Probabilistic hesitant fuzzy sets (PHFSs) are superior to hesitant fuzzy sets (HFSs) in avoiding the problem of preference information loss among decision makers (DMs). Owing to this benefit, PHFSs have been extensively investigated. In probabilistic hesitant fuzzy environments, the correlation coefficients have become a focal point of research. As research progresses, we discovered that there are still a few unresolved issues concerning the correlation coefficients of PHFSs. To overcome the limitations of existing correlation coefficients for PHFSs, we propose new correlation coefficients in this study. In addition, we present a multi-criteria group decision-making (MCGDM) method under unknown weights based on the newly proposed correlation coefficients. In addition, considering the limitations of DMs\' propensity to use language variables for expression in the evaluation process, we propose a method for transforming the evaluation information of the DMs\' linguistic variables into probabilistic hesitant fuzzy information in the newly proposed MCGDM method. To demonstrate the applicability of the proposed correlation coefficients and MCGDM method, we applied them to a comprehensive clinical evaluation of orphan drugs. Finally, the reliability, feasibility and efficacy of the newly proposed correlation coefficients and MCGDM method were validated.

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To evaluate the impacts of the 2017 adjustment of National Reimbursement Drug List (NRDL) on orphan drugs hospital procurement volumes and spending in China.
We used an interrupted time series design covering the period from 2016 to 2018 to analyse changes in hospital procurement volumes and spending of orphan drugs for which were included in the 2017 NRDL.
The study was conducted in China. Orphan drug procurement data of 789 public hospitals (594 tertiary hospitals and 195 secondary hospitals) were derived from the Chinese Medical Economic Information (CMEI).
Monthly orphan drugs hospital procurement volumes and spending.
Nine orphan drugs were included in the 2017 NRDL (seven were directly included, and two were included after price negotiation). Comparing to orphan drugs not included in the NRDL, hospital procurement volumes ([Formula: see text] =43 312, p<0.001) and spending ([Formula: see text] =6 48 927, p<0.001) of the nine included drugs showed significant upward trends after implementation of the 2017 NRDL adjustment.
Our results suggest that the 2017 adjustment of NRDL significantly changed the usage and spending on certain orphan drugs. The increase in orphan drug hospital procurement volumes should improve rare disease patients\' access to these orphan drugs.

The normative regimens recommendations for treating metastatic uveal melanoma (mUM) are absent in the US. Recently, a phase III randomized clinical trial revealed that tebentafusp yielded a conspicuously longer overall survival than the control group. Based on the prominent efficacy, this study aimed to assess whether tebentafusp is cost-effective compared to the control group in patients with untreated mUM. A three-state partitioned survival model was developed to assess the costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) from the perspective of US payers. Scenario analyses and sensitivity analyses were conducted to explore the conclusion uncertainty. Compared with control group, tebentafusp therapy yielded an additional 0.47 QALYs (1.19 vs. 0.72 QALYs) and an incremental cost of $444 280 ($633 822 vs. $189 542). The resultant ICER of $953 230/QALY far outweighed the willingness-to-pay threshold of $200 000/QALY. The ICER was always more than $750 000/QALY in all the univariable and probabilistic sensitivity analyses. Scenario analyses indicated that reducing the unit price of tebentafusp to $33.768/µg was associated with a favorable result of tebentafusp being cost-effective. For treatment-naive patients with mUM, the cost of tebentafusp therapy was not worth the improvement in survival benefits at the current price compared to the investigator\'s choice of therapy. The cost-effectiveness of tebentafusp could be promoted using value-based pricing.

