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A matched-group study protocol to evaluate the implementation of an Integrated Care Pathway programme for chronic obstructive pulmonary disease in Singapore

Introduction The treatment of chronic obstructive pulmonary disease (COPD) involves different care providers across care sites. This fragmentation of care increases the morbidity and mortality burden, as well as acute health services use. The COPD-Integrated Care Pathway (ICP) was designed and implemented to integrate the care across different sites from primary care to acute hospital and home. It aims to reduce the prevalence of COPD among the population in the catchment, reduce risk of hospital admissions, delay or prevent the progression of the disease and reduce mortality rate by adopting a coordinated and multidisciplinary approach to the management of the patients’ medical conditions. This study on the COPD-ICP programme is undertaken to determine the impact on processes of care, clinical outcomes and acute care utilisation. Methods and analysis This will be a retrospective, pre-post, matched-groups study to evaluate the effectiveness of the COPD-ICP programme in improving clinical outcomes and reducing healthcare costs. Programme enrolees (intervention group) and non-enrolees (comparator group) will be matched using propensity scores. Administratively, we set 30% as our target for proportion admission difference between programme and non-programme patients. A sample size of 62 patients in each group will be needed for statistical comparisons to be made at 90% power. Adherence with recommended care elements will be measured at baseline and quarterly during 1-year follow-up. Risk of COPD-related hospitalisations as primary outcome, healthcare costs, disease progression and 1-year mortality during 1-year follow-up will be compared between the groups using generalised linear regression models. Ethics and dissemination This protocol describes the implementation and proposed evaluation of the COPD-ICP programme. The described study has received ethical approval from the NHG Domain Specific Review Board (DSRB Ref: 2013/01200). Results of the study will be reported through peer-review publications and presentations at healthcare conferences.


BACKGROUND
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic disease morbidity and mortality worldwide. The disease is a global health problem with a worldwide prevalence of 10.1%. [1] In Singapore, there are about 60,000 cases of COPD which constitute about one-fifth of all deaths. Moreover, COPD is the seventh principal cause of death and the seventh most common condition for hospitalisation. [2] The disease places a large financial burden on healthcare systems and society. A study conducted measured that the mean cost was approximately USD$9.9 million per year in Singapore, with inpatient admission being the major cost driver, contributing an average of USD$7.2 million per year. [3] The disease also accounts for high average length of stay (ALOS) and 30-day readmission rate.
Many of the patients who experienced repeated exacerbations are seen in the acute setting in Singapore. However, they can be appropriately managed at the secondary and/or primary care level, thereby freeing up tertiary resources for more advanced treatments, such as lung transplants and lung volume reduction surgeries. For patients discharged from the acute setting, more can be done to streamline and coordinate their care at the primary care levels. Early diagnosis and intervention efforts for at-risk individuals are also insufficient in the primary care setting as many GP clinics do not offer spirometry services. Furthermore, COPD patients in the community experience poor quality of life due to the lack of convenient access to pulmonary rehabilitation.  The programme adopts a coordinated and multi-disciplinary approach to the management of the patients' medical conditions. Dedicated case managers work with JurongHealth's multidisciplinary team of doctors, nurses, respiratory technologists, pharmacists, physiotherapists and medical social workers to develop a customised care plan for each patient, empower patients towards self-management through education and help coordinate referrals and patients' appointments across care sites.

Objective
This study is designed to evaluate the effect of the COPD-ICP programme on the following primary outcome measures: 1) Health services utilisation and cost; 2) 1-year mortality rate; 3) 30-day readmission rate. The impact on the care costs for COPD patients will also be investigated via economic-effectiveness analysis.
The secondary aims of this study include looking at the recommended care compliance and quality of life. Patients' perception of the extent to which the service is congruent with five of the Decision Support, Self-Management Support and Community will also be evaluated.

Methods/Design
Design A prospective, pre-post, matched-groups design will be implemented for this study. Such a design will be utilised instead of the randomised controlled trial design as the COPD-ICP programme has been implemented in JurongHealth for almost two years. Care resources may also be unnecessarily stretched if two care programmes (usual care and COPD-ICP) were run concurrently. In order to strengthen the evidence obtained from this study, a matched control group will also be formed from non-enrolees using methods described in later sections. Patients for this control group will be sourced from another healthcare cluster in Singapore. Primary outcome measures will then be compared between programme patients and this control group.

Study Setting
The setting for this study is Alexandra Hospital, an acute care hospital in Singapore managed by JurongHealth. The hospital provides a range of clinical services mainly for the population in the south-western region of Singapore. Since April 2012, the COPD-ICP programme has been used as the care model for all COPD patients seen in JurongHealth. For the purpose of this study evaluation, COPD patients seen at National Healthcare Group (NHG) and National Healthcare Group Polyclinics (NHGP) institutions will act as the control group database. The study period will also be fixed from Apr 2012 to Jul 2013. Patients are enrolled into the programme if they are 40 years old and above; are current or exsmokers; present with persistent (>3 months) or recurrent respiratory complaints compatible with COPD; have spirometry reading of FEV 1 / FVC < 70%; and showed no increase in FEV 1 > 15% above baseline value or >200 mL after bronchodilator administration. [5][6] Patients were excluded if they have illnesses other than COPD that was likely to result in death within 2 years;

Inclusion and exclusion criteria
Bronchial asthma, Bronchiectasis, Active Pulmonary Tuberculosis, and uncontrolled heart diseases such as unstable angina, heart failure refractory to treatment (New York Heart Association class III or IV). [5,7] Patients who have been enrolled into other care programmes (such as The Airways Programme, TAP) are also excluded.

Intervention
The COPD-ICP programme classifies each patient enrolled into the programme based on the Patient Group Classification from updated GOLD guidelines (see Figure 1). [5][6] This programme has a customised set of interventions and right-siting plans for patients in each of the four groups. Group A patients exhibit less symptoms and can be managed at the primary care setting in this programme. Group B patients exhibit more symptoms and present an opportunity to be managed well by primary care doctors to move into Group A with appropriate drug therapy in this programme. [8][9][10][11][12] Group C patients exhibit less symptoms but have a more severe airflow limitation. Patients belonging to this group are currently admitted to the hospital due to exacerbations but those with stabilised conditions can be managed at the Specialist Outpatient Clinics (SOCs) at 6 monthly interval. Group D patients exhibit more symptoms and are the target of Advance Care Planning (ACP) and home care service in this programme. [13][14] F o r p e e r r e v i e w o n l y 8 There are 6 recommended care elements for Group A and Group B patients, namely; smoking cessation, patient education, drug optimisation, influenza vaccination, Body Mass Index (BMI) assessment and COPD Assessment Test (CAT) score measurement. [15][16] There are two additional ones recommended for the COPD patients classified into Group C and D category, namely; home oxygen whenever relevant and ACP when patients are ready for the conversation (Table 1 and 2).   9 In order to reduce the risk of deterioration in disease condition, five standards of care along the care continuum model has been adopted for the programme. This involves collaboration with healthcare providers from different care settings to close the current gaps in service provision (Table 3). Training courses have also been organised to upgrade GPs' and polyclinic doctors' knowledge in managing COPD patients. The sessions are also an avenue for the primary care physicians to obtain specialist advice if necessary. With a reduction in deterioration incidences, resources at the acute hospital level will be conserved while the prognosis of patients will be improved. Table 3 Five Standards of care with care continuum model

Prevention of COPD
Primary and secondary prevention strategies will be implemented. Primary prevention strategies such as social marketing campaigns and lifestyle modifications targeting the general population can help reduce smoking incidence rates. Common secondary prevention strategies, such as patient education and smoking cessation counseling can minimise the impact of the disease.  10 The primary outcome measures are at the system level. They include 1) health services utilisation and cost; 2) 1-year mortality rate; 3) 30-day readmission rate.
Healthcare utilisation and cost Hospital costs will be estimated by multiplying the diagnosis-related group (DRG) cost per patient day by the inpatient length of stay (LOS). DRG average cost estimates include manpower, room, procedure, medication and allocated fixed costs. The average cost by DRG will be provided by the finance department. Direct medical costs for emergency department (ED), specialist and primary care visits will be derived by multiplying the standardised unit cost by the number of visits to each level of care. For primary care visits, costs per visit estimates for both acute and chronic conditions will be used. Unit cost estimates include manpower, medication and allocated fixed cost which will be obtained from the finance department. [17] The administrative cost of operating the COPD-ICP programme will be derived from its financial statement.
1-year mortality rate The 1-year mortality rate for each enrolment group refers to the proportion of patients who died (all causes) before the 1-year post-baseline time point.

