Inverse probability weighting to control for censoring in a post hoc analysis of quality-adjusted survival data from a clinical trial of temsirolimus for renal cell carcinoma

Abstract

Objectives: The Belgian third-party payer wishes to set reimbursement tariffs at a level that reflects the costs of orthotic braces. This article aims to calculate production and distribution costs of a prefabricated hard neck and knee brace and to explore whether Belgian tariffs and actual retail prices correspond with estimated costs of these two braces.

Methods: The cost model considered manufacturing costs, general overheads, research and development costs, warehousing costs, profit and distribution margins. Data were gathered from manufacturers, a production site visit, desk research, a decomposition of finished products and stakeholder interviews. The price year was 2007.

Results: The cost model estimated a retail price of €55–€150 for the neck brace, depending on assumptions. The estimated retail price for the neck brace was lower than the reimbursement tariff of €194 and the actual retail price of €241. The estimated retail price of €331–€694 for the knee brace was lower than the actual retail price of €948.

Conclusions: Actual retail prices and reimbursement tariffs for a neck brace and a knee brace exceeded prices based on estimated costs. Therefore, there appears to be scope for reducing tariffs.     

Feasibility of using administrative claims data for cost-effectiveness analysis of a clinical trial

Objective: This study was performed retrospectively to determine if Medicare claims data could be used to evaluate the cost effectiveness, from a payer perspective, of different radiation treatment schedules evaluated in a national clinical trial.

Methods: Medicare costs from all providers and all places of service were obtained from the Centers for Medicare & Medicaid Services for patients treated in the period 1992–1996 on Radiation Therapy Oncology Group 90-03, and combined with data on outcomes from the trial.

Results: Of the 1,113 patients entered, Medicare cost data and clinical outcomes were available for 187 patients. Significant differences in tolerance of treatment and outcome were noted between patients with Medicare data included in the study and patients without Medicare data, and non-Medicare patients excluded from it. Ninety-five percent confidence ellipses on the incremental cost-effectiveness scatterplots crossed both axes, indicating non-significant differences in cost effectiveness between radiation treatment schedules.

Conclusions: Claims data permit estimation of cost effectiveness, but Medicare data provide inadequate representation of results applicable to patients from the general population.

Keywords:     

Cost analysis for different sequential treatment regimens for metastatic renal cell carcinoma in China

Abstract

Purpose: Targeted therapies, including sunitinib, sorafenib, axitinib, and everolimus, have recently become the mainstay for the treatment of metastatic renal cell carcinoma (mRCC). The objective of this study was to estimate the costs of sequential treatment regimens for mRCC and associated adverse events (AEs) from the Chinese payers’ perspective.

Methods: Key inputs included in the calculation were patient population, dosing information, incidence rates and associated costs of Grade 3/4 AEs, treatment costs (including drug discount programs), and patients’ progression-free survival (PFS) as a proxy for length of treatment. To calculate PFS, this study identified pivotal clinical trials and generated a reconstructed individual patient data set from the published Kaplan-Meier survival curves. The median PFS from the pooled estimates were used in the calculation. In the base-case scenario, sunitinib was used as first line and the other three therapies were used as second line. Sensitivity analyses were conducted where (1) sorafenib was used as first line, or (2) a third-line therapy was added to the base-case scenario.

Results: In the base case, the cost per patient per treatment month (PPPM) cost was the lowest for sunitinib?+?axitinib among all sequential regimens (¥14,898) and was the highest for sunitinib?+?sorafenib (¥20,103). If sorafenib is used as first line, everolimus had lower per patient per months (PPPM) cost than axitinib (¥17,046 vs ¥23,337), but also had shorter PFS (13.5 months vs 15 months). Second sensitivity analysis with an additional third-line therapy showed consistent results with the base-case scenario; axitinib as second line was the least costly.

Conclusions: This study demonstrates that, for mRCC sequential treatment, sunitinib followed by axitinib generates the highest cost savings from the Chinese payers’ perspective. Future studies are warranted to examine the cost-effectiveness of various mRCC treatment regimens in Chinese populations.     

