Phase III clinical studies and long-term safety studies are obviously pivotal as the clinical data from the viewpoint of new drug approval. To conduct successfully those clinical studies, appropriate dose or dose range setting prior to performing those studies is extremely important.

There are not a few drugs, approved daily dosages of which are noticeably different between Japan and the West, and even between USA and Europe.

When both the maximum and minimum approved doses for drugs belonging to five therapeutic classes (non-steroidal anti-inflammatory/analgesics, antipsychotics, cardiovascular, gastrointestinal and antibiotics) were compared between Japan and foreign countries, the approved doses in Japan tend to be lower than in other countries for both minimum and maximum approved dose, such as in the non-steroidal anti-inflammatory/analgesics and antibiotics, while for cardiovascular drugs the maximum range seems to be lower than in other countries. On the other hand, the mean values of pharmacokinetic parameters of many drugs are, in general, quite similar between Japanese and Caucasians.

These differences in approved daily dosages may suggest existence of some ethnic differences. Ethnic differences can be classified into intrinsic and extrinsic factors. Several studies performed in Japan and in Europe suggested that in many cases extrinsic factors, such as medical practice and custom, might more influence the dose setting than intrinsic factors.

Recently, many pharmaceutical industries try to get the approval of the new drug by utilizing foreign clinical data package with the bridging study. In most cases the industries want to extrapolate Phase III study data and/or long-term safety study data by conducting Phase II dose finding studies as the bridging study. However, quite a few dose finding studies performed in the past, before clinical trial consultation in OPSR was started, were poorly planned and/or inadequately performed: too small subjects for each dose group; inappropriate selection of dose levels examined; use of vague endpoint; tendency of selecting the lower dosage as the recommended regular dose without sound scientific rationale, reflecting the old concept in Japan, namely safety is preferable to efficacy. Fortunately, the situation in dose setting studies in Japan has recently been changing very quickly in the right direction.