Status: Finalised
First registered on:
19/04/2016
Last updated on:
16/01/2019
1. Study identification
EU PAS Register NumberEUPAS13218
Official titleHistorical matched-cohort study assessing whether the use of inhaled corticosteroids shortens time to first diagnosis or accelerates the progression of side effects compared to non-ICS therapies in patients with Chronic Obstructive Pulmonary Disease.
Study title acronymICS use in COPD patients and risk of side effects
Study typeObservational study
Brief description of the studyThe objective is to analyze the relationship between ICS use and Type 2 Diabetes onset, Type 2 Diabetes worsening disease control and disease progression, osteoporosis onset, pneumonia incidence and overuse of ICS. Firstly, these endpoints will be compared between an ICS therapy cohort and non-ICS therapy cohort. Subsequently, they will be analyzed within the ICS-therapy cohort only and compared by ICS average daily dose, ICS cumulative dose, and ICS drug and inhaler device type.
This is a historical, matched-cohort study. The study time period is 1990 - present. To account for changes in ICS prescribing in the study period, patients will be matched on index date to ensure they follow a similar time path. For both treatment cohorts a 1-year baseline period prior to the date of first prescription of ICS therapy or first/additional prescription of non-ICS therapy (i.e. the index date) will be followed by a minimum 1-year outcome period. All of the patient’s available data post index date will be utilized.
To be included in the ICS cohort, patients may switch between different types of ICS in the outcome period as long as ICS remain part of therapy. Exposure of ICS will be measured from the index date to realization of the outcome (e.g. a Type 2 Diabetes diagnosis) or from index date to the end of the follow up period if the outcome does not occur. A variable will be created, exposure time, to be used as an adjustment in all multivariable analyses. To be included in the non-ICS cohort, patients may be prescribed SABA, LABA, SAMA, LAMA, Methylxanthines and/or compound bronchodilator preparations and may switch between therapies in the outcome period as long as ICS are not prescribed. The number of OCS prescriptions per year of the outcome period and overall prescriptions in the outcome period will be accounted for in the analysis.
Was this study requested by a regulator?No
Is the study required by a Risk Management Plan (RMP)?
Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Department/Research groupResearch in Real Life Ltd
Organisation/affiliationOPRI Pte Ltd
Details of (Primary) lead investigator
Title Professor
Last name Price
First name David
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
United Kingdom
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed01/12/2015
Start date of data collection01/05/201614/07/2016
Start date of data analysis26/06/2016
Date of interim report, if expected
Date of final study report12/04/201710/07/2017
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesNovartis100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Professor
Last name Price
First name David
Address line 15a Coles Lane
Address line 2Oakington
Address line 3
CityCambridge
PostcodeCB24 3BA
CountryUnited Kingdom
Phone number (incl. country code)44-1223-967835
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Professor
Last name Price
First name David
Address line 15a Coles Lane
Address line 2Oakington
Address line 3
CityCambridge
PostcodeCB24 3BA
CountryUnited Kingdom
Phone number (incl. country code)44-1223-967835
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Substance class (ATC Code)C05AA (Corticosteroids)
7. Medical conditions to be studied
Medical condition(s)Yes
Chronic obstructive pulmonary disease
Type 2 diabetes mellitus
Osteoporosis
Pneumonia
8. Population under study
Age
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects100000
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Sources of data
Routine primary care electronic patient registry
11. Scope of the study
What is the scope of the study?
Risk assessment
Drug utilisation study
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
The objective is to analyze the relationship between ICS use and Type 2 Diabetes onset, Type 2 Diabetes worsening disease control and disease progression, osteoporosis onset, pneumonia incidence and overuse of ICS.
Are there primary outcomes?Yes
The primary objective of the study is to evaluate whether ICS therapy is associated with an increased onset, shortened time to first diagnosis or accelerated progression of Type 2 Diabetes compared to non-ICS therapies.
Are there secondary outcomes?Yes
- To evaluate whether ICS are associated with an increased onset or shortened time to first diagnosis of osteoporosis or increased incidence of pneumonia compared to non-ICS therapies.
- To evaluate the effects of average daily ICS dose, cumulative dose of ICS, ICS drug and inhaler device type on the aforementioned conditions.
- To measure overuse of ICS in COPD patients according to guidelines.
13. Study design
What is the design of the study?
Cohort study
14. Follow-up of patients
Will patients be followed up?Yes
Please describe duration of follow up
For both treatment cohorts a 1-year baseline period prior to the date of first prescription of ICS therapy or first/additional prescription of non-ICS therapy (i.e. the index date) will be followed by a minimum 1-year outcome period. All of the patient’s available data post index date will be utilized. Multivariable models will account for varying lengths of time at risk for side effects.
15. Data analysis plan
Please provide a brief summary of the analysis method
Summary statistics will be produced for unmatched and matched data for all baseline variables by group. Time to event outcomes will be analyzed using multivariable Cox proportional hazards models, reporting hazard ratios with 95% confidence intervals. Continuous progression outcomes will be analyzed using paired t-tests and generalized estimating equations reporting mean changes with 95% confidence intervals. Count outcomes will be analyzed using conditional Poisson regression, reporting incidence rate ratios with 95% confidence intervals.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
18. Study Results
Not submitted
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
None
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documentsNot
submitted
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
