Is adding maternal vaccination to prevent whooping cough cost-effective in Australia?

Pertussis or whooping cough, a highly infectious respiratory infection, causes significant morbidity and mortality in infants. In adolescents and adults, pertussis presents with atypical symptoms often resulting in under-diagnosis and under-reporting, increasing the risk of transmission to more vulnerable groups. Maternal vaccination against pertussis protects mothers and newborns. This evaluation assessed the cost-effectiveness of adding maternal dTpa (reduced antigen diphtheria, Tetanus, acellular pertussis) vaccination to the 2016 nationally-funded pertussis program (DTPa [Diphtheria, Tetanus, acellular Pertussis] at 2, 4, 6, 18 months, 4 years and dTpa at 12-13 years) in Australia. A static cross-sectional population model was developed using a one-year period at steady-state. The model considered the total Australian population, stratified by age. Vaccine effectiveness against pertussis infection was assumed to be 92% in mothers and 91% in newborns, based on observational and case-control studies. The model included conservative assumptions around unreported cases. With 70% coverage, adding maternal vaccination to the existing pertussis program would prevent 8,847 pertussis cases, 422 outpatient cases, 146 hospitalizations and 0.54 deaths per year at the population level. With a 5% discount rate, 138.5 quality-adjusted life-years (QALYs) would be gained at an extra cost of AUS$ 4.44 million and an incremental cost-effectiveness ratio of AUS$ 32,065 per QALY gained. Sensitivity and scenario analyses demonstrated that outcomes were most sensitive to assumptions around vaccine effectiveness, duration of protection in mothers, and disutility of unreported cases. In conclusion, dTpa vaccination in the third trimester of pregnancy is likely to be cost-effective from a healthcare payer perspective in Australia.

Cost effectiveness of darunavir/ritonavir 600/100 mg bid in protease inhibitor-experienced, HIV-1-infected adults in Belgium, Italy, Sweden and the UK.

BACKGROUND: Two phase II trials (POWER 1 and 2) have demonstrated that darunavir co-administered with low-dose ritonavir (DRV/r) provides significant clinical benefit compared with control protease inhibitors (PIs) in highly treatment-experienced, HIV-1-infected adults, when co-administered with optimized background therapy (OBR). OBJECTIVE: To determine whether DRV/r is cost effective compared with control PIs, from the perspective of Belgian, Italian, Swedish and UK reimbursement authorities, when used in treatment-experienced patients similar to those included in the POWER 1 and 2 trials. METHODS: An existing Markov model containing health states defined by CD4 cell count ranges (> 500, 351-500, 201-350, 101-200, 51-100 and 0-50 cells/mm³) and death was adapted for use in four European healthcare settings. Baseline demographics, CD4 cell count distribution and antiretroviral drug usage reflected those reported in the POWER 1 and 2 trials. Virological/immunological response rates and matching transition probabilities over the patient's lifetime were based on results from the POWER trials and published data. After treatment failure, patients were assumed to switch to a tipranavir-containing regimen plus OBR. For each CD4 cell count range, utility values and HIV-related mortality rates were obtained from the published literature. National all-cause mortality data and published data on the increased risk of non HIV-related mortality in HIV-infected individuals were taken into account in the model. Data from observational studies conducted in each healthcare setting were used to determine resource-use patterns and costs associated with each CD4 cell count range. Unit costs were derived from official local sources; a lifetime horizon was taken and discount rates were selected based on local guidelines. RESULTS: In the base-case analysis, quality-adjusted life-year (QALY) gains of up to 1.397 in Belgium, over 1.171 in Italy, 1.142 in Sweden and 1.091 in the UK were predicted when DRV/r-based therapy was used instead of control PI-based treatment. The base-case analyses predicted an incremental cost-effectiveness ratio (ICER) of €11,438/QALY in Belgium, €12,122/QALY in Italy,€10,942/QALY in Sweden and €16,438/QALY in the UK. Assuming an acceptability threshold of €30,000/QALY, DRV/r-based therapy remained cost effective over all parameter ranges tested in extensive one-way sensitivity analyses. Probabilistic sensitivity analysis revealed a 95% (Belgium), 97% (Italy), 92% (Sweden) or 78% (UK) probability of attaining an ICER below this threshold. CONCLUSION: From four European payer perspectives, DRV/r-based antiretroviral therapy is predicted to be cost effective compared with currently available control PIs, when both are used with an OBR in treatment-experienced, HIV-1-infected adults who failed to respond to more than one PI-containing regimen.

Cost effectiveness of darunavir/ritonavir 600/100 mg bid in treatment-experienced, lopinavir-naive, protease inhibitor-resistant, HIV-infected adults in Belgium, Italy, Sweden and the UK.

