Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis for febrile neutropenia in patients with non-Hodgkin's lymphoma in the United Kingdom (UK)

Introduction: We report a cost-effectiveness evaluation of granulocyte colony-stimulating factors (G-CSFs) for prevention of febrile neutropenia (FN) following chemotherapy for non-Hodgkin’s lymphoma (NHL) in the United Kingdom (UK). Methods: A mathematical model was constructed simulating the experience of patients with NHL undergoing chemotherapy. Three strategies were modelled: primary prophylaxis (G-CSFs administered in all cycles); secondary prophylaxis (G-CSFs administered in all cycles following an FN event), and no G-CSF prophylaxis. Three G-CSFs were considered: filgrastim; lenograstim and pegfilgrastim. Costs were taken from UK databases and utility values from published sources with the base case analysis using list prices for G-CSFs and a willingness to pay (WTP) threshold of £20,000 per QALY gained. A systematic review provided data on G-CSF efficacy. Probabilistic sensitivity analyses examined the effects of uncertainty in model parameters. Results: In the base-case analysis the most cost-effective strategy was primary prophylaxis with pegfilgrastim for a patient with baseline FN risk greater than 22%, secondary prophylaxis with pegfilgrastim for baseline FN risk 8-22%, and no G-CSFs for baseline FN risk less than 8%. Using a WTP threshold of £30,000, primary prophylaxis with pegfilgrastim was cost-effective for baseline FN risks greater than 16%. In all analyses, pegfilgrastim dominated filgrastim and lenograstim. Sensitivity analyses demonstrated that higher WTP threshold, younger age, or reduced G-CSF prices result in G-CSF prophylaxis being cost-effective at lower baseline FN risk levels. Conclusions: Pegfilgrastim was the most cost-effective G-CSF. The most cost-effective strategy (primary or secondary prophylaxis) was dependent on underlying FN risk level, patient age, and G-CSF price

Consistency between direct trial evidence and Bayesian Mixed Treatment Comparison: Is head-to-head evidence always more reliable?

Objectives: This study aims to highlight the benefits of Bayesian mixed treatment comparison (MTC), within a case study of the efficacy of three treatments (pegfilgrastim, filgrastim and lenograstim) for the prevention of febrile neutropenia (FN) following chemotherapy. Methods: Two published meta-analyses have assessed the relative efficacy of the three treatments based on head-to-head trials. In the present study, all the trials from these meta-analyses were synthesised within a single network in a Bayesian MTC. Following a systematic review, the evidence base was then updated to include further recently-published trials. The metaanalyses and MTC were re-analysed using the updated evidence base. Results: Using data from the previously-published meta-analyses only, the relative risk of FN for pegfilgrastim vs. no treatment was estimated at 0.08 (95% confidence interval: 0.03, 0.18) from the head-to-head trial and 0.27 (95% credible interval: 0.12, 0.60) from the MTC, reflecting strong inconsistency between the results of the direct and indirect methodologies. When subsequently-published head-to-head trials were included, the meta-analysis estimate increased to 0.29 (95% confidence interval: 0.15, 0.55), while the MTC gave a relative risk of 0.34 (95% credible interval: 0.23, 0.54). The initial MTC results were therefore a better predictor of subsequent study results than was the direct trial. The MTC was also able to estimate the probability that there were clinically significant difference in efficacy between the treatments. Conclusions: Bayesian MTC provides clinically relevant information, including a measure of the consistency of direct and indirect evidence. Where inconsistency exists, it should not always be assumed that the direct evidence is more appropriate

The psychometric properties of ADCS - activities of daily living inventory and comparison of different ADL scores

