The Impact of Regulatory Reforms in China on Drug Lag: The Role of Clinical Development Strategies.

In recent years, there has been significant focus on China's new drug lag, but relevant research is limited. This study explores the reasons for drug lag by assessing the impact of reforms in China's drug review system, particularly focusing on the influence of clinical development strategies. This study selected drugs first launched in the United States between 2017 and 2022, examining absolute and relative lag between China and the first-launch country (including submission and review lag). These delays with drugs approved in the European Union and Japan during the same period were compared with uncover the roots of delays in China, further identifying potential factors that could reduce these delays. The results indicate that the National Medical Products Administration (NMPA) has a longer relative lag compared with the European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency (PMDA). The submission lag time of the NMPA significantly surpasses that of the EMA and PMDA, whereas the review lag time of the NMPA exceeds that of the PMDA but falls short of the EMA. Focusing on clinical trial strategies, bridging trials and multiregional clinical trials (MRCTs) are typically required by the NMPA in East Asia, resulting in longer clinical delay time. Whereas the EMA and PMDA primarily require international MRCTs in Europe and America, with a clinical delay of < 5 months. It is evident that there is a significant gap in clinical trial durations between China and other countries. Further optimization of clinical trial management is necessary to address the lag for new drugs in China.

Correlates of residents' enrolment intention toward inclusive commercial health insurance in China: involvement, perceived benefit, perceived sacrifice, and government participation.

Background: As an application of inclusive finance in health insurance, inclusive commercial health insurance (ICHI) is a new public-private partnership-based health insurance scheme and has been vigorously promoted by the Chinese government in recent years to develop China Multi-level Health Insurance System, a system that aims to seek a mix of public and private sources to provide more affordable financial protection to all levels of society in line with their needs. However, the overall enrolment of ICHI scheme is still at a low level, and little is known about what influences residents' enrolment intentions. The aim of this study was to examine the multidimensional factors influencing residents' behavioral intentions and to develop a multivariate conceptual model to explore the psychographic process in the formation of enrolment intention. Methods: The empirical data used for model validation were obtained from a cross-sectional study conducted in Nanjing, China, a representative pilot city of ICHI scheme in 2022. Exploratory factor analysis, ANOVA, standard multiple regression, and hierarchical multiple regression were mainly employed for hypothesis testing. Results: The findings revealed that involvement, perceived benefit, and perceived sacrifice are all crucial psychographic process factors in the formation of residents' enrolment intentions. Government participation positively moderates the influence path of "perceived benefit-enrolment intention" but negatively moderates the path of "perceived sacrifice-enrolment intention". Moreover, it was discovered that perceived benefit mediates the effect of involvement on enrolment intention, while perceived sacrifice does not. Conclusions: Improving residents' perceived benefit and involvement degree of the product, as well as reducing their perceived sacrifice, are both key to increasing their enrolment intentions. This study also points out that one of the main dilemmas in the current development of ICHI scheme is the low level of involvement among residents, and that optimizing the product design to make it more relevant to residents' lives is a more beneficial strategy to increase overall involvement.

Factors associated with delayed diagnosis of Crohn's disease: A systematic review and meta-analysis.

Background: Delayed diagnosis is a major barrier to the effective management of Crohn's disease (CD). Several studies have investigated factors responsible for delays in diagnosis, but no meta-analyses have systematically assessed the impact of these factors. Aim: To assess the impact of various factors on the delayed diagnosis of CD. Methods: PubMed, EMBASE, and Web of Science databases were searched to identify observational studies published before April 2022 that assessed factors associated with delays in CD diagnosis. Further, we excluded review articles, case reports, or commentaries without original data. We pooled effect siee distinct samples. The assessment of study quality was performed utilizing the Newcastle-Ottawa Scale, while the presence of between-study heterogeneity was investigated. For a visual appraisal of potential publication bias, a funnel plot was employed. The study protocol was registered with PROSPERO, CRD42022322251. Results: A total of 18 studies were included in the paper, covering 13 countries. The study sample consisted of 9669 cases. Ileal CD (OR = 1.46, 95 % CI = 1.21-1.76), smoking at the time of diagnosis (OR = 1.19, 95 % CI = 1.02-1.38), and use of NSAIDs (OR = 1.34, 95 % CI = 1.04-1.72) were significantly associated with a delay in CD diagnosis. However, no significant associations were observed between diagnostic delay and sex, age, endoscopic ileocolonoscopy, or diarrhea. Funnel plot analysis, indicating potential risks of publication bias, suggested the existence of unpublished or unreported study findings. Conclusion: The findings suggest that ileal CD, use of NSAIDs, and smoking are risk factors for the delayed diagnosis of CD. Enhancing education of patients and primary care providers about these factors is warranted.

