Guiding the choice of analytic approach for economic evaluations of oncology treatments

Different modelling approaches are used to address the same decision problem but can lead to different estimates of life years gained and quality-adjusted life years. Three common methods are used in health economics: the partitioned (PSM), the state-transition (STM) and more recently the multi-state model (MSM). Novel methods were also identified to jointly model progression and survival using a copula to jointly model survival outcomes and MSMs with transitions estimated simultaneously. Differences in model predictions may have the propensity to change the conclusions of an economic analysis and the decisions made on the basis of such analyses. A simulation study was conducted to identify whether one approach is consistently superior to others under particular circumstances, or in general. The simulation study suggests that no single method is satisfactory in all circumstances and that approaches cannot be selected based on observed data characteristics alone. Case studies using real trial data also indicated that different assumptions could be made when modelling treatment effects, that PSMs and STMs may be inaccurate to varying degrees when estimating incremental outcomes and that neither is bias-free. This thesis demonstrated that it is not possible to determine with certainty a priori which approach to select, based only on the observed characteristics of the available data; thus, analysts and decision-makers need be careful when relying on predictions from a single approach. Recommendations are formulated to improve the transparency of health economic analyses and increase decision-makers’ confidence in the use of those models. Because it is unknown whether ICERs generated using a single analytic approach are adequate, in some cases, decision-making should consider ICERs from a range of alternative approaches to account for structural uncertainty. This thesis also highlights the importance of clinical input in selecting the most appropriate approach for the extrapolation of survival data

Gene expression profiling and expanded immunohistochemistry tests to guide selection of chemotherapy regimens in breast cancer management: a systematic review

OBJECTIVES: The aim of this report was to assess the clinical effectiveness of two Gene expression profiling (GEP) and two expanded immunohistochemistry (IHC) tests compared with current prognostic tools in guiding the use of adjuvant chemotherapy in patients with early breast cancer. METHODS: A systematic review of the evidence on clinical effectiveness of OncotypeDX, IHC4, MammaPrint and Mammostrat, compared with current clinical practice using clinicopathological parameters, in women with early breast cancer was conducted. Ten databases were searched to include citations to May 2016. RESULTS: Searches identified 7064 citations, of which 41 citations satisfied the criteria for the review. A narrative synthesis was performed. Evidence for OncotypeDX demonstrated the impact of the test on decision-making and there was some support for OncotypeDX predicting chemotherapy benefit. There were relatively lower levels of evidence for the other three tests included in the analysis. MammaPrint, Mammostrat and IHC4 tests were limited to a small number of studies. Limitations in relation to study design were identified for all tests. CONCLUSIONS: The evidence base for OncotypeDX is considered to be the most robust. Methodological weaknesses relating to heterogeneity of patient cohorts and issues arising from the retrospective nature of the evidence were identified. Further evidence is required for all of the tests using prospective randomised controlled trial data

Vedolizumab for Treating Moderately to Severely Active Crohn’s Disease After Prior Therapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost effectiveness of vedolizumab for the treatment of patients with moderate-to-severe, active Crohn’s disease. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned as the Evidence Review Group (ERG) and produced a critical review of the evidence of the clinical effectiveness and cost effectiveness of the technology, based upon the company’s submission to NICE. The GEMINI II and III trials formed the main supporting evidence for the intervention. Both studies were phase III, randomised, double-blind, placebo-controlled, multicentre trials designed to evaluate the efficacy and safety of vedolizumab. They included patients who were naïve to tumour necrosis factor alpha antagonist (anti-TNF-α) therapy and patients who had an inadequate response to, loss of response to or intolerance of immunomodulators or anti-TNF-α agents. GEMINI II was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment (dosing at weeks 0 and 2, with assessment at week 6) and maintenance treatment (during weeks 6–52). In contrast, GEMINI III was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment only, with doses at weeks 0, 2 and 6, and assessment at weeks 6 and 10. In the absence of any direct head-to-head, randomised, controlled trials comparing vedolizumab with other relevant biologic therapies (adalimumab and infliximab) for the treatment of moderate-to-severe Crohn’s disease, the company conducted a network meta-analysis, which compared vedolizumab, adalimumab, infliximab and placebo for the outcomes of clinical response, enhanced clinical response, clinical remission and discontinuation due to adverse events. The company model estimated the incremental cost-effectiveness ratio (ICER) for vedolizumab compared with the standard of care (consisting of 5-aminosalicylic acids, corticosteroids and immunosuppressants) to be £21,620 per quality-adjusted life-year (QALY) gained within the anti-TNF-α-failure population (which included a confidential patient access scheme for vedolizumab). The ICERs were above £30,000 per QALY gained for the mixed intention-to-treat population (including both anti-TNF-α-naïve and anti-TNF-α-failure populations) and in patients who were anti-TNF-α naïve only. The ERG identified a number of limitations that were believed to limit the robustness of the results presented by the company. These limitations could not be addressed by the ERG without major restructuring of the economic model. Therefore, the ERG concluded that the results from the company’s model needed to be interpreted with caution and that it was unclear whether the ICERs would increase or decrease following amendment of the identified structural issues

