Improvements in the health-related quality-of-life benefit of cancer drugs approved in China, 2005-2020: an observational study.

Background: Health-related quality of life (HRQoL), along with overall survival (OS), is a critical study endpoint for measuring the clinical benefits of cancer drugs. Previous studies have examined the OS benefit of new cancer drugs approved in China. However, their HRQoL benefits have not been systematically evaluated. We aimed to characterise the measurement and improvement of HRQoL associated with cancer drugs approved in China. Methods: This mixed-methods study comprises of a literature review and a cross-sectional study, including all antineoplastic agents approved in China between January 1, 2005 and December 31, 2020. A systematic search was conducted on December 31, 2023 to extract HRQoL information of identified drugs. We extracted information on the characteristics of HRQoL assessment and statistically significant HRQoL gains compared with the control treatment. Findings: A total of 64 novel cancer drugs, corresponding to 115 cancer indications, supported by randomised clinical trials were approved in China between 2005 and 2020. Among the indications, 78 (67.8%) used HRQoL as an endpoint in the pivotal trial. By December 31, 2023, after a median follow-up of 5.3 (range, 3.0-18.8) years from approval, HRQoL information was available for more than half of the indications (75, 65.2%). Thirty-three indications (28.7%) reported statistically significant improvement in HRQoL, with 22 (19.1%) also having documented OS benefit. Approximately one-third of the indications (39, 33.9%) showed no difference in HRQoL, with 21 (18.3%) having documented OS gains. Three indications (2.6%) reported worsening HRQoL. The most commonly used HRQoL measurements were individual disease-specific instruments (62 of 75, 82.7%) while the most frequently employed analysis metric was the mean change scores from baseline (56 of 75, 74.7%). Interpretation: Fewer than one-third of cancer indications approved in China had shown HRQoL improvements. There was considerable heterogeneity in the analysis and reporting of HRQoL benefits associated with new cancer drugs approved in China. These findings emphasise the important role of HRQoL evaluation and analysis in clinical research and the necessity of improving the standardization of HRQoL assessment. Funding: National Natural Science Foundation of China (72274004).

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.

Prevalence of aggressive care among patients with cancer near the end of life: a systematic review and meta-analysis.

Background: Aggressive care near patients' end-of-life (EOL) entails limited therapeutic values, high costs, and compromised quality of life (QoL). In this study, we aimed to estimate the global prevalence of aggressive care in patients with cancer and explore potential subgroup differences. Methods: We searched PubMed, Embase, and the Cochrane Library from database inception to Feb 16, 2024. Eligible studies reported the prevalence of aggressive EOL care using at least one quantifiable measure. Random-effects models were used to derive the pooled prevalence and subgroup analyses were performed to investigate differences in the prevalence of aggressive care across regions, the country's level of economic development, tumor types, ages, and sample sizes. This review is registered with PROSPERO, number CRD42023467839. Findings: A total of 129 studies were included in this systematic review, of which 118 (91.5%) were from high-income countries. Studies were mostly conducted in the Americas (60, 46.5%), Europe (34, 26.4%), and Western Pacific (31, 24.0%). Measures of aggressive care were inconsistent across studies, with the most commonly used measure being the use of chemotherapy in the last 14 days of life (DOLs) (n = 87, 67.4%) and intensive care unit (ICU) stay in the last 30 DOLs (n = 87, 67.4%). The prevalence of the five claims-based measures of aggressive care, i.e., chemotherapy in the last 14 DOLs, ICU stay in the last 30 DOLs, repeated hospital admission in the last 30 DOLs, repeated emergency room (ER) visit in the last 30 DOLs, and hospice care <3 days before death were 11.6% (95% CI, 9.8%-13.4%), 14.4% (95% CI, 11.8%-17.0%), 17.9% (95% CI, 14.4%-21.4%), 14.8% (95% CI, 12.0%-17.6%), and 14.4% (95% CI, 11.2%-17.6%), respectively. Regional differences were statistically significant in the prevalence of ICU stay and repeated hospital admission in the last 30 DOLs (p < 0.01; p = 0.03). Patients with hematologic malignancies were more likely to receive aggressive care than those with solid tumors, as seen in their higher rates of chemotherapy in the last 14 DOLs (21.7% versus 11.6%; p = 0.03), ICU stay in the last 30 DOLs (25.5% versus 10.8%; p < 0.01), and hospice care <3 days before death (26.7% versus 14.2%; p < 0.01). In addition, the prevalence of chemotherapy in the last 14 DOLs (26.2%; p < 0.01) and repeated hospital admission in the last 30 DOLs (31.4%; p < 0.01) were highest among pediatric patients with cancer. Interpretation: This meta-analysis found that aggressive EOL care was common in patients with cancer, regardless of the definition used, and varied by regions and populations. It is necessary to be aware of the global burden of aggressive care for patients with cancer near their EOL and take prompt action to address it. Funding: National Natural Science Foundation of China (Grant No. 72274004).

