Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
This was a retrospective cohort design using administrative claims data from Jan 1, 2003 through Sep 30, 2007, representing the years of available data, were used for this study. Managed care enrollees having at least one pharmacy claim for tiotropium (TIO) during the study period were identified as the target population. An index TIO prescription was defined as the first chronologically occurring pharmacy claim for TIO during the period Jan 1, 2004 to Aug 31, 2006, called the enrollment period. The date of the index TIO prescription was termed as the index Rx date, and the 1-year period before the index Rx date was termed as the pre-index period. The period after the index date was termed as the post-index date, and is further divided into a 30-day combination assessment period and a 1-year follow-up period. COPD clinical and economic outcomes were measured in a variable length follow up period. The combination assessment period, defined as the 30-day period following the index Rx date, was used to categorize patients into 2 cohorts: TIO alone or TIO + FSC (fluticasone propionate/salmeterol xinofoate combination) depending on whether they use FSC in combination with TIO during this period. Combination therapy with TIO + FSC was defined as having an FSC claim on the same date as the TIO claim or a TIO and FSC pharmacy claim with overlapping days supply occurring within 30 days of index Rx date. Enrollees adding FSC for the first time after the 30-day combination assessment period were excluded from the sample, thus ensuring that the TIO-alone cohort is not using FSC. No outcomes were assessed in the 30-day combination assessment period. The 1-year period after the end of the 30-day combination assessment period was termed as the follow-up period and was used to assess all study outcomes. Enrollees were required to be continuously eligible in their health plans during the pre-index and post-index periods for a total of 25 months. An intent-to-treat approach was used for the analyses. Thus, patients identified to be in a drug therapy cohort were considered to be using that therapy during the entire follow-up period, regardless of therapy discontinuations. Specifically the study hypothesis for the primary outcome being tested was: Ho: There is no difference in risk of any COPD-related exacerbation between TIO+FSC and TIO cohorts Ha: There is a difference in risk of any COPD-related exacerbation between TIO+FSC and TIO cohorts Hypothesis for the key secondary outcome of COPD-related costs that was tested was: Ho: There is no difference in COPD-related costs between TIO+FSC and TIO cohorts Ha: There is a difference in COPD-related costs between TIO+FSC and TIO cohorts
Interventions
DRUGTIO
Patients receiving tiotropium bromide at index within the study period.
DRUGTIO+FSC
Patients receiving tiotropium bromide plus fluticasone propionate-salmeterol xinafoate combination at time of index within the study period.
Sponsors
GlaxoSmithKline
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Inclusion criteria
* Continuous health plan eligibility in the pre- and post-index periods * age ≥40 years at the index date * Presence of at least 1 claim with an ICD-9-CM code for COPD in any diagnosis field (490.xx, 491.xx, 492.xx, 496.xx) in the pre- and post-index period * ≥1 exacerbation in the pre-index period (defined as a COPD-related Emergency Room visit or hospitalization) * ≥1 prescription claim for ipratropium or ipratropium/albuterol combination in the pre-index period * an index event of at least one pharmacy claim for TIO (tiotropium) combination in the pre-index period during the study period (January 1, 2003 through April 30, 2008) * ≥2 prescriptions for TIO (including the index prescription) during the post-index period
Exclusion criteria
* presence of comorbid conditions (respiratory cancer, cystic fibrosis, fibrosis due to tuberculosis \[TB\], and bronchiectasis, pneumonociosis, pulmonary fibrosis, pulmonary TB, sarcoidosis) during the pre- and post-index periods * use of FSC in pre-index period * exacerbation (emergency room visit or hospitalization) within 30 days after the index date
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate Per 100 Person Years of Hospitalization or Emergency Department (ED) Visit Related to Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) | Data were collected over a maximum period of 4 years | A severe exacerbation is defined as one with a primary diagnosis of COPD. A moderate exacerbation is an ED visit with a primary diagnosis of COPD, a physician visit with a diagnosis of COPD and a prescription for an oral corticosteroid, a physician visit with a diagnosis code for COPD and an antibiotic for respiratory infection, or physician administration of nebulized albuterol within 3 days of an office visit. Incidence rate is calculated by dividing the number of exacerbations by the number of person years. Person years adjust for different lengths of follow up for participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Hospitalizations and Emergency Room Visits Per 100 Person Years | Data were collected over a maximum period of 4 years | Unadjusted incidence rates per 100 person years of chronic obstructive pulmonary disease (COPD)-related hospitalizations and emergency department visits by treatment group are presented. Incidence rate is calculated by dividing the number of healthcare service encounters by the number of person years of follow up. Person years adjust for different lengths of follow up for individual participants |
| Adjusted Mean Monthly Costs Per COPD Patient by Treatment Group | Data were collected over a maximum period of 4 years | The mean costs of health care encounters adjusted to control for baseline differences between treatment groups and reported in 2008 United States dollars as calculated with the consumer price index (CPI) are presented. CPI is standard multiplier for adjusting the cost of goods and services to a single year. Total costs include pharmacy and medical costs. Medical costs were computed from the paid amounts of medical claims with a primary diagnosis code for COPD. COPD-related pharmacy costs were computed from paid amounts of COPD-related prescription medications. |
Participant flow
Recruitment details
Participants were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymized and used to develop a cohort. All diagnoses and treatments are recorded in the course of routine medical practice.
