terms of its impact, difficulties, 
or limitations on a range of tasks, activities, or roles that are considered typical of 
everyday life. Examples of affected activities include basic aspects of daily living such as 
eating, bathing, dressing, household chores and meal preparation, or participation in 
society, or participation in work.  
 

 
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For public health purposes disability is becoming increasingly important as an outcome 
measure. Despite this, no data, within our knowledge, on the effectiveness of adalimumab 
on health-related QoL and work productivity in patients with Rheumatoid Arthritis (RA) 
in China.  
 
Results from study of effect of adalimumab on Work Productivity and Activity 
Impairment (WPAI) scores and other Patient-Reported Outcomes (PROs) of work activity 
and well-being will be of interest to a variety of stakeholders in the healthcare system 
including patients, healthcare practitioners and payers in China. 
 
The Chinese government has for some time been deeply concerned with an impending 
productivity fall associated with ageing and chronic illnesses, including musculoskeletal 
disorders.  These concerns have a large impact on their health financing and structuring 
policies.  Having the economic and health outcomes “real world evidence” (RWE) for the 
use of Humira in moderate RA patients will be helpful to fill in data gaps which will be 
valuable for Chinese Health Authorities.  
 
In China, Humira is not listed on either provincial reimbursed drug list (PRDL) or 
national provincial reimbursed drug list (NRDL), which means that patients have to pay 
for the use of Humira. However, on August 30th, 2012, National Development and 
Reform Commission (NDRC), Ministry of Health (MOH) and other four ministries and 
commissions of China issued “Guidance about implementation of urban and rural 
residents’ critical illness insurance (CDI) system”. The CDI system aims to expand the 
coverage of the country’s health care insurance system to include the treatment of critical 
illness, aiming to relieve urban and rural families of the heavy burden of catastrophic 
medical spending. By the end of August 2013, 94 regions across 23 provinces had piloted 
the critical illness cover system and seven provinces had fully implemented the system, 
benefiting 210 million people. 
 
On Jan 2015, Humira was listed on the CDI in Qingdao. Patients with RA who are 
covered by CDI are reimbursed for 70 percent of the total costs. And on Oct 2015, 
Humira is also listed on the CDI in Shenzhen. Given CDI is new systems in China, the 
officials of CDI cities encourage company to collect the RWE associated with the use of 
Humira to further demonstrate the value of Humira to Chinese patients, especially in their 
local regions. The result will assist decision makers to evaluate the CDI from a broader 
perspective and to determine the value of continuing the program. In addition, generating 
RWE related the use of Humira in patients with RA will be extremely valuable for 
application of Humira on the CDI list in other provinces in China.  
 

 
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The objective of this non-interventional, observational study is to assess the effect of 
adalimumab on health-related QoL, work productivity, and healthcare resource utilization 
(HCRU) in patients with RA in China. 
 
Adalimumab therapy has a well-established and well described safety profile based on 
extensive post marketing experience and continued clinical trial patient exposure since the 
first approved indication in 2002 for rheumatoid arthritis. A detailed discussion of the pre-
clinical toxicology, metabolism, pharmacology and safety experience with adalimumab 
can be found in the current Investigator's Brochure. AbbVie is committed to continue to 
collect safety information including those events that may occur in this trial in order to 
confirm this established safety profile and to identify any unknown potential adverse 
reactions, rare events and those events with a long latency. AbbVie is participating in an 
FDA-requested, TNF inhibitor class wide exploration of the rare appearance of 
malignancy in subjects/patients who are 30 years of age or younger at the time of 
diagnosis. The risk of malignancy in this age group has not been established and is 
difficult to study due to its rarity. AbbVie appreciates your attention to the additional 
reporting requirements needed in this unlikely event, outlined in Section 11.1.2b under 
Adverse Event Reporting. 
 
 
8.0 
Research Question and Objectives 
The objective of this study is to assess the effect of adalimumab on health and disability 
outcomes in patients with the immune-mediated inflammatory diseases of rheumatoid 
arthritis. The effect of adalimumab on health and disability outcomes in these patients will 
be assessed by the primary outcome measure which is the change in Health Assessment 
Questionnaire Disability Index (HAQ DI) score at week 24 after the initiation of 
adalimumab. The HAQ DI is selected as the primary point as it is commonly used to 
assess improvements in physical function in RA clinical trials and recommended by the 
US Food and Drug Administration (FDA) guidance on RA treatment development (3, 4). 
In addition, the HAQ-DI has been utilized as a predictor variable in investigations of 
productivity (5). The HAQ-DI has been demonstrated to be significantly correlated with 
work-related measures such as work capacity, household work performance, work task 
performance, and work disability (6-9). In addition, the effect of adalimumab will also be 
assessed by the secondary outcome measures which are changes to the WPAI, EuroQol 5 
dimension (EQ-5D) score, and Short Form 36-Item Health Survey (SF-36) domain scores 
at weeks 12 and 24 after the initiation of adalimumab in RA. All the analysis will be 
based on the data as observed.  

 
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9.0 
Research Methods 
9.1 
Study Design 
This study is designed as a prospective, observational study to assess the effect of 
adalimumab on health-related QoL and work productivity in patients with RA in China in 
clinical practice. 
 
The study population will include Chinese adult patients with a diagnosis of RA who meet 
the requirements per the local label for treatment with adalimumab at the baseline visit. 
The decision to prescribe adalimumab for RA should be based on clinical practice criteria 
without taking participation in this study into account. Patients will be included in the 
study after a physician’s decision of initiating Humira. 
 
Approximately 52 patients diagnosed with RA that meet the inclusion and exclusion 
criteria will be enrolled at approximately 16 sites. 
 
This study is non-interventional and the subjects/investigator will follow the current 
clinical practice in each site. Not additional task will be required other than current 
practice to keep the data as “real world data collect”. 
 
The observation period for each patient is 24 weeks. All visits are to be scheduled as per 
routine clinical practice, regardless of study participation. Patients may discontinue 
adalimumab treatment or the study at any time without prejudice.  
 
The physician will follow the patient during regular clinic visits at intervals as determined 
by routine clinical practice. Data at the clinic visits within ± 7 days of the study-defined 
time points will be collected and data at the clinic visits closest to the study-defined time 
points will be used for statistical analysis (If there are 2 clinic visits equidistant from a 
study-defined time point which do not correspond to any other visit, data from the 
EARLIER clinic visit shall be used for the study-defined time point).  
 
The HAQ DI data will be collected at baseline, Week 12 and Week 24 after treatment 
initiation with adalimumab, as per standard daily clinical practice. In addition, when 
available, other PROs of work activity and well-being, including the WPAI, EQ-5D, and 
SF-36, will also be collected.  
 

 
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20 
The HCRU will also be collected, when available. This includes surgical procedures, 
hospitalizations, bed days in hospital, physician consultations etc. Costs will be assigned 
based on the HCRU using standardized costs for each participating countries. 
 
