Research on Incentive Policies for Chinese Innovative Drug R&D - Taking Innovative Anti-tumor Drugs as an Example

Objective To provide reference for improving Chinese innovative drug research and development incentive policies.Methods Based on investigating the incentive policies for innovative drug research and development in clinical research,evaluation and approval in China,anti-tumor drugs were taken as the research object to discuss relevant policies from the perspective of clinical trials and registration approval based on data statistics and current situation analysis.Results and Conclusion Driven by a series of incentive policies for innovative drug R&D,great achievements have been made on anti-tumor drugs.However,there are problems such as concentration of drug targets,homogenization of clinical trials,and gaps in some drugs with large clinical needs.To improve incentive policies for innovative drug R&D,China should adhere to the orientation of clinical value,focusing on basic research and translational research,improving evaluation and approval capabilities,and establishing a sound ecosystem for innovative drugs.

Research on Reimbursement Management of Innovative Drugs Abroad and Its Enlightenment to China

Objective To analyze the reimbursement policies of innovative drugs in some developed countries,and to provide reference for future reimbursement management in China.Methods Literature research method was used to study the policies related to the reimbursement management of innovative drugs in Germany,France and Japan,and their successful experience was summarized.Results and Conclusion China should establish an open and transparent value evaluation standard to improve the medical insurance reimbursement management of innovative drugs.Besides,the value of innovative drugs should be taken as an important basis for reimbursement decisions,and an independent third-party value evaluation agency must be established.

Identifying and Managing Technical Risks in the Process of Innovative Drugs Development in China

Objective To identify technical risks in the process of innovative drug development,and to provide reference for technical risk management so as to reduce the uncertainties and improve the efficiency of research and development.Methods The initial risk index was investigated by literature research.Then,the Likert scale was used to design a questionnaire,and the experts’opinion was used to analyze the risk factors affecting the different stages of the development of innovative drugs in China.Results and Conclusion Based on the analysis of questionnaire,31 risk indicators of five key stages in the development of innovative drugs from drug discovery to marketing authorization were established.The key risk indicators constructed in this study can provide reference for technology-related risk management in the process of innovative drug development.

Analytic Hierarchy Process for Technological Risks in the Process of Innovative Drug Development in China

Objective To identify the critical risks in the process of innovative drug research and development,and to provide reference for improving the efficiency of innovative drug development and risk control in China.Methods Expert investigation and analytic hierarchy process were used to determine the weights of different risks.Results and Conclusion The research and analysis results showed that the risks at different stages of development had different effects on the success rate of drug development,among which the risk at the drug discovery stage influenced the most.In the drug discovery stage,inappropriate target selection had the greatest impact on the success rate of drug development.The lack of appropriate cell tissue or animal models had the greatest impact on the success rate of drug development from the discovery of a compound to the application for clinical trials.The difference in changes between nonclinical and clinical studies had the greatest impact on the success rate of drug development from early clinical studies to pivotal clinical studies.Incorrect dose selection had the greatest impact on the success rate of drug development from pivotal clinical studies to marketing authorization applications.The biggest impact from the marketing authorization application to the approval stage was inadequate communication with regulators.After investigating the weight of risk factors in the process of innovative drug development based on scientific methods,a new perspective for the risk control of new drug development and improving the research and development efficiency is provided.

An investigation into the occupational protection status of clinical nursing staff exposed to anti-tumor drugs

Objective:To investigate the occupational protection status of clinical nursing staff vocationally exposed to anti-tumor drugs.Methods:A self-designed questionnaire was used to survey 180 clinical nursing staff vocationally exposed to anti-tumor drugs.Results:Recognition of the need for protection and dependent occupational protection behaviors were very poor in clinical nursing staff vocationally exposed to anti-tumor drugs.The management of the occupational protection of clinical nursing staff vocationally exposed to anti-tumor drugs was also seriously underdeveloped.Conclusion:There is deficiency in the understanding and related protection practices of clinical nursing staff vocationally exposed to anti-tumor drugs in our hospital.The protection measures currently employed in medical practice are inadequate in virtually every aspect considered.It is recommended that all clinical nursing staff should receive full occupational protection training in these matters.The training must raise nursing staff's awareness of the need for occupational protection and standardize their occupational protection behaviors to conform to "best practice" models.These "best practice" models should be quickly established and all staff made cognizant of them forthwith.In addition,where occupational protection systems are already in place,they should be improved to come into line with the new "best practice" models instigated.