Patients rank toxicity against progression free survival in second-line treatment of advanced renal cell carcinoma

Abstract

Background:

The aims of this study were to quantify and contrast patient preferences between second-line advanced renal cell carcinoma (RCC) medication profiles and their associated benefits and toxicities, and to help frame the doctor–patient discussion about selecting appropriate RCC therapies.

Research design and methods:

Adult residents of the US with a diagnosis of RCC completed a Web-enabled choice-format conjoint survey consisting of a series of 10 treatment-choice questions, each of which included a pair of hypothetical RCC medication profiles. Each profile was described by various medication attributes (features or outcomes) with varying levels. The attributes included efficacy (progression-free survival [PFS]), tolerability (fatigue, stomach problems, mucositis or stomatitis, hand–foot syndrome [HFS]), serious but rare adverse events (pneumonitis, hepatic impairment), and mode of administration. Treatment-choice questions were based on an experimental design with known statistical properties. Random-parameters logit regression was used to estimate relative preference weights for each attribute level. Benefit equivalent measures (additional months of PFS in exchange for toxicities) were also calculated.

Results:

Of the 272 patients who completed the survey, the majority were female (53%), white (92%), and had at least a college degree (66%). The mean age was 57 years (standard deviation: 10 years). Over the range of attributes and attribute levels included in the survey, PFS was the most important attribute, followed by fatigue, stomach problems, hepatic impairment, mucositis or stomatitis, HFS, pneumonitis, and mode of administration. To reduce severe fatigue to mild-to-moderate fatigue, patients on average would be willing to forego 4.4 months of PFS. To reduce hepatic impairment risk from 0.5% to 0.0%, patients on average would be willing to forego 1.0 month of PFS. The main study limitation was that patients answered hypothetical treatment-choice questions.

Conclusions:

This study provides information to physicians about patient priorities when reviewing and selecting RCC therapies with patients.     

Understanding the effects on HR-QoL of treatment for overactive bladder: a detailed analysis of EQ-5D clinical trial data for mirabegron

Abstract

Background:

Analysis of EQ-5D data often focuses on changes in utility, ignoring valuable information from other parts of the instrument. The objective was to explore how the utility index, EQ-5D profile, and EQ-VAS captured change in clinical trials of mirabegron, a new treatment for overactive bladder (OAB).

Data:

Data were pooled from three phase III clinical trials that investigated the efficacy and safety of mirabegron vs placebo. Tolterodine ER 4?mg was included as an active control in one study: (1) placebo, mirabegron 50?mg and 100?mg, and tolterodine 4?mg ER; (2) placebo, mirabegron 50?mg and 100?mg; (3) placebo, and mirabegron 25?mg and 50?mg. Data were collected at baseline, week 4, 8, and 12.

Methods:

Analyses were performed on full analysis and modified intention to treat (ITT) data sets using UK utilities. Analysis controlled for relevant patient characteristics. Analysis of Covariance identified changes from baseline at each time point in utilities and EQ-VAS. Areas Under the Curve were estimated to summarize inter-temporal differences in effect. EQ-5D profile data were analysed using the Paretian Classification of Health Change.

Results:

In modified ITT analyses, mirabegron 50?mg was superior to tolterodine 4?mg in changes from baseline utilities after 12 weeks (p?<?0.05); similarly, AUC results showed mirabegron 50?mg to be superior to tolterodine (p?<?0.05) and placebo (p?<?0.05) with the benefit already apparent at 4 weeks (p?<?0.05). EQ-VAS more consistently indicated superior outcomes: all three mirabegron doses showed statistically significant greater effectiveness compared to tolterodine at 12 weeks. Individual EQ-5D dimensions and the overall profile showed no significant differences between study arms.

Conclusion:

Mirabegron showed quicker and superior improvement in HR-QoL compared to tolterodine 4?mg ER. A limitation of the study is that EQ-5D was a secondary outcome in the pivotal trials, which were not powered to measure differences on EQ-5D.     

