Identification and application of STOPP-J drug substances
The efforts to reduce inappropriate drug use in elderly patients are likely to have a substantial impact on reducing drug-related morbidity. One major required step is a change in the prescription behavior of physicians, which is influenced by their knowledge and alert systems involving pharmacists, computerized reminders , and promotional information from pharmaceutical companies . The current JGS guidelines provide concept and review steps for prescribing to the elderly but do not fully detail specific substances. Thus, our computerized database of standard drug substances, reflecting the STOPP-J with a corresponding coding system, will provide an efficient way to improve physician knowledge about medication for the elderly.
This study revealed that some substances approved in Japan were omitted from the ATC classification system, which was also reported by Groot et al.  in reference to the STOPP/START. This may occur when a drug is marketed in Japan only, and the substance or combination is not registered with the WHO Collaborating Center for Drug Statistics. When other countries have the same situation, it would also be necessary to set up the framework to ask the WHO Collaboration Center to include medicinal substances limited to them. This would enhance ATC completeness. To support ATC users, the Uppsala Monitoring Center/WHO Collaborating Centre for International Drug Monitoring does provide the WHO Drug Global with drug information, including Japanese approved drugs and referencing ATC codes at the 5th level, for global pharmacovigilance . Their service supports linking Japanese substances with the ATC, and major global companies use this service for internal databases. It is important to make ATC codes useful in pharmacovigilance and pharmacoepidemiology studies for all Japanese and worldwide drugs and create an official framework to register new substance as soon as possible. This would facilitate drug safety monitoring by pharmaceutical companies and the review of drugs at the class and substance levels. We excluded some medicinal products from the first listing step of the drug indication categories. This paradoxically suggests that researchers run the risk of including appropriately prescribed drugs when extracting data from the drug classification systems.
When the Beers criteria were applied to studies on Japanese elderly patients, hospitalization risk was higher in potentially inappropriate medication users  and, in contrast, no association was observed between potentially inappropriate medication use and adverse outcomes . The study using STOPP and START addressed the notion that potentially inappropriate prescribing increased healthcare utilization . Although some drug utilization studies have been reported on the STOPP-J, the future applications of our results to pharmacoepidemiologic clinical studies are worth considering in Japan, similar to a previous study using the Beers criteria in Japan [12, 13]. The use of large databases has become more sophisticated, and 13 Japanese healthcare databases are acknowledged by other entities  (e.g., JMDC Claims Database® , which provides the names and ATC codes of drugs prescribed from 2005). Some unlisted domestic databases also exist, including the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), which maintain data records from April 2013 provided by the ministry . Currently, no ATC codes are available in the NDB, but the National Health Insurance Drug Price List codes are provided and, therefore, our proposed codes can be used. Another database is the Japanese Adverse Drug Event Report database (JADER), which records spontaneous reports of adverse events to the regulatory agency and lists drug names in plain text, without codes . MID-NET is another prospective database, which was launched in April 2018 by the regulatory agency . It is noteworthy that global comparisons based on the guidelines for medication in the elderly would be complicated or difficult to analyze because substances and their corresponding codes vary.
Currently, there are many therapeutic guidelines and principles for the proper use of medicines, and different definitions are presented worldwide or even in certain countries. Since those guidelines are to be updated periodically in several years, the guidelines propose their philosophies and examples, without identification of drugs. Therefore, interpretation and practice tend to vary by users. When adopting the guidelines, it is important to first define drugs of interest at the component molecule level; however, papers that do not identify the studied drug names might exist. In this research, with reference to the research method of Groot et al.  of Ireland, we presented concrete pharmaceutical molecules intended by the STOPP-J proposed by the JGS and proposed corresponding drug codes to be widely used in Japan. The results of this research are expected to be helpful in designing research and validating the actual condition of medical service at a clinical institute. Another important application is to import the drug code list into electronic prescription systems and health information systems so that the system can aid physicians in prescribing cautiously. This application is expected to be used in practice in the near future.
Limitations of using the list
This study was limited to Japanese drugs for internal use, except insulin, because the JGS guidelines focus on the long-term use of drugs to promote appropriate medications and avoid systemic adverse events in the elderly. The study also excluded drugs mainly used for short-term treatments of less than 1 month, e.g., antipyretics. In addition, based on the JGS, the target population in our list comprised patients older than 75 years who are with or without frailty, which is quite different from other guidelines. The drug list would be useful in research to understand the status of drug prescribing or hypothesize about the trends in total drug use and polypharmacy. However, more information such as dosage regimens and comorbidities is normally required to answer clinical questions. Users also need to consider how to interpret the output. For example, the alerted drug should be able to be monitored or stopped for individual patients. Because the JGS tool is not meant to be a prescription rule, but rather provides information to support physicians’ judgment when prescribing, the dosage regimen and underlying diseases should be mentioned. Lastly, a periodic update of the list is critical for efficient use in practice.
This was the first challenge to identify the STOPP-J substances to be coded. Some difficulties were found through the work in the interpretation of the STOPP-J, for example, insulins, and healthcare data users may misunderstand what the guidelines really proposed. In addition, new medicines need to be timely evaluated to determine whether they should be prescribed with special caution or considered for medication.