Pre-assignment details
Participants were treated with tiotropium bromide (TIO) or tiotropium bromide plus fluticasone propionate/salmeterol xinafoate combination (TIO + FSC) by their practitioners, and the database included information about their healthcare encounters.
Participants by arm
| Arm | Count |
|---|---|
| Tiotropium Bromide (TIO) Patients receiving tiotropium bromide (TIO) at the index date within the study period. | 2,481 |
| TIO Plus FSC/Salmeterol Xinafoate in Combination (TIO + FSC) Patients receiving TIO plus fluticasone propionate (FSC)/salmeterol xinafoate combination (TIO + FSC) at the time of the index date within the study period | 852 |
| Total | 3,333 |
Baseline characteristics
| Characteristic | Tiotropium Bromide (TIO) | TIO Plus FSC/Salmeterol Xinafoate in Combination (TIO + FSC) | Total |
|---|---|---|---|
| Age, Continuous | 66.1 Years STANDARD_DEVIATION 10.9 | 64.6 Years STANDARD_DEVIATION 11 | 65.7 Years STANDARD_DEVIATION 10.9 |
| Mean number of health care encounters, as a measure of resource utilization Number of physician visits for COPD | 3.3 number of encounters STANDARD_DEVIATION 3.6 | 2.9 number of encounters STANDARD_DEVIATION 3.4 | 3.2 number of encounters STANDARD_DEVIATION 3.6 |
| Mean number of health care encounters, as a measure of resource utilization Oral corticosteriod prescriptions | 2.1 number of encounters STANDARD_DEVIATION 2.9 | 1.9 number of encounters STANDARD_DEVIATION 2.3 | 2.0 number of encounters STANDARD_DEVIATION 2.8 |
| Mean number of health care encounters, as a measure of resource utilization SABA containers | 2.4 number of encounters STANDARD_DEVIATION 5 | 2.2 number of encounters STANDARD_DEVIATION 5.4 | 2.4 number of encounters STANDARD_DEVIATION 5.1 |
| Number of health care encounters, as a measure of resource utilization Emergency department visit for COPD | 570 number of encounters | 199 number of encounters | 769 number of encounters |
| Number of health care encounters, as a measure of resource utilization Home oxygen therapy | 801 number of encounters | 248 number of encounters | 1049 number of encounters |
| Number of health care encounters, as a measure of resource utilization Hospitalization for COPD | 467 number of encounters | 228 number of encounters | 695 number of encounters |
| Number of health care encounters, as a measure of resource utilization Intensive care unit stays for COPD | 81 number of encounters | 29 number of encounters | 110 number of encounters |
| Number of health care encounters, as a measure of resource utilization Moderate exacerbation of COPD | 2274 number of encounters | 747 number of encounters | 3021 number of encounters |
| Number of health care encounters, as a measure of resource utilization Severe exacerbation of COPD | 360 number of encounters | 175 number of encounters | 535 number of encounters |
| Sex: Female, Male Female | 1166 Participants | 399 Participants | 1565 Participants |
| Sex: Female, Male Male | 1315 Participants | 453 Participants | 1768 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Incidence Rate Per 100 Person Years of Hospitalization or Emergency Department (ED) Visit Related to Exacerbation of Chronic Obstructive Pulmonary Disease (COPD)
A severe exacerbation is defined as one with a primary diagnosis of COPD. A moderate exacerbation is an ED visit with a primary diagnosis of COPD, a physician visit with a diagnosis of COPD and a prescription for an oral corticosteroid, a physician visit with a diagnosis code for COPD and an antibiotic for respiratory infection, or physician administration of nebulized albuterol within 3 days of an office visit. Incidence rate is calculated by dividing the number of exacerbations by the number of person years. Person years adjust for different lengths of follow up for participants.