Use of suboptimal control arms in randomized clinical trials of investigational cancer drugs in China, 2016-2021: An observational study.

BACKGROUND: The use of suboptimal controls in randomized trials of new cancer drugs can produce potentially unreliable clinical efficacy results over the current standard of care and expose patients to substandard therapy. We aim to investigate the proportion of randomized trials of investigational cancer drugs that used a suboptimal control arm and the number of trial participants at risk of exposure to suboptimal treatments in China. The association between the use of a suboptimal control and concluding statistical significance on the primary endpoint was also examined. METHODS AND FINDINGS: This observational study included randomized controlled trials (RCTs) of cancer drugs that were authorized by specific Chinese institutional review boards between 2016 and 2021, supporting investigational new drug applications of these drugs in China. The proportion of trials that used a suboptimal control arm and the total number of trial participants at risk of exposure to suboptimal treatments were calculated. In a randomized trial for a specific condition, a comparator was deemed suboptimal if it was not recommended by clinical guidelines published in priori or if there existed a regimen with a higher level of recommendation for the indication. The final sample included 453 Phase II/III and Phase III randomized oncology trials. Overall, 60 trials (13.2%) adopted a suboptimal control arm. Among them, 58.3% (35/60) used comparators that were not recommended by a prior guideline for the indication. The cumulative number of trial participants at risk of exposure to suboptimal treatments totaled 18,610 by the end of 2021, contributing 15.1% to the total number of enrollees of all sampled RCTs in this study. After adjusting for the year of ethical approval, region of participant recruitment, line of therapy, and cancer site, second-line therapies (adjusted odds ratio [aOR] = 2.7, 95%CI [1.2, 5.9]), adjuvant therapies (aOR = 8.9, 95% CI [3.4, 23.1]), maintenance therapies (aOR = 5.2, 95% CI [1.6, 17.0]), and trials recruiting participants in China only (aOR = 4.1, 95% CI [2.1, 8.0]) were more likely to adopt a suboptimal control. For the 105 trials with publicly available results, no statistically significant difference was observed between the use of a suboptimal control and concluding positive on the primary endpoint (100.0% [12/12] versus 83.9% [78/93], p = 0.208). The main limitation of this study is its reliance on clinical guidelines that could vary across cancer types and time in assessing the quality of the control groups. CONCLUSIONS: In this study, over one-eighth of randomized trials of cancer drugs registered to apply for regulatory approval in China used a suboptimal comparator. Our results highlight the necessity to refine the design of randomized trials to generate optimal clinical evidence for new cancer therapies.

Potentially inappropriate medications among older patients with Parkinson's disease: a cross-sectional analysis of a national health insurance database in China.

