Enlightenment of Japan expanded access clinical trial system to China’s compassionate drug use system / 中国药房

The system of compassionate drug use in China is in the preliminary exploration stage， and the formal management methods and specific implementation rules have not been promulgated， which needs to be further optimized and perfected. Japan realizes the advanced use of unapproved drugs by expanded access clinical trial system， and makes clear provisions on information acquisition， target patient， informed consent， subject of application， implementation plan， handling of refusal to administer medication， drug expenses， implementation deadline， compensation for accidental damages， post-approval data review after expanded access clinical trials. When the enterprise refuses to give drugs because of the “legitimacy reasons of the system”， the attending physician can also apply to the Ministry of Health， Labor and Welfare， and the Ministry of Health， Labor and Welfare will conduct the licensing evaluation to maximize the drug for patients. This “refusal to administer” reprocessing is a unique regulation in Japan， which ensures the accessibility of drugs to the greatest extent possible. Based on the analysis of the expanded access clinical trial system in Japan， it is found that our country could further build the information platform for compassionate drug use， play the leading role of physicians， protect the interests of enterprises， pay attention to the ethical review， and make drug cost payment problems further clear in order to improve and optimize the system of compassionate drug use.

Insulation of cross-talk between signalingpathways-inspiration for innovative drug design / 中国药理学通报

Cross-talk of intracellular signaling pathways that share common components (hubs) is organized in form of a bow-tie network topology.Signaling cross-talk is functionally pleiotropic for target genes regulation, resulting in functional redundancy, synergism and antagonism, which should be precisely controlled to prevent signaling 'leaking' or 'spillover'.Thus, the biological system has evolved multiple insulating mechanisms to achieve stimulus-specific response that maintains intracellular homeostasis.The insulation mechanism of signaling cross-talk suggests: (1) the functional duality of cross-talk molecules that determine cell fate requires selectively targeting dysregulated cross-talk molecules while protecting the normal ones from off-target or unintended effects, and we propose them as the targetable cross-talk molecules;(2) cross-talk molecules are usually carried on the macromolecular complex as their functional platforms, thus the structural plasticity of conformational changes at the interaction surface of cross-talk molecules asks for intensive work on the relationship study between drug binding and biological activity, which we propose as the accessible cross-talk molecules.Therefore, signaling cross-talk and its insulation mechanism play instructive leading roles in resolving the bottlenecks of current drug R&D and improve the clinical outcome.

Introduction and Profound Consideration on Intellectual Property Rights Protection Standard Terms Relat-ed to Drugs beyond the Regulations of TRIPS / 中国药房

OBJECTIVE:To improve response capacity of China to deal with intellectual property rights protection standard terms (Trips-plus terms) beyond the regulations of Agreement on Trade-related Aspects of Intellectual Property Rights (TRIPS), and to provide reference for improving national intellectual property rights protection policy. METHODS:Trips-plus terms and their common types were introduced to analyze their characteristics and consider about their adverse effects. RESULTS & CONCLU-SIONS:Common TRIPS-plus terms involve data protection,patent interlinkage,patent period extension,limitation of compulsory licensing and parallel importation,etc. These terms pose a significant challenge to developing countries,resulting in delaying entry of generics,increasing drug price,influencing drug accessibility and posing a great threat to public health. China,as the largest de-veloping country mostly relying on generic drugs,should scientifically assess the effects of TRIPS-plus on public health,drug ac-cessibility and pharmaceutical industry in the process of domestic legislation and negotiating a free trade agreement,and make effec-tive use of the TRIPS flexibility to protect the public health.

