COPD Disease Burden, Patient Characteristics, Maintenance Treatment Patterns and Factors Influencing Treatment Decisions in China Tier 2 and Tier 3 Hospitals
Conditions: Pulmonary Disease, Chronic Obstructive
Sponsor: GlaxoSmithKline

Protocol
Study ID:  213550
Official Title of Study: COPD disease burden, patient characteristics, 
maintenance treatment patterns and factors influencing treatment decisions in 
China Tier 2 and Tier 3 hospitals  
NCT ID: NCT04853238
Date of Document: 26-May-2022

 
CONFIDENTIAL  
Copyright 2020 the GlaxoSmithKline group of companies. All rights reserved. 
Unauthorized copying or use of this information is prohibited. 
HEALTH OUTCOMES STUDY PROTOCOL - QUALITATIVE RESEARCH 
UNIQUE IDENTIFIER 
213550 
FULL TITLE 
COPD disease burden, patient characteristics, maintenance 
treatment patterns and factors influencing treatment 
decisions in China Tier 2 and Tier 3 hospitals  
ABBREVIATED TITLE 
COPD maintenance treatment patterns in China 
FINAL PROTOCOL APPROVED 
SPONSORSHIP 
Sponsored  
DIVISION 
Pharma  
BUSINESS UNIT 
Medical Affairs 
DEPARTMENT 
Medical Affairs  
STUDY ACCOUNTABLE PERSON 
CONTRIBUTING AUTHORS 
ASSET ID 
GSK2834425, GW685698/GW642444/GSK573719 
GSK ASSET 
Trelegy 
INDICATION 
Chronic Obstructive Pulmonary Disease 
REVISION CHRONOLOGY:   
Version Date 
Document Type 
Change(s) since last version 
Version ID: 2.0 
1.0 
Description: COPD maintenance treatment patterns in China 
Unique Identifier: 213550 
PPD

2 
 
SPONSOR SIGNATORY 
 
 
  
 
[Xiao Hu], Medical Affairs Manager 
Primary Author/ Project officer 
 
Date 
 
 
[Jody Goh], Head of Respiratory Therapy Area 
 
Date 
 
 
[ Pauling Ng], Country Medical Director 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PPD
PPD
PPD

3 
 
 
Description: COPD maintenance treatment patterns in China 
 
Unique Identifier: 213550 
 
 
Investigator Protocol Agreement Page 
 
• 
I confirm agreement to conduct the study in compliance with the protocol. 
• 
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described clinical study. 
• 
I agree to ensure that all associates, colleagues and employees assisting in the conduct 
of the study are informed about their obligations. Mechanisms are in place to ensure 
that site staff receives the appropriate information throughout the study. 
 
 
Investigator Name:  
_________________________________ 
 
 
 
 
 
 
 
 
 
  
Investigator Signature 
 
Date (DD-MMM-YYYY) 
 
 
 
 

4 
 
 
PROTOCOL SYNOPSIS  
 
Unique Identifier 
213550 
Abbreviated Title  
COPD maintenance treatment patterns in China 
GSK Product 
Trelegy 
Rationale 
Pharmacological treatment of COPD, as perceived by physicians in 
China, appears very complicated, especially with the increasing 
number of therapeutic options available and recommendations to 
personalise treatment of COPD patients to individual needs. 
Physicians also use different treatment strategies for symptom 
reduction and exacerbation prevention. For example, many use a 
step-up approach but some use intensive treatment initially, 
followed by step down. In addition, treatments depend on the socio-
economic condition of the patient such as occupation, educational 
level, income and environment. 
 
A further complication in China is that there are different tiers of 
hospitals with different formularies and patients move between 
hospitals and doctors very readily. In addition, the re-attendance 
rate to the same clinic/physician is low, resulting in little continuity 
of care. 
 
Therefore, this study is conducted to gain an adequate 
understanding of the complex COPD management environment and 
doctors’ treatment strategy of COPD in China. 
Objectives  
(Primary, Secondary)  
Primary 
To quantify the pattern of COPD maintenance treatment 
prescribing in different patient groups in Tier 2 and 3 hospitals in 
China 
Secondary  
x To examine factors (including disease severity and socio-
economic factors) that are associated with different patterns of 
COPD maintenance treatment 
x To assess the proportion of patients whose prescribed 
maintenance treatment is stepped up, stepped down, switched, 
stopped or remains the same across the different study time 
points  
x Assess the disease burden of the patients 

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x To assess the proportion of patients receiving each treatment 
class at 3 months. 
Study Design 
This will be a 3-month, multicentre, prospective, low-interventional 
study in newly diagnosed and previously diagnosed patients with 
COPD presenting to clinics, either in stable state or with an acute 
exacerbation, in Tier 2 and 3 hospitals in China. The study will be 
conducted at around 35 sites (±5 sites). For the primary analysis, 
the patients will be categorised into 3 cohorts: 
1. 
Cohort 1: Patients presenting with stable disease 
2. 
Cohort 2: Patients presenting with a moderate exacerbation 
not requiring hospitalization 
3. 
Cohort 3: Patients requiring hospitalisation for an 
exacerbation 
Study Population 
Inclusion Criteria 
Male or female patients with ≥40 years of age at the time of signing 
the informed consent with a diagnosis of COPD confirmed by 
spirometry (According to GOLD 2019 criteria).  
Exclusion Criteria 
x Patients with a current primary diagnosis of asthma, active 
tuberculosis, bronchiectasis, lung cancer or other active 
pulmonary disease, other unstable diseases or cognitive 
behaviour, which could influence COPD assessment test 
(CAT) and lung function results in the view of their 
physicians.  
x Patients who experienced a physician-treated moderate or 
severe COPD exacerbation within the last 1 month before 
screening.  
x Patient participating in another COPD clinical study using 
investigational medication and/or disease management 
process. 
Data Source  
 Primary Endpoints  
x The data source will be the study case record form (CRF) 
x COPD prescription for maintenance therapy (Long-Acting 
Muscarinic Antagonist [LAMA], Long-Acting Beta-Agonist 
[LABA]; dual bronchodilator, inhaled corticosteroid [ICS]/ Long-
Acting Beta-Agonist [LABA], triple therapy, theophylline and n-
acetyl cysteine/carbocysteine) at baseline. 

6 
 
x COPD prescription for maintenance therapy collected at 3 
months (all patients) and at 1 week after a moderate 
exacerbation or on discharge following hospitalisation. 
 
Secondary Endpoints 
x Data source mentioned in primary endpoints 
x FEV1, exacerbations in previous 1 year, CAT score, Modified 
Medical Research Council (mMRC) score, co-morbidity, socio-
economic status, COPD medication history (within past 1 
month) 
Data Analysis Methods 
The number and percentage of patients who use the maintenance 
treatment at each visit will be summarized. Moreover, for those 
who use maintenance treatment, the number and percentage of 
patients will be summarized for each of the following pattern of 
maintenance treatment: 
x Long-Acting Muscarinic Antagonist [LAMA] 
x Long-Acting Beta-Agonist [LABA] 
x Dual bronchodilator 
x Inhaled corticosteroid [ICS]/ Long-Acting Beta-Agonist 
[LABA] 
x Triple therapy 
x Theophylline 
x N-acetyl cysteine/carbocysteine 
The results for patients with stable disease and patients with 
exacerbation at baseline will be analysed separately for the 
following visits: baseline visit, 1-week follow up (for moderate 
exacerbations) and discharge follow-up (for hospitalised 
exacerbations). The results for patients with stable disease and 
patients with exacerbation will be pooled together for analysis for 
3-month follow-up visit. 
Sample Size and Power For this study, around 1500 patients with COPD will be enrolled 
including stable patients (~50% of the total patients) and patients 
with exacerbations (~50% of the total patients). All enrolled 
patients will be included in the analysis. A large overall sample size 
was chosen to ensure adequate patient representation across 
China. It is estimated that 750 patients each from tier 2 and tier 3 
hospitals will be enrolled to provide adequate representation on 
healthcare status for COPD in China.  After 500 patients have been 

7 
 
recruited, the numbers will be reviewed to assess whether an 
adequate number of patients from each of the 3 cohorts have been 
enrolled for each tier of hospital. Recruitment policy might be 
changed to ensure an adequate distribution of patients. 
Limitations 
Potential limitations have been listed below.  
1) The study has covered major Chinese provinces as 
comprehensively as possible, choosed 1-2 sites from major 
Chinese province but this may not be fully representative of all 
the Tier 2&3 hospitals in each province.   
2) The study includes only those Tier 2 hospitals at a minimum 
have respiratory department which have LAMA and ICS/LABA 
and spirometry available; however, this will not fully reflect 
COPD management in all Tier 2 hospitals, because not all 
currently have such drugs available. This situation is changing so 
that all Tier 2 hospitals will have these treatments available 
relatively soon. 
3) It is a 3-month follow-up study and the duration is adequate to 
measure short-medium term changes, but COPD requires 
lifelong treatment, so this reflects only a short period of a 
patient’s management. 
4) The adherence data is reliant on the patients accurate reporting 
of which prescribed treatments they are taking, there can be an 
underestimation or overestimation of adherence to medication.  
 
