Although doxazosin, a subtype nonselective α1-adrenoceptor antagonist, has been shown to improve hypertension and benign prostatic hyperplasia, it is recommended that the two disease entities should be treated independently with the best available drugs. Therefore, we compared the efficacy and safety of three α1-adrenoceptor antagonists with different selectivity for the α1-adrenoceptor subtypes ; doxazosin, silodosin and tamsulosin, for lower urinary tract symptoms in male patients with hypertension and benign prostatic hyperplasia. In a retrospective study, the medical records of 58 hypertensive patients with benign prostatic hyperplasia treated with doxazosin, silodosin plus amlodipine, or tamsulosin plus amlodipine between January 2013 and December 2015 were evaluated. International Prostate Symptom Score (I-PSS), QOL score and maximum urinary flow rate were assessed at baseline and after a 12-week treatment period in all patients. Treatment with doxazosin and amlodipine resulted in a significant reduction in blood pressure from baseline. Doxazosin, silodosin and tamsulosin were similarly effective in improving total I-PSS, QOL score and maximum urinary flow rate. While dizziness was reported in 1 of the 21 patients receiving doxazosin, abnormal ejaculation was reported with subtype selective α1-adrenoceptor antagonists but not with doxazosin. Our data demonstrate that all three α1 -adrenoceptor antagonists have similar clinical efficacy and that there are slight differences in the adverse event profiles of these drugs. These findings suggest that doxazosin is a safe and effective treatment in hypertensive patients with benign prostatic hyperplasia.
Background: In Japan, delay in marketing approval of new drugs, known as “drug lag”, was believed to hinder patient access to innovative treatments. The Japanese government took several corrective measures, and the median review time for new drugs was shortened. However, in many cases, new drugs are developed in the United States (US) and European Union (EU) , and these drugs are usually approved first in the US and EU prior to approval in Japan. Increase of drugs approved in Japan before the rest of the world or simultaneous with other countries is expected to further improve patient access to innovative drugs.
Method: For all New Active Substances (NASｓ）that were approved in Japan between January 2008 and December 2014 , detailed information including the regions where the new drugs were developed and the countries of first global approval were identified. We also collected information about safety concerns that were identified before approval.
Result: Two hundred and thirty-nine NASｓ obtained Japanese approval during the study period. Of the 239 NASｓ, 44 (18.4%) were approved in Japan before the rest of the world. Drugs that obtained Japanese approval first in the world were more often developed in Japan from the early stage. Furthermore, the data suggested that these drugs were launched with relatively limited safety information.
Conclusion: For better patient access to new drugs, it is important to facilitate early development of new drugs in Japan and at the same time to ensure further strengthening of post-marketing safety measures.
Drug development in Japan is very important to the nation from the point of view of providing the highest level of medical care in Japan. Grouping multiple medical institutions to form a large clinical trial network is indispensable for drug development with respect to improvement of case recruitment. Showa University has eight affiliated hospitals in Tokyo and Kanagawa with a total of 3,200 beds, and is engaged actively in the promotion of clinical trials and clinical research. From July 2012, the Showa University Hospital Clinical Trial Support Center played a leading role to coordinate with the Clinical Trial Support Offices of the eight affiliated hospitals, holding a clinical trial support joint meeting once every three months. A working system was established for standardization of formats and costs as well as joint operation of the IRB, eventually leading to the establishment of a clinical trial network for the eight hospitals of Showa University. Also, a large number of clinical studies that can only be conducted in the university hospital setting have been conducted. Education on clinical trial and clinical research is important not only for medical staff including physicians, dentists, pharmacists, nurses, and laboratory technicians, together with students of medical sciences, but also for staff outside medical institutions including pharmaceutical companies. In this article, we report the issues encountered and their solutions while constructing the clinical trial network for eight hospitals of Showa University. Furthermore, we propose the future challenges of this network, which we hope will provide a reference for other organizations.