scholarly journals Exploration Of Run-Time Requirements In Probabilistic Sensitivity Analysis Utilizing A Patient Level Based Type 2 Diabetes Simulation Model

2017 ◽  
Vol 20 (9) ◽  
pp. A748-A749
Author(s):  
V Foos ◽  
M Lamotte ◽  
A Sathananthan ◽  
E Altrabsheh ◽  
P McEwan
Keyword(s):  
Type 2 Diabetes ◽  
Sensitivity Analysis ◽  
Simulation Model ◽  
Probabilistic Sensitivity Analysis ◽  
Patient Level ◽  
Time Requirements ◽  
Run Time

scholarly journals Exploring the Appropriate Price of Semaglutide for Type 2 Diabetes Patients Based on Cost-Utility Analysis in China

2021 ◽  
Vol 12 ◽  
Author(s):  
Shanshan Hu ◽  
Xiaorong Su ◽  
Xun Deng ◽  
Yong Wang
Keyword(s):  
Type 2 Diabetes ◽  
Sensitivity Analysis ◽  
Scenario Analysis ◽  
Probabilistic Sensitivity Analysis ◽  
Annual Cost ◽  
Cost Utility ◽  
Binary Search ◽  
Cost Utility Analysis ◽  
Utility Analysis

Introduction: Semaglutide is the first and only oral version of a glucagon-like peptide-1 analogue approved by the FDA for the treatment of type 2 diabetes (T2D). This research was designed to explore the appropriate price of once-weekly (OW) semaglutide for T2D patients in China based on cost-utility analysis.Methods: The baseline patient cohorts of OW semaglutide and once-daily (OD) empagliflozin were sourced from a patient-level meta-analysis integrating the SUSTAIN 2, SUSTAIN 3, SUSTAIN 8 and PIONEER 2 trials. The long-term health and economic outcomes were simulated using the United Kingdom Prospective Diabetes Study Outcome Model 2 from the Chinese healthcare provider’s perspective. The appropriate price of semaglutide was explored by binary search. One-way sensitivity analysis (one-way SA), probabilistic sensitivity analysis and scenario analysis were applied to solve the uncertainty.Results: Under the assumption that the annual cost of semaglutide is equal to that of OD empagliflozin, OW semaglutide was superior to OD empagliflozin due to its higher quality adjusted life years and lower total costs. After binary search, the incremental cost-utility ratio of OW semaglutide vs. OD empagliflozin was approximately equal to 3λ with an annual cost of semaglutide of $1,007.18 and approximately equal to λ with an annual cost of semaglutide of $708.11. Subsequently, the incremental cost-utility ratio of OW semaglutide vs. OD empagliflozin was approximately 3λ and λ, with annual costs of semaglutide of $877.43 and $667.04, respectively, adjusted by one-way SA. Ultimately, the cost-utility results with annual costs of semaglutide of $877.43 and $667.04 were robust to probabilistic sensitivity analysis and scenario analysis.Conclusion: In conclusion, the annual cost of semaglutide appears to be appropriate between $667.04 and $877.43 for T2D patients in China.

Estimating cardiovascular disease-free life-years with the addition of semaglutide in people with type 2 diabetes using pooled data from SUSTAIN 6 and PIONEER 6

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Westerink ◽  
K Sommer Matthiessen ◽  
S Nuhoho ◽  
U Fainberg ◽  
M Lyng Wolden ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Funding Source ◽  
Cvd Risk ◽  
Private Company ◽  
Pooled Data ◽  
Patient Level ◽  
Life Years ◽  
Geographical Regions

