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Objective: Our objective was to describe the administration of glucocorticoids (GCs) and characterize its association with organ damage in a longitudinal systemic lupus erythematosus (SLE) cohort over a time period spanning the introduction of biologics in Canada. Methods: A retrospective observational study was conducted using data from a large SLE cohort in Canada, including adults without lupus nephritis or central nervous system lupus. Patients were observed from time of entry into the cohort to the last available clinic visit (up to December 31, 2020), with a minimum of 24 months of follow‐up. Demographic and clinical characteristics, including average disease activity, treatment administration, and prevalence of organ damage, were examined. Organ damage was stratified by GC administration. Results: A total of 1,255 patients were included. The mean follow‐up duration was 10.5 (SD 8.6) years. One hundred eighty‐two (15%) patients had organ damage at baseline. More than 80% of patients were prescribed GCs over the follow‐up period, almost all patients had long‐term GC treatment, and only 5% of patients took any biologics. Organ damage was more frequent in patients with a higher average GC dose and greater years of GC exposure. Conclusion: In this large cohort of patients with SLE, the majority of patients continue to rely on GC for SLE symptom management, with limited administration of biologics. GC administration was correlated with increased irreversible organ damage. Access to novel GC‐sparing treatment options is critical to improve long‐term outcomes for patients with SLE, especially given the continued reliance on GC despite the introduction of biologics. [ABSTRACT FROM AUTHOR]

Background: Structural uncertainty can affect model-based economic simulation estimates and study conclusions. Unfortunately, unlike parameter uncertainty, relatively little is known about its magnitude of impact on life-years (LYs) and quality-adjusted life-years (QALYs) in modeling of diabetes. We leveraged the Mount Hood Diabetes Challenge Network, a biennial conference attended by international diabetes modeling groups, to assess structural uncertainty in simulating QALYs in type 2 diabetes simulation models. Methods: Eleven type 2 diabetes simulation modeling groups participated in the 9th Mount Hood Diabetes Challenge. Modeling groups simulated 5 diabetes-related intervention profiles using predefined baseline characteristics and a standard utility value set for diabetes-related complications. LYs and QALYs were reported. Simulations were repeated using lower and upper limits of the 95% confidence intervals of utility inputs. Changes in LYs and QALYs from tested interventions were compared across models. Additional analyses were conducted postchallenge to investigate drivers of cross-model differences. Results: Substantial cross-model variability in incremental LYs and QALYs was observed, particularly for HbA1c and body mass index (BMI) intervention profiles. For a 0.5%-point permanent HbA1c reduction, LY gains ranged from 0.050 to 0.750. For a 1-unit permanent BMI reduction, incremental QALYs varied from a small decrease in QALYs (−0.024) to an increase of 0.203. Changes in utility values of health states had a much smaller impact (to the hundredth of a decimal place) on incremental QALYs. Microsimulation models were found to generate a mean of 3.41 more LYs than cohort simulation models (P = 0.049). Conclusions: Variations in utility values contribute to a lesser extent than uncertainty captured as structural uncertainty. These findings reinforce the importance of assessing structural uncertainty thoroughly because the choice of model (or models) can influence study results, which can serve as evidence for resource allocation decisions. Highlights: The findings indicate substantial cross-model variability in QALY predictions for a standardized set of simulation scenarios and is considerably larger than within model variability to alternative health state utility values (e.g., lower and upper limits of the 95% confidence intervals of utility inputs). There is a need to understand and assess structural uncertainty, as the choice of model to inform resource allocation decisions can matter more than the choice of health state utility values. [ABSTRACT FROM AUTHOR]

