The price, efficacy, and safety of within-class targeted anticancer medicines between domestic and imported drugs in China: a comparative analysis.

Background: Affordability to novel anticancer drugs has become a major health issue in China. It is encouraging to note that China initiated its drug regulatory reform and national price negotiation policies since 2015. As a growing number of domestic within-class targeted anticancer drugs are approved in China, it is expected that this may reduce the price of novel anticancer drugs and improve the affordability of anticancer drugs. This study aimed to evaluate the price, efficacy, and safety of the within-class anticancer drugs between domestic and imported drugs approved in China from 2010 to 2022. Methods: The domestic and imported within-class targeted drugs for solid cancers approved in China between 2010 and 2022 were extracted. We classified it as a class of anticancer drugs based on the same indication and similar biological mechanism. The published literature derived from pivotal clinical trials of these domestic and imported drugs was identified based on the review report and the latest labels issued by the China National Medical Products Administration. We evaluated the monthly treatment price at launch and the latest (2022), primary efficacy endpoint and safety between domestic and imported anticancer drugs. Meta-analyses were further employed to evaluate the efficacy and safety of the domestic and imported anticancer drugs, including pooled hazard ratios (HR) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR) for solid cancers, and relative risk for serious adverse events (SAE) and Grade ≥3 adverse events (AEs). Findings: In our cohort study, 12 within-class anticancer drugs with 7 cancer diseases were analyzed, including 18 domestic (21 indications; 21 pivotal trials) and 18 imported (21 indications; 27 pivotal trials) novel anticancer drugs, respectively. The median monthly treatment price of domestic and imported drugs from the years of launch to 2022 had significantly decreased by 71% and 62%, respectively. Moreover, the median monthly treatment price of domestic targeted anticancer drugs on the market at launch ($3786 vs. $5393, P = 0.007) and the latest ($1222 vs. $2077, P = 0.011) was significantly lower than that of imported drugs. No significant differences in median PFS gains (9.0 vs. 11.0 months; P = 0.24), OS gains (9.3 vs 10.6 months; P = 0.66), and ORR (57% vs 62%, P = 0.77) of targeted anticancer drugs in their pivotal trials were observed between the domestic and imported drugs. Additionally, there was no significant difference between domestic and imported drugs in the incidence of SAE (23% vs. 24%; P = 0.41) and Grade ≥3 AEs (59% vs. 57%; P = 0.45). These findings were also further confirmed in the meta-analyses for primary efficacy endpoints and safety outcomes. Interpretation: The prices of both domestic and imported anticancer drugs significantly decreased after market entry mainly due to the role of national price negotiations. The median monthly treatment price of domestic within-class targeted anticancer drugs was significantly lower than that of imported drugs. Furthermore, the efficacy and safety of domestic anticancer drugs were comparable to that of imported drugs. This evidence implicated that the development of within-class anticancer drugs with national price negotiations in China significantly improved the affordability for patients. Funding: This study was supported by postdoctoral fellowship from Tsinghua-Peking Joint Centers for Life Sciences (CLS).

Continuous ultrafiltration/diafiltration using a 3D-printed two membrane single pass module.

A 3D printed ultrafiltration/diafiltration (UF/DF) module is presented allowing the continuous, simultaneous concentration of retained (bio-)molecules and reduction or exchange of the salt buffer. Differing from the single-pass UF concepts known from the literature, DF operation does not require the application of several steps or units with intermediating dilution. In contrast, the developed module uses two membranes confining the section in which the molecules are concentrated while the sample is passing. Simultaneously to this concentration process, the two membranes allow a perpendicular in and outflow of DF buffer reducing the salt content in this section. The module showed the continuous concentration of a dissolved protein up to a factor of 4.6 while reducing the salt concentration down to 47% of the initial concentration along a flow path length of only 5 cm. Due to single-pass operation the module shows concentration polarization effects reducing the effective permeability of the applied membrane in case of higher concentration factors. However, because of its simple design and the capability to simultaneously run UF and DF processes in a single module, the development could be economically beneficial for small scale UF/DF applications.

Typical Endocrine Disrupting Compounds in Rivers of Northeast China: Occurrence, Partitioning, and Risk Assessment.

Liao River Basin (LRB), located in northeast China, is one of seven largest river basins in China. The Daliao River Watershed (DLRW) is severely disturbed by human activities in the LRB. In this study, three rivers within the DLRW-Xi River (XR), Hun River (HR), and Daliao River (DLR)-were selected as sampling locations. The distribution, partitioning, and risk assessment of four endocrine-disrupting compounds (EDCs), e.g., bisphenol A (BPA), 17ß-estradiol (E2), estrone (E1), and 17α-ethinyl estradiol (EE2), in the rivers were investigated. The results showed that the concentration of BPA was generally higher than those of the other three steroidal estrogens in the sampling locations. The estrogen levels in the XR were greater than those in the HR and DLR. As a result of a decreasing river flow rate during the frozen season and irregular wastewater discharge from human domestic activities and manufacture processing, the total concentration of selected EDCs in the frozen season was much greater than those in nonfrozen season with the highest concentration in surface water of the XR at 1131.0 ng/L for BPA, 1235.0 ng/L for E1, 1253.5 ng/L for E2, and 17,111.5 ng/L for EE2, respectively. Based on the field-measured BPA concentrations in the sediment and water, the organic carbon-normalized partition coefficient (K oc) of BPA were calculated with the values of 2884-45,031 L/kg; the concentration of BPA in sediment was positive correlated with the content of OC (R 2 = 0.932). The risk assessment made by estradiol equivalent (EEQ) and risk quotient (RQ) showed that 64.7% of sampling sites were exposed to high estrogenic activity (∑EEQ > 1) and high risk in surface water, whereas the RQ values of all selected estrogens in sediment were in medium or minimal risk. Both EE2 and E1 were the major contributors to the total estrogenic activity and risk quotient in surface water.

Spatial distribution and ecological risk assessment of phthalic acid esters and phenols in surface sediment from urban rivers in Northeast China.

Concentration and spatial distribution of six phthalic acid esters (PAEs) and eight phenols in sediments of urban rivers, namely the Xi River (XR) and Pu River (PR) in Shenyang city, Northeast China were investigated and the ecological risk of these target pollutants was assessed based on the risk quotient (RQ) approach. Target PAEs and phenols were detected in most of sediment samples collected from the XR and PR. The concentrations of total PAEs in sediments varied from 22.4 to 369 µg/g dw in the XR and 3.71-46.9 µg/g dw in the PR. The levels of phenols ranged from 2.72 to 106 µg/g dw in the XR and 0.811-25.0 µg/g dw in the PR, respectively. The dominant pollutants in both XR and PR were DEHP, phenol and 4-methylphnol. The sampling locations XR1-3 in the XR suffered severe contamination from PAEs and phenols. The sites PR1 and PR6 were heavily polluted by phenols and PAEs, respectively. Almost all target PAEs and phenolic compounds in sediment of the XR exhibited medium or high ecological risk to organisms and the ecological risk in the PR mainly originated from PEAs, phenol and 4-methylphenol. These results would provide guidance for individual pollutant control and indicate that it is imperative to take some effective measures to reduce the pollution of those contaminants.