A cost-effectiveness analysis of avelumab plus best supportive care versus best supportive care alone as first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma in Taiwan.

BACKGROUND: Patients with locally advanced or metastatic urothelial carcinoma have limited treatment options and a poor prognosis. The JAVELIN Bladder 100 trial showed that avelumab as first-line maintenance plus best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with locally advanced or metastatic urothelial carcinoma that had not progressed with first-line platinum-containing chemotherapy. AIMS: We assessed whether avelumab plus best supportive care is a cost-effective treatment option versus best supportive care alone in this patient group in Taiwan. METHODS AND RESULTS: A partitioned survival model was used to estimate the costs and effects of avelumab plus best supportive care versus best supportive care alone over a 20-year time horizon from the perspective of Taiwan's National Health Insurance Administration. Patient-level data from JAVELIN Bladder 100 on efficacy, safety, utility, and time on treatment were analyzed to provide parameters for the model. Log-normal and Weibull distributions were used for overall survival and progression-free survival, respectively. Costs of healthcare resources, drug acquisition, adverse events, and progression were identified through publicly available data sources and clinician interviews. The model estimated total costs, life years, and quality-adjusted life years. In the modeled base case, avelumab plus best supportive care increased survival versus best supportive care alone by 0.79 life years (2.93 vs. 2.14) and 0.61 quality-adjusted life years (2.15 vs. 1.54). The incremental cost-effectiveness ratio for avelumab plus best supportive care versus best supportive care alone was NT$1 827 680. Most (78%) of the probabilistic sensitivity analyses fell below three times the gross domestic product per capita. Scenario analysis indicated that life year and quality-adjusted life year gains were most sensitive to alternative survival extrapolations for both avelumab plus best supportive care and best supportive care alone. CONCLUSION: Avelumab first-line maintenance therapy combined with best supportive care was determined as a cost-effective treatment strategy for patients in Taiwan diagnosed with locally advanced or metastatic urothelial carcinoma that had not progressed with platinum-containing chemotherapy.

Systematic literature review of current treatments for stage I-III Merkel cell carcinoma.

Aim: There is a need to evaluate current treatments for stages I-III of Merkel cell carcinoma (MCC). Materials & methods: A systematic literature review was conducted to understand how patients with stage I-III MCC are treated and assess efficacy, safety, health-related quality of life and economic impact of current therapies. Embase was searched using the following inclusion criteria: publications from 2014 to 2019, in English, with adult patients (≥18 years) with early-stage MCC (i.e., stages I-III) and any interventions/comparators. Publications were excluded if they included only patients with stage IV MCC, had no distinction between early and advanced or metastatic MCC or had no extractable data. Results: A total of 18 retrospective studies were included. Few studies had evidence that surgery plus adjuvant radiotherapy significantly increased survival versus surgery alone in early MCC. Limited safety data were reported in three studies. None of the studies reported data on health-related quality of life or economic impact of treatment in patients with early-stage MCC. Conclusion: Although surgery plus adjuvant radiotherapy was a common treatment, no clear standard of care exists for stages I-III MCC and treatment outcomes need to be improved. All studies were retrospective with a high variability in sample sizes; hence, findings should be interpreted with caution.

A cost-utility analysis of avelumab for metastatic Merkel cell carcinoma in Taiwan.

BACKGROUND: Metastatic Merkel cell carcinoma (mMCC) has traditionally been managed with palliative chemotherapy regimens or best supportive care (BSC). Avelumab, a novel anti-programmed death-ligand 1 (PD-L1) human monoclonal antibody for mMCC treatment, is being studied in the pivotal JAVELIN Merkel 200 trial. AIM: Incorporating trial results, this analysis aimed to evaluate the cost-utility of avelumab in Taiwan. METHODS AND RESULTS: A de novo partitioned-survival model with three key health states related to survival (progression-free disease, progressed disease, and death) was applied in this study. The data of clinical efficacy, safety, and patient utilities were obtained from the JAVELIN Merkel 200 trial, literature review, and Taiwanese clinical expert opinion. Cost-utility analysis was performed, and results were presented as cost per quality-adjusted life year (QALY) gained. For treatment-naïve patients, the incremental cost-effectiveness ratios (ICERs) for avelumab vs BSC and avelumab vs chemotherapy were US$44885.06 and US$42993.06 per QALY gained, respectively. As to treatment-experienced mMCC patients, avelumab was associated with ICERs of US$27243.06 (vs BSC)/US$26557.43 (vs chemotherapy) per QALY gained. All ICERs remained consistently within the willingness-to-pay (WTP) threshold of US$53,333.33 per QALY gained. CONCLUSION: This study demonstrated avelumab to be a cost-effective treatment option for both treatment-experienced and treatment-naïve mMCC patients with very poor prognosis in Taiwan.