Progress and Challenges of the New Conditional Approval Process in China: A Pooled Analysis From 2018 to 2021.

PURPOSE: To speed the review and approval of drugs and address pressing medical needs, China began to advocate for the implementation of the conditional approval process in 2017. We aimed to assess the implementation of the conditional approval process in China and further analyze its potential problems and future challenges. METHODS: This study examined the new drug approval with conditions in China between 2018 and 2021, based on an analysis of drug technical review documents from the Center for Drug Evaluation (CDE). Using publicly available information, we further analyzed the characteristics and results of pivotal clinical trials of conditionally approved drugs, postmarketing study requirements and progress. FINDINGS: Between 2018 and 2021, China conditionally approved 50 drugs, with 80% (40/50) being antineoplastic agents. Premarketing pivotal trials predominantly used single-arm clinical trials (83.7%, 41/49), while postmarketing trials mainly employed randomized controlled clinical trials (81.0%, 34/42). In oncology drugs, conditionally approved drugs with progression-free survival (PFS) and overall survival (OS) as primary endpoints achieved significant clinical value in terms of efficacy. However, there were also pivotal clinical trials with response rate (RR) as the primary endpoint that demonstrated lower clinical benefits (8.9% of drugs with RR below 20%). Safety analysis revealed substantial variations in the proportions of grade ≥3 adverse events (AEs) and serious adverse events (SAEs) across pivotal trials (Grade ≥ 3 AEs: 9.0%-99.0%; SAEs: 8.0%-83.0%). For nononcology drugs, pivotal trials also demonstrated an acceptable risk-benefit ratio but exhibited methodological issues. Meanwhile, Most postmarketing studies lacked completion date restrictions (43.2%, 17/47), and no requirements were specified for the transition to full approval. Furthermore, surrogate endpoints were primarily utilized both pre- and postmarketing, but the rational selection of surrogate endpoints remains to be investigated. IMPLICATIONS: The conditional approval process expedites patient access to drugs for serious diseases. However, challenges pertaining to evidence assessment during approval and design flaws in postmarketing studies exist in China's conditional approval system, necessitating future improvements.

Comparison of novel oncology drugs that received dual approval from the US accelerated approval and EU conditional marketing authorisation pathways, 2006-2021: a cross-sectional study.

OBJECTIVE: We aimed to provide insight into differences in drug review decisions made by the US Food and Drug Administration's (FDA) accelerated approval (AA) pathway and the European Medicines Agency's (EMA) conditional marketing authorisation (CMA) pathway, and to add to the current knowledge base of drug approval processes. DESIGN, SETTING, PARTICIPANTS: This cross-sectional study thoroughly examines novel oncology drugs with dual approval through FDA AA and EMA CMA between 2006 and 2021. Statistical analysis was performed from June to July 2022. PRIMARY AND SECONDARY OUTCOME MEASURES: The study examined the regulatory differences between regions for dually approved novel oncology drugs, including approval decisions, pivotal efficacy clinical trials, speed of review and postmarketing obligations. RESULTS: During this time period, there was a difference in the use of the FDA AA and the EMA CMA (FDA: EMA: 41.2%: 70.0%, p<0.05). Of the 25 drugs approved by both the FDA AA and the EMA CMA, 22 (88.0%) of the regulatory decisions were based on the same pivotal clinical trials. But there were more differences in the requirements for postmarketing obligations, with the EMA's postmarketing obligations focusing on the efficacy and safety of the drug (EMA: FDA: 63.0%: 27.0%, p＜0.05) and the FDA's postmarketing obligations focusing more on the efficacy (FDA: EMA: 73.0%: 23.9%, p＜0.05). In addition, both the USA and EU had some postmarketing obligations completed beyond the schedule (30.4% and 19.2% in the USA and EU, respectively), with the longest delays lasting 3.7 years (0.2-3.7 years) and 3.3 years (0.04-3.3 years) in the USA and EU, respectively. CONCLUSIONS: The FDA and EMA have different orientations and benefit-risk balance considerations in the use of AA or CMA. It is also the case that the shortcomings in the design and implementation of postmarketing studies have made it a challenge to obtain the evidence needed to confirm a drug's benefits.

Female perspective: the burden of Alzheimer's disease and other dementias in China from 1990 to 2019 and prediction of their prevalence up to 2044.