Several multi-item activities of daily living (ADL) scales have been developed for assessment of functional status of patients with Alzheimer’s Disease (AD) in the last few decades. A disadvantage of the large number of scales is that scores of different ADL scales cannot be compared directly with each other. ADL scales which are used by McNamee’s (Townsend's disability scale) and Hill’s (Medicare Beneficiary definitions and Katz index of ADL) provide suitable tools for modelling the cost-effectiveness of different treatments in patients with Alzheimer’s disease, since they report empirical results about the relationship between the degree of functional impairment (healthcare costs) and the prevalence of institutionalisation. The IDEAL trial examines the efficacy of Exelon Patch with the ADCS - Activities of Daily Living Inventory (ADCS-ADL). This ADL instrument is not directly comparable to the ADL scales used by McNamee and Hill. However, the use of the ADL scale from the IDEAL study to predict the prevalence of institutionalisation with scales by Hill and McNamee would be desirable. Because of the generic nature of the ADL construct, and considering the fact that these well validated ADL instruments identify the main physical impairments and functional disabilities in Alzheimer's disease, we should expect high overlap in item content between different ADL instruments. The high overlap in item content between instruments, and the similar wording and scoring criteria, makes it possible to pair each impairment with another. The intention of this study was to establish the link between these ADL scales in order to provide appropriate conditions for further economic analyses on the dataset provided by the IDEAL study

Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis: systematic review and mixed method treatment comparison

Background This study assesses the efficacy of three granulocyte colony-stimulating factors (G-CSFs; pegfilgrastim, filgrastim and lenograstim) in preventing febrile neutropenia (FN). Methods A systematic review was undertaken. Head-to-head studies were combined using direct meta-analyses. In addition, an indirect Bayesian mixed treatment comparison (MTC) was undertaken to facilitate comparison between G-CSFs where there were no direct trials, and to allow data from all trials to be synthesised into a coherent set of results. Results The review identified the following studies comparing G-CSF prophylaxis to no primary G-CSF prophylaxis: 5 studies of pegfilgrastim, 9 studies of filgrastim and 5 studies of lenograstim. In addition, 5 studies were identified comparing pegfilgrastim to filgrastim. The two synthesis methods (meta-analysis and MTC) demonstrated that all three G-CSFs significantly reduced FN rate. Pegfilgrastim reduced FN rate to a greater extent than filgrastim (significantly in the head-to-head meta-analysis and in the MTC of all studies, and not quite significantly when the MTC was restricted to RCTs only). In the absence of direct trials, the MTC gave an 80-86% probability that pegfilgrastim is superior to lenograstim in preventing FN, and a 71-72% probability that lenograstim is superior to filgrastim. Conclusions Prophylaxis with G-CSFs significantly reduces FN rate. A head-to-head meta-analysis shows pegfilgrastim to be significantly superior to filgrastim in preventing FN events, while an MTC demonstrates that pegfilgrastim is likely to be superior to lenograstim

Granulocyte colony-stimulating factors for prevention of febrile neutropenia following chemotherapy: systematic review and meta-analysis

Background: Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs) stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy. Methods: A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in preventing FN in adults undergoing chemotherapy for solid tumours or lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one another. Nine databases were searched in December 2009. Meta-analysis used a random effects model due to heterogeneity. Results: Twenty studies compared primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 – 0.65) for pegfilgrastim, 0.57 (95% CI: 0.48 – 0.69) for filgrastim, and 0.62 (95% CI: 0.44 – 0.88) for lenograstim. Five studies compared pegfilgrastim with filgrastim; FN incidence was significantly lower for pegfilgrastim than filgrastim, with relative risk 0.66 (95% CI: 0.44 – 0.98). Conclusions: Primary prophylaxis with G-CSFs significantly reduces FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. Pegfilgrastim reduces FN incidence to a significantly greater extent than filgrastim

Consistency between direct trial evidence and Bayesian Mixed Treatment Comparison: Is head-to-head evidence always more reliable?