30-day readmission rate
The proportion of patients who were discharged from either an NHG or JurongHealth institution and re-admitted (all causes) to the same hospital within 30 days of their discharge date.  11 In addition, the following measure will be used to gauge the level of achievement of the study's secondary aims.
CAT score This is an eight-question health survey used to measure COPD control in individuals. Scores range from 0 to 40 and lower scores indicate better control. The quality of life of the patients is measured using the CAT at baseline and during their follow-up visits within the first year of enrolment. It is used to measure the impact of COPD on a patient's wellbeing and daily life. A CAT score difference of 2 or more (or >10%) suggests clinically significant changes in the quality of life. [18] The CAT score difference is taken as the difference between the baseline and the best reading within 1 year. This outcome is only available for programme enrolees.

Patient Assessment of Care for Chronic Conditions (PACIC) score
This is a twenty-question survey used to measure the patients' perception on the congruency of the service to five aspects of the Chronic Care Model. [19] These aspects have been widely recognised as the key to improving quality and experience of chronic disease care. [20]

Data collection
The parameters and outcomes of interest for which data shall be collected have been summarised in 3. NHG administrative databases: Source of data for healthcare utilisation cost.

COPD patients will be identified based on the International Classification of Diseases Tenth
Revision (ICD-10-AM) diagnostic codes (J40.xx and J47.xx). All data will be collected for the COPD-ICP enrolees over 1 year pre-enrolment and 1 year follow up post-enrolment (3 monthly interval) and over a 1-year period for non-enrolees. They include patient demographics and socio-economic indicators (Age, race, gender, nationality, postal code, Medisave/Medifund, Medical social worker referral); programme enrolment date; smoking history; medication; comorbidities; severity of COPD (GOLD classification) and quality of life assessment (CAT Table 4 Overall of assessments used in COPD-ICP implementation study  13 score). The Patient Assessment of Care for Chronic Conditions (PACIC) survey will be administered during baseline and every follow-up visit.

Sample size
Using a mean CAT scores difference of 2.1 as the threshold for clinical significance,standard deviation of 6.9 (approximated from routinely collected data) and ratio between groups of 1, a sample size of 115 patients in each group will be needed for statistical comparisons to be made at 90% power. Hence, 200 enrolees (to account for missing data) will be sampled from amongst those who were enrolled into the programme during the study period and their matching controls will be drawn from the control group database who have at least one visit to NHG or NHGP institutions during the study period.

Statistical Analysis
Propensity Score Matching Since patients are enrolled into the programme based on the institution which they were seen in, there is likely to be imbalance in baseline characteristics between enrolees and non-enrolees.
Matching will be performed via propensity scores. [21] These scores will be derived from a multivariate logistic regression with programme enrolment as the dependent variable and the following covariates: age, gender, race, hospital, ward class, number of hospitalisation or emergency attendances in the past year, comorbid conditions and use of medication.
Patient baseline characteristics from both enrolee and the matched-control groups will be described with mean and standard deviation for continuous variables and number and percentage  14 for categorical variables. Differences between COPD-ICP enrolees and non-enrolees will be compared using chi-square statistics for categorical variables and Wilcoxon rank sum tests for continuous variables.
Comparing the primary outcomes Healthcare utilisation & cost will be compared using a gamma regression while mortality and 30day readmission will be compared with a logistic regression. [22] Since certain unmeasured clinical characteristics may influence whether a patient is enrolled into the programme and their outcome directly, there is a need to reduce systematic bias from these unmeasured risk factors.
Hence, the direct distance between the postal code of patients' residential address and Alexandra Hospital's postal code will be used as an instrumental variable for programme enrolment in each of the regression models. [23] This variable is considered to be a good instrument for programme enrolment as it should generally be uncorrelated with most clinical outcomes but is correlated with whether the patient is enrolled into the programme (patients with longer direct distances from Alexandra Hospital are more likely to be seen in NHG/NHGP institution).

CAT score comparison
To evaluate the quality of life improvement of the COPD patients using CAT score as the outcome, the change in CAT score over the 1-year post-enrolment time frame will be examined using longitudinal modelling.

PACIC score
To evaluate the congruency of the COPD-ICP programme to the CCM, the average PACIC score for programme enrolees will be computed and benchmarked with PACIC results of other

Economic-effectiveness Analysis
To assess the economic effectiveness of the COPD-ICP to the hospital, a Markov model will be developed to simulate patient movement between patient classifications. [24] Specific parameters (cost incurred and transition probabilities) of the model will be estimated from the data. The five- year healthcare utilisation cost and mortality rate of each programme arm will be computed.
Probability sensitivity analysis will also be used to assess the robustness of analysis results. [25] Software All analyses will be conducted using Stata version 12 and Treeage Pro 2011.

Discussion
In designing the COPD-ICP programme, three key principles have been adopted: right-siting, integration and patient-centredness. It also involves the five standards of care: COPD prevention, further support JurongHealth to launch and maintain the COPD-ICP programme.

Benefits of study evaluation
The rationale behind this programme evaluation stems from the motivation to bolster support for the programme. In this evaluation, two outcomes -30-day re-admission rate and CAT score will be used by the team to identify any care gaps, so as to improve the COPD-ICP programme. In addition, two other outcomes measure -healthcare utilisation cost and mortality rate are indicators used to assess the practicality of sustaining the programme. This study can also potentially add to the mounting evidence in support of integrated care in healthcare literature. This study design has several strengths. The PACIC survey will be used assess patients' experience of care which they received. This is in line with the organisation's aim to deliver patient-centred care.

Strengths of study design
The choice of the matched-control group patients using propensity scores will replicate the balance in baseline characteristics between compared cohorts achieved through randomisation.
This will in turn reduce the effect of selection bias due to the lack of randomisation.
[30] This step will be vital for making valid conclusions from the economic effectiveness analysis. By introducing direct distance between residential address and Alexandra Hospital as an instrument variable for programme status, systematic bias introduced by unmeasured baseline characteristics will also be attenuated.
By looking at several outcomes (economic-effectiveness, clinical outcomes, patients' experience), this study also allows the COPD-ICP team to identify areas in the programme which requires a change of implementation approach.

Limitations of the study
The study design may have some limitations. Firstly, the data collection process does not account for both enrolees and non-enrolees who choose to have their follow-up medical appointments at non-NHG/NHGP/JurongHealth institutions. Such non-compliance may potentially skew results.
In addition, the assumption that direct distance is uncorrelated with unmeasured confounders may not be true. It is still unclear whether direct distance is correlated with household income which influences both outcome (more resources to control disease) and baseline characteristics.
However, these limitations affect the evaluation of the programme only but not the quality of care provided at any institution. As a whole, the COPD-ICP programme serves to equip primary care partners with the adequate knowledge and skills for managing stable COPD patients and to right-site patients in order to provide excellent and appropriate care while optimising available healthcare resources. We believe that this evaluation study can provide an evidence-based assessment of the impact and economic-effectiveness of the COPD-ICP programme. The lessons learnt from this study may also be extended to the evaluations of other ICP programmes that JurongHealth is implementing in the near future.

Ethics and Dissemination
This study has received ethical approval from the NHG Domain Specific Review Board (DSRB Ref: 2013/01200).

Confidentiality
Names and National Registration Identity Card (NRIC) number of patients will be removed and replaced with unique study IDs after merging of datasets. The link between these study IDs and the NRIC number it represents will only be known to the principal investigator of the study.

Introduction
The treatment of chronic obstructive pulmonary disease (COPD) involves different care providers across care sites. This fragmentation of care increases the morbidity and mortality burden, as well as acute health services use. The COPD-Integrated Care Pathway (ICP) was designed and implemented to integrate the care across different sites from primary care to acute hospital and home. It aims to reduce the prevalence of COPD among the population in her catchment, reduce risk of hospital admissions, delay or prevent the progression of the disease and reduce mortality rate by adopting a coordinated and multi-disciplinary approach to the management of the patients' medical conditions. This study on the COPD-ICP programme is undertaken to determine the impact on processes of care, clinical outcomes, and acute care utilisation.

Methods and analysis
This will be a retrospective, pre-post, matched-groups study to evaluate the effectiveness of COPD-ICP programme in improving clinical outcomes and reducing healthcare costs.
Programme enrolees (intervention group) and non-enrolees (comparator group) will be matched using propensity scores. Administratively, we set 30% as our target for proportion admission difference between programme and non-programme patients. A sample size of 56 patients in each group will be needed for statistical comparisons to be made at 90% power. Adherence with recommended care elements will be measured at baseline and quarterly during one year followup. Risk of COPD-related hospitalisations as primary outcome, healthcare costs, disease  3 progression, and one-year mortality during one-year follow-up will be compared between the groups using generalised linear regression models.

Ethics and dissemination
This protocol describes the implementation and proposed evaluation of the COPD-ICP programme. The described study has received ethical approval from the NHG Domain Specific Review Board (DSRB Ref: 2013/01200). Results of the study will be reported through peerreview publications and healthcare conferences presentation.

