Oxycodone is a widely used opioid for cancer analgesia. A 62-year-old woman who was diagnosed with metastatic malignant melanoma (stage Ⅳ) received oxycodone for pain control. While adequate analgesia was achieved at 60 mg/day of oxycodone without central adverse reactions, she eventually developed laxative-resistant constipation. Bowel movements were induced by an oral administration of a prokinetic agent, erythromycin (800 mg/day), whereas the patient developed somnolence four days after the commencement of the drug. Her symptoms disappeared promptly after withdrawal of erythromycin (dechallenge), and administration of oxycodone was continued. The dose of oxycodone was increased to 120 mg/day without central adverse reactions. Two weeks later she was given erythromycin (re-challenge) for refractory constipation and again developed nausea. Upon withdrawal of erythromycin (de-challenge), the symptom disappeared within two days while the same dose of oxycodone (120 mg/day) was maintained. There was a definite causal relationship between co-administration of the two drugs and developments of central adverse reactions, since the Naranjo's probability score of the drug interaction was 9. We considered that the developments of somnolence and nausea may be attributed to the drug interaction between oxycodone and erythromycin. An assumed mechanism might have been an inhibition of cytochrome P-450 (CYP) 3A4 by erythromycin and a resultant increase in plasma concentrations of oxycodone. Analyses of the Japanese Adverse Drug Event Report (JADER) and the FDA Adverse Event Reporting System (FAERS) databases revealed no significant excessive signals of somnolence or nausea for patients receiving oxycodone with macrolide antibiotics. We consider that a caution should be exercised for prescribing erythromycin to patients receiving oxycodone. Spontaneous reporting systems may not be sensitive for detecting a drug interaction mimicking commonly observed augmented pharmacologic effects of a victim drug.

Although the Japanese government has been promoting academia-industry collaboration since the 1990s, inappropriate relationship between some companies and researchers has become a problem. The government has issued the guidance for conflict of interest (COI) management, which will need to be revised as per the current situation in the hospitals. The objective of this study was to examine the current situation of COI management structure in Japanese hospitals that may be involved in multi-center clinical trials. We sent questionnaires on topics relevant to COI management to 590 hospitals. Among the 190 respondents (response rate＝32%), 100 hospitals had independent COI management committees. The committees had an average of 7 members, including one external member. In 76 hospitals, the secretariat of COI management committee was placed in the administration and management department. In the previous year, 48 committees collected additional information from researchers through interviews and 35 committees provided advice. Our survey showed wide diversity among hospitals regarding management standards and activities of independent COI management committees. However, they shared a common point in that the COI management committees do not function actively. Although the Clinical Trials Act has provided a standardized COI management strategy, further studies are required to develop more practical guidelines for COI management in clinical trials.

Many believe, based on the respect for persons ethical principle, that informed assent forms for pediatric clinical research should be prepared based on children's ability to understand the given information on a proposed research.

However, what the modality of an appropriate assent form for children should be, namely, how the form should be worded in Japanese and for which children it should be targeted, are yet to be answered in clinical research. This study tackled those profound questions through a 6-year longitudinal observation and interviews with one particular minor child and pedagogical analyses. At the age of 11.2 the observed child was asked to give her comments and make modifications to informed consent forms originally prepared for competent adults. Drawing on her elaboration as well as our analyses, we have created two models of informed assent forms and make seven proposals that elucidate the modality of child assent forms. Taking all 7 propositions is necessary to prepare an appropriate assent form for pediatric clinical research.

We report our experience with GCP inspection by FDA. Prior to the inspection, preparations were made by conducting a preliminary consultation with the client and a mock inspection. The inspection by FDA was conducted by one inspector for a duration of 8 days. The inspection revealed no problem. Compared with the GCP inspection by EMA that we received previously, the GCP inspection by FDA involved the same procedures of confirming the documents related to the clinical trial, including all the primary outcomes and adverse events. The two inspections differed in the number of inspectors and the inspection schedule. Based on the experience with the FDA and EMA inspections, construction of quality control system in medical institutions is considered necessary.