Quality of life related to oral versus subcutaneous iron chelation: a time trade-off study.

OBJECTIVE: To investigate the utility associated with subcutaneous infusion (deferoxamine) compared with once-daily oral administration (deferasirox) of iron chelation therapy. METHODS: Interviews using the time trade-off technique were used to estimate preferences (utility) for health states by finding the point at which respondents were indifferent between a longer but lower quality of life (QoL) and a shorter time in full health. Participants (n = 110) were community-based, 51% women, median age 35 years, from four regions in Sydney, Australia. Respondents rated three health states involving equal outcomes for people with thalassemia but with different treatment modalities for iron chelation; an "anchor state" describing a patient receiving iron chelation without administration mode specified, anchor state plus iron chelation via subcutaneous infusion, and anchor state plus iron chelation through once-daily oral medication. RESULTS: On an interval scale between 0 (death) and 1 (full health), median (interquartile range) utility of 0.80 (0.65-0.95) for the anchor state, 0.66 (0.45-0.87) for subcutaneous infusion, and 0.93 (0.80-0.97) for once-daily oral administration was obtained. The mean (median) difference of 0.23 (0.27) between the two treatments was statistically significant (Wilcoxon-signed rank test, P < 0.001). Subcutaneous infusion was associated with a mean (median) utility 0.13 (0.14) lower than the anchor state (P < 0.001), and once-daily oral treatment had a utility 0.10 (0.13) higher (P < 0.001). CONCLUSION: Community respondents associate oral administration of an iron chelator such as deferasirox with enhanced QoL compared with subcutaneous treatment. Assuming equal safety and efficacy, QoL gains from once-daily oral treatment compared with subcutaneous infusion are significant.

Effects of facilitated family case conferencing for advanced dementia: A cluster randomised clinical trial.

BACKGROUND: Palliative care planning for nursing home residents with advanced dementia is often suboptimal. This study compared effects of facilitated case conferencing (FCC) with usual care (UC) on end-of-life care. METHODS: A two arm parallel cluster randomised controlled trial was conducted. The sample included people with advanced dementia from 20 Australian nursing homes and their families and professional caregivers. In each intervention nursing home (n = 10), Palliative Care Planning Coordinators (PCPCs) facilitated family case conferences and trained staff in person-centred palliative care for 16 hours per week over 18 months. The primary outcome was family-rated quality of end-of-life care (End-of-Life Dementia [EOLD] Scales). Secondary outcomes included nurse-rated EOLD scales, resident quality of life (Quality of Life in Late-stage Dementia [QUALID]) and quality of care over the last month of life (pharmacological/non-pharmacological palliative strategies, hospitalization or inappropriate interventions). RESULTS: Two-hundred-eighty-six people with advanced dementia took part but only 131 died (64 in UC and 67 in FCC which was fewer than anticipated), rendering the primary analysis under-powered with no group effect seen in EOLD scales. Significant differences in pharmacological (P < 0.01) and non-pharmacological (P < 0.05) palliative management in last month of life were seen. Intercurrent illness was associated with lower family-rated EOLD Satisfaction with Care (coefficient 2.97, P < 0.05) and lower staff-rated EOLD Comfort Assessment with Dying (coefficient 4.37, P < 0.01). Per protocol analyses showed positive relationships between EOLD and staff hours to bed ratios, proportion of residents with dementia and staff attitudes. CONCLUSION: FCC facilitates a palliative approach to care. Future trials of case conferencing should consider outcomes and processes regarding decision making and planning for anticipated events and acute illness. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12612001164886.

Modelling the cost effectiveness of rituximab in chronic lymphocytic leukaemia in first-line therapy and following relapse.

BACKGROUND: The efficacy and safety of adding rituximab to fludarabine and cyclophosphamide (R-FC) for the treatment of chronic lymphocytic leukaemia (CLL) has been demonstrated in two randomised trials: CLL-8 was conducted in previously untreated patients, and REACH was conducted in previously treated patients. In both trials, progression-free survival was increased in the R-FC treatment groups compared with the FC treatment groups. In CLL-8, overall survival was also significantly increased. OBJECTIVE: To develop an economic model to assess the cost effectiveness, from the Australian healthcare perspective, of rituximab when used as a treatment for both previously untreated and relapsed/refractory CLL. METHODS: A Markov model with three health states (unprogressed, progressed and death) was developed to extrapolate the trial results over a 15-year time horizon. A treatment algorithm was developed with Australian haematologists to inform the treatments to be modelled. The base-case compares up to three courses of six cycles of R-FC ('first-line' treatment) followed by three courses of post-progression salvage ('Salvage') treatment (including rituximab) with three courses of FC followed by three courses of Salvage treatment (excluding rituximab). Subsequent treatments are incorporated into the model by repeating the unprogressed and progressed health states for each treatment. Time-dependent transition probabilities for the model were estimated from an analysis of individual patient data from CLL-8 and REACH. Comparisons of the hazard rates for the CLL-8 and REACH trials enabled an assessment of the impact on the transitions of receiving the same regimen as the first or second treatment, and hence inform assumptions regarding transitions for third and subsequent treatments. Costs applied in the model were based on published Australian prices in 2009. RESULTS: The model predicts patients receive an average of approximately two courses of treatment, and the addition of rituximab results in an incremental gain of 0.94 quality-adjusted life-years (QALYs). The incremental cost associated with the addition of rituximab is A$40,268, and hence the cost per QALY gained (QALYG) is A$42,906. CONCLUSION: Rituximab, in combination with chemotherapy, when used multiple times throughout the treatment algorithm, appears to be cost effective for CLL from the Australian healthcare perspective, with a cost/QALYG within the range generally accepted as providing value.