Value of clinical trial narrative data to estimate the costs of adverse event management: a feasibility study

Abstract

Aims: The objective of this feasibility study was to determine the extent to which data from randomized controlled trials (RCTs) may serve as a useful source for collecting health care resource use (HCRU) for the purposes of estimating costs of managing adverse events (AEs), specifically, grade 3–4 nausea and thrombocytopenia, which may be experienced during chemotherapy treatment.

Materials and Methods: The feasibility study was conducted in four steps: (1) HCRU data were extracted from patient narratives in four phase 3 RCTs in non–small cell lung cancer; (2) missing HCRU data were imputed; (3) unit costs were applied to the resulting HCRU data set and costs of managing AEs were estimated; and (4) the overall utility of using RCT data as a source for estimating costs of AEs was evaluated.

Results: 33 nausea and 68 thrombocytopenia AEs met eligibility criteria and were evaluated in this study. Medication usage was recorded as a treatment in 76% of nausea AEs, although only 14% of the instances of medication usage included the minimum data elements required for costing. Platelet transfusions were provided in 24% of thrombocytopenia AEs; however, in only one instance were the minimum data elements recorded. Of nausea and thrombocytopenia AEs, 18% and 72%, respectively, required no missing data assumptions or imputation.

Limitations: Only two AEs were considered, and they may not be representative of all AEs in terms of suitability for use in estimating HCRU and costs of managing AEs. Not all grade 3–4 AEs met the criteria for requiring a patient narrative. HCRU data in the narratives were incomplete.

Conclusions: The usefulness of RCTs for estimating the costs of AEs may be improved by using a standardized form to collect HCRU data for key AEs, including an appropriate level of detail required to estimate costs of managing the AEs.     

Cost-effectiveness of droxidopa in patients with neurogenic orthostatic hypotension: post-hoc economic analysis of Phase 3 clinical trial data

Objective:

Falls are associated with neurogenic orthostatic hypotension (nOH) and are an economic burden on the US healthcare system. Droxidopa is approved by the US FDA to treat symptomatic nOH. This study estimates the cost-effectiveness of droxidopa vs standard of care from a US payer perspective.

Methods:

A Markov model was used to predict numbers of falls and treatment responses using data from a randomized, double-blind trial of patients with Parkinson’s disease and nOH who received optimized droxidopa therapy or placebo for 8 weeks. The severity of falls, utility values, and injury-related costs were derived from published studies. Model outcomes included number of falls, number of quality-adjusted life-years (QALYs), and direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated. Outcomes were extrapolated over 12 months.

Results:

Patients receiving droxidopa had fewer falls compared with those receiving standard of care and gained 0.33 QALYs/patient. Estimated droxidopa costs were $30,112, with estimated cost savings resulting from fall avoidance of $14,574 over 12 months. Droxidopa was cost-effective vs standard of care, with ICERs of $47,001/QALY gained, $24,866 per avoided fall with moderate/major injury, and $1559 per avoided fall with no/minor injury. The main drivers were fall probabilities and fear of fall-related inputs.

Limitations:

A limitation of the current study is the reliance on falls data from a randomized controlled trial where the placebo group served as the proxy for standard of care. Data from a larger patient population, reflecting ‘real-life’ patient use and/or comparison with other agents used to treat nOH, would have been a useful complement, but these data were not available.

Conclusion:

Using Markov modeling, droxidopa appears to be a cost-effective option compared with standard of care in US clinical practice for the treatment of nOH.     

Pharmacological control of secondary hyperparathyroidism in hemodialysis subjects: a cost consequences analysis of data from the FARO study

Abstract

Background and objectives:

Secondary hyperparathyroidism (SHPT) is a frequent complication of CKD with incidence, prevalence, and costs increasing worldwide. The objective of this analysis was to estimate therapy cost of SHPT in a sub-population of the FARO study.

Materials and Methods:

In the FARO study, an observational survey aimed to evaluate patterns of treatment in patients with SHPT who had undergone hemodialysis, pharmacological treatments and biochemical parameters evolution data were collected in four surveys. Patients maintaining the same treatment in all sessions were grouped by type of treatment and evaluated for costs from the Italian National Health Service perspective.

