Relationship between drug lag and factors associated with clinical trials in Japan.

Abstract

Drug lag is a major public concern in Japan. During the development of new drugs, some factors related to clinical trials in the marketing application package, such as trial design and the number of trials, can affect drug approval. The aim of this study was to determine whether those clinical trial factors were associated with drug lag in Japan. We investigated new drug applications for new molecular entities that were approved in Japan between April 2009 and March 2012. We collected information on clinical trials in the marketing application package from review reports. We constructed a multiple regression model to predict drug lag using the review period, use of foreign clinical trial data, the number of confirmatory trials, the design of the pivotal trial, failures of confirmatory trials and the death rate (n = 59). No use of foreign trial data was significantly associated with a longer drug lag (84% increase; 95% confidence interval [CI], 1·03-3·29). Compared to the open-label, one-armed design, drugs that underwent pivotal trials of placebo-controlled superiority, active-controlled superiority and active-controlled non-inferiority designs had a significantly shorter drug lag (74% decrease, 95% CI: 0·08-0·83; 74% decrease, 95% CI: 0·07-0·99; and 85% decrease, 95% CI: 0·04-0·58, respectively). Our findings suggest that new drug application packages that do not use data from foreign clinical trials and that involve pivotal trials of open-label, one-armed design contribute to drug lag in Japan. To reduce this lag, improved strategies for the development of new drugs should be identified.