Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
To evaluate COPD-related clinical outcomes and total healthcare utilization in commercially insured (at least 40 years with a subanalysis of those aged 65 years and older) COPD population associated with the use of fluticasone/salmeterol combination (FSC) 250/50mcg compared to other initial maintenance therapies (IMTs), specifically, tiotropium bromide (TIO), and either ipratropium bromide or ipratropium bromide/albuterol (IP). This is a hypothesis testing study Ho: There is no difference in time to first COPD-related events between FSC and TIO and FSC and IP Ha: There is a difference in time to first COPD-related events between FSC and TIO and FSC and IP Hypothesis for the key secondary outcome of COPD-related costs that was tested was: Ho: There is no difference in COPD-related costs between FSC and TIO and FSC and IP Ha: There is a difference in COPD-related costs between FSC and TIO and FSC and IP
Detailed description
All population i.e. at least 40 years: Each initial maintenance treatment (IMT) cohort (FSC 250/50mcg dose only, IP, and TIO) includes patients aged 40 years and older with at least 9 months of continuous enrollment (6 months pre-index and at least three months post-index) with a primary or secondary diagnosis of COPD \[International Classification of Disease, 9th revision, Clinical Modification (ICD-9-CM) codes 491.xx, 492.xx or 496.xx\]. Patients are observed such that everyone provides minimum 6 months of pre index baseline data and minimum 3 months post index (risk analysis) and minimum 12 months post index for cost analysis. Patients must receive either a 30-day supply of FSC or IP or TIO as the initial IMT medication, indicating intent to treat. Patients may not also have a prescription filled for the other IMT medication within 60 days of the index date, or for the combination therapy budesonide/ formoterol (BFC), an inhaled corticosteroid (ICS) or a long acting beta agonist (LABA). Six months of observation (continuous enrollment) prior to the index date is assessed to confirm that the patient meets the inclusion and exclusion criteria as well as to identify baseline characteristics and covariates. Cost analysis was done using a 12 months fixed follow up period. Outcome measures are assessed during the post-index period Elderly cohort 65+: Identical methods and design were used for subanalyses in patients aged 65 years and over except comparison was FSC vs. TIO only. 75+ cohort: Identical methods and design were used for subanalyses in patients aged 75 years and over except comparison was FSC vs. TIO only.
Interventions
DRUGfluticasone/salmeterol combination (FSC) 250/50mcg
patients initiating treatment with fluticasone/salmeterol combination (FSC) 250/50mcg
DRUGtiotropium
patients initiating treatment with tiotropium
DRUGipratropium bromide alone or in fixed dose combination with albuterol
patients initiating treatment with ipratropium/albuterol
Sponsors
GlaxoSmithKline
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- IMT Cohorts (subjects selected by order of criteria) * claim for one of the study medications and must not receive another study medication within 60 days of the initial maintenance therapy, indicating intent to treat. * at least one COPD-related ED or one COPD-related hospitalization, or two COPD-related outpatient visits (OV) associated with primary or secondary diagnosis for COPD (ICD-9-CM code 491.xx, 492.xx or 496.xx), at any time during the observation period (July 1, 2005 through June 30, 2008) in the database. * Aged 65+ years on the index date or aged 40 and over for the sub-analysis. * Continuous enrollment in a health plan for at least 6 months prior (pre-index) to initiation of IMT and at least three months after the first initiation of IMT (post-index). * at least one prescription claim in the pre-index and each year of the post-index period for which they have follow-up.
