Survival Benefit of Myeloablative Therapy with Autologous Stem Cell Transplantation in High-Risk Neuroblastoma: A Systematic Literature Review.

BACKGROUND: Multimodal treatment of newly diagnosed high-risk neuroblastoma (HRNB) includes induction chemotherapy, consolidation with myeloablative therapy (MAT) and autologous stem cell transplantation (ASCT), followed by anti-disialoganglioside 2 (GD2) immunotherapy, as recommended by the Children's Oncology Group (COG) and the Society of Paediatric Oncology European Neuroblastoma (SIOPEN). Some centres proposed an alternative approach with induction chemotherapy followed by anti-GD2 immunotherapy, without MAT+ASCT. OBJECTIVE: The aim of this systematic literature review was to compare survival outcomes in patients with HRNB treated with or without MAT+ASCT and with or without subsequent anti-GD2 immunotherapy. PATIENTS AND METHODS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE via PubMed and EMBASE databases were systematically searched for randomised controlled trials (RCT) and observational comparative studies in patients with HRNB using search terms for 'neuroblastoma' and ('myeloablative therapy' OR 'stem cell transplantation'). Reporting of at least one survival outcome [event-free survival (EFS), progression-free survival, relapse-free survival and/or overall survival (OS)] was required for inclusion. Outcomes from RCTs were synthesized in meta-analysis, while meta-analysis of non-RCTs was not planned owing to expected heterogeneity. RESULTS: Literature searches produced 2587 results with 41 publications reporting 34 comparative studies included in the review. Of these, 7 publications reported 4 RCTs, and 34 publications reported 30 non-RCT studies. Studies differed with respect to included populations, induction regimen, response to induction, additional treatments and transplantation procedures. Subsequent treatments of relapse were rarely reported and could not be compared. In the meta-analysis, EFS was in favour of MAT+ASCT over conventional chemotherapy or no further treatment [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.67-0.91, p = 0.001] with a trend favouring MAT+ASCT for OS (HR = 0.86, 95% CI 0.73-1.00, p = 0.05). Tandem MAT+ASCT was found to improve EFS compared with the single procedure, with improvement in both EFS and OS in patients treated with anti-GD2 therapy. Non-RCT comparative studies were broadly consistent with evidence from the RCTs; however, not all reported survival benefits of MAT+ASCT (single or tandem). Limited comparative evidence on treatment without MAT+ASCT in patients treated with anti-GD2 immunotherapy suggests an increased risk of relapse. In relapsed patients, MAT+ASCT appears to improve OS, but evidence remains scarce. CONCLUSIONS: Survival benefits in patients treated with MAT+ASCT confirm that the procedure should remain an integral part of multimodal therapy. In patients treated with anti-GD2 immunotherapy, limited evidence suggests that omitting MAT+ASCT is associated with an increased risk of relapse, and therefore, a change in clinical practice can currently not be recommended. Evidence suggests the use of tandem MAT+ASCT compared with the single procedure, with greater benefits observed in patients treated with anti-GD2 immunotherapy. Limited evidence also suggests improved survival following MAT+ASCT in relapsed patients, which needs to be viewed in light of emerging chemoimmunotherapy in this setting.

Cost-saving treatment strategies in in vitro fertilization: a combined economic evaluation of two large randomized clinical trials comparing highly purified human menopausal gonadotropin and recombinant follicle-stimulating hormone alpha.

OBJECTIVE: To assess the cost-effectiveness of two gonadotropin treatments that are available in the United Kingdom in light of limited public funding and the fundamental role of costs in IVF treatment decisions. DESIGN: An economic evaluation based on two large randomized clinical trials in IVF patients using a simulation model. SETTING: Fifty-three fertility clinics in 13 European countries and Israel. PATIENT(S): Women indicated for treatment with IVF (N = 986), aged 18-38, participating in double-blind, randomized controlled trials. INTERVENTION(S): Highly purified menotropin (HP-hMG, Menopur) or recombinant follitropin alpha (rFSH, Gonal-F). MAIN OUTCOME MEASURE(S): Cost per IVF cycle and cost per live birth for HP-hMG and rFSH alpha. RESULT(S): HP-hMG was more effective and less costly versus rFSH for both IVF cost per live birth and for IVF cost per baby (incremental cost-effectiveness ratio was negative). The mean costs per IVF treatment for HP-hMG and rFSH were 2408 pounds (95% confidence interval [CI], 2392 pounds, 2421 pounds) and 2660 pounds (95% CI 2644 pounds, 2678 pounds), respectively. The mean cost saving of 253 pounds per cycle using HP-hMG allows one additional cycle to be delivered for every 9.5 cycles. CONCLUSION(S): Treatment with HP-hMG was dominant compared with rFSH in the United Kingdom. Gonadotropin costs should be considered alongside live-birth rates to optimize outcomes using scarce health-care resources.