Obinutuzumab with Bendamustine for Treating Follicular Lymphoma Refractory to Rituximab: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of obinutuzumab (Roche) to submit evidence on its clinical and cost effectiveness when used in combination with bendamustine in patients with follicular lymphoma (FL) refractory to rituximab. The Evidence Review Group (ERG), the School of Health and Related Research Technology Appraisal Group at the University of Sheffield, produced a document summarising the key points from the company submission alongside a critical review. Efficacy for progression-free survival (PFS) and safety was positively demonstrated in the pivotal GADOLIN trial, which compared obinutuzumab in combination with bendamustine followed by obinutuzumab maintenance (O-Benda+O) against bendamustine monotherapy. Data on overall survival were immature. The company submitted a model-based economic analysis, including a patient access scheme. The ERG identified a number of limitations, in particular the absence of subgroup analysis and the approach used by the company to estimate overall survival (OS), which was more favourable to the intervention arm. The key uncertainty was the duration of the treatment effect on OS. This uncertainty is expected to be reduced when the final analysis of the GADOLIN trial is reported. Consequently, the NICE appraisal committee recommended O-Benda+O in the population covered by the marketing authorisation within the Cancer Drug Fund until NICE is able to review the guidance following publication of the final analysis of GADOLIN

Pirfenidone for Treating Idiopathic Pulmonary Fibrosis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

The National Institute for Health and Care Excellence (NICE) published guidance on the use of pirfenidone (Esbriet®, Roche) for the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF) in 2013. NICE decided to review existing guidance following publication of an additional clinical trial, and invited the manufacturer of pirfenidone to submit evidence of its clinical and cost effectiveness for the treatment of mild to moderate IPF when compared with best supportive care (BSC) or nintedanib; nintedanib was a comparator only for moderate IPF. An independent Evidence Review Group (ERG) critiqued the company submission and this paper summarises their report and subsequent NICE guidance. The key clinical effectiveness evidence was based on three randomised controlled trials (RCTs) and an open-label extension study. Supportive data were provided from two additional RCTs conducted in Japan, while one additional open-label study was included for safety outcomes. Meta-analysis of the three key RCTs found pirfenidone to be effective at reducing disease progression compared with placebo, but statistically significant differences were not identified in all of the RCTs. A statistically significant reduction in all-cause mortality was only demonstrated when pooling data across studies. The treatment effects of pirfenidone and nintedanib were broadly similar, based on an indirect comparison using network meta-analysis, although they have slightly different adverse event profiles. There remains considerable uncertainty in the cost-effectiveness estimates for pirfenidone versus BSC, particularly due to uncertainty regarding the duration of treatment effect and the method used to implement the stopping rule within the economic model

Cost-Effectiveness Modeling of Surgery Plus Adjuvant Endocrine Therapy Versus Primary Endocrine Therapy Alone in UK Women Aged 70 and Over With Early Breast Cancer

