Biomedical subjects
Publications and source records attributed to J Karnon.
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OBJECTIVE: To assess the long-term cost effectiveness of 1 year's treatment with clopidogrel on top of standard therapy (including aspirin; ASA) compared with standard therapy alone, in patients diagnosed with non-ST-segment-elevation acute coronary syndromes (ACS) in the UK. DESIGN: Cost utility analysis using a Markov model, incorporating clinical data from CURE (a multicentre randomised controlled trial, involving 12,562 patients) and data from UK observational studies. SETTING: Health economic evaluation carried out from the perspective of the UK NHS. PATIENTS: A representative cohort of 1000 UK patients aged 66 years, diagnosed with non-ST-segment-elevation ACS. INTERVENTIONS: Either a combination of 75 mg/day clopidogrel (300 mg loading dose, within 24 h prior to hospital admission) and standard therapy (including ASA, 75-325 mg/day) for 1 year followed by standard therapy alone for their remaining lifetime, or standard therapy alone (including ASA, 75-325 mg/day) for life. MAIN OUTCOME MEASURES: Incremental cost per life-year gained and incremental cost per quality-adjusted life-year (QALY) gained. RESULTS: In the base case, the incremental cost effectiveness of the clopidogrel combination vs standard therapy alone is estimated as pounds 6991 per life-year gained and pounds 7365 per QALY gained. The probability that clopidogrel remains cost effective within the generally accepted pounds 30,000 per QALY threshold is more than 80%. The confidence interval around the relative risk for vascular death was identified as the main parameter affecting the estimated cost effectiveness. CONCLUSIONS: One year's treatment with clopidogrel is a cost effective intervention compared with standard therapy that should be considered as a routine treatment for patients with non-ST-segment-elevation ACS.
OBJECTIVES: To update an earlier published report reviewing the effectiveness and cost-effectiveness of liquid-based cytology (LBC). DATA SOURCES: Electronic bibliographic databases, relevant articles, sponsor submissions and various health services research-related resources. REVIEW METHODS: The selected data were reviewed and assessed with respect to the quality of the evidence. Pooled estimates of the parameters of interest were derived from the original and the updated studies. Meta-analyses were undertaken where appropriate. The mathematical model developed for the original rapid review of LBC was adapted to synthesise the updated data to estimate costs, survival and quality-adjusted survival of patients tested using LBC and using Papanicolaou (Pap) smear testing. Cost data from published sources were incorporated into the above model to allow economic, as well as clinical, implications of treatment to be assessed. The primary incremental cost-effectiveness ratio is the cost per life year gained (LYG), although estimates of the cost per quality-adjusted life-year (QALY) gained are also presented. A sensitivity analysis was undertaken to identify the key parameters that determine the cost-effectiveness of the treatments, with the objective of identifying how robust the results of the economic analysis are, given the current level of evidence. RESULTS: From the evidence available, it is likely that the LBC technique will reduce the number of false-negative test results. Modelling analyses undertaken as part of this study indicate that this would reduce the incidence of invasive cancer. There is now more evidence to support improvements emanating from the use of LBC screening in terms of a reduced number of unsatisfactory specimens and a decrease in the time needed to obtain the smear samples. The estimated annual gross cost of consumables and operating equipment, and other one-off conversion costs associated with introducing the new technique, will be between 17 British pounds and 38 British pounds million in England and Wales, depending on the LBC system and the configuration of the service. Analyses based on models of disease natural history, conducted in this study, showed that conventional Pap smear screening was extendedly dominated by LBC (LBC was always more cost-effective than conventional Pap smear testing over the same screening interval). Comparing LBC across alternative screening intervals gave a cost-effectiveness of under 10,000 British pounds per LYG when screening was undertaken every 3 years. The cost-effectiveness results were relatively stable under most conditions, although if screening outcomes such as borderline results and colposcopy are assumed to induce even small amounts of disutility then LBC screening at 5-yearly intervals may be the most cost-effective option. CONCLUSIONS: This updated analysis provides more certainty with regard to the potential cost-effectiveness of LBC compared with conventional Pap smear testing. However, there is uncertainty regarding the relative effectiveness (and cost-effectiveness) of the two main LBC techniques. Further research in the area of utility assessment may be worthwhile and possibly a full cost-effectiveness study of LBC based on a trial of its introduction in a low-prevalence population, although the results of the modelling analysis provide a robust argument that LBC is a cost-effective alternative to conventional cervical cancer screening. A randomised comparison of the two main techniques may also be useful.
