A Survey Regarding the Price Calculation Method for New Drugs Based on the Chuikyo-Document about the NHI Drug Price List / 医薬品情報学

In Japan, the National Health Insurance (NHI) prices of new drugs are set according to the NHI Drug Price Standard (NHI Price Standard).　The NHI Price Standard was notified by the Ministry of Health, Labour, and Welfare based on the ”Drug Price Calculation Criteria” proposed by the Central Social Insurance Medical Council (Chuikyo) in Japan.　The NHI Price Standard affects the research and development strategy of pharmaceutical companies.　In order to discover undetected relationships, the factors influencing the ”drug price” were evaluated through the association rule mining technique.　We surveyed the Chuikyo‐documents about NHI price listing over the period October 27, 2006 to February 8, 2007.　The number of approved new drugs was 874, while that of drugs completed (”drug price per day”) was 314.　The numbers of new compounds corresponding to a drug price per day of ”below 200 yen,” ”between 200 yen and 1,000 yen,” ”between 1,000 and 10,000 yen,” and ”above or equal to 10,000 yen” were 87 (27.7%), 91 (29.0%), 79 (25.2%), and 57 (18.2%), respectively.　In the association rule mining method, we observed high lift values of the combined items ”above or equal to 30,000 patients expected to be administrated” and ”drugs affecting sensory organs” in the group of drug price per day below 200 yen.　The lift values of the combinations of ”biological preparations” and ”similar efficacy comparison‐based price setting (Ⅱ)” or ”below 30,000 patients expected to be administrated” and ”antineoplastic drug” in the group of ”above or equal to 10,000 yen of drug price per day” were high.　These results provide a basis for the development and application of new drugs in Japan.

Evaluation of Dermatological Disorders Caused by Anti-neoplastic Agents with an Adverse Event Spontaneous Reporting Database / 医薬品情報学

<b>Introduction</b>: Dermatological disorders are one of the adverse events caused by cancer chemotherapy and are a dose-limiting factor for some anti-neoplastic agents.  The severe symptoms associated with these disorders affect the patients’ quality of life (QOL).  Early countermeasures for the onset of dermatological disorders associated with anti-neoplastic agent administration might be important.<br><b>Materials and Methods: </b>We analyzed the occurrences of dermatological disorders after administration of an anti-neoplastic agent in the Food and Drug Administration Adverse Event Reporting System (FAERS), and compared the adverse event (AE) reporting ratio of the total reports.  In addition, we studied the association between anti-neoplastic agents and dermatological disorders using cluster analysis.  Reports for 15 anti-neoplastic agents (4 anti-neoplastic agents and 11 molecular target drugs) were analyzed.<br><b>Results: </b>After excluding duplicate data in FAERS, 6,157,897 reports were analyzed.  The number of reports that showed a dermatological disorder was 534,934.  The reporting ratio of hand-foot syndrome with sorafenib and capecitabine was 11.20% and 7.05%, respectively.<br><b>Conclusions: </b>We set the cluster number at six; cluster features obtained were as follows: (1) the reporting ratio of hand-foot syndrome was especially high, followed by the reporting ratio of rash, (2) the reporting ratio of rash and erythema was high.  Similar anti-neoplastic agents may demonstrate similar occurrence tendencies of AEs and cluster features.  Further studies are required to draw conclusions over these findings.  Information services based on the feature of each cluster might be useful to improve patient QOL at the clinical site.

Analysis of the Association between Neuraminidase Inhibitors and Neuropsychiatric Adverse Events Using Japanese Adverse Drug Event Report (JADER) / 医薬品情報学

There have been concerns that neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir) cause neuropsychiatric adverse events (NPAEs).  We evaluated the number of relevant reports, reporting ratio, and reporting odds ratio (ROR) by using spontaneous reporting database, such as the Japanese Adverse Drug Event Report (JADER) (April 2004 to July 2014).  The RORs of oseltamivir, zanamivir, laninamivir, and peramivir were 11.8 (95% confidence interval (CI), 10.8-13.0), 47.0 (95% CI, 40.0-55.3), 9.5 (95% CI, 6.8-13.2), and 3.3 (95% CI, 2.1-5.1), respectively.  The lower limit of the ROR 95% CI of NPAEs of all neuraminidase inhibitors was ≥1.  We analyzed the association of age and gender with NPAEs in patients treated with oseltamivir using a logistic regression model.  The adjusted ROR of NPAEs was 66.9 (95% CI, 50.3-88.9) in male patients treated with osletamivir aged 10-19 years.  The adjusted RORs of NPAEs were increased in male and female patients under the age of 20 years.  Neuraminidase inhibitors including oseltamivir treatment could be associated with NPAEs.  Therefore, these drugs should be used carefully in clinical practice.