DSP-5423P (DSP) is a transdermal delivery formulation containing 20 mg of blonanserin per 40 cm² patch. This open-label, single-arm study was conducted to evaluate the safety and tolerability of repeated application of DSP for 2 weeks in 8 patients with schizophrenia. Four patches of DSP per day (80 mg/day of blonanserin), possessing nearly equivalent striatum dopamine D₂ receptor occupancy to oral administration of 16 mg/day of blonanserin, were applied to the upper back of the patient once per day for 2 weeks. Adverse events (AEs) and pharmacokinetics and schizophrenia rating scales (PANSS and CGI-S) were used to evaluate safety. AEs were reported in 7 out of 8 cases, with application site erythema (n＝5) the most common, followed by application site pruritus (n＝3), and akathisia (n＝3). No serious AEs occurred, and all AEs were determined to be mild in severity. Extrapyramidal AEs were reported in 4 cases, including akathisia (n＝3), bradykinesia (n＝2), and tremor (n＝1). Adverse drug reactions related to the application site occurred in 5 cases; however, all patients recovered with or without treatment with topical agents and completed the study. No apparent change was found in the Drug Induced Extra-Pyramidal Symptoms Scale total score during the study. Regarding pharmacokinetics, plasma concentration of blonanserin and its metabolites did not show any significant changes after application of DSP. Changes in PANSS and CGI-S scores revealed no worsening of schizophrenia during the study. This study demonstrated that there were no safety or tolerability issues with 2 weeks' administration of DSP. (Trial No. JapicCTI-142423)

Background: Clinical research conducted under the Clinical Trials Act, which came into effect in April 2018 in Japan, must be reviewed by a Certified Review Board (CRB) which is accredited by the Ministry of Health, Labor and Welfare (MHLW). There are no reports of substantial investigations of CRBs on a nationwide basis.

Methodology: Questionnaires were sent to 96 CRBs certified by MHLW as on November 22, 2019 to investigate the number of clinical research proposals each CRB reviewed, how technical experts were involved in the review process, the CRBs' own rules of operation, their income and expenditure, and the intention of accreditation renewal.

Results: Responses were received from 73 out of the 96 CRBs (76％). The CRBs had reviewed 382 new clinical research proposals and 848 transitional proposals, 1,230 in total. Since the total number of proposals, 1,230, was approximately 86％ of the 1,422 clinical studies that had got registered in Japan Registry of Clinical Trials (jRCT) as on October 29, 2019 under the Clinical Trials Act, the results of this survey are considered as valid. Regarding renewal of accreditation, 89％ CRBs (63/71) intend to renew their accreditation by MHLW as scheduled, 1％ (1/71) “Will not renew and will discontinue” and 10％ (7/71) are “Undecided.”

Conclusion: This study provides a clear picture of the current status of CRBs in the country. As some of the CRBs will be refraining from renewing their initial accreditation, we were able to provide meaningful information and suggest a direction for future operations.

Pediatric pharmacokinetics and pediatric clinical pharmacology have attracted attention because of recent emphasis on drug development for the pediatric population in the US and Europe. Specifically, the US Food and Drug Administration (FDA) and Europe Medical Agency (EMA) have recommended using pharmacometric approaches in order to prepare a pediatric study plan (PSP) and a pediatric investigation plan (PIP), respectively. One of the approaches of interest is physiologically-based pharmacokinetic (PBPK) modeling and simulations, which can take into account age-dependent growth of body-size and developmental changes in organ functions. This paper is aimed at introducing the current status and ongoing discussions about applications of PBPK modeling for: pediatric drug development; understanding of pediatric PBPK modeling with pediatric physiology related drug disposition; and learning from case studies; and future perspectives.

Objective: There is an increase in post-marketing studies (PMS) that require ethical review of matters such as informed consent from patients and the questionnaire used. In order to present the problems related to PMS faced by medical institutions, we investigated the contract status of the PMS at Tokai University Hospital and the PMS that required ethical considerations and reviews.

Methods: We classified the PMS contracts received by the Pharmaceutical Committee at our hospital from April 2014 to March 2018 according to the type of PMS and calculated the summary statistics. We also calculated the contents of PMSs that required ethical review.

Results: The PMS contracts received at our hospital were as follows: 77 single cohort studies, 74 specific cohort studies, 90 adverse event reports, and two others. In 16 PMS protocols, there were problems with the method of describing the study items, obtaining informed consent from patients, and handling personal information. Among them, seven were related to acquisition of informed consent forms and six were related to conduct of questionnaire survey.

Conclusion: As solutions to the problems, standardization of the contents and methods of descriptions in PMS protocols, clear distinction between the investigation items for re-examination and the additional investigation items in PMS protocols, descriptions of the purpose and reason of the investigation, and revision of laws and regulations for reusing the contents as materials for submission to regulatory bodies overseas.

In order to realize the above, it is important to develop a better environment for conducting PMS taking into consideration the current situation, under the guidance of the government and with collaboration among the pharmaceutical industry, medical institutions, and other industrial organizations.