An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

Antibacterial resistance is a global health threat that requires further concrete action on the part of all countries.In this context,one of the biggest concerns is whether enough new antibacterial drugs are being discovered and developed.Although several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides comprehensive information on original antibacterial drugs at clinical stages in China.In this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since 2019.Information was obtained by consulting official websites,searching commercial databases,retrieving literature,asking personnel from institutions or companies,and other means,and a considerable part of the data covered here has not been included in other reviews.As of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and updated.Among them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in phase-1.Most of the clinical candidates are new analogs or monocomponents of traditional antibacterial pharmacophore types,including two dual-acting hybrid antibiotics and a recombinant antibacterial protein.Overall,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in China.Hopefully,Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.

A living cell-based fluorescent reporter for high-throughput screening of anti-tumor drugs

Suppression of cellular O-linkedβ-N-acetylglucosaminylation(O-Glc NAcylation)can repress proliferation and migration of various cancer cells,which opens a new avenue for cancer therapy.Based on the regulation of insulin gene transcription,we designed a cell-based fluorescent reporter capable of sensing cellular O-Glc NAcylation in HEK293 T cells.The fluorescent reporter mainly consists of a reporter(green fluorescent protein(GFP)),an internal reference(red fluorescent protein),and an operator(neuronal differentiation 1),which serves as a"sweet switch"to control GFP expression in response to cellular OGlc NAcylation changes.The fluorescent reporter can efficiently sense reduced levels of cellular OGlc NAcylation in several cell lines.Using the fluorescent reporter,we screened 120 natural products and obtained one compound,sesamin,which could markedly inhibit protein O-Glc NAcylation in He La and human colorectal carcinoma-116 cells and repress their migration in vitro.Altogether,the present study demonstrated the development of a novel strategy for anti-tumor drug screening,as well as for conducting gene transcription studies.

Study on an innovative natural drug for Alzheimer's disease reported as a sham

The number of patients with dementia is estimated to be as high as 24 million and is predicted to double every 20 years,i.e.,by 2040,leading to a tremendous financial disease burden[1].Therefore,we urgently need to identify drugs that can prevent,delay the onset,slow the progression,or improve the symptoms of Alzheimer's disease(AD).Drug development for AD has proven to be extremely difficult[2].

Research Progress on Dimension and Indicators of Comprehensive Value Assessment of Anti-Tumor Drugs

Objective To sort out the dimension and indicators of comprehensive value assessment of anti-tumor drugs abroad,and provide a reference for constructing a similar system in China.Methods The keywords such as anti-tumor drugs,value,assessment,method,and framework were used to search CNKI,WanFang database,VIP database,Embase,PubMed and Web of Science.Results and Conclusion According to the research on the value framework of anti-tumor drugs,6 first-level dimensions and 8 second-level indicators with common characteristics were summarized.In view of China’s national conditions,this study summarizes the available value judgment dimensions of anti-tumor drugs at home and abroad,so as to learn from international experience and their mature methodologies,and provide ideas for constructing a multi-dimensional value system of anti-tumor drugs in China.

Inspiration of Foreign Innovative Drug Pricing Methods and Medical Insurance Payment Standards to China

Objective To study the innovative drug pricing methods and medical insurance payment standards in foreign countries and to provide reference for China’s government.Methods The official websites were searched for information and related literature,and literature review was used.Results and Conclusion In foreign countries,the clinical value of innovative drugs and their impact on medical insurance funds were comprehensively evaluated based on factors such as quality-adjusted life years,clinical benefit,and improvement of clinical benefit.Then,the evaluation results were taken as an important basis for whether innovative drugs were admitted to the medical insurance catalog and establishing medical insurance payment standards.By using international experience for reference,innovative drug pricing methods and medical insurance payment standards for China’s national conditions can be improved by establishing a basic database of clinical value and drug economic evaluation of innovative drugs,as well as innovative drug payment models based on decision thresholds.