 
Primary Endpoint 
x Change in HAQ DI score at week 24 after the initiation of adalimumab, in those 
patients continuing on adalimumab. This change will be summarized as the mean 
and 95% confidence interval and will be tested with a paired t-test.  
 
Secondary Endpoint Analysis 
x Change in HAQ DI score at week 12 after the initiation of adalimumab, in those 
patients continuing on adalimumab. This change will be summarized as the mean 
and 95% confidence interval and will be tested with a paired t-test.  
x Change in other patient reported outcomes (SF-36 domain scales, EQ-5D Index, 
WPAI total lost productivity) at weeks 12 and 24 after the initiation of 
adalimumab, in those patients continuing on adalimumab. These changes will be 
summarized as the means and 95% confidence intervals and will be tested with 
paired t-tests. 
x Number and percent of patients achieving a clinically meaningful improvement on 
the HAQ DI, as defined by a -0.22 point improvement or greater, at weeks 12 and 
24 after the initiation of adalimumab, in those patients continuing on adalimumab. 
Additional Secondary Endpoint Analysis 
x Change in HAQ DI score at week 24 after the initiation of adalimumab, in those 
patients continuing on adalimumab, compared with those patients not continuing 
on adalimumab. The mean changes in these two groups will be compared using an 
independent t-test. 
x Healthcare resource utilization will be described using number and percentage 
within each category (number of consultations, number of procedures received, 
number of surgeries, number of hospitalizations and length of stay, number of 
concomitant medications) 
x Associations between disease severity and PROs 
x Associations between change in disease severity and change in PROs 
 
Exploratory Endpoint Analysis 
x Change in patient satisfaction questions at weeks 12 and 24 after the initiation of 
adalimumab, in those patients continuing on adalimumab. These changes will be 
summarized as number and percentage of each response and compared with 

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Kruskal–Wallis test. Satisfaction will also be dichotomized and analysed over time 
with Cochrane-Armitage test for trends. 
x
Patient’s impression of change at weeks 12 and 24 after the initiation of 
adalimumab, in those patients continuing on adalimumab (as observed 
population). These changes will be summarized as number and percentage of each 
response and compared with Kruskal–Wallis test. 

Note: Patient who misses 2 consecutive adalimumab injections or a total of 3 non-
consecutive injections within 24 weeks of treatment will be regarded as “the patient 
not continuing on adalimumab”.
9.1.1 
Study Activities 
Table 1 
Study Activities (Day 1/Baseline Through 6 months) 
Data Collection/Observation
Baselinea Week 12 
(V2)
± 7 days
Week 24 
(V3)
± 7 days
Early 
Termination 
/ Drop out
70 days
after the 
Week 24 or 
the last dose
150 days
after the
Week 24 or 
the last dose
Clinician 
Packet
Inclusion/exclusion form
X
Clinical history/patient demographics
X
Comorbidities
X
DAS28 (ESR) or DAS28 (CRP)
X
X
X
X
Patient Packet
EuroQoL 5-Dimension (EQ-5D)
X
X
X
X
Short Form 36-Item Health Survey (SF-
36)
X
X
X
X
Health Assessment Questionnaire (HAQ)
X
X
X
X
Work Productivity and Activity 
Impairment Questionnaire (WPAI)
X
X
X
X
Healthcare Resource Utilization (HCRU)
X
X
X
X
Patient Global Impression of Change 
(PGIC)
X
X
X
Patient Treatment Satisfaction Questions
X
X
X
X
Clinicia
n
P
k t
Adverse events (including malignancy)
Pregnancy

 
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a. The Baseline visit date will serve as the reference for all subsequent visits. A ± 7 day window is permitted 
around scheduled study visits. 
9.2 
Setting 
The study will take place in China with multiple centers. The study sites will be identified 
and selected by AbbVie. The study population shall comprise of male and/or female 
patients who are attending a routine clinical visit and meet all of the inclusion criteria and 
none of the exclusion criteria. Overall, approximately 52 subjects with clinically 
diagnosed RA are planned to be enrolled in the study at up to 16 sites. 
 
The recruiting investigators will select potentially eligible patients from consecutive visits 
within their clinic based on the inclusion and exclusion criteria (Section 9.2.1 and Section 
9.2.2). It is the responsibility of each physician to ask every consecutive patient who 
meets the inclusion criteria of the study to participate to avoid selection bias, and if 
investigators hold different types of clinics (e.g. routine visit clinics versus emergency 
clinics), only patients visiting their routine clinics will be used for patient selection. Site 
personnel should thoroughly assess the eligibility criteria and evidence of this should be 
stored with the source documentation at site. 
 
Where there is any deviation from the inclusion/exclusion criteria, the patient should be 
excluded from the study. 
 
 
9.2.1 
Inclusion Criteria:  
Patients meeting all of the following inclusion criteria at baseline will be included: 
1. Subject has a diagnosis of RA as defined by the 1987 revised ACR classification 
criteria and/or the ACR/ the European League against Rheumatism (EULAR) 
2010 classification criteria (any duration since diagnosis) 
2. Male or female subjects ≥18 years of age  who is in compliance with eligibility for 
adalimumab based on the local label 
3. Patients with moderate to severe RA defined as DAS28 (ESR) or DAS28 
(CRP)>3.2 
4. Biologically treatment naïve and initiated adalimumab at baseline visit, as per 
standard daily clinical practice 
5. Availability of clinical data of the previous 12 weeks prior to baseline 
6. Ability to self-complete patient questionnaires 

 
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7. Patients have signed the authorization (or informed consent where applicable) to 
disclose and use personal health information after been prescribed with 
adalimumab.  
Additional Inclusion Criteria 
8. If female subject, is either not of childbearing potential, defined as postmenopausal 
for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy 
and/or hysterectomy) or is of childbearing potential and is practicing an approved 
method of birth control throughout the study and for 150 days after last dose of study 
drug.  
9. Subject is judged to be in good health as determined by the Principal Investigator 
based upon the results of medical history, laboratory profile, physical examination, 
chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during 
Screening;  
10. Subject has a negative TB Screening Assessment. If the subject has evidence of a 
latent TB infection; the subject must initiate and complete a minimum of 4 weeks of 
an ongoing TB prophylaxis or have documented completion of a full course of TB 
prophylaxis, prior to Baseline  
 
9.2.2 
Exclusion Criteria:  
Patients meeting any of the following exclusion criteria at baseline will be excluded: 
1. Patients who are pregnant or breast feeding at enrolment or wish to become 
pregnant in the next 24 weeks 
2. Participation in any RA-related clinical trial at the time of enrolment, at baseline 
or at any point during the past 24 weeks prior to baseline 
3. Patients, who in the clinician’s view, may not be able to accurately report their 
QoL or prior resource utilization 
4. Patients, who in the clinician’s view, may not be able to adhere to adalimumab 
therapy over 24 weeks 
Additional Exclusion Criteria                                                                                  
5. Subject has been treated with any investigational drug of chemical or biologic 
nature within a minimum of 30 days or five half-lives (whichever is longer) of the 
drug prior to the Baseline Visit                                                                           
6. Prior exposure to biologics that have a potential or known association with PML 
(i.e., natalizumab (Tysabri®), or rituximab (Rituxan)  
7. Positive pregnancy test at Baseline 
8. Patients with contraindication or are not appropriate to use adalimumab according 
to local label or investigators’ judgment 
 

 
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9.2.3 Investigator Selection Criteria 
Selection of investigators will be made based on qualification by training and experience. 
AbbVie will provide a list of clinicians that would be able to able to assist in recruiting in 
a timely manner. AbbVie will contact each clinician to obtain their participation in the 
study and provide an expected number of patients to be enrolled from that clinic. The 
ethical review boards recognized by the respective participating sites are required to 
review and approve the study and patient informed consent. 
 