Results:

Four cohorts were identified: patients treated with oral (PO) calcitriol (n?=?182), intravenous (IV) calcitriol (n?=?34), IV paricalcitol (n?=?62), and IV paricalcitol?+?cinacalcet therapy (n?=?20); the cinacalcet monotherapy group was not analysed due to low number of patients (n?=?9). Parathyroid hormone (PTH) level at baseline and effectiveness of treatments in suppressing PTH level were assessed to test comparability among cohorts: calcitriol PO patients were significantly less severe than others (PTH level at baseline lower than 300?pg/ml; p?<?0.0001); calcitriol IV patients did not reach significant reduction in PTH level. Paricalcitol and paricalcitol?+?cinacalcet treatment groups results were comparable, while only the IV paricalcitol cohort’s PTH level, weekly dosage, and cost decreased significantly from the first to the fourth survey (p?=?0.020, p?=?0.012, and p?=?0.0124, respectively). Total costs per week of treatment (including calcium-based phosphate binder and sevelamer) were significantly lower in the paricalcitol vs paricalcitol?+?cinacalcet cohort (p?<?0.001). Major limitations of this study are related to the survey design: not controlled and lack of comparability between cohorts; however, reflective of true practice patterns.

Conclusions:

The IV Paricalcitol cohort had significantly lower treatment costs compared with patients treated with paricalcitol?+?calcimemtics (p?<?0.001), without a significant difference in terms of baseline severity and PTH control.     

Role of transfusion in stem cell transplantation: a freedom-from-transfusion (FFT), cost and survival analysis

Abstract

Background: Transfusion of blood products is often necessary for patients undergoing stem cell transplantation (SCT). The need for red cell and platelet transfusion may vary significantly depending on the type of transplantation and underlying disease.

Methods: In an attempt to evaluate the need and volume of transfusions in patients undergoing SCT at University of Kansas Medical Center, the authors retrospectively evaluated the transfusion data of all patients who received SCT between 2000 and 2005.

Results: A total of 138 (90%) out of 154 patients undergoing autologous SCT and 24 (43%) out of 56 patients with allogeneic SCT exhibited total hematopoietic engraftment and freedom from transfusion (FFT). Time to achieve FFT (median; range) for RBC units for autologous SCT (12; 0–183) was significantly shorter compared with allogeneic SCT (16.5; 0–373). Number of RBC units (median; range) transfused were significantly less in patients undergoing autologous SCT (4; 0–26) compared to patients undergoing allogeneic SCT (6.5; 0–54). The median cost of transfusion was significantly higher in patients undergoing allogeneic SCT (red cell: $2,015; platelet: $4,480) compared to patients undergoing autologous SCT (red cell: $1,240; platelet: $2,520). The authors recognize that this was a retrospective single-center study and practice guidelines may vary from center to center.

Conclusion: Authors conclude that transfusion of blood products is an expensive but integral part of SCT, more so for allogeneic SCT than for patients undergoing autologous SCT. Total FFT is a desirable long-term goal of successful marrow transplantation.     

Ready-steady-go for emerging technologies in post catch-up countries: a longitudinal network analysis of nanotech in Korea

This paper presents a case study of government R&D nanotech networks in Korea to elaborate the characteristics of post catch-up countries on the border line between developing and developed countries. Using to longitudinal network analysis, this paper examines expectation building and learning process as key components for the emerging technology development during the post catch-up era. Findings suggest that a change of the global R&D landscape sparks the development of emerging technologies by expectation building and resource attraction for technology development. Prior to this spark, however, an internal learning mechanism is ready for the development process.     

Assessing the burden of illness from cervical dystonia using the Toronto Western Spasmodic Torticollis Rating Scale scores and health utility: a meta-analysis of baseline patient-level clinical trial data

Purpose:

This study aimed to explore the burden of illness associated with cervical dystonia (CD), including possible demographic and humanistic correlates of baseline disease severity.

