Bayesian network analysis of risk classification strategies in the regulation of cellular products.

Cell therapy, a burgeoning therapeutic strategy, necessitates a scientific regulatory framework but faces challenges in risk-based regulation due to the lack of a global consensus on risk classification. This study applies Bayesian network analysis to compare and evaluate the risk classification strategies for cellular products proposed by the Food and Drug Administration (FDA), Ministry of Health, Labour and Welfare (MHLW), and World Health Organization (WHO), using real-world data to validate the models. The appropriateness of key risk factors is assessed within the three regulatory frameworks, along with their implications for clinical safety. The results indicate several directions for refining risk classification approaches. Additionally, a substudy focuses on a specific type of cell and gene therapy (CGT), chimeric antigen receptor (CAR) T cell therapy. It underscores the importance of considering CAR targets, tumor types, and costimulatory domains when assessing the safety risks of CAR T cell products. Overall, there is currently a lack of a regulatory framework based on real-world data for cellular products and a lack of risk-based classification review methods. This study aims to improve the regulatory system for cellular products, emphasizing risk-based classification. Furthermore, the study advocates for leveraging machine learning in regulatory science to enhance the assessment of cellular product safety, illustrating the role of Bayesian networks in aiding regulatory decision-making for the risk classification of cellular products.

Real-world treatment patterns and outcomes for patients with advanced hepatocellular carcinoma initially treated with PD-1 inhibitors.

BACKGROUND: Programmed cell death protein-1 (PD-1) inhibitors have shown promising clinical efficacy in treating advanced hepatocellular carcinoma (HCC). However, little evidence exists regarding their treatment patterns and outcomes in real-world practice in China. This study aimed to investigate real-world treatment patterns and outcomes of PD-1 inhibitors as first-line therapies for patients with advanced HCC in China. METHODS: The study population included adult patients with advanced HCC who were initially treated with PD-1 inhibitors from April 2020 to November 2022 in China. Descriptive statistics were used to report first-line treatment patterns and associations between patient characteristics and the most frequently used treatment patterns. The effectiveness of first-line treatment with PD-1 inhibitors was also evaluated according to survival and tumor response. RESULTS: The analyses enrolled 480 patients. The four most frequently used first-line treatment patterns of camrelizumab, tislelizumab, camrelizumab + TACE, and tislelizumab + TACE showed statistical differences in patient characteristics of gender, HBV infection, liver cirrhosis, BCLC stage, and portal vein tumor thrombus (all P < 0.05). However, there was no significant difference in median progression-free survival among the first-line treatments of tislelizumab, camrelizumab, and tislelizumab + TACE (not reached vs. 4.4 months vs. 3.6 months, P = 0.5178). The three groups had similar objective response rates (25.0 % vs. 28.6 % vs. 28.6 %, P = 0.927), and disease control rates (73.1 % vs. 78.6 % vs. 64.3 %, P = 0.573) with no statistical significance. CONCLUSIONS: Our findings provided insights into potential therapeutic strategies of PD-1 inhibitors in first-line settings for advanced HCC in real-world practice in China. It was recommended to consider patient characteristics associated with therapeutic options when making clinical decisions. Prospective randomized controlled studies with larger sample sizes and longer follow-up times were warranted further to verify the potential clinical benefits of PD-1 inhibitors.

Digital Medical Information Services Delivered by Pharmaceutical Companies via WeChat: Qualitative Analytical Study.