9.2.4 Study Procedures 
The study procedures outlined in Table 1 will be discussed in detail in this section with 
the exception of adverse events procedures (discussed in Section Error! Reference 
source not found.). 
9.2.4.1 Informed Consent 
Prior to any study-related data being collected, patient authorization (or informed consent 
where applicable) will be reviewed, signed and dated by the patient and the person who 
administered the patient authorization (or informed consent). A copy of the signed patient 
authorization (or informed consent) will be given to the patient and the original will be 
placed in the patient's medical record. 
 
9.2.4.2 Patient Assignment 
Once the recruiting clinician has obtained the subject’s authorization to release medical 
information and written consent to participate in the study, the clinician will be asked to 
complete an inclusion and exclusion form (Error! Reference source not found.) for 
patients, thus confirming the patient’s eligibility to participate in this study.   
Each participating patient will be assigned a 3-digit patient identification number. The 
numbers should be assigned in sequential, ascending order per site as shown below: 
 
• 
Site ID; and 
 
• 
Patient ID: First eligible patient number will be 001, and then the second patient 
number would be 002 
 
X X  X X X 

 
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Site ID        Patient ID 
 
9.2.4.3 Investigator Recruitment 
AbbVie will provide a list of clinicians that would be able to assist in recruiting in a 
timely manner. AbbViewill contact each clinician to obtain their participation in the study 
and provide an expected number of patients to be enrolled from that clinic. The ethical 
review boards recognized by the respective participating sites are required to review and 
approve the study and patient informed consent. 
 
9.2.4.4 Study site monitoring 
AbbVie will closely track enrolment progress for monthly reporting. AbbVie will work 
closely with the study coordinator at each site to ensure they check the forms when 
returned from the patients and physicians (e.g., all questions were answered). AbbVie will 
also be available to answer questions and follow up with the sites if the recruitment 
process is slow or if there are any errors on the forms. Periodic phone follow-up will be 
conducted to ensure data collection completeness and quality. 
 
9.2.4.5 Patient Selection 
The recruiting investigators will select potentially eligible patients from consecutive visits 
within their clinic based on the inclusion and exclusion criteria (Section 9.2.1 and Section 
9.2.2). It is the responsibility of each physician to ask every consecutive patient who 
meets the inclusion criteria of the study to participate to avoid selection bias, and if 
investigators hold different types of clinics (e.g. routine visit clinics versus emergency 
clinics), only patients visiting their routine clinics will be used for patient selection. The 
intent is to enroll patients who have been prescribed adalimumab upon the physicians’ 
own discretion.  
 
Medical and Surgical History
A detailed medical history with respect toTB exposure needs to be documented.  This 
information needs to include BCG vaccination, cohabitation with individuals who have 
had TB, and/or who reside or work in TB endemic locations. 
Pregnancy Tests 
At the Baseline Visit, subjects of childbearing potential will have a urine pregnancy test 
performed locally by designated study personnel.  If any urine pregnancy test is positive, a 

 
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serum pregnancy test will be performed.  A lactating or pregnant female will not be 
eligible for participation or continuation in this study. 
All women of childbearing potential will have a repeat urine pregnancy test at the final 
Study Visit performed locally by designated study personnel.  
 
9.2.4.6 Data Collection 
AbbVie will coordinate data collection with each site. At study initiation (Baseline, D0), 
patients will be asked to provide their written informed consent.  
 
When available, the PRO data as observed will be collected -. The CRF completed by 
physicians will be returned to the study coordinator/nurse at each site as well.   
 
All data filled in by the patient and physician will be collected by the study 
coordinator/nurse at each site and returned directly to AbbVie.  
 
All patient and clinician data will be handled preserving confidentiality. 
 
9.2.4.7 Study Documents 
Clinical case report form (CRF) 
The clinical CRF will document the patient’s current status (moderate, severe RA), 
Disease Activity Score in 28 joints (DAS28), prior and current treatments and other 
relevant clinical and demographic data to be used in segmenting the population during 
analysis.  
 
To calculate the DAS28 the physician or specialist nurse will:  
1. Count the number of swollen joints (out of the 28) 
2. Count the number of tender joints (out of the 28) 
3. Take blood to measure the erythrocyte sedimentation rate (ESR) or C reactive 
protein (CRP); the latest measurement in the medical records may also be used if a 
blood draw is not standard for that visit 
4. Ask the patient to make a ‘global assessment of health’ which will be indicated by 
marking a 10 cm line between very good and very bad 

 
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The physician or specialist nurse will then mark each component score on the CRF and 
the DAS28 score if calculated (an online scoring calculator for the DAS28 can be found at 
http://www.das-score.nl/das28/DAScalculators/dasculators.html).  
 
The DAS28 will be scored using the following formula: 
DAS28(CRP) = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.36 * ln(CRP+1) + 
0.014 * (Patient Global assessment of Health in mm)+0.96 
DAS28(ESR) = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.70 * ln(ESR) + 
0.014 * (Patient Global assessment of Health in -mm) 
 
DAS28 scores will be interpreted using the following categorization: 
• 
Remission: DAS28 ≤ 2.6  
• 
Low Disease activity: 2.6 < DAS28 ≤ 3.2  
• 
Moderate Disease Activity: 3.2 < DAS28 ≤ 5.1  
• 
High Disease Activity: DAS28 >5.1  
 
The full CRF is presented in Error! Reference source not found..  
 
PRO questionnaires 
The following PRO questionnaires will be included in the patient questionnaire packet.  
 
Health Assessment Questionnaire Disability Index (HAQ DI) 
The HAQ DI is a patient-reported questionnaire to assess functioning impacted by RA. It 
includes the categories of dressing and grooming, arising, eating, walking, hygiene, reach, 
grip and common daily activities. It asks patients about the amount of difficulty they 
experience in these activities as well as the use of aids and/or devices. The HAQ also has 
a numeric rating scale (NRS) (13)  to assess pain on a scale from 0 to 10. Self-
administered by the patient, the completion time is approximately 3-4 minutes. The full 
version of HAQ DI is presented in Error! Reference source not found.. 
  
