Survival, quality-adjusted survival, and other clinical end points in older advanced non-small-cell lung cancer patients treated with albumin-bound paclitaxel.

BACKGROUND: This analysis compared the quality-adjusted survival and clinical outcomes of albumin-bound paclitaxel+carboplatin (nab-PC) vs solvent-based paclitaxel+carboplatin (sb-PC) as first-line therapy in advanced non-small-cell lung cancer (NSCLC) in older patients. METHODS: Using age-based subgroup data from a randomised Phase-3 clinical trial, nab-PC and sb-PC were compared with respect to overall response rate (ORR), overall survival (OS), progression-free survival (PFS), quality of life (QoL), safety/toxicity, and quality-adjusted time without symptoms or toxicity (Q-TWiST) with ages ⩾60 and ⩾70 years as cut points. RESULTS: Among patients aged ⩾60 years (N=546), nab-PC (N=265) significantly increased ORR and prolonged OS, despite a non-significant improvement in PFS, vs sb-PC (N=281). Nab-PC improved QoL and was associated with less neuropathy, arthralgia, and myalgia but resulted in more anaemia and thrombocytopenia. Nab-PC yielded significant Q-TWiST benefits (11.1 vs 9.8 months; 95% CI of gain: 0.2-2.6), with a relative Q-TWiST gain of 10.8% (ranging from 6.4% to 15.1% in threshold analysis). In the ⩾70 years age group, nab-PC showed similar, but non-significant, ORR, PFS, and Q-TWiST benefits and significantly improved OS and QoL. CONCLUSION: Nab-PC as first-line therapy in older patients with advanced NSCLC increased ORR, OS, and QoL and resulted in quality-adjusted survival gains compared with standard sb-PC.

Cost effectiveness of zoledronic acid in the management of skeletal metastases in hormone-refractory prostate cancer patients in France, Germany, Portugal, and the Netherlands.

OBJECTIVE: Zoledronic acid (ZOL) reduces the risk of skeletal related events (SREs) in hormone-refractory prostate cancer (HRPC) patients with bone metastases. This study assessed the cost effectiveness of ZOL for SRE management in French, German, Portuguese, and Dutch HRPC patients. METHODS: This analysis was based on the results of a randomized phase III clinical trial wherein HRPC patients received up to 15 months of ZOL (n = 214) or placebo (n = 208). Clinical inputs were obtained from the trial. Costs were estimated using hospital tariffs, published, and internet sources. Quality adjusted life-years (QALYs) gained were estimated from a separate analysis of EQ-5D scores reported in the trial. Uncertainty surrounding outcomes was addressed via univariate sensitivity analyses. RESULTS: ZOL patients experienced an estimated 0.759 fewer SREs and gained an estimated 0.03566 QALYs versus placebo patients. ZOL was associated with reduced SRE-related costs [net costs] (-€2396 [€1284] in France, -€2606 [€841] in Germany, -€3326 [€309] in Portugal and -€3617 [€87] in the Netherlands). Costs per QALY ranged from €2430 (Netherlands) to €36,007 (France). CONCLUSIONS: This analysis is subject to the limitations of most cost-effectiveness analyses: it combines data from multiple sources. Nevertheless, the results strongly suggest that ZOL is cost effective versus placebo in French, German, Portuguese, and Dutch HRPC patients.

Cost-effectiveness of zoledronic acid in the prevention of skeletal-related events in patients with bone metastases secondary to advanced renal cell carcinoma: application to France, Germany, and the United Kingdom.