 
 

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TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ....................................................................................................................... 4 
TABLE OF CONTENTS ........................................................................................................................ 8 
ABBREVIATIONS ................................................................................................................................. 9 
1 
INTRODUCTION/BACKGROUND ............................................................................................... 12 
2 
RESEARCH OBJECTIVES .......................................................................................................... 14 
 
Primary Objective: ................................................................................................................ 14 
 
Secondary Objectives ........................................................................................................... 14 
3 
RESEARCH METHODOLOGY .................................................................................................... 15 
 
Study Design ......................................................................................................................... 15 
 
Study Population ................................................................................................................... 16 
 
Eligibility Criteria ............................................................................................................ 16 
 
Sampling ....................................................................................................................... 17 
 
Data Source / Data Collection .............................................................................................. 22 
 
Endpoints data source .................................................................................................. 22 
 
Exposure and outcomes ............................................................................................... 23 
4 
SAMPLE SIZE / POWER CALCULATIONS ................................................................................ 27 
 
Hypotheses ........................................................................................................................... 28 
5 
DATA ANALYSIS CONSIDERATIONS ....................................................................................... 28 
 
Primary analyses .................................................................................................................. 28 
 
Secondary analyses ............................................................................................................. 29 
 
Other analysis ....................................................................................................................... 30 
6 
LIMITATIONS ............................................................................................................................... 31 
7 
STUDY CONDUCT, MANAGEMENT & ETHICS ........................................................................ 31 
 
Ethics Committee/IRB Approval ........................................................................................... 31 
 
Informed Consent ................................................................................................................. 31 
 
Data Protection ..................................................................................................................... 32 
 
Personally Identifiable Information (PII) ............................................................................... 32 
 
Adverse Event (AE), Pregnancy Exposure, and Incident Reporting .................................... 32 
 
Legal Basis for Processing Individual Human Data ............................................................. 32 
8 
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS ........................... 33 
 
Target Audience ................................................................................................................... 33 
 
Study reporting and publications .......................................................................................... 33 
9 
REFERENCES ............................................................................................................................. 34 
10 APPENDICES .............................................................................................................................. 36 
 
Appendix 1: SCHEDULE OF ACTIVITIES ........................................................................... 36 
CCI
CCI

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Appendix 2: COPD assessment test .................................................................................... 40 
 
Appendix 3: Modified British Medical Research Council (mMRC) Dyspnoea Scale ........... 42 
 
Appendix 4: DECAF score .................................................................................................... 43 
 
Appendix 5: Patient survey and questionnaire ..................................................................... 44 
Social Economics Information˖ ...................................................................................................... 44 
Disease Knowledge˖ ........................................................................................................................ 45 
If you don’t go for follow-up visits regularly, why not˛˄Choose as many as you want˅ ..... 46 
Emotions (PHQ9):............................................................................................................................... 48 
Social Economics Information˖ ...................................................................................................... 50 
Disease Knowledge˖ ........................................................................................................................ 50 
Emotions (PHQ9):˖ ........................................................................................................................... 53 
 
Appendix 6: sPVP and PVP APPROVAL FORM ................................................................. 55 
 
ABBREVIATIONS  
 
AE 
Adverse Event 
BMI 
Body Mass Index 
CAT 
COPD assessment test 
CE 
Concept Elicitation 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
COPD 
Chronic Obstructive Pulmonary Disease 
CRF 
Case Report Form 
CVD 
Cardiovascular Disease 
DECAF Score 
Dyspnoea, Eosinopenia, Consolidation, Acidaemia and atrial 
Fibrillation (DECAF) Score 
eMRCD 
Extended MRC Dyspnea Scale 
ER 
Emergency room 
FEV1 
Forced expiratory volume in one minute 
FSFV 
First subject first visit 
GCP 
Good Clinical Practice 
GERD 
Gastroesophageal Reflux Disease 
GSE 
General Self-Efficacy Scale 
GP 
General Physician 
GSK 
GlaxoSmithKline 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 

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ICH 
International Conference on Harmonization 
ICS 
Inhaled corticosteroid 
IEC 
Independent Ethics Committee 
IHD 
Individual human data 
IPAQ 
International physical activity questionnaire 
IRB 
Institutional Review Board 
LABA 
Long-acting beta agonists 
LAMA 
Long-acting muscarinic antagonist 
LSLV 
Last subject’s last visit 
mMRC 
Modified Medical Research Council 
OR 
Odds Ratio 
OSAS 
Obstructive Sleep Apnea Syndrome 
SAMA 
Short-acting muscarinic antagonist 
SABD 
Short acting bronchodilator 
OPD 
Outpatient department 
PHQ9 
The patient health questionnaire 
PI 
Principle Investigator 
PII 
Personally Identifiable Information 
PRO 
Patient Reported Outcome 
PVP 
Pharmacovigilance Program 
V 
Visit 

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Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
COPD assessment test (CAT) 
 
 
 
 

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1 
INTRODUCTION/BACKGROUND  
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease 
characterized by persistent respiratory symptoms and airflow limitation that is due to airway 
and/or alveolar abnormalities usually caused by significant exposure to noxious particles or 
gases [GOLD, 2019]. This is associated with increased morbidity and risk of early death [Agusti, 
2005; Qaseem, 2011; Rodríguez, 2010].  
COPD is the third most prevalent disease in China after hypertension and diabetes [Wang 2018]. 
A study conducted between 2012-2015 found that 8.6% of Chinese aged ≥20 years met 
spirometry-defined COPD criteria and the COPD prevalence in adults ≥40 years was 13.7%. This 
amounts to 99.9 million people with potential COPD in China [Wang, 2018]. Annually, around 8 
million Chinese patients are hospitalised due to COPD exacerbations, but a larger but 
unquantified number of patients experiencing moderate exacerbations are treated as an 
outpatient. A survey in China, reported that the average exacerbation rate in patients diagnosed 
with COPD was approximately 2.5 exacerbations per year per patient [Jia, 2018].The frequency 
of exacerbations may be influenced by patients’ level of education and treatment adherence, 
physicians’ treatment decisions and disparity in prescription practice [Cai, 2015; Fang, 2012; Zha, 
2019]. The failure of patients and physicians to recognise the significance of exacerbations adds 
to the challenges in COPD treatment.  
Hospitalisation due to COPD exacerbations is associated with high healthcare costs. In China, 
patients with an acute exacerbation of COPD are admitted to a Tier-3 hospital with an average 
total cost of $1323 per admission [Yang, 2012]. Reducing hospitalisation through more effective 
maintenance treatment would greatly reduce healthcare costs in China. Appropriate 
management of COPD starts with diagnosis. In a study conducted in Beijing, 29% of the patients 
with high-risk COPD were undiagnosed [Rui, 2014] and many physicians do not consider 
spirometry as the most appropriate test when a diagnosis of COPD is suspected [Wang, 2018].  
In China, there are three tiers of hospital. Tier 1 hospitals have very basic facilities and limited 
formularies for the long-term management of COPD. Tier 2 hospitals have more facilities and get 
access to a wider range of treatments, which usually includes the main treatment classes for 
COPD, but not the latest therapies. The Tier 3 hospitals have the full range of COPD therapies; 
however, the government is actively encouraging a shift of COPD patients from Tier 3 to Tier 2 
hospitals. One more complication in China is that patients move between hospitals and doctors 
very readily, resulting in very little continuity of care. The experts with an interest in COPD are in 
a view that the re-attendance rate to the same clinic/physician is very low (approx below 50%). 
In a prescription survey conducted between 2010 and 2011 in China, it was observed that, as 
elsewhere in the world, physicians do not follow GOLD recommendations. [Fang, 2012]. In 

