Objective: In this study, we analyzed the Japanese Adverse Drug Event Report (JADER) database in order detect unexpected adverse events using three polypharmacy machine learning models.

Methods: The patient’s age, weight, height, gender, date and time of onset, subsequent appearance, and the taking medicines were preprocessed. They were applied for the prediction of adverse events using three machine learning procedures such as support vector machine (SVM), deep neural network (DNN) and random forest (RF).

Results: Precision, matching, reproduction and F-values were almost same between the three techniques. Polypharmacy effects were predicted in approximately 80% of adverse events. Unexpected predictions were observed between DNN and RF, but different from SVM.

Conclusion: Results suggest that the combination of DNN or RF and SVM can yield accurate predictions. We also suggest that RF is more useful because of its easy validation.

Objective: Risk Management Plan (RMP) is created and submitted by a pharmaceutical company while applying for new drug approval; it is published to be used by healthcare professionals. For example, healthcare professionals utilize RMP when considering whether to adopt a drug. However, there is no stipulation for the release date of RMPs; moreover, surveys regarding this are limited. We conducted a cross-sectional survey on the relationship between RMP-related timing and regulatory affairs-related timing.

Methods: The surveyed drugs were those for which the first version of RMP was notified by PMDA Medinavi (mail delivery service) in FY2014 and FY2018. We examined regulatory affairs-related timing (i.e., “manufacturing and marketing approval date,” “drugprice standards listing date,” and “release date”) and RMP-related timing (i.e., “RMP creation date” and “Medinavi delivery date”).

Results: For 7 of 43 items in FY2014 and 5 of 41 items in FY2018, the “RMP creation date” occurred later than the “drug-price standards listing date.” For one item in FY2014, the “RMP creation date” occurred later than the “release date.” For 12 items in FY2014 and 13 items in FY2018, the “Medinavi delivery date” occurred later than the “release date.”

Conclusion: No considerable difference was confirmed between FY2014 and FY2018 regarding RMP-related timing and regulatory affairs timing. It was confirmed that there were several items for which the RMP creation occurred later than drug-price standard listing and items for which the publishing notice by Medinavi was delayed for drug marketing release. To promote the utilization of RMPs by healthcare professionals, RMPs must be created and published without delay.

Objective: In Japan, healthcare professionals are required to report the adverse drug events that occur with the use of medicines to the Minister of Health, Labor, and Welfare. The reported information is collected in the Japanese Adverse Drug Event Report database (JADER) and is freely available. There are no reports that evaluated the adverse events (AEs) in JADER based on the need for a physician’s diagnosis. This study classified AEs by pharmacists or physicians in JADER based on the need for a physician’s diagnosis and evaluated the differences in their contents.

Methods: AEs reported by pharmacists, physicians, pharmacists and physicians in the economic years 2004 to 2017 in JADER were collected annually, and the trends were compared. The AEs of methotrexate in 2017 were classified into two groups based on the need for a physician’s diagnosis. The necessity of a physician’s diagnosis was judged by two senior pharmacists and compared using the chi-squared test.

Results: The number of AEs reported by pharmacists and physicians from 2004 to 2017 increased from 689 to 7,127 and from 20,933 to 39,382, respectively. Among the AEs of methotrexate in 2017, AEs requiring physician’s diagnosis reported by pharmacists were 337 events and physicians were 2,413 events. Whereas, AEs that did not require a physician’s diagnosis reported by pharmacists were 172 events and physicians were 321 events. Physicians had significantly more AEs requiring diagnosis than pharmacists did (p＜ 0.0001).

Conclusion: The reports of pharmacists with JADER have fewer AEs with the diagnosis than those of physicians.