Short Form (36) Health Survey (SF-36) 
The SF-36 is a patient-reported questionnaire of patient health-related QoL. It measures 
generic health concepts relevant across age, disease, and treatment groups. There are 36 
items in total and the recall period is the last 4 weeks. The SF-36 consists of eight scaled 
scores, which are the weighted sums of the questions in their section. Each scale is 
directly transformed into a 0-100 scale. Completion time for the SF-36 is approximately 

 
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10 minutes. The full version of SF-36 is presented in Error! Reference source not 
found..  
 
EuroQol 5 dimension, 3 level quality of life questionnaire (EQ-5D-3L) 
The EQ-5D-3L measures the patient’s overall health state in a descriptive system of 
health-related QoL states consisting of five dimensions (mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression) each of which can take one of three 
responses. The responses record three levels of severity (‘no problems’, ‘some problems’, 
and ‘extreme problems) within a particular EQ-5D-3L dimension (14, 15). In addition, a 
VAS rates current health state between 0-100. The EQ-5D-3L results can be converted to 
health utility scores. Completion time for the EQ-5D-3L is approximately 2-3 minutes. 
The full version of EQ-5D-3L is presented in Error! Reference source not found..  
 
Work Productivity and Activity Impairment (WPAI) 
The WPAI is a patient-reported questionnaire to measure work and activity impairment 
during the past seven days. It determines employment status, hours missed from work due 
to the disease (i.e. RA), hours missed from work for other reasons, hours actually worked, 
the degree to which the disease affected work productivity while at work and the degree to 
which the disease affected activities outside of work. Additional questions around 
employment status will be incorporated into the survey. The completion time for the 
WPAI is approximately 2-5 minutes. The full version of WPAI is presented in Error! 
Reference source not found..  
 
All of the above questionnaires will be used with the validated Chinese version. 
 
Patient Global Impression of Change (PGIC) 
The PGIC measures the patient’s perceptions of changes in their disease. It consists of one 
question asking about the change in their condition; for this study, the base will be “since 
you initiated your adalimumab treatment”. The completion time for the PGIC is less than 
1 minute. The full version of PGIC is presented in Error! Reference source not found..  
 
Patient Treatment Satisfaction Questions 
The patient treatment satisfaction questions were developed de novo for this study and are 
not considered “validated” questions.  Self-administered by the patient, the completion 
time for the patient treatment satisfaction questions is approximately 1-2 minutes. The full 
version of patient treatment satisfaction questions are presented in Error! Reference 
source not found.I.  
 

 
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Healthcare Resource Utilization (HCRU) Questionnaire 
The HCRU questionnaire will collect data on the healthcare resources consumed in the 
prior 3 months, as recall beyond 3 months may be problematic in an older population (16). 
HCRU collection will include data such as the number of physician visits and to which 
physician (GP, specialist), Emergency Department visits, hospitalizations, and other drugs 
as well as devices and aids purchased to assist in their mobility due to RA. The HCRU 
questionnaire will be part of the patient questionnaire and will be distributed to patients 
together with the PRO questionnaires (Appendix D to Appendix I). The full HCRU 
questionnaire is presented in Error! Reference source not found.J and will be used with 
the validated Chinese version. 
 
 
9.2.5 Adverse Events 
Adverse events, whether in response to a query, observed by site personnel, or reported 
spontaneously by the subject will be recorded. Adverse events definition and serious 
adverse event categories are described in detail in Section 11.0. 
 
 
9.2.6 Removal of Subjects from Therapy or Assessment 
 
1. Discontinuation of Individual Subjects 
 
A subject may withdraw from the study at any time.  The Investigator may discontinue 
any subject's participation for any reason, including an adverse event, safety concerns or 
failure to comply with the protocol. 
Subjects will be withdrawn from the study immediately if any one of the following 
occurs: 
● Clinically significant abnormal laboratory result(s) or adverse event(s), as 
determined by the Investigator in consultation with the AbbVie Medical 
Monitor. 
● The Investigator believes it is in the best interest of the subject. 
● The subject requests withdrawal from the study. 
● Inclusion and exclusion criteria violation was noted after the subject started 
study drug, when continuation of the study drug would place the subject at risk 
as determined by the AbbVie Medical Monitor (see Section 5.2 and 
Section 7.0). 

 
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● Introduction of prohibited medications or dosages when continuation of the 
study drug would place the subject at risk as determined by the AbbVie 
Medical Monitor. 
● Subject is non-compliant with TB prophylaxis. 
● The subject becomes pregnant while on study medication. 
● Subject has dysplasia of the gastrointestinal tract or a malignancy, except for 
localized non-melanoma skin cancer.  Discontinuation for carcinoma in-situ of 
the cervix is at the discretion of the Investigator.   
● Subject is diagnosed with lupus-like syndrome, multiple sclerosis or 
demyelinating disease. 
● Subject is significantly non-compliant with study procedures which would put 
the subject at risk for continued participation in the trial, as determined by the 
Investigator, in consultation with the AbbVie Medical Monitor.    
 
Following discontinuation of the study drug, the subject will be treated in accordance with 
the Investigator's best clinical judgment.  A final phone call will be made to the subject 
approximately 70 days after the last dose of study drug to determine the status of any 
ongoing AEs/SAEs or the occurrence of any new AEs/SAEs.  
For subjects that are considered lost to follow-up, reasonable attempts should be made to 
obtain information on the final status of the subject.   
 
9.3 
Variables 
Variables: 
Primary Variable 
x Change in HAQ DI score at week 24 from the baseline  
 
Secondary Variable 
x Change in HAQ DI score at week 12 from the baseline 
x Change in other PROs (SF-36 domain scales, EQ-5D Index, Work Productivity 
and Activity Impairment Questionnaire [WPAI])  from baseline to weeks 12 and 
24  
x Number and percent of patients achieving a clinically meaningful improvement on 
the HAQ DI, from baseline to weeks 12 and 24  

 
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Additional Secondary Variable  
x Change in HAQ DI score from baseline to week 24  
x Changes in the disease severity and PROs from baseline to week 24  
x Healthcare Resource Utilization (HCRU) at baseline, weeks 12 and 24  
Exploratory Variable 
x Change in patient satisfaction questions from baseline to weeks 12 and 24 
x Patient’s impression of change at weeks 12 and 24 from baseline 
 
9.4 
Data Sources 
Case Report Forms (CRFs) and patient questionnaires.  
Collection of data includes but not limited to subject demographics, clinical history, 
comorbidities, spontaneous adverse events, and concomitant medications. The following 
questionnaires will be utilized to collect data directly from participating subjects: 
x EQ-5D 
x SF-36 
x HAQ DI 
x WPAI 
x HCRU 
x Patient Global Impression of Change (PGIC) 
x Patient Treatment Satisfaction Questions 
 
9.5 
Study Size 
Approximately 52 patients diagnosed with RA will be recruited. The planned sample size 
provides 80% power for detecting a statistically significant improvement in HAQ-DI (Ѭ
HAQ-DI < 0) assuming a mean ѬHAQ-DI of -0.21 and a standard deviation of 0.5 
(reference 11), at two-sided significance level of 0.05 and accounting for a 10% dropout 
rate. The sample size also provides 99% power for detecting a statistically significant 
clinically meaningful improvement in HAQ-DI (ѬHAQ-DI < -0.22) assuming a mean Ѭ
HAQ-DI of -0.5 and a standard deviation of 0.7, at two-sided significance level of 0.05 
and accounting for a 10% dropout rate.  
 