BACKGROUND: Social media has become one of the primary information sources for medical professionals and patients. Pharmaceutical companies are committed to using various social media platforms to provide stakeholders with digital medical information services (DMISs), which remain experimental and immature. In China, WeChat tops the list of popular social media platforms. To date, little is known about the service model of DMISs delivered by pharmaceutical companies via WeChat. OBJECTIVE: This study aims to explore the emerging service model of DMISs delivered by pharmaceutical companies via WeChat in China. METHODS: This study applied a qualitative research design combining case study and documentary analysis to explore the DMISs of 6 leading pharmaceutical companies in China. Materials were collected from their official WeChat platforms. Thematic analysis was conducted on the data. RESULTS: The DMISs of 6 pharmaceutical companies were investigated. Themes emerged regarding 2 essential information services delivered by pharmaceutical companies via WeChat: business operation services and DMISs (ie, public information services, professional services, science and education services, and e-commerce services). Business operation services mainly function to assist or facilitate the company's operations and development trends for general visitors. Public-oriented information services are realized through health science popularization, academic frontiers, product information, and road maps to hospitals and pharmacies. Internet hospital and pharmacy services are the main patient-oriented professional services. Medical staff-oriented science and education services commonly include continuing education, clinical assistance, academic research, and journal searching. Public-oriented e-commerce services include health products and health insurance. CONCLUSIONS: Pharmaceutical companies in China use WeChat to provide stakeholders with diversified DMISs, which remain in the exploratory stage. The service model of DMISs requires more distinct innovations to provide personalized digital health and patient-centric services. Moreover, specific regulations on the DMISs of pharmaceutical companies need to be established to guard public health interests.

Pharmacoeconomic evaluation of anti-obesity drugs for chronic weight management: a systematic review of literature.

Introduction: Pharmacological therapy is recommended as a second-line alternative to reverse obesity. Currently, five anti-obesity drugs (AODs) have been approved by the U.S. Food and Drug Administration (FDA) for chronic weight management. The aim of this paper is to investigate the pharmacoeconomic evaluation of AODs through a systematic review with a special focus on methodological considerations. Methods: We searched the general and specific databases to identify the primary pharmacoeconomic evaluation of AODs. Results: A total of 18 full-text articles and three conference abstracts were included in this review. Most of the economic assessments were still about Orlistat. And the observations we could make were consistent with the previous systematic review. A few studies were on the combined therapies (i.e. PHEN/TPM ER and NB ER) compared to different comparators, which could hardly lead to a generalized summary of the cost-effectiveness. Most recently, pharmacoeconomic evidence on the newest GLP 1 RA approved for the indication of obesity or obesity with at least one comorbidity emerged gradually. Modelling-based cost-utility analysis is the major type of assessment method. In the modelling studies, a manageable number of the key health states and the state transitions were structured to capture the disease progression. In particular, the principal structure of the decision model adopted in the three studies on the newly approved drug was nearly the same, which enables more in-depth comparisons and generalizations of the findings. Conclusion: This study provided an up-to-date overview of the strengths and areas for improvement in the methodological design of the pharmacoeconomic evaluation of the licensed drugs for chronic weight management. Future modelling evaluations would benefit from a better understanding of the long-term weight loss effects of the current therapeutic options and the weight rebound process after the discontinuation of treatment. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022302648, identifier CRD42022302648.

Comparative analysis of disease modelling for health economic evaluations of systemic therapies in advanced hepatocellular carcinoma.

BACKGROUND: The objective of this study was to systematically analyse methodological and structural assumptions utilised in model-based health economic evaluations of systemic advanced hepatocellular carcinoma (HCC) therapies, discuss the existing challenges, and develop methodological recommendations for future models in advanced HCC. METHODS: We performed literature searches using five databases (Embase, PubMed, Web of Science, Econlit, and CNKI) up to December 4, 2022. Technology appraisals from Canada, England, Australia, and the United States were also considered. Model-based full economic evaluations of systemic advanced HCC therapies in English or Chinese met the eligibility criteria. The reporting quality was assessed by using the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. RESULTS: Of 12,863 records retrieved, 55 were eligible for inclusion. Markov model (n = 29, 53%) and partitioned survival model (n = 27, 49%) were the most commonly used modelling techniques. Most studies were based on health-state-driven structure (n = 51, 93%), followed by treatment-line-driven structure (n = 2, 4%) and combination structure (n = 1, 2%). Only three studies (5%) adopted external real-world data to extrapolate the overall survival or calibrate the extrapolation. Few studies reported the assumptions of transition probabilities. Utility modelling approaches were state-based (n = 51, 93%) and time-to-death (n = 1, 2%). Only 13 studies (24%) reported five types of model validation. Economic evaluation results of specific treatment strategies varied among studies. CONCLUSIONS: Disease modelling for health economic evaluations of systemic therapies in advanced HCC has adopted various modelling approaches and assumptions, leading to marked uncertainties in results. By proposing methodological recommendations, we suggest that future model-based studies for health economic evaluation of HCC therapies should follow good modelling practice guidelines and improve modelling methods to generate reliable health and economic evidence.

