A cost-effectiveness model of smoking cessation based on a randomised controlled trial of varenicline versus placebo in patients with chronic obstructive pulmonary disease.

OBJECTIVES: Smoking is an important risk factor in chronic obstructive pulmonary disease (COPD). A recent clinical trial demonstrated the efficacy of varenicline versus placebo as an aid to smoking cessation in patients with COPD. This study examines the cost-effectiveness of varenicline from the perspective of the healthcare systems of Spain (base case), the UK, France, Germany, Greece and Italy. METHODS: A Markov model was developed to determine the cost-effectiveness of varenicline as an aid to smoking cessation, compared to a placebo, in a COPD population. Cost-effectiveness was determined by the incremental cost per quality-adjusted life year (QALY) gained. RESULTS: In the Spanish base case varenicline had an incremental cost of €1021/person for an average of 0.24 life years (0.17 QALYs), gained over the lifetime of a cohort of COPD patients, resulting in an incremental cost-effectiveness ratio (ICER) of €5,566. In the other European countries, the ICER varied between €4,519 (UK) and €10,167 (Italy). Probabilistic sensitivity analysis suggested varenicline had a high probability (>95%) of being cost-effective at a threshold of €30,000/QALY. CONCLUSIONS: Varenicline is expected to be a cost-effective aid to smoking cessation in COPD patients in all of the countries studied.

The impact of CT colonography for colorectal cancer screening on the UK NHS: costs, healthcare resources and health outcomes.

BACKGROUND: Biennial faecal occult blood testing (FOBT) for individuals aged 60-69 years is the primary screening tool for colorectal cancer (CRC) in the UK NHS, despite a large number of patients undergoing an unnecessary optical colonoscopy (OC) and evidence from modelling studies to suggest that more cost-effective technologies exist. CT colonography (CTC) is an emerging CRC screening technology with the potential to prevent CRC by detecting pre-cancerous polyps and to detect cancer at an earlier stage. OBJECTIVE: to assess the impact of introducing CTC into the UK NHS screening programme for CRC on key health outcomes as well as the NHS budget and healthcare resource capacity. METHODS: a discrete Markov model was used to reflect the natural history of CRC and the impact of three screening scenarios (biennial FOBT with and without CTC triage of patients referred to OC, and CTC every 5 years) on a range of health outcomes, including the incidence and prevalence of CRC, in a hypothetical cohort of individuals. The yearly costs, health outcomes and healthcare resource capacity requirements were estimated over a 10-year period (2009-18). RESULTS: using CTC to follow up FOBT-positive patients (scenario 2) was less costly than directing all FOBT-positive patients to OC (scenario 1); saving £776 283 over 10 years for 100 000 individuals invited for screening (year 2007 values), primarily by avoiding approximately 1700 OCs, but was estimated to require 2200 additional CT scans. Implementing a programme of 5-yearly CTC as a primary screen is expected to be more expensive than FOBT screening over the short term (driven by high screening and diagnosis costs), despite substantial savings in treatment costs for CRC over the 10-year time horizon of the model and improved health outcomes. CONCLUSIONS: adding CTC into the existing NHS Bowel Cancer Screening Programme as part of a preventive screening strategy could be less costly to the NHS over the longer term when used to triage FOBT-positive patients to appropriate follow-up. Increased demand for radiology services may be compensated for by reduced demand in endoscopy units.

Cost effectiveness of CT colonography for UK NHS colorectal cancer screening of asymptomatic adults aged 60-69 years.

BACKGROUND: Screening of populations at risk for colorectal cancer (CRC) allows the detection and successful treatment of tumours and their precursor polyps. The current UK CRC screening programme is faecal occult blood testing (FOBT), despite evidence from modelling studies to suggest that more cost-effective technologies exist. OBJECTIVE: To assess the cost effectiveness of CT colonography (CTC) for colorectal cancer screening from the perspective of the UK NHS. METHODS: A state-transition Markov model was constructed to estimate lifetime costs and health outcomes of a cohort of individuals screened at age 60-69 years using four different CRC screening technologies: FOBT, flexible sigmoidoscopy, optical colonoscopy and CTC. RESULTS: CTC screening offered every 10 years was cost saving compared with the current UK programme of biennial FOBT screening. This strategy also yielded greater health benefits (QALYs and life-years) than biennial FOBT screening. The model fit observed CRC epidemiology data well and was robust to changes in underlying parameter values. CTC remained cost effective under a range of assumptions in the univariate sensitivity analysis. However, in the probabilistic sensitivity analysis, CTC dominated FOBT in only 5.9% of simulations and was cost effective at a threshold of pound30,000 per QALY gained in 48% of simulations. CONCLUSIONS: CTC has the potential to provide a cost-effective option for CRC screening in the UK NHS and may be cost saving compared with the current programme of biennial FOBT. Further analysis is required to assess the impact of introducing CTC to the UK CRC screening programme on the NHS budget and capacity.