BACKGROUND: The use of zoledronic acid (ZOL) has recently been shown to significantly reduce the risk of new skeletal-related events (SREs) in renal cell carcinoma (RCC) patients with bone metastases. The present exploratory study assessed the cost-effectiveness of ZOL in this population, adopting a French, German, and United Kingdom (UK) government payer perspective. MATERIALS AND METHODS: This cost-effectiveness model was based on a post hoc retrospective analysis of a subset of patients with RCC who were included in a larger randomized clinical trial of patients with bone metastases secondary to a variety of cancers. In the trial, patients were randomized to receive ZOL (n = 27) or placebo (n = 19) with concomitant antineoplastic therapy every 3 weeks for 9 months (core study) plus 12 months during a study extension. Since the trial did not collect costs or data on the quality-adjusted life years (QALYs) of the patients, these outcomes had to be assumed via modeling exercises. The costs of SREs were estimated using hospital DRG tariffs. These estimates were supplemented with literature-based costs where possible. Drug, administration, and supply costs were obtained from published and internet sources. Consistent with similar economic analyses, patients were assumed to experience quality of life decrements lasting 1 month for each SRE. Uncertainty surrounding outcomes was addressed via multivariate sensitivity analyses. RESULTS: Patients receiving ZOL experienced 1.07 fewer SREs than patients on placebo. Patients on ZOL experienced a gain in discounted QALYs of approximately 0.1563 in France and Germany and 0.1575 in the UK. Discounted SRE-related costs were substantially lower among ZOL than placebo patients (-€ 4,196 in France, - € 3,880 in Germany, and -€ 3,355 in the UK). After taking into consideration the drug therapy costs, ZOL saved € 1,358, € 1,223, and € 719 in France, Germany, and the UK, respectively. In the multivariate sensitivity analyses, therapy with ZOL saved costs in 67-77% of simulations, depending on the country. The cost per QALY gained for ZOL versus placebo was below € 30,000 per QALY gained threshold in approximately 93-94% of multivariate sensitivity analyses simulations. CONCLUSIONS: The present analysis suggests that ZOL saves costs and increases QALYs compared to placebo in French, German, and UK RCC patients with bone metastases. Additional prospective research may be needed to confirm these results in a larger sample of patients.

Economic evaluation of zoledronic acid for the prevention of osteoporotic fractures in postmenopausal women with early-stage breast cancer receiving aromatase inhibitors in the UK.

BACKGROUND: Aromatase inhibitors are used as adjuvant therapy for breast cancer (BC) and are associated with accelerated bone loss. Zoledronic acid (ZOL) prevents aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women with BC. This analysis assessed the cost-effectiveness of ZOL for prevention of fractures in postmenopausal women with BC. MATERIALS AND METHODS: A Markov model was developed to project lifetime incidence of fractures, quality-adjusted life years (QALY), and costs as a function of bone mineral density (BMD) for women with early-stage BC receiving letrozole alone or with ZOL. Two strategies of ZOL therapy were compared with no treatment: starting ZOL treatment only when BMD levels decreased ('delayed ZOL') and starting ZOL simultaneously with letrozole therapy ('upfront ZOL'). RESULTS: Delayed ZOL therapy was estimated to cost 16,069 pounds per QALY, when compared with not administering bisphosphonates for AIBL prevention. The corresponding cost per QALY gained for upfront ZOL versus no treatment was estimated at 21,973 pounds. The cost-effectiveness ratio for upfront versus delayed therapy was estimated at 24,868 pounds per QALY gained. CONCLUSION: Both delayed and upfront therapy with ZOL for the prevention of AIBL and fractures in BC patients in the UK appear to result in highly acceptable cost-effectiveness ratios.

Efficacy of recombinant activated factor VII vs. activated prothrombin complex concentrate for patients suffering from haemophilia complicated with inhibitors: a Bayesian meta-regression.

