-
[show abstract]
[hide abstract]
ABSTRACT: The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of rituximab (RTX) [Roche] to submit evidence for the clinical and cost effectiveness of RTX as first-line maintenance treatment for patients with follicular non-Hodgkin's lymphoma (fNHL) whose disease has responded to induction therapy with RTX plus cytotoxic chemotherapy (R-CTX) in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the manufacturer and provides a summary of the Appraisal Committee's (AC) decision. The clinical evidence was derived from a multi-centred, open-label, randomized phase III study (PRIMA) comparing first-line maintenance treatment with RTX with observation only in 1,018 patients with previously untreated advanced fNHL. Median time to event (MTE) for the primary endpoint of progression-free survival (PFS) in the RTX arm was not estimable due to data immaturity; median PFS in the observation arm was 48.36 months. A statistically significant benefit of RTX maintenance therapy for PFS was reported (hazard ratio [HR] 0.55, 95 % CI 0.44-0.68; p < 0.0001). Statistically significant differences in favour of RTX were also reported for a range of secondary endpoints. Assessment of overall survival benefit could be not made due to insufficient events. The ERG's main concern with the clinical-effectiveness data presented was their lack of maturity. The submitted incremental cost-effectiveness ratio was within the NICE threshold. The ERG questioned the model on a number of grounds, particularly the use of Markov methodology rather than patient simulations, the impact of patient age on the outcome and the projective PFS modelling. The ERG considered it impossible to draw firm conclusions regarding the clinical or cost effectiveness of the intervention as the dataset was as yet too immature. At a third meeting, the AC concluded that RTX could be recommended as first-line maintenance treatment for patients with fNHL whose disease has responded to induction R-CTX.
PharmacoEconomics 04/2013; · 2.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Warfarin is a highly effective anticoagulant however its effectiveness relies on maintaining INR in therapeutic range. Finding the correct dose is difficult due to large inter-individual variability. Two genes, CYP2C9 and VKORC1, have been associated with this variability, leading to genotype-guided dosing tables in warfarin labeling. Nonetheless, it remains unclear how genotypic information should be used in practice. Navigating the literature to determine how genotype will influence warfarin response in a particular patient is difficult, due to significant variation in patient ethnicity, outcomes investigated, study design, and methodological rigor. Our systematic review was conducted to enable fair and accurate interpretation of which variants affect which outcomes, in which patients, and to what extent.
A comprehensive search strategy was applied and 117 studies included. Primary outcomes were stable dose, time to stable dose and bleeding events. Methodological quality was assessed using criteria of Jorgensen and Williamson and data synthesized in meta-analyses using advanced methods. Pooled effect estimates were significant in most ethnic groups for CYP2C9*3 and stable dose (mutant types requiring between 1.1(0.7-1.5) and 2.3 (1.6-3.0)mg/day). Effect estimates were also significant for VKORC1 and stable dose for most ethnicities, although direction differed between asians and non-asians (mutant types requiring between 0.8(0.4-1.3) and 1.5(1.1-1.8)mg/day more in asians and between 1.5(0.7-2.2) and 3.1(2.7-3.6)mg/day less in non-asians). Several studies were excluded due to inadequate data reporting. Assessing study quality highlighted significant variability in methodological rigor. Notably, there was significant evidence of selective reporting, of outcomes and analysis approaches.
Genetic associations with warfarin response vary between ethnicities. In order to achieve unbiased estimates in different populations, a high level of methodological rigor must be maintained and studies should report sufficient data to enable inclusion in meta-analyses. We propose minimum reporting requirements, suggest methodological guidelines and provide recommendations for reducing the risk of selective reporting.