Cost of illness associated with Niemann-Pick disease type C in the UK.

OBJECTIVE: Niemann-Pick disease type C (NP-C) is a rare and devastating genetic disorder characterised by a range of progressive neurological symptoms, which imposes a burden on patients, family members, the healthcare system and society overall. The objective of this study was to assess direct and indirect costs associated with NP-C in the UK. METHODS: This was a non-interventional, retrospective, cross-sectional cohort study based on responses from patients and/or their carers/guardians recruited from a UK NP-C database. Resource use and direct medical, direct non-medical and indirect costs were evaluated using data collected via postal survey in October 2007, which included a Medical Resource Use questionnaire. Total annual costs per patient were estimated. RESULTS: In total, 18 Medical Resource Use questionnaires (29% response rate) were received and analysed. The mean total annual cost (SD) of NP-C per patient was 39,168 pounds (50,315 pounds); 46% were direct medical costs, to which home visits and residential care contributed 68% and 15%, respectively. Direct non-medical costs accounted for 24% of the average annual cost per patient, mainly due to specialist education, and indirect costs 30%. If only direct medical costs were considered, the mean annual cost (SD) per patient was reduced to 18,012 pounds (46,536 pounds). CONCLUSIONS: The direct annual per-patient cost of NP-C illness in 2007 appears moderate when compared with other rare and severely disabling diseases. However, cost estimates may be conservative, since findings are limited by a small sample size, low survey response rate and potential recall bias. As demonstrated by this study, a substantial proportion of the cost is shifted from the healthcare system to the patient, family and non-medical providers. These findings highlight the need for treatments that can slow or stop disease progression in NP-C.

Expression of CD33-related siglecs on human mononuclear phagocytes, monocyte-derived dendritic cells and plasmacytoid dendritic cells.

Siglecs are sialic acid binding Ig-like lectins mostly expressed in the haemopoietic and immune systems. Amongst the 11 human siglecs, there are eight proteins highly related to CD33 which have biochemical features of inhibitory receptors, containing two conserved tyrosine-based inhibitory motifs. Five of these (CD33/siglec-3, -5, -7, -9 and -10) are expressed on circulating monocytes. Here we show that monocytes cultured to differentiate into macrophages using either GM-CSF or M-CSF retained expression of these siglecs and their levels were unaffected following stimulation with LPS. In comparison, monocyte-derived dendritic cells down-modulated siglec-7 and -9 following maturation with LPS. Plasmacytoid dendritic cells in human blood expressed siglec-5 only. On monocytes, siglec-5 was shown to mediate rapid uptake of anti-siglec-5 (Fab)2 fragments into early endosomes. This suggests, in addition to inhibitory signalling, a potential role in endocytosis for siglec-5 and the other CD33-related siglecs. Our results show that siglecs are differentially expressed on mononuclear phagocytes and dendritic cells and that some can be modulated by stimuli that promote maturation and differentiation.

Ganglioside GD3 expression on target cells can modulate NK cell cytotoxicity via siglec-7-dependent and -independent mechanisms.

Siglec-7 is a sialic acid binding receptor with inhibitory potential, expressed on human NK cells and monocytes. It has an unusual binding preference for alpha2,8-linked disialic acids, such as those displayed by ganglioside GD3. Here we have investigated whether siglec-7-GD3 interactions are able to modulate NK cell cytotoxicity. Using synthetic polyacrylamide glycoprobes, siglec-7 was found to be masked at the NK cell surface but it could be unmasked by sialidase treatment of NK cells. GD3 synthase-transfected P815 target cells expressed high levels of GD3 and bound strongly to recombinant siglec-7-Fc protein. Surprisingly, GD3 synthase-transfected P815 cells were killed more effectively by untreated cells in a siglec-7-independent manner. However, following sialidase treatment of NK cells, a siglec-7-dependent inhibition of killing was observed. These findings have important implications for NK cell cytotoxicity against tumor cells like melanoma that express high levels of GD3 ganglioside.