An innovative approach for the treatment of Alzheimer's disease: the role of peroxisome proliferator-activated receptors and their ligands in development of alternative therapeutic interventions

Alzheimer＇s disease is a multifactorial pathology, for which no cure is currently available. Nowadays, researchers are moving towards a new hypothesis of the onset of the illness, linking it to a metabolic impairment, q-his innovative approach will lead to the identification of new targets for the preparation of new effective drugs. Peroxisome proliferator-activated receptors and their ligands are the ideal candidates to reach the necessary breakthrough to defeat this complicate disease.

Overview of Research and Development for Anticancer Drugs

Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.

Strategies for overcoming anti-tumor necrosis factor drug antibodies in inflammatory bowel disease:Case series and review of literature

Anti-tumor necrosis factor(TNF) biologics are currentlyamongst the most widely used and efficacious therapies for inflammatory bowel disease(IBD). The development of therapeutic drug monitoring for infliximab and ada-limumab has allowed for measurement of drug levels and antidrug antibodies. This information can allow for manipulation of drug therapy and prediction of response. It has been shown that therapeutic anti-TNF drug levels are associated with maintenance of remission, and development of antidrug antibodies is predictive of loss of response. Studies suggest that a low level of drug antibodies, however, can at times be overcome by dose escalation of anti-TNF therapy or addition of an immunomodulator. We describe a retrospective case series of twelve IBD patients treated at the University of California-Irvine, who were on infliximab or adalimumab therapy and were found to have detectable but low-level antidrug antibodies. These patients underwent dose escalation of the drug or addition of an immunomodulator, with subsequent follow-up drug levels obtained. Eight of the twelve patients(75%) demonstrated resolution of antidrug antibodies, and were noted to have improvement in disease activity. Though data regarding overcoming low-level anti-TNF drug antibodies remains somewhat limited, cases described in the literature as well as our own experience suggest that this may be a viable strategy for preserving the use of an anti-TNF drug. Low-level anti-TNF drug antibodies may be overcome by dose escalation and/or addition of an immunomodulator, and can allow for clinical improvement in disease status. Therapeutic drug monitoring is an important tool to guide this strategy.

Therapeutic drug monitoring in patients with inflammatory bowel disease

Thiopurine analogs and anti-tumor necrosis factor (TNF) agents have dramatically changed the therapeutics of inflammatory bowel diseases (IBD), improving short and long-term outcomes. Unfortunately some patients do not respond to therapy and others lose response over time. The pharmacokinetic properties of these drugs are complex, with high inter-patient variability. Thiopurine analogs are metabolized through a series of pathways, which vary according to the patients’ pharmacogenetic profile. This profile largely determines the ratios of metabolites, which are in turn associated with likelihoods of clinical efficacy and/or toxicity. Understanding these mechanisms allows for manipulation of drug dose, aiming to reduce the development of toxicity while improving the efficacy of treatment. The efficacy of anti-TNF drugs is influenced by many pharmacodynamic variables. Several factors may alter drug clearance, including the concomitant use of immunomodulators (thiopurine analogs and methotrexate), systemic inflammation, the presence of anti-drug antibodies, and body mass. The treatment of IBD has evolved with the understanding of the pharmacologic profiles of immunomodulating and TNF-inhibiting medications, with good evidence for improvement in patient outcomes observed when measuring metabolic pathway indices. The role of routine measurement of metabolite/drug levels and antibodies warrants further prospective studies as we enter the era of personalized IBD care.

Exploring of drug leads from diversity-oriented Michael-acceptor library derived from natural products

A potential strategy for drug lead identification and in-active natural products re-discovery is elaborated.Starting from fifteen structurally diverse natural products,a focused library featured by Michael acceptors is constructed with IBX mediated oxidation.Biological assay on five tumor cell lines indicates that four Michael acceptors,8a,11a,12a,14a,are with improved cytotoxicity(3-10 folds more potent than the parent compounds),which merit further investigations.Further thiol-sensitive assay of the active hit 8a revealed that it was an irreversible Michael acceptor.The results suggest that the strategy is not only effective and relatively high discovery rate(28%),but also resource saving.