PLoS ONE 01/2012; 7(8):e44064. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The UK National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of erlotinib (Roche) to submit evidence for the clinical and cost effectiveness of erlotinib as monotherapy for the maintenance treatment of patients with non-small cell lung cancer (NSCLC) and stable disease following previous treatment with four cycles of platinum-containing therapy. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG) for this appraisal. The ERG reviewed the clinical- and cost-effectiveness evidence in two stages and in accordance with the decision problem defined by NICE. The analysis of the submitted models assessed the appropriateness of the approach taken by the manufacturer in modelling the decision problem. Analysis also included reliability of model implementation and the extent of conformity to published standards and prevailing norms of practice within the health economics modelling community. Particular attention was paid to issues likely to have substantial impact on the base-case cost-effectiveness results. Clinical evidence was derived from a multi-centre, double-blind, randomized, phase III study designed to address the overall population of NSCLC patients. Outcomes included progression-free survival (PFS) and overall survival (OS). The recruited population was mainly from outside of Western Europe and no patients in the pivotal trial had received pemetrexed as a first-line therapy, which is now accepted clinical practice in the UK. The evidence considered in this article includes only the population for whom marketing authorizations has been received--that is, patients with stable disease following first-line therapy. The trial reported a small but statistically significant increase in both PFS and OS in patients with stable disease receiving erlotinib compared with placebo. However, no significant difference was identified in OS when patients with non-squamous disease and stable disease were considered as a subgroup. The economic evidence was focussed on the ERG's assessment of three economic models that related to patients with stable disease and compared erlotinib with placebo in the squamous and non-squamous populations and erlotinib with pemetrexed in the non-squamous population. The incremental cost-effectiveness ratios (ICERs) reported by the manufacturer were £39,936 per QALY gained (stable disease, all); £35,491 per QALY gained (stable disease, squamous); and £40,020 per QALY gained (stable disease, non-squamous). In comparison with pemetrexed, in the cases where erlotinib was considered to be superior or equivalent, erlotinib dominated. In the cases where erlotinib was considered to be slightly inferior, then the ICERs ranged between £91,789 and £511,351 per QALY gained; these ICERs appear in the south-west corner of a cost-effectiveness plane, i.e. erlotinib is cheaper but less effective than pemetrexed. The ERG recalculated the base-case cost-effectiveness results in the manufacturer's submission, considering nine key areas where corrections and/or adjustments were required, related to time horizon, discounting logic, costs of erlotinib and pemetrexed, cost of second-line chemotherapy, unit costs, utility values, PFS and OS. This resulted in ERG-revised ICERs for the stable disease squamous population of £44,812 per QALY gained, in the stable disease non-squamous population of £68,120 per QALY gained, and, when erlotinib was compared with pemetrexed, the result was £84,029 per QALY gained. All values were above NICE's perceived willingness-to-pay threshold. After the second Appraisal Committee meeting, the Committee did not recommend the use of erlotinib in this patient population.
PharmacoEconomics 10/2011; 29(12):1051-62. · 2.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Alcohol dependence affects approximately 3% of the English population, and accounts for significant medical and psychiatric morbidity. Only 5.6% of alcohol-dependent individuals ever access specialist treatment and only a small percentage ever seek treatment. As people who are alcohol dependent are more likely to have experienced health problems leading to frequent attendance at acute hospitals it would seem both sensible and practical to ensure that this setting is utilised as a major access point for treatment, and to test the effectiveness of these treatments.
This is a randomised controlled trial with a primary hypothesis that extended brief interventions (EBI) delivered to alcohol-dependent patients in a hospital setting by an Alcohol Specialist Nurse (ASN) will be effective when compared to usual care in reducing overall alcohol consumption and improving on the standard measures of alcohol dependence. Consecutive patients will be screened for alcohol misuse in the Emergency Department (ED) of a district general hospital. On identification of an alcohol-related problem, following informed written consent, we aim to randomize 130 patients per group. The ASN will discharge to usual clinical care all control group patients, and plan a programme of EBI for treatment group patients. Follow-up interview will be undertaken by a researcher blinded to the intervention at 12 and 24 weeks. The primary outcome measure is level of alcohol dependence as determined by the Severity of Alcohol Dependence Questionnaire (SADQ) score. Secondary outcome measures include; Alcohol Use Disorders Identification Test (AUDIT) score, quantity and frequency of alcohol consumption, health-related quality of life measures, service utilisation, and patient experience. The trial will also allow an assessment of the cost-effectiveness of EBI in an acute hospital setting. In addition, patient experience will be assessed using qualitative methods.
This paper presents a protocol for a RCT of EBI delivered to alcohol dependent patients by an ASN within an ED. Importantly; the trial will also seek to understand patients' perceptions and experiences of being part of a RCT and of receiving this form of intervention.
ISRCTN: ISRCTN78062794.
BMC Public Health 01/2011; 11:528. · 2.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The introduction of a quadrivalent human papillomavirus (HPV; types 6, 11, 16, 18) vaccine is expected to significantly reduce the burden of cervical cancer, cervical intraepithelial neoplasia (CIN), genital warts and other HPV-related diseases.
To determine the cost effectiveness of providing a quadrivalent (6,11,16,18) HPV vaccine programme in adolescent females aged 12 years in addition to the existing cervical cancer screening programme in Belgium.
