ABSTRACT
Background: Synovial sarcoma (SS) is a rare, aggressive soft tissue sarcoma with a poor prognosis after metastasis. The objective of this study was to conduct a systematic review of the clinical evidence for therapeutic options for adults with metastatic or advanced SS. Materials & methods: Relevant databases were searched with predefined keywords. Results: Thirty-nine publications reported clinical data for systemic treatment and other interventions. Data on survival outcomes varied but were generally poor (progression-free survival: 1.0-7.7 months; overall survival: 6.7-29.2 months) for adults with metastatic and advanced SS. A high frequency of neutropenia with systemic treatment and low quality of life post-progression were reported. Conclusion: Reported evidence suggests poor outcomes in adults with metastatic and advanced SS and the need for the development of new treatment modalities.
Subject(s)
Sarcoma, Synovial/therapy , Adult , Humans , Neoplasm Metastasis , Quality of Life , Sarcoma, Synovial/mortality , Sarcoma, Synovial/pathology , Sarcoma, Synovial/psychologyABSTRACT
Objectives: In Japan, a cost-effectiveness evaluation (CEE) for pricing was introduced in April 2019 and potentially covers orphan drugs (ODs) within its scope. The purpose of this study was to explore a reasonable approach to evaluate the utility of health technology assessment (HTA) for ODs in Japan. Methods: We extracted ODs that were approved in Japan from 2009 to 2018, and investigated their appraisals in the United Kingdom, Canada, and Australia, where HTA and different frameworks on ODs have been implemented. Results: Overall, 76 ODs were identified, with high recommendation rates in the three countries (80.6%-90.9%). The major reason for negative recommendation was uncertainty regarding clinical effectiveness, with actual decisions varying across countries. This indicates difficulties in setting an objective evaluation for the uncertainty of clinical effectiveness. The results of the CEE were mainly used to adjust prices. Conclusion: As Japan's CEE is expected to be used only for price adjustment after reimbursement is secured, the approach seems to be similar to the other countries. However, pre-launch clinical data are limited and the peak sales of ODs vary in Japan. Therefore, the careful introduction of CEE and multifaceted measures referring to the policies for ODs in other countries should be considered.
Subject(s)
Drug Costs , Orphan Drug Production/economics , Rare Diseases/drug therapy , Technology Assessment, Biomedical , Cost-Benefit Analysis , Costs and Cost Analysis , Decision Making , Drug Approval , Humans , Japan , Rare Diseases/economics , Reimbursement Mechanisms , UncertaintyABSTRACT
The aim of this study was to develop a pharmacokinetic model to describe the transplacental transfer of drugs, based on the human placental perfusion study. The maternal and fetal sides of human placentas were perfused with salicylic acid together with antipyrine, a passive diffusion marker. The drug concentration in the placental tissue was determined at the end of perfusion. A compartment model consisting of maternal space, fetal intravascular space, and placental tissue was fitted to the observed concentration profiles of salicylic acid in the maternal and fetal effluents. The developed model could adequately explain the concentration profiles of salicylic acid in the effluents with influx clearances from maternal and fetal perfusates to placental tissue of 0.0407 and 0.0813 ml/min/g cotyledon and efflux rate constants from placental tissue to maternal and fetal perfusates (k2 and k3) of 0.0238 and 0.176 min(-1), respectively. The kinetics of antipyrine was adequately described by assuming rapid equilibrium between fetal perfusate and placental tissue compartments. The influx plasma clearance from the maternal side (K''1) in humans was estimated by taking into account the protein binding. The K''1/k2 value of salicylic acid was 1.07 ml/g cotyledon and was larger than that of antipyrine (0.642 ml/g cotyledon). We evaluated the transplacental transfer kinetics of salicylic acid by human placental perfusion study with various perfusion protocols. Based on the data obtained, we developed a pharmacokinetic model, which should enable us to estimate the influx profile of drugs into umbilical arterial blood from the maternal plasma concentration profile.