Background: Dementia is more prevalent in women than in men across the world, and sex differences are reflected in the burden of dementia borne by women and men. However, a few studies have specifically analyzed the disease burden of dementia in Chinese women. Objective: This article aims to raise awareness of Chinese females with dementia (CFWD), outline an effective response to future trends in China from a female perspective, and provide a reference for the scientific formulation of dementia prevention and treatment policies in China. Methods: In this article, epidemiological data on dementia in Chinese women were obtained from the Global Burden of Disease Study 2019, and three risk factors, namely, smoking, a high body mass index, and a high fasting plasma glucose, were selected for the analysis. This article also predicted the burden of dementia in Chinese women in the next 25 years. Results: The prevalence of dementia, mortality, and disability-adjusted life year rates increased with age in CFWD in 2019. All three risk factors provided by the Global Burden of Disease Study 2019 showed positive correlations for the effect of disability-adjusted life years (DALYs) rates on CFWD. Among them, a high body mass index had the greatest effect (8%) and smoking had the smallest effect (6.4%). Over the next 25 years, the number of CFWD and its prevalence are expected to be on the rise, while mortality is expected to remain relatively stable and decline slightly, but deaths from dementia will continue to increase. Conclusions: The situation arising due to the spread of dementia among Chinese women in the future is going to become a serious issue. To reduce the burden of dementia, the Chinese government should prioritize its prevention and treatment. A multi-dimensional, long-term care system involving families, community, and hospitals should also be established and supported.

Effects of rapid stretching on explosive power of the lower extremity in long jump athletes / Efeitos do alongamento rápido no poder explosivo da extremidade inferior dos atletas em salto em distância / Efectos de los estiramientos rápidos en la potencia explosiva de las extremidades inferiores de los atletas en salto de longitud

ABSTRACT Introduction: The long jump is characterized by a high degree of combination of speed and strength. It belongs to the group of fast power items dominated by physical conditioning. To achieve good results in long jump, it is necessary to have good physical conditioning. Objective: In order to explore the effect of compound fast stretch training on the explosive power of lower limbs of athletes in long jump. Methods: Athletes from a certain city were selected as the research objects of the experiment, with a total of 100 people, and were divided into groups by random drawing, there were 50 people in the control group and 50 people in the experimental group, who received rapid stretching compound training. Results: After collecting the independent samples, statistical analysis was performed with T-test, the results showed confidence of P=0.09, higher than 0.05, indicating that there is no significant difference in the special performance of long jump between the two groups of students, the mean score of students in the experimental group was 0.13 meters higher than the control group. Conclusions: Rapid training composed of relaxation and contraction can effectively improve the special quality in long jump students. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O salto em distância é caracterizado por um alto grau de combinação de velocidade e força. Pertence ao grupo de itens de energia rápida dominados pelo condicionamento físico. Para alcançar bons resultados no salto à distância, é necessário ter bom condicionamento físico. Objetivo: A fim de explorar o efeito do treinamento composto de alongamento rápido sobre o poder explosivo dos membros inferiores dos atletas em salto à distância. Métodos: Atletas de uma determinada cidade foram selecionados como objetos de pesquisa do experimento, com um total de 100 pessoas, e foram divididos em grupos por sorteio aleatório, havia 50 pessoas no grupo controle e 50 pessoas no grupo experimental, que receberam treinamento composto de alongamento rápido. Resultados: Após a coleta das amostras independentes, efetuou-se análise estatística com Teste-T, os resultados mostraram confiança de P=0,09, superior a 0,05, indicando que não há diferença significativa no desempenho especial do salto em distância entre os dois grupos de alunos, a pontuação média dos alunos no grupo experimental foi 0,13 metros maiores que a do grupo controle. Conclusões: O rápido treinamento composto de relaxamento e contração pode melhorar efetivamente a qualidade especial nos alunos de salto em distância. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El salto de longitud se caracteriza por un alto grado de combinación de velocidad y fuerza. Pertenece al grupo de ítems de potencia rápida dominados por el acondicionamiento físico. Para conseguir buenos resultados en salto de longitud, es necesario tener una buena condición física. Objetivo: Explorar el efecto del entrenamiento de estiramiento rápido compuesto sobre la potencia explosiva de los miembros inferiores de los atletas en salto de longitud. Métodos: Se seleccionaron atletas de una determinada ciudad como objetos de investigación del experimento, con un total de 100 personas, y se dividieron en grupos por sorteo, había 50 personas en el grupo de control y 50 personas en el grupo experimental, que recibieron un entrenamiento de estiramiento rápido compuesto. Resultados: Después de recoger las muestras independientes, se realizó el análisis estadístico con la prueba T, los resultados mostraron una confianza de P=0,09, superior a 0,05, lo que indica que no hay diferencias significativas en el rendimiento especial de salto de longitud entre los dos grupos de alumnos, la puntuación media de los alumnos del grupo experimental fue 0,13 metros superior a la del grupo de control. Conclusiones: El entrenamiento rápido compuesto de relajación y contracción puede mejorar eficazmente la calidad especial en los alumnos de salto de longitud. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Virus transmission risk of college students in railway station during Post-COVID-19 era: Combining the social force model and the virus transmission model.