A Markov state-transition model was developed for the Belgian context in order to evaluate the long-term impact of vaccinating a cohort of girls aged 12 years alongside the existing screening programme. Women were followed until the age of 85 years. A vaccine that would prevent 100% of diseases associated with HPV-6, -11, -16 and -18, with lifetime duration of efficacy, 80% coverage, in conjunction with current screening, was compared with screening alone. For this analysis, 35% of cases of CIN-1, 55% of CIN-2/3, 75% of cervical cancer and 90% of genital warts were considered to be attributable to HPV-6, -11, -16 or -18. The model estimated lifetime risks and total lifetime healthcare costs, survival and QALYs for cervical cancer, CIN and genital warts. Outcomes validation was applied. Model outcomes also included incremental costs per life-year gained and incremental costs per QALY gained. The analysis was conducted from the perspective of the Belgian healthcare payer, and costs were in year 2006 values.
The model estimated a reduction in the lifetime risk of cervical cancer from 0.94% to 0.34%, therefore preventing 362 cases of cervical cancer and 131 related deaths in a cohort of 60,000 girls aged 12 years in Belgium. The base-case scenario suggests quadrivalent HPV vaccination in addition to current cervical screening in Belgium to be cost effective at euro 10,546 per QALY. This is within the accepted range of cost-effective interventions in Europe. This cost effectiveness is maintained for different parameter assumptions in the sensitivity analysis, with the exception of very high discount rates for costs and medical benefits, but, even in the worst case, ratios were still less than euro 50,000 per QALY. Even when a separate scenario modelled the requirement for a booster vaccination to sustain a lifetime duration of protection, the results remained cost effective at eruo 17,388 per QALY.
Vaccination with a quadrivalent HPV vaccine appears to be a cost-effective public health intervention in conjunction with the existing screening programme in Belgium. The additional costs of introducing vaccination to the established screening programme would be offset by the potential savings from not having to treat the diseases caused by HPV-6, -11, -16 or -18.
PharmacoEconomics 02/2009; 27(3):231-45. · 2.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Background
Background The introduction of a quadrivalent human papillomavirus (HPV; types 6, 11, 16, 18) vaccine is expected to significantly reduce the burden of cervical cancer, cervical intraepithelial neoplasia (CIN), genital warts and other HPV-related diseases. Abstract: Objective
Objective To determine the cost effectiveness of providing a quadrivalent (6,11,16,18) HPV vaccine programme in adolescent females aged 12 years in addition to the existing cervical cancer screening programme in Belgium. Abstract: Methods
Methods A Markov state-transition model was developed for the Belgian context in order to evaluate the long-term impact of vaccinating a cohort of girls aged 12 years alongside the existing screening programme. Women were followed until the age of 85 years. A vaccine that would prevent 100% of diseases associated with HPV-6, -11, -16 and -18, with lifetime duration of efficacy, 80% coverage, in conjunction with current screening, was compared with screening alone. For this analysis, 35% of cases of CIN-1, 55% of CIN-2/3, 75% of cervical cancer and 90% of genital warts were considered to be attributable to HPV-6, -11, -16 or -18. The model estimated lifetime risks and total lifetime healthcare costs, survival and QALYs for cervical cancer, CIN and genital warts. Outcomes validation was applied. Model outcomes also included incremental costs per life-year gained and incremental costs per QALY gained. The analysis was conducted from the perspective of the Belgian healthcare payer, and costs were in year 2006 values. Abstract: ResultsResults The model estimated a reduction in the lifetime risk of cervical cancer from 0.94% to 0.34%, therefore preventing 362 cases of cervical cancer and 131 related deaths in a cohort of 60 000 girls aged 12 years in Belgium. The base-case scenario suggests quadrivalent HPV vaccination in addition to current cervical screening in Belgium to be cost effective at &U20AC;10 546 per QALY. This is within the accepted range of cost-effective interventions in Europe. This cost effectiveness is maintained for different parameter assumptions in the sensitivity analysis, with the exception of very high discount rates for costs and medical benefits, but, even in the worst case, ratios were still less than &U20AC;50 000 per QALY. Even when a separate scenario modelled the requirement for a booster vaccination to sustain a lifetime duration of protection, the results remained cost effective at &U20AC;17 388 per QALY. Abstract: Conclusions
Conclusions Vaccination with a quadrivalent HPV vaccine appears to be a cost-effective public health intervention in conjunction with the existing screening programme in Belgium. The additional costs of introducing vaccination to the established screening programme would be offset by the potential savings from not having to treat the diseases caused by HPV-6, -11, -16 or -18.
PharmacoEconomics 01/2009; 27(3):231-245. · 2.66 Impact Factor