Objectives This study aims to highlight the benefits of Bayesian mixed treatment comparison (MTC), within a case study of the efficacy of three treatments (pegfilgrastim, filgrastim and lenograstim) for the prevention of febrile neutropenia (FN) following chemotherapy. Methods Two published meta-analyses have assessed the relative efficacy of the three treatments based on head-to-head trials. In the present study, all the trials from these meta-analyses were synthesised within a single network in a Bayesian MTC. Following a systematic review, the evidence base was then updated to include further recently-published trials. The metaanalyses and MTC were re-analysed using the updated evidence base. Results Using data from the previously-published meta-analyses only, the relative risk of FN for pegfilgrastim vs. no treatment was estimated at 0.08 (95% confidence interval: 0.03, 0.18) from the head-to-head trial and 0.27 (95% credible interval: 0.12, 0.60) from the MTC, reflecting strong inconsistency between the results of the direct and indirect methodologies. When subsequently-published head-to-head trials were included, the meta-analysis estimate increased to 0.29 (95% confidence interval: 0.15, 0.55), while the MTC gave a relative risk of 0.34 (95% credible interval: 0.23, 0.54). The initial MTC results were therefore a better predictor of subsequent study results than was the direct trial. The MTC was also able to estimate the probability that there were clinically significant difference in efficacy between the treatments. Conclusions Bayesian MTC provides clinically relevant information, including a measure of the consistency of direct and indirect evidence. Where inconsistency exists, it should not always be assumed that the direct evidence is more appropriate

Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis for febrile neutropenia in patients with non-Hodgkin's lymphoma in the United Kingdom (UK)

Introduction: We report a cost-effectiveness evaluation of granulocyte colony-stimulating factors (G-CSFs) for prevention of febrile neutropenia (FN) following chemotherapy for non-Hodgkin’s lymphoma (NHL) in the United Kingdom (UK). Methods: A mathematical model was constructed simulating the experience of patients with NHL undergoing chemotherapy. Three strategies were modelled: primary prophylaxis (G-CSFs administered in all cycles); secondary prophylaxis (G-CSFs administered in all cycles following an FN event), and no G-CSF prophylaxis. Three G-CSFs were considered: filgrastim; lenograstim and pegfilgrastim. Costs were taken from UK databases and utility values from published sources with the base case analysis using list prices for G-CSFs and a willingness to pay (WTP) threshold of £20,000 per QALY gained. A systematic review provided data on G-CSF efficacy. Probabilistic sensitivity analyses examined the effects of uncertainty in model parameters. Results: In the base-case analysis the most cost-effective strategy was primary prophylaxis with pegfilgrastim for a patient with baseline FN risk greater than 22%, secondary prophylaxis with pegfilgrastim for baseline FN risk 8-22%, and no G-CSFs for baseline FN risk less than 8%. Using a WTP threshold of £30,000, primary prophylaxis with pegfilgrastim was cost-effective for baseline FN risks greater than 16%. In all analyses, pegfilgrastim dominated filgrastim and lenograstim. Sensitivity analyses demonstrated that higher WTP threshold, younger age, or reduced G-CSF prices result in G-CSF prophylaxis being cost-effective at lower baseline FN risk levels. Conclusions: Pegfilgrastim was the most cost-effective G-CSF. The most cost-effective strategy (primary or secondary prophylaxis) was dependent on underlying FN risk level, patient age, and G-CSF price

Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis for febrile neutropenia in breast cancer in the United Kingdom