13 
 
addition, the economic burden poses a big challenge, since the social insurance bureau and 
private companies in China generally reimburse treatment costs due to hospitalisation, rather 
than maintenance treatment. Such policies are one of the leading causes of under-prescribing 
of drugs by physicians, because patients fail to receive adequate reimbursement [Li, 2018] and 
this leads to suboptimal treatment.  
Another important factor is the patients’ adherence to maintenance therapy, which remains a 
substantial barrier to optimal disease control. Despite evidence that adherence to inhaled 
COPD therapy is associated with improved symptom control, lung function and reductions in 
healthcare resource utilisation and costs, patients non-compliance to treatment remains a 
major problem [Davis, 2017;  
Mäkelä, 2013; Toy, 2011]. Studies in patients with COPD in the Western countries have shown 
that around 50% patients have suboptimal adherence to treatment [Restrepo, 2008], this is 
likely to be further low in China, due to low educational qualification of the patient attending 
COPD units.  
Smoking is a major risk factor for COPD. In China, in a study by Jiangna et al, around 82% of the 
patients recruited in tertiary care hospital were current or ex-smokers. However, there are 
COPD patients who are never-smokers [GOLD, 2020], due to a range of causes including but not 
limited to, childhood chest illnesses, passive cigarette, biomass fuel exposure and pollution. 
Therefore, to ensure an adequate representation of treatment for COPD in China, all patients 
with a clinical diagnosis of COPD, confirmed on spirometry, will be recruited and their smoking 
history will be recorded.  
Rationale 
In recent years, physicians in China have perceived pharmacological treatment of COPD to be 
very complicated, especially with the increasing number of therapeutic options available and 
recommendations to personalise treatment. Physicians also use different treatment strategies. 
A further complication is that treatment will depend on socio-economic factors such as 
occupation, educational level, income and patients’ preference. Besides, patients move 
between hospitals and doctors very readily, resulting in very little continuity of care. The 
experts with an interest in COPD are in view that the re-attendance rate to the same 
clinic/physician is very low (approx. below 50%). 
To improve COPD management in China, it is important to understand current patterns of 
COPD medication prescription and assess the effect of patient characteristics and other factors 
on treatment decisions made by physicians. Whilst data on physicians’ prescribing practises can 
be obtained through surveys or market research, this can’t capture the impact of the broad 
range of factors that a physician may take into account when deciding on treatment for an 

14 
 
individual patient, hence answers to paper-based scenarios may not accurately reflect 
behaviour in routine practice. In China, there are currently no databases that would permit 
analysis of prescribing to well characterised COPD patient groups. A prospective study of actual 
prescribing at an individual patient level is required, coupled with an assessment of the 
patient’s clinical severity and socio-economic status. This will allow a detailed analysis of the 
maintenance treatment used for different patient groups and give an insight into the factors 
that physicians take into account when deciding on treatment.  
There are three main clinical scenarios seen in Chinese hospitals: 
1. Patients presenting with stable disease 
2. Patients presenting with a moderate exacerbation 
3. Patients requiring hospitalisation for an exacerbation 
In each scenario, the patients may be treated differently, so it is necessary to determine 
prescribing practices of the physician in each case and identify factors associated with the 
prescription. It is also necessary to know how the maintenance treatment of the patients 
changes over time, and the level of the patient’s adherence to their prescriptions, as this 
thought to be low in China, but has not been measured. 
In China clinical practice, some patients may be admitted to hospital with an exacerbation but 
not because of the severity of the exacerbation (i.e. by the request of the patient). To ensure 
that patients are only recruited to the study because of the severity of the exacerbation, an 
inclusion criterion of the requirement for intravenous therapy is needed, since this treatment 
cannot be administered at home. 
2 
RESEARCH OBJECTIVES 
 
Primary Objective: 
x To quantify the pattern of COPD maintenance treatment prescribing in different patient 
groups in Tier 2 and 3 hospitals in China 
 
Secondary Objectives 
• To examine factors (including disease severity and socio-economic factors) that are 
associated with different patterns of COPD maintenance treatment 
• To assess the disease burden of patients (using baseline data) 
• To assess the proportion of patients whose prescribed maintenance treatment is 
stepped up (adding another maintenance treatment), stepped down (withdraw any of 
the maintenance medication but kept the maintenance treatment), switch (between 

15 
 
LAMA+LABA and ICS/LABA), stopped (stop all maintenance treatment) or remains the 
same across the different study time points  
• To assess the proportion of patients receiving each treatment class at 3 months 
3 
RESEARCH METHODOLOGY 
 
Study Design  
This will be a 3-month, multicentre, prospective study in newly diagnosed and previously 
diagnosed patients with COPD presenting to clinics, either in a stable state, defined as no 
exacerbation for at least 1 month, or with acute exacerbation, in Tier 2 and 3 hospitals 
distributed across China. The study will be conducted at around 35 sites (±5 sites). The patients 
will be categorised into 3 cohorts: 
1. Cohort 1: Patients presenting with stable disease (newly and previously diagnosed) 
2. Cohort 2: Patients presenting with a moderate acute exacerbation not requiring 
hospitalization 
3. Cohort 3: Patients requiring hospitalisation for an acute exacerbation 
 
Tel.-Telephone 
Figure 1: The study schematic 
CCI

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At site evaluation (conducted to evaluate if the sites can be included in the study), the types of 
medical insurance covered by the hospital, types of COPD maintenance medication available to 
be supplied to patients and reimbursement rate for each out-patient and in-patient medication 
will be collected before patient recruitment. 
 
 
Study Population 
The study population comprises COPD patients in stable status or with acute exacerbation in 
tier 2 and tier 3 hospitals. Stable status at enrolment is defined as no exacerbation events in the 
preceding month. An exacerbation of COPD is as an acute worsening of respiratory symptoms 
that results in additional therapy. Moderate exacerbation is defined as worsening of symptoms 
for which a patient seeks medical care and is treated by antibiotics and/or systemic 
corticosteroids /or corticosteroids nebulization, severe exacerbation is defined as patient 
requires hospitalization or visits the emergency room (ER)  
 Eligibility Criteria  
3.2.1.1 Inclusion Criteria 
In order to be eligible to participate in this study, a subject must meet all of the following 
criteria: 
x Patients ≥40 years of age  
x Male or female 
x A diagnosis of COPD confirmed by spirometry (According to GOLD 2019 criteria) in 
Tier 2 and Tier 3 hospitals 
x In hospitalized patients, recruit only patients who receive any intravenous therapy  
x A signed and dated written informed consent must be obtained from the patient 
prior to study participation 
x Patients can communicate normally  
3.2.1.2 Exclusion Criteria 
A subject who meets any of the following criteria will be excluded from participation in this 
study: 
x Current primary diagnosis of asthma, active tuberculosis, bronchiectasis, lung cancer 
or other active pulmonary disease 
x Other unstable diseases or cognitive behaviour, which could influence CAT and lung 
function results (judged by physicians) 
x Experienced a moderate/severe COPD exacerbation treated by a physician within 
last 1 month 

17 
 
x Currently participating in another COPD clinical study, which provides the patient 
investigational medication and/or disease management 
 Sampling 
For this study, around 1500 patients with COPD will be enrolled including stable patients and 
patients with exacerbations. It is planned that approximately equal number of patients will be 
recruited from Tier 2 and Tier 3 hospitals. After 500 patients have been recruited a review will 
be carried out to assess whether an adequate number of patients from each of the 3 cohorts 
defined in section 3.1 has been enrolled. At this point, recruitment policy might be changed to 
ensure an adequate distribution across type of hospital and type of patient. Thereafter, 
recruitment to each cohort will be monitored weekly and further corrective action will be taken 
if needed. 
At least one site in each of the main provinces of China will be selected. There is a variability of 
spirometry and inhaled therapy availability across Tier 2 hospitals, although this is improving. 
As the Government is actively encouraging patients to shift from Tier 3 to Tier 2 hospitals, the 
study will only include Tier 2 hospitals that, at a minimum have respiratory department, supply 
of LAMA and ICS/LABA, and facilities for spirometry, since this will be the minimum standard of 
care for patients with COPD in Tier 2 hospitals in the future. 
3.2.2.1 Patients presenting with stable disease 
Baseline visit (Day 1): 
Newly or previously diagnosed patients with stable COPD who attend the clinic will be screened 
by the study physician. Once eligible patients have been identified, informed consent will be 
obtained. The physician will then make their treatment decision, before any other study 
assessments are made. 
This visit will be considered as Baseline visit (V1). During the Baseline visit, the following 
information will be collected; 
1. Demography 
2. Time since first COPD diagnosis 
3. Co-morbidities 
4. COPD exacerbation history in prior 12 months 
5. COPD medication history (within past 1 month˅ 
6. Concomitant medication 
7. COPD medication prescribed at baseline visit (including the drugs prescribed this 
time and the drugs that the subject needs to continue to use) 