 

 
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9.6 
Data Management and Storage Process 
9.6.1 
Data Management 
Data management and data quality check will be performed to remove errors and 
inconsistencies in order to assure the appropriateness of the study data set to assess the 
study objectives. Data entry screens will be developed and tested prior to initiating data 
collection to reduce data entry errors.  If required, IMS will provide AbbVie with data for 
analysis.  
 
Each site coordinator will be instructed to answer patients’ queries which may arise in 
relation to the questionnaires and check the patients’ input to make sure all questions are 
answered. 
 
9.6.2 
Storage Process 
Following data quality checks, each dataset will be converted to SAS and merged for 
analysis. All information included in the CRF and the patients’ questionnaires will be 
checked in order to detect possible queries to solve and will be extracted to a specifically 
designed database, where it will be validated by IMS personnel to ensure its quality. 
Finally, data analysis will be conducted and final results reported. 
 
The databases will be stored in IMS data servers. Data servers are submitted to daily 
backups in order to increase the security on all data managed in the collection process. 
 
All paper based questionnaires will be stored in a secured, locked area for a period of 
seven (7) years, after which all data will be shred using an agency specialized in disposal 
of confidential documents.   
 
9.7 
Data Analysis 
9.7.1 
Statistical and Analytic plans 
A statistical analysis plan (SAP) will be developed describing the specific analysis that 
will be performed including, and in addition to, the analysis described here. All analysis 
will be performed in accordance with the approved analysis plan. The following provides 
an overview of some of the analysis.  
 

 
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The scoring of the PRO questionnaires will be done in accordance to the developers’ 
recommendations.   
 
A separate statistical analysis plan will be developed describing the specific analysis that 
will be performed including and in addition to the analysis described here. 
 
9.7.2 
Analyzable population 
All subjects who received at least one dose of adalimumab during the study will be 
included. The main analysis will be conducted on the pooled population, where 
appropriate, with each individual country analyzed separately as supportive data.  
 
9.7.3 
Planned Methods of Statistical Analysis 
All statistical tests will be two-tailed with a significance level of 0.05. Descriptive 
statistics will be provided. Descriptive analysis will be conducted on all key parameters 
and presented as mean, standard deviation, minimum, maximum, and median when 
continuous and as “n” and percent when categorical. Change from adalimumab initiation 
to 24 weeks will be calculated and evaluated for significant improvements using paired t-
tests / ANOVA for parametric and Wilcoxon signed-rank for non-parametric data. 
Analysis will be also be conducted by severity level (moderate vs severe), disease 
duration quartile (to compare to prior work) and up to two (2) other subgroups. Cochran-
Armitage test of trends or other similar methods may be used to compare categories of 
subjects. 
 
9.7.4 
Primary Endpoint Analysis 
The primary endpoint variable will be the change in HAQ DI score at week 24 after the 
initiation of adalimumab, in those patients continuing on adalimumab. 
 
The objective of the primary endpoint analysis will be to demonstrate that treatment with 
adalimumab improves functioning as measured by the HAQ DI in subjects with RA 
following treatment initiation. This change will be summarized as the mean and 95% 
confidence interval and will be tested with a paired t-test.  
 
The primary analysis will be summarized as the mean and 95% confidence interval and 
will be tested with a paired t-test without adjusting for baseline disease severity. For 
sensitivity analysis, the mean change in HAQ DI at week 24 will be analyzed using 
ANOVA adjusting for baseline disease severity. 

 
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9.7.5 
Secondary Endpoint Analysis 
The main secondary endpoint variable will be the change in HAQ DI at week 12 after the 
initiation of adalimumab. 
 
The objective of endpoint analysis will be to demonstrate that treatment with adalimumab 
improves functioning as measured by HAQ DI in subjects with RA compared to baseline. 
 
The main secondary analysis will be summarized as the mean and 95% confidence 
interval and will be tested with a paired t-test without adjusting for baseline disease 
severity. For sensitivity analysis, the mean change in HAQ DI at week 12 will be analyzed 
using ANOVA adjusting for baseline disease severity. 
 
Other secondary analysis include: 
 
x Change in other patient reported outcomes (SF-36 domain scales, EQ-5D Index, 
WPAI total lost productivity) at weeks 12 and 24 after the initiation of 
adalimumab, in those patients continuing on adalimumab. These changes will be 
summarized as the means and 95% confidence intervals and will be tested with 
paired t-tests. 
x Number and percent of patients achieving a clinically meaningful improvement on 
the HAQ DI, as defined by a -0.22 point improvement or greater, at weeks 12 and 
24 after the initiation of adalimumab, in those patients continuing on adalimumab. 
 
9.7.6 
Additional Secondary Endpoint Analysis 
Additional efficacy analysis include:  
x Change in HAQ DI score at 24 weeks after the initiation of adalimumab, in those 
patients continuing on adalimumab, compared with those patients not continuing 
on adalimumab. The mean changes in these two groups will be compared using an 
independent t-test. 
x Healthcare resource utilization will be described using number and percentage 
within each category (number of consultations, number of procedures received, 
number of surgeries, number of hospitalizations and length of stay, number of 
concomitant medications) 
x Associations between disease severity and PROs 
x Associations between change in disease severity and change in PROs 
 

 
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9.7.7 
Exploratory Endpoint Analysis 
x Change in patient satisfaction questions at weeks 12 and 24 after the initiation of 
adalimumab, in those patients continuing on adalimumab. These changes will be 
summarized as number and percentage of each response and compared with 
Kruskal–Wallis test. Satisfaction will also be dichotomized and analyzed over time 
with Cochrane-Armitage test for trends.  
x Patient’s impression of change at weeks 12 and 24 after the initiation of 
adalimumab, in those patients continuing on adalimumab (as observed 
population). These changes will be summarized as number and percentage of each 
response and compared with Kruskal–Wallis test. 
 
9.7.8 
Safety Analysis 
Adverse events occurring while participants are on adalimumab will be coded using 
Common Terminology Criteria for Adverse Events (CTCAE) classification individually 
listed by indication groups. The incidences and percentages of individuals experiencing 
AEs and SAEs within each indication will be summarized by System Organ Class (SOC) 
with further summaries by severity and relatedness (causality) categories. Adverse events 
leading to discontinuation and concomitant medications will also be listed and 
summarized. 
 