The Accessibility of Imported Orphan Drugs in China: A Survey Study / 中国药学杂志

OBJECTIVE: To search the orphan drug list from the countries which had initiated orphan drug policies and give reference to improve the orphan drug accessibility in our country. METHODS: We searched the official medicine management websites of the United States, Singapore, Japan, Australia, European Union, Chinese Taiwan and South Korea and extracted information of orphan drugs which had been approved to the market. Then those orphan drugs were investigated whether had been imported and reimbursed in China, through the website of China Food and Drug Administration. Drug classification was according to the "pharmacopoeia of the People's Republic of China" (2010 version). Disease classification was according to the ICD-10.Insurance information was according to the "national basic medical insurance, employment injury insurance and maternity insurance drug catalogue"(2009 version).RESULTS: The United States, Japan and Australia had launched orphan drug list. A total of 1 133 drugs were improved to the market, covering 26 diseases. 329 anticancer drugs, 168 endocrine, nutritional and metabolic disease drugs, 122 hematologic disease drug ranked in the top three, accounted for 29.04%, 14.83% and 10.77% of all drugs respectively. China has imported no more than 30%, with the anticancer drugs, infectious and parasitic diseases drugs, endocrine, nutritional and metabolic disease drugs ranking in the top three. In the imported drugs, 33 were included in the insurance list. CONCLUSION: Orphan drug accessibility is lack in our country. To improve this status, the related department were suggested to develop national drug policies for orphan drugs, evidence-based select the orphan drug list appling to burden of disease, establish priority approach for approval of imported orphan drug and motivate the R&D enthusiasm of local companies.

Effect of Canceling the Maximum Retail Price Limit on the Accessibility of Low-cost Drugs in Our Hospital / 中国药房

OBJECTIVE:To study the effect of canceling the maximum retail price limit on the accessibility of low-cost drugs in our hospital. METHODS:Based on the policies of canceling the maximum retail price,the low-cost drugs in the hospital man-agement system were extracted to adjust the relevant data of price,compare the drug supply changes before and after the price ad-justment and summarize the effect of canceling the maximum retail limit on the accessibility of low-cost drugs in our hospital. RE-SULTS:The price of 19 kinds of low-cost drugs in our hospital were adjusted,which were raised,for 1-4 times,the average daily cost increased to 0.06-2.51 yuan,with an increase proportion of 11%-309%. 16 varieties of order delivery rate increased,with in-crease proportion of 2%-100%,1 variety decreased,with decrease proportion of 32%,2 varieties showed the same distribution rate. CONCLUSIONS:Canceling the maximum retail price limit can promote the accessibility of low-cost drugs in our hospital.

Management strategy for raising the accessibility to orphan drugs in China / 中华医院管理杂志

Objective To probe into the strategies for improving the accessibility to orphan drugs for patients of rare diseases in China. Methods Analysis of typical cases of orphan drug use in recent years in China, interviews of hospital administrators and clinical doctors, and analysis of the present health insurance policies in China for orphan drugs, definition of the concept of drug accessibility, clarification of the factors hindering orphan drug accessibility. Results Four factors are found to hinder orphan drug accessibility in such aspects of science and technology, supply, information transfer and medical assurance in China's medicine and healthcare system. These subjective and objective factors affect drug accessibility of the patients of rare diseases, denying them of drug accessibility, of drug use in time, and of affordability of such drugs. Conclusion To raise the orphan drug accessibility in China, it is necessary to define basic concepts and incentive mechanism of rare diseases and orphan drug, design and raise the response mechanism of the medicine and health system in orphan drug supply, build a three dimensional cooperation model between such parties as the government, enterprise and patient, and reduce patients' economic burdern.

On Accessibility and Patent Protection of Drugs / 中国药房

OBJECTIVE: To seek approach for the protection of domestic pharmaceutical enterprises with immature creativity and to ensure drug accessibility. METHODS: An analysis was performed applying the theory of demand elasticity by comparing the attributes of health right and patent right etc based on TRIPS protocol and the related practice abroad. RESULTS & CONCLUSIONS: For a developing country, China should give top priority to the short-term urgent needs, such as to meet people's medication demands, followed by meeting the long-term demands, such as to encourage independent intellectual property rights. Hence, drug accessibility-related system in drug patent system should be evolved step by step.