18 
 
8. Smoking history 
9. Spirometry (within 7 days of enrollment)† 
10. Modified Medical Research Council (mMRC) dyspnea scale, CAT 
11. Socio-Economic status (refer to 3.3.2.10 ) 
12. Patient questionnaire and survey †† 
13. Physician survey †† 
14. Collect spontaneously AE/SAE reports on GSK products  
15. Maintenance treatment class availability in hospital internal pharmacy††† 
16. Prescribing physician’s name†††. 
† FEV1 performed within 6 months before the index date will be acceptable. Index date is the date when physician 
collect data for baseline. A 7-day time window was set between the time when the V1 lung function results were 
obtained and the day of enrollment to ensure that there was sufficient time to obtain the lung function report 
results to deal with the interference of the COVID-19 epidemic on the study. 
†† Patient questionnaires include International physical activity questionnaire (IPAQ), The patient health 
questionnaire (PHQ9), General self-efficacy scale. Patient’s survey is developed by the study initiator. The 
physician’s survey is developed by the study initiator. 
††† Data will not be collected from patient 
3-month Follow-up visit (Day 90 ± 7): 
All patients will be followed-up telephonically after 3 months. Following information will be 
collected: 
1. Current COPD medication taken by the patient, including prescription of current 
treatment and time of prescription, physician and hospital name#.  
2. COPD Clinic revisit times and reason 
3. Frequency of COPD exacerbation between baseline visit and 3 months follow up 
4. Reason for the last hospital visit (i.e. routine or exacerbation) 
5. Identify prescribed treatments that the patients did not take on the day of the call*. 
6. CAT 
7. Patient questionnaire and survey † 
8. Collect spontaneously AE/SAE reports on GSK products  
# A photo of the physician’s prescription which includes COPD medication and medical records will provide all 
that information. If medical records couldn’t’ be provided, CRC can collect this information by patients’ recall. 
* This will be evaluated by Clinical research coordinator (CRC) from the photo of the physicians’ prescription 
collected from the patients.  
† Patient questionnaire is General self-efficacy scale. Patient’s survey is developed by the study initiator 
Note: During the 3-month period, there might be changes in prescription, but only the 
current treatment prescribed to the patient and the patient’s use of the treatment on the 
day or before the day of the call will be documented.  

19 
 
If the patient cannot be contacted telephonically at the first attempt, a minimum of 3 attempts 
should be made. This should be documented in a medical note. If the subject meets the 
conditions to withdraw from the project, no further data will be collected from the subject. 
3.2.2.2 Patients presenting with a moderate exacerbation (non-hospitalized) 
Baseline visit (Day 1) 
Data will be collected as per stable patient in section 3.2.2.1- Baseline visit. If a FEV1 
measurement from the last 6 months is not available, spirometry will be performed at the 
discretion of treating physician, dependent on whether it is possible or reasonable for the 
patient to do this.  
1-week follow-up (Day 8 ± 3) 
This follow-up visit will be telephonic on day 8 (+3 days window). The patient will be 
interviewed to obtain the following details; 
1. Any visit to hospital for COPD treatment in the last week? (Yes/No) 
a. If Yes - name of the hospital(s), physician’s name, date(s) and physician 
prescription(s). These can be all collected by taking a picture of the prescription 
2. CAT  
3. Collect spontaneous AE/SAE reports on GSK products 
If the patient cannot be contacted at first attempt, a minimum of 3 attempts should be made. 
This should be documented in a medical note. 
3-month Follow-up (Day 90 ± 7) 
Patients will be followed-up telephonically after 3 months. Data will be collected as per section 
3.2.2.1- Follow-up visit for stable COPD patients. 
Note: During the 3-month period, there might be changes in prescription, but only the current 
treatment prescribed to the patient and the patient’s use of the treatment on the day or before 
the day of the call will be documented.  If the subject meets the conditions to withdraw from 
the project, no further data will be collected from the subject. 
3.2.2.3 Patients requiring hospitalisation for an exacerbation 
Baseline visit (Day 1) 

20 
 
Baseline information as per section 3.2.2.1 will be collected on admission to the hospital, but if 
the patient is too ill, then baseline data will be collected before discharge. In the event that no 
historical FEV1 data within 6 months are available, spirometry will be performed if it is possible 
or reasonable for the patient to do.Dyspnoea, Eosinopenia, Consolidation, Acidaemia and atrial 
Fibrillation (DECAF) Score will be collected for the hospitalized patients during hospitalization 
period. 
Discharge Follow-up (Discharge day ± 1) 
At the day of discharge (±1 day) patient will be interviewed face to face for obtaining data as 
follow; 
1. Discharge date 
2. COPD prescription at discharge (including the drugs prescribed this time and the drugs 
that the subject needs to continue to use) 
3. CAT  
4. Concomitant medication review 
5. Total direct cost of the hospitalization  
6. Medical insurance reimbursement amount 
7. All other data under 3.2.2.1  (if not already collected) 
8. Collect spontaneous AE/SAE reports on GSK products 
9. Spirometry if no spirometry record within 6 months before baseline 
 
3-month Follow-up (Day 90 ± 7) 
Patients will be followed-up telephonically after 3 months. Data will be collected as per section 
3.2.2.1- Follow-up visit. 
Note: During the 3-month period, there might be changes in prescription, but only the current 
treatment prescribed to the patient and the patient’s use of the treatment on the day or the 
day before of the call will be documented. If the subject meets the conditions to withdraw from 
the project, no further data will be collected from the subject. 
The sampling plans specified in sections 3.2.2.1-3.2.2.3 are summarised in Table 1. 
 
Table 1: Visit & Observations recording 
Patients 
classification 
Baseline Visit 
 
1-week Follow-up 
or discharge 
Follow-up ±3 days 
3-month 
Follow-up 
(Telephonic) ±7 days 

21 
 
Stable patients 
(Newly and 
previously 
diagnosed) 
 
Demography, time since first 
COPD diagnosis, co-
morbidities, COPD 
exacerbation and medication 
history, concomitant 
medication, FEV1%pred, CAT 
score and mMRC, medicines 
prescribed at visit, smoking 
status, socio economic status, 
patient survey and 
questionnaire, physician 
survey, inhaler availability, 
spontaneous AE/SAE report 
collection, Maintenance 
treatment class availability in 
hospital internal pharmacy, 
prescribing physician’s name. 
 Not required 
Telephone 
CAT score; current 
treatment taken by 
patient, the prescription 
of current treatment and 
time of prescription (or 
last hospital visit time 
and prescription); Name 
of hospital and name of 
physician; COPD clinic 
revisit times and reason, 
Frequency of COPD 
exacerbation between 
baseline visit and 3 
months follow up, 
patient survey, 
concomitant medication 
review, spontaneous 
AE/SAE report collection 
 
Exacerbation 
Patients 
(Non-Admitted) 
Demography, time since first 
COPD diagnosis, co-
morbidities, COPD 
exacerbation and medication 
history, concomitant 
medication, FEV1%pred*, CAT 
score and mMRC,  medicines 
prescribed at visit, smoking 
status, socio economic status, 
patient survey and 
questionnaire, physician 
survey, inhaler availability, 
spontaneous AE/SAE report 
collection, Maintenance 
treatment class availability in 
hospital internal pharmacy, 
prescribing physician’s name.  
Telephone 
CAT score, any 
visit to 
hospital(Y/N), If 
Yes - name of the 
hospital(s), 
date(s) and 
physician 
prescription(s); 
spontaneous 
AE/SAE report 
collection 
Exacerbation 
patients 
(Hospitalized)** 
Demography, time since first 
COPD diagnosis, co-
morbidities, COPD 
exacerbation and medication 
history, concomitant 
medication, FEV1%pred*, CAT 
score and mMRC, medicines 
Onsite 
CAT score  
Prescription at 
discharge, 
discharge date 
spontaneous 