Exclusion criteria
- All Cohorts * primary or secondary diagnosis of respiratory tract cancer (larynx, trachea, or pleura). (ICD-9-CM codes 161, 161.X, 162, 163, 163.X, 231, 231.X). * In the pre-index period, no claims for any of the cohort IMT medications, nor for any other Advair or budesonide/formoterol fixed dose combination, FSC combination medications, and may only have respiratory medication pharmacy claims for drugs included in the pre-index severity of illness assessment (Methylxanthines, Leukotriene Modifiers/Inhibitors, Omalizumab and Mast Cell Stabilizers).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Chronic Obstructive Pulmonary Disease (COPD) Event | Anytime from 30 days to 12 months after initial treatment arm prescription | The first COPD event occurring after 30 days from initial treatment arm prescription was measured. Four categories of COPD events were analyzed; either a hospitalization or emergency department visit; an emergency department visit; an outpatient visit followed by an oral corticosteroid prescription claim within 10 days; an outpatient visit followed by an oral antibiotic prescription claim within 10 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Annual Adjusted Post-Index COPD-Related Costs | Incurred over the 12 month period after initial treatment arm prescription | Medical costs are associated with COPD-related medical care (claims submitted with a primary International Classification of Diseases, 9th Revision, Clinical Modification diagnosis of COPD) and pharmaceutical care (treatment arm medications, oral corticosteroids, oral antibiotics, short-acting beta-agonists, long-acting beta-agonists \[LABA\], inhaled corticosteroids \[ICS\], ICS/LABA combinations, etc.. Means are adjusted for age, sex, geographic region, pre-initial treatment comorbidities, and COPD-related utilization. Total costs are the sum of medical care and pharmacy costs. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Risk Population: FSC Participants in the Overall Risk Population (participants with 3-12 months of follow-up after initial treatment arm prescription) receiving fluticasone propionate/salmeterol combination (FSC) 250 mcg/50 mcg | 16,684 |
| Risk Population: IP Participants in the Overall Risk Population (participants with 3-12 months of follow-up after initial treatment arm prescription) receiving ipratropium bromide 18 mcg or ipratropium bromide/albuterol 18 mcg/103 mcg (IP) | 14,449 |
| Risk Population: TIO Participants in the Overall Risk Population (participants with 3-12 months of follow-up after initial treatment arm prescription) receiving tiotropium bromide (TIO) 18 mcg | 12,659 |
| Cost Population: FSC Participants in the Overall Cost Population (participants with 12 months of follow-up after initial treatment arm prescription) receiving fluticasone propionate/salmeterol combination (FSC) 250 mcg/50 mcg | 12,595 |
| Cost Population: IP Participants in the Overall Cost Population (participants with 12 months of follow-up after initial treatment arm prescription) receiving ipratropium bromide 18 mcg or ipratropium bromide/albuterol 18 mcg/103 mcg (IP) | 10,617 |
| Cost Population: TIO Participants in the Overall Cost Population (participants with 12 months of follow-up after initial treatment arm prescription) receiving tiotropium bromide (TIO) 18 mcg | 9,126 |
| Total | 76,130 |
Baseline characteristics
| Characteristic | Risk Population: FSC | Risk Population: IP | Risk Population: TIO | Cost Population: FSC | Cost Population: IP | Cost Population: TIO | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 62.8 Years STANDARD_DEVIATION 12 | 65.2 Years STANDARD_DEVIATION 12.59 | 64.5 Years STANDARD_DEVIATION 11.33 | 62.8 Years STANDARD_DEVIATION 11.92 | 65.0 Years STANDARD_DEVIATION 12.42 | 64.5 Years STANDARD_DEVIATION 11.34 | 64.0 Years STANDARD_DEVIATION 12.06 |
| Sex: Female, Male Female | 9127 Participants | 7143 Participants | 5862 Participants | 6914 Participants | 5298 Participants | 4256 Participants | 38600 Participants |
| Sex: Female, Male Male | 7557 Participants | 7306 Participants | 6797 Participants | 5681 Participants | 5319 Participants | 4870 Participants | 37530 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Time to First Chronic Obstructive Pulmonary Disease (COPD) Event
The first COPD event occurring after 30 days from initial treatment arm prescription was measured. Four categories of COPD events were analyzed; either a hospitalization or emergency department visit; an emergency department visit; an outpatient visit followed by an oral corticosteroid prescription claim within 10 days; an outpatient visit followed by an oral antibiotic prescription claim within 10 days.