BACKGROUND: With the rapid aging trend of China's population, the issue of drug rational use in older adults has become more and more prominent. Parkinson's disease (PD) is the one of the most common age-related neurodegenerative disorders. Pharmaceutical treatment plays a cardinal role in alleviating motor and non-motor symptoms to improve the quality of life of patients with PD. Patients with PD have complex medical needs yet little is known about the use of potentially inappropriate medications (PIM) among them in China. We quantify the prevalence of PIM use and identify its predictors among older persons with PD in China. METHODS: We conducted a cross-sectional analysis using a national representative database of all medical insurance beneficiaries across China, extracting records of ambulatory visits of older adults with PD between 2015 and 2017. Beneficiaries aged 65 and above were eligible for inclusion. The prevalence of patients exposed to overall PIMs and PIMs related to motor and cognitive impairment was calculated based on Beers Criteria 2015 version. Potential predictors of PIM concerning patients' characteristics were estimated using multivariate logistic regression. RESULTS: A total of 14,452 older adults with PD were included. In total, 8,356 (57.8%) patients received at least one PIM; 2,464 (17.1%) patients received at least one motor-impairing PIM and 6,201 (42.9%) patients received at least one cognition-impairing PIM. The prevalence of overall PIM use was higher in patients of older age group (54.7% [65-74] vs. 59.5% [75-84; OR, 1.22; 95% CI, 1.14-1.31] vs.65.5% [≥ 85; OR, 1.58; 95% CI, 1.38-1.80) and females (61.4% [female] vs. 55.0% [males; OR, 0.77; 95% CI, 0.72-0.82). CONCLUSIONS: Prescribing PIMs for older adults with PD was common in China, especially for females and older age groups, yet younger patients were more inclined to be prescribed with motor or cognition-impaired PIMs. Our findings represent a clear target awaiting multidimensional efforts to promote the rational prescribing of medications for this vulnerable population.

Evaluation of prescription review and feedback policy on rational antibiotic use in primary healthcare settings in Beijing, China: a qualitative study using the Theoretical Domains Framework and the behaviour change wheel.

Objectives: To decelerate antibiotic resistance driven by inappropriate antibiotic prescribing, a prescription review and feedback (PRF) policy is implemented in primary healthcare institutions (PHIs) in Beijing, China. However, evaluation of PRF implementation in PHIs is scarce. This study aims to systematically identify the barriers and facilitators of PRF policy implementation to provide evidence for antimicrobial stewardship. Methods: We conducted key informant interviews with 40 stakeholders engaged in the implementation of PRF in Beijing, including physicians, pharmacists and administrators. Interviews were audio recorded and transcribed verbatim. We coded the interview transcripts and mapped informant views to domains of the Theoretical Domains Framework. We then used a behaviour change wheel to suggest possible behavioural interventions. Results: Procedural knowledge (Knowledge) and skills (Skill) of PRF were possessed by stakeholders. They felt responsible to promote the appropriate use of antibiotics (Social/professional role and identity) and believed that PRF could help to change inappropriate provider behaviours (Behavioural regulation) in prescribing antibiotics (Beliefs about consequences) under increased intention on antibiotic use (Stages of change). Moreover, informants called for a more unified review standard to enhance PRF implementation (Goals). Frequently identified barriers to PRF included inadequate capacity (Skill), using punishment mechanism (Behaviour regulation), reaching consistently lower antibiotic prescription rates (Goals), lack of resources (Environmental context and resources) and perceived pressure coming from patients (Social influences). Conclusions: Stakeholders believed that PRF implementation promoted the rational use of antibiotics at PHIs in Beijing. Still, PRF was hampered by inconsistencies in review process and resources needed for PRF implementation.

'I feel that I should decide on my own .': who should be involved in the decision-making process for adolescent involvement in HIV research?