Key message
This study aims to evaluate the effectiveness of the programme in improving adherence with recommended processes of care, and lowering COPD-related hospitalisation and inpatient costs.
This study will also compare the one-year mortality rate and disease progression rate between enrolees and non-enrolees. This study will use CAT score to measure COPD control in patients and Patient Assessment of Chronic Illness Care (PACIC) score to measure patients' experience of care congruent to the Chronic Care Model.

Strengths and limitation of this study
This study will use a retrospective, pre-post, matched-groups design to evaluate the effectiveness of the programme in terms of adherence with processes of care, clinical outcomes, healthcare costs, and quality of life. It is envisioned that through this study, the COPD-ICP team will be able to identify potential gaps in the programme implementation and design, and implement necessary changes to improve care. This is in line with the organisation's aim to deliver patient-centred care.  This study will use propensity score matching to reduce selection bias due to the lack of randomisation.

BACKGROUND
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic disease morbidity and mortality worldwide. The disease is a global health problem with a worldwide prevalence of 10.1%. [1] In Singapore, COPD is the seventh principal cause of death and the seventh most common condition for hospitalisation. [2] COPD patients with complications spent 8.5 days or 69% longer in hospital and accounted for the high 30-day readmission rate. [3][4] The COPD 30day readmission in JurongHealth is around 30% which is higher than the all-cause national 30day readmission rate of 11.6% and other condition-specific readmission rates. [5] The GOLD international standards for COPD advise spirometry for the gold standard for accurate and repeatable measurement of lung function. [6] However, in Singapore, most solo general practice (GP) clinics do not offer spirometer services necessary for early diagnosis of COPD and for the staging of COPD severity to enable appropriate disease management. Patients with COPD in the community experience poor quality of life due to lack of convenient access to pulmonary rehabilitation. [7] Therefore, most patients are diagnosed in the acute care setting and those who experienced repeated exacerbations also obtain care in the specialist outpatient settings.   The programme adopts a coordinated and multi-disciplinary approach to the management of the patients' medical conditions. Case managers work with JurongHealth's multi-disciplinary team of doctors, nurses, respiratory technologists, pharmacists, physiotherapists and medical social workers to develop a customised care plan for each patient, empower patients towards selfmanagement through education, and help coordinate referrals and patients' appointments across care sites.
The current scope of our study will focus on the evaluation of the hospital-based segment of the ICP programme. We will use propensity-score matching method to select a suitable comparator group. Specifically, the aim of our study will be to assess whether the intervention group compared to comparator group has 1) better adherence to the recommended processes of care; 2) lower risk of COPD-related hospitalisation as our primary outcome; 3) lower overall healthcare and COPD-related inpatient costs; 4) slower disease progression; and 5) lower one-year mortality rate. We will use PACIC score to measure patients' experience of chronic care delivery in congruence to the Chronic Care Model (CCM). [9] In addition, we will also use CAT score to measure COPD control and hence the quality of life of patients with COPD. Our study will focus on the second, third and fourth objectives of the programme as written above.

The Regional Healthcare System
In Singapore, public healthcare is provided by six regional healthcare systems (RHSs): Alexandra Health, Eastern Health Alliance, National Healthcare Group (NHG), National University Health System (NUHS), JurongHealth, and Singapore Health Services (SHS).
Together, these RHSs provide 80% of all acute care service. The government primary care clinics under NHG and SHS provide approximately 20% of primary care services consumed. Figure 1 shows the inclusion and exclusion criteria for patients' enrolment into the COPD-ICP programme. [10][11] We will exclude patients who have medical conditions other than COPD that are likely to result in death within the next two years.

Target Patient
We classify each patient enrolled into the programme based on the Patient Group Classification from updated GOLD guidelines ( Figure 2). [10][11] Intervention With the implementation of the programme, care plans are designed to cater to each patient's disease severity. Patients are followed up by case managers regularly to ensure that the care elements as mentioned above are strictly adhered to. Case managers will also call the patient 48 hours post discharge to reinforce patient education and drugs optimisation, where they play a pivotal role in linking patients to community resources. Hence, with the coordination by case managers, the programme has made care delivery a more seamless and integrated process as compared to when such an initiative is absent.

Evaluation Design
A retrospective pre-post, matched-groups design will be implemented for this study. Such a design will be utilised instead of the randomised controlled trial design as the COPD-ICP programme has been implemented in JurongHealth for almost two years. Care resources may also be unnecessarily stretched if two care programmes (usual care and COPD-ICP) were run concurrently.
The study cohort will include individuals diagnosed with COPD who had at least one Specialist  Patients in the intervention group will be sampled from programme patients in the COPD registry who received care from JurongHealth from Apr 2012 to Dec 2013. A comparator group will be formed from non-enrolees using matching method described in later sections. Patients for the comparator group will be sampled from non-programme patients in the COPD registry who received care from non-JurongHealth institutions from Apr 2012 to Dec 2013. All data will be collected over one-year pre-enrolment and one-year follow up post-enrolment (three-month interval) for enrolees, and over one-year period for non-enrolees. The outcomes will be compared between enrolees and non-enrolees ( Figure 1).

Sample size
Administratively, we set 30% as our target for proportion admission difference between programme and non-programme patients. Thus, a sample size of 51 patients in each group will be needed for statistical comparisons to be made at 90% power. Hence, 56 enrolees (to account for 10% missing data) will be sampled from amongst those who were enrolled into the programme during the study period and their matching group will be drawn from the comparator group COPD management registry.

Data Sources and Data
The three main sources of data are (1) COPD Registry: patient demographics; clinical information and outcome variables for both enrolees and non-enrolees; (2) Patient Case Covariates include patient demographics and socio-economic indicators (Age, race, gender, nationality, Medisave/Medifund and Medical social worker referral); programme enrolment date; smoking history; medication; comorbidities; severity of COPD (GOLD classification) and CAT score.
The parameters and outcomes of interest for which data shall be collected have been summarised in Table 3.

Study Outcomes
Hospital admissions and Healthcare costs The primary outcome of this study is hospital admission. Hospital admission refers to inpatient episodes at acute care hospital managed by three regional health clusters (JurongHealth, NHG, and NUHS). Total annual healthcare costs refer to the cost of resources utilised at the primary care clinics, emergency departments, specialist outpatient clinics, and inpatient wards of these regional health clusters. To define specific COPD-related hospitalisations and inpatient costs, we have adopted the COPD-related hospitalisation ICD-10-codes used in . [12] Disease progression and one-year mortality rate Different medications are used during different disease progression stages. [10] Due to the absence of GOLD guidelines in measuring disease progression, we will utilise medication usage to determine the disease progression of patients with COPD. This will be compared between the intervention group and the comparator group. One-year mortality rate is defined as the proportion of patients who died (all causes) during one-year follow up for both intervention and comparator groups. Adherence with recommended processes of care and PACIC score We will monitor the adherence with the recommended key care elements for Group A, B, C and D patients (Table 1) at baseline and three-month interval. In addition, we will use PACIC score to measure patients' experience of chronic care delivery. PACIC score is a 20-question survey used to measure patients' perception on the congruency of the service to the Chronic Care Model (CCM). [9] CCM is a guideline which recognises six aspects as key to improving quality of chronic disease management. [9,13] The score obtained from PACIC assessment tool will allow us to assess if the COPD-ICP programme is aligned with CCM.

Quality of life
As there is no locally validated tool to measure quality of life in patients with COPD and the COPD-specific version of St. George's Respiratory Questionnaire is too long to administer, we will use CAT score, which is an eight-question health survey, to measure COPD control in individuals. [14] Scores range from 0 to 40 and lower scores indicate better control. Due to its strong correlation with the COPD-specific version of the St. George's Respiratory Questionnaire, it has been used as an alternative tool for assessing quality of life of patients with COPD. [14,[15][16][17][18] Enrolees' CAT score will be measured at baseline and during their follow-up visits within the first year of enrolment. A CAT score difference of 2 or more (or >10%) suggests clinically significant changes in the quality of life. [19] The CAT score difference is taken as the difference between the baseline and the best reading within 1 year. This outcome is only available for programme enrolees as CAT score is not routinely collected for non-enrolees. Key recommended processes of care (Table 1) will be monitored quarterly to track the adherence and progress of the COPD-ICP programme. Patient baseline characteristics from both enrolees and non-enrolees will be described with mean and standard deviation for continuous variables and number and percentage for categorical variables. Differences between COPD-ICP enrolees and non-enrolees will be compared using chi-square statistics for categorical variables and

Statistical Analysis
Wilcoxon rank sum tests for continuous variables.
Since patients are enrolled into the programme based on the institution which they were seen in, there is likely to be imbalance in baseline characteristics between enrolees and non-enrolees.
Hence, we will use propensity score matching to balance the baseline characteristics across enrolees and non-enrolees. [20] We will start off with estimating the propensity score, which is the conditional probability of each patient enrolling into the programme given their baseline characteristics, by using multivariate logistic regression. [20] Covariates to be included in the regression are: age, gender, race, hospital, subsidy term, the number of hospitalisation or emergency attendances in the past year, number and severity of comorbid conditions and COPD severity based on medication use. We will then form pairs of enrolee and non-enrolee by using the caliper matching method, within a range of 0.2 of the standard deviation of propensity score. [21] Hospital admissions, healthcare costs and mortality We will compare healthcare costs using generalised linear model with log link and gamma distribution. For odds of hospital admission and one-year mortality, we will compare using logistic regression. [22] CAT score comparison To evaluate the quality of life improvement of the patients with COPD using CAT score as the outcome, the change in CAT score over the 1-year post-enrolment time frame will be examined.
A paired-sample t-test will be used to compare baseline CAT score and the best achieved CAT score over the 1-year time frame.