A review of patient-reported outcome measures to assess female infertility-related quality of life.

BACKGROUND: Infertility has a negative impact on quality of life (QoL) and well-being of affected individuals and couples. A variety of patient-reported outcome (PRO) measures to assess infertility-related QoL are available; however, there is a concern regarding potential issues with their development methodology, validation and use. This review aimed to i) identify PRO measures used in infertility interventional studies ii) assess validation evidence to identify a reliable, valid PRO measure to assess changes in QoL or treatment satisfaction in clinical studies with female patients following treatment with novel therapies iii) identify potential gaps in evidence for validity. METHODS: A structured literature search of Medline, Embase, and the Cochrane Library (accessed in September 2015) was conducted using pre-defined search terms. The identified publications were reviewed applying eligibility criteria to select interventional female infertility studies using PROs. Infertility-specific PRO measures assessing QoL, treatment satisfaction or psychiatric health, and included in studies by ≥2 research groups were selected and critically reviewed in light of scientific and regulatory guidance (e.g. FDA PRO Guidance for Industry) for evidence of content validity, psychometric strength, and patient acceptability. RESULTS: The literature search and hand-searching yielded 122 publications; 78 unique PRO measures assessing QoL, treatment satisfaction or psychiatric health were identified. Five PRO measures met the selection criteria for detailed review: Fertility Quality of Life (FertiQoL); Fertility Problem Inventory (FPI); Fertility Problem Stress (FPS); Infertility Questionnaire (IFQ); Illness Cognitions Questionnaire adapted for Infertility (ICQ-I). None of the PRO measures met all validation criteria. The FertiQoL was the most widely used infertility-specific PRO measure to assess QoL in interventional studies, with reasonable evidence for adequate content validity, psychometric strength, and linguistic validation. However, gaps in evidence remain including test-retest reliability and thresholds for interpreting clinically important changes. While the FPI demonstrated reasonable evidence for content and psychometric validity, its utility as an outcome measure is limited by a lack of recall period. CONCLUSION: The FertiQoL and the FPI are potentially useful measures of infertility-related QoL in interventional studies. Further research is recommended to address gaps in evidence and confirm both PRO measures as reliable assessments of patient outcomes.

Treatment satisfaction in type 2 diabetes patients taking empagliflozin compared with patients taking glimepiride.

PURPOSE: This exploratory analysis assessed and compared patients' treatment satisfaction with empagliflozin plus metformin versus glimepiride plus metformin, using data obtained from the Diabetes Treatment Satisfaction Questionnaire, status version (DTSQs) collected in a randomized, double-blind, double-dummy clinical trial. METHODS: Observed values for DTSQs scale score and each of its eight items were summarized by visit and treatment arm. Changes from baseline in these scores were analyzed using linear mixed models for repeated measures. RESULTS: The baseline scale score and item scores were comparable between empagliflozin plus metformin (n = 765) and glimepiride plus metformin (n = 780). Compared with baseline, patients reported significant treatment satisfaction increases and significant decreases in perceived hyperglycemia with both treatments at all visits. Also, compared with baseline, a significant increase in perceived frequency of hypoglycemia was observed in the glimepiride treatment group at all visits. No statistically significant treatment difference was observed in DTSQs scale score and its items at week 104. The difference between the treatment groups was significant and in favor of empagliflozin from week 28 onward for perceived frequency of hyperglycemia (P ≤ 0.006) and perceived frequency of hypoglycemia (P ≤ 0.011). CONCLUSIONS: Despite positive trends in favor of empagliflozin, there was no significant difference in DTSQs scale score between empagliflozin and glimepiride at 104 weeks. However, when compared with glimepiride, empagliflozin demonstrated significantly lower perceived frequency of hyperglycemia and hypoglycemia at all visits from week 28 onward. This finding is consistent with the clinical results reported for the EMPA-REG H2H-SU trial.