The optimal on-demand treatment of joint bleeds in haemophilia patients with inhibitors is a source of debate, with studies reporting various efficacy levels for different drugs and dosage regimens. To analyse, in a unified Bayesian meta-regression model, the published efficacy of recombinant activated factor VII (rFVIIa) and/or activated prothrombin complex concentrate (aPCC) as on-demand treatments for joint bleeds in haemophilia patients with inhibitors. A systematic search was carried out to identify studies reporting on dosage and efficacy of rFVIIa and aPCC in the treatment of joint bleeds in the target patient population. Data were abstracted and included in the model and adjusted for potential sources of heterogeneity. Pooled efficacy levels for typical rFVIIa and aPCC regimens were estimated. Seventeen studies, collectively reporting on >2000 joint bleeds, were included. Medication type combined with dosage was the only significant explanatory parameter. The model predicts that a typical regimen of 90 microg kg(-1) rFVII repeated every 3 h if needed results in cumulative joint bleed resolution of 66%, 88% and 95% after 12, 24 and 36 h, respectively. In comparison, a typical regimen of 75 IU kg(-1) aPCC repeated every 12 h if needed results in cumulative joint bleed resolution of 39%, 62% and 76%, respectively. These differences were statistically significant and were also robust in sensitivity analyses. This analysis suggests that a typical rFVIIa regimen will resolve joint bleeds more effectively than a typical aPCC regimen after 12, 24 and 36 h.

Cost effectiveness of adalimumab for the treatment of ankylosing spondylitis in the United Kingdom.

OBJECTIVES: This study evaluated the cost effectiveness of adalimumab vs conventional therapy in patients with active ankylosing spondylitis (AS). METHODS: The analysis was based on pooled data from two Phase III studies of adalimumab in active AS. Patients with an inadequate response to >/=1 NSAID received adalimumab 40 mg every other week (n = 246) or placebo (n = 151) for 24 weeks. A microsimulation model was developed with patients being treated with adalimumab according to the International ASAS Consensus Statement and BSR guidelines. The pooled adalimumab data, as well as data from the Outcome Assessment in AS International Study (OASIS) database and the literature, were used to model patients' BASDAI and BASFI scores and costs and health-related quality of life associated with various degrees of disease activity. Costs (in 2004 British pound) of AS, drug, administration, monitoring, hospitalization and AEs were calculated from the perspective of the UK NHS. Discounting was applied at 3.5% per year for costs and benefits as per the NICE reference case for economic evaluations. Uncertainty was addressed via sensitivity analyses. RESULTS: The incremental cost-effectiveness ratio (ICER) of adalimumab vs conventional therapy was estimated to improve with longer time horizons (48 weeks to 5 and 30 yrs). The central estimate was that, over 30 yrs, adalimumab therapy yielded 1.03 more quality-adjusted life-years (QALYs) per patient initiating therapy. Some AS treatment-related costs were estimated to be offset by adalimumab (at 10,750 pounds/patient), leaving a total incremental cost (adalimumab vs conventional therapy) at 23,857 pounds per patient. The 30-yr ICER of adalimumab vs conventional therapy was estimated at 23 pounds 097/QALY. Sensitivity analyses demonstrated robustness of results. When indirect costs were also included (analysis from societal perspective), ICER improved to 5093 pounds/QALY. CONCLUSIONS: This analysis indicates that adalimumab, when used according to UK treatment guidelines, is cost-effective vs conventional therapy for treating AS patients.

Economic burden of haematological adverse effects in cancer patients: a systematic review.

OBJECTIVE: Patients receiving cancer treatments commonly experience haematological adverse effects (AEs) related to chemotherapy or molecularly targeted therapies, which may be associated with high healthcare costs. The objective of this review was to summarise the published literature on the economic burden of neutropenia, thrombocytopenia and anaemia as AEs of cancer treatment. METHODS: A systematic search of the medical literature published between 1990 and 2006 was conducted using PubMed/MEDLINE, EMBASE, BIOSIS, related article links and supplemental searches. References selected for inclusion were prospective or retrospective studies specifically designed to examine the burden of illness, direct medical costs, indirect costs and/or cost drivers associated with neutropenia, thrombocytopenia and anaemia in adult cancer patients. All costs are reported as originally published and adjusted to 2006 US dollars. RESULTS: In the US, the cost of neutropenia ranged from $US 1893 (2006 value $US 2632) per outpatient episode to $US 38,583 ($US 49,917) per febrile neutropenia hospitalisation. For countries outside the US, the cost of neutropenia appeared to be lower. The cost of thrombocytopenia ranged from $US 1035 ($US 1395) to $US 5328 ($US 7635) per cycle or episode in the US. Costs attributable to anaemia ranged from $US 18,418 ($US 22,775) to $US 69,478 ($US 93,454) per year in the US. The costs of AEs for patients with haematological malignancies appeared to be up to 2-3 times higher than those for patients with solid tumours. Economic studies of the cost of haematological AEs specific to new molecularly targeted treatments for haematological malignancy have not been published. CONCLUSIONS: Chemotherapy-related haematological AEs result in a substantial economic burden on patients, payers, caregivers and society in general. Because of their burden, the frequency and severity of these toxicities should be one of the key factors in the selection of optimal treatments for patients with cancer, especially those with haematological malignancies. Future research is needed to assess the economic burden of AEs associated with new molecularly targeted treatments for haematological malignancies.