22 
 
prescribed at visit, smoking 
status, socio economic status, 
Dyspnoea, Eosinopenia, 
Consolidation, Acidaemia and 
atrial Fibrillation (DECAF) Score, 
patient survey and 
questionnaire, physician 
survey,  inhaler availability**, 
spontaneous AE/SAE report 
collection, Maintenance 
treatment class availability in 
hospital internal pharmacy, 
prescribing physician’s name. 
AE/SAE report 
collection, 
Concomitant 
medication, Total 
direct cost of the 
hospitalization, 
Medical insurance 
reimbursement 
amount 
 
* If FEV1 data is not available, it will be performed at the discretion of treating physician/collected 
during discharge 
** The baseline information can be collected at discharge 
 
Data Source / Data Collection 
 Endpoints data source 
3.3.1.1 Primary Endpoints  
x 
The data source will be the study case record form (CRF) 
x 
The prescription for COPD maintenance therapy, grouped into one or more of the 
following treatment classes: (Long-Acting Muscarinic Antagonist [LAMA], Long-Acting 
Beta-Agonist [LABA], dual bronchodilator, inhaled corticosteroid [ICS]/ Long-Acting Beta-
Agonist [LABA], triple therapy, theophylline and n-acetyl cysteine/carbocysteine) at 
baseline. The categories will be binary, e.g. treatment class used: Yes/No.  
x COPD prescription for maintenance therapy collected at 3 months (all patients) and at 1 
week after a moderate exacerbation or on discharge following hospitalisation. 
3.3.1.2 Secondary Endpoints 
• This will include the prescribing data listed in 3.3.1.1 
• FEV1, exacerbations in previous 1 year, medication history within 1 month before 
baseline visit, CAT score, mMRC score, DECAF score in hospitalised patients, co-
morbidity, socio-economic status.  
• The change in treatment over 3 months, (baseline medication will be used, as 
described, coupled with current prescribing collected at telephone interview at 3 
months). 

23 
 
 Exposure and outcomes 
3.3.2.1 Demographics 
x Sex: Male, Female  
x Age, years (below 65 years old vs. 65 years old and above)   
x Height, meters 
x Weight, kg 
x Body mass index (BMI=kg/m2, BMI<18.5 underweight, BMI18.5~23.9 normal, BMI≥24 
overweight, BMI≥28 obesity) 
x Smoking status: never a smoker; former smoker (previously smoked and has not 
smoked for at least 6 months prior to this visit); current smoker (10 pack years and 
smoked within 6 months of this visit); the number of pack years for former smoker and 
current smoker should be calculated (round up to the nearest integer) 
x Co-morbid diseases: Cardiovascular Disease (CVD defined as ischemic heart disease, 
heart failure, atrial fibrillation, hypertension), Diabetes, Hyperlipemia, Anxiety, 
Depression, Gastroesophageal reflux disease (GERD), obstructive sleep apnea syndrome 
(OSAS), concurrent asthma with COPD, past history of tuberculosis. 
x Class of maintenance treatment available at hospital internal pharmacy 
3.3.2.2 COPD assessment test (CAT):  
The CAT is an 8-item unidimensional measure of health status impairment in patients with 
COPD. It is applicable worldwide. The development of the CAT has involved well accepted 
methodologies used to develop psychometric tools [Jones, 2009a; Jones, 2009b]. With CAT, 
patients are scored on eight items (cough, phlegm, chest tightness, breathlessness, activity 
limitation, confidence, sleep and energy) on a scale of 0-5 depending on their impact. The sum 
of scores for each item gives the patient’s impact score ranging from 0 
 to 40 
 
   
After being instructed how to use the CAT (following the COPD assessment test manual 
www.CATestonline.org), the subjects will complete it by themselves, without supervision or 
assistance from investigator. If the CAT is normally used by the investigator in their routine 
clinical work, they should use it as they would do normally; if the investigator does not 
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24 
 
routinely use the CAT, it should be completed after the treatment decision has been made. The 
investigator should check whether the subjects complete all items before the patient leaves. 
3.3.2.3 Modified British Medical Research Council (mMRC) Questionnaire 
The mMRC was developed in 1960 [Fletcher, 1960], and relates well to other measures of 
health status [Bestall, 1999] and predicts future mortality risk [Sundh, 2012; Nishimura, 2002]. 
With mMRC, patients are scored on a scale of 0-4 depending on their disability due to shortness 
of breath from 0 
 to 4 
   
The mMRC will be completed by each patient by themselves, without supervision, after the 
CAT. If the mMRC is normally used by the investigator in their routine clinical work, they should 
use it as they would do normally; if the investigator does not routinely use the mMRC, it should 
be completed after the treatment decision has been made. The investigator should check 
whether the patient has completed the mMRC adequately but cannot assist in completing it. 
3.3.2.4 Spirometry: 
Spirometry data will be obtained for all patients at each site. If lung function data are available 
within the previous 6 months, this should be recorded, and no test will be required at the study 
visit. If previous FEV1 data are not available and the patient cannot perform adequate 
spirometry because they are being hospitalized for an exacerbation, this will be performed 
before discharge from hospital.  
Subjects should wear a nose clip while performing spirometry maneuvers. For FEV1 and FVC 
determinations, at least 3 acceptable spirometry efforts (with no more than 8) should be 
obtained. Acceptable spirometry efforts should have a satisfactory start of test and end of test 
(i.e, a plateau in the volume-time curve) and should be free from artifacts due to cough, early 
termination, poor effort, obstructed mouthpiece, equipment malfunction, or other reasons [ 
Miller, 2005;Pelligrino, 2005].The largest FEV1 and FVC from the 3 acceptable efforts should be 
recorded, even if they do not come from the same effort. 
Based on the spirometry results, subjects will be stratified into airflow limitation category (Gold 
1 - Gold 4) as per Table 2 . 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws 
and therefore have been excluded.
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25 
 
3.3.2.5 Physician survey 
Physician will be asked questions on why they follow their prescription practices. The survey 
will give brief idea on grounds which physicians prescribe treatment to patients. 
¾ In addition to the severity of the patient’s disease, which factors have influenced your 
prescription for THIS patient? (choose one or more options) 
Aˊ Patient or family ‘s economic condition  
Bˊ Patient’s reimbursement position 
Cˊ Drug availability of your hospital 
Dˊ Patient’s ability to use the inhaler  
Eˊ Patient’s preference 
¾ If none of the above factors applies, which treatment would you choose for THIS patient?  
(Choose one option) 
A. None 
B. SABA or SAMA (or both) 
C. LAMA or LABA 
D. LAMA+LABA 
E. ICS+LABA 
F. ICS+LABA+LAMA 
3.3.2.6 Patient survey and questionnaire  
To gain a better understanding of patient-related factors including socioeconomic status, 
knowledge of COPD and ideas on COPD treatment, a patient survey developed by the study 
initiator will be administered, together with questionnaires at the baseline visit and at the 3-
month visit. The questionnaires will be administered in validated Chinese versions. These are 
physical activity, assessed using the International Physical Activity Questionnaire (IPAQ), mood 
state measured with the Patient Health Questionnaire (PHQ9), and self-efficacy using the, 
General Self-Efficacy Scale (see appendix for full details). The survey and questionnaires will 
deepen our understanding of the patients’ behaviors and beliefs and how they influence 
adherence to treatment.   
3.3.2.7 Exacerbation history and hospitalization for exacerbation in preceding year: 
The patient’s exacerbation history in the preceding year will be recorded. COPD exacerbation is 
an acute event characterized by a worsening of the patient’s respiratory symptoms that is 
beyond normal day-to-day variations and leads to a change in medication [GOLD, 2019]. The 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws 
and therefore have been excluded.

