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Purpose: We aimed to develop a reliable identification algorithm combining diagnostic codes with several treatment factors for inpatients with acute ischemic stroke (AIS) to conduct pharmacoepidemiological studies using the administrative database MID‐NET® in Japan. Methods: We validated 11 identification algorithms based on 56 different diagnostic codes (International Classification of Diseases, Tenth Revision; ICD‐10) using Diagnosis Procedure Combination (DPC) data combined with information on AIS therapeutic procedures added as "AND" condition or "OR" condition. The target population for this study was 366 randomly selected hospitalized patients with possible cases of AIS, defined as relevant ICD‐10 codes and diagnostic imaging and prescription or surgical procedure, in three institutions between April 1, 2015 and March 31, 2017. We determined the positive predictive values (PPVs) of these identification algorithms based on comparisons with a gold standard consisting of chart reviews by experienced specialist physicians. Additionally, the sensitivities of them among 166 patients with the possible cases of AIS at a single institution were evaluated. Results: The PPVs were 0.618 (95% confidence interval [CI]: 0.566–0.667) to 0.909 (95% CI: 0.708–0.989) and progressively increased with adding or limiting information on AIS therapeutic procedures as "AND" condition in the identification algorithms. The PPVs for identification algorithms based on diagnostic codes I63.x were >0.8. However, the sensitivities progressively decreased to a maximum of ~0.2 after adding information on AIS therapeutic procedures as "AND" condition. Conclusions: The identification algorithms based on the combination of appropriate ICD‐10 diagnostic codes in DPC data and other AIS treatment factors may be useful to studies for AIS at a national level using MID‐NET®. [ABSTRACT FROM AUTHOR]

What is known and Objective: Since its introduction in April 2012, denosumab has been administered to approximately 7,300 patients as of August 2012, and 32 cases of serious hypocalcaemia after denosumab administration, including two deaths, have been reported in Japan. A Dear Healthcare Professional Letter of Rapid Safety Communication ('Blue letter') was released to warn about the risks of hypocalcaemia associated with denosumab. The goal of this study therefore was to measure the impact of regulatory action on denosumab‐induced hypocalcaemia in Japan by using an electronic medical information database (MID). Methods: We used two different aggregated data sets based on MIDs (data sets one and two). The patients studied were those who were newly prescribed denosumab or zoledronic acid between April 2012 and September 2014. We assessed four indicators: (a) the proportion of patients with calcium supplementation at the initial denosumab treatment, (b) the proportion of patients who underwent a serum calcium test, (c) the average number of serum calcium tests performed and (d) the prevalence of hypocalcaemia. All indices were aggregated by every 3 months. To evaluate the impact of regulatory action, we used difference in difference (DID) analysis. Results and Discussion: The proportion of patients with calcium supplementation at the initial denosumab treatment increased year by year in both data sets. The average number of serum calcium tests increased year by year in data set two. There was a significant difference in the prevalence of hypocalcaemia in data set two. This suggests that the estimate of impact of the regulatory action may vary according to the database. In DID analysis, however, significant influences of the regulatory action on combination use with a calcium supplement were detected in both data sets. What is New and Conclusion: There was a significant influence on combination use of denosumab with vitamin D and/or calcium supplement in both data sets. That there was no apparent increase in the prevalence of denosumab‐induced hypocalcaemia, suggests that the regulatory action had an impact in the clinical setting studied. Such regulatory actions may play an important role in the promotion of drug safety. [ABSTRACT FROM AUTHOR]

Purpose To establish a new medical information database network (designated MID‐NET®) to provide real‐world data for drug safety assessments in Japan. Methods: This network was designed and developed by the Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency in collaboration with 23 hospitals from 10 healthcare organizations across Japan. MID‐NET® is a distributed and closed network system that connects all collaborative organizations through a central data center. A wide variety of data are available for analyses, including clinical and administrative information. Several coding standards are used to standardize the data stored in MID‐NET® to allow the integration of information originating from different hospitals. A rigorous and consistent quality management system was implemented to ensure that MID‐NET® data are of high quality and meet Japanese regulatory standards (good post‐marketing study practice and related guidelines). Results: MID‐NET® was successfully established as a reliable and valuable medical information database and was officially launched in April 2018. High data quality with almost 100% consistency was confirmed between original data in hospitals and the data stored in MID‐NET®. A major advantage is that approximately 260 clinical laboratory test results are available for analysis. Conclusions: MID‐NET® is expected to be a major data source for drug safety assessments in Japan. Experiences and best practices established in MID‐NET® may provide a model for the future development of similar database networks. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study is to evaluate the accuracy of gastrointestinal (GI) perforation ICD‐10 coding in the Diagnosis Procedure Combination (DPC) database and to examine drug exposure risk factors for GI perforation. Methods: A total of 100 patients with GI perforation ICD‐10 codes were selected randomly from Kagawa University Hospital's DPC database between April 2011 and December 2016. Two experienced specialist physicians independently reviewed the medical records and classified cases as "definite A," "definite B," "probable," or "no GI perforation." The positive predictive values (PPVs) of "definite A/B" cases were calculated after stratification by sex, age, ICD‐10 code, and diagnostic information in the DPC data. The number of prescribed drugs with side effects of GI perforation according to historical data was compared between "definite A/B" and "no GI perforation" cases. Results: The overall PPV was 47.0% (95% confidence interval [CI], 36.9‐57.2). However, the PPVs for the three categories of diagnostic information in the DPC data ("main diagnosis," "diagnosis causing admission," and "most resource‐intensive diagnosis") were each more than 70% after excluding inappropriate patients. Additionally, the PPV focused on these three categories was 76.3% (95% CI, 59.8‐88.6). Prescribed drugs with side effects of GI perforation were more frequently detected in "definite A/B" cases (P = .028). Conclusions: Although the overall PPV for GI perforation based on ICD‐10 code was low, our results suggest that the PPV could be improved by appropriate selection of DPC diagnosis category and that use of multiple medications enhances the risk of GI perforation. [ABSTRACT FROM AUTHOR]

Purpose To examine the potential role of Medical Information Database Network (MID‐NET®), a newly established Japanese medical information database network, in postmarketing drug safety assessments through the characterization of its advantages and limitations in five pilot studies. Methods: The pilot studies were designed to address three major objectives in postmarketing drug safety assessments, ie, the examination of actual drug utilization, the impact of safety‐related regulatory actions, and drug‐associated risks. The five studies were conducted on the following topics: (a) utilization of codeine‐containing products and its relationship with respiratory depression, (b) impact of a Dear Healthcare Professional letter on hypocalcemia incidence associated with denosumab (Ranmark®) use, (c) risk of acute myocardial infarction associated with antidiabetic drug use, (d) risk of glucose metabolism disorders associated with atypical antipsychotic drug use, and (e) prospective monitoring of abnormal laboratory test results during new drug prescriptions. Results: The pilot studies were successfully conducted and demonstrated the value of MID‐NET® in postmarketing drug safety assessments. In particular, the ability to utilize laboratory test results as objective clinical indicators is a major advantage of this database. Potential limitations include a relatively small sample size and a lack of patient‐level data linkages among hospitals. Conclusions: MID‐NET® was confirmed to be a valuable database for postmarketing drug safety assessments. The use of laboratory test results to define clinical outcomes may allow more objective and accurate analyses to be conducted. These studies furthered our understanding of the characteristics of MID‐NET®, including its advantages and limitations. [ABSTRACT FROM AUTHOR]