PACIC score
To evaluate patients' perception on the programme's congruency with CCM, the average PACIC score for programme enrolees will be computed and benchmarked with PACIC results of other integrated care programmes in present literature that have showed substantial congruency to the CCM. At present, recommended cut-offs for CCM concordance is set at ≥3.5 in a study with veterans and at ≥4 in another study with older adults at risk of high healthcare costs. [23][24].

Software
All analyses will be conducted using Stata version 12.

DISCUSSION
In designing the COPD-ICP programme, three key principles have been adopted: right-siting, integration and patient-centeredness. It also involves the five standards of care: COPD  The rationale behind this programme evaluation stems from the motivation to bolster support for the programme and to identify care gaps for improvement. As such, adherence with processes of care and outcomes such as risk of hospitalisation, CAT score and PACIC score will be used by the team to identify any care gaps, so as to improve the COPD-ICP programme. In addition, healthcare costs, disease progression and one-year mortality rate will also be used to assess the practicality of sustaining the programme. Furthermore, this study can also potentially add to the mounting evidence in support of integrated care in healthcare literature.
This study protocol has several strengths. The PACIC survey will be used to assess patients' experience of the congruency of care to CCM. This is in line with the organisation's aim to deliver patient-centred care.  16 The choice of the matched group patients using propensity scores will replicate the balance in baseline characteristics between compared cohorts achieved through randomisation. This will in turn reduce the effect of selection bias due to the lack of randomisation. [21] This step will be vital for making valid conclusions from the economic effectiveness analysis.
This study protocol is limited in several areas. Firstly, even though we will use propensity score matching to reduce the selection bias due to non-randomisation, there might be unmeasured confounders which can affect our results. Secondly, the data collection process will only account for both enrolees and non-enrolees who choose to have their follow-up medical appointments at JurongHealth, NHG and NUHS. Due to non-captive nature of the healthcare system in Singapore, patients in Singapore are free to choose healthcare providers outside these clusters on an episodic basis. Hence, such exclusion might lead to underestimation. However, these limitations affect the evaluation of the programme only but not the quality of care provided at any institution.
In conclusion, the COPD-ICP programme serves to equip primary care partners with the adequate knowledge and skills for managing stable patients with COPD and to right-site patients in order to provide excellent and appropriate care while optimising available healthcare resources. With the support from case managers, the programme does so by discharging patients to primary care doctors so that the clinically stable patients can be managed without the need to see a specialist if not clinically necessary. We believe that this evaluation study can provide an evidence-based assessment of the impact and effectiveness of the COPD-ICP programme. The lessons learnt from this study will be fed back to the COPD-ICP programme team and be useful in informing the design evaluations of other ICP programmes nationally.

ETHICS AND DISSEMINATION
This protocol describes the implementation and proposed evaluation of the COPD-ICP programme. The described study has received ethical approval from the NHG Domain Specific Review Board (DSRB Ref: 2013/01200). Results of the study will be reported through peerreview publication and healthcare conferences presentation.

CONFIDENTIALITY
Names and National Registration Identity Card (NRIC) number of patients will be removed and replaced with unique study IDs after merging of datasets. The link between these study IDs and the NRIC number it represents will only be known to the principal investigator of the study.

DATA ACCESS
Access rights to the data will be given to the Clinical Analytics team in JurongHealth, the project manager and the clinician lead of the COPD-ICP programme.

COMPETING INTERESTS
The authors declare that they have no competing interests.

Methods and analysis
This will be a retrospective, pre-post, matched-groups study to evaluate the effectiveness of COPD-ICP programme in improving clinical outcomes and reducing healthcare costs.
Programme enrolees (intervention group) and non-enrolees (comparator group) will be matched using propensity scores. Administratively, we set 30% as our target for proportion admission difference between programme and non-programme patients. A sample size of 56 patients in each group will be needed for statistical comparisons to be made at 90% power. Adherence with recommended care elements will be measured at baseline and quarterly during one year followup. Risk of COPD-related hospitalisations as primary outcome, healthcare costs, disease progression, and one-year mortality during one-year follow-up will be compared between the groups using generalised linear regression models.

Ethics and dissemination
This protocol describes the implementation and proposed evaluation of the COPD-ICP programme. The described study has received ethical approval from the NHG Domain Specific Review Board (DSRB Ref: 2013/01200). Results of the study will be reported through peerreview publications and healthcare conferences presentation.

Keywords
Chronic Obstructive Pulmonary Disease, Integrated Care Pathway, Evaluation, Propensity Score Matching

Key message
This study aims to evaluate the effectiveness of the programme in improving adherence with recommended processes of care, and lowering COPD-related hospitalisation and inpatient costs.
This study will also compare the one-year mortality rate and disease progression rate between enrolees and non-enrolees. This study will use CAT score to measure COPD control in patients and Patient Assessment of Chronic Illness Care (PACIC) score to measure patients' experience of care congruent to the Chronic Care Model.

Strengths and limitation of this study
This study will use a retrospective, pre-post, matched-groups design to evaluate the effectiveness of the programme in terms of adherence with processes of care, clinical outcomes, healthcare costs, and quality of life. It is envisioned that through this study, the COPD-ICP team will be able to identify potential gaps in the programme implementation and This study will use propensity score matching to reduce selection bias due to the lack of randomisation.

BACKGROUND
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic disease morbidity and mortality worldwide. The disease is a global health problem with a worldwide prevalence of 10.1%. [1] In Singapore, COPD is the seventh principal cause of death and the seventh most common condition for hospitalisation. [2] COPD patients with complications spent 8.5 days or 69% longer in hospital and accounted for the high 30-day readmission rate. [3][4] The COPD 30day readmission in JurongHealth is around 30% which is higher than the all-cause national 30day readmission rate of 11.6% and other condition-specific readmission rates. [5] The GOLD international standards for COPD advise spirometry for the gold standard for accurate and repeatable measurement of lung function. [6] However, in Singapore, most solo general practice (GP) clinics do not offer spirometer services necessary for early diagnosis of COPD and for the staging of COPD severity to enable appropriate disease management. Patients with COPD in the community experience poor quality of life due to lack of convenient access to pulmonary rehabilitation. [7] Therefore, most patients are diagnosed in the acute care setting and those who experienced repeated exacerbations also obtain care in the specialist outpatient settings.
In response to the need for a cost-effective care model, JurongHealth launched a COPD Integrated Care Pathway (COPD-ICP) programme in April 2012. This was funded by the The current scope of our study will focus on the evaluation of the hospital-based segment of the ICP programme. We will use propensity-score matching method to select a suitable comparator group. Specifically, the aim of our study will be to assess whether the intervention group compared to comparator group has 1) better adherence to the recommended processes of care; 2) lower risk of COPD-related hospitalisation as our primary outcome; 3) lower overall healthcare and COPD-related inpatient costs; 4) slower disease progression; and 5) lower one-year mortality rate. We will use PACIC score to measure patients' experience of chronic care delivery in congruence to the Chronic Care Model (CCM). [9] In addition, we will also use CAT score to measure COPD control and hence the quality of life of patients with COPD. Our study will focus on the second, third and fourth objectives of the programme as written above.

METHODS/DESIGN The Regional Healthcare System
In Singapore, public healthcare is provided by six regional healthcare systems (RHSs): Alexandra Health, Eastern Health Alliance, National Healthcare Group (NHG), National University Health System (NUHS), JurongHealth, and Singapore Health Services (SHS).
Together, these RHSs provide 80% of all acute care service. The government primary care clinics under NHG and SHS provide approximately 20% of primary care services consumed. Figure 1 shows the inclusion and exclusion criteria for patients' enrolment into the COPD-ICP programme. [10][11] We will exclude patients who have medical conditions other than COPD that are likely to result in death within the next two years.

Target Patient
We classify each patient enrolled into the programme based on the Patient Group Classification from updated GOLD guidelines ( Figure 2). [10][11] Intervention  Table 2).
With the implementation of the programme, care plans are designed to cater to each patient's disease severity. Patients are followed up by case managers regularly to ensure that the care elements as mentioned above are strictly adhered to. Case managers will also call the patient 48 hours post discharge to reinforce patient education and drugs optimisation, where they play a pivotal role in linking patients to community resources. Hence, with the coordination by case managers, the programme has made care delivery a more seamless and integrated process as compared to when such an initiative is absent.