There are more than 7 000 rare diseases and approximately 475 million individuals with rare diseases globally, with children accounting for two-thirds of this population. Due to a relatively small patient population and limited financial resources allocated for drug research and development in pharmaceutical enterprises, there are still no drugs approved for the treatment of several thousands of these rare diseases. At present, there are no drugs for 95% of the patients with rare diseases, and consequently, the therapeutic drugs for rare diseases have been designated as orphan drugs. In order to guide pharmaceutical enterprises to strengthen the research and development of orphan drugs, various nations have enacted the acts for rare disease drugs, promoted and simplified the patent application process for orphan drugs, and provided scientific recommendations and guidance for the research and development of orphan drugs. Since there is a relatively high incidence rate of rare diseases in children, this article reviews the latest research on pharmacotherapy for children with rare diseases.
罕见病有7 000余种，全球罕见病患者总数约4.75亿，其中儿童占2/3。因每种罕见病的患病人群基数小，制药企业研发资金有限，仍有几千种罕见病还没有获得批准的治疗药物。目前，95%的罕见病患者尚无药可治，因此能够治疗罕见病的药物被称为孤儿药。为引导制药公司加大孤儿药开发力度，多国制定了罕见病药物法案，推进简化孤儿药专利申请程序，积极为孤儿药研发提供科学建议和指导。儿童是罕见病的高发群体，该文将围绕儿童罕见病药物治疗新进展进行综述。.

Rare diseases are a global public health issue with a more pressing situation in China. Unfortunately, the relevant research and development in this country are still in its infancy, leading to limited drug accessibility. In view of this, the Chinese government has taken a series of countermeasures to promote orphan drug R&D in recent years, which has presented encouraging results. This paper aims to review incentive policies and funding initiatives formulated by the Chinese government and examine their implications on orphan drug R&D.
Policies targeting orphan drug R&D during 2012-2022 were retrieved from the relevant official websites, categorized into different themes and analyzed for the contents. Data on government funding, drug approval, clinical trial approval and orphan drug designation were collected through internet search to analyze the implications of those incentive policies and initiatives on orphan drug R&D in China.
A total of 20 relevant policy documents were identified and five major themes were revealed through content analysis, including national strategy, expedited approval, safety and efficacy requirements, data protection and technical support. The government input in orphan drug R&D has witnessed a steady annual increase. Driven by those incentives, the numbers of orphan drugs approved for marketing and drug candidates entering clinical studies are increasing year by year, and more domestic pharmaceutical companies are actively involved in the R&D of orphan drugs.
Orphan drug development in China is growing rapidly under the stimulation of incentive regulatory policies and more investment in researches. China is working toward a more standardized and comprehensive rare disease ecosystem. However, there are still some challenges, such as the lack of sufficient financial support and the call for systematic legislation on rare diseases, to be addressed for future success.

BACKGROUND: After the inclusion of more high-cost orphan drugs in China\'s National Reimbursement Drugs List, this study investigated issues relating to patient access to the 7 medicines for 4 rare diseases after listing.
METHODS: This study collected data from a national survey conducted in China. Three aspects associated with the accessibility of medicines, namely, approachability, availability, and affordability, were analyzed using descriptive statistics. In addition, multilevel logistic regression models were used to investigate the associations between patient characteristics and the accessibility of surveyed orphan drugs.
RESULTS: Of the 999 completed responses included in the study, 15% of the patients (n = 150) did not use the medicines because of non-medicine-related issues. Among the 849 patients using the surveyed medications, 64.4% (n = 547) encountered the problem of unavailability, whereas 51.2% (n = 435) reported affordability as an issue, and 49.6% (n = 320) had health expenditure beyond the catastrophic threshold. The data also indicated that Commercial Medical Insurance helped patients to relieve the cost burden on orphan drugs, but the payout of Commercial Medical Insurance failed to influence patients\' decisions to continue the treatments.
CONCLUSIONS: Accessibility of orphan drugs has improved in China after their inclusion in the National Reimbursement Drugs List. Nevertheless, the availability and affordability of medicines remained the barriers for patients to access the desired treatments. It is recommended that further policy refinement in conjunction with the collaboration among healthcare stakeholders is required to deliver better care for patients with rare disease.

