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PAL suggests that for each additional formulation, data on not fewer than 40 cases in not fewer than two institutions should be submitted. Guidelines for the clinical evaluation of 11 categories of drugs are available (Table 4); however, only the first 7 have easily available English translations. Efforts to deviate from the outlined course of clinical trials or their design regularly causes difficulties, in part because of the dominant role of the supervisory investigator. |
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The ability to use foreign data is limited at present and those inclined to use it in a Japanese NDA should consult beforehand with members of the NDD of the PAB. The PAB Notification 660 sets out the conditions necessary for acceptance of foreign data [29]. Foreign clinical trials must meet the Japanese clinical practice standards or be applicable to medical care as carried out in Japan. They should have been conducted by experienced researchers from reliable medical institutions and the results, as with the preclinical data, should be published. In addition, individual patient case records and statistical analysis records of the study must be available for inspection. Given all this, foreign clinical data are only accepted in relation to safety information. Currently one must conduct the ADME and dose-range-finding studies and a full Phase III program within Japan. Yet it would not be unreasonable to expect that if the ADME and dose-range-finding studies conducted in Japan agreed with the results from such studies conducted outside Japan, that the Koseisho would accept Phase III data conducted elsewhere to GCP standards. There is support for such a move within the Koseisho; however, there is little corresponding enthusiasm within the powerful Senior Physician Lobby. |
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In Japan there is a distinct reluctance to use a surrogate marker in trials defining dosage, unless the hypothesis supporting its use as a predictor of the desired effect has been proven. Thus in a global development program, if one |
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| Table 4 Guidelines for Clinical Evaluations Are Available for Eleven Categories of Drugs | | Antihypertensive drugs (established in 1979 and amended 1989) | | Antiarrhythmic drugs (established in 1984) | | Antiangina pectoris drugs (established in 1985) | | Analgesic, anti-inflammatory drugs (established in 1982 and amended 1985) | | Oral contraceptives (established in 1987) | | Cerebral vasodilators (established in 1987) | | Antihyperlipemies (established in 1988) | | Antidepressant drugs (established in 1988) | | Hypnotic drugs (established in 1988) | | Drugs for heart failure (established in 1988) | | Anticancer drugs (established in 1991) |
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