Methods:

The analysis involved the five multinational randomized, placebo-controlled clinical trials that had evaluated the efficacy and safety of Dysport® in patients with CD, including assessment using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Patient-level TWSTRS scores from the individual studies were meta-analysed to estimate disease severity at baseline. One of the studies had reported Short Form-36 (SF-36) Health Survey quality-of-life measures, and these data were used to investigate whether the severity of CD was associated with humanistic outcomes, as measured by health utility. A generalized regression model was then applied to explore potential correlation between TWSTRS scores and utilities.

Results:

The estimated pooled mean baseline severity of CD in clinical trial entrants, as measured by TWSTRS score, was 43.23 (95% CI?=?39.31–47.15). In general, disease severity was significantly greater in patients aged over 40 years (compared to the reference group aged 18–30 years). However, there was no correlation between disease severity and other demographic characteristics (e.g., weight, height, gender). Higher TWSTRS scores correlated with worse health-related quality of life as perceived by patients and was reflected in health utility (R^2?=?0.133).

Conclusions:

This study was able to define TWSTRS scores in patients with CD in terms of associated utility. This approach could help in capturing the disease’s burden through measures that are more tangible than TWSTRS scores to patients, carers, clinicians, and healthcare payers.     

Real-world dosing and drug costs with everolimus or axitinib as second targeted therapies for advanced renal cell carcinoma: a retrospective chart review in the US

Objective:

To describe dosing patterns and to compare the drug costs per month spent in progression-free survival (PFS) among patients with advanced renal cell carcinoma (aRCC) treated with everolimus or axitinib following a first tyrosine kinase inhibitor (TKI).

Methods:

A medical record retrospective review was conducted among medical oncologists and hematologists/oncologists in the US. Patient eligibility criteria included: (1) age ≥18 years; (2) discontinuation of first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons; (3) initiation of axitinib or everolimus as a second targeted therapy during February 2012–January 2013. Real-world dosing patterns were summarized. Dose-specific drug costs (as of October 2014) were based on wholesale acquisition costs from RED BOOK Online. PFS was compared between everolimus and axitinib using a multivariable Cox proportion hazards model. Everolimus and axitinib drug costs per month of PFS were compared using multivariable gamma regression models.

Results:

A total of 325 patients received everolimus and 127 patients received axitinib as second targeted therapy. Higher proportions of patients treated with axitinib vs everolimus started on a higher than label-recommended starting dose (14% vs 2%) or experienced dose escalation (11% vs 1%) on second targeted therapy. The PFS did not differ significantly between patients receiving everolimus or axitinib (adjusted hazard ratio (HR)?=?1.16; 95% confidence interval [CI]?=?0.73–1.82). After baseline characteristics adjustment, axitinib was associated with 17% ($1830) higher drug costs per month of PFS compared to everolimus ($12,467 vs $10,637; p?<?0.001).

Limitations:

Retrospective observational study design and only drug acquisition costs considered in drug costs estimates.

Conclusions:

Patients with aRCC receiving axitinib as second targeted therapy were more likely to initiate at a higher than label-recommended dose and were more likely to dose escalate than patients receiving everolimus. With similar observed durations of PFS, drug costs were significantly higher—by 17% per month of PFS—with axitinib than with everolimus.     

Cost-effectiveness of ranibizumab and aflibercept to treat diabetic macular edema from a US perspective: analysis of 2-year Protocol T data

Abstract

Aims: Protocol T (NCT01627249) was a head-to-head study conducted by the Diabetic Retinopathy Clinical Research Network that compared intravitreal aflibercept, bevacizumab, and ranibizumab for the treatment of diabetic macular edema (DME). A cost-effectiveness analysis accompanying the 1-year data of Protocol T revealed that aflibercept was not cost-effective vs ranibizumab for all patients, but could have been cost-effective in certain patient sub-groups if the 1-year results were extrapolated out to 10?years. The present study evaluated the cost-effectiveness of US Food and Drug Administration-approved anti-vascular endothelial growth factor agents (ranibizumab, aflibercept) for treatment of DME using the 2-year data from Protocol T.