To explore whether a societal preference for orphan drugs exists in Chinese general public and to quantitatively measure the personal trade-off between essential attributes of orphan drugs through a discrete choice experiment.
A labeled discrete choice experiment was employed to measure public preference. Six attributes (impact of diseases on life-years, impact of diseases on quality of life, availability of alternative drug treatments, annual cost per patient paid by medical insurance, expected increases in life-expectancy, and improvements to the quality of life) were identified through a literature review, experts\' suggestions, and stakeholders\' semi-structured interviews, then refined through a pre-survey. The current study used a D-efficient design to yield 27 choice sets divided into three blocks with nine questions containing the labeled treatment (either orphan drugs or common drugs). Information on sociodemographic characteristics and individual preferences was collected through a web-based questionnaire using convenience sampling. A mixed logit model was used to test societal preferences for orphan drugs over common drugs, while a binary logit model was used to measure the relative importance of each attribute in orphan drug access for the National Reimbursement Drug List and its willingness to pay.
A total of 323 persons participated in this study. Respondents largely had indifferent attitudes toward orphan drugs and common drugs. The binary logit model results showed that 5 of the 6 attributes were significant, except for the availability of alternative drug treatments. The most impacted factor was the annual cost per patient paid by medical insurance (β = -1.734, odds ratio [OR] = 0.177). Among non-economic attributes, the impact of diseases on life-years-with no treatment, the patient will die in the prime of life (β = 0.523, OR = 1.688, willingness to pay = 301,895)-was most concerning, followed by significant improvements to the quality of life (β = 0.516, OR = 1.676, willingness to pay = 297,773).
The general public in China does not value rarity as a sufficient reason to justify special consideration in funding orphan drugs. When making orphan drug coverage decisions, the public prioritized the annual cost, disease severity, and drug effects.

There are about 7000 rare diseases worldwide, of which only 5% of the diseases can be treated with medicines, showing that it\'s important to improve patient access to orphan drugs. Recently, China has actively worked to set up a national system for rare diseases to improve the diagnosis and treatment capabilities and ensure the accessibility of drugs. However, the benefits of the system have yet not to be measured. This study aimed to provide an overview of orphan drug access based on the Compendium of China\'s First List of Rare Diseases and National Network to Collaborate on Diagnosis and Treatment of Rare Diseases, expecting to map a blueprint for orphan drug access in China.
Framework of China\'s national system for rare diseases was summarized. We surveyed the availability and affordability of 79 approved orphan drugs based on the Compendium of China\'s First List of Rare Diseases in 30 leading provincial institutions from 2017 to 2020. The availability was measured annually at 3 levels (market, hospital and drug), and affordability was reflected by comparing costs of daily defined dose with per capita income of urban and rural residents, with the National Basic Medical Insurance considered.
The market availability of orphan drugs in China showed an upward trend. As of 2020, the median hospital-level availability was 41.1% (increased by 1.5 times), highly available drugs increased by 16.5%. There were 64/74 orphan drugs that were affordable to rural/urban residents with the National Basic Medical Insurance considered (an increase of 14.1%), and the urban-rural gap of affordability ratio was narrowed (down by 6.0%). Comprehensive analysis showed the proportions of drugs with better availability and affordability in urban and rural areas by 2020 were 39.4% and 32.3%, respectively, which had increased but were still at a low level.
China\'s national system for rare diseases has made great progress in orphan drug access, indicating that it\'s been functioning under the joint reformation of medical treatment, medical insurance and medicines supply. The list of rare diseases will be updated and collaboration in networks will be enhanced to further improve the system.

Rare diseases have been increasingly recognized as unmet medical and health needs worldwide; a growing demand for the development of orphan drugs emerges subsequently. Therefore, it is of great interest for both the Chinese regulatory agency and pharmaceutical companies to keep tract on the clinical development of orphan drugs in China.
This study aims to reveal the current situation and trend of the clinical development of orphan drugs in China, based on the data collected from the Chinese official platform, dating from January 1, 2013 to December 31, 2021.
A total of 331 clinical trials for orphan drugs were extracted from the platform, covering 31 rare diseases and 124 drugs. Increases were seen in the annual number of clinical trials and drugs being tested, with a sharp increase after 2018. About the disease types of the 331 trials, Parkinson disease (young-onset, early-onset) (86, 26%), hemophilia (70, 21%), homozygote hypercholesterolemia (60, 18%) were the most common. Furthermore, it was also observed that the largest number of clinical trial units for rare disease in east China (90, 41%) and the smallest number located in northwest China (18, 6%) and northeast China (18, 6%).
The growth trends illustrate the progress in clinical trial and drug development of rare diseases from 2013 to 2021. However, promoting orphan drugs development still is an important issue in China; at the same time, further efforts should be made for meet the unmet needs of disease types and balance the uneven distribution of medical resources for clinical trial on rare diseases.