Budget Impact Analysis of Treatment Flow Optimization in Epilepsy Patients: Estimating Potential Impacts with Increased Referral Rate to Specialized Care.

Objectives: We developed a Markov model to simulate a treatment flow of epilepsy patients who refer to specialized care from non-specialized care, and to surgery from specialized care for estimation of patient distributions and expenditures caused by increasing the referral rate for specialized care. Methods: This budget impact analysis of treatment flow optimization in epilepsy patients was performed as a long-term simulation using the Markov model by comparing the current treatment flow and the optimized treatment flow. In the model, we simulated the prognosis of new onset 5-year-old epilepsy patients (assuming to represent epilepsy occurring between 0 and 10 years of age) treated over a lifetime period. Direct costs of pharmacotherapies, management fees and surgeries are included in the analysis to evaluate the annual budget impact in Japan. Results: In the current treatment flow, the number of refractory patients treated with four drugs by non-specialized care were estimated as 8766 and yielded JPY5.8 billion annually. However, in the optimized treatment flow, the number of patients treated with four drugs by non-specialized care significantly decreased and who continued the monotherapy increased. The costs for the four-drug therapy by non-specialized care were eliminated. Hence cost-saving of JPY9.5 billion (-5% of the current treatment flow) in total national expenditures would be expected. Conclusion: This study highlights that any policy decision-making for referral optimization to specialized care in appropriate epilepsy patients would be feasible with a cost-savings or very few budget impacts. However, important information in the decision-making such as transition probability to the next therapy or excuse for sensitive limitations is not available currently. Therefore, further research with reliable data such as big data analysis or a national survey with real-world treatment patterns is needed.

Treatment pathways of Japanese prostate cancer patients - A retrospective transition analysis with administrative data.

BACKGROUND: Limited availability of real-world data that describe treatment patterns of Japanese prostate cancer (PCA) patients. METHODS: A biweekly transition analysis of PCA treatment was performed for patients with PCA diagnosis and a specific treatment between 2010 and 2015. To account for different cancer stages, two patient populations were analyzed. The first group consisted of patients on medication for hormone-sensitive prostate cancer (HSPC). The second group is comprised of patients who ended up receiving specific therapy for castration-resistant prostate cancer (CRPC). For each treatment, the average of treatment duration and the portion of patients transitioning to a consecutive treatment was calculated. RESULTS: We identified 59,626 patients from the Japanese administrative database with a PCA diagnosis and specific treatment. In the first year of our observational study 786 patients commenced a HSPC treatment and 695 received a CRPC specific therapy Among the HSPC group, we found that combination hormonal therapy, comprised of a gonadotrophin releasing hormone agonist or antagonist with an antiandrogen was more common than monotherapy. The results of the CRPC group indicated that chemotherapy administration was for a shorter time period in a real-world setting as compared to published clinical studies. CONCLUSION: Utilizing a novel method to visualize real-world treatment pathways for PCA patients we found that real treatment pathways are in line with international guidelines.

Burden of illness of chemotherapy in castration-resistant prostate cancer patients in Japan: a retrospective database analysis.

OBJECTIVE: The objective was to assess the burden of chemotherapy for castration-resistant prostate cancer (CRPC) in Japan. METHODS: Utilizing a large administrative hospital database we compared a set of outcome measures 12 months before and after initiation of chemotherapy, namely total medical costs, number of outpatient visits, number of hospital admissions and number of days spent in hospital. RESULTS: A total of 598 CRPC patients were identified in the database. Total healthcare costs increased from 143,578 Japanese Yen (JPY) per patient per month (PPPM), before chemotherapy, to 333,628 JPY after start of chemotherapy. The number of hospital admissions increased by 280%, and the number of days spent in hospital by 380%. CONCLUSIONS: The overall costs of chemotherapy for patients diagnosed with castration-resistant prostate cancer in Japan are high. Our findings can serve as a basis for health economic evaluations.

Cost of Illness of Japanese Patients with Chronic Lymphocytic Leukemia (CLL), and Budget Impact of the Market Introduction of Ibrutinib.

BACKGROUND: Ibrutinib was introduced in Japan in 2016 as a new oral treatment option for patients with relapsed/refractory (RR) chronic lymphocytic leukemia (CLL). There is increasing interest from the Japanese government to assess economic aspects of new medical interventions, especially in the area of oncology. OBJECTIVE: We describe the treatment patterns of Japanese patients with CLL, estimate the cost of the disease from a health insurance perspective, and predict the budget impact of the introduction of ibrutinib. METHODS: A budget impact model was set up and populated with data that were collected from a survey of Japanese hematologists (n = 202) and official statistics. Uncertainty was addressed by one-way sensitivity analysis of several model parameters. RESULTS: Among the 2000 Japanese CLL patients, 42.2% have not yet commenced medical treatment, 29.1% were on a treatment break, and 26.8% received medical treatment, mainly rituximab in combination with either fludarabine or bendamustine. Among the patients under medical treatment, 65.7% were receiving first-line treatment and 34.3% were receiving second-line or later treatment. In Japan, the estimated burden of illness for 2015 was ¥1563 million for RR CLL and ¥5471 million for overall CLL. The expected average budget impact of introducing ibrutinib is ¥3077 million per year for the next 5 years. CONCLUSION: Due to low disease prevalence, the burden of illness in Japan is low compared with Western countries.

Mild recessive bullous congenital ichthyosiform erythroderma due to a previously unidentified homozygous keratin 10 nonsense mutation.

We have identified a previously unreported homozygous nonsense mutation p.Cys427X in the keratin 10 (K10) gene (KRT10) in a Turkish girl with recessive bullous congenital ichthyosiform erythroderma (BCIE) showing superficial blistering. p.Cys427X is located upstream of the previously reported homozygous truncation mutation within the same exon 6 causing mRNA decay. Immunohistochemical examination showed a complete absence of K10 protein in the patient's epidermis. The findings of this study suggest that K10 knockout patients show unique clinicopathological features of clinically mild BCIE with blisters occurring within the granular layer. In addition, the unaffected, heterozygous carriers of the mutation indicate that the K10 peptide from one normal allele alone is sufficient for keratin network formation.

Keratin 1 gene mutation detected in epidermal nevus with epidermolytic hyperkeratosis.

Since 1994, four cases of epidermal nevus with epidermolytic hyperkeratosis (EH) caused by keratin 10 gene mutations have been reported, although no keratin 1 (K1) gene mutation has yet been reported. We detected a K1 gene (KRT1) mutation in epidermal nevus with EH in a 10-year-old Japanese male. The patient showed well-demarcated verrucous, hyperkeratotic plaques mainly on the trunk, covering 15% of the entire body surface. No hyperkeratosis was seen on the palms or soles. He had no family history of skin disorders. His lesional skin showed typical granular degeneration and, ultrastructurally, clumped keratin filaments were observed in the upper epidermis. Direct sequence analysis of genomic DNA extracted from lesional skin revealed a heterozygous 5' donor splice site mutation c.591+2T>A in KRT1. This mutation was not detected in genomic DNA samples from the patient's peripheral blood leukocytes or those of other family members. The identical splice mutation was previously reported in a family with palmoplantar keratoderma and mild ichthyosis, and was demonstrated to result in a 22 amino-acid deletion p.Val175_Lys196del in the H1 and 1A domains of K1. To our knowledge, the present patient is the first reported case of epidermal nevus associated with EH caused by a K1 gene mutation in a mosaic pattern.