INTRODUCTION: Efforts to improve health outcomes among adolescents and young adults living with HIV (ALHs) are hampered by limited adolescent engagement in HIV-related research. We sought to understand the views of adolescents, caregivers and healthcare workers (HCWs) about who should make decisions regarding ALHs' research participation. METHODS: We conducted focus group discussions (FGDs) and in-depth interviews (IDIs) with ALHs (aged 14-24 years), caregivers of ALHs and HCWs from six HIV care clinics in Western Kenya. We used semi-structured guides to explore ALHs' involvement in research decisions. Transcripts were analysed using thematic analysis; perspectives were triangulated between groups. RESULTS: We conducted 24 FGDs and 44 IDIs: 12 FGDs with ALHs, 12 with caregivers, and 44 IDIs with HCWs, involving 216 participants. HCWs often suggested that HIV research decision-making should involve caregivers and ALHs deciding together. In contrast, ALHs and parents generally thought decisions should be made individually, whether by HCWs/research teams (although this is likely ethically problematic), adolescents or caregivers. Caregiver and ALH preferences depended on ALHs' age, with younger ALHs requiring more support. A few caregivers felt that ALHs should consult with the research team/HCWs due to their greater knowledge of clinical care. ALHs emphasised that they should independently decide because they thought they had the right to do so and the capacity to consent. Poor communication and parental non-disclosure of HIV status influenced ALHs' views to exclude caregivers from decision-making. Regarding influences on research decision-making, ALHs were more willing to participate based on perceived contribution to science and less interested in participating in studies with potential risks, including loss of confidentiality. DISCUSSION: While research teams and HCWs felt that adolescents and caregivers should jointly make research decisions, ALHs and caregivers generally felt individuals should make decisions. As ALHs sometimes find caregiver support lacking, improving family dynamics might enhance research engagement.

Sponsorship bias in published pharmacoeconomic evaluations of national reimbursement negotiation drugs in China: a systematic review.

BACKGROUND: China's National Reimbursement Drug List (NRDL) has become the primary route for drug reimbursement in China. More recently, the authority has made pharmacoeconomic evaluation an integral part of the application for NRDL inclusion. The underlying financial conflict of interests (FCOI) of pharmacoeconomic evaluations, however, has the potential to influence evidence generated and thus subsequent decision-making yet remains poorly understood. METHODS: We searched for studies published between January 2012 and January 2022 on the 174 drugs added to the 2017-2020 NRDLs after successful negotiation. We categorised the study's FCOI status into no funding, industry funding, non-profit funding and multiple fundings based on authors' disclosure and assessed the reporting quality of included studies using the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. We compiled descriptive statistics of funding types and study outcomes using t-tests and χ2 tests and conducted multivariate regression analysis. RESULTS: We identified 378 records and our final sample included 92 pharmacoeconomic evaluations, among which 69.6% were conducted with at least one funding source. More than half (57.6%) of the evaluations reached favourable conclusions towards the intervention drug and 12.6% reached a dominant result of the intervention drug over the comparison from model simulation. The reporting quality of included studies ranged from 19 to 25 (on a scale of 28), with an average of 22.3. The statistical tests indicated that industry-funded studies were significantly more likely to conclude that the intervention therapy was economical (p<0.01) and had a significantly higher proportion of resulting target drug economically dominated the comparison drug (p<0.05). CONCLUSION: The study revealed that FCOI bias is common in published pharmacoeconomic evaluations conducted in Chinese settings and could significantly influence the study's economical results and conclusions through various mechanisms. Multifaceted efforts are needed to improve transparency, comparability and reporting standardisation.

The impact of government reimbursement negotiation on targeted anticancer medicines use and cost in China: A cohort study based on national health insurance data.

Background: High prices of targeted anticancer medicines (TAMs) result in financial toxicity for patients and the health insurance system. How national price negotiation and reimbursement policy affect the accessibility of TAMs for cancer patients remains unknown. Methods: In this population-based cohort study, we used national health insurance claims data in 2017 and identified adult patients with cancer diagnoses for which price-negotiated TAMs were indicated. We estimated the half-month prevalence of price-negotiated TAMs use before and after the policy implementation in September 2017. We calculated direct medical costs, out-of-pocket (OOP) costs, and the proportion of OOP cost for each cancer patient to measure their financial burden attributable to TAMs use. We performed segmented linear and multivariable logistic regression to analyse the policy impact. Results: We included 39 391 of a total 118 655 cancer beneficiaries. After September 2017, the prevalence of price-negotiated TAMs use increased from 1.4%-2.1% to 2.9%-3.1% (P = 0.005); TAMs users' daily medical costs increased from US$261.3 to US$292.5 (P < 0.001), while median daily OOP costs (US$68.2 vs US$65.7; P = 0.134) and OOP costs as a proportion of daily medical costs persisted (28.5% vs 28.5%; P = 0.995). Compared with resident beneficiaries, the relative probability of urban employee beneficiaries on TAMs uses decreased after the policy (adjusted odds ratio (aOR) = 2.4 vs aOR = 2.2). Conclusions: The government price negotiation and reimbursement policy improved patient access to TAMs and narrowed disparities among insurance schemes. China's approach to promoting the affordability of expensive medicines provides valuable experience for health policy decision-makers.