9.7.9 
Additional Analysis 
Additional analysis will explore the potential modifying effects of baseline measures on 
the changes in primary and secondary efficacy outcomes. These measures will include age, 
gender, baseline severity, and other diagnoses/co-morbidities. The analysis will 
specifically test for differential changes across the subgroups defined by the potential 
modifiers using general linear models.  
 
9.7.10 
Missing Data 
Efficacy measures are not assessed after a participant discontinues adalimumab. The 
exception to this will be the analysis of proportion of patients at 24 weeks who remain on 
adalimumab. Item level data on the PROs will be imputed according to the developers’ 
recommendations. There will be no other imputation for missing data.  
 

 
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9.8 
Quality Control 
9.8.1 
Ethics and Quality 
Prior to any study-related data being collected, informed consent form will be reviewed, 
signed and dated by the patient and the person who administered the informed consent. A 
copy of the signed informed consent will be given to the patient and the original will be 
placed in the patient's medical record. 
 
9.8.2 
Quality Assurance 
Prior to the initiation of the study, physician and site personnel will be trained on the 
study. Training will include a detailed discussion of the protocol, performance of study 
procedures, and completion of the CRFs and paper questionnaires. 
 
All sites will be monitored during the course of study participation. One hundred percent 
(100%) source document review for safety will be performed. 
 
All clinical data will be documented via the CRF. Study coordinators at each site will 
check the paper CRFs completed by the physicians and questionnaires completed by 
patients (e.g., all questions were answered). Data entry will be conducted by IMS. After 
entry of the data, computer logic checks will be run to check for inconsistent data. Any 
necessary corrections will be made to the database and documented via addenda, queries, 
and source data clarification forms.  
 
Steps to be taken to ensure the accuracy and reliability of data include the selection of 
qualified investigators and appropriate study centers, review of protocol procedures with 
the investigator and associated personnel before the study and periodic monitoring visits 
by the sponsor. Written instructions will be provided for administration and collection of 
study questionnaires.   
 
Guidelines for CRF completion will be provided and reviewed with study personnel 
before the start of the study. The sponsor will review CRFs and patient questionnaires for 
accuracy and completeness after transmission to the sponsor; any discrepancies will be 
resolved with the investigator or designee, as appropriate. After upload of the data into the 
clinical study database they will be verified for accuracy and consistency with the data 
sources. 
 
Protocol Deviation 
For the purposes of this protocol, reportable deviations are defined as: 

 
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● Subject entered into the study even though she/he did not satisfy entry criteria 
● Subject who developed withdrawal criteria during the study and was not 
withdrawn 
● Subject who received wrong treatment  
● Subject who received excluded or prohibited concomitant treatment 
 
9.9 
Limitations of the Research Methods 
The study is to be performed as a non-interventional study. Unlike clinical studies, 
obtainable data are limited and there is a possibility of missing data. 
9.10 
Other Aspects 
9.10.1 
Note To File 
The Principal Investigator or designee will be responsible for documenting study relevant 
information and occurrences that affects the course of the study. The information and 
occurrences are not protocol deviations but will be documented in a note to file and will 
be communicated to the sponsor.  
 
9.10.2 
Training Log 
All designated study personnel must be trained on the study protocol and procedures.  
Training and retraining are documented on the Training Log. 
 
9.10.3 
Visitor Log  
All Sponsor or other related individuals who visit the study site must sign the Visitor Log.   
 
9.10.4 
Responsibilities of the Principal Investigator  
The Principal Investigator is responsible for oversight of enrolment, the patient consent 
process, study related procedures, compliance with the protocol, all institutional, state and 
local guidelines.  
 
It is the responsibility of the Principal Investigator to select, supervise, and delegate 
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responsible for determining the appropriate staff qualifications required for specific study-
related tasks to be delegated. Study-related tasks delegated to staff members will be 
documented on the Site Signature and Delegation Log. 
 
9.10.5 
End of Trial 
End of Trial is defined as last subject’s last visit (LPLV).  
 
10.0 
Protection of Human Subjects 
This study must be conducted in compliance with the recommendations of the Declaration 
of Helsinki, 2008 (World Medical Association). In addition, this study will adhere to all 
general and local legal and regulatory requirements applicable to non-interventional 
studies. 
 
Informed consent will be obtained from each subject before the subject can 
participate in the study. The contents and process of obtaining informed consent 
will be in accordance with all applicable regulatory requirements. 
 
As required by applicable local regulations, the sponsor’s Regulatory Affairs group will 
ensure all legal regulatory aspects are covered, and obtain approval of the appropriate 
regulatory bodies, prior to study initiation in regions where an approval is required. 
 
This study is non-interventional and falls outside the scope of the EU Directive 
2001/20/EC, the EU Directive 2005/28/EC and International Conference on 
Harmonization (ICH) Good Clinical Practice (GCP) guidelines.  
 
This study complies with the EU Directive 95/46/EC of the European Parliament and of 
the Council of 24 October 1995 on the protection of individuals with regard to the 
processing of personal data and on the free movement of such data. 
 

 
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11.0 
Management and Reporting of Adverse 
Events/Adverse Reactions 
11.1 
Adverse Event Definition and Serious Adverse Event 
Categories 
 An adverse event (AE) is defined as any untoward medical occurrence in a patient, which 
does not necessarily have a causal relationship with their treatment.  An adverse event can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not the event is considered causally related to the use of the product. 
 
Such an event can result from use of the drug as stipulated in the labeling, as well as from 
accidental or intentional overdose, drug abuse, or drug withdrawal. Any worsening of a 
pre-existing condition or illness is considered an adverse event. 
 
If an adverse event meets any of the following criteria, it is considered a serious adverse 
event (SAE): 
 
Death of Patient: 
An event that results in the death of a patient. 
Life-Threatening: 
An event that, in the opinion of the investigator, 
would have resulted in immediate fatality if medical 
intervention had not been taken. This does not include 
an event that would have been fatal if it had occurred 
in a more severe form. 
Hospitalization: 
An event that results in an admission to the hospital 
for any length of time. This does not include an 
emergency room visit or admission to an outpatient 
facility. 
Prolongation of 
Hospitalization: 
An event that occurs while the study patient is 
hospitalized and prolongs the patient's hospital stay. 
Congenital Anomaly: 
An anomaly detected at or after birth, or any anomaly 
that results in fetal loss. 
Persistent or Significant 
Disability/Incapacity: 
An event that results in a condition that substantially 
interferes with the activities of daily living of a study 
patient. Disability is not intended to include 

 
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experiences of relatively minor medical significance 
such as headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained 
ankle). 
Important Medical Event 
Requiring Medical or 
Surgical Intervention to 
Prevent Serious Outcome: 
An important medical event that may not be 
immediately life-threatening or result in death or 
hospitalization, but based on medical judgment may 
jeopardize the patient and may require medical or 
surgical intervention to prevent any of the outcomes 
listed above (i.e., death of patient, life threatening, 
hospitalization, 
prolongation 
of 
hospitalization, 
congenital anomaly, or persistent or significant 
disability/incapacity). Additionally, any elective or 
spontaneous abortion or stillbirth is considered an 
important medical event. Examples of such events 
include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
 
11.2 
Severity 
 The following definitions will be used to rate the severity for any adverse event being 
collected as an endpoint/data point in the study and for all serious adverse events. 
 
