Does the new cooperative medical scheme reduce inequality in catastrophic health expenditure in rural China?

Background In 2003, the New Cooperative Medical Scheme (NCMS) was introduced in China to re-establish health insurance for the country’s vast rural population. In addition, the coverage of NCMS has been expanding after the new health care reform launched in 2009. This study aims to examine whether the NCMS and its recent expansion have reached the goal of reducing the risk and inequality of catastrophic health spending for rural residents in China. Methods We conducted a face-to-face household survey in three counties of the Shandong province in 2009 and 2012. Using this unique panel data, we examined the changes in the incidence and intensity of catastrophic health expenditures (CHEs) before and after NCMS reimbursement. We used concentration index (CI) and decomposition method to study the changes in inequality in CHEs. Results We found that NCMS reimbursement played a role of reducing both the incidence and intensity of CHEs, and that this impact was stronger after the new health care reform was launched. After reimbursement, the concentration indices for CHEs were 0.073 and 0.021 in 2009 and 2012, indicating that the rich had a greater tendency to incur CHEs and there existed less inequality in the incidence of CHEs after reimbursement in 2012 compared with 2009. The decomposition analysis results suggested that changes in CHE inequality between 2009 and 2012 were attributed to changes in economic status and household size rather than reimbursement levels. Conclusions Our results indicated that inequality was shrinking from 2009 to 2012, which could be a result of fewer rich people having CHEs in 2012 compared with 2009. The impact of NCMS in alleviating the financial burden of rural residents was still limited, especially among the poor. Health care reform policies in China that aim to reduce CHEs must continue to place an emphasis on improving reimbursement, cost containment, and reducing income inequalities

Comparisons of diabetic retinopathy events associated with glucose‐lowering drugs in patients with type 2 diabetes mellitus: A network meta‐analysis

Aim To assess the comparative effects of glucose‐lowering drugs (GLDs) on the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods We systematically searched Cochrane Central Register of Controlled Trials, PUBMED and EMBASE from inception to January 17, 2017 to identify randomized controlled trials (RCTs) that reported DR events among T2DM patients receiving any GLD. Random‐effects pairwise and network meta‐analyses were performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Results A total of 37 independent RCTs with 1806 DR events among 100 928 patients with T2DM were included. The mean duration of diabetes was 8.7 years and mean baseline HbA1c was 8.2% (SD, 0.5%). Our network meta‐analysis found that DPP‐4i (OR, 1.20; 95% CI, 0.87‐1.65), GLP‐1RA (OR, 1.19; 95% CI, 0.94‐1.52) and SGLT2 inhibitors (OR, 0.79; 95% CI, 0.49‐1.28) were not associated with a higher risk of DR than placebo; however, a significantly increased risk of DR was associated with DPP‐4i in the pairwise meta‐analysis (OR, 1.27; 95% CI, 1.05‐1.53). Sulfonylureas, on the other hand, were associated with a significantly increased risk of DR compared to placebo (OR, 1.67; 95% CI, 1.01‐2.76). Conclusions Current evidence indicates that the association between DPP‐4i, GLP‐1RA or SGLT2 inhibitors and risk of DR remains uncertain in patients with T2DM. Some evidence suggests that sulfonylureas may be associated with increased risk of DR. However, given that DR events were not systematically assessed, these effects should be explored further in large‐scale, well‐designed studies