Appropriate use of antibiotics for acute respiratory infections at primary healthcare facilities in China: a nationwide cross-sectional study from 2017 to 2019.

Background: The appropriateness of antibiotic use for acute respiratory infections (ARIs) in Chinese primary healthcare facilities (PHFs) remained uncertain. We aimed to evaluate to what degree antibiotic prescribing for ARIs were aligned with guideline recommendations in primary settings across China. Methods: We collected outpatient prescriptions from 262 Chinese PHFs in 27 cities of six provinces between 2017 and 2019. The appropriate antibiotic prescribing was defined as prescribing antibiotic classes that were recommended by Chinese clinical guidelines, if patients were prescribed antibiotics. We evaluated the magnitude of antibiotics prescribed for acute upper respiratory infections (AURIs), acute bronchitis, and community-acquired pneumonia (CAP) and their appropriateness. Findings: Overall, 55.1% (87,684/159,150), 66.8% (30,836/46,153), and 68.5% (4615/6733) of outpatients with AURIs, acute bronchitis, and CAP treated at PHFs in China were prescribed with antibiotics. Of all antibiotic prescriptions, only 20.0% (17,542/87,684), 18.6% (5724/30,836) and 69.6% (3211/4615) used antibiotic classes that were recommended by the guidelines for AURIs, acute bronchitis, and CAP, respectively. Patients residing in the Chinese central region (17.0%, 15.4%, 69.3% for AURIs, acute bronchitis, and CAP, respectively) were less likely to be prescribed with antibiotics that were appropriately selected. Interpretation: Unnecessary antibiotics were widely prescribed for patients with AURIs or acute bronchitis and most patients with ARIs did not receive guideline-recommended antibiotic classes in Chinese PHFs. Interventions to promote evidence-based treatment and the appropriate use of antibiotics are urgently needed at the primary level across China. Funding: This work was supported by the National Natural Science Foundation of China [grant number 72074007, 81973294].

Effectiveness of hierarchical medical system policy: an interrupted time series analysis of a pilot scheme in China.

The Chinese healthcare system faces a dilemma between its hospital-centric approach to healthcare delivery and a rapidly ageing population that requires strong primary care. To improve system efficiency and continuity of care, the Hierarchical Medical System (HMS) policy package was issued in November 2014 and fully implemented in 2015 in Ningbo, Zhejiang province, China. This study aimed to investigate the impact of the HMS on the local healthcare system. We conducted a repeated cross-sectional study with quarterly data collected between 2010 and 2018 from Yinzhou district, Ningbo. The data were analysed with an interrupted time series design to assess the impact of HMS on the changes in levels and trends of three outcome variables: primary care physicians' (PCPs') patient encounter ratio (i.e. the mean quarterly number of patient encounters of PCPs divided by that of all other physicians), PCP degree ratio (i.e. the mean degree of PCPs divided by the mean degree of all other physicians, with the mean degree revealing the mean activity and popularity of physicians, which reflected the extent to which he/she coordinated with others in delivering health services), and PCP betweenness centrality ratio (i.e. the mean betweenness centrality of PCPs divided by the mean betweenness centrality of all other physicians; the mean betweenness centrality was interpreted as the mean relative importance of physicians within the network, indicating the centrality of the network). Observed results were compared with counterfactual scenarios computed based on pre-HMS trends. Between January 2010 and December 2018, 272 267 patients visited doctors for hypertension, a representative non-communicable disease with a high prevalence of 44.7% among adults aged 35-75 years, amounting to a total of 9 270 974 patient encounters. We analysed quarterly data of 45 464 observations over 36 time points. Compared to the counterfactual, by the fourth quarter of 2018, the PCP patient encounter ratio rose by 42.7% [95% confidence interval (CI): 27.1-58.2, P < 0.001], the PCP degree ratio increased by 23.6% (95%CI: 8.6-38.5, P < 0.01) and the PCP betweenness centrality ratio grew by 129.4% (95%CI: 87.1-171.7, P < 0.001). The HMS policy can incentivize patients to visit primary care facilities and enhance the centrality of PCPs within their professional network.