Defining and supporting a professional role for pharmacists associated with traditional and complementary medicines: a cross-country survey of pharmacists.

Introduction: An estimated 80% of the world's population use traditional and complementary medicine (T&CM) products as part of their healthcare, with many accessed through pharmacy. This cross-cultural study posed a set of professional practice responsibilities and actions to pharmacists related to T&CM products, with a view toward developing consensus, safeguarding, and promoting the health of the public. Methods: Data were collected from 2,810 pharmacists across nine countries during 2022 via a cross-sectional online survey reported in accordance with the guidelines of STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) and the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Results: Of the 2,810 participants from nine countries, 2,341 completed all sections of the survey. Of these, most agreed (69%) that T&CM product use was common in the community they served, but most did not have adequate training to support consumer needs. Over 75% acknowledged that there were known and unknown safety risks associated with T&CM use. Of 18 professional responsibilities posed, 92% agreed that pharmacists should be able to inform consumers about potential risks, including T&CM side effects and drug-herb interactions. The provision of accurate scientific information on the effectiveness of T&CM products, skills to guide consumers in making informed decisions, and communication with other healthcare professionals to support appropriate and safe T&CM product use were all ranked with high levels of agreement. In order to effectively fulfill these responsibilities, pharmacists agreed that regulatory reforms, development of T&CM education and training, and access to quality products supported by high-quality evidence were needed. Conclusion: General agreement from across nine countries on eighteen professional responsibilities and several stakeholder actions serve as a foundation for the discussion and development of international T&CM guidelines for pharmacists.

Economic Burden and Quality of Life of Hepatocellular Carcinoma in Greater China: A Systematic Review.

Background: Hepatocellular carcinoma (HCC) accounts for more than 85%-90% of primary liver cancer globally, and approximately 45% of deaths from HCC occur in greater China. This disease poses a significant economic burden for patients, payers and society and significantly affects patients' quality of life (QoL). However, such impact of HCC in greater China has not been well characterized. This review was conducted to analyze the current evidence about the economic and humanistic impact of HCC in greater China for informing national disease management and identifying clinical gaps yet to be resolved. Methods: A systematic search literature using seven databases (Web of Science, PubMed, Medline, Cochrane Central, China National Knowledge Infrastructure, Wanfang, and Weipu) was performed to identify interventional and observational studies that reported the impact of HCC on cost or QoL and published before April 6, 2021. The focus population included adult patients with HCC in greater China. This review excluded any studies that focused on any specific treatment. Study quality was assessed using the Effective Public Health Practice Project tool. Results: Of 39,930 studies retrieved, 27 were deemed eligible for inclusion. The methodologies, perspectives and data sources used in studies were heterogeneous. In greater China, while few studies reported the health expenditures of HCC patients and investigations about economic burden at national level was lacking, the significant economic impact of HCC on patients and their families had been reported. Health-related costs increased as the disease deteriorated. Additionally, HCC also has a negative impact on the QoL of patients, mostly in terms of physical, cognitive, social functioning and severe symptoms. Conclusions: HCC has brought significant economic and QoL burden to patients in greater China. Both physical and psychological factors predicted QoL in patients with HCC in greater China. Future studies should explore the disease-related economic effects on Chinese patients and their families, the effects of physical and psychological factors on QoL and the relationships of physical and psychological factors in the region.Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?RecordID=278421, PROSPERO: CRD42021278421.

