Study design
We retrospectively analyzed aggregated monthly surveillance data on antibiotic sales to 586 hospitals from 28 provinces in China from January 2011 to December 2018 (Table 1).
Table 1 Distribution of sample hospitals
Region a
|
Tertiary b
|
Secondary c
|
Eastern
|
256 (26.1)
|
73 (3.7)
|
Middle
|
132 (21.9)
|
36 (1.4)
|
Western
|
64 (13.2)
|
25 (1.7)
|
Total
|
452 (21.9)
|
134 (2.3)
|
a: Classification of the regions was reference to China Health Statistics Yearbook. Eastern region: Beijing, Tianjin, Hebei, Liaoning, Shanghai, Jiangsu, Zhejiang, Shandong, and Guangdong; Middle region: Shanxi, Jilin, Heilongjiang, Anhui, Jiangxi, Henan, Hubei, and Hunan; Western region: Inner Mongolia, Chongqing, Guangxi, Sichuan, Guizhou, Yunnan, Shaanxi, Gansu, Ningxia, and Xinjiang.
b: Percentage in the brackets was calculated by dividing the number of sampled tertiary hospitals by total number of tertiary hospitals in the region.
c: Percentage in the brackets was calculated by dividing the number of sampled secondary hospitals by total number of secondary hospitals in the region.
Data source
All the data was obtained from China Medicine Economic Information (CMEI), an observational database containing information of drug sales records in medical institutions from 28 provinces (out of 34) across the country (Qinghai, Tibet, Hainan, Hongkong, Macau, and Taiwan excluded). The details of the data source were described elsewhere [14]. Hospitals were selected on the basis that they each had full records of antibiotic consumption during the study period of 8 years, among which 452 tertiary hospitals accounts for 21.9% of the total tertiary hospitals and 134 secondary hospitals accounts for 2.3% of the total secondary hospitals in study regions.
Data collection and management
We extracted monthly antibiotic sales records data from the CMEI electronic database. Information including the generic name, sales amount, dosage form, strength, the route of administration, and geographical data were collected. Hospital names were concealed to protect confidentiality.
Sales data were categorized according to Anatomical Therapeutic and Chemical (ATC) classification J01 (i.e. antibacterial for systemic use) expressed in defined daily dose (DDD) as measurement unit, following the recommendation of the WHO Collaborating Center for Drug Statistic Methodology [15]. The DDD of the drugs which could not be coded in the ATC system were calculated as the recommended daily amounts for each study medication based on dosage regimen recommended in the manufacturers’ instructions, as approved by China Food and Drug Administration. A total of 186 unique chemical substance names were identified in single or combination antibiotics. These antibiotics were aggregated into 32 ATC-4 classes then into 9 ATC-3 groups. Data were managed and analysed in Microsoft Excel 2013 and STATA 14.0 (StataCorp LLC, Texas, USA).
Data analysis
To make the antibiotic sales data available to provide internationally comparable information, the data were converted into DDD per 1,000 inhabitants per day (DID) at the level of the active substance. Based on the following two assumptions, equation1 was adopted to calculate the weighted population as a proxy for the population our sample hospitals had covered. First, there was no significant difference in the distribution of the sample hospitals across the provinces; second, there was no significant difference in the distribution of the population which was covered by the sample hospitals across the provinces. To avoid bias in calculating inhabitants, the inhabitants of outpatients and inpatients were calculated altogether instead of separately calculated as we did before [14]. Coverage inhabitants for secondary hospitals and tertiary hospitals were calculated separately.
(1) [Due to technical limitations, please see supplementary files for formula.]
Yi: Coverage inhabitants in a given year;
Pi: Total population in a given year in province i;
ni: Number of sample hospitals in province i;
Ni: Number of total hospitals in province i;
mi: Number of inpatients and outpatients in sample hospitals in province i;
Mi: Number of inpatients and outpatients in all hospitals in province i.
In addition to ATC classification, we adopted ‘Access, Watch, Reserve’ (AWaRe) categorization established by WHO as part of the update of the WHO Model List of Essential Medicines in 2017 to analyze the antibiotic consumption [16].
To derive a comparable metric of antibiotic consumption across time, we calculated the compound annual growth rate (CAGR) of antibiotic consumption.
(2) [See supp. files.]
C2018: Total antibiotic consumption for year 2018 (expressed in DID).
C2011: Total antibiotic consumption for year 2011 (expressed in DID).
All the relevant census data for calculating inhabitants were collected from China Health Statistics Yearbook and China Statistics Year Book [17]. Linear regression analysis was adopted to determine the trends in antibiotic use with time. A difference with p < 0.05 was considered to indicate statistical significance.