26 
 
standard definition used in clinical studies requires a worsening of respiratory symptoms 
(including increased cough, sputum, breathlessness, chest tightness or wheeze) for 2 or more 
days. 
The severity of the exacerbation will be determined using the following standard categories: 
1. Mild – a worsening of symptoms treated by the patient through an increase in use of 
their usual medicine, typically increased SABA use 
2. Moderate – worsening of symptoms for which a patient seeks medical care and is 
treated by antibiotics and/or systemic corticosteroids/or corticosteroids 
nebulization 
3. Severe –exacerbation requiring hospital admission.  
3.3.2.8 Safety 
The data on AE/SAE should not be collected directly by physician. If an AE (serious or non-
serious) or complaint with any specifically named GSK product is reported spontaneously by a 
patient during the course of the study, this will be documented by the site staff.  
3.3.2.9 Physician prescription-COPD-Related Medication 
This will be collected by treatment class: Long-Acting Muscarinic Antagonist [LAMA], Long-
Acting Beta-Agonist [LABA], dual bronchodilator, inhaled corticosteroid [ICS]/ Long-Acting Beta-
Agonist [LABA], triple therapy, theophylline and n-acetyl cysteine/carbocysteine.  Information 
which includes such COPD medication and related medical records will be request.  
3.3.2.10  Socioeconomic status 
The objective questions will be asked to patients understand their socioeconomic status  
x Education (illiteracy, primary school, junior mid-school, high-school, university) 
x 
Living area (in city, outside city) 
x Marriage condition  
x Family total income in the past 12 months 
x Individual total income in the past 12 months 
x Economic support from others in the past 12 months 
x Total health expenditure in the past 12 months 
x Out-of-pocket health expenditure in the past 12 months 
x COPD expenditure in the past 12 months 
x Out-of-pocket COPD expenditure in the past 12 months 
x National basic medical insurance  
x Commercial insurance 

27 
 
3.3.2.11 DECAF score 
The is a 5-point scale that uses items from the MRC dyspnoea scale, together with blood eosinophils (<0.05 x 
109/L, consolidation (pneumonia) on CXR , moderate or severe acidaemia (pH < 7.3) and presence or history 
of atrial fibrillation. It has been extensively tested and validated [Echevarria,  2016]. 
4 
SAMPLE SIZE / POWER CALCULATIONS 
The primary objective of the study is to understand the prescription pattern of COPD 
maintenance treatment in Tier 2 and Tier 3 hospitals in China. Around 1500 patients with COPD 
will be enrolled which includes stable patients and patients with COPD exacerbations 
(moderate and severe). All enrolled patients will be included in the analysis. This sample size 
was chosen to ensure adequate patient representation and provide sufficient size for reliable 
analysis of different patient groups and key subgroups. 
It is estimated that 750 patients each from tier 2 and tier 3 hospitals will be enrolled to provide 
adequate representation on healthcare status for COPD in China. The target number of patients 
in each tier of hospital and patient groups is shown in Table 3. After 500 patients have been 
recruited, the numbers will be reviewed to assess whether adequate number of participants 
have been enrolled for patient in stable state or with COPD exacerbations in each tier of 
hospital. At this point, recruitment policy might be changed to ensure an adequate distribution 
of patients. Thereafter, recruitment to different patient groups will be monitored monthly and 
further corrective action taken if needed. 
Table 3:  
Patient recruitment strategy (estimated distribution ratio) 
Patient group 
Tier 2 hospital (% of total patients) 
Tier 3 hospital (% of total 
patients) 
Stable 
25%  
25% 
Moderate acute or 
Hospitalized exacerbation 
25% 
25% 
 
The secondary objective of this study is to examine factors (include baseline disease severity 
and baseline socio-economic factors) that are associated with different patterns of 
maintenance treatment. In the secondary analysis, we attempt to find significant association 
between disease severity (GOLD Group: A&B vs. C&D) and triple therapy at baseline for COPD 
patients.  
Based on a previous study [Brusselle, 2015], about 24% COPD patients in Group A&B were 
prescribed triple therapy at diagnosis and about 46% COPD patients in Group C&D were 
prescribed triple therapy at diagnosis. The proportion of patients in Group A&B accounted for 

28 
 
66% of the total. We will use logistic regression to test this association and the parameters 
mentioned will be used for power calculation.  
With a two-sided 5% level of significance and a sample size of 375subjects of each patient 
group in each Tier of hospital, we will have a power bigger than 98% for demonstrating a 
statistically significant result for the association between disease severity (GOLD Group: A&B vs. 
C&D) and triple therapy at baseline for COPD patients. 
 
Hypotheses  
The null hypothesis used to test the association between disease severity and triple therapy will 
be: 
H0: There is no association between disease severity (GOLD grade: A&B vs. C&D) and triple 
therapy at diagnosis for COPD patients. 
The alternative hypothesis will be: 
H1: There is association between disease severity (GOLD grade: A&B vs. C&D) and triple therapy 
at diagnosis for COPD patients. 
5 
DATA ANALYSIS CONSIDERATIONS  
This section summarizes the statistical approaches that will be implemented to assess the study 
objectives. The descriptive statistical results will be displayed for Tier 2 and 3 hospitals 
separately for all the analyses. All analyses will be conducted using SAS, version 9.4 or above. 
 Primary analyses 
 
The primary objective of this study is to quantify the pattern of maintenance treatment 
prescribing in different patient groups in Tier 2 and 3 hospitals in China. Firstly, the number and 
percentage of patients who use the maintenance treatment at each visit will be summarized. 
Moreover, for those who use maintenance treatment, the number and percentage of patients 
will be summarized for each of the following pattern of maintenance treatment: 
x Long-Acting Muscarinic Antagonist [LAMA] 
x Long-Acting Beta-Agonist [LABA] 
x Dual bronchodilator 
x Inhaled corticosteroid [ICS]/ Long-Acting Beta-Agonist [LABA] 
x Triple therapy 
x Theophylline 
x N-acetyl cysteine/carbocysteine 

29 
 
The results for patients with stable disease and patients with exacerbation at baseline will be 
analysed separately for the following visits: baseline visit, 1-week follow up (for moderate 
exacerbations) and discharge follow-up (for hospitalised exacerbations). The results for patients 
with stable disease and patients with exacerbation will be pooled together for analysis for 3-
month follow-up visit. The percentage will be compared between stable and exacerbating 
patients by maintenance treatment. 
 
Secondary analyses 
 
The secondary objective of this study is to examine factors (include baseline disease severity 
and baseline socio-economic factors) that are associated with different patterns of 
maintenance treatment at baseline. Separate analyses will be performed for stable and 
exacerbating patients, since it is possible that the factors that influence a physician’s choice of 
treatment may differ between the two conditions. 
 
This part of analysis will be conducted in the group of the patients with stable disease and 
patients with exacerbation. The number and percentage of patients in each pattern of 
maintenance treatment will be summarized by the following factors: 
 
x Age 
x Gender: female/male 
x Smoking history 
x Any comorbidity 
x Baseline GOLD 2019 grade: A/B/C/D 
x Annual income 
x Proportion of outpatient medical insurance 
x Place of residence (in city, outside city) 
x Educational level (illiterate, primary school, junior mid-school, high-school, university) 
x Baseline FEV1 stage: I-IV 
 
Multivariate logistic regression will be used to identify adjusted odds ratios (ORs) and 95% 
confidence intervals (95% CIs) for having a certain maintenance treatment versus none, using 
the above factors as covariates. 
Another secondary objective is to assess the proportion of patients whose prescribed 
maintenance treatment was stepped up, stepped down, stopped, switched or remained the 
same across the different study time points. The number and percentage of patients whose 
prescribed maintenance treatment was stepped up, stepped down, stopped, switched or 
remained the same will be summarized for each visit. 

30 
 
The results for patients with stable disease and patients with exacerbation will be analysed 
separately. For those with exacerbation, the results for patients with a moderate exacerbation 
and patients requiring hospitalisation for an exacerbation will be further analysed separately. 
The proportion of who have changed from one pattern of maintenance treatment at baseline 
to another pattern at 3-month will be summarized separately for the group of patients with 
stable disease at baseline and those with an exacerbation. 
One more secondary objective is to assess the disease burden of the patients. The number and 
percentage of patients in different mMRC score intervals, CAT score intervals, numbers of 
historic exacerbation will be summarized according to the usage of different historic 
treatments. Moreover, mMRC score, CAT score and number of historic exacerbations will be 
summarized by mean and standard deviation in different patterns of maintenance treatment. 
Another secondary objective is to assess the proportion of patients actually receiving each 
treatment class at 3 months.  
 