Overall survival benefits of cancer drugs approved in China from 2005 to 2020

Importance: Of approximately 9 million patients with cancer in China in 2020, more than half were diagnosed with late-stage cancers. Recent regulatory reforms in China have focused on improving the availability of new cancer drugs. However, evidence on the clinical benefits of new cancer therapies authorized in China is not available. Objective: To characterize the clinical benefits of cancer drugs approved in China, as defined by the availability and magnitude of statistically significant overall survival (OS) results. Design, Setting, and Participants: This mixed-methods study comprising a systematic review and cross-sectional analysis identified antineoplastic agents approved in China between January 1, 2005, and December 31, 2020, using publicly available data and regulatory review documents issued by the National Medical Products Administration. The literature published up to June 30, 2021, was reviewed to collect results on end points used in pivotal trials supporting cancer drug approvals. Main Outcomes and Measures: The primary outcome measure was a documented statistically significant positive OS difference between a new cancer therapy and a comparator treatment. Secondary outcome measures were the magnitude of OS benefit and other primary efficacy measures in pivotal trials. Results: Between 2005 and 2020, 78 cancer drugs corresponding to 141 indications were authorized in China, including 20 drugs (25.6%) (for 30 indications) approved in China only. Of all indications, 26 (18.4%) were evaluated in single-arm or dose-optimization trials, most of which were authorized after 2017. By June 30, 2021, 34 drug indications (24.1%) had a documented lack of OS gain. For 68 indications (48.2%) that had documented evidence of OS benefit, the median magnitude of OS improvement was 4.1 (range, 1.0-35.0) months. After a median follow-up of 1.9 (range, 1.0-11.1) years from approval, OS data for 13 indications (9.2%) were either not reported or were still not mature. Fewer than one-third of cancer drug indications approved in China only had documented evidence of OS benefits (9 of 30 [30.0%]), whereas more than one-half of the cancer drug indications also available in the US or Europe had OS benefits (59 of 111 [53.1%]). Conclusions and Relevance: In this study, almost half of cancer drug indications approved in China had demonstrated OS gain. With the increase of cancer drug approvals based on single-arm trials or immature survival data in recent years, these findings highlight the need to routinely monitor the clinical benefits of new cancer therapies in Chin

Cancer drug indication approvals in China and the United States: a comparison of approval times and clinical benefit, 2001–2020

BACKGROUND: Perceived delays in cancer drug approvals have been a major concern for policymakers in China. Policies have been implemented to accelerate the launch of new cancer drugs and indications. This study aimed to assess similarities and differences between China and the United States in the approvals, timing, and clinical benefit evidence of cancer drug indications between 2001 and 2020. METHODS: This study retrospectively identified all cancer drugs and indications approved in both China and the United States from January 1st, 2001 to December 31, 2020, and described differences in approval times as well as in submission and review times. Information on the availability of overall survival benefit evidence by December 31, 2020, was collected. Univariate and multiple logistic regression analyses were used to assess whether evidence of benefit and other factors affected the propensity and timing of approvals of cancer drug indications in China. FINDINGS: Between 2001 and 2020, 229 indications corresponding to 145 cancer drugs approved in the United States were identified. Of those, 80 indications (34.9%) were also approved in China by the end of 2020. Cancer drug indications were approved in China at a median of 1273.5 days after approval in the United States. The median submission and review time differences for cancer drug indications in China were 1198.0 days and 180.0 days respectively. Submission time differences accounted for most of the approval time differences (p < 0.001). Indications supported by overall survival benefit evidence had shorter median review time differences (145.0 days) than those without such evidence (235.0 days, p = 0.008). Indications with overall survival benefit evidence were 3.94 times more likely to be approved in China compared to those without such evidence (p = 0.001), controlling for approval year, cancer type, and the prevalence of cancer by site. INTERPRETATION: FDA-approved cancer drug indications demonstrating a survival benefit were more likely to receive approvals in China with shorter regulatory review times compared to indications without such evidence. Given that manufacturer submission times were the main driver of cancer drug approval times in China, factors influencing submission timing should be explored. FUNDING: No funding

Effect of quercetin on the transport of ritonavir to the central nervous system in vitro and in vivo