Evaluation Design
A retrospective pre-post, matched-groups design will be implemented for this study. Such a design will be utilised instead of the randomised controlled trial design as the COPD-ICP programme has been implemented in JurongHealth for almost two years. Care resources may also be unnecessarily stretched if two care programmes (usual care and COPD-ICP) were run concurrently.
The study cohort will include individuals diagnosed with COPD who had at least one Specialist Outpatient Visit (SOC) record in COPD Registry from Apr 2012 to Dec 2013. For our study, we will use the same inclusion and exclusion selection criteria as those for the COPD-ICP programme enrolment (Figure 1). Patients with COPD will be identified based on the  Patients in the intervention group will be sampled from programme patients in the COPD registry who received care from JurongHealth from Apr 2012 to Dec 2013. A comparator group will be formed from non-enrolees using matching method described in later sections. Patients for the comparator group will be sampled from non-programme patients in the COPD registry who received care from non-JurongHealth institutions from Apr 2012 to Dec 2013. All data will be collected over one-year pre-enrolment and one-year follow up post-enrolment (three-month interval) for enrolees, and over one-year period for non-enrolees. The outcomes will be compared between enrolees and non-enrolees ( Figure 1).

Sample size
Administratively, we set 30% as our target for proportion admission difference between programme and non-programme patients. Thus, a sample size of 51 patients in each group will be needed for statistical comparisons to be made at 90% power. Hence, 56 enrolees (to account for 10% missing data) will be sampled from amongst those who were enrolled into the programme during the study period and their matching group will be drawn from the comparator group COPD management registry.

Data Sources and Data
The three main sources of data are ( Covariates include patient demographics and socio-economic indicators (Age, race, gender, nationality, Medisave/Medifund and Medical social worker referral); programme enrolment date; smoking history; medication; comorbidities; severity of COPD (GOLD classification) and CAT score.
The parameters and outcomes of interest for which data shall be collected have been summarised in Table 3.

Study Outcomes
Hospital admissions and Healthcare costs The primary outcome of this study is hospital admission. Hospital admission refers to inpatient episodes at acute care hospital managed by three regional health clusters (JurongHealth, NHG, and NUHS). Total annual healthcare costs refer to the cost of resources utilised at the primary care clinics, emergency departments, specialist outpatient clinics, and inpatient wards of these regional health clusters. To define specific COPD-related hospitalisations and inpatient costs, we have adopted the COPD-related hospitalisation ICD-10-codes used in . [12] Disease progression and one-year mortality rate Different medications are used during different disease progression stages. [10] Due to the absence of GOLD guidelines in measuring disease progression, we will utilise medication usage to determine the disease progression of patients with COPD. This will be compared between the intervention group and the comparator group. One-year mortality rate is defined as the proportion of patients who died (all causes) during one-year follow up for both intervention and comparator groups.
Adherence with recommended processes of care and PACIC score  12 We will monitor the adherence with the recommended key care elements for Group A, B, C and D patients (Table 1) at baseline and three-month interval. In addition, we will use PACIC score to measure patients' experience of chronic care delivery. PACIC score is a 20-question survey used to measure patients' perception on the congruency of the service to the Chronic Care Model (CCM). [9] CCM is a guideline which recognises six aspects as key to improving quality of chronic disease management. [9,13] The score obtained from PACIC assessment tool will allow us to assess if the COPD-ICP programme is aligned with CCM.

Quality of life
As there is no locally validated tool to measure quality of life in patients with COPD and the COPD-specific version of St. George's Respiratory Questionnaire is too long to administer, we will use CAT score, which is an eight-question health survey, to measure COPD control in individuals. [14] Scores range from 0 to 40 and lower scores indicate better control. Due to its strong correlation with the COPD-specific version of the St. George's Respiratory Questionnaire, it has been used as an alternative tool for assessing quality of life of patients with COPD. [14,[15][16][17][18] Enrolees' CAT score will be measured at baseline and during their follow-up visits within the first year of enrolment. A CAT score difference of 2 or more (or >10%) suggests clinically significant changes in the quality of life. [19] The CAT score difference is taken as the difference between the baseline and the best reading within 1 year. This outcome is only available for programme enrolees as CAT score is not routinely collected for non-enrolees.

Statistical Analysis
Key recommended processes of care (Table 1) will be monitored quarterly to track the adherence and progress of the COPD-ICP programme. Patient baseline characteristics from both enrolees and non-enrolees will be described with mean and standard deviation for continuous variables and number and percentage for categorical variables. Differences between COPD-ICP enrolees and non-enrolees will be compared using chi-square statistics for categorical variables and Wilcoxon rank sum tests for continuous variables.
Since patients are enrolled into the programme based on the institution which they were seen in, there is likely to be imbalance in baseline characteristics between enrolees and non-enrolees.
Hence, we will use propensity score matching to balance the baseline characteristics across enrolees and non-enrolees. [20] We will start off with estimating the propensity score, which is the conditional probability of each patient enrolling into the programme given their baseline characteristics, by using multivariate logistic regression. [20] Covariates to be included in the regression are: age, gender, race, hospital, subsidy term, the number of hospitalisation or emergency attendances in the past year, number and severity of comorbid conditions and COPD severity based on medication use. We will then form pairs of enrolee and non-enrolee by using the caliper matching method, within a range of 0.2 of the standard deviation of propensity score. [21] Hospital admissions, healthcare costs and mortality We will compare healthcare costs using generalised linear model with log link and gamma distribution. For odds of hospital admission and one-year mortality, we will compare using logistic regression. [22] CAT score comparison To evaluate the quality of life improvement of the patients with COPD using CAT score as the outcome, the change in CAT score over the 1-year post-enrolment time frame will be examined. A paired-sample t-test will be used to compare baseline CAT score and the best achieved CAT score over the 1-year time frame.

PACIC score
To evaluate patients' perception on the programme's congruency with CCM, the average PACIC score for programme enrolees will be computed and benchmarked with PACIC results of other integrated care programmes in present literature that have showed substantial congruency to the CCM. At present, recommended cut-offs for CCM concordance is set at ≥3.5 in a study with veterans and at ≥4 in another study with older adults at risk of high healthcare costs. [23][24].

Software
All analyses will be conducted using Stata version 12.

DISCUSSION
In designing the COPD-ICP programme, three key principles have been adopted: right-siting, integration and patient-centeredness. It also involves the five standards of care: COPD  The rationale behind this programme evaluation stems from the motivation to bolster support for the programme and to identify care gaps for improvement. As such, adherence with processes of care and outcomes such as risk of hospitalisation, CAT score and PACIC score will be used by the team to identify any care gaps, so as to improve the COPD-ICP programme. In addition, healthcare costs, disease progression and one-year mortality rate will also be used to assess the practicality of sustaining the programme. Furthermore, this study can also potentially add to the mounting evidence in support of integrated care in healthcare literature.
This study protocol has several strengths. The PACIC survey will be used to assess patients' experience of the congruency of care to CCM. This is in line with the organisation's aim to deliver patient-centred care.
The choice of the matched group patients using propensity scores will replicate the balance in baseline characteristics between compared cohorts achieved through randomisation. This will in  16 turn reduce the effect of selection bias due to the lack of randomisation. [21] This step will be vital for making valid conclusions from the economic effectiveness analysis.
This study protocol is limited in several areas. Firstly, even though we will use propensity score matching to reduce the selection bias due to non-randomisation, there might be unmeasured confounders which can affect our results. Secondly, the data collection process will only account for both enrolees and non-enrolees who choose to have their follow-up medical appointments at JurongHealth, NHG and NUHS. Due to non-captive nature of the healthcare system in Singapore, patients in Singapore are free to choose healthcare providers outside these clusters on an episodic basis. Hence, such exclusion might lead to underestimation. However, these limitations affect the evaluation of the programme only but not the quality of care provided at any institution.
In conclusion, the COPD-ICP programme serves to equip primary care partners with the adequate knowledge and skills for managing stable patients with COPD and to right-site patients in order to provide excellent and appropriate care while optimising available healthcare resources. With the support from case managers, the programme does so by discharging patients to primary care doctors so that the clinically stable patients can be managed without the need to see a specialist if not clinically necessary. We believe that this evaluation study can provide an evidence-based assessment of the impact and effectiveness of the COPD-ICP programme. The lessons learnt from this study will be fed back to the COPD-ICP programme team and be useful in informing the design evaluations of other ICP programmes nationally.

CONFIDENTIALITY
Names and National Registration Identity Card (NRIC) number of patients will be removed and replaced with unique study IDs after merging of datasets. The link between these study IDs and the NRIC number it represents will only be known to the principal investigator of the study.

DATA ACCESS
Access rights to the data will be given to the Clinical Analytics team in JurongHealth, the project manager and the clinician lead of the COPD-ICP programme.