Time frame: Data were collected over a maximum period of 4 years
Population: Managed care enrollees (aged \>40 years) with at least one COPD-related exacerbation at baseline and newly initiating therapy with TIO with or without the addition of FSC during the study enrollment period was the target population. The date of TIO-alone therapy or TIO+FSC add-on date was the index date.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tiotropium Bromide (TIO) | Incidence Rate Per 100 Person Years of Hospitalization or Emergency Department (ED) Visit Related to Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) | Any exacerbation | 95.58 exacerbations per 100 person years |
| Tiotropium Bromide (TIO) | Incidence Rate Per 100 Person Years of Hospitalization or Emergency Department (ED) Visit Related to Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) | Severe exacerbation | 7.86 exacerbations per 100 person years |
| Tiotropium Bromide (TIO) | Incidence Rate Per 100 Person Years of Hospitalization or Emergency Department (ED) Visit Related to Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) | Moderate exacerbation | 88.65 exacerbations per 100 person years |
| TIO Plus FSC/Salmeterol Xinafoate in Combination (TIO + FSC) | Incidence Rate Per 100 Person Years of Hospitalization or Emergency Department (ED) Visit Related to Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) | Any exacerbation | 75.38 exacerbations per 100 person years |
| TIO Plus FSC/Salmeterol Xinafoate in Combination (TIO + FSC) | Incidence Rate Per 100 Person Years of Hospitalization or Emergency Department (ED) Visit Related to Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) | Severe exacerbation | 5.06 exacerbations per 100 person years |
| TIO Plus FSC/Salmeterol Xinafoate in Combination (TIO + FSC) | Incidence Rate Per 100 Person Years of Hospitalization or Emergency Department (ED) Visit Related to Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) | Moderate exacerbation | 69.74 exacerbations per 100 person years |
p-value: 0.00795% CI: [0.641, 0.93]Regression, Logistic
p-value: 0.14695% CI: [0.328, 1.18]Regression, Logistic
p-value: 0.01395% CI: [0.646, 0.949]Regression, Logistic
Secondary
Adjusted Mean Monthly Costs Per COPD Patient by Treatment Group
The mean costs of health care encounters adjusted to control for baseline differences between treatment groups and reported in 2008 United States dollars as calculated with the consumer price index (CPI) are presented. CPI is standard multiplier for adjusting the cost of goods and services to a single year. Total costs include pharmacy and medical costs. Medical costs were computed from the paid amounts of medical claims with a primary diagnosis code for COPD. COPD-related pharmacy costs were computed from paid amounts of COPD-related prescription medications.
Time frame: Data were collected over a maximum period of 4 years
Population: Managed care enrollees (aged \>40 years) with at least one COPD-related exacerbation at baseline and newly initiating therapy with TIO with or without the addition of FSC during the study enrollment period was the target population. The date of TIO-alone therapy or TIO+FSC add-on date was the index date.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tiotropium Bromide (TIO) | Adjusted Mean Monthly Costs Per COPD Patient by Treatment Group | Total costs | 721 United States dollars |
| Tiotropium Bromide (TIO) | Adjusted Mean Monthly Costs Per COPD Patient by Treatment Group | Pharmacy Costs | 190 United States dollars |
| Tiotropium Bromide (TIO) | Adjusted Mean Monthly Costs Per COPD Patient by Treatment Group | Medical costs | 543 United States dollars |
| TIO Plus FSC/Salmeterol Xinafoate in Combination (TIO + FSC) | Adjusted Mean Monthly Costs Per COPD Patient by Treatment Group | Total costs | 721 United States dollars |
| TIO Plus FSC/Salmeterol Xinafoate in Combination (TIO + FSC) | Adjusted Mean Monthly Costs Per COPD Patient by Treatment Group | Pharmacy Costs | 223 United States dollars |
| TIO Plus FSC/Salmeterol Xinafoate in Combination (TIO + FSC) | Adjusted Mean Monthly Costs Per COPD Patient by Treatment Group | Medical costs | 490 United States dollars |
Secondary
Incidence Rate of Hospitalizations and Emergency Room Visits Per 100 Person Years
Unadjusted incidence rates per 100 person years of chronic obstructive pulmonary disease (COPD)-related hospitalizations and emergency department visits by treatment group are presented. Incidence rate is calculated by dividing the number of healthcare service encounters by the number of person years of follow up. Person years adjust for different lengths of follow up for individual participants
Time frame: Data were collected over a maximum period of 4 years
Population: Managed care enrollees (aged \>40 years) with at least one COPD-related exacerbation at baseline and newly initiating therapy with TIO with or without the addition of FSC during the study enrollment period was the target population. The date of TIO-alone therapy or TIO+FSC add-on date was the index date.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tiotropium Bromide (TIO) | Incidence Rate of Hospitalizations and Emergency Room Visits Per 100 Person Years | COPD-related hospital and emergency room visits | 95.58 visits per 100 person years |
| Tiotropium Bromide (TIO) | Incidence Rate of Hospitalizations and Emergency Room Visits Per 100 Person Years | Hospitalizations | 11.14 visits per 100 person years |
| Tiotropium Bromide (TIO) | Incidence Rate of Hospitalizations and Emergency Room Visits Per 100 Person Years | Emergency department visits | 12.63 visits per 100 person years |
| TIO Plus FSC/Salmeterol Xinafoate in Combination (TIO + FSC) | Incidence Rate of Hospitalizations and Emergency Room Visits Per 100 Person Years | COPD-related hospital and emergency room visits | 75.38 visits per 100 person years |
| TIO Plus FSC/Salmeterol Xinafoate in Combination (TIO + FSC) | Incidence Rate of Hospitalizations and Emergency Room Visits Per 100 Person Years | Hospitalizations | 7.43 visits per 100 person years |
| TIO Plus FSC/Salmeterol Xinafoate in Combination (TIO + FSC) | Incidence Rate of Hospitalizations and Emergency Room Visits Per 100 Person Years | Emergency department visits | 9.90 visits per 100 person years |