Randomized controlled trials (RCTs) are the key method to investigate the treatment effect with methodologic rigor. An essential goal of RCTs is to provide robust and interpretable quantitative information about the treatment effect for clinicians/patients to balance risk/benefit and make a treatment decision. However, for time-to-event outcomes, such as overall survival or progression-free survival in cancer trials, the present analytic practice that routinely uses the hazard ratio for summarizing the magnitude of the treatment effect has significant limitations, which makes it harder to achieve the goal. The issues of hazard ratio and several good alternatives (such as difference or ratio of t-year event rates, median, and restricted mean survival time) have been extensively discussed in recent medical journals. In this paper, we highlight these recent discussions, introducing the reports of three RCTs published in major oncology journals and the letter-to-editor for each of the three RCTs. We conclude that choosing a robust and interpretable metric, rather than simply relying on the routine hazard ratio approach, would be important for summarizing the treatment effect in future clinical trials with time-to-event outcomes, which will ultimately foster better informed treatment decision making.

Focusing on the Pharmaceutical Intervention Records (PIR) project conducted in collaboration with the Gifu Pharmaceutical Association and Gifu Pharmaceutical University, this study analyzed characteristics and economic effects of the audit of dispensing fees for the prevention of duplications or interactions of prescription drugs by pharmacists. The pharmacists registered audit data of 1,105 prescriptions into the PIR database in 2017. For the analysis, we divided 1,105 prescriptions into those that incurred dispensing fees for the prevention of duplications or interactions of prescription drugs (the subject group) and a control group comprising other prescriptions. The reduction in drug cost per prescription was 1,689 yen in the subject group, which was significantly higher than the reduction of 563 yen in the control group. In the subject group, pharmacists tend to use a medicine notebook for identifying duplicate administrations or drug interactions. There is a high ratio of cancellation of drugs as a result of such inquiries. This is considered a factor in the reduction of the cost of drugs. The reduction per prescription in the subject group is higher than the medical fees for the prevention of duplications or interactions of prescription drugs, and it can be evaluated that activities related to preventing duplications and interactions of prescription drugs contribute to medical economy.

We previously reported a positive correlation between the oral clearance (CL/F) and the apparent volume of distribution (V/F) of drugs with variable bioavailability (F). The aim of the present study using a computer simulation method was to further evaluate the usefulness of the population pharmacokinetic analysis model assuming the covariance of CL/F and V/F (ω_CL/F,V/F). We assumed variable bioavailability (F) not only in intestinal absorption, but also in hepatic first-pass extraction and transdermal absorption. The log likelihood difference (LLD) between the covariance and conventional (non-covariance) model analysis was very similar to the LLD between the true and conventional model analysis. The individual relative F (F_rel) values estimated with the covariance model analysis was also similar to the F_rel values estimated with the true model analysis. Therefore, we should use the covariance model and/or the true model positively for population pharmacokinetic analysis for drugs with variable F.

We began to print laboratory data on prescriptions and introduced a system called the checking prescription assist system (the assist system) for a high-quality, effective system of checking prescriptions. The assist system prints drug information for each registered drug and we registered drugs affected by renal function. When a registered drug for a patient with a creatinine clearance of less than 60 mL/min is prescribed, an assist sheet on which information of recommended dosage for each renal function is printed. The purpose of this study is to evaluate a change of prescription questions and the utility of using prescriptions on which laboratory data is printed and the assist system. We investigated inquired prescriptions in three periods: from January 1st to March 31th, 2013; from May 22th to August 21th, 2016; and from January 1st to March 31th, 2017. The results showed that the rate of prescription questions using laboratory data significantly increased after printing laboratory data on prescriptions. Furthermore, by using the assist system, the rate of prescription questions about the drugs registered with this system increased. Besides, we investigated the number of prescriptions including levofloxacin regarding which we needed to inquire. The assist system significantly decreased the rate of prescriptions regarding which we did not inquire regarding the levofloxacin dosage. In conclusion, we suggest that by using prescriptions on which laboratory data was printed and the assist system, we can utilize laboratory data more effectively in order to being prepared to avoid the adverse reaction of drugs.

Peripheral neuropathy (PN), a serious side effect of oxaliplatin (L-OHP), is classified as either acute PN or chronic PN. The incidence of acute PN is high, and cold hypersensitivity reduces the quality of life of patients. It is suggested that the frequency of acute PN can facilitate the evaluation of the onset and severity of chronic PN. Therefore, this study retrospectively analyzed the risk factors for the onset of acute PN.

Seventy-one subjects who received chemotherapy, including L-OHP, were included in the study. The subjects were assigned into two categories: groups in which the subjects experienced the onset of acute PN during the first course (n = 37); and groups in which the subjects did not develop acute PN during the first course (n = 34). For each item, including patient background, a comparison was made between the two groups. The initial dose of L-OHP was significantly higher in the subjects that experienced acute PN onset group during the first course (P < 0.001). In addition, in the highdose group such as SOX or CapeOX, the incidence of acute PN was significantly higher in the first course than in the low-dose group such as FOLFOX4/6 or FOLFIRINOX (P < 0.001).

As the initial dose of L-OHP is strongly suggested as a risk factor for acute PN, it was estimated that there was a high risk of developing acute PN in the first course of a high-dose regimen. Therefore, it is important to provide sufficient guidance on countermeasures at the initial administration.

　Everolimus (ERL) is the first oral molecular targeted drug in the therapeutic area of breast cancer, inducing a wide range of side effects. Stomatitis occurs at high frequency in treatment with ERL. Stomatitis at Grade 2 and above not only deteriorates the quality of life but also leads to withdrawal of ERL. We administered azulene gargle to prevent stomatitis, but 3 out of 9 cases suffered stomatitis at Grade 2 and above. Therefore, we introduced a method of applying dexamethasone ointment (DEX) until recovery as a preventive measure for stomatitis at Grade 2 and above at the time in which stomatitis at Grade 1 occurred, and then examined the usefulness of such method. In this method, electronic medical records were examined retrospectively with respect to 35 breast cancer patients treated with ERL in our hospital from April 2014 to February 2018. Eleven cases had no administration of DEX for the treatment of stomatitis at Grade 1 (non-DEX group). Seven cases had the onset of stomatitis at Grade 2 and above with an incidence rate of 63.6％. Twenty-four cases had an application of DEX (DEX group). One case had an onset of stomatitis at Grade 2 and above with an incidence rate of 4.2％. Stomatitis at Grade 2 and above could be significantly reduced in the DEX group (P < 0.05). This examination suggests the usefulness of treatment of stomatitis at Grade 1 with DEX for the prevention of ERL-induced stomatitis at Grade 2 and above.