Epidemiology and disease burden of non-alcoholic steatohepatitis in greater China: a systematic review.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a progression of non-alcoholic fatty liver disease. The increasing burden of NASH has become a major concern of public health in greater China. This study aimed to characterize the epidemiology, disease burden, and treatment of NASH in greater China to better inform national disease management and delivery of health services. METHODS: We conducted a systematic review searching four English databases (Web of Science, PubMed, Medline, and Cochrane Central) and three Chinese databases (CNKI, Wanfang, and VIP). We identified articles published from database inception to October 10, 2020 which reported NASH epidemiology, disease burden, and/or intervention in Chinese adults. RESULTS: Of 44,115 articles retrieved, 33 were eligible for inclusion. Overall prevalence of NASH ranged from 2.4 to 6.1% in greater China, with a more substantial burden among males, the aged, and those in Hong Kong and Taiwan. Most NASH patients suffered from several comorbidities, including obesity, diabetes, and cardiovascular conditions. PNPLA3 rs738409 G allele and haptoglobin 2-2 genotype drove the fibrosis progression in NASH. Increasingly prevalent cases of cirrhosis and hepatocellular carcinoma caused a higher NASH-related mortality. Compared with normal population, NASH patients experienced markedly poorer quality of life and heavier costs. CONCLUSION: This is the first comprehensive overview of NASH among Chinese population that revealed an overwhelming impact of social and healthcare burden associated with the condition. Further high-quality studies are needed to improve the understanding and management of NASH in greater China.

Market access of Chinese patent medicine products to healthcare security system in China: implications for international integration of traditional medicine into health systems.

BACKGROUND: China has introduced a series of polices and practice to manage the market access of Chinese patent medicine (CPM) products into its healthcare security system, which is less analyzed and reported in current literature. Therefore, this paper aimed to investigate the mechanisms managing market access of CPM products into healthcare security system in China, expecting to provide implications for international integration of traditional medicine products into health systems. METHOD: This paper used a documentary analysis approach as a qualitative research method. Data were collected from four sources and analyzed in a thematic way. RESULTS: Four mechanisms to manage entry, price adjustment, and exit of innovative brand and generic CPM products are identified, including: (1) price negotiation, mechanism of new entry of innovative brand CPM products into the national reimbursement list; (2) price re-negotiation, mechanism of price adjustment of innovative brand CPM products within the national reimbursement list; (3) mass procurement, mechanism of generic CPM products to healthcare security system; and (4) direct removal, mechanism of removal from the national reimbursement list. CONCLUSIONS: China has established market access framework of CPM products by focusing on price negotiation for innovative brand CPM products and mass procurement for generic CPM products. Further studies of CPM products based real-world data are needed to provide clinical and pharmacoeconomic evidence to support market access of CPM products into healthcare security systems.

Budget Impact Analysis of Diabetes Drugs: A Systematic Literature Review.

Background: Budget impact analysis (BIA) is an economic assessment that estimates the financial consequences of adopting a new intervention. BIA is used to make informed reimbursement decisions, as a supplement to cost-effectiveness analyses (CEAs). Objectives: We systematically reviewed BIA studies associated with anti-diabetic drugs and assessed the extent to which international BIA guidelines were followed in these studies. Methods: We conducted a literature search on PubMed, Web of Science, Econlit, Medline, China National Knowledge Infrastructure (CNKI), Wanfang Data knowledge Service platform from database inception to June 30, 2021. ISPOR good practice guidelines were used as a methodological standard for assessing BIAs. We extracted and compared the study characteristics outlined by the ISPOR BIA Task Force to evaluate the guideline compliance of the included BIA. Results: A total of eighteen studies on the BIA for anti-diabetic drugs were identified. More than half studies were from developed countries. Seventeen studies were based on model and one study was based on real-world data. Overall, analysis considered a payer perspective, reported potential budget impacts over 1-5 years. Assumptions were mainly made about target population size, market share uptake of new interventions, and scope of cost. The data used for analysis varied among studies and was rarely justified. Model validation and sensitivity analysis were lacking in the current BIA studies. Rebate analysis was conducted in a few studies to explore the price discount that was required for new interventions to demonstrate cost equivalence to comparators. Conclusion: Existing studies evaluating budget impact for anti-diabetic drugs vary greatly in methodology, some of which showed low compliance to good practice guidelines. In order for the BIA to be useful for assisting in health plan decision-making, it is important for future studies to optimize compliance to national or ISPOR good practice guidelines on BIA. Model validation and sensitivity analysis should also be improved in future BIA studies. Continued improvement of BIA using real-world data is necessary to ensure high-quality analyses and to provide reliable results.