BACKGROUND: Third-generation aromatase inhibitors are being considered as an alternative to tamoxifen as first-line therapy for advanced breast cancer. These newer therapies are more expensive, and will gain greater acceptance if they can demonstrate cost-effectiveness. METHODS: Life table analyses are used to compare the costs and benefits [life years gained and quality-adjusted life years (QALYs) gained] of treating postmenopausal women with advanced breast cancer with first-line letrozole (with the option of second-line tamoxifen) compared with first-line tamoxifen (with the option of second-line letrozole). Patient-level data from a large clinical trial describes the effectiveness of the therapy options, clinicians estimate resource usage and utility values are obtained from the literature. RESULTS: The mean cost of providing first- and second-line hormonal therapy is pound 4765 if letrozole is the first-line therapy and pound 3418 if tamoxifen is provided first (a difference of pound 1347). However, patients receiving letrozole as first-line therapy gain an additional 0.228 life years, or 0.158 QALYs. The cost-effectiveness analysis found that first-line hormonal therapy with letrozole gains additional life years at a cost of pound 5917, whilst the cost per additional QALY gained is pound 8514. CONCLUSION: The strategy of letrozole as first-line hormonal therapy not only provides an opportunity for extending and improving patient's quality of life, but also is highly cost-effective compared with other generally accepted medical treatments.
AIMS: To compare, using a decision model, performance, treatment pathways and effects of different newborn screening strategies for developmental hip dysplasia with no screening. METHODS: Detection rate, radiological absence of subluxation at skeletal maturity and avascular necrosis of the femoral head, as favourable and unfavourable treatment outcomes respectively, were compared for the following strategies: clinical screening alone using the Ortolani and Barlow tests; the addition of static and dynamic ultrasound examination of the hips of all infants (universal ultrasound) or restricted to infants with defined risk factors (selective ultrasound); "no screening" (that is, clinical diagnosis only). RESULTS: Universal or selective ultrasound detects more more affected children (76% and 60% respectively) than clinical screening alone (35%), results in a higher proportion of affected children with favourable treatment outcomes (92% and 88% respectively) than clinical screening alone (78%) or no screening (75%), and the highest proportion of these achieved without recourse to surgery (64% and 79% respectively) compared with clinical screening alone (18%). However, ultrasound based strategies are also associated with the highest number of unfavourable treatment outcomes arising in unaffected children treated following a false positive screening result. The detection rate of clinical screening alone becomes similar to that reported for universal ultrasound when based on studies using experienced examiners (80%) rather than junior medical staff (35%). CONCLUSION: From the largely observational data available, ultrasound based screening strategies appear to be most sensitive and effective but are associated with the greatest risk of potential adverse iatrogenic effects arising in unaffected children.
AIMS: To assess, using a decision model, the efficiency of ultrasound based and clinical screening strategies for developmental dysplasia of the hip. METHODS: The additional cost per additional favourable outcome was compared for the following strategies: clinical screening alone using the Ortolani and Barlow tests; addition of static and dynamic ultrasound examination of the hips of all infants (universal ultrasound) or restricted to infants with defined risk factors (selective ultrasound); "no screening" (that is, clinical diagnosis only). RESULTS: Ultrasound based screening strategies are predicted to be more effective but more costly than clinical screening or no screening. Estimated total costs per 100,000 live births are approximately pound 4 million for universal ultrasound, pound 3 million for selective ultrasound, pound 1 million for clinical screening alone, and pound 0.4 million for no screening. The relative efficiency of selective ultrasound and clinical screening is poorly differentiated, and depends on how infants are selected for ultrasound as well as the expertise of clinical screening examiners. If training costs less than pound 20 per child screened, clinical screening alone would be more efficient than selective ultrasound. Relative to no screening, each of the 16 additional favourable outcomes achieved as a result of selective ultrasound costs approximately pound 0.2 million, while each of the five favourable outcomes achieved through universal ultrasound screening, over and above selective ultrasound, costs approximately pound 0.3 million. CONCLUSIONS: Policy choice depends on values attached to the different outcomes, willingness to pay to achieve these and total budget.