Methods and analysis
This will be a retrospective, pre-post, matched-groups study to evaluate the effectiveness of COPD-ICP programme in improving clinical outcomes and reducing healthcare costs.
Programme enrolees (intervention group) and non-enrolees (comparator group) will be matched using propensity scores. Administratively, we set 30% as our target for proportion admission difference between programme and non-programme patients. A sample size of 62 patients in each group will be needed for statistical comparisons to be made at 90% power. Adherence with recommended care elements will be measured at baseline and quarterly during one year followup. Risk of COPD-related hospitalisations as primary outcome, healthcare costs, disease progression, and one-year mortality during one-year follow-up will be compared between the groups using generalised linear regression models.

Ethics and dissemination
This protocol describes the implementation and proposed evaluation of the COPD-ICP programme. The described study has received ethical approval from the NHG Domain Specific Review Board (DSRB Ref: 2013/01200). Results of the study will be reported through peerreview publications and healthcare conferences presentation.

Keywords
Chronic Obstructive Pulmonary Disease, Integrated Care Pathway, Evaluation, Propensity Score

Key message
This study aims to evaluate the effectiveness of the programme in improving adherence with recommended processes of care, and lowering COPD-related hospitalisation and inpatient costs.
This study will also compare the one-year mortality rate and disease progression rate between enrolees and non-enrolees. This study will use CAT score to measure COPD control in patients and Patient Assessment of Chronic Illness Care (PACIC) score to measure patients' experience of care congruent to the Chronic Care Model.

Strengths and limitation of this study
This study will use a retrospective, pre-post, matched-groups design to evaluate the effectiveness of the programme in terms of adherence with processes of care, clinical outcomes, healthcare costs, and quality of life. It is envisioned that through this study, the COPD-ICP team will be able to identify potential gaps in the programme implementation and This study will use propensity score matching to reduce selection bias due to the lack of randomisation.

BACKGROUND
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic disease morbidity and mortality worldwide. The disease is a global health problem with a worldwide prevalence of 10.1%. [1] In Singapore, COPD is the seventh principal cause of death and the seventh most common condition for hospitalisation. [2] COPD patients with complications spent 7.7 days or 79% longer in hospital than COPD patients without complications. [3] The COPD 30-day readmission in JurongHealth is around 30% which is higher than the all-cause national 30-day readmission rate of 11.6% and other condition-specific readmission rates. [4] The GOLD international standards for COPD advise spirometry for the gold standard for accurate and repeatable measurement of lung function. [5] However, in Singapore, most solo general practice (GP) clinics do not offer spirometer services necessary for early diagnosis of COPD and for the staging of COPD severity to enable appropriate disease management. Patients with COPD in the community experience poor quality of life due to lack of convenient access to pulmonary rehabilitation. [6] Therefore, most patients are diagnosed in the acute care setting and those who experienced repeated exacerbations also obtain care in the specialist outpatient settings.
3. Delay or prevent the deterioration of disease condition of COPD patients.

Reduce mortality of patients with COPD.
The programme adopts a coordinated and multi-disciplinary approach to the management of the patients' medical conditions. Case managers work with JurongHealth's multi-disciplinary team of doctors, nurses, respiratory technologists, pharmacists, physiotherapists and medical social workers to develop a customised care plan for each patient, empower patients towards selfmanagement through education, and help coordinate referrals and patients' appointments across care sites.
The current scope of our study will focus on the evaluation of the hospital-based segment of the ICP programme. We will use propensity-score matching method to select a suitable comparator group. Specifically, the aim of our study will be to assess whether the intervention group compared to comparator group has 1) primary outcome: lower risk of COPD-related hospitalisation; and 2) secondary outcomes: better adherence to the recommended processes of care, lower overall healthcare and COPD-related inpatient costs, slower disease progression, and lower one-year mortality rate. We will use PACIC score to measure patients' experience of chronic care delivery in congruence to the Chronic Care Model (CCM). [8] In addition, we will also use CAT score to measure COPD control and hence the quality of life of patients with COPD.

METHODS/DESIGN The Regional Healthcare System
In Singapore, public healthcare is provided by six regional healthcare systems (RHSs): Alexandra Health, Eastern Health Alliance, National Healthcare Group (NHG), National University Health System (NUHS), JurongHealth, and Singapore Health Services (SHS).
Together, these RHSs provide 80% of all acute care service. The government primary care clinics under NHG and SHS provide approximately 20% of primary care services consumed. Figure 1 shows the inclusion and exclusion criteria for patients' enrolment into the COPD-ICP programme. [9][10] We will exclude patients who have medical conditions other than COPD that are likely to result in death within the next two years.
With the implementation of the programme, care plans are designed to cater to each patient's disease severity. Patients are followed up by case managers regularly to ensure that the care elements as mentioned above are strictly adhered to. Case managers will also call the patient 48 hours post discharge to reinforce patient education and drugs optimisation, where they play a pivotal role in linking patients to community resources. Hence, with the coordination by case managers, the programme has made care delivery a more seamless and integrated process as compared to when such an initiative is absent.

Evaluation Design
A retrospective pre-post, matched-groups design will be implemented for this study. Such a design will be utilised instead of the randomised controlled trial design as the COPD-ICP programme has been implemented in JurongHealth for almost two years. Care resources may also be unnecessarily stretched if two care programmes (usual care and COPD-ICP) were run concurrently.
The study cohort will include individuals diagnosed with COPD who had at least one Specialist Outpatient Visit (SOC) record in COPD Registry from Apr 2012 to Dec 2013. For our study, we will use the same inclusion and exclusion selection criteria as those for the COPD-ICP  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  Patients in the intervention group will be sampled from programme patients in the COPD registry who received care from JurongHealth from Apr 2012 to Dec 2013. A comparator group will be formed from non-enrolees using matching method described in later sections. Patients for the comparator group will be sampled from non-programme patients in the COPD registry who received care from non-JurongHealth institutions from Apr 2012 to Dec 2013. All data will be collected over one-year pre-enrolment and one-year follow up post-enrolment (three-month interval) for enrolees, and over one-year period for non-enrolees. The outcomes will be compared between enrolees and non-enrolees ( Figure 1).

Sample size
Administratively, we set 30% as our target for proportion admission difference between programme and non-programme patients. Thus, a sample size of 56 patients in each group will be needed for statistical comparisons to be made at 90% power. Hence, 62 enrolees (to account for 10% missing data) will be sampled from amongst those who were enrolled into the programme during the study period and their matching group will be drawn from the comparator group COPD management registry.

Study Outcomes
Hospital admissions and Healthcare costs The primary outcome of this study is hospital admission. Hospital admission refers to inpatient episodes at acute care hospital managed by three regional health clusters (JurongHealth, NHG, and NUHS). Total annual healthcare costs refer to the cost of resources utilised at the primary care clinics, emergency departments, specialist outpatient clinics, and inpatient wards of these regional health clusters. To define specific COPD-related hospitalisations and inpatient costs, we have adopted the COPD-related hospitalisation ICD-10-codes used in . [11] Disease progression and one-year mortality rate Different medications are used during different disease progression stages. [9] Due to the absence of GOLD guidelines in measuring disease progression, we will utilise medication usage to determine the disease progression of patients with COPD. This will be compared between the intervention group and the comparator group. One-year mortality rate is defined as the proportion of patients who died (all causes) during one-year follow up for both intervention and comparator groups.
Adherence with recommended processes of care and PACIC score  12 We will use all-or-none care bundle to monitor adherence with the recommended key care elements for Group A, B, C and D patients (Table 1) at baseline and three-month interval. All-ornone care bundle is a process indicator which measures the percentage of patients who adhere with all of the recommended key care elements according to each patient group. [12] In addition, we will use PACIC score to measure patients' experience of chronic care delivery. PACIC score is a 20-question survey used to measure patients' perception on the congruency of the service to the Chronic Care Model (CCM). [8] CCM is a guideline which recognises six aspects as key to improving quality of chronic disease management. [8,13] The score obtained from PACIC assessment tool will allow us to assess if the COPD-ICP programme is aligned with CCM.