The cost of renal dialysis in a UK setting--a multicentre study.

BACKGROUND: The UK National Health Service (NHS) will fund renal services using Payment by Results (PbR), from 2009. Central to the success of PbR will be the creation of tariffs that reflect the true cost of medical services. We have therefore estimated the cost of different dialysis modalities in the Cardiff and Vale NHS Trust and six other hospitals in the UK. METHODS: We used semi-structured interviews with nephrologists, head nurses and business managers to identify the steps involved in delivering the different dialysis modalities. We assigned costs to these using published figures or suppliers' published price lists. The study used mixed costing methods. Dialysis costs were estimated by a combination of microcosting and a top-down approach. Where we did not have access to detailed accounts, we applied values for Cardiff. RESULTS: The most efficient modalities were automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD), the mean annual costs of which were pound21 655 and pound15 570, respectively. Hospital-based haemodialysis (HD) cost pound35 023 per annum and satellite-unit-based HD cost pound32 669. The cost of home-based HD was pound20 764 per year (based on data from only one unit). The main cost drivers for PD were the costs of solutions and management of anaemia. For HD they were costs of disposables, nursing, the overheads associated with running the unit and management of anaemia. CONCLUSIONS: Renal tariffs for PbR need to reflect the true cost of dialysis provision if choices about modalities are not to be influenced by erroneous estimates of cost. Knowledge of the true costs of modalities will also maximize the number of established renal failure patients treated by dialysis within the limited funds available from the NHS.

An economic evaluation of highly purified HMG and recombinant FSH based on a large randomized trial.

Public funding for IVF is increasingly being challenged by health authorities in an attempt to minimize health service costs. In light of treatment rationing, the need to consider costs in relation to outcomes is paramount. To assess the cost implications of gonadotrophin treatment options, an economic evaluation comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) has been conducted. The analysis is based on individual patient data from a large randomized controlled trial (n = 731) in a long agonist IVF protocol. The economic evaluation uses a discrete event simulation model to assess treatment costs in relation to live births for both treatments based on published UK costs. After one cycle the mean costs per IVF treatment for HP-HMG and rFSH were pound2396 (95% CI pound2383-2414) and pound2633 ( pound2615-2652), respectively. The average cost-saving of pound237 per IVF cycle using HP-HMG allows one additional cycle to be delivered for every 10 cycles. With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was pound8893 compared with pound11,741 for rFSH (P < 0.001). The cost-saving potential of HP-HMG in IVF was still apparent after varying critical cost parameters in the probabilistic sensitivity analysis.

An economic evaluation of vasoactive agents used in the United Kingdom for acute bleeding oesophageal varices in patients with liver cirrhosis.

OBJECTIVE: To conduct an economic evaluation of terlipressin, octreotide and placebo in the treatment of bleeding oesophageal varices (BOV) where endotherapy could be used concomitantly. METHODS: A discrete event simulation model was created with transition states: bleeding, no bleeding, no bleeding post transjugular intrahepatic portosystemic shunt, post-salvage surgery, and death. Efficacy data on survival, re-bleeding and control of bleeding were obtained from high quality studies reported in Cochrane meta-analyses. Baseline outcomes related to the course of disease and health-state utilities were derived from published sources. Vasoactive treatment costs and all related BOV costs were obtained from published UK sources. RESULTS: The average aggregated treatment cost per person for all medical interventions at 1 year was lower for terlipressin-treated patients (2623 pounds sterling) compared with those treated using octreotide (2758 pounds sterling) or placebo (2890 pounds sterling). The incremental analysis comparing terlipressin with octreotide and placebo using a cost per quality adjusted life year (QALY) and cost per life year gained (LYG) approach indicated that terlipressin was the dominant BOV treatment option (i.e. it cost less and it was more effective). Based on a maximum willingness to pay of 20,000 pounds sterling/QALY terlipressin was more effective and cost-saving compared to octreotide and placebo for simulations ranging from 42 days to 2 years. In point estimation analyses octreotide was dominant compared to placebo; however, probabilistic sensitivity analysis indicated that octreotide was unlikely to be cost-effective compared to placebo. CONCLUSIONS: The findings indicated that vasoactive treatment in BOV was cost-saving compared to no vasoactive treatment. Furthermore, terlipressin was the more cost-effective vasoactive treatment for BOV in cirrhotic patients.