Purpose: This study aimed to assess the safety risks associated with using nonsteroidal anti‐inflammatory drugs (NSAIDs) in elderly patients (≥65 years) compared with younger patients (70 years compared with younger patients (18–30 years) and was remarkable in patients >80 years with 2‐fold, 10‐fold, and 7‐fold higher risk for developing GI, renal, and AMI events, respectively.Conclusion: Risk for developing NSAID‐associated events was higher in the elderly; particularly, renal and AMI events that remarkably increased in patients >80 years. To reduce them, NSAIDs should be prescribed at the lowest effective dose for the shortest duration possible.

Purpose: Musculoskeletal diseases, including osteoarthritis (OA) and low back pain (LBP), are the leading causes of years lived with disability, and are associated with lowered quality-of-life, lost productivity, and increased healthcare costs. However, information publicly available regarding the Japanese real-world usage of prescription medications is limited. This study aimed to describe the clinical characteristics of patients with OA and chronic LBP (CLBP), and to investigate the patterns of medications and opioid use in Japanese real-world settings. Materials and methods: A retrospective study was conducted using a Japanese administrative claims database between 2013 and 2017. The outcomes were patient characteristics and prescription medications, and they were evaluated separately for OA and CLBP. Results: The mean age of 118,996 patients with OA and 256,402 patients with CLBP was 68.8±13.1 years and 64.8±16.4 years, respectively. Approximately 90% of patients with OA and CLBP were prescribed non-steroidal anti-inflammatory drugs (NSAIDs). Other prescriptions included hyaluronate injection (35.6%), acetaminophen (21.4%), and steroid injection (20.0%) in patients with OA, and pregabalin (39.0%) and acetaminophen (22.4%) in patients with CLBP. Weak opioids were prescribed to 10.7% and 20.6% of patients with OA and CLBP, respectively. The prescription of COX-2 inhibitors (OA: +6.5%; CLBP: +6.7%) and acetaminophen (OA: +16.4%; CLBP: +14.4%) increased between 2013 and 2017. The first commonly prescribed medication among patients with OA and CLBP were NSAIDs; hyaluronate injection (patients with OA) and pregabalin (patients with CLBP) were also common first-line medications. Acetaminophen, steroid injection (patients with OA), and weak opioids were prescribed more in the later phases of treatment. Conclusion: Most patients were prescribed limited classes of pain drugs, with NSAIDs being the most common pain medication in Japan for patients with OA and CLBP. Opioid prescription was uncommon, and were weak opioids when prescribed.

In clinical trials, interim analyses are often performed before the completion of the trial. The intention is to possibly terminate the trial early or adjust the sample size. The time of conducting an interim analysis affects the probability of the early termination and the number of subjects enrolled until the interim analysis. This influences the expected total number of subjects. In this study, we examine the optimal time for conducting interim analyses with a view to minimizing the expected total sample size. It is found that regardless of the effect size, the optimal time of one interim analysis for the early termination is approximately two-thirds of the planned observations for the O'Brien–Fleming type of spending function and approximately half of the planned observations for the Pocock type when the subject enrollment is halted for the interim analysis. When the subject enrollment is continuous throughout the trial, the optimal time for the interim analysis varies according to the follow-up duration. We also consider the time for one interim analysis including the sample size adjustment in terms of minimizing the expected total sample size.

Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) have long-term benefits but are limited by side effects. We assessed the health and economic burden of renal events associated with NSAID use in patients with osteoarthritis (OA) and/or chronic low back pain (CLBP). Methods This retrospective, large-scale, medical claims database study of Japanese patients receiving NSAIDs for OA and/or CLBP between 2009 and 2018 assessed the incidence of renal events and effect of treatment duration, mode of administration, and usage consistency of NSAIDs. Results Of 180,371 patients, NSAIDs were prescribed as first-line analgesics in 89.3%. Incidence per 10,000 person-years (95% confidence interval [CI]) for renal events was 23.46 (21.84–25.08) and for progression of chronic kidney disease (CKD) was 267.12 (189.93–344.32). Longer treatment duration (> 1 to ≤ 3 years, risk ratio [RR] 1.32, 95% CI 1.12–1.54; P = 0.0007; > 3 to ≤ 5 years, RR: 1.38, 95% CI 1.04–1.84; P = 0.0254 vs. < 1 year) and consistent use (RR: 1.24, 95% CI 0.99–1.55; P = 0.0595) increased the risk of renal events but the latter did not reach statistical significance. The risk was similar in patients using patch/oral NSAIDs and high in elderly patients and in those with diabetes, hypertension, and other cardiovascular disease. Following a renal event, median 1-year cost of drug treatment was $27.90; hospitalization, $1779.40; and dialysis, $33,018.40. Conclusions Risk of renal events significantly increased with prolonged and consistent NSAID use (irrespective of mode of administration), with age, and in patients with certain comorbidities. Careful NSAID use is recommended in patients with CKD and those at high risk for CKD.

The Japanese National Immunization Program currently includes the pediatric 13valent pneumococcal conjugate vaccine (PCV13) to prevent pneumococcal infections. We aimed to evaluate the cost-effectiveness of 20-valent PCV (PCV20) as a pediatric vaccine versus PCV13. A decision-analytic Markov model was used to estimate expected costs, qualityadjusted life-years (QALYs), and prevented cases and deaths caused by invasive pneumococcal disease, pneumonia, and acute otitis media over a ten-year time horizon from the societal and healthcare payer perspectives. PCV20 (price: 8,102 Japanese yen [JPY]) was dominant, i.e. less costly and more effective, over PCV13 (gained 294,599 QALYs and reduced JPY 352.6 billion [2.6 billion United States dollars, USD] from the societal perspective and JPY 178.9 billion [USD 1.4 billion] from the payer perspective). Sensitivity and scenario analyses validated the robustness of the base scenario results. When comparing PCV20 with PCV13, the threshold analysis revealed an incremental cost-effectiveness ratio that was within the threshold value (JPY 5 million/QALY) at a maximum acquisition price of JPY 74,033 [USD 563] (societal perspective) and JPY 67,758 [USD 515] (payer perspective). As a pediatric vaccine, PCV20 was dominant over PCV13 regardless of the study perspective.

Introduction Respiratory syncytial virus (RSV) is one of the major causes of respiratory tract infections among children. Until recently, the monoclonal antibody palivizumab was the only RSV prophylaxis available in Japan. In 2024, the bivalent RSV prefusion F protein-based (RSVpreF) vaccine was approved for the prevention of RSV infection in infants by active immunization of pregnant women. In this study, we assessed the cost-effectiveness of a combined strategy of RSVpreF vaccine and palivizumab in Japanese setting. Methods Using a Markov model, we evaluated prevented cases and deaths of medically attended RSV infections from birth to age 11 months for each of the three healthcare settings: inpatient (hospitalization), emergency department visits, and outpatient visits. Incremental cost-effectiveness ratios (ICERs) were calculated from economic outcomes (intervention costs, medication costs, and productivity losses) and quality-adjusted life years (QALYs). Further, we calculated the maximum price of RSVpreF vaccine within which the program would be cost-effective. Results In comparison with the current prophylaxis (palivizumab alone), a combined prophylaxis of year-round RSVpreF vaccination of pregnant women and palivizumab prescription for premature infants born in < 32 weeks gestational age (wGA) and all infants with high risk prevented 14,382 medically attended cases of RSV (hospitalization, 7490 cases; emergency department, 2239 cases; outpatient, 4653 cases) and 7 deaths, respectively. From a healthcare payer perspective, when the price of RSVpreF vaccine was equal to or less than ¥23,948 (US $182), a combination prophylaxis was cost-effective under the ICER threshold of ¥5 million per QALY. The other combination prophylaxis of year-round RSVpreF vaccination and palivizumab prescription of premature born in < 32 wGA regardless of risk in infants was a dominant strategy (more effective and less costly). Conclusion A combined prophylaxis of year-round RSVpreF vaccine and palivizumab could be a cost-effective strategy to protect neonates throughout the infant stage (< 1 years old) in Japan.