Directly extracting research data via a query from the EMR system can impact the performance of the system for routine hospital use. A clinical data warehouse (CDW) provides numerous benefits to researchers for quality data collection and decision-making capabilities through quick and efficient access to patient information and links to multiple operational data sources. Furthermore, it can be used to discover disease relationships and drugs in addition to repositioning drugs by combining different data sources and validating the consistency of information. Therefore, we established the study dataset to include diagnosis and laboratory data based on a CDW system [16]. The CDW system of Seoul St. Mary's Hospital is currently comprised of 30 tables that include all clinical, prescription, laboratory, radiology, pathology, and other information of all patients at the hospital since 1997. Currently, data exist in the system for approximately 2.8 million patients, 47 million medication prescription events, and laboratory results for 150 million cases. Of the 2.2 billion total records, we developed a research DB from a subset of the data based on a study protocol. It additionally provides comprehensive views of clinical data for specific purposes [17,18].

Data for patients who were prescribed a statin for the first time at Seoul St. Mary's Hospital between January 1, 2009 and December 31, 2015 were extracted from the CDW. Cases were identified as those who did not have a statin prescription for at least six months before a statin was initially prescribed. The date on which the initial statin prescription occurred was defined as visit 0 (index date, baseline) (Fig. 1). Visit 1 (an average of 3 months later) was defined as the next occurrence of a laboratory test and subsequent renewal of the statin prescription within 45 to 135 days of the baseline. Visit 2 was defined as the subsequent visit that occurred within 136 to 225 days after the baseline (an average of 6 months later). Visit 3 was defined as 226 to 315 days after the baseline (an average of 9 months later), and visit 4 was defined as 316 to 405 days after the baseline (an average of 1 year later). Cases were checked when the prescription changed to a different statin type or the statin prescription was suspended during the study period. When the patients visited the hospital or had a blood test performed more than once within one period of a visit, the test results of the dates closest to the 91th, 182th, 273th, and 365th day were retrieved.

This study covered all statin types that are prescribed at Seoul St. Mary's Hospital. According to American College of Cardiology/American Heart Association guidelines [15], we classified statins based on intensity, type, and dose. The statin types and dosages are as follows: atorvastatin (10, 20, and 40 mg), fluvastatin (40 and 80 mg), pitavastatin (2 and 4 mg), pravastatin (10, 20, and 40 mg), rosuvastatin (5, 10, and 20 mg), simvastatin (20 and 40 mg), and simvastatin plus ezetimibe (10/10 and 20/10 mg). The combination statins and other drugs with other effects were excluded from the study (atorvastatin plus amlodipine or pravastatin plus fenofibrate).

Patient data were extracted, including date of birth, age (when first prescribed statins), sex, department in which the statins were first prescribed, first statin prescription date, days of prescription, etc. Besides total cholesterol, TG, HDL-C, LDL-C, which are indicators relevant to hyperlipidemia, blood tests were also covered in this study, such as blood urea nitrogen, creatinine, aspartate aminotransferase/alanine aminotransferase (AST/ALT), hemoglobin/hematocrit, glycated hemoglobin, alkaline phosphatase, high-sensitivity C-reactive protein, γ-glutamyl transpeptidase, thyroid function test (thyroid stimulating hormone, free thyroxine), and others. In modeling the DB, we structuralized relations between objects of unique features comprising it (Fig. 2).

In addition to hyperlipidemia, various diseases, including cardiovascular disorders, diabetes, and others, have been recently reported as relevant to statins; thus, they were included. Moreover, to study statin side effects, consideration was given to whether a patient used fenofibrate, omega-3 fatty acids, propranolol, thyroxine, warfarin, nicotinic acid, etc., which are known to affect hepatotoxicity.

This study was a retrospective cohort study using EMR data retained by one hospital. All files of extracted data were encoded to prevent personal identification of patients during the extraction process. Only one managing researcher was allowed to access the data; observers and analysts received the data with all personally identifying patient information deleted. Thus, they were unable to identify the actual patient numbers. Data utilized in this study did not include patient's personal information, and there was no risk of physical or psychological damage to the patient subject. Because the data were encoded and anonymized, and because the study was a retrospective cohort type, this study did not affect the patient subjects' rights and welfare. Therefore, informed consent was not required. This study was approved by the Institutional Review Board of the Catholic University of Korea.

We employed initial clinical data of statin obtained from a CDW that was established to support clinical studies. Through a data quality management (DQM) process, the initial clinical data were refined. Because data was extracted from the EMRs of patients, there were many duplicates and errors. For example, the most frequent case was the inclusion of letters or inequality in the extracted clinical laboratory scores field. We performed pre-processing work and DQM operations on these data successively. As part of the DQM, abnormal data (redundant data, out-of-range data, meaningless data, null space, etc.) were identified using clinical judgments as well as statistical methods. The abnormal data were re-confirmed by direct chart review. This enabled further extraction of patient data in accordance with the objective of each clinical study and the use of an optimized DB. In this study, clinical information of patients who were prescribed statins for the first time was extracted from the CDW. A data mart for analysis appropriate to the study objective was established, and relevant DB information was obtained. Various structured or encoded clinical information could be automatically incorporated into the DB. However, unstructured free text content, such as patient height and weight, was manually inputted by direct chart review. To enhance the reliability of the data, problematic values were reviewed and compared with the original data. A data description table was developed (Fig. 3). Personal identification information (name, social security number, etc.) was not included when extracting the requisite clinical data. Patient numbers were collected anonymously during the data collection.

The data included patient personal information, such as height, weight, age, sex, etc. Patient laboratory results included glucose levels, AST/ALT values, and others, as shown in Table 1 for the baseline, visit 1 (an average of 3 months later), visit 2 (an average of 6 months later), visit 3 (an average of 9 months later), and visit 4 (an average of 12 months later) (Fig. 1). The presence of a diagnosis, such as hypertension, diabetes mellitus, etc., and the date when the diagnosis was first provided were together extracted. Accordingly, it was possible to distinguish whether certain diseases occurred before or after the first statin prescription and how soon the diseases occurred after the first statin prescription. Additionally extracted were various medications that were prescribed besides statins or those that could interact with statins.

Data were extracted of a total of 21,368 patients who were prescribed statins for the first time at the hospital over 7 years, from January 2009 to December 2015 (Fig. 4). The percentage of males was 44.2% (9,439/21,368); the percentage of females was 55.8% (11,929/21,368). The mean age was 63±12 years. A total of 17 different statins were extracted. Atorvastatin (10 mg; 21.0%, 4,490/21,368) and rosuvastatin (10 mg; 20.4%, 4,364/21,368) were the most commonly prescribed, followed by simvastatin (20 mg; 11.7%, 2,493/21,368) and pitavastatin (2 mg; 11.1%, 2,364/21,368). Statins were most often first prescribed by the endocrinology department (69.6%, 14,865/21,368), followed by cardiology (13.0%, 2,770/21,368) and neurology (3.9%, 832/21,368).