Benzodiazepine Receptor Agonists Prescribing for Insomnia Among Adults in Primary Health Care Facilities in Beijing, China.

This cross-sectional study examines the benzodiazepine receptor agonists (BZRA) prescribing rate for insomnia among adult patients in primary health care facilities (PHFs) in China.

"[T]he laws need to change to reflect current society": Insights from stakeholders involved in development, review or implementation of policies about adolescent consent for HIV testing, care and research in Kenya.

INTRODUCTION: Engaging adolescents in HIV care and research promotes the development of interventions tailored to their unique needs. Guidelines generally require parental permission for adolescents to receive HIV care/testing or participate in research, with exceptions. Nevertheless, parental permission requirements can restrict adolescent involvement in care and research. To better appreciate prospects for policy reform, we sought to understand the perspectives of stakeholders involved in the development, review and implementation of policies related to adolescents living with HIV. METHODS: Semi-structured individual interviews (IDIs) were conducted from October 2019 to March 2020 with 18 stakeholders with expertise in the (1) development of policy through membership in the Law Society of Kenya or work as a health policy official; (2) review of policy through ethics review committee service; or (3) implementation of policy through involvement in adolescent education. IDIs were conducted in English by Kenyan social scientists, audio-recorded and transcribed verbatim. We used thematic analysis to identify themes around how policies can be reformed to improve adolescent engagement in HIV care and research. RESULTS: Our analysis identified three major themes. First, policies should be flexible rather than setting an age of consent. Stakeholders noted that adolescents' capacity for engagement in HIV care and research depended on context, perceived risks and benefits, and "maturity"-and that age was a poor proxy for the ability to understand. Second, policies should evolve with changing societal views about adolescent autonomy. Participants recognized a generational shift in how adolescents learn and mature, suggesting the need for a more frequent review of HIV care and research guidelines. Third, adults should empower adolescent decision-making. Stakeholders felt that caregivers can gradually involve adolescents in decision-making to equip them to gain ownership over their health and lives, improving their confidence and capacity. CONCLUSIONS: Revising relevant laws to consider context, alternative measures of maturity, and evolving societal views about adolescence, along with supporting caregivers to assist in developing adolescent autonomy may promote more equitable and representative participation of adolescents in HIV care and research. Additional research should explore how to support caregivers and other adults to empower adolescents and improve stakeholder engagement in a more routine process of policy reform.

Inappropriate antibiotic prescribing in primary healthcare facilities in China: a nationwide survey, 2017-2019.

