Gabriel Tremblay

Costing bias in economic evaluations

Abstract Determining the cost-effectiveness of healthcare interventions is key to the decision-making process in healthcare. Cost comparisons are used to demonstrate the economic value of treatment options, to evaluate the impact on the insurer budget, and are often used as a key criterion in treatment comparison and comparative effectiveness; however, little guidance is available to researchers for establishing the costing of clinical events and resource utilization. Different costing methods exist, and the choice of underlying assumptions appears to have a significant impact on the results of the costing analysis. This editorial describes the importance of the choice of the costing technique and it’s potential impact on the relative cost of treatment options. This editorial also calls for a more efficient approach to healthcare intervention costing in order to ensure the use of consistent costing in the decision-making process.

Systematic review of health state utility values for acute myeloid leukemia

Background Cost-utility analyses for acute myeloid leukemia (AML) require health state utility values (HSUVs) in order to calculate quality-adjusted life-years (QALYs) for each health state. Aim This study reviewed AML-related HSUVs that could be used in economic evaluation studies. Materials and methods EMBASE, MEDLINE, and Cochrane databases were searched from January 2000 to November 2016 for relevant studies that reported quality of life (QoL) and HSUVs in AML. Identified relevant European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 values were mapped to HSUVs. HSUVs for each health state in the AML treatment pathway were then collated. Results Ten relevant studies were identified. Six were cost-effectiveness analyses utilizing HSUVs for calculation of QALYs, one was an effectiveness analysis (incremental QALY), and two were QoL studies reporting AML-specific utilities. An additional study reported QoL for patients undergoing stem cell transplantation (SCT). Since no study reported HSUVs for relapse, values from a study of secondary AML patients who failed prior treatment for myelodysplastic syndrome were used. Where multiple HSUVs were available, collected values were given priority over assumed values. AML treatment (induction, consolidation, or SCT) was associated with decreased HSUV, while post-treatment complete remission led to increased HSUV. Conclusion There are some methodologically robust HSUVs that can be directly used in economic evaluations for AML. Careful interpretation is advised considering significant differences in methodologies and patient population (inclusion, size). We need to develop HSUVs with larger-sized studies, making greater use of condition-specific data.

Comparative effectiveness research in renal cell carcinoma: Lenvatinib with everolimus as a potential new treatment option.

27 Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer and represents about 90% of all kidney cancers. As comprehensive comparison of the efficacy associated with mRCC treatments is not available, the goal of this research was to provide a comparative effectiveness analysis including overall survival (OS) and progression free survival (PFS) for first and second line treatments. METHODS Systematic literature review yielded the following randomized active-controlled studies: lenvatinib + everolimus (LEN+EVE) versus everolimus (EVE), axinitib (AXI) versus sorafenib (SOR), cabozantinib (CAB) versus EVE, nivolumab (NIV) versus EVE, and pazopanib (PAZ) versus sunitinib (SUN). In addition, placebo-controlled studies were identified for EVE, PAZ, and SOR. An indirect treatment comparison (ITC) was performed on OS and PFS hazard ratios (HR). RESULTS Scenario A presents the HR and confidence intervals (95% CI) generated with ITC of all treatments against EVE. In scenario B, the HR of LEN + EVE are compared to all treatment options. Only LEN + EVE and CAB demonstrated significance against EVE for both OS and PFS. LEN + EVE proved to be significant against EVE, PAZ, SOR, SUN, AXI and NIV for PFS and against EVE, SOR and AXI for OS. The use of crossover trials in the network for the treatment compared to placebo remains a potential bias in the results. CONCLUSIONS Even if limitations exist regarding the use of ITC, the option of LEN+EVE demonstrated a strong comparative effectiveness profile for both OS and PFS. [Table: see text].

Number needed to treat in indirect treatment comparison

AIM For dichotomous outcomes, odds ratio (OR) is one of the usual summary measures of indirect treatment comparison. A corresponding number needed to treat (NNT) estimate may facilitate understanding of the treatment effect. METHODS We show how to estimate NNT based on OR results of a matching adjusted indirect comparison. We also have derived the explicit formula of its 95% CIs by applying the delta method, and as an alternative, a simulation-based method. RESULTS The method was applied in a case study example in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients, comparing lenvatinib to sorafenib. For every two RR-DTC patients treated with lenvatinib instead of sorafenib, one fewer would have progressed and for every eight RR-DTC patients treated with lenvatinib instead of sorafenib, one fewer would have died. CONCLUSION Using NNT to summarize the results of a matching adjusted indirect comparison can help the clinicians to better understand the results in addition to OR.

A decision framework for treating chronic immune thrombocytopenia with thrombopoietin receptor agonists

AIM Eltrombopag and romiplostim are comparable second-line therapies in chronic immune thrombocytopenia. Treatment decisions are made in different contexts. A framework was created to outline decision pathways for physicians and payers. MATERIALS & METHODS The costs of drugs, administration, routine care, bleeding, other adverse events and mortality were included in the year-long calculation of total costs from a US private payer perspective. Treatment parameters and outcome data were obtained from relevant clinical trials. RESULTS The total cost per year, per patient of eltrombopag was US

Cost-effectiveness of perampanel for the treatment of primary generalized tonic-clonic seizures (PGTCS) in epilepsy: A Spanish perspective

51,000 versus US

Matching-adjusted indirect treatment comparison of ribociclib and palbociclib in HR+, HER2− advanced breast cancer

76,000 for romiplostim. Drug costs and costs associated with bleeding-related events were the main drivers of cost difference. CONCLUSION This framework facilitates decision-making in the management of chronic immune thrombocytopenia with eltrombopag and romiplostim.

Is progression-free survival a more relevant endpoint than overall survival in first-line HR+/HER2− metastatic breast cancer?