BACKGROUND: Using data from the phase IIb POWER trials, darunavir boosted with low-dose ritonavir (DRV/r; 600/100 mg twice daily; bid)-based highly active antiretroviral therapy (HAART) was shown to be significantly more efficacious and cost effective than other protease inhibitor (PI)-based therapy in highly treatment-experienced, HIV-1-infected adults. Furthermore, in the phase III TITAN trial (TMC114-C214), DRV/r 600/100 mg bid-based HAART generated a superior 48-week virological response rate compared with standard-of-care lopinavir/ritonavir (LPV/r; 400/100 mg bid)-based therapy in treatment-experienced, lopinavir-naive patients, and in particular those with one or more International AIDS Society - USA (IAS-USA) primary PI resistance-associated mutations at baseline. These patients had a broader degree of previous PI use/failure (0 - ≥ 2) than the POWER patients. OBJECTIVES: To determine whether DRV/r 600/100 mg bid-based HAART is cost effective compared with LPV/r-based therapy, from the perspective of Belgian, Italian, Swedish and UK reimbursement authorities, when used in treatment-experienced patients similar to TITAN patients with one or more IAS-USA primary PI mutations at baseline. METHODS: An existing Markov model containing health states defined by CD4 cell count ranges (>500, 351-500, 201-350, 101-200, 51-100 and 0-50 cells/mm³) and an absorbing state of death was adapted for use in the above-mentioned healthcare settings. Baseline demographics, CD4 cell count distribution, antiretroviral drug usage, virological/immunological response rates and matching transition probabilities were based on data collected during the first 48 weeks of therapy in the modelled subgroup of TITAN patients and the published literature. After treatment failure, patients were assumed to switch to a follow-on combination regimen. For each health state, utility values and mortality rates were obtained from the published literature. Data from local observational studies (Belgium, Sweden and Italy) or the published literature (UK) were used to determine resource-use patterns and costs associated with each CD4 cell count range. Unit costs were derived from official local sources; a lifetime horizon was taken and discount rates were chosen based on local guidelines. RESULTS: The base-case analysis predicted quality-adjusted life year (QALY) gains of 0.785 in Belgium, 0.608 in Italy, 0.584 in Sweden and 0.550 in the UK when DRV/r-based therapy was used instead of LPV/r-based treatment. The estimated base-case incremental cost-effectiveness ratios (ICERs) were €6964/QALY gained in Belgium, €9277/QALY gained in Italy, €6868 (SEK69,687)/QALY gained in Sweden and €14,778 (£12 612)/QALY gained in the UK. Assuming a threshold of €30,000/QALY gained, DRV/r-based therapy remained cost effective over most parameter ranges tested in extensive one-way sensitivity analyses. The variation of immunological response rates and the time horizon were identified as important drivers of cost effectiveness. Probabilistic sensitivity analysis revealed a greater than 70% probability of achieving an ICER below this threshold in all four healthcare settings. CONCLUSION: From the perspective of Belgian, Italian, Swedish and UK payers, DRV/r 600/100 mg bid-based HAART is predicted to be cost effective compared with LPV/r 400/100 mg bid-based therapy, when used to manage treatment experienced, lopinavir-naive, PI-resistant, HIV-infected adults with a broad range of previous PI use/failure.

Critical appraisal of scientific posters comparing anemia treatments for cancer patients: applying ISPOR Task Force guidelines on methodological quality of retrospective studies.

Two independent reviewers used the methodological criteria published by the ISPOR Task Force on Retrospective Data to assess the quality of four posters presenting the results of retrospective database studies on the use of erythropoiesis-stimulating agents (epoetin alfa, epoetin beta, or darbepoetin alfa) for treating patients with cancer. A third reviewer consolidated the results. Overall, from the information reported in the four posters, their methodological quality ranged from poor to very poor; only a few of the criteria were satisfactorily addressed. The quality of the data sources and the research design received very poor scores. Key elements such as selection bias were not considered. These findings caution against the use of posters without appropriate assessment of their methodological quality. The ISPOR guidelines for the evaluation of retrospective analyses are a useful tool for assessing the quality of scientific posters.

Estimating the cost-effectiveness of quality-improving interventions in oral anticoagulation management within general practice.

OBJECTIVES: A clinical trial, "Belgian Improvement Study on Oral Anticoagulation Therapy (BISOAT)," significantly improved the quality after implementing four different quality-improving interventions in four randomly divided groups of general practitioners (GPs). The quality-improving interventions consisted of multifaceted education with or without feedback reports on their performance, international normalized ratio (INR) testing by the GP with a CoaguChek device or computer-assisted advice for adapting oral anticoagulation therapy. The quality improvement in INR control versus baseline was similar in the four groups. The aim of the current study was to calculate the cost-effectiveness and influencing factors of the four quality-improving interventions compared with usual care. METHODS: Activity-based costing techniques with questionnaires were used to determine the global costs per patient per month in the different intervention groups. Effectiveness data were obtained from the BISOAT study. Cost-effectiveness was expressed as cost per additional day within a 0.5 range from INR target. RESULTS: The one-time cost of multifaceted education was 49,997 euro for the whole study. Monthly continuous costs per intervention ranged between 37 euro and 54 euro per patient. Using the CoaguChek in combination with the multifaceted education was associated with net savings and quality improvement, hence dominated usual care. Sensitivity analyses showed improved cost-effectiveness with extended duration and with increased program size. CONCLUSION: Implementation of the combination multifaceted education with the use of the CoaguChek is a cost-effective new organizational model of oral anticoagulation management in general practice.