Quality of life
As there is no locally validated tool to measure quality of life in patients with COPD and the COPD-specific version of St. George's Respiratory Questionnaire is too long to administer, we will use CAT score, which is an eight-question health survey, to measure COPD control in individuals. [14] Scores range from 0 to 40 and lower scores indicate better control. Due to its strong correlation with the COPD-specific version of the St. George's Respiratory Questionnaire, it has been used as an alternative tool for assessing quality of life of patients with COPD. [14,[15][16][17][18] Enrolees' CAT score will be measured at baseline and during their follow-up visits within the first year of enrolment. A CAT score difference of 2 or more (or >10%) suggests clinically significant changes in the quality of life. [19] The CAT score difference is taken as the difference between the baseline and the best reading within 1 year. This outcome is only available for programme enrolees as CAT score is not routinely collected for non-enrolees.  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  Key recommended processes of care (Table 1) will be monitored quarterly to track the adherence and progress of the COPD-ICP programme. Patient baseline characteristics from both enrolees and non-enrolees will be described with mean and standard deviation for continuous variables and number and percentage for categorical variables. Differences between COPD-ICP enrolees and non-enrolees will be compared using chi-square statistics for categorical variables and

Statistical Analysis
Wilcoxon rank sum tests for continuous variables.
Since patients are enrolled into the programme based on the institution which they were seen in, there is likely to be imbalance in baseline characteristics between enrolees and non-enrolees.
Hence, we will use propensity score matching to balance the baseline characteristics across enrolees and non-enrolees. [20] We will start off with estimating the propensity score, which is the conditional probability of each patient enrolling into the programme given their baseline characteristics, by using multivariate logistic regression. [20] Covariates to be included in the regression are: age, gender, race, hospital, subsidy term, the number of hospitalisation or emergency attendances in the past year, number and severity of comorbid conditions and COPD severity based on medication use. We will then form pairs of enrolee and non-enrolee by using the caliper matching method, within a range of 0.2 of the standard deviation of propensity score. [21] Hospital admissions, healthcare costs and mortality We will compare healthcare costs using generalised linear model with log link and gamma distribution. For odds of hospital admission and one-year mortality, we will compare using logistic regression. [22] CAT score comparison  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  To evaluate the quality of life improvement of the patients with COPD using CAT score as the outcome, the change in CAT score over the 1-year post-enrolment time frame will be examined.
A paired-sample t-test will be used to compare baseline CAT score and the best achieved CAT score over the 1-year time frame.

PACIC score
To evaluate patients' perception on the programme's congruency with CCM, the average PACIC score for programme enrolees will be computed and benchmarked with PACIC results of other integrated care programmes in present literature that have showed substantial congruency to the CCM. At present, recommended cut-offs for CCM concordance is set at ≥3.5 in a study with veterans and at ≥4 in another study with older adults at risk of high healthcare costs. [23][24].

Software
All analyses will be conducted using Stata version 12.

DISCUSSION
In designing the COPD-ICP programme, three key principles have been adopted: right-siting, integration and patient-centeredness. It also involves the five standards of care: COPD  The rationale behind this programme evaluation stems from the motivation to bolster support for the programme and to identify care gaps for improvement. As such, adherence with processes of care and outcomes such as risk of hospitalisation, CAT score and PACIC score will be used by the team to identify any care gaps, so as to improve the COPD-ICP programme. In addition, healthcare costs, disease progression and one-year mortality rate will also be used to assess the practicality of sustaining the programme. Furthermore, this study can also potentially add to the mounting evidence in support of integrated care in healthcare literature.
This study protocol has several strengths. The PACIC survey will be used to assess patients' experience of the congruency of care to CCM. This is in line with the organisation's aim to deliver patient-centred care.  16 The choice of the matched group patients using propensity scores will replicate the balance in baseline characteristics between compared cohorts achieved through randomisation. This will in turn reduce the effect of selection bias due to the lack of randomisation. [21] This step will be vital for making valid conclusions from the economic effectiveness analysis.
This study protocol is limited in several areas. Firstly, even though we will use propensity score matching to reduce the selection bias due to non-randomisation, there might be unmeasured confounders which can affect our results. Secondly, the data collection process will only account for both enrolees and non-enrolees who choose to have their follow-up medical appointments at JurongHealth, NHG and NUHS. Due to non-captive nature of the healthcare system in Singapore, patients in Singapore are free to choose healthcare providers outside these clusters on an episodic basis. Hence, such exclusion might lead to underestimation. However, these limitations affect the evaluation of the programme only but not the quality of care provided at any institution.
In conclusion, the COPD-ICP programme aims to equip primary care partners with the adequate knowledge and skills for managing stable patients with COPD and to right-site patients in order to provide excellent and appropriate care while optimising available healthcare resources. With the support from case managers, the programme does so by discharging patients to primary care doctors so that the clinically stable patients can be managed without the need to see a specialist if not clinically necessary. We believe that this evaluation study can provide an evidence-based assessment of the impact and effectiveness of the COPD-ICP programme. The lessons learnt from this study will be fed back to the COPD-ICP programme team and be useful in informing the design evaluations of other ICP programmes nationally.

ETHICS AND DISSEMINATION
This protocol describes the implementation and proposed evaluation of the COPD-ICP programme. The described study has received ethical approval from the NHG Domain Specific Review Board (DSRB Ref: 2013/01200). Results of the study will be reported through peerreview publication and healthcare conferences presentation.

CONFIDENTIALITY
Names and National Registration Identity Card (NRIC) number of patients will be removed and replaced with unique study IDs after merging of datasets. The link between these study IDs and the NRIC number it represents will only be known to the principal investigator of the study.

DATA ACCESS
Access rights to the data will be given to the Clinical Analytics team in JurongHealth, the project manager and the clinician lead of the COPD-ICP programme.

Methods and analysis
This will be a retrospective, pre-post, matched-groups study to evaluate the effectiveness of COPD-ICP programme in improving clinical outcomes and reducing healthcare costs.
Programme enrolees (intervention group) and non-enrolees (comparator group) will be matched using propensity scores. Administratively, we set 30% as our target for proportion admission difference between programme and non-programme patients. A sample size of 62 patients in each group will be needed for statistical comparisons to be made at 90% power. Adherence with recommended care elements will be measured at baseline and quarterly during one year followup. Risk of COPD-related hospitalisations as primary outcome, healthcare costs, disease progression, and one-year mortality during one-year follow-up will be compared between the groups using generalised linear regression models.

Ethics and dissemination
This protocol describes the implementation and proposed evaluation of the COPD-ICP programme. The described study has received ethical approval from the NHG Domain Specific Review Board (DSRB Ref: 2013/01200). Results of the study will be reported through peerreview publications and healthcare conferences presentation.

Keywords
Chronic Obstructive Pulmonary Disease, Integrated Care Pathway, Evaluation, Propensity Score

Key message
This study aims to evaluate the effectiveness of the programme in improving adherence with recommended processes of care, and lowering COPD-related hospitalisation and inpatient costs.
This study will also compare the one-year mortality rate and disease progression rate between enrolees and non-enrolees. This study will use CAT score to measure COPD control in patients and Patient Assessment of Chronic Illness Care (PACIC) score to measure patients' experience of care congruent to the Chronic Care Model.

Strengths and limitation of this study
This study will use a retrospective, pre-post, matched-groups design to evaluate the effectiveness of the programme in terms of adherence with processes of care, clinical outcomes, healthcare costs, and quality of life. It is envisioned that through this study, the COPD-ICP team will be able to identify potential gaps in the programme implementation and  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60   F  o  r  p  e  e  r  r  e  v  i  e  w  o  n  l  y   4 design, and implement necessary changes to improve care. This is in line with the organisation's aim to deliver patient-centred care.
This study will use propensity score matching to reduce selection bias due to the lack of randomisation.

BACKGROUND
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic disease morbidity and mortality worldwide. The disease is a global health problem with a worldwide prevalence of 10.1%. [1] In Singapore, COPD is the seventh principal cause of death and the seventh most common condition for hospitalisation. [2] COPD patients with complications spent 7.7 days or 79% longer in hospital than COPD patients without complications. [3] The COPD 30-day readmission in JurongHealth is around 30% which is higher than the all-cause national 30-day readmission rate of 11.6% and other condition-specific readmission rates. [4] The GOLD international standards for COPD advise spirometry for the gold standard for accurate and repeatable measurement of lung function. [5] However, in Singapore, most solo general practice (GP) clinics do not offer spirometer services necessary for early diagnosis of COPD and for the staging of COPD severity to enable appropriate disease management. Patients with COPD in the community experience poor quality of life due to lack of convenient access to pulmonary rehabilitation. [6] Therefore, most patients are diagnosed in the acute care setting and those who experienced repeated exacerbations also obtain care in the specialist outpatient settings.