In the post-epidemic era, people's lives are gradually returning to normal, and travel is gradually resuming. The safe evacuation of cross-regional travelers in railway station has also attracted more and more attention, especially the evacuation behavior of college students in railway station. In this paper, considering the pedestrian dynamics mechanism in the emergency evacuation process during the COVID-19 normalized epidemic prevention and control, an Agent-based social force model was established to simulate the activities of college students in railway station. Combined with the virus infection transmission model, Monte Carlo simulation was used to calculate the total exposure time and the number of high-risk exposed people in the railway station evacuation process. In addition, sensitivity analysis was conducted on the total exposure time and the number of high-risk exposed people under 180 combinations of the number of initial infections, social distance, and the proportion of people wearing masks incorrectly. The results show that with the increase of social distances, the total exposure time and the number of high-risk exposures do not always decrease, but increase in some cases. The presence or absence of obstacles in the evacuation scene has no significant difference in the effects on total exposure time and the number of high-risk exposures. During the evacuation behavior of college students in railway station, choosing the appropriate number of lines can effectively reduce the total exposure time and the number of high-risk exposures. Finally, some policy suggestions are proposed to reduce the risk of virus transmission in the railway station evacuation process, such as choosing dynamic and reasonable social distance and the number of queues, and reducing obstacles.

Thyroid Disturbance in Patients with Chronic Hepatitis C Infection: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: The involvement of thyroid autoimmunity and dysfunction in patients with chronic hepatitis C virus (HCV) infection before interferon-α (IFN-α) therapy remains controversial. We performed this meta-analysis to evaluate the association of HCV infection with the presence of anti-thyroid antibodies and dysthyroidism. METHODS: A literature search was carried out to collect articles dated up to August 2015 to identify observational studies which compared the prevalence of anti-thyroid antibodies and thyroid dysfunction in IFN-α naïve chronic HCV-infected subjects with non-HCV infected controls. Random-effect or fixed-effect meta-analyses were applied and results reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Twelve studies were included, involving 1,735 HCV-infected and 1,868 non-HCV infected subjects. Pooled anti-thyroid antibody prevalence tended to be higher in HCV-infected subjects. The prevalence of anti-thyroglobulin antibody (TGAb), anti-thyroid peroxidase antibody (TPOAb), anti-thyroid microsomal antibody (ATMA) were 2.40-fold, 1.96-fold and 1.86-fold higher in HCV-infected subjects than in controls, respectively. The prevalence of hypothyroidism also differed by HCV infection status, with a pooled risk of 3.10 (95%CI: 2.19-4.40) in HCV-infected subjects. However, the results did not show a significant difference in the prevalence of hyperthyroidism between the two groups. CONCLUSION: Chronic HCV infection may be an independent risk factor for thyroid disturbance. It is advisable for the clinicians to monitor both thyroid antibodies and function in the course of chronic HCV infection, independent of IFN-α treatment.

Effect of temperature and pH on postmortem color development of porcine M. longissimus dorsi and M. semimembranosus.

BACKGROUND: Purchasing pork that is boned within 1 h postmortem and not aged is customary in China, and final pork color would not be fully realized. The relationship between early postmortem, pre-rigor meat color and 24 h postmortem, post-rigor pork color was investigated and related to the rate of pH and temperature decline within the longissimus dorsi (LD) and the semimembranosus (SM) muscles of pork carcasses. Muscle color, pH and temperature were measured at 45 min and at 3, 9, 15 and 24 h postmortem in carcasses of F2 White Duroc and Chinese Erhualian pigs. RESULTS: Pork color at 45 min postmortem was not indicative of that at 24 h postmortem in LD and SM, although muscle pH values and temperature at 45 min postmortem were significantly correlated with the LD and SM ultimate color. High muscle pH was associated with decreased L*, whereas high muscle temperature increased L*. Muscle pH and temperature had little effect on a* and b* in LD and color evolution in SM. CONCLUSIONS: Results indicated that meat color inspected shortly after slaughter does not reflect post-rigor meat quality.