Analysis of Pharmaceutical Safety-Related Regulatory Actions in Japan: Do Tradeoffs Exist Between Safer Drugs and Launch Delay?

Abstract

The occurrence of SRRAs was associated with the accumulation of both foreign and domestic postmarketing evidence rather than with clinical trial data upon launch. Considering the paradigm shift to simultaneous global drug development and filing for regulatory approval, this study indicates the importance of intensive data collection in the early postmarketing phase and use of safety information in early markets. However, even if we would be sufficiently cautious about safety risks of new drugs, a population that enjoys first-in-class drugs probably has to bear the risks.

Analysis of the success rates of new drug development in Japan and the lag behind the US

“…In a recent study, launch delay in Japan was associated with fewer post-marketing safety risks in the Japanese market [14]. This type of advantage in drug safety may also strengthen the incentive to be followers rather than firstmovers, especially in Japan where both drug companies and customers are very sensitive to safety problems due to serious drug safety scandals in past decades [15].…”

Factors associated with spontaneous reporting of adverse drug reactions in Japan

“…This suggests that post‐marketing information (e.g., phase 4 clinical trials, pharmacoepidemiological studies, and regulatory actions) collected in the early markets during the lag period had a beneficial impact on drug safety in follow‐up markets. This result was consistent with the finding for safety‐related regulatory actions (SRRAs) in Japan, which indicated that there were 0.37 times fewer SRRAs for drugs with a lag of at least 60 months before approval in Japan. Japanese patients seem to benefit from foreign safety data.…”

“…It is quite common for new drugs to be filed and approved in Japan several years after being approved in the United States and/or European Union and thus newly approved drugs in Japan would have information both from clinical trials and from post‐market utilization of the early markets. We used the launch lag, that is, the gap between United States/European Union and Japan approval as a proxy variable reflecting the amount of information obtained after marketing in other countries Foreign information: Foreign information such as serious AE reporting or study results can affect the numbers of AEs reported .…”

“…All‐case surveillance is typically imposed as an approval condition for some drugs, and in these cases, it is only after the evaluation of the all‐case surveillance data is completed that marketing for broader populations is actually allowed. The all‐case surveillance may also enhance spontaneous ADR reporting. Approval year: This variable was included to adjust for any possible trend in the count of spontaneous ADRs in a given year, as has been done in many previous studies …”

“…This article explored how the accumulation of safety information, status in foreign countries, drug company attributes, and regulatory actions were associated with the numbers of spontaneously reported ADRs in Japan. We established six models (Models A–F), each of which had a slightly different set of variables and samples . The choice of variables was based on the models used in previous studies, our experience, and research interest (Table ).…”