A systematic literature review of the clinical and epidemiological burden of acute lymphoblastic leukaemia (ALL).

Our goal was to identify and summarize the published literature pertaining to the incidence, prevalence, mortality, aetiology, clinical diagnosis, and management of acute lymphoblastic leukaemia (ALL). Acute lymphoblastic leukaemia represents 12% of all leukaemia cases, with a worldwide incidence projected to be 1-4.75 per 100,000 people. Italy, the United States (US), Switzerland, and Costa Rica are the countries with the highest incidence of ALL. Hereditary link, genetic defects, and possibly radiation or chemical exposures are listed amongst the most significant risk factors. Acute lymphoblastic leukaemia is predominantly a disease of childhood, but it affects adults as well. It accounts for 80% of all leukaemia cases in children. The incidence is slightly higher in men than in women and greater in white people than in black people. In 2003 in the US, there were an estimated 5800 deaths from ALL. Presenting signs and symptoms of ALL are fairly non-specific and include fever, anaemia, petechiae, and bone and joint pain. Staging of the disease and patient risk profile are routinely performed to define ALL subtypes and guide management. Chemotherapy, cranial radiation in patients with high-risk disease, and stem cell transplantation for selected patients are the prevalent therapies. Complete remission rates are high, especially amongst children (even 100%); however, long-term survival at 10 years (event-free survival) is in the range of 63% for children and 25-35% for adults. This implies that there is still a strong need for new therapies to maintain remission and prolong survival. Future treatment strategies may be driven by the patient's minimal residual disease status, a measure that more precisely defines remission, prognosis, responsiveness to therapy, and expected long-term survival.

The clinical and epidemiological burden of chronic lymphocytic leukaemia.

The purpose of this literature review was to identify and summarize published studies describing the epidemiology and management of chronic lymphocytic leukaemia (CLL). Chronic lymphocytic leukaemia represents 22-30% of all leukaemia cases with a worldwide incidence projected to be between < 1 and 5.5 per 100,000 people. Australia, the USA, Ireland and Italy have the highest CLL incidence rates. Chronic lymphocytic leukaemia presents in adults, at higher rates in males than in females and in whites than in blacks. Median age at diagnosis is 64-70 years. Five-year survival rate in the USA is 83% for those < 65 years old and 68% for those 65 + years old. Hereditary and genetic links have been noted. Persons with close relatives who have CLL have an increased risk of developing it themselves. No single environmental risk factor has been found to be predictive for CLL. Patients are usually diagnosed at routine health care visits because of elevated lymphocyte counts. The most common presenting symptom of CLL is lymphadenopathy, while difficulty exercising and fatigue are common complaints. Most patients do not receive treatment after initial diagnosis unless presenting with clear pathologic conditions. Pharmacological therapy may consist of monotherapy or combination therapy involving glucocorticoids, alkylating agents, and purine analogs. Fludarabine may be the most effective single drug treatment currently available. Combination therapy protocols have not been shown to be more effective than fludarabine alone. As no cure is yet available, a strong unmet medical need exists for innovative new therapies. Experimental treatments under development include allogeneic stem cell transplant, mini-allogeneic transplants, and monoclonal antibodies (e.g. alemtuzumab against CD52; rituximab against CD20).