OBJECTIVES: To identify the role of modelling in planning and prioritising trials. The review focuses on modelling methods used in the construction of disease models and on methods for their analysis and interpretation. DATA SOURCES: Searches were initially developed in MEDLINE and then translated into other databases. REVIEW METHODS: Systematic reviews of the methodological and case study literature were undertaken. Search strategies focused on the intersection between three domains: modelling, health technology assessment and prioritisation. RESULTS: The review found that modelling can extend the validity of trials by: generalising from trial populations to specific target groups; generalising to other settings and countries; extrapolating trial outcomes to the longer term; linking intermediate outcome measures to final outcomes; extending analysis to the relevant comparators; adjusting for prognostic factors in trials; and synthesising research results. The review suggested that modelling may offer greatest benefits where the impact of a technology occurs over a long duration, where disease/technology characteristics are not observable, where there are long lead times in research, or for rapidly changing technologies. It was also found that modelling can inform the key parameters for research: sample size, trial duration and population characteristics. One-way, multi-way and threshold sensitivity analysis have been used in informing these aspects but are flawed. The payback approach has been piloted and while there have been weaknesses in its implementation, the approach does have potential. Expected value of information analysis is the only existing methodology that has been applied in practice and can address all these issues. The potential benefit of this methodology is that the value of research is directly related to its impact on technology commissioning decisions, and is demonstrated in real and absolute rather than relative terms; it assesses the technical efficiency of different types of research. Modelling is not a substitute for data collection. However, modelling can identify trial designs of low priority in informing health technology commissioning decisions. CONCLUSIONS: Good practice in undertaking and reporting economic modelling studies requires further dissemination and support, specifically in sensitivity analyses, model validation and the reporting of assumptions. Case studies of the payback approach using stochastic sensitivity analyses should be developed. Use of overall expected value of perfect information should be encouraged in modelling studies seeking to inform prioritisation and planning of health technology assessments. Research is required to assess if the potential benefits of value of information analysis can be realised in practice; on the definition of an adequate objective function; on methods for analysing computationally expensive models; and on methods for updating prior probability distributions.
The n-of-1 trial is a particularly flexible form of randomized controlled trial that involves a single patient receiving multiple episodes of alternative therapies. Although n-of-1 trials are only applicable in certain treatment areas, the collection of economic data within such trials may provide unique advantages. This paper illustrates the issues around the use of economic n-of-1 trials with a hypothetical example, and discusses their potential for the estimation of individualized cost-effectiveness.
BACKGROUND: The aim of this project was to model clinically important events experienced by lung transplant patients (from the day after transplant to 5 years or death) and costs associated with these events, and to assess the economic impact of different immunosuppression therapies. METHODS: The population comprised 356 lung transplant patients (223 heart-lung, 102 single lung and 31 double lung) transplanted between April 1984 and December 1997. All patients received a cyclosporine-based triple-immunosuppression protocol. We designed a Markov model that included 3 time periods (0 to 6, 7 to 12, and 13 to 60 months), 5 clinical states (well, acute rejection, cytomegalovirus infection, non-cytomegalovirus infection and bronchiolitis obliterans syndrome), and death. For the well state, cost elements were immunosuppression, prophylaxis, and routine clinic visits. For all other states, cost elements were diagnosis, treatment, and bed days/visits. We excluded costs of the procedure. RESULTS: The monthly costs associated with the well state decreased over time, from pound sterlings 1,778 ($2,658) in the first 6 months to pound sterlings 503 ($752) in months 7 to 12 and pound sterlings 350 ($523) after the first 12 months. The cost per event of the acute states remained reasonably constant over the 3 periods: pound sterlings 1,850 ($2,766) for rejection, pound sterlings 3,380 ($5,053) for cytomegalovirus, and pound sterlings 2,790 ($4,171) for other infections. The average cost per patient, discounted at 6%, over 5 years was pound sterlings 35,429 ($52,966) (95% range, pound1,435 [$2,145] to pound67,079 [$100,283]). This estimate is most sensitive to changes in immunosuppression. Substituting tacrolimus for cyclosporine increased 5-year costs by 5%; substituting mycophenolate mofetil for azathioprine increased 5-year costs by 26%. CONCLUSIONS: This model is valuable in estimating the effect of new immunosuppression agents on the costs of follow-up care.