Abstract The objective of this study was to quantify the direct medical resources used and the corresponding burden of disease in the treatment of patients with schizophrenia. Because low-frequency administration (LFA) of risperidone guarantees adherence during treatment intervals and offers fewer opportunities to discontinue, adherence and persistence were assumed to improve, thereby reducing relapses of major symptoms. A decision tree model including Markov processes with monthly cycles and a five-year maximum timeframe was constructed. Costs were adapted from the literature and discounted at a 3% annual rate. The population is a demographically homogeneous cohort of patients with schizophrenia, differentiated by initial disease severity (mildly ill, moderately ill, and severely ill). Treatment parameters are estimated using published information for once-daily risperidone standard oral therapy (RIS-SOT) and once-monthly risperidone long-acting injection (RIS-LAI) with LFA therapy characteristics derived from observed study trends. One-year and five-year results are expressed as discounted direct medical costs and mean number of relapses per patient (inpatient, outpatient, total) and are estimated for LFA therapies given at three, six, and nine month intervals. The one-year results show that LFA therapy every 3 months (LFA-3) ($6,088) is less costly than either RIS-SOT ($10,721) or RIS-LAI ($9,450) with similar trends in the 5-year results. Moreover, the model predicts that LFA-3 vs. RIS-SOT vs. RIS LAI therapy will reduce costly inpatient relapses (0.16 vs. 0.51 vs. 0.41). Extending the interval to six (LFA-6) and nine (LFA-9) months resulted in further reductions in relapse and costs. Limitations include the fact that LFA therapeutic options are hypothetical and do not yet exist and limited applicability to compare one antipsychotic agent versus another as only risperidone therapy is evaluated. However, study results have quantified the potential health state improvements and potential direct medical cost savings achievable with the development and use of LFA medication delivery technologies.

Background: The treatment for patients with type 2 diabetes mellitus (T2DM) follows a stepwise progression. As a treatment loses its effectiveness, it is typically replaced with a more complex and frequently more costly treatment. Eventually this progression leads to the use of basal insulin typically with concomitant treatments (e.g., metformin, a GLP-1 RA [glucagon-like peptide-1 receptor agonist], a TZD [thiazolidinedione] or a DPP-4i [dipeptidyl peptidase 4 inhibitor]) and, ultimately, to basal-bolus insulin in some forms. As the cost of oral antidiabetics (OADs) and noninsulin injectables have approached, and in some cases exceeded, the cost of insulin, we reexamined the placement of insulin in T2DM treatment progression. Our hypothesis was that earlier use of insulin produces clinical and cost benefits due to its superior efficacy and treatment scalability at an acceptable cost when considered over a 5-year period., Objectives: To (a) estimate clinical and payer cost outcomes of initiating insulin treatment for patients with T2DM earlier in their treatment progression and (b) estimate clinical and payer cost outcomes resulting from delays in escalating treatment for T2DM when indicated by patient hemoglobin A1c levels., Methods: We developed a Monte Carlo microsimulation model to estimate patients reaching target A1c, diabetes-related complications, mortality, and associated costs under various treatment strategies for newly diagnosed patients with T2DM. Treatment efficacies were modeled from results of randomized clinical trials, including the time and rate of A1c drift. A typical treatment progression was selected based on the American Diabetes Association and the European Association for the Study of Diabetes guidelines as the standard of care (SOC). Two treatment approaches were evaluated: two-stage insulin (basal plus antidiabetics followed by biphasic plus metformin) and single-stage insulin (biphasic plus metformin). For each approach, we analyzed multiple strategies. For each analysis, treatment steps were sequentially and cumulatively removed from the SOC until only the insulin steps remained. Delays in escalating treatment were evaluated by increasing the minimum time on a treatment within each strategy. The analysis time frame was 5 years., Results: Relative to SOC, the two-stage insulin approach resulted in 0.10% to 1.79% more patients achieving target A1c (<7.0%), at incremental costs of $95 to $3,267. (The ranges are due to the different strategies within the approach.) With the single-stage approach, 0.50% to 2.63% more patients achieved the target A1c compared with SOC at an incremental cost of -$1,642 to $1,177. Major diabetes-related complications were reduced by 0.38% to 17.46% using the two-stage approach and 0.72% to 25.92% using the single-stage approach. Severe hypoglycemia increased by 17.97% to 60.43% using the two-stage approach and 6.44% to 68.87% using the single-stage approach. In the base case scenario, the minimum time on a specific treatment was 3 months. When the minimum time on each treatment was increased to 12 months (i.e., delayed), patients reaching A1c targets were reduced by 57%, complications increased by 13% to 76%, and mortality increased by 8% over 5 years when compared with the base case for the SOC. However, severe hypoglycemic events were reduced by 83%., Conclusions: As insulin was advanced earlier in therapy in the two-stage and single-stage approaches, patients reaching their A1c targets increased, severe hypoglycemic events increased, and diabetes-related complications and mortality decreased. Cost savings were estimated for 3 (of 4) strategies in the single-stage approach. Delays in treatment escalation substantially reduced patients reaching target A1c levels and increased the occurrence of major nonhypoglycemic diabetic complications. With the exception of substantial increases in severe hypoglycemic events, earlier use of insulin mitigates the clinical consequences of these delays.