Introduction: We report a cost-effectiveness evaluation of granulocyte colony–stimulating factors (G-CSFs) for the prevention of febrile neutropenia (FN) after chemotherapy in the United Kingdom (UK). Methods: A mathematical model was constructed simulating the experience of women with breast cancer undergoing chemotherapy. Three strategies were modelled: primary prophylaxis (G-CSFs administered in all cycles), secondary prophylaxis (G-CSFs administered in all cycles after an FN event), and no G-CSF prophylaxis. Three G-CSFs were considered: filgrastim, lenograstim, and pegfilgrastim. Costs were taken from UK databases and utility values from published sources. A systematic review provided data on G-CSF efficacy. Probabilistic sensitivity analyses examined the effects of uncertainty in model parameters. Results: In the UK, base-case analysis with a willingness-to-pay (WTP) threshold of £20,000 per quality-adjusted life-year gained and using list prices, the most cost-effective strategy was primary prophylaxis with pegfilgrastim for a patient with baseline FN risk greater than 38%, secondary prophylaxis with pegfilgrastim for baseline FN risk 11% to 37%, and no G-CSFs for baseline FN risk less than 11%. Using a WTP threshold of £30,000 and list prices, primary prophylaxis with pegfilgrastim was cost-effective for baseline FN risks greater than 29%. In all analyses, pegfilgrastim dominated filgrastim and lenograstim. Sensitivity analyses demonstrated that higher WTP threshold, younger age, earlier stage at diagnosis, or reduced G-CSF prices result in G-CSF prophylaxis being cost-effective at lower baseline FN risk levels. Conclusion: Pegfilgrastim was the most cost-effective G-CSF. The most cost-effective strategy (primary or secondary prophylaxis) was dependent on the FN risk level for an individual patient, patient age and stage at diagnosis, and G-CSF price

The effect of cultural and environmental factors on potato seed tuber morphology and subsequent sprout and stem development

Seed crops of the variety Estima were grown in each of 2 years using two planting dates, two harvest dates, two plant densities and two irrigation regimes to produce seed tubers which had experienced different cultural and environmental conditions. The effects of these treatments on tuber characteristics, sprout production and stem development in the ware crop were then determined in subsequent experiments using storage regimes of 3 and 10 °C. Time of planting the seed crop affected numbers of eyes, sprouts and above ground stems in the subsequent ware crop because environmental conditions around the time of tuber initiation appeared to alter tuber shape. Cooler, wetter conditions in the 7 days after tuber initiation were associated with tubers which were longer, heavier and had more eyes, sprouts and above ground stems. In contrast, the time of harvesting the seed crop did not affect tuber shape or numbers of above ground stems and there was no interaction with tuber size. The density of the seed crop had no effect on any character measured and irrigation well after tuber initiation did not affect tuber shape, numbers of sprouts or numbers of stems. Seed production treatments, which resulted in earlier dormancy break, were associated with tubers that produced more sprouts and above ground stems, in contrast to the conventional understanding of apical dominance. Storage at 3 °C gave fewer sprouts, a lower proportion of eyes with sprouts and fewer stems than storage at 10 °C. The major effects on stem production appear to result from environmental conditions at the time of tuber initiation of the seed crop and sprouting temperature

Cost-effectiveness of eplerenone in patients with systolic heart failure and mild symptoms

Aim In the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), aldosterone blockade with eplerenone decreased mortality and hospitalisation in patients with mild symptoms (New York Heart Association class II) and chronic systolic heart failure (HF). The present study evaluated the cost-effectiveness of eplerenone in the treatment of these patients in the UK and Spain.<p></p> Methods and results Results from the EMPHASIS-HF trial were used to develop a discrete-event simulation model estimating lifetime direct costs and effects (life years and quality-adjusted life years (QALYs) gained) of the addition of eplerenone to standard care among patients with chronic systolic HF and mild symptoms. Eplerenone plus standard care compared with standard care alone increased lifetime direct costs per patient by £4284 for the UK and €7358 for Spain, with additional quality-adjusted life expectancy of 1.22 QALYs for the UK and 1.33 QALYs for Spain. Mean lifetime costs were £3520 per QALY in the UK and €5532 per QALY in Spain. Probabilistic sensitivity analysis suggested a 100% likelihood of eplerenone being regarded as cost-effective at a willingness-to-pay threshold of £20 000 per QALY (UK) or €30 000 per QALY (Spain).<p></p> Conclusions By currently accepted standards of value for money, the addition of eplerenone to optimal medical therapy for patients with chronic systolic HF and mild symptoms is likely to be cost-effective.<p></p&gt