Mild: 
The adverse event is transient and easily tolerated by the patient. 
Moderate: 
The adverse event causes the patient discomfort and interrupts the 
patient's usual activities. 
Severe: 
The adverse event causes considerable interference with the 
patient's usual activities and may be incapacitating or life 
threatening. 
 
11.3 
Relationship to Pharmaceutical Product 
 The following definitions will be used to assess the relationship of the adverse event to 
the use of product: 

 
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Reasonable Possibility 
An adverse event where there is evidence to suggest a 
causal relationship between the product and the adverse 
event. 
No Reasonable Possibility 
An adverse event where there is no evidence to suggest a 
causal relationship between the product and the adverse 
event. 
 
If no reasonable possibility of being related to product is given, an alternate etiology must 
be provided for the adverse event. 
 
11.4 
Serious Adverse Event Collection Period 
 Serious adverse events will be reported to AbbVie from the time the physician obtains the 
patient's authorization to use and disclose information (or the patient's informed consent) 
until 70 days following the intake of the last dose of adalimumab taken during the study. 
11.5 
Serious Adverse Event Reporting 
 In the event of a serious adverse event, the physician will: 
● For events from patients using an AbbVie product - notify the AbbVie 
Emergency contact person (ASR) identified at the beginning of the protocol 
within 24 hours of the physician becoming aware of the event. 
 
11.6 
Pregnancy Reporting 
Pregnancies in patients will be collected from the date of the first dose through 150 days 
following the last dose of adalimumab taken during the study.  In the event of a pregnancy 
occurrence in the patient, the physician will notify AbbVie Emergency contact person 
identified in protocol section 3.0 within 24 hours of the physician becoming aware of the 
pregnancy. 
Information regarding a pregnancy occurrence in a study subject and the outcome of the 
pregnancy will be collected. 
 
This protocol requires all SAEs and AESIs as outlined in protocol section 11.1 to be 
actively solicited.  The safety profile of adalimumab which has over 3.5 million patient 
years of post-marketing exposure is stable and well established; non-serious events will 
not be actively solicited as these events are not likely to contribute to the further 

 
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understanding of the safety profile of the product.   Any non-serious AEs will be collected 
as spontaneous reports if AbbVie is notified. 
 
11.7 
Malignancy Reporting 
 
In the event of a serious adverse event, and additionally, any non-serious event of 
malignancy in patients 30 years of age and younger, whether related to study drug or not, 
the physician will notify the AbbVie contact person identified in protocol section 3.0 
within 24 hours of the physician becoming aware of the event.  
Adalimumab therapy has a well-established and well described safety profile based on 
extensive postmarketing experience and continued clinical trial patient exposure since the 
first approved indication in 2002 for rheumatoid arthritis. A detailed discussion of the pre-
clinical toxicology, metabolism, pharmacology and safety experience with adalimumab 
can be found in the current Investigator's Brochure. AbbVie is committed to continue to 
collect safety information including those events that may occur in this trial in order to 
confirm this established safety profile and to identify any unknown potential adverse 
reactions, rare events and those events with a long latency. AbbVie is participating in an 
FDA-requested, TNF inhibitor class wide exploration of the rare appearance of 
malignancy in subjects/patients who are 30 years of age or younger at the time of 
diagnosis. The risk of malignancy in this age group has not been established and is 
difficult to study due to its rarity. AbbVie appreciates your attention to the additional 
reporting requirements needed in this unlikely event, outlined in Section 11.7 under 
Malignancy Reporting. 
11.8 
Product Complaint  
A Product Complaint is any Complaint related to the biologic or drug component of the 
product or to the medical device component(s). 
For a product this may include, but is not limited to, damaged/broken product or 
packaging, product appearance whose color/markings do not match the labeling, labeling 

 
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discrepancies/inadequacies in the labeling/instructions (example:  printing illegible), 
missing components/product, device not working properly, or packaging issues. 
For medical devices, a product complaint also includes all deaths of a patient using the 
device, any illness, injury, or adverse event in the proximity of the device, an adverse 
event that could be a result of using the device, any event needing medical or surgical 
intervention including hospitalization while using the device and use errors. 
Any information available to help in the determination of causality by the device to the 
events outlined directly above should be captured. 
 
12.0 
Plans for Disseminating and Communicating Study Results 
At the end of this observational study, a report will be written by AbbVie or a CRO 
working on behalf of AbbVie. The required standard study report template will be 
followed. This report will contain a description of the objectives of the study, the 
methodology and its results and conclusions. The completed CRFs, [patient 
questionnaires, interim assessments], the final study output and study report are the 
confidential property of AbbVie and may not be released to unauthorized people in any 
form (publications or presentations) without express written approval from AbbVie. The 
study results will be submitted to local authorities per local laws and regulations. 
The results of this PMOS may be published by AbbVie or by any one of the participating 
investigators after agreement with AbbVie. 
 
 
12.1  Ethical and Legal Consideration 
 
All participant data will be handled in a manner compliant with all local regulatory and 
privacy laws. All parties will ensure protection of subject personal data and will not 
include subject names on any sponsor forms, reports, publications, or in any other 
disclosures, except where required by law. Appropriate role-based access to minimum 
necessary information will be maintained so that only authorized individuals have access 
to protected health information (PHI).  
 
Abbvie shall comply with all applicable laws regarding the reporting of spontaneous 
adverse events (AEs) to the relevant local authorities in China-. Abbvie will follow the 
International Conference on Harmonization of Good Clinical Practice (ICH-GCP) 

 
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guidelines for AE reporting and report all spontaneously reported AEs within the required 
timeframe (usually within 24 hours of discovery).  
 
All staff working directly with patient data and/or having direct contact with healthcare 
practitioners will have received formal training to ensure they have a clear understanding 
of how to recognize an AE and inform Affiliate Safety Specialist so that they are in full 
compliance with local laws regarding AE reporting. 
 
The study will be reviewed and approved by the appropriate Ethics Committee(s) at each 
site prior to the start of patient recruitment, according to the specific legal requirements in 
each country.  
 
12.2 
Confidentiality 
12.2.1 
Patient confidentiality 
Information on patients’ identity shall be considered as confidential for all effects and 
purposes. Each site and patient will have a code in the study. Sites will be automatically 
coded by AbbVie. Patients will be assigned a sequential number by the site coordinator 
upon meeting all inclusion and no exclusion criteria.  
 