Economic evaluation of the prevention and management of systemic fungal infections in neutropenic patients.

Systemic fungal infections in neutropenic patients remain a clinical problem that is associated with morbidity and mortality. Continuing efforts are being made to develop improved (i.e., more effective or safe) drugs, and several new treatments have recently become available. These have increased the therapeutic options available to clinicians to address the problem of systemic fungal infections. Therapeutic choices are difficult when taking into account aspects of efficacy, safety and costs that are associated with the available alternatives. This review summarises the present status of health economic knowledge of the standard therapies that have been available for many years, and also reports on the most recent health economic evidence available for the newly developed treatment alternatives.

European guidelines for the management of chemotherapy-induced anaemia and health economic aspects of treatment.

Patients with cancer receiving myelosuppressive chemotherapy frequently develop anaemia; platinum-based chemotherapy, in particular, leads to reduced production of the bone marrow-stimulating hormone erythropoietin. The European Cancer Anaemia Survey showed that many patients do not receive erythropoiesis-stimulating agent (ESA) therapy and highlighted the need for clear guidelines for the diagnosis and treatment of anaemia in cancer patients. In response to a fast-moving therapeutic environment and guidelines produced in the USA, the European Organisation for Research and Treatment of Cancer established an independent task force to develop evidence-based guidelines for the use of ESAs in European anaemic cancer patients that were first published in 2004. The guidelines recommend that, in patients receiving chemotherapy/radiotherapy, ESA therapy should be initiated at haemoglobin levels of 9-11 g/dL based on the severity of symptoms (target haemoglobin concentration: 12-13 g/dL) to improve quality of life and prevent the need for red blood cell transfusions. Treatment should be maintained as long as Hb levels remain <12-13 g/dL and patients continue to show symptomatic improvement, and should be discontinued, due to marginally elevated risks of thromboembolic events, when haemoglobin levels exceed 14 g/dL. Treatment of anaemia with ESAs is cost-effective and is associated with long-term gains in quality-adjusted life years.

Cost-effectiveness analysis of bicalutamide (Casodex) for adjuvant treatment of early prostate cancer.

OBJECTIVES: To assess the cost-effectiveness of bicalutamide (Casodex) as adjuvant treatment in early prostate cancer (EPC). METHODS: A Markov state transition model was developed, using disease progression rates from a large (N = 8113) clinical trial program comparing bicalutamide in addition to standard care with standard care alone. Utility scores for different disease stages were obtained from published reports. Costs of disease progression were obtained from a retrospective patient chart analysis in six Belgian centers (n = 60). The time horizon was 15 years and the analysis was conducted from the public payer perspective. RESULTS: The model showed good validity in predicting clinical outcomes. At a time horizon of 15 years, an incremental cost-effectiveness of 27,059 euros/QALY was obtained. The main factors influencing conclusions included the time horizon, the duration of bicalutamide treatment, which was set at a maximum (5 years) in the base case, and possible differences in prognosis of metastatic cancer between comparators. Also the discounting of health effects significantly altered cost-effectiveness ratios. Many of these influences are inherently associated with any cost-effectiveness analysis related to treatment of early, slowly progressing malignancies because such an analysis requires a sufficient time horizon to include not only the treatment costs but its benefits as well. CONCLUSION: Based on the current data, bicalutamide appears to be a cost-effective option for adjuvant treatment of EPC.

Modeling costs and cost-effectiveness of different CMV management strategies in liver transplant recipients as a support for current and future decision making.

OBJECTIVES: To develop a generic decision-analytic model to predict health and economic outcomes of different management options for cytomegalovirus (CMV) infection and disease in liver transplant patients. METHODS AND DATA: The model considers different CMV management strategies, thereby emphasizing the important difference between infection and disease. The first strategy starts with prophylaxis prior to transplantation, followed by preemptive treatment if infection, based on positive CMV diagnostic tests, is confirmed. The second strategy is a preemptive strategy consisting of only testing followed by preemptive treatment. Finally, in the wait-and-treat strategy, antiviral treatment is only started when clinical signs of CMV disease appear. Management and resource-use data were obtained from clinical experts in large transplant centers in France, Germany, and the United Kingdom. Cost data were collected from the health care payer's perspective. A Bayesian revision technique was applied to distinguish effectiveness of current management options for CMV infection vs. CMV disease, an aspect that is currently underreported in literature. RESULTS: CMV prophylaxis in liver transplant recipients is generally more cost-effective than preemptive and wait-and-treat strategies. In order of importance, changes in drug costs, drug efficacy, specificity of CMV testing, cost of hospitalization, probability of CMV relapse and baseline CMV risk are the most important factors influencing the cost-effectiveness. CONCLUSION: This model describes different strategies applied for management of CMV in liver transplant patients and is useful both for current decision making, optimal disease management, and assessment of future research targets.