Quality of life aspects of bladder cancer: a review of the literature.

Not much is generally known regarding the burden imposed by bladder cancer upon patient health-related quality of life (HRQL). The role of HRQL in affecting patient preferences and utility assessment and, ultimately, the selection of therapeutic regimen, or patient satisfaction with that selection, is considered increasingly important by the medical community. Therefore, the main focus of this evaluation was to review the international medical literature to better understand the impact of bladder cancer on patient HRQL. A search was performed using electronic and manual databases for published articles on HRQL and bladder cancer for the years 1966 onward. Thirty-five references dealing with HRQL were analyzed as part of this review. Of these, 29 were published after 1989. Most studies have identified urinary and sexual HRQL domains as being of greatest concern to patients. However, little is known about the short- and long-term impacts of specific therapeutic options for either superficial bladder cancer (SBC) or invasive bladder cancer (IBC). Increased awareness and use of the HRQL instruments such as the FACT-BL as well as the EORTC-QLQ-BLS24 and the EORTC-QLQ-BLM30 (when they are validated for SBC and IBC, respectively), should increase our understanding of the impact of this disease and its management options on patient HRQL.

Quality of life of patients with Fabry disease.

This paper is the first of its kind to study the impact of Fabry disease (FD) in affected males, and shows that FD is associated with a significant decline in several domains. Using the medical outcomes study (MOS) SF-36 and a FD-specific questionnaire, we compared the observations found among these patients with that obtained for the general US population and other chronic disease states, including Gaucher disease (GD) (another lysosomal storage disorder), end-stage renal disease, stoke and AIDS. Patients with FD have a score profile most similar to patients with AIDS. In comparison with patients with GD, Fabry patients score substantially lower across all domains. Using simple linear regression, potential predictors of health-related quality of life (HRQOL) for Fabry patients were also determined. As in the general population, stroke, cardiac problems and renal disease lead to substantial decrement in HRQOL. In addition, two disease specific symptoms (acroparesthesia and anhidrosis) and pain are also predictors of decreased quality of life. Currently, no specific therapy for FD exists. As enzyme therapy for FD becomes increasingly available, it will be interesting to evaluate the therapy's impact on the quality of life of patients.

A short-term cost-of-treatment model for type 2 diabetes: comparison of glipizide gastrointestinal therapeutic system, metformin, and acarbose.

OBJECTIVE: To compare, from a managed care perspective, the 3-year costs of 3 first-line monotherapy strategies in type 2 diabetes patients: glipizide gastrointestinal therapeutic system (GITS), metformin, and acarbose. STUDY DESIGN: A Markov model, with a Monte Carlo simulation, was developed to compare the costs to achieve full glycemic control (hemoglobin A1c of < or = 7%) with each first-line strategy. PATIENTS AND METHODS: The patient population for the model was assumed to be all newly diagnosed type 2 diabetes patients eligible for monotherapy with an oral agent. Each monotherapy could be succeeded by add-on treatments. The model included the costs of routine medical care and supplies, medication, adverse events, and treatment failures. RESULTS: Using a Monte Carlo simulation, the mean 3-year cumulative costs per patient were $4971, $5273, and $5311 for glipizide GITS, metformin, and acarbose first-line strategies, respectively. The main cost drivers were drug prices. Mean 3-year cost savings for first-line glipizide GITS were $301 over metformin and $340 over acarbose. Between 83% and 85% of all simulations showed cost savings with glipizide GITS compared with the other agents. CONCLUSIONS: The model suggests first-line monotherapy with glipizide GITS should result in desirable short-term economic benefits for managed care. Because the model incorporates recommended glycemic goals and performed well in sensitivity analyses, it should be applicable to a variety of clinical practices and useful for economic assessments of new therapies. Results of this model should be verified prospectively in typical care settings.