OBJECTIVES: We aimed to generate comprehensive estimates of the appropriateness of outpatient antibiotic prescriptions at primary healthcare facilities (PHFs) in China. METHODS: Between 2017 and 2019, we collected outpatient-visit prescriptions from 269 Chinese PHFs in 31 cities located in 6 provinces. Conditions that resulted in antibiotic use were classified into appropriate, potentially appropriate, and inappropriate using a well-established classification approach. We then assessed the magnitude, appropriateness, and costs of antibiotic prescribing, overall and by antibiotic classification group, diagnostic categories, and patient characteristics. RESULTS: Of all eligible 209 662 antibiotic prescriptions, 147 758 (70.5%) were inappropriate, which accounted for 66.8% (558.0/835.3 thousand US dollars) of costs for antibiotics. Upper respiratory tract infections, acute bronchitis, and non-infectious gastroenteritis were responsible for 68.9% (101 744/147 758) of inappropriately antibiotic prescriptions. High inappropriate antibiotic prescribing rates were observed among children aged 0-5 years (78.5% (21 049/26 799)) and patients living in economically undeveloped areas (77.5% (38 430/49 587)). A total of 256 474 individual antibiotics were prescribed, of which 82.2% (210 885/256 474) were broad-spectrum antibiotics, with second-generation cephalosporins (15.1% (38 705/256 474)) and third-generation cephalosporins (14.6% (37 491/256 474)) being the most commonly prescribed subgroups. DISCUSSION: Our findings highlight the excessive and inappropriate use of antibiotics in Chinese PHFs pending multidimensional efforts.

Effect of the full coverage policy of essential medicines on medication adherence: A quasi-experimental study in Taizhou, China.

Objective: Different forms of full coverage policy of essential medicines (FCPEMs) have been adopted worldwide to lower medication expenditure and improve adherence. This study aims to analyse the effect of FCPEMs on patients' medication adherence in Taizhou city, China. Methods: This study was a quasi-experimental study and set treatment and control groups. We extracted Electronic Health Records (EHRs) for hypertension and diabetes 1 year before and after FCPEMs implementation and their medication adherence level assessed by physicians. We applied the propensity score matching (PSM) method to balance the bias between the two groups. Then, the descriptive analysis was used to compare the differences in the reported medication adherence. Using the Difference-In-Differences (DIDs) method, the fixed-effect model with the logistic regression was built to analyse the effects of FCPEMs. Results: 225,081 eligible patients were identified from the original database. In the baseline year, FCPEM covered 39,251 patients. After PSM, 6,587 patients in the treatment group and 10,672 patients in the control group remained. We found that the proportion of patients with high adherence in the treatment group increased by 9.1% (60.8 to 69.9%, P < 0.001) and that in the control group increased by 2.6% (62.5 to 65.2%, P < 0.001). The regression results showed that FCPEMs significantly increased patients' medication adherence (OR = 2.546, P < 0.001). Conclusion: FCPEMs significantly improved medication adherence. Socially disadvantaged individuals might benefit more from continuing FCPEM efforts. Expanding the coverage of FCPEMs to other medicines commonly used in patients with chronic diseases may be a promising strategy to manage chronic diseases and promote patient outcomes.

The Impact of Sanming Healthcare Reform on Antibiotic Appropriate Use in County Hospitals in China.

Background: The excessive use of resources and poor quality of care are great concerns worldwide, particularly in China. In 2013, a model of systematic reforms was developed in Sanming to address the inefficiency and waste in public hospitals. However, limited empirical studies have evaluated the effect of Sanming healthcare reform on antibiotic appropriate use. This study aims to evaluate the impact of the healthcare reform on the appropriate use of antibiotics in county-level public hospitals in Sanming, China. Methods: We conducted a retrospective observational study exploring trends in antibiotic use with an interrupted time series design. We selected three county-level hospitals in Sanming and extracted outpatient prescriptions of the Departments of Internal Medicine and the Department of Pediatrics between January 2011 and December 2017. Acute Upper Respiratory Tract Infection (AURI), Acute Bronchitis (AB) and Community Acquired Pneumonia (CAP) were selected as the sample diseases for our analysis. The primary outcome was the percentage of prescriptions conformed with standard treatment guidelines (STGs). Results: A total of 142,180 prescriptions were included in the analysis. During the study period, the percentage of antibiotics prescriptions conformed with STGs boosted from 32.4% in 2011 to 82.3% in 2017. Moreover, after the reform, the rate of prescriptions that conformed with STGs showed significant increasing trends in children with AURI (ß = 1.624, p < 0.001), children with AB (ß = 3.123, p < 0.001), adult with AB (ß = 1.665, p < 0.001), children with CAP (ß = 3.123, p < 0.001), adult with CAP (ß = 4.385, p < 0.001), but not in adult patients with AURI (ß = -0.360, p = 0.022). Conclusion: Our study confirmed that the Sanming healthcare reform helped to promote the appropriate use of antibiotics in county-level hospitals. This systematic approach to healthcare reform, characterized by an effective governance structure, dynamic financial compensation mechanisms, and specialized drug stewardship, is promising for future public hospital reforms.