Lenvatinib hasapplicationsin thyroid and hepatocellular carcinomas. When lenvatinib wasapproved for hepatocellular carcinoma in Japan, the manufacturer noted an increase of 5% in the incidence of side effects than those observed in thyroid cancer, based on the clinical-trial data. The monitoring of side effectsisimportant during chemotherapy. It isdifficult to confirm all the side effects within a single practice, and it is important to consider the incidence and severity of side effects before prescribing a particular treatment regimen. An antineoplastic agent is often used for different diseases, and it may be difficult to confirm a specific side effect. Because clinical conditions vary among different diseases, it is likely that the onset of side effects also differs. We investigated the difference between the onset of side effects in thyroid and hepatocellular carcinomas using the Japanese Adverse Drug Event Report database. The main side effects reported for thyroid cancer included bleeding, hypertension, cardiac disorders, myelosuppression,acute cholecystitis, delayed wound healing, infection, gastrointestinal perforation, fistula formation, and pneumothorax. In addition,patients with hepatocellular carcinoma experienced liver damage and hepatic encephalopathy. A significant strong correlation was observed between the drug dose and number of reports of the varied side effects. We compared the side effects in patients with thyroid cancer to those with hepatocellular carcinoma; although the same drug was used, there was varied expression of the side effects. Thisneedsto be taken into account when determining which drugsare to be used for the treatment of a particular cancer type.

Objective: Glaucoma is the most frequent cause of blindness in Japan and is primarily treated using IOP-lowering ophthalmic solutions. Although the patients themselves frequently instill ophthalmic solutions, instillation by caregivers may be necessary for various reasons. Therefore, we evaluated pharmaceutical characteristics of antiglaucoma ophthalmic solutions and their usability from the caregivers' viewpoint.

Methods: Five dorzolamide hydrochloride-timolol maleate ophthalmic solutions and 2 travoprost-timolol maleate ophthalmic solutions were evaluated concerning the pharmaceutical characteristics and subjective squeezability rated by adults aged 20 years or above.

Results: Among the dorzolamide hydrochloride-timolol maleate compounding ophthalmic solutions, the squeeze force was the lowest in COSOPT^® ophthalmic solution (11.8 N), and DORMOLOL^® combination ophthalmic solution NITTEN was rated highest, with 68.2% of the subjects placing it within the top 3 levels of a 7-level scale. Of the travoprost-timolol maleate ophthalmic solutions, the squeeze force was 9.8 N, lower than the pioneer drug, in TraTimo^® combination ophthalmic solution NITTO, which was also rated in the top 3 levels by 90.3% of the subjects. A strong negative correlation was observed between the squeeze force and squeezability.

Conclusion: In instillation by caregivers, the squeeze force was shown to be correlated with subjective squeezability as in instillation by patients themselves. This study provided information concerning the usability of ophthalmic solutions from the caregivers' viewpoint. For the future, it is necessary to select ophthalmic solutions from the caregivers' as well as the patients' viewpoints by utilizing information obtained in this study.

Objective: Owing to inconspicuous memory impairment during early disease stage, patients with dementia with Lewy bodies (DLB) are often diagnosed with mental disorders according to depressive symptoms and visual hallucinations. Severe sensitivity to antipsychotic agents, a DLB characteristic, increases mortality. Herein, we reviewed current challenges and approaches for early DLB detection and appropriate drug use by evaluating pharmacists' ability to recognition of DLB and their level of involvement in medication consultation with dementia patients.

Designs: This is a cross-sectional study in Japan.

Methods: We provided an anonymous self-administered survey questionnaire to 372 community pharmacists. Descriptive statistics,chi-square test (attributes, recognition, and experiences with medication consultation), and content analysis (free description of drug hypersensitivity) were used for data analysis.

Results: The recognition rates for questions on DLB symptoms were as follows: visual hallucinations, 76%; delusion, 63%; other symptoms, including those categorized as core clinical features, such as fluctuating cognition, and REM sleep behavior disorder,＜40%. The rate of other symptoms was similar to that of false recognition of Alzheimer's disease symptoms. The recognition rate of certain DLB symptoms varied depending on pharmacists' experience in medication consultation with dementia patients and drug-induced evaluation during delirium/cognitive decline over the previous month. Approximately 65% of the participants did not respond to open questions on symptoms suggestive of drug hypersensitivity, whereas 55% of those who responded referred to allergic symptoms such as rashes.

Conclusion: Owing to their lack of recognition of DLB symptoms, the current contribution of pharmacists to early DLB detection and proper drug use is limited. Thus, it is important to provide patients' observation points and method of questioning during interviews so that pharmacists can easily recognize DLB symptoms. It is critical to clarify that DLB drug hypersensitivity is attributed to mechanisms different from that of drug allergy.