Methods: Costs of aflibercept 2.0?mg or ranibizumab 0.3?mg, visual acuity (VA)-related medical costs, and quality-adjusted life-years (QALYs) were simulated for eight VA health states. Treatment, adverse event management, and VA-related healthcare resource costs (2016 US dollars) were based on Medicare reimbursement and published literature. VA-related health utilities were determined using a published algorithm. Patients were stratified by baseline VA: 20/40 or better; 20/50 or worse.

Results: Total 2-year costs were higher, and QALYs similar, for aflibercept vs ranibizumab in the full cohort ($44,423 vs $34,529; 1.476 vs 1.466), 20/40 or better VA sub-group ($40,854 vs $31,897; 1.517 vs 1.519), and 20/50 or worse VA sub-group ($48,214 vs $37,246; 1.433 vs 1.412), respectively. Incremental cost-effectiveness ratios in the full cohort and 20/50 or worse VA sub-group were $986,159/QALY and $523,377/QALY, respectively. These decreased to $711,301 and $246,978 when analyses were extrapolated to 10?years.

Limitations: Key potential limitations include the fact that VA was the only QALY parameter analyzed and the uncertainty surrounding the role of better- and worse-seeing eye VA in overall functional impairment.

Conclusions: This analysis suggests that aflibercept is not cost-effective vs ranibizumab for patients with DME, regardless of baseline vision.     

A UK analysis of the cost of switching renal transplant patients from an immediate-release to a prolonged-release formulation of tacrolimus based on differences in trough concentration variability

Background and aims:

Randomized controlled trials have shown that a once-daily prolonged-release (PR) tacrolimus formulation (PR tacrolimus; Advagraf), is non-inferior to a twice-daily immediate-release (IR) tacrolimus formulation (IR tacrolimus; Prograf) in terms of biopsy-proven acute rejection, graft failure and mortality in renal transplant recipients. However, relative to IR tacrolimus, PR tacrolimus exhibits reduced tacrolimus trough concentration variability, which has been associated with reduced graft failure. Based on these data, the present study evaluated the cost of switching UK renal transplant patients from IR tacrolimus to PR tacrolimus.

Methods:

UK-specific data on acute rejection, graft failure, and mortality were used to construct a budget impact model to assess the costs of switching from IR tacrolimus to PR tacrolimus on a 1:1?mg:mg basis. The model assumed that 3.1% of patients on PR tacrolimus had high tacrolimus trough concentration variability compared with 17.4% on IR tacrolimus, based on a study comparing PR tacrolimus and IR tacrolimus pharmacokinetics. A relative graft failure risk of 2.38 was applied to high variability patients based on data from a tacrolimus variability study in which 10/148 patients with low variability experienced graft failure, compared with 24/149 in the high variability group. Cost data were taken from the British National Formulary and 2012–2013 NHS tariff information.

Results:

The mean per-patient cost (including tacrolimus, concomitant immunosuppressive medications, dialysis after graft failure, and treatment for acute rejection) was GBP 26,941 (standard deviation [SD]?=?GBP 2765) with PR tacrolimus vs GBP 30,356 (SD?=?GBP 3085) for IR tacrolimus over a 5-year period, corresponding to a saving of GBP 3415 (SD?=?GBP 516) per patient or GBP 341,500 in a hypothetical 100-patient transplant center. Cost savings were driven primarily by lower dialysis costs resulting from the lower proportion of PR tacrolimus patients with high tacrolimus trough concentration variability (leading to lower graft failure risk).

Limitations:

The main limitation of the study was the use of heterogeneous data sources to capture the effect of within-patient variability on graft failure. The most important difference between the studies was the definition of the threshold between low and high within-patient variability. This was explored in sensitivity analyses in which the inter-arm difference in the inter-arm proportions of patients with high and low variability was abolished.

Conclusions:

Converting UK renal transplant recipients from IR tacrolimus to PR tacrolimus was associated with lower pharmacy and dialysis costs.     

The cost-effectiveness of celecoxib vs diclofenac in the treatment of osteoarthritis in the UK; an update to the NICE model using data from the CONDOR trial

Abstract

Objectives:

The National Institute for Health and Clinical Excellence (NICE) health economic model for assessing the cost-effectiveness of celecoxib plus a proton pump inhibitor (PPI) compared to diclofenac plus PPI in the treatment of osteoarthritis has been updated using new adverse event (AE) risks from the CONDOR trial. In light of this new information, this study aimed to evaluate the incremental cost-effectiveness ratio (ICER) of celecoxib plus PPI compared to diclofenac plus PPI.