Other analysis 
Safety information will be summarized. 
CCI

31 
 
6 
LIMITATIONS 
x 
At least one site in each of the main province of China will be selected. However, only 
1-2 sites per province will be selected and these may not be fully representative of all 
the Tier 2 and 3 hospitals in each province.   
x 
The study includes only those Tier 2 hospitals which at a minimum to have LAMA and 
ICS/LABA and spirometry available; however, this will not fully reflect COPD 
management in all Tier 2 hospitals, because not all currently have such drugs available.  
x 
It is a 3-month follow-up study and the duration is adequate to measure short-medium 
term changes, but COPD requires lifelong treatment, so this reflects only a short period 
of a patient’s management 
x 
The adherence data is reliant on the patients accurate reporting of which prescribed 
treatments they are taking, there can be an underestimation or overestimation of 
adherence to medication. 
7 
STUDY CONDUCT, MANAGEMENT & ETHICS 
 
Ethics Committee/IRB Approval  
This study will be conducted in accordance with GCP and all applicable regulatory 
requirements, including, where applicable, the current version of the Declaration of Helsinki. 
The investigator is responsible for ensuring that this protocol, the site’s informed consent form, 
and any other information that will be presented to potential subjects (e.g., advertisements or 
information that supports or supplements the informed consent) are reviewed and approved 
by the appropriate Independent Ethics Committee (IEC). The investigator agrees to allow the 
IEC direct access to all relevant documents. The IEC must be constituted in accordance with all 
applicable regulatory requirements. GSK will provide the investigator with relevant 
document(s)/data that are needed for IEC review and approval of the study. Before CRFs can be 
shipped to the site, GSK must receive copies of the IEC approval, the approved informed 
consent form, and any other information that the IEC has approved for presentation to 
potential subjects. 
 
Informed Consent 
x 
The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions 
regarding the study.  
x 
Participants will be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed 
consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, 

32 
 
Health Insurance Portability and Accountability Act (HIPAA) requirements, where 
applicable, and the IRB/IEC or study centre.  
x 
The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
x 
A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorized representative. 
 
Data Protection 
Subject to participant consent, it is expected that patient number, date of birth, postal code 
and sex will be the only patient identifiable data that will be included in this transfer.  
The data will be housed within secure servers. Access to information is restricted by role and is 
project specific. Data are analysed on these secure servers, and only the output may be 
extracted.  
The output from this study will not include any individually identifiable data.  
 
 Personally Identifiable Information (PII) 
All efforts will be made to ensure compliance with all applicable human subject protection and 
data protection laws in China and regulations in effect. To this end, all analytical datasets will be 
in a format that does not allow subjects to be identified, whether directly or through identifiers 
linked to the subject. 
 
Adverse Event (AE), Pregnancy Exposure, and Incident Reporting 
If an AE (serious or non-serious) or complaint with any specifically with GSK product is reported 
spontaneously by a subject during the course of the study, the PI or site staff must report to 
GSK local safety department within 24 hours of first becoming aware of the event in accordance 
with SOP_54834 Management of Adverse Event, Pregnancy Exposure, and Incident Reports 
from Human Subject Research.  
Per SOP 52214 (Pharmacovigilance Planning for Epidemiology and Health Outcomes human 
subject research), a Pharmacovigilance Plan (PVP) is required for research with and without 
safety-related objectives.   
 
Legal Basis for Processing Individual Human Data 
The authors confirm that study data is Individual Human Data (IHD) owned by GSK and that:  
The proposed use of the IHD is Study Use* as outlined in the patient consent.  

33 
 
* Study Use means - the use of IHD is as stated in the original study protocol and/or aligned 
with the informed consent form to answer the study objectives and satisfy regulatory 
requirements and learn more about the product studied and the disease/condition studied. 
This includes bringing the product to market or maintaining market access, which includes 
working with government agencies, insurers or health care payers and aiding GSK’s 
understanding of clinical efficacy, safety, or effectiveness of the product. 
8 
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS 
 
Target Audience 
GSK stakeholders will require the information generated by this study, as well as contribute to 
the published literature. The results will be disseminated externally via manuscripts or 
presentations. 
 
Study reporting and publications 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK site or other mutually agreeable 
location.  
GSK will also provide the investigator with the full summary of the study results. The 
investigator is encouraged to share the summary results with the study subjects, as 
appropriate.  
The results summary will be posted to the Clinical Study Register no later than 12 months after 
the last subject’s last visit (LSLV) or sooner if required by legal agreement, local law or 
regulation. In addition, a manuscript will be submitted to a peer-reviewed journal for 
publication within 18 months of LSLV. When manuscript publication in a peer- reviewed journal 
is not feasible, further study information will be posted to the GSK Clinical Study Register to 
supplement the results summary.  
A manuscript will be progressed for publication in the scientific literature if the results provide 
important scientific or medical knowledge. 
 
 

34 
 
9 
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infarction, lung cancer and death in COPD patients: a UK primary care study. Respir Med. 2010 
Nov;104(11):1691-9. 

36 
 
Rui T, Bian Y, Balwinder S, Liu Z, Wang T, Li G. Under diagnosis of COPD in high risk population in 
China American Journal of Respiratory and Critical Care Medicine 2014 189 (Meeting Abstracts) 
Sundh J, Janson C, Lisspers K, Stallberg B,Montgomery S. The dyspnoea, Obstruction, Smoking, 
Exacerbation (DOSE) index is predictive of mortality in COPD. Prim Care Respir J 2012;21(3):295-
301. 
Toy EL, Beaulieu NU, McHale JM, Welland TR, Plauschinat CA, Swensen A, et al. Treatment of 
COPD: relationships between daily dosing frequency, adherence, resource use, and costs. 
Respir Med. 2011 Mar;105(3):435-41. 
Wang C, Xu J, Yang L, Xu Y, Zhang X, Bai C, et al. Prevalence and risk factors of chronic 
obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national 
cross-sectional study. Lancet. 2018 Apr 28;391(10131):1706-1717. 
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Calverley PMA. Spirometric changes during exacerbations of COPD: a post hoc analysis of the 
WISDOM trial. Respir Res. 2018 Dec 13;19(1):251. 
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exacerbations of chronic obstructive pulmonary disease in CHINA (abstract). Proceedings of the 
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Med. 2019 May 29;19(1):102. 
10 APPENDICES 
 Appendix 1: SCHEDULE OF ACTIVITIES 
Procedure 
Baseli
ne  
Visit  
Dischar
ge 
follow-
up for 
admitte
d 
patients  
1-week 
follow up 
for non-
admitted 
patients 
Day 8+3  
(Telephon
e) 
3 months 
follow up ±7 
(Telephone) 
 
 
Notes 
Informed consent 
X 
 
 
 
 
Inclusion and exclusion 
criteria 
X 
 
 
 
 
Demography 
X 
 
 
 
 

37 
 
Full physical 
examination including 
height and weight 
X 
 
 
 
 
Co-morbidities 
X 
 
 
 
 
COPD diagnosed history X 
 
 
 
 
COPD exacerbation 
history in prior 12 
month 
X 
 
 
 
 
Current COPD disease 
condition (stable or 
acute) 
X 
 
 
 
 
Smoking history 
X 
 
 
 
 
Physician name (code) 
X 
 
 
 
a. will be collected 
from medical 
records (will not be 
collected from 
patients) 
COPD prescription 
X 
Xa 
Xb 
Xc 
a. COPD 
prescription when 
discharge 
b. the latest COPD 
prescription at 1-
week follow up 
c. the latest COPD 
prescription at 3-
month follow up 
Current COPD 
medication  
Xa 
 
X 
X 
a. within past 1 
month before 
baseline visit 
Prescription date, 
physician and hospital 
of current COPD 
medication  
 
 
 
