What does cell therapy manufacturing cost? A framework and methodology to facilitate academic and other small-scale cell therapy manufacturing costings.

BACKGROUND AIMS: Recent technical and clinical advances with cell-based therapies (CBTs) hold great promise in the treatment of patients with rare diseases and those with high unmet medical need. Currently the majority of CBTs are developed and manufactured in specialized academic facilities. Due to small scale, unique characteristics and specific supply chain, CBT manufacturing is considered costly compared to more conventional medicinal products. As a result, biomedical researchers and clinicians are increasingly faced with cost considerations in CBT development. The objective of this research was to develop a costing framework and methodology for academic and other small-scale facilities that manufacture cell-based therapies. METHODS: We conducted an international multi-center costing study in four facilities in Europe using eight CBTs as case studies. This study includes costs from cell or tissue procurement to release of final product for clinical use. First, via interviews with research scientists, clinicians, biomedical scientists, pharmacists and technicians, we designed a high-level costing framework. Next, we developed a more detailed uniform methodology to allocate cost items. Costs were divided into steps (tissue procurement, manufacturing and fill-finish). The steps were each subdivided into cost categories (materials, equipment, personnel and facility), and each category was broken down into facility running (fixed) costs and operational (variable) costs. The methodology was tested via the case studies and validated in developer interviews. Costs are expressed in 2018 euros (€). RESULTS: The framework and methodology were applicable across facilities and proved sensitive to differences in product and facility characteristics. Case study cost estimates ranged between €23 033 and €190 799 Euros per batch, with batch yield varying between 1 and 88 doses. The cost estimations revealed hidden costs to developers and provided insights into cost drivers to help design manufacturing best practices. CONCLUSIONS: This framework and methodology provide step-by-step guidance to estimate manufacturing costs specifically for cell-based therapies manufactured in academic and other small-scale enterprises. The framework and methodology can be used to inform and plan cost-conscious strategies for CBTs.

Web-Based Dashboard for the Interactive Visualization and Analysis of National Risk-Standardized Mortality Rates of Sepsis in the US.

Sepsis mortality is heavily influenced by the quality of care in hospitals. Comparing risk-standardized mortality rate (RSMR) of sepsis patients in different states in the United States has potentially important clinical and policy implications. In the current study, we aimed to compare national sepsis RSMR using an interactive web-based dashboard. We analyzed sepsis mortality using the National Inpatient Sample Database of the US. The RSMR was calculated by the hierarchical logistic regression model. We wrote the interactive web-based dashboard using the Shiny framework, an R package that integrates R-based statistics computation and graphics generation. Visual summarizations (e.g., heat map, and time series chart), and interactive tools (e.g., year selection, automatic year play, map zoom, copy or print data, ranking data by name or value, and data search) were implemented to enhance user experience. The web-based dashboard (https://sepsismap.shinyapps.io/index2/) is cross-platform and publicly available to anyone with interest in sepsis outcomes, health inequality, and administration of state/federal healthcare. After extrapolation to the national level, approximately 35 million hospitalizations were analyzed for sepsis mortality each year. Eight years of sepsis mortality data were summarized into four easy to understand dimensions: Sepsis Identification Criteria; Sepsis Mortality Predictors; RSMR Map; RSMR Trend. Substantial variation in RSMR was observed for different states in the US. This web-based dashboard allows anyone to visualize the substantial variation in RSMR across the whole US. Our work has the potential to support healthcare transparency, information diffusion, health decision-making, and the formulation of new public policies.

Traditional Chinese medicine therapy reduces the risk of total knee replacement in patients with knee osteoarthritis.

Knee osteoarthritis is a degenerative disease occurring in elderly people worldwide. For severe knee osteoarthritis, total knee replacement is the final treatment option. Traditional Chinese medicine (TCM) is popular in Taiwan and has been shown to exert therapeutic effects on knee osteoarthritis. We investigated the long-term clinical effects of TCM for reducing the need for total knee replacement risk in patients with knee osteoarthritis.We used the National Health Insurance Research Database to conduct a retrospective study of patients with knee osteoarthritis between 1997 and 2003 in Taiwan. Data from the date of diagnosis of knee osteoarthritis to total knee replacement were assessed using the Cox regression proportional hazards model, and the Kaplan-Meier survival curve was used to determine the association between total knee replacement risk and TCM use.A total of 34,231 patients with knee osteoarthritis, who were diagnosed by orthopedic or rehabilitation physicians between 1997 and 2003 were included. Patients were categorized into 2 groups: 26,257 (76.7%) were TCM users and 7974 (23.3%) were TCM non-users. The mean follow-up period was 9.26 years. Multivariate regression demonstrated that using TCM may decrease the need for total knee replacement in patients with knee osteoarthritis (adjusted hazards ratio [aHR] = 0.69, 95% confidence interval [95% CI]: 0.64-0.77) compared with TCM non-users. A relationship between longer TCM use and reduced total knee replacement use was observed, especially in patients who used TCM for ≥120 days (aHR = 0.49, 95% CI: 0.42-0.56).The results of this study suggested that TCM is associated with a reduced risk of total knee replacement in patients with knee osteoarthritis, with enhanced benefits from longer durations of TCM use.