Prices and Clinical Benefit of National Price-Negotiated Anticancer Medicines in China.

BACKGROUND: High prices of anticancer medicines have increased the economic burden for both patients and health insurance systems. Since 2017, China has implemented national price negotiations for medicines, relying on evidence from health technology assessments. We aim to assess the relation between negotiated price and value of anticancer medicines listed in China's National Reimbursement Drug List (NRDL). METHODS: For all price-negotiated anticancer medicines and corresponding indications listed in the latest NRDL between 2017 and 2020, we collected their clinical outcomes data, including overall survival (OS) and progression-free survival (PFS), in supporting trials. Pearson correlation coefficient was calculated to estimate the association between the daily cost and clinical benefit of each indication. RESULTS: In total, 75 indications of 46 branded anticancer medicines were included for analysis. The median daily costs for the anticancer therapies that had gone through negotiation in 2017-2020 were US$87.6, US$71.8, US$58.9, and US$39.7, respectively. For indications supported by randomized trials, no correlation between daily costs and OS and PFS benefit of the price-negotiated cancer therapies was observed (N = 41, r = -0.05, and N = 49, r = 0.04, respectively). For cancer indications newly listed in NRDL in 2020, the association between their daily cost and OS benefit was -0.78 (N = 4, p = 0.221) and 0.01 (N = 8, p = 0.986) before and after the price negotiation. CONCLUSION: Though the negotiation policy decreased prices of anticancer medicines in China, no statistically significant correlation was observed between their daily costs and clinical benefits. A more transparent and credible pricing approach needs to be established to promote value-based anticancer medicines and healthcare system efficiency.

Effects of the Full Coverage Policy of Essential Medicines on Inequality in Medication Adherence: A Longitudinal Study in Taizhou, China.

The full coverage policy for essential medicines (FCPEMs) was proposed and implemented in Taizhou city of Zhejiang Province, China, to promote equal access and adherence to medicines. This study aimed to examine the effects of FCPEMs on the income-related inequality in medication adherence among local patients with hypertension or diabetes. We collected electronic health records of patients with hypertension or diabetes of three districts of Taizhou from 2011 to 2016. As the implementation schedule of the FCPEMs varied across districts, we applied a retrospective longitudinal study design and assigned records from 1 year before to 3 years following the implementation of FCPEMs as baseline and follow-up data. We thus generated a dataset with 4-year longitudinal data. The concentration index (CI) and its decomposition method were employed to measure factors contributing to inequality in medication adherence and the role played by FCPEMs. The sample size rose from 264,836 at the baseline to 315,677, 340,512, and 355,676 by each follow-up year, and the proportion of patients taking free medicines rose from 17.6 to 25.0 and 29.8% after FCPEMs implementation. The proportion of patients with high adherence increased from 39.9% at baseline to 51.6, 57.2, and 60.5%, while CI decreased from 0.073 to -0.011, -0.029, and -0.035. The contribution of FCPEMs ranked at 2nd/13, 7th/13, and 2nd/13 after the implementation of FCPEMs. Changes in CI of medication adherence for every 2 years were -0.084, -0.018, and -0.006, and the contribution of FCPEMs was -0.006, 0.006, and 0.007, ranking at 2nd/13, 2nd/13, and 1st/13, respectively. Most changes in CI of medication adherence can be attributed to FCPEMs. The medication adherence of patients with hypertension or diabetes improved after the implementation FCPEMs in Taizhou, although inequality did not improve consistently. In general, FCPEMs could be a protective factor against income-related inequalities in access and adherence to medicines. Future research is needed to investigate the change mechanism and the optimal design of similar interventions.