Methods:

NICE developed a health economic model as part of their 2008 multiple technology assessment of treatments for osteoarthritis. The model was adapted for this study to update the relative risks of adverse events, using data from the CONDOR trial.

Results:

Using the AE data from the CLASS trial alone, celecoxib plus PPI has an ICER of £9538 per QALY when compared to diclofenac plus PPI. When the AE data from CONDOR alone is used, this ICER decreases to £4773 per QALY. Using the pooled data from both trials, celecoxib plus PPI has an ICER of £9377 per QALY compared to diclofenac plus PPI.

Discussion:

The results suggest that when new AE risks are used, celecoxib plus PPI remains a cost-effective treatment for OA when compared to diclofenac plus PPI. However, this analysis is limited by the short time horizon, and additional AEs that have not been considered.     

Economic impact of switching from metoprolol to nebivolol for hypertension treatment: a retrospective database analysis

Objective:

To estimate the real-world economic impact of switching hypertensive patients from metoprolol, a commonly prescribed, generic, non-vasodilatory β₁-blocker, to nebivolol, a branded-protected vasodilatory β₁-blocker.

Methods:

Retrospective analysis with a pre–post study design was conducted using the MarketScan database (2007–2011). Hypertensive patients continuously treated with metoprolol for ≥6 months (pre-period) and then switched to nebivolol for ≥6 months (post-period) were identified. The index date for switching was defined as the first nebivolol dispensing date. Data were collected for the two 6-month periods pre- and post-switching. Monthly healthcare resource utilization and healthcare costs pre- and post-switching were calculated and compared using Wilcoxon test and paired t-test. Medical costs at different years were inflated to the 2011 dollar.

Results:

In total, 2259 patients (mean age: 60 years; male: 52%; cardiovascular [CV] disease: 37%) met the selection criteria. Switching to nebivolol was associated with statistically significant reductions in the number of all-cause hospitalization (?33%; p?p?p?p?p?Conclusions:

This real-world study suggests that switching from metoprolol to nebivolol is associated with an increase in medication costs and significant reductions in hospitalizations and outpatient visits upon switching, resulting in an overall neutral effect on healthcare costs. These results may be interpreted with caution due to lack of a comparator group and confounding control caused by design and limitations inherent in insurance claims data.     

A review and validation of overall survival extrapolation in health technology assessments of cancer immunotherapy by the National Institute for Health and Care Excellence: how did the initial best estimate compare to trial data subsequently made available?

Background: Validation of overall survival (OS) extrapolations of immune-checkpoint inhibitors (ICIs) during the National Institute for Health and Care Excellence (NICE) Single Technology Assessment (STA) process is limited due to data still maturing at the time of submission. Inaccurate extrapolation may lead to inappropriate decision-making. The availability of more mature trial data facilitates a retrospective analysis of the plausibility and validity of initial extrapolations. This study compares these extrapolations to subsequently available longer-term data.

Methods: A systematic search of completed NICE appraisals of ICIs from March 2000 to December 2017 was performed. A targeted search was also undertaken to procure published OS data from the pivotal clinical trials for each identified STA made available post-submission to NICE. Initial Kaplan-Meier curves and associated extrapolations from NICE documentation were extracted to compare the accuracy of OS projections versus the most mature data.

Results: The review identified 11 STAs, of which 10 provided OS data upon submission to NICE. The extrapolations undertaken considered parametric or piecewise survival models. Additional data cut-offs provided a mean of 18 months of OS beyond the end of the original data. Initial extrapolations typically under-estimated OS from the most mature data cut-off by 0.4–2.7%, depending on the choice of assessment method and use of the manufacturer- or ERG-preferred extrapolation.