Utility estimates for patients with Type 2 diabetes mellitus after experiencing a myocardial infarction or stroke: a systematic review.

A systematic review identified studies eliciting utility decrements from myocardial infarction (MI) and stroke in patients with Type 2 diabetes mellitus (T2DM) and examined their use in economic models of new diabetes treatments. In 16 utility studies in patients with T2DM, utility decrements in the first year ranged from 0.017 to 0.226 for MI and from 0.034 to 0.590 for stroke. Sixteen of 19 economic evaluations of new treatments for T2DM included utility decrements for an MI and/or stroke from one of the 16 utility studies. Decrements for MI ranged from 0.012 to 0.180 in the first year. Decrements for stroke ranged from 0.044 to 0.690 in the first year. Utility studies in patients with T2DM provide little information about changes in utility decrements by time since the event and by disease severity. Cost-effectiveness studies do not always indicate how these values were used in the analysis.

Incremental costs associated with myocardial infarction and stroke in patients with type 2 diabetes mellitus: an overview for economic modeling.

OBJECTIVE: To identify cost estimates related to myocardial infarction (MI) or stroke in patients with type 2 diabetes mellitus (T2DM) for use in economic models. METHODS: A systematic literature review was conducted. Electronic databases and conference abstracts were screened against inclusion criteria, which included studies performed in patients who had T2DM before experiencing an MI or stroke. Primary cost studies and economic models were included. Costs were converted to 2012 pounds sterling. RESULTS: Fifty-four studies were identified: 13 primary cost studies and 41 economic evaluations using secondary sources for complication costs. Primary studies provided costs from 10 countries. Estimates for a fatal event ranged from £2482-£5222 for MI and from £4900-£6694 for stroke. Costs for the year a non-fatal event occurred ranged from £5071-£29,249 for MI and from £5171-£38,732 for stroke. Annual follow-up costs ranged from £945-£1616 for an MI and from £4704-£12,926 for a stroke. Economic evaluations from 12 countries were identified, and costs of complications showed similar variability to the primary studies. DISCUSSION: The costs identified within primary studies varied between and within countries. Many studies used costs estimated in studies not specific to patients with T2DM. Data gaps included a detailed breakdown of resource use, which affected the ability to compare data across countries. CONCLUSIONS: In the development of economic models for patients with T2DM, the use of accurate estimates of costs associated with MI and stroke is important. When country-specific costs are not available, clear justification for the choice of estimates should be provided.

Prevalence of hypertension and obesity in patients with type 2 diabetes mellitus in observational studies: a systematic literature review.

BACKGROUND: Hypertension and obesity are known to contribute, directly or indirectly, to the development of long-term complications of type 2 diabetes mellitus (T2DM). Knowing the prevalence of these comorbidities is important for determining the size of the population that may benefit from strategies that reduce blood pressure and weight while controlling blood glucose. METHODS: In this systematic literature review, electronic searches of PubMed, Embase, and the Cochrane Library were conducted to identify observational studies of hypertension and/or obesity prevalence in patients with T2DM throughout the world. The searches were limited to studies reported in English from January 1, 2001 to February 16, 2012. RESULTS: From a total of 2,688 studies, 92 observational studies provided prevalence rates for hypertension and/or obesity specifically in adults with T2DM. Fifteen studies of specific subtypes of hypertension or subpopulations with T2DM were subsequently excluded, leaving 78 studies (in 77 articles) for inclusion in this article. Of these, 61studies reported hypertension prevalence, 44 reported obesity prevalence, and 12 reported the prevalence of hypertension with obesity. Most studies had a low risk of bias regarding diagnosis of T2DM (70/78), hypertension (59/69), or obesity (45/47). The continental regions with the most observational studies of hypertension or obesity prevalence were Europe (n = 30) and Asia (n = 26). Hypertension rates typically were high in all regions; most studies presented rates above 50%, and many presented rates above 75%. Obesity rates exceeded 30% in 38 of 44 studies and 50% in 14 of 44 studies, especially those assessing central obesity (based on waist circumference). Among obese adults, hypertension rates were at or above 70% in Asia and above 80% in Europe; rates were lower in North and South America but still above 30%. CONCLUSION: Around the world, hypertension and obesity, separately or together, are common comorbidities in adults with T2DM.