Anti-tumor Effects of Aspirin: Progress in Clinical and Basic Studies

Beyond the antipyretic analgesic and anti-inflammatory effects for which aspirin has historically been used,studies have shown that aspirin also plays an important role in the prevention or treatment a variety of diseases.The anti-tumor effects of aspirin have received increasing attention during the past decade.Many studies have explored the molecular mechanisms underlying these anti-tumor effects in vitro and in vivo,and abundant discoveries have been made through observational or interventional clinical studies.In terms of its molecular function,aspirin has been shown to prevent tumor cell growth through inhibiting the signal transduction of the COX,tumor necrosis factor-related apoptosis-inducing ligand(TRAIL),NFκB/IκB,and Bcl-2/Bax pathways.Under certain conditions,aspirin can also induce autophagy,which is an inhibitory mechanism for some tumors.This article provides a comprehensive overview of the anti-tumor effects of aspirin and discusses the concrete mechanisms underlying aspirin’s anti-tumor effects that have been discovered in the past 30 years.

药物临床试验培训导入临床药学教学的分析与思考

基于国家大健康产业、医药产业创新发展对临床药学和临床试验人才数量和质量的新需求,初步探讨在临床药学人才教学中导入药物临床试验相关理论、实践的必要性和方式。依据院校临床药学培养教学内容和特点,将临床试验相关理论和实践整合到临床药学培养的不同阶段开展教学,在临床药学基础理论教学中导入药物临床试验理论和案例教学,在临床药学毕业实践中进行临床试验实践教学提升能力,在临床药学研究生培养阶段进行临床试验创新培养。一方面提高临床药学专业学生实践能力,扩大临床试验人才培养路径;另一方面提升临床药学学生的创新思维和能力,满足社会大健康产业多元需求。

新上市药品首发价格形成机制与鼓励高质量创新的经济学理论分析

目的:本研究旨在探究新上市药品首发价格形成机制的经济学本质,及其面临的挑战与待解决的问题。方法:从药品价格形成机制的基本原理出发,本文引入了内生与外生价格、非对称信息博弈、创新药品市场竞争以及新制度经济学的相关理论,探索药品首发价格形成机制的经济学理论基础。结论及建议:建立合理的药品首发价格形成机制,是发挥市场在资源配置中起决定性作用的同时更好发挥政府作用的举措。以鼓励高质量创新为目标的药品首发价格形成机制,应当以降低制度性交易成本为核心目标。建议以创新价值、竞争情况等相关信息披露为基础,对新上市药品合理分类,降低信息不对称程度,治理当前新药市场的逆向选择问题。在保证高质量创新药定价权最大化的同时约束同质化创新的垄断定价权,兼顾效率和公平。

关注新生血管性年龄相关性黄斑变性的创新药物治疗

湿性年龄相关性黄斑变性(nAMD)是老年人致盲的主要原因,抗VEGF是其主要治疗方法。目前,nAMD治疗仍面临诸多不足和挑战,开发新的治疗药物和给药方法是其主要研究的方向。近年来治疗nAMD的药物研发方向呈现多样化,包括开发新靶点/新机制药物及新型给药方式、优化给药剂量和基因疗法等,达到降低治疗频率、延长治疗间隔、提高患者治疗依从性和长期维持或改善视力的目的。眼科临床医师应对新的药物有较为全面的了解,进而发掘出适合不同nAMD亚型患者的优化方案,实现向精准化医疗迈进。

中外创新药物医保支付的比较研究

按疾病诊断相关分组(DRG)付费是当前我国医保支付改革的重要研究方向,但在一定程度上限制了创新药物的临床推广使用。许多国家已对创新药物的额外支付进行了深入研究。该文以美国、法国、德国为例,分析总结DRG付费体系下创新药物额外支付的国际经验,并结合我国创新药物医保支付现状及DRG付费对创新药物发展的影响,提出了明确的纳入标准、选择合适支付模式、建立动态调整机制、完善支付方式等政策建议,以期在全面推进DRG付费改革中,为进一步建立和完善我国创新药物医保支付机制提供参考。