Time frame: Anytime from 30 days to 12 months after initial treatment arm prescription
Population: All participants from a large database comprised of information from enrollment files and facility, professional service, and outpatient pharmacy claims from a variety of private healthcare benefit plans covering over 40 million patients enrolled in over 70 health plans (providing data continuously) across the United States.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Risk Population: FSC | Time to First Chronic Obstructive Pulmonary Disease (COPD) Event | Hospitalization or emergency department visit | 325.17 days | Standard Error 0.39 |
| Risk Population: FSC | Time to First Chronic Obstructive Pulmonary Disease (COPD) Event | Emergency department visit | 330.24 days | Standard Error 0.28 |
| Risk Population: FSC | Time to First Chronic Obstructive Pulmonary Disease (COPD) Event | Outpatient visit with oral steroid fill | 332.74 days | Standard Error 0.22 |
| Risk Population: FSC | Time to First Chronic Obstructive Pulmonary Disease (COPD) Event | Outpatient visit with antibiotic fill | 329.96 days | Standard Error 0.3 |
| Risk Population: IP | Time to First Chronic Obstructive Pulmonary Disease (COPD) Event | Outpatient visit with antibiotic fill | 326.73 days | Standard Error 0.39 |
| Risk Population: IP | Time to First Chronic Obstructive Pulmonary Disease (COPD) Event | Hospitalization or emergency department visit | 315.89 days | Standard Error 0.56 |
| Risk Population: IP | Time to First Chronic Obstructive Pulmonary Disease (COPD) Event | Outpatient visit with oral steroid fill | 328.23 days | Standard Error 0.31 |
| Risk Population: IP | Time to First Chronic Obstructive Pulmonary Disease (COPD) Event | Emergency department visit | 324.47 days | Standard Error 0.43 |
| Risk Population TIO | Time to First Chronic Obstructive Pulmonary Disease (COPD) Event | Outpatient visit with antibiotic fill | 326.70 days | Standard Error 0.39 |
| Risk Population TIO | Time to First Chronic Obstructive Pulmonary Disease (COPD) Event | Emergency department visit | 328.48 days | Standard Error 0.37 |
| Risk Population TIO | Time to First Chronic Obstructive Pulmonary Disease (COPD) Event | Outpatient visit with oral steroid fill | 331.23 days | Standard Error 0.3 |
| Risk Population TIO | Time to First Chronic Obstructive Pulmonary Disease (COPD) Event | Hospitalization or emergency department visit | 321.59 days | Standard Error 0.51 |
95% CI: [1.5, 1.79]
95% CI: [1.17, 1.41]
95% CI: [1.59, 2]
95% CI: [1.17, 1.51]
95% CI: [1.41, 1.94]
95% CI: [1.26, 1.76]
95% CI: [1.23, 1.57]
95% CI: [1.17, 1.51]
Secondary
Average Annual Adjusted Post-Index COPD-Related Costs
Medical costs are associated with COPD-related medical care (claims submitted with a primary International Classification of Diseases, 9th Revision, Clinical Modification diagnosis of COPD) and pharmaceutical care (treatment arm medications, oral corticosteroids, oral antibiotics, short-acting beta-agonists, long-acting beta-agonists \[LABA\], inhaled corticosteroids \[ICS\], ICS/LABA combinations, etc.. Means are adjusted for age, sex, geographic region, pre-initial treatment comorbidities, and COPD-related utilization. Total costs are the sum of medical care and pharmacy costs.
Time frame: Incurred over the 12 month period after initial treatment arm prescription
Population: All participants from a large database comprised of information from enrollment files and facility, professional service, and outpatient pharmacy claims from a variety of private healthcare benefit plans covering over 40 million patients enrolled in over 70 health plans (providing data continuously) across the United States
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Risk Population: FSC | Average Annual Adjusted Post-Index COPD-Related Costs | Pharmacy | 972 United States dollars | Standard Deviation 175 |
| Risk Population: FSC | Average Annual Adjusted Post-Index COPD-Related Costs | Medical | 1076 United States dollars | Standard Deviation 1119 |
| Risk Population: FSC | Average Annual Adjusted Post-Index COPD-Related Costs | Total | 2068 United States dollars | Standard Deviation 1190 |
| Risk Population: IP | Average Annual Adjusted Post-Index COPD-Related Costs | Total | 2841 United States dollars | Standard Deviation 1858 |
| Risk Population: IP | Average Annual Adjusted Post-Index COPD-Related Costs | Medical | 2481 United States dollars | Standard Deviation 2770 |
| Risk Population: IP | Average Annual Adjusted Post-Index COPD-Related Costs | Pharmacy | 614 United States dollars | Standard Deviation 225 |
| Risk Population TIO | Average Annual Adjusted Post-Index COPD-Related Costs | Total | 2408 United States dollars | Standard Deviation 1511 |
| Risk Population TIO | Average Annual Adjusted Post-Index COPD-Related Costs | Pharmacy | 985 United States dollars | Standard Deviation 355 |
| Risk Population TIO | Average Annual Adjusted Post-Index COPD-Related Costs | Medical | 1419 United States dollars | Standard Deviation 1572 |