The patients’ identity should not be revealed nor published under any circumstances. 
Patient data recorded in the CRF will be documented anonymously, coded with a patient 
number in such a way that only the investigator and site staff may associate particular data 
with an identified or identifiable individual or his/her medical record. All other parties 
involved in data management, analysis and storage will receive, and subsequently analyze, 
non-identifiable patient data. 
 
12.2.2 
Data confidentiality 
By signing the investigator’s confidentiality agreement, the investigator affirms to 
AbbVie/IMS that information furnished by AbbVie/IMS to the investigator will be kept in 
confidence and such information will be divulged to any expert committee, affiliated 
institution, and employees only under an appropriate understanding of confidentiality with 
such committee, affiliated institution and employees.  
 

 
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12.3 
Study administration 
The entire study will be managed by a project coordinator at AbbVie who will coordinate 
the project and maintain fluid communication with the study sponsor, the study team and 
the director at AbbVie. 
 
As part of the monitoring plan, regular phone calls (at least every two weeks) will be 
made between AbbVie and local site coordinator in order to check inclusion status, 
resolve any issues, check data plausibility, etc.  
 
12.4 
Investigators compliance 
By signing the investigator’s agreement, the investigator agrees to conduct the study in an 
efficient and diligent manner and in conformance with this protocol, generally accepted 
standards of good clinical practice and all applicable laws, rules and regulations relating to 
the conduct of the study. 
 
The investigator shall prepare and maintain complete and accurate study documentation in 
compliance with applicable national and local laws, rules and regulations and, for each 
patient participating in the study, promptly record all data in the CRF as required by this 
protocol. 
 
12.5 
Risks, Insurance, Indemnity and compensation 
This is a non-interventional observational study. It does not involve any direct patient 
intervention with respect to laboratory tests, examinations or drug treatment.  
 
The Sponsor will provide Product Liability insurance for all subjects included in the 
study. 
 
12.6 
Discontinuation or Drop-out 
Patients’ participation in the study is completely voluntary, and they are allowed to 
withdraw or discontinue from the study. The following three situations will be counted as 
study drop-out:  
1) Patient is switched off Adalimumab  
2) Patient is not willing to continue participation in the study  
3) Patient disappears and cannot be contacted anymore 

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For the first two situations, the Early Termination Form (Error! Reference source not 
found.) will be provided for the patients and their physicians to fill in. 
Patients not completing questionnaires will not be classified as drop-out. For example, if a 
patient missed Week 12 questionnaires for some reason, he/she can still fill in Week 24 
questionnaires.  
12.7 
Quality control and audit 
Steps to be taken to ensure the accuracy and reliability of data include the selection of 
qualified investigators and appropriate study centers, review of protocol procedures with 
the investigator and associated personnel before the study and periodic monitoring visits 
by the sponsor. Written instructions will be provided for administration and collection of 
study questionnaires.   
Guidelines for CRF completion will be provided and reviewed with study personnel 
before the start of the study. The sponsor will review CRFs and patient questionnaires for 
accuracy and completeness during on-site monitoring visits and after transmission to the 
sponsor; any discrepancies will be resolved with the investigator or designee, as 
appropriate. After upload of the data into the clinical study database they will be verified 
for accuracy and consistency with the data sources. 
The study will be performed following AbbVie Standard Operating Procedures (SOPs) for 
Observational Studies.  
13.0 
References 
1 World Healht Organisation. Disability Fact Sheet.   [cited May 7, 2015]; Available 
from: http://www.who.int/disabilities/world report/2011/factsheet.pdf
2 AbbVie Limited. Adalimumab Data Sheet. 27 November 2014(Version 32). 
3 U.S. Department of Health and Human Services, Food and Drug Administration, Center 
for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and 
Research (CBER), (CDRH) CfDaRH. Guidance for Industry Rheumatoid Arthritis: 
Developing Drug Products for Treatment. 2013. 
4 Bruce B, Fries J. The health assessment questionnaire (HAQ). Clinical and experimental 
rheumatology. 2005;23(5):S14. 

 
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5 Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: a review of its 
history, issues, progress, and documentation. The Journal of rheumatology. 
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6 Barrett EM, Scott DG, Wiles NJ, Symmons DP. The impact of rheumatoid arthritis on 
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7 Wolfe F, Hawley DJ. The longterm outcomes of rheumatoid arthritis: Work disability: a 
prospective 18 year study of 823 patients. The Journal of rheumatology. 1998 
Nov;25(11):2108-17. 
8 Jantti J, Aho K, Kaarela K, Kautiainen H. Work disability in an inception cohort of 
patients with seropositive rheumatoid arthritis: a 20 year study. Rheumatology (Oxford, 
England). 1999 Nov;38(11):1138-41. 
9 Fex E, Larsson BM, Nived K, Eberhardt K. Effect of rheumatoid arthritis on work status 
and social and leisure time activities in patients followed 8 years from onset. The 
Journal of rheumatology. 1998 Jan;25(1):44-50. 
10 Dougados M, Schmidely N, Le Bars M, et al. Evaluation of different methods used to 
assess disease activity in rheumatoid arthritis: analysis of abatacept clinical trial data. 
Annals of the rheumatic diseases. 2009 Apr;68(4):484-9. 
11 van der Bijl AE, Breedveld FC, Antoni CE, et al. An open-label pilot study of the 
effectiveness of adalimumab in patients with rheumatoid arthritis and previous 
infliximab treatment: relationship to reasons for failure and anti-infliximab antibody 
status. Clinical rheumatology. 2008 Aug;27(8):1021-8. 
12 Bejarano V, Quinn M, Conaghan PG, et al. Effect of the early use of the anti-tumor 
necrosis factor adalimumab on the prevention of job loss in patients with early 
rheumatoid arthritis. Arthritis and rheumatism. 2008 Oct 15;59(10):1467-74. 
13 Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog 
Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain 
Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain 
Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of 
Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis care & research. 2011 
Nov;63 Suppl 11:S240-52. 
14 The EuroQol Group. EuroQol--a new facility for the measurement of health-related 
quality of life. Health policy (Amsterdam, Netherlands). 1990 Dec;16(3):199-208. 
15 Oemar M, Oppe M. EQ-5D-3L User Guide: Basic information on how to use the EQ-
5D-3L instrument. The EuroQol Group; 2013. 
16 Evans C, Crawford B. Patient self-reports in pharmacoeconomic studies. Their use and 
impact on study validity. PharmacoEconomics. 1999 Mar;15(3):241-56. 
 
 
 

 
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AbbVie Inc. (AbbVie) 
Post Marketing Observational Study 
Protocol 
Real-World Outcome of Adalimumab on Rheumatoid Arthritis Patients in China 
Approved by: 
Name 
Study Designated Physician
Date
/
/
Name
Date
Name
Date
Name
Date
Name
Date

 
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