2005 Fiscal Year Final Research Report Summary
New study design on Phase I studies for hematological disorders, especially in translational research.
| Project/Area Number |
16590929
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAGAMURA Fumitaka The University of Tokyo, The Institute of Medical Science, Instructor of Center of Excellence, 医科学研究所・研究拠点形成特任教員(特任講師) (90282491)
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| Co-Investigator(Kenkyū-buntansha) |
TOJO Arinobu The University of Tokyo, The Institute of Medical Science, Professor, 医科学研究所, 教授 (00211681)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Translational Research / Hematological Malignancies / Phase I studies |
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| Research Abstract |
By the analysis of approved drugs between the U.S. and Japan, following results/conclusions were obtained : Among 27 drugs approve in both countries, 22 were approved faster in the U.S. (mean 46 Mo) ; "Indication" described in the package inserts in Japan are less detailed ; Some of endpoints used in Japanese studies were not appropriate ; The number of drug approved under Accelerated Approval has increased rapidly, and 8 of 11 drug approved after 1999 were under Accelerated Approval ; Most of drugs approved under Accelerated Approval belong to "molecular target drugs" ; Drugs approved only in Japan belong to analogs of approved drugs, or approved for other indications those did in the U.S. No entirely new molecular entities were approved in Japan ; The number of patients enrolled in the pivotal studies of approved drugs in Japan was around one-tenth to one-half of that in the U.S. We pointed out above problems, and studies the new study design of Phase I studies for hematological malignancies, especially for translational research, so as not to repeat the same mistakes in the future studies. We propose the following study design of Phase I studies on new concept of therapies for patients with hematological malignancies. Dose increment should be half-log increment, and x5, x2, two-step log increment should be used in the case of antibodies. Single dose study would be avoided to evaluate the biological activities more precisely. In terms of patient cohorts, three patient cohorts should be used to evaluate the biological activities. As for stopping rule, two target points should be used. One is toxicities, and the other is biological response and/or PK/PD of administered materials. By this concept, most of therapies would be tested appropriated in Phase I studies
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