The aim of this study was to identify an effective flavonoid that could improve the intracellular accumulation of ritonavir in human brain-microvascular endothelial cells (HBMECs). An in vivo experiment on Sprague-Dawley rats was then designed to further determine the flavonoid’s impact on the pharmacokinetics and tissue distribution of ritonavir. In the accumulation assay, the intracellular level of ritonavir was increased in the presence of 25 mmol L–1of flavonoids in HBMECs. Quercetin showed the strongest effect by improving the intracellular accumulation of ritonavir by 76.9 %. In the pharmacokinetic study, the presence of quercetin in the co-administration group and in the pretreatment group significantly decreased the area under the plasma concentration-time curve (AUC0-t) of ritonavir by 42.2 % (p < 0.05) and 53.5 % (p < 0.01), and decreased the peak plasma concentration (Cmax) of ritonavir by 23.1 % (p < 0.05) and 45.8 % (p < 0.01), respectively, compared to the control group (ritonavir alone). In the tissue distribution study, the ritonavir concentration in the brain was significantly increased 2-fold (p < 0.01), during the absorption phase (1 h) and was still significantly higher (p < 0.05) during the distribution phase (6 h) in the presence of quercetin

Impact of GLP-1 Receptor Agonists on Major Gastrointestinal Disorders for Type 2 Diabetes Mellitus: A Mixed Treatment Comparison Meta-Analysis

Aim. We aimed to integrate evidence from all randomized controlled trials (RCTs) and assess the impact of different doses of exenatide or liraglutide on major gastrointestinal adverse events (GIAEs) in type 2 diabetes (T2DM). Methods. RCTs evaluating different doses of exenatide and liraglutide against placebo or an active comparator with treatment duration ≥4 weeks were searched and reviewed. A total of 35, 32 and 28 RCTs met the selection criteria evaluated for nausea, vomiting, and diarrhea, respectively. Pairwise random-effects meta-analyses and mixed treatment comparisons (MTC) of all RCTs were performed. Results. All GLP-1 dose groups significantly increased the probability of nausea, vomiting and diarrhea relative to placebo and conventional treatment. MTC meta-analysis showed that there was 99.2% and 85.0% probability, respectively, that people with exenatide 10 μg twice daily (EX10BID) was more vulnerable to nausea and vomiting than those with other treatments. There was a 78.90% probability that liraglutide 1.2 mg once daily (LIR1.2) has a higher risk of diarrhea than other groups. A dose-dependent relationship of exenatide and liraglutide on GIAEs was observed. Conclusions. Our MTC meta-analysis suggests that patients should be warned about these GIAEs in early stage of treatment by GLP-1s, especially by EX10BID and LIR1.2, to promote treatment compliance

The impacts of implementation of National Essential Medicines Policies on primary healthcare institutions: a cross-sectional study in China

Abstract Background In 2009, China implemented the National Essential Medicines Policies (NEMPs) as part of a new round of medical system reforms. This study aims to evaluate the impacts of the NEMPs on primary healthcare institutions and discuss the roles of the policies in the new healthcare reforms of China. Methods The study selected a total of six representative provinces of China, generating a sample of 261 primary healthcare institutions from August to December in 2010. A questionnaire survey developed by the study team was distributed to all of the primary healthcare institutions. Nine indicators from three dimensions as the outcome variables were used and calculated to evaluate the impacts of implementation of policies. All of the outcome variables were tested using independent-samples T test between the treatment group (with the NEMPs implemented) and the control group (without the NEMPs implemented). Results The ratio of drug sales and institution revenues at primary healthcare institutions was 42.99% in the treatment group, which was significantly lower than the control group (53.90%, p < 0.01), while the ratio of financial subsidies of the treatment group was shown to be higher (30.78% VS 20.82%, p < 0.01). The rate of healthcare workers income growth was greater in the treatment group (15.35% VS 5.79%, p = 0.006). The treatment group exhibited higher outpatient and emergency visits per month in urban areas (2720 VS 1763 visits per month) and rural areas (3830 VS 3633), and higher prescriptions per month in urban areas (2048 VS 1025, p = 0.005) and rural areas (3806 VS 3251). The treatment group used more essential medicines and received greater income from essential medicines while the drug price markup rate was lower. Conclusions The NEMPs appear to affect the transformation of the operation mechanisms of primary healthcare institutions, the improvement of the mechanisms for government investment, and the healthcare pricing system. Meanwhile, the gaps between urban and rural areas need to be addressed. In conclusion, the NEMPs of China are instrumental to the aim of providing basic healthcare services to every citizen