BACKGROUND Persistent seizures are associated with physical injury, reduced quality of life, and psychosocial impairment. Perampanel is approved for the adjunctive treatment of primary generalized tonic-clonic seizures (PGTCS). OBJECTIVE This study aimed to determine the cost-effectiveness of perampanel as adjunctive therapy to other antiepileptic drugs (AED) compared with AED maintenance therapy alone for the treatment of PGTCS. METHODS We developed a Markov model for PGTCS where transitions were based on treatment response rates. The analysis was conducted over a 33-year time horizon from the Spanish National Health Service (NHS) and societal perspectives. Efficacy data were derived from clinical studies. Resource use, market shares, costs, and utilities were obtained from Kantar Healths National Health and Wellness Survey. Drug costs were obtained from the Consejo General de Colegios Oficiales de Farmacéuticos. One-way and probabilistic sensitivity analyses were performed. RESULTS In the base case analysis from the NHS perspective, perampanel was associated with an incremental cost-effectiveness ratio (ICER) of €16,557/quality-adjusted life year (QALY) relative to AED maintenance therapy for the treatment of PGTCS. Incremental costs were €5475 and incremental QALYs were 0.33. In one-way sensitivity analyses, the ICERs were strongly influenced by discounting rate for costs and health effects, with little influence of other parameters, including perampanel cost and utilities. In probabilistic sensitivity analyses, the probability of perampanel being cost-effective at a willingness-to-pay threshold of €30,000/QALY was 89.3%. From the societal perspective, perampanel provided a cost-savings of €5288 per patient compared with AED maintenance therapy alone. CONCLUSION Our study demonstrates that perampanel is likely to be a cost-effective option.

Progression-free survival/time to progression as a potential surrogate for overall survival in HR+, HER2– metastatic breast cancer

Background Ribociclib (RIBO) and palbociclib (PALBO), combined with letrozole (LET), have been evaluated as treatments for hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in separate Phase III randomized controlled trials (RCTs), but not head-to-head. Population differences can lead to biased results by classical indirect treatment comparison (ITC). Matching-adjusted indirect comparison (MAIC) aims to correct these differences. We compared RIBO and PALBO in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer using MAIC. Methods Patient-level data were available for RIBO (MONALEESA-2), while only published summary data were available for PALBO (PALOMA-2). Weights were assigned to MONALEESA-2 patient data such that mean baseline characteristics matched those reported for PALOMA-2; the resulting matched cohort was used in comparisons. Limited by the results reported in PALOMA-2, progression-free survival (PFS) was the primary comparison. Cox regression models were used to calculate adjusted hazard ratios (HRs) for PFS, before indirect treatment comparison (ITC) was performed with 95% confidence intervals. An exploratory analysis was performed similarly for overall survival using earlier PALBO data (PALOMA-1). Grade 3/4 adverse events were also compared. Results Racial characteristics, prior chemotherapy setting, and the extent of metastasis were the most imbalanced baseline characteristics. The unadjusted PFS HRs were 0.556 (0.429, 0.721) for RIBO+LET versus LET alone and 0.580 (0.460, 0.720) for PALBO+LET versus LET alone. MAIC adjustment resulted in an HR of 0.524 (0.406, 0.676) for RIBO+LET versus LET. PFS ITC using unadjusted trial data produced an HR of 0.959 (0.681, 1.350) for RIBO versus PALBO, or 0.904 (0.644, 1.268) with MAIC. Unadjusted overall survival HR of RIBO versus PALBO was 0.918 (0.492, 1.710); while exploratory MAIC was 0.839 (0.440, 1.598). ITC of grade 3/4 adverse events yielded a risk ratio of 0.806 (0.604, 1.076). Conclusion MAIC was performed for RIBO and PALBO in the absence of a head-to-head trial: though not statistically significant, the results favored RIBO.

Budget impact of perampanel as adjunctive treatment of uncontrolled partial-onset and primary generalized tonic–clonic seizures in the United States

Background Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−), metastatic breast cancer (MBC) accounts for 73% of all MBCs. Endocrine therapy (ET) is the basis of first-line (1L) therapy for patients with HR+/HER2− MBC. Novel therapies have demonstrated improvements in progression-free survival (PFS) compared to ET. The clinical relevance of PFS is being debated, as there is no proven direct correlation with overall survival (OS) benefit to date. We reviewed studies of HR+/HER2− MBC to assess PFS and other factors that influence OS and treatment response, and health-related quality of life (HRQoL). Methods The Embase®, Medline®, and Cochrane databases were systematically searched to identify studies in adult women with HR+/HER2− MBC, published between January 2006 and January 2017, and written in English. Phase II and III randomized controlled trials (RCTs), observational, and retrospective studies were included. Results Seventy-nine RCTs were identified: 58 (73%) in the 1L+ setting and 21 (27%) in second-line or greater settings. PFS hazard ratios (HRs) were reported in 61 (77%) studies; 31 (39%) reported significant PFS improvements. OS was reported in 44 (41%) studies; 12 (15%) reported significant OS improvements. Significant improvements in both PFS and OS were reported in only 6 (8%) studies (1 Phase II; 5 Phase III). Patients with HER2− MBC received, on average, ≥5 lines of therapy, with no consistent treatment pathway. Baseline characteristics, prior therapies, and the type and number of post-progression therapies significantly impacted OS. PFS, response rates, and HRQoL decreased with each line of therapy (EuroQol 5 Dimensions: 0.78 1L vs. 0.70 post-progression). Conclusion Few RCTs in HR+/HER2− MBC have demonstrated significant improvements in OS. Factors other than choice of 1L therapy impact OS, including post-progression therapies, which cannot be controlled in RCTs. This study emphasizes the importance of PFS improvement in 1L treatment of HR+/HER2− MBC.