Objectives: Approximately 20% of UK women aged 70+ with early breast cancer receive primary endocrine therapy (PET) instead of surgery. PET reduces surgical morbidity but with some survival decrement. To complement and utilize a treatment dependent prognostic model, we investigated the cost-effectiveness of surgery plus adjuvant therapies versus PET for women with varying health and fitness, identifying subgroups for which each treatment is cost-effective. Methods: Survival outcomes from a statistical model, and published data on recurrence, were combined with data from a large, multicenter, prospective cohort study of over 3400 UK women aged 70+ with early breast cancer and median 52-month follow-up, to populate a probabilistic economic model. This model evaluated the cost-effectiveness of surgery plus adjuvant therapies relative to PET for 24 illustrative subgroups: Age {70, 80, 90} × Nodal status {FALSE (F), TRUE (T)} × Comorbidity score {0, 1, 2, 3+}. Results: For a 70-year-old with no lymph node involvement and no comorbidities (70, F, 0), surgery plus adjuvant therapies was cheaper and more effective than PET. For other subgroups, surgery plus adjuvant therapies was more effective but more expensive. Surgery plus adjuvant therapies was not cost-effective for 4 of the 24 subgroups: (90, F, 2), (90, F, 3), (90, T, 2), (90, T, 3). Conclusion: From a UK perspective, surgery plus adjuvant therapies is clinically effective and cost-effective for most women aged 70+ with early breast cancer. Cost-effectiveness reduces with age and comorbidities, and for women over 90 with multiple comorbidities, there is little cost benefit and a negative impact on quality of life

Healthcare costs and productivity losses directly attributable to ankylosing spondylitis

This study shows that direct healthcare costs alone do not describe the total costs associated with AS and that productivity losses associated with AS are considerable

Effect of Precursor Concentration on Structural Optical and Electrical Properties of NiO Thin Films Prepared by Spray Pyrolysis

Undoped nickel oxide (NiO) thin films were deposited on 500°C heated glass substrates using spray pyrolysis method at (0.015–0.1 M) range of precursor. The latter was obtained by decomposition of nickel nitrate hexahydrate in double distilled water. Effect of precursor concentration on structural, optical, and electrical properties of NiO thin films was investigated. X-ray diffraction (XRD) shows the formation of NiO under cubic structure with single diffraction peak along (111) plane at 2θ=37.24°. When precursor concentration reaches 0.1 M, an increment in NiO crystallite size over 37.04 nm was obtained indicating the product nano structure. SEM images reveal that beyond 0.04 M as precursor concentration the substrate becomes completely covered with NiO and thin films exhibit formation of nano agglomerations at the top of the sample surface. Ni-O bonds vibrations modes in the product of films were confirmed by FT-IR analysis. Transparency of the films ranged from 57 to 88% and band gap energy of the films decreases from 3.68 to 3.60 eV with increasing precursor concentration. Electrical properties of the elaborated NiO thin films were correlated to the precursor concentration

Estimated effect of alcohol pricing policies on health and health economic outcomes in England: an epidemiological model

Background Although pricing policies for alcohol are known to be effective, little is known about how specific interventions affect health-care costs and health-related quality-of-life outcomes for different types of drinkers. We assessed effects of alcohol pricing and promotion policy options in various population subgroups. Methods We built an epidemiological mathematical model to appraise 18 pricing policies, with English data from the Expenditure and Food Survey and the General Household Survey for average and peak alcohol consumption. We used results from econometric analyses (256 own-price and cross-price elasticity estimates) to estimate effects of policies on alcohol consumption. We applied risk functions from systemic reviews and meta-analyses, or derived from attributable fractions, to model the effect of consumption changes on mortality and disease prevalence for 47 illnesses. Findings General price increases were effective for reduction of consumption, health-care costs, and health-related quality of life losses in all population subgroups. Minimum pricing policies can maintain this level of effectiveness for harmful drinkers while reducing effects on consumer spending for moderate drinkers. Total bans of supermarket and off-license discounting are effective but banning only large discounts has little effect. Young adult drinkers aged 18–24 years are especially affected by policies that raise prices in pubs and bars. Interpretation Minimum pricing policies and discounting restrictions might warrant further consideration because both strategies are estimated to reduce alcohol consumption, and related health harms and costs, with drinker spending increases targeting those who incur most harm