Assessment of factors associated with dose differences between Japan and the United States.

Although it is well known that there are differences in approved doses between Japan and the United States, there has been no comprehensive research into the causes thereof. This study furthers the discussion of our previous investigation in 2010, with particular focus on pharmaceutical industry strategy and regulatory policy, among drugs approved in Japan between 2001 and 2009. Dose differences were observed in 73 of 190 drugs. Non-Japanese firms were more likely to have a similar dose approved between Japan and the United States, the association being more pronounced when limiting the analysis to drugs for which a Japanese dose-finding study was not conducted. Furthermore, dose differences were less frequent when non-Japanese efficacy data were included in the application data package. No relation between potential intrinsic ethnic difference and dose difference could be identified. The results suggest that the pathway of drug development is more strongly associated with dose difference than are drug characteristics.

Exploring differences in drug doses between Japan and Western countries.

Japan is unique among Asian countries in that it requires inclusion of substantial domestic clinical trial data in new drug application data packages. Some question the need for this and call for globalization of approved doses. The current study examines international differences in maximum daily dose of drugs approved in Japan between 2001 and 2007, and for all cardiovascular system (CVS) and central nervous system (CNS) drugs marketed in Japan. For 32% of the drugs approved in Japan between 2001 and 2007, the maximum recommended dose in the United States was > or =2 times higher than the maximum dose approved in Japan. Dose differences were rare for antitumor and antiviral drugs and also for priority-review and orphan drugs. Of all the price-listed CVS drugs currently available in Japan, 65% had maximum doses that were > or =2 times higher in the Netherlands than in Japan; similarly, 57% of the drugs had maximum doses that were > or =2 times higher in the United States than in Japan. For CNS drugs, these figures were 32% (the Netherlands) and 29% (United States). These results underscore the necessity to carry out quantitative analyses to determine the causes of these differences.

Performance improvement with a hybrid FOCUS-PDCA methodology.

BACKGROUND: In 1995 a team of three members of the quality improvement (QI) department at Hardin Memorial Hospital, Elizabethtown, Kentucky, constructed a unified, simple system of tools and activities drawing on the foundation of FOCUS-PDCA and integrating it with the Joint Commission Improving Organizational Performance (IOP) function and language. METHOD: The team developed documentation tools and educational activities to support each part of the cycle for improving performance: plan--a planning workshop; design--a hybrid FOCUS-PDCA model; measure and assess--a three-part indicator workshop; and measure, assess, and improve--a redesigned QI report form. To document the entire cycle, the team developed an IOP Notebook and a workshop introducing it. Requirements for process design were established based on the standards. Next, the C phase, traditionally interpreted to clarify the current process by flowcharting, was broadened to include internal and external clarification of the process. APPENDIX-USING THE FOCUS--PDCA HYBRID TO REDESIGN AN ANTIBIOGRAM: The hybrid model's hallmark is its flexibility in supporting projects where the need for redesign over improvement is not clear at the outset. In a year-long study in 1995, a "Critter Ridder" Team at Hardin Memorial Hospital used the model to design an innovative antibiogram. In the C phase, customer input was gathered from physicians and a literature search was conducted to identify other antibiogram formats. The team constructed the antibiogram to meet key quality characteristics-accessibility, information, accuracy, timelines, and layout. Documentation on the IOP Notebook templates demonstrates the team's implementation of the performance improvement standards in its design.