Conclusion: Long-term extrapolation of OS is required for NICE STAs based on initial immature OS data. The results of this study demonstrate that the initial OS extrapolations employed by manufacturers and ERGs generally predicted OS reasonably well when compared to more mature data (when available), although on average they appeared to underestimate OS. This review and validation shows that, while the choice of OS extrapolation is uncertain, the methods adopted are generally aligned with later-published follow-up data and appear appropriate for informing HTA decisions.     

Economic burden of chemotherapy-treated recurrent and/or metastatic squamous cell carcinoma of the head and neck in France: real-world data from the permanent sample of national health insurance beneficiaries

Aims: Overall survival (OS) of patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) is extremely poor. New therapeutic options emerge but need to establish their economic value. The objective was to describe the direct and related costs of R/M SCCHN in France.

Materials and methods: We selected all adult patients treated with chemotherapy for R/M SCCHN between 1 January 2009 and 31 December 2014 from the permanent sample of the French national health insurance database (EGB). Data were analyzed from the index date (first chemotherapy) until patients’ death or 31 December 2015. “Treatment period” and “end-of-life” (EoL) (from last chemotherapy until death) were distinguished. Costs included all hospitalizations for SCCHN and ambulatory care. Costs of hospitalized and non-hospitalized adverse events (AEs) were estimated.

Results: Among 267 patients identified, 85% were men, 44% had metastases at the index date and the mean age was 62.0 years (±9.9). The most common tumor location was oropharynx (29%) but 39% of patients had multiple locations. Median OS was 9.3 (95% CI: 7.9–11.8) months for the overall population. The average total direct cost per patient was €49,954, broken down into €32,908 (95% CI: 29,525–36,290) for hospitalizations and €17,047 (14,941–19,152) for ambulatory care. Main cost drivers were drug acquisition and administration (€14,538) during the treatment period (209?days on average) and palliative care (€3,750) during the EoL period (125?days). Regarding related costs, around 12% of patients received disability pensions (€1,397 per patient [624–2,171]) and sick leave payments (€1,592 [888–2,297]). “Metabolism and nutrition disorders” and “Infections and infestations” were the most expensive hospitalized AEs (€1,513 and €1,180 per patient, respectively). Febrile neutropenia was the most expensive non-hospitalized AE (€766 per patient).

Conclusions: This analysis of real-world data confirms the poor prognosis of patients with R/M SCCHN and provides cost data for future economic evaluations.     

Historical clinical and economic consequences of anemia management in patients with end-stage renal disease on dialysis using erythropoietin stimulating agents versus routine blood transfusions: a retrospective cost-effectiveness analysis

Abstract

Objective:

To determine whether Medicare’s decision to cover routine administration of erythropoietin stimulating agents (ESAs) to treat anemia of end-stage renal disease (ESRD) has been a cost-effective policy relative to standard of care at the time.

Methods:

The authors used summary statistics from the actual cohort of ESRD patients receiving ESAs between 1995 and 2004 to create a simulated patient cohort, which was compared with a comparable simulated cohort assumed to rely solely on blood transfusions. Outcomes modeled from the Medicare perspective included estimated treatment costs, life-years gained, and quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratio (ICER) was calculated relative to the hypothetical reference case of no ESA use in the transfusion cohort. Sensitivity of the results to model assumptions was tested using one-way and probabilistic sensitivity analyses.

Results:

Estimated total costs incurred by the ESRD population were $155.47B for the cohort receiving ESAs and $155.22B for the cohort receiving routine blood transfusions. Estimated QALYs were 2.56M and 2.29M, respectively, for the two groups. The ICER of ESAs compared to routine blood transfusions was estimated as $873 per QALY gained. The model was sensitive to a number of parameters according to one-way and probabilistic sensitivity analyses.

Limitations:

This model was counter-factual as the actual comparison group, whose anemia was managed via transfusion and iron supplements, rapidly disappeared following introduction of ESAs. In addition, a large number of model parameters were obtained from observational studies due to the lack of randomized trial evidence in the literature.

Conclusions:

This study indicates that Medicare’s coverage of ESAs appears to have been cost effective based on commonly accepted levels of willingness-to-pay. The ESRD population achieved substantial clinical benefit at a reasonable cost to society.