Rationale and background
The WHO 2023 AWaRe classification (who.int) of antibiotics for evaluation and monitoring of use classifies 258 antibiotics into 3 categories (Access/Watch/Reserve) according to their impact on antimicrobial resistance.
The ‘Access’ category includes antibiotics that are recommended as first- or second-line treatments for a wide range of common infectious diseases. These antibiotics are generally active against a broad spectrum of commonly encountered, susceptible pathogens and have a relatively lower risk of promoting antimicrobial resistance compared to agents in other categories. The WHO emphasizes that ‘Access’ antibiotics should be widely available, affordable, and of assured quality across all healthcare settings to ensure equitable treatment, especially in low- and middle-income countries. As of the 2023 update, the ‘Access’ group includes 84 antibiotics, such as amoxicillin and doxycycline, which are used to treat high-burden infections like pneumonia and urinary tract infections.(1, 2) Promoting the use of ‘Access’ antibiotics for appropriate indications is a key component of global antimicrobial stewardship strategies aimed at reducing the need for broader-spectrum agents and mitigating the spread of resistance.
The DARWIN EU®_ P1-C1-003 study focused on the Watch category but there is now interest in including also the other category (‘Access’) to characterise the use of most antibiotics, and increased focus on the indication for use.
This study will improve the understanding of the use of antibiotics in routine health care delivery, including indication, treatment duration and trends over time. The results will contribute to the EU efforts to monitor use of antibiotics as part of the global fight against antimicrobial resistance.
Research question and objectives
Research question
What is the incidence of prescription of the antibiotics in the ‘Access’ category, including indication and treatment duration, from 2012 to 2024, stratified by demographic characteristics, calendar year/month, and country?
Objectives
1. To investigate the incidence of use of antibiotics (from the WHO AWaRe ‘Access’ category) stratified by age, sex, calendar year/month, and country/database during the study period 2012-2024.
MODEL DE SOL·LICITUD
2 IMP-126-CT Versió 07
2. To characterise antibiotic (WHO AWaRe ‘Access’ category 2023) use by duration of use over the study period 2012 to 2024.
3. To characterise antibiotic use (WHO AWaRe ‘Access’ list 2023) by indication of use over the period 2012 to 2024 stratified by calendar year.
Methods
Study design
• Population level cohort study (Objective 1, Population-level drug utilisation study on ‘Access’ category antibiotics)
• New drug user cohort study (Objectives 2 and 3, Patient-level drug utilisation analysis with regard to duration and indication of antibiotic use)
Population
Population-level utilisation of antibiotics (objective 1): All individuals present in the database in the period between 01/01/2012 and 31/12/2024 will be included in the analysis after 365 days of database history.
Patient-level antibiotic utilisation (Objectives 2 and 3): All new users of antibiotics (i.e. no use of the antibiotic of interest in the preceding 30 days) in the period between 01/01/2012 and 31/12/2024, with at least 365 days of visibility prior to the date of their first antibiotic prescription.
Study period
Study period will start from 2012 until the end of available data. In the NAJS data source, accurate data will be available from 2017 on.
Variables
Exposures
All antibiotics from the WHO AWaRe ‘Access’ category.
Outcome
n/a
Relevant covariates
Age groups, sex, calendar year/month, predefined conditions of interest.
Data source
1. Danish Data Health Registries (DK-DHR), Denmark
2. Finnish Care Register for Health Care (FinOMOP-HILMO), Finland
3. The Integrated Primary Care Information (IPCI), the Netherlands
4. IQVIA Disease Analyser (DA) Germany, Germany
5. National Public Health Information System (NAJS), Croatia
6. Information System for Research in Primary Care (SIDIAP), Spain
Sample size
No sample size has been calculated as this is an exploratory study which will not test a specific hypothesis.
Statistical analysis
Population-level antibiotic use: Yearly and monthly incidence rates of antibiotic prescriptions per 100,000 person-months (PMs) will be estimated. Overall incidence rates will be reported as well as stratified by age, sex, calendar year/month, and country/database. Incidence rates will be reported together with 95% Poisson confidence intervals.
Patient-level antibiotic use: Proportions of indication of use at index date will be assessed. Index date will be the date of each prescription of the specific antibiotic for each person. Cumulative treatment duration will be estimated and the minimum, p25, median, p75, and maximum will be provided.
The statistical analyses will be performed based on OMOP-CDM mapped data using “IncidencePrevalence” and “DrugUtilizationCharacteristics” R packages. A minimum cell counts of 5 will be used when reporting results, with any smaller count reported as “<5”.