OBJECTIVES: To examine whether, from a National Health Service (NHS) and local authority social services' viewpoint, a hospital-at-home service was cost saving compared with conventional inpatient care. METHODS: The subjects of this part-retrospective and part-prospective cost analysis were 51 elderly medical and orthopaedic surgical patients assessed at Hillingdon Hospital, West London, as being suitable for hospital-at-home care. Thirty patients received hospital-at-home care, provided for up to 14 days, while 21 patients remained in hospital and received standard inpatient care. All direct costs to the NHS hospital, community health services' provider and social services' department during the initial episode of care and the three months after discharge were collected for each group of patients. Costs and clinical event data were entered in a discrete event simulation model which generated baseline results. Uncertainty surrounding the model's parameters was explored using sensitivity analysis. RESULTS: The baseline simulation performed with 1000 patients in each group showed the mean cost per patient for hospital-at-home care and three-month follow-up to be around three-fifths the mean cost per patient of inpatient care and follow-up. Most of the excess cost in the inpatient group was attributable to the initial period of hospitalisation. Under all assumptions used in the sensitivity analysis, the hospital-at-home service was less costly. CONCLUSIONS: For elderly patients assessed as needing no more than 14 days of hospital care, hospital-at-home care is cost saving to health and social care agencies when compared with conventional inpatient care.
BACKGROUND: The aim of the study was to calculate the cost to the UK National Health Service of providing treatment services for patients with sickle cell disorders. The rates of differential morbidity and mortality, in the first 10 years of life, between screen-detected early diagnosed and clinically presenting late diagnosed cohorts of sickle cell disorder patients are also estimated. METHOD: A cost model was developed, based on predictions of survival and the incidence of sickle cell disorder-related events. Direct data from the NHS are lacking, so data were incorporated from disparate sources. Patients with sickle cell disorders were divided into two categories: those with sickle cell anaemia and those with sickle HbC disease. RESULTS: Differentiating between sickle cell anaemia and sickle HbC disorder patients, the results show that the undiscounted (discounted at 6 per cent) lifetime treatment costs range from pound sterling 92323 (pound sterling 24917) to pound sterling 185614 (pound sterling 53861). The number of early deaths avoided per 100 births, as a result of early diagnosis through screening, ranges from 0.57 to 1.25. CONCLUSIONS: The resulting estimates may act as a guide to those involved in the planning of health care provision with regard to the resources required to treat sickle cell disorder patients. Such information may also be incorporated into the evaluation of both antenatal and neonatal screening programmes for sickle cell disorders.
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Beta-thalassaemia major is a serious genetic disorder, which results in a considerable increase in both acute and chronic morbidity, and mortality. Although beta-thalassaemia major is a rare disease affecting approximately 600 people in the UK, treatment is intensive and predictions of the costs incurred may aid health care planning. In this report, the cost to the health service of providing treatment services for beta-thalassaemia major patients, over the course of a lifetime, is calculated in order to assist resource allocation decisions. A cost model was developed, incorporating data from disparate sources. The undiscounted lifetime cost of treating a beta-thalassaemia major patient was estimated to be pound 803,002, although when the costs were discounted at a rate of 6%, the lifetime cost was reduced to pound 219,068. Within sensitivity analyses, the discounted cost ranged from approximately pound 188,000 to pound 226,000. This report may act as a guide to those involved in the planning of health care provision with regard to the resources required to treat beta-thalassaemia major patients. Such information may also be incorporated into the decision-making process for the provision of antenatal screening programmes for beta-thalassaemia major.
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The increased use of modelling techniques as a methodological tool in the economic evaluation of health care technologies has, in the main, been limited to two approaches--decision trees and Markov chain models. The former are suited to modelling simple scenarios that occur over a short time period, whilst Markov chain models allow longer time periods to be modelled, in continuous time, where the timing of an event is uncertain. In the context of economic evaluation, a less well developed technique is discrete event simulation, which may allow even greater flexibility. Taking the economic evaluation of adjuvant therapies for breast cancer as an illustrative example, the process of building a decision tree, a Markov chain model, and a discrete event simulation model are described. The potential benefits and problems of each approach are discussed. The suitability of the modelling techniques to economic evaluations of health care programmes in general is then discussed. This section aims to illustrate the areas in which the alternative modelling methods may be most appropriately employed.