Xa 
a. will be collected 
from medical 
records or 
patients’ recall (the 
physician’s  name 
will not be 
collected from 
patients) 
Spirometry 
X 
Xa 
 
 
a. the lung function 
can be collected 
before discharge if 
the patient's 

38 
 
disease is too 
serious 
DECAF score 
assessment (admitted 
patients)  
Xa 
 
 
 
a. can be assessed 
during 
hospitalization 
period 
Physician’s survey 
Xa 
 
 
 
a. to collect 
outpatients  
Patient’s survey and 
questionnaire 
X 
 
 
X 
1. Baseline period: 
Patient 
questionnaires 
include IPAQ, 
PHQ9, self-efficacy 
energy scale (GSE); 
baseline patient 
survey 
2. 3-month follow-
up period: patient 
questionnaires 
include self-
efficacy energy 
scale (GSE); follow-
up period patient 
survey 
CAT 
X 
X 
X 
X 
 
mMRC Dyspnea Scale 
X 
 
 
 
 
Socio-economic  
X 
 
 
 
 
Insurance details 
X 
 
 
 
 
Inhaler availability  
X 
 
 
 
 
Discharge time 
 
X 
 
 
 
COPD Clinic revisit 
times and reason 
 
 
Xa 
Xa 
a. If patient visits 
to clinic 
Frequency of COPD 
exacerbation between 
baseline visit and 3 
months follow up 
 
 
 
X 
 
Concomitant 
medication review 
X 
X 
X 
X 
 
AE review 
 
-------------------X------------------- 
*AE data will not 
be collected 
directly. A 
physician can 
document the 
adverse event or 

39 
 
concern reported 
by the patients. 
SAE review 
 
-------------------X------------------- 
*SAE data will not 
be collected 
directly. A 
physician can 
document the 
event or concern 
reported by the 
patients. 
 

40 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party 
copyright laws and therefore have been excluded.

41 
 
 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party 
copyright laws and therefore have been excluded.

42 
 
 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws 
and therefore have been excluded.

43 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws and 
therefore have been excluded.

44 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws and 
therefore have been excluded.

45 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws and 
therefore have been excluded.

46 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws 
and therefore have been excluded.

47 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws and 
therefore have been excluded.

48 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws and 
therefore have been excluded.

49 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws and 
therefore have been excluded.

50 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws and 
therefore have been excluded.

51 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws 
and therefore have been excluded.

52 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws 
and therefore have been excluded.

53 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws 
and therefore have been excluded.

54 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws and therefore have been 
excluded.

55 
 
 Appendix 6: sPVP and PVP APPROVAL FORM 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws and therefore 
have been excluded.

56 
 
Study-Specific Pharmacovigilance Plan (sPVP) 
 
Unique Identifier 
213550 
Full title of protocol 
COPD disease burden, patient characteristics, maintenance 
treatment patterns and factors influencing treatment decisions 
in China Tier 2 and Tier 3 hospitals 
Abbreviated title of protocol 
COPD maintenance treatment patterns in China 
Department 
China Medical Respiratory TA 
Study Accountable Person 
 
Type of Study                               
(tick type of study that 
applies) 
  Interventional (interaction) study with data collection - 
face-to-face or phone-based interviews  
  Interventional (interaction) study with data collection - 
digital or paper surveys  
 Non-interventional study with data collection where data 
source includes identifiable patient information (e.g., data 
extraction from medical records, existing registry) 
 Other, please describe: Low-interventional study with data 
collection where data source includes identifiable patient 
information (e.g., data extraction from medical records, existing 
registry) 
Study-Specific 
Pharmacovigilance Plan 
Approval Date 
24-Aug-2020  
 
Safety and Medical 
Governance (SMG) 
Representative: 
  
 
Revision Chronology:   
 
Version Date   
Document Type 
Change(s) since last version 
Enter original sPVP approval 
date 
Original 
n/a 
Enter amended sPVP 
approval date 
NA 
NA 
 
 
 
PPD
PPD

57 
 
sPVP Element 
Study-Specific Pharmacovigilance Plan (sPVP)  
(tick applicable statements) 
Supplier PV 
training 
 N/A – No supplier/vendor involved that could identify Human Safety 
Information (HSI) following exposure of GSK/ViiV products 
 Supplier/vendor PV training will be conducted using the agreed method 
and current, approved content, prior to beginning the study. Training will be 
completed annually and documented. 
Investigator 
and site staff 
PV training  
 N/A – No Investigator and/or site staff involved that could be in receipt of 
Human Safety Information (HSI) following exposure of GSK/ViiV products 
 Investigator and/or site staff PV training will be conducted using the 
agreed method and current, approved content, prior to beginning the study. 
Training will be completed annually and documented.  
Safety-
specific roles  
 SAP is responsible for the collection, reporting, and reconciliation process 
for HSI. 
 Supplier/vendor is responsible for the collection, reporting, and 
reconciliation process for HSI. 
HSI Collection 
Processes 
 The protocol includes details about collection of HSI, including all adverse 
reaction/event, following exposure to any GSK/ViiV product  
 
OR 
 
 The protocol includes the rationale for collection of specific types of 
adverse reaction/event (e.g. objectives of the study, the stage of the asset 
development, level of clinical oversight).  
 
Required response if second option is selected: 
 The rationale for the collection of data differs from minimum criteria, this 
has been approved by the Central Safety Department. 
 
HSI Reporting 
Processes 
Please select one of the following options 
 The protocol includes details about reporting of all HSI following exposure 
of GSK/ViiV products. 
 
OR 
 The protocol includes details about the rationale for reporting (e.g., 
objectives of the study, the stage of asset development, level of clinical 
oversight) targeted follow-up requirements 
AE, pregnancy 
exposure, and 
 GSK Global Adverse Event, Pregnancy Exposure, and Incident Reporting 
Form for Epidemiology and Health Outcome studies  

58 
 
sPVP Element 
Study-Specific Pharmacovigilance Plan (sPVP)  
(tick applicable statements) 
incident 
collection 
forms 
 Alternative collection form(s) will be utilized  
 (if ticked, please specify the form title here - e.g. standard clinical trial SAE 
form, Pregnancy Notification Form, and/or any additional study/product-
specific safety data collection form, if appropriate) 
Frequency of 
data review  
 N/A – No batch reviewing of the data.  
 Batch review will be conducted  
(if ticked, please specify the frequency of review) 
During the visit and follow-ups in this study, once AEs, pregnancy exposures 
is identified, the investigator will collect and report.   
Reviewing 
and reporting 
study results 
Specify review and timing for the communication of study results to SMG 
 
For serious related AE (SADR) or pregnancy exposure safety report sent to 
local PV team, the report would be forwarded to the global service provider 
(IQVIA) for their further processing to the drug safety headquarters (CSD) 
within 24 hours (the next working day in case of weekends); For non serious 
related AE (ADR), the report would be forwarded to the global service 
provider (IQVIA) for their further processing to the drug safety headquarters 
(CSD) within 5 calendar days. 
 
Interim study 
reports 
 N/A – No interim study reports are planned. 
 Interim study reports will be shared with the SERM product specialist / 
physician for review of the interim report safety data  
Reconciliation 
process 
 Reconciliation process defined in protocol  
 Reconciliation process defined in sPVP, please describe 
x Study manager is responsible for sending AE reconciliation form to local 
PV team monthly. 
x Local PV team will assist in forwarding the AE reconciliation form to the 
case management group (CMG), CMG is responsible for FKHFNLQJ. 
PVP 
monitoring 
process 
 SAP will review the sPVP elements and discuss during regular study team 
and/or supplier meetings to ensure the plan is working effectively.  
 Other, please describe 
Provision of 
final study 
report 
 Defined in protocol  
 Defined in sPVP, please describe 
x All serious and non-serious AEs, pregnancy exposures, and incidents 
related to any GSK product will be reported in the final report. 
x Detail table shells will be attached to the research analysis plan. 

59 
 
 
 
 
 
 
 
 
 
 
 
 
Study-specific Pharmacovigilance Plan (sPVP) 
Approval Page for: 
213550 
 
 
Approval 
 
I confirm that this sPVP is appropriate for the above study and has been completed 
in accordance with SOP 52214. 
 
Name 
Job Title or Role & Qualification 
Signature 
Date 
(dd-mmm-yyyy) 
 
 
 
 
 
 
 
 
 
Please forward this signed copy by e-mail to the Study Accountable Person and cc the sPVP mailbox: 
Epi_&_HO_PVP_Queries@gsk.com