Clinical trials of new antibiotics in children in Japan

Japan is the most advanced of the industrialized nations in the development of antibiotics. Compared to the United States and countries of the European Union, there is a rich selection and availability of new and appropriate antibiotics for patients with infectious diseases in Japan that is unchallenged under a medical system where its people are all covered by a national health insurance plan. This can also be said in the area of antimicrobial treatment of children and newborns. In Japan, the turning point (T-point), which the author defines as the point when the average life expectancy of newborns equals that of 1 year olds, was in 1970. Keeping infant deaths from infectious diseases under control was indispensable for this achievement, to which antibiotics had greatly contributed. After the T-point, another methodology was needed in pediatrics. The situation in Japan, where most newly developed antibiotics are equipped with statements concerning methods of administration, dosage and safety for children or newborns, differs considerably from overseas situations. The procedures and methods of the clinical trials on children that were performed in strict compliance with good clinical practice are described. Trial studies cannot be performed easily in Japan. Next, the reason why the clinical trials of the antibiotics in pediatrics were performed and accurately evaluated without incident over 50 years by comparatively small numbers of specialists and facilities is described historically and retrospectively. During the 30 years since modern methods were established, clinical trials of antibiotics with children and newborns have been performed only on essential agents; about one-half and one-third, respectively, of the 91 new antibiotics on which clinical trials with adults were conducted. The author has recently published evaluation criteria for clinical studies on antibiotics in the pediatric field. In addition, as the trial's director/administrator, the author states his concept for future clinical development of new antibiotics for children.     

Autologous Bone Marrow Transplantation in Acute Lymphoblastic Leukemia following In Vitro Treatment with Monoclonal Antibodies and with Complement: Analyses for Two Cases of Failure

Two children with acute lymphoblastic leukemia (ALL) receivedautologous bone marrow transplantation (BMT) using remissionbone marrow treated in vitro with the monoclonal antibodies,CD24 (BA-1), CD9 (BA-2) and CD 10 (BA-3), and with rabbit complement. In one child with second remission ALL, hematopoietic recoveryafter BMT was prompt but, 81 days after BMT, isolated centralnervous system (CNS) relapse occurred. Bone marrow relapse developedthree months later, and she died 11 months after BMT. In patientswith CNS leukemia prior to BMT, as in the present case, moreintensive pretransplant CNS treatment and/or a conditioningregimen may reduce the risk of relapse. In the other patient, with primary refractory ALL in first remission,marrow reconstitution was slower. The patient developed interstitialpneumonitis with pleural effusion, and died 54 days after BMT.No infectious causes could be detected by culture or from serologicalstudies of the pleural effusion. The rationale for applying autologous BMT to children with secondremission ALL and first remission refractory ALL is discussed.