Modeling hard clinical end-point data in economic analyses.

OBJECTIVE: The availability of hard clinical end-point data, such as that on cardiovascular (CV) events among patients with type 2 diabetes mellitus, is increasing, and as a result there is growing interest in using hard end-point data of this type in economic analyses. This study investigated published approaches for modeling hard end-points from clinical trials and evaluated their applicability in health economic models with different disease features. METHODS: A review of cost-effectiveness models of interventions in clinically significant therapeutic areas (CV diseases, cancer, and chronic lower respiratory diseases) was conducted in PubMed and Embase using a defined search strategy. Only studies integrating hard end-point data from randomized clinical trials were considered. For each study included, clinical input characteristics and modeling approach were summarized and evaluated. RESULTS: A total of 33 articles (23 CV, eight cancer, two respiratory) were accepted for detailed analysis. Decision trees, Markov models, discrete event simulations, and hybrids were used. Event rates were incorporated either as constant rates, time-dependent risks, or risk equations based on patient characteristics. Risks dependent on time and/or patient characteristics were used where major event rates were >1%/year in models with fewer health states (<7). Models of infrequent events or with numerous health states generally preferred constant event rates. LIMITATIONS: The detailed modeling information and terminology varied, sometimes requiring interpretation. CONCLUSIONS: Key considerations for cost-effectiveness models incorporating hard end-point data include the frequency and characteristics of the relevant clinical events and how the trial data is reported. When event risk is low, simplification of both the model structure and event rate modeling is recommended. When event risk is common, such as in high risk populations, more detailed modeling approaches, including individual simulations or explicitly time-dependent event rates, are more appropriate to accurately reflect the trial data.

The costs of planned cesarean versus planned vaginal birth in the Term Breech Trial.

BACKGROUND: The Term Breech Trial compared the safety of planned cesarean and planned vaginal birth for breech presentations at term. The combined outcome of perinatal or neonatal death and serious neonatal morbidity was found to be significantly lower among babies delivered by planned cesarean section. In this study we conducted a cost analysis of the 2 approaches to breech presentations at delivery. METHODS: We used a third-party-payer (i.e., Ministry of Health) perspective. We included all costs for physician services and all hospital-related costs incurred by both the mother and the infant. We collected health care utilization and outcomes for all study participants during the trial. We used only the utilization data from countries with low national rates of perinatal death (< or = 20/1000). Seven hospitals across Canada (4 teaching and 3 community centres) were selected for unit cost calculations. RESULTS: The estimated mean cost of a planned cesarean was significantly lower than that of a planned vaginal birth (7165 dollars v. 8042 dollars per mother and infant; mean difference -877 dollars, 95% credible interval -1286 dollars to -473 dollars). The estimated mean cost of a planned cesarean was lower than that of a planned vaginal birth for both women having a first birth (7255 dollars v. 8440 dollars) and women having had at least one prior birth (7071 dollars v. 7559 dollars). Although the treatment effect was largest in the subgroup of women having their first child, there was no statistically significant interaction between treatment and parity since the 95% credible intervals for difference in treatment effects between parity equalling zero and parity of one or greater all include zero. INTERPRETATION: Planned cesarean section was found to be less costly than planned vaginal birth for the singleton fetus in a breech presentation at term in the Term Breech Trial.