Abstract Introduction Cardiovascular disease (CVD) is the leading cause of disability and death in people with type 2 diabetes (T2D). In a post hoc analysis of pooled data (POOLED cohort) from two phase 3, randomized CV outcomes trials, SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716), the addition of the glucagon-like peptide-1 analogue semaglutide to standard of care (SoC) in people with T2D at high risk of CVD significantly reduced the risk of major adverse CVD events (3-point MACE: CV death, non-fatal stroke and non-fatal myocardial infarction). Purpose To estimate the effect of adding semaglutide to SoC on CVD-free life-years and 10-year CVD risk in patients with T2D by predicting individual patient-level risk of CVD events in the POOLED cohort using the DIAL CVD risk model. Methods The 3-point MACE hazard ratio from the POOLED cohort (N=6480; HR = 0.76 [95% confidence interval [CI]: 0.62–0.92]) was applied to the patient-level lifetime risk of CVD events derived from the DIAL model. CVD-free life-years and 10-year CVD risk were then calculated based on the age-specific risks of CVD events and non-vascular mortality, using standard actuarial methods. Both new and recurrent CVD events were considered. The DIAL model was validated by comparing the predicted and observed number of CVD events after 1 year. The DIAL model was previously developed using data from people with T2D in the Swedish National Diabetes Registry and validated across geographical regions. Results The DIAL model was considered valid for use in the POOLED cohort because the predicted number of CVD events at 1 year was within 5% of the number observed. Adding semaglutide to SoC was associated with a mean reduction in 10-year CVD risk of 20.0% (95% CI: 6.4–32.6%) and a mean increase of 1.72 (95% CI: 0.52–2.96) CVD-free life-years. The number of mean CVD-free life-years gained ranged from 0.62–2.91 years between age groups (Table). For a 60-year-old male with baseline characteristics matched to the average male from the POOLED cohort, adding semaglutide to SoC reduced 10-year CVD risk by 20.8% and provided 2.53 additional CVD-free life-years. The number of CVD-free life-years decreased when baseline age was increased (Figure). Conclusions The addition of semaglutide to SoC was associated with a gain in CVD-free life-years. This analysis helps contextualize the results of CV outcomes trials and may help to inform clinical decision-making. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novo Nordisk A/S

scholarly journals Causal Association Between mTOR-Dependent eIF4E mRNA Cap-Dependent Translation and Type 2 Diabetes: A Mendelian Randomization Study (OR31-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ghada Soliman ◽  
C Mary Schooling
Keyword(s):  
Type 2 Diabetes ◽  
Sensitivity Analysis ◽  
Confidence Interval ◽  
Mendelian Randomization ◽  
Protein Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
P Value ◽  
Weighted Median

Abstract Objectives Type 2 diabetes is a prevalent chronic disease and is often associated with obesity and other comorbidities. The mammalian Target of Rapamycin complex 1 (mTORC1) nutrient-signaling pathway is a central regulator of cell growth and metabolism and is dysregulated in chronic diseases including diabetes and obesity. The eukaryotic translation initiation factor 4E (eIF-4E), a key regulator of gene translation and protein function, is under the control of mTOR and eIF4E Binding Proteins (4E-BPs). eIF-4E binds to the m7G (7-methylguanosine) cap at the 5’-UTR of most eukaryotic mRNA and mediates the recruitment of mRNA on ribosomes to start the protein translation. Both 4E-BP and ribosomal protein S6K kinase (S6K) are downstream effectors regulated by mTORC1 but converge to regulate two independent pathways. We investigated whether the risk of type 2 diabetes varied with genetically predicted eIF-4E and S6K levels using Mendelian Randomization (MR). Methods We estimated the causal role of eIF-4E and S6K plasma proteins, mTOR downstream targets, on type 2 diabetes, based on 16 single nucleotide polymorphisms (SNPs) for eIF-4E and 16 SNPs for S6K at P-value < 5x10−6. We applied these SNPs per exposure to publically available genetic associations with diabetes from the DIAbestes Genetics Replication And Meta-analysis (DIAGRAM) case (n = 26,676), and control (n = 132,532) study (mean age 57.4 years). We meta-analyzed SNP-specific Wald estimates using inverse variance weighting with multiplicative random effects. Sensitivity analysis was conducted using the weighted median, and MR-Egger estimates. Results eIF-4E cap-dependent translation factor was associated with lowered risk of type 2 diabetes with an odds ratio (OR) 0.94 per effect size, 95% confidence interval (0.88, 0.99, P = 0.03) with similar estimates from the weighted median and MR-Egger. S6K was not associated with diabetes, OR 0.95, 95% confidence interval (0.89, 1.01, P = 0.08). Sensitivity analysis using MR-Egger and weighed median analysis did not indicate pleiotropic effects suggesting a unique protective effect of eIF-4E on type 2 diabetes. Conclusions This unbiased Mendelian Randomization estimate is consistent with a causally protective association of eIF-4E on type 2 diabetes. eIF-4E may be a target for intervention by repurposing existing therapeutics to reduce the risk of type 2 diabetes. Funding Sources No specific funding.

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