METHODS/DESIGN The Regional Healthcare System
In Singapore, public healthcare is provided by six regional healthcare systems (RHSs): Alexandra Health, Eastern Health Alliance, National Healthcare Group (NHG), National University Health System (NUHS), JurongHealth, and Singapore Health Services (SHS).
Together, these RHSs provide 80% of all acute care service. The government primary care clinics under NHG and SHS provide approximately 20% of primary care services consumed. Figure 1 shows the inclusion and exclusion criteria for patients' enrolment into the COPD-ICP programme. [9][10] We will exclude patients who have medical conditions other than COPD that are likely to result in death within the next two years.
With the implementation of the programme, care plans are designed to cater to each patient's disease severity. Patients are followed up by case managers regularly to ensure that the care elements as mentioned above are strictly adhered to. Case managers will also call the patient 48 hours post discharge to reinforce patient education and drugs optimisation, where they play a pivotal role in linking patients to community resources. Hence, with the coordination by case managers, the programme has made care delivery a more seamless and integrated process as compared to when such an initiative is absent.  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59

Evaluation Design
A retrospective pre-post, matched-groups design will be implemented for this study. Such a design will be utilised instead of the randomised controlled trial design as the COPD-ICP programme has been implemented in JurongHealth for almost two years. Care resources may also be unnecessarily stretched if two care programmes (usual care and COPD-ICP) were run concurrently.
The study cohort will include individuals diagnosed with COPD who had at least one Specialist Outpatient Visit (SOC) record in COPD Registry from Apr 2012 to Dec 2013. For our study, we will use the same inclusion and exclusion selection criteria as those for the COPD-ICP  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  Patients in the intervention group will be sampled from programme patients in the COPD registry who received care from JurongHealth from Apr 2012 to Dec 2013. A comparator group will be formed from non-enrolees using matching method described in later sections. Patients for the comparator group will be sampled from non-programme patients in the COPD registry who received care from non-JurongHealth institutions from Apr 2012 to Dec 2013. All data will be collected over one-year pre-enrolment and one-year follow up post-enrolment (three-month interval) for enrolees, and over one-year period for non-enrolees. The outcomes will be compared between enrolees and non-enrolees ( Figure 1).

Sample size
Administratively, we set 30% as our target for proportion admission difference between programme and non-programme patients. Thus, a sample size of 56 patients in each group will be needed for statistical comparisons to be made at 90% power. Hence, 62 enrolees (to account for 10% missing data) will be sampled from amongst those who were enrolled into the programme during the study period and their matching group will be drawn from the comparator group COPD management registry.

Study Outcomes
Hospital admissions and Healthcare costs The primary outcome of this study is hospital admission. Hospital admission refers to inpatient episodes at acute care hospital managed by three regional health clusters (JurongHealth, NHG, and NUHS). Total annual healthcare costs refer to the cost of resources utilised at the primary care clinics, emergency departments, specialist outpatient clinics, and inpatient wards of these regional health clusters. To define specific COPD-related hospitalisations and inpatient costs, we have adopted the COPD-related hospitalisation ICD-10-codes used in . [11] Disease progression and one-year mortality rate Different medications are used during different disease progression stages. [9] Due to the absence of GOLD guidelines in measuring disease progression, we will utilise medication usage to determine the disease progression of patients with COPD. This will be compared between the intervention group and the comparator group. One-year mortality rate is defined as the proportion of patients who died (all causes) during one-year follow up for both intervention and comparator groups.
Adherence with recommended processes of care and PACIC score  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59 12 We will use all-or-none care bundle to monitor adherence with the recommended key care elements for Group A, B, C and D patients (Table 1) at baseline and three-month interval. All-ornone care bundle is a process indicator which measures the percentage of patients who adhere with all of the recommended key care elements according to each patient group. [12] In addition, we will use PACIC score to measure patients' experience of chronic care delivery. PACIC score is a 20-question survey used to measure patients' perception on the congruency of the service to the Chronic Care Model (CCM). [8] CCM is a guideline which recognises six aspects as key to improving quality of chronic disease management. [8,13] The score obtained from PACIC assessment tool will allow us to assess if the COPD-ICP programme is aligned with CCM.

Quality of life
As there is no locally validated tool to measure quality of life in patients with COPD and the COPD-specific version of St. George's Respiratory Questionnaire is too long to administer, we will use CAT score, which is an eight-question health survey, to measure COPD control in individuals. [14] Scores range from 0 to 40 and lower scores indicate better control. Due to its strong correlation with the COPD-specific version of the St. George's Respiratory Questionnaire, it has been used as an alternative tool for assessing quality of life of patients with COPD. [14,[15][16][17][18] Enrolees' CAT score will be measured at baseline and during their follow-up visits within the first year of enrolment. A CAT score difference of 2 or more (or >10%) suggests clinically significant changes in the quality of life. [19] The CAT score difference is taken as the difference between the baseline and the best reading within 1 year. This outcome is only available for programme enrolees as CAT score is not routinely collected for non-enrolees. Key recommended processes of care (Table 1) will be monitored quarterly to track the adherence and progress of the COPD-ICP programme. Patient baseline characteristics from both enrolees and non-enrolees will be described with mean and standard deviation for continuous variables and number and percentage for categorical variables. Differences between COPD-ICP enrolees and non-enrolees will be compared using chi-square statistics for categorical variables and

Statistical Analysis
Wilcoxon rank sum tests for continuous variables.
Since patients are enrolled into the programme based on the institution which they were seen in, there is likely to be imbalance in baseline characteristics between enrolees and non-enrolees.
Hence, we will use propensity score matching to balance the baseline characteristics across enrolees and non-enrolees. [20] We will start off with estimating the propensity score, which is the conditional probability of each patient enrolling into the programme given their baseline characteristics, by using multivariate logistic regression. [20] Covariates to be included in the regression are: age, gender, race, hospital, subsidy term, the number of hospitalisation or emergency attendances in the past year, number and severity of comorbid conditions and COPD severity based on medication use. We will then form pairs of enrolee and non-enrolee by using the caliper matching method, within a range of 0.2 of the standard deviation of propensity score. [21] Hospital admissions, healthcare costs and mortality We will compare healthcare costs using generalised linear model with log link and gamma distribution. For odds of hospital admission and one-year mortality, we will compare using logistic regression. [22] CAT score comparison To evaluate the quality of life improvement of the patients with COPD using CAT score as the outcome, the change in CAT score over the 1-year post-enrolment time frame will be examined.
A paired-sample t-test will be used to compare baseline CAT score and the best achieved CAT score over the 1-year time frame.

PACIC score
To evaluate patients' perception on the programme's congruency with CCM, the average PACIC score for programme enrolees will be computed and benchmarked with PACIC results of other integrated care programmes in present literature that have showed substantial congruency to the CCM. At present, recommended cut-offs for CCM concordance is set at ≥3.5 in a study with veterans and at ≥4 in another study with older adults at risk of high healthcare costs. [23][24].

Software
All analyses will be conducted using Stata version 12.

DISCUSSION
In designing the COPD-ICP programme, three key principles have been adopted: right-siting, integration and patient-centeredness. It also involves the five standards of care: COPD  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  The rationale behind this programme evaluation stems from the motivation to bolster support for the programme and to identify care gaps for improvement. As such, adherence with processes of care and outcomes such as risk of hospitalisation, CAT score and PACIC score will be used by the team to identify any care gaps, so as to improve the COPD-ICP programme. In addition, healthcare costs, disease progression and one-year mortality rate will also be used to assess the practicality of sustaining the programme. Furthermore, this study can also potentially add to the mounting evidence in support of integrated care in healthcare literature.
This study protocol has several strengths. The PACIC survey will be used to assess patients' experience of the congruency of care to CCM. This is in line with the organisation's aim to deliver patient-centred care.  16 The choice of the matched group patients using propensity scores will replicate the balance in baseline characteristics between compared cohorts achieved through randomisation. This will in turn reduce the effect of selection bias due to the lack of randomisation. [21] This step will be vital for making valid conclusions from the economic effectiveness analysis.
This study protocol is limited in several areas. Firstly, even though we will use propensity score matching to reduce the selection bias due to non-randomisation, there might be unmeasured confounders which can affect our results. Secondly, the data collection process will only account for both enrolees and non-enrolees who choose to have their follow-up medical appointments at JurongHealth, NHG and NUHS. Due to non-captive nature of the healthcare system in Singapore, patients in Singapore are free to choose healthcare providers outside these clusters on an episodic basis. Hence, such exclusion might lead to underestimation. However, these limitations affect the evaluation of the programme only but not the quality of care provided at any institution.
In conclusion, the COPD-ICP programme aims to equip primary care partners with the adequate knowledge and skills for managing stable patients with COPD and to right-site patients in order to provide excellent and appropriate care while optimising available healthcare resources. With the support from case managers, the programme does so by discharging patients to primary care doctors so that the clinically stable patients can be managed without the need to see a specialist if not clinically necessary. We believe that this evaluation study can provide an evidence-based assessment of the impact and effectiveness of the COPD-ICP programme. The lessons learnt from this study will be fed back to the COPD-ICP programme team and be useful in informing the design evaluations of other ICP programmes nationally.

ETHICS AND DISSEMINATION
This protocol describes the implementation and proposed evaluation of the COPD-ICP programme. The described study has received ethical approval from the NHG Domain Specific Review Board (DSRB Ref: 2013/01200). Results of the study will be reported through peerreview publication and healthcare conferences presentation.

CONFIDENTIALITY
Names and National Registration Identity Card (NRIC) number of patients will be removed and replaced with unique study IDs after merging of datasets. The link between these study IDs and the NRIC number it represents will only be known to the principal investigator of the study.