Estimating outcomes and cost effectiveness using a single-arm clinical trial: ofatumumab for double-refractory chronic lymphocytic leukemia.

BACKGROUND: Ofatumumab (Arzerra®, Novartis) is a treatment for chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab [double refractory (DR-CLL)]. Ofatumumab was licensed on the basis of an uncontrolled Phase II study, Hx-CD20-406, in which patients receiving ofatumumab survived for a median of 13.9 months. However, the lack of an internal control arm presents an obstacle for the estimation of comparative effectiveness. METHODS: The objective of the study was to present a method to estimate the cost effectiveness of ofatumumab in the treatment of DR-CLL. As no suitable historical control was available for modelling, the outcomes from non-responders to ofatumumab were used to model the effect of best supportive care (BSC). This was done via a Cox regression to control for differences in baseline characteristics between groups. This analysis was included in a partitioned survival model built in Microsoft® Excel with utilities and costs taken from published sources, with costs and quality-adjusted life years (QALYs) were discounted at a rate of 3.5% per annum. RESULTS: Using the outcomes seen in non-responders, ofatumumab is expected to add approximately 0.62 life years (1.50 vs. 0.88). Using published utility values this translates to an additional 0.30 QALYs (0.77 vs. 0.47). At the list price, ofatumumab had a cost per QALY of £130,563, and a cost per life year of £63,542. The model was sensitive to changes in assumptions regarding overall survival estimates and utility values. CONCLUSIONS: This study demonstrates the potential of using data for non-responders to model outcomes for BSC in cost-effectiveness evaluations based on single-arm trials. Further research is needed on the estimation of comparative effectiveness using uncontrolled clinical studies.

Utility elicitation study in the UK general public for late-stage chronic lymphocytic leukaemia.

OBJECTIVES: In the United Kingdom (UK), chronic lymphocytic leukaemia (CLL) makes up 40 % of all leukaemias in patients over 65 years. The study objective was to obtain societal preferences in the UK for "progression-free" and "progressive" states of late-stage CLL, refractory to current first and second line regimens. Preferences were also obtained for selected treatment-related adverse events (AEs). METHODS: A utility elicitation study, using the time trade-off (TTO) method, was conducted by face-to-face interviews with 110 subjects for a baseline disease state (before treatment), three primary disease states [progression-free survival (PFS) and treatment responder, PFS and treatment non-responder and disease progression], and 4 AE sub-states (PFS responder with thrombocytopenia, neutropenia, and infection, and PFS non-responder with infection). TTO scores were converted into utility values, and disutilities were calculated for AEs. Visual analogue scale (VAS) scores were obtained. RESULTS: The primary disease state mean TTO utility scores were: baseline: 0.549; PFS response: 0.671; PFS non-response: 0.394; and progression: 0.214. The mean TTO utility (disutility) scores for the AEs were: PFS response with thrombocytopenia, 0.563 (-0.108), neutropenia, 0.508 (-0.163), and infection, 0.476 (-0.195); PFS non-response with infection, 0.333 (-0.061). The VAS results were in line with the TTO results. CONCLUSIONS: The utility was higher for the PFS state than baseline, but decreased below baseline in non-response and disease progression states. AEs had an impact on utility within the PFS response state. The severe infection AE had a greater impact on utilities for the responding to treatment state compared to the non-responder state.

Economic efficiency of genetic screening to inform the use of abacavir sulfate in the treatment of HIV.

BACKGROUND: Abacavir sulfate (abacavir) is associated with a hypersensitivity reaction (HSR) that affects 5-8% of patients. While serious complications are rare, failure to identify it, or abacavir re-challenge following HSR, can be fatal. Genetic screening for HLA-B*5701 can identify patients who are likely to experience an HSR and reduces the incidence of the reaction. OBJECTIVE: We assessed the intrinsic and practical value, from the US healthcare system perspective, of prospective HLA-B*5701 screening among a population of antiretroviral-naive patients without elevated risk factors for cardiovascular disease, plasma HIV RNA >100,000 copies/mL, or pre-existing renal insufficiency. METHODS: Two approaches were used to evaluate the costs and benefits of prospective screening. First, the efficiency of HLA-B*5701 screening compared with no screening prior to abacavir initiation (intrinsic value of screening) was evaluated using a 60-day decision-tree model. Next, the practical value of screening was assessed using a lifetime discrete-event simulation model that compared HLA-B*5701 screening prior to abacavir use versus initiation with a tenofovir-containing regimen. Screening-effectiveness parameters were taken from an open-label trial that incorporated screening prior to abacavir initiation and other published studies. Treatment efficacy was derived from clinical trials. Modelling assumptions, costs ($US, year 2007 values) and other parameters were derived from published sources, primary data analysis and expert opinion. Multiple one-way sensitivity and scenario analyses were performed to assess parameter uncertainty. The primary outcome measure for the short-term screening versus no screening analysis was cost per patient. For the long-term analysis, outcomes were presented as QALYs. Costs and effects were discounted at 3% per year. RESULTS: Over the first 60 days of treatment, prospective screening prior to abacavir initiation cost an additional $US17 per patient and avoided 537 HSRs per 10,000 patients. The per-patient cost of screening was sensitive to the cost of the genetic test, HSR costs and screening performance. In the lifetime model, screening-informed abacavir use was more effective and less costly than initiation with a tenofovir-containing regimen in the base case and in sensitivity analyses. CONCLUSIONS: Our results suggest that prospective HLA-B*5701 screening prior to abacavir initiation produces cost savings and should become a standard component of HIV care.