Fludarabine phosphate for the first-line treatment of chronic lymphocytic leukaemia

Abstract

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of fludarabine phosphate or fludarabine plus cyclophosphamide for the firstline treatment of chronic lymphocytic leukaemia, based upon the evidence submission from Schering Health Care (SHC) to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission was of good quality with no major errors or omissions in the clinical evidence. Two published studies and seven abstracts were included in the company submission, which showed improvements in overall response and progression-free survival (PFS) and a higher complete response rate in the fludarabinecontaining arms; however, until the complete data are made available for evaluation these results must be interpreted with caution. The manufacturer's decision-analytic Markov model to estimate the cost-effectiveness of treatment with fludarabine monotherapy, fludarabine plus cyclophosphamide and chlorambucil was considered to be the most relevant source for informing this STA; it was appropriate for the decision problem and the data sources used to inform the model were appropriate from a UK NHS perspective. The incremental cost-effectiveness ratio of fludarabine plus cyclophosphamide compared with chlorambucil from the revised model presented in the manufacturer's addendum was £3244 per additional quality-adjusted life-year. The results were robust to a range of subgroup Discussion of ERG reports is invited. Visit the HTA website correspondence forum (www.hta.ac.uk/ correspond). DOI: 10.3310/hta13suppl1/06Fludarabine phosphate for the first-line treatment of chronic lymphocytic leukaemia 36 and sensitivity analyses. Additional sensitivity and survival analyses were carried by the ERG to investigate possible bias in the results. This brought into question the validity of the assumptions underpinning the extrapolation of data over a lifetime time horizon and showed that the ICER estimates submitted by the manufacturer were not calculated correctly and uncertainty surrounding the decision problems was not expressed fully. Based on these analyses the ERG suggests that further evidence is needed to enable an accurate assessment to be made of the clinical and costeffectiveness of fludarabine as first-line treatment for chronic lymphocytic leukaemia. The guidance issued by NICE in December 2006 as a result of the STA states that fludarabine monotherapy, within its licensed indication, is not recommended for the first-line treatment of chronic lymphocytic leukaemia; no recommendations have been made with respect to fludarabine plus cyclophosphamide combination therapy because the current marketing authorisation does not specifically provide a recommendation that fludarabine should be used concurrently with other drugs for the treatment of chronic lymphocytic leukaemia.

Economic implications of using bendamustine, alemtuzumab, or chlorambucil as a first-line therapy for chronic lymphocytic leukemia in the US: a cost-effectiveness analysis

“…The costs associated with the management of infections and other adverse events were derived from US hospital databases (inpatient costs) and Centers for Medicaid and Medicare Services files12 (outpatient costs). Utilities were derived from published literature where patients on treatment were assigned a utility score of 0.74, those who showed a response (complete or partial response) received a utility score of 0.80, and those who had progressive disease were assigned a utility score of 0.60 16. All costs were from a payer perspective and were in 2012 US dollars (Table 2).…”

Model-Based Cost-Effectiveness Analyses for the Treatment of Chronic Lymphocytic Leukaemia: A Review of Methods to Model Disease Outcomes and Estimate Utility

“…Schering (2006) was a submission to NICE (TA119). The Evidence Review Group (ERG) that reviewed the submission considered the approach adopted to be appropriate, but identified a number of concerns [33]. First, there was no evidence presented to support the assumption that the rate of progression after first-line therapy was constant and could be maintained beyond the period observed in the trial.…”

Survival Time Outcomes in Randomized, Controlled Trials and Meta-Analyses: The Parallel Universes of Efficacy and Cost-Effectiveness

“…This could improve the accuracy of the review we have conducted and would certainly offer rich insights into how the analyses were motivated and used, but it would be unlikely to change the conclusions of this study. In cases in which de novo survival analyses were undertaken by the evidence review group [8,11,15,26], one looked at further parametric curves, two examined the area under the KM curve, and one used external data. It is therefore unlikely that further examination of our sample of studies would change our conclusions.…”

“…In Table 1 ([ [7][8][9][10][11][12][13][14][15][16][17][18][19] 14 of the 16 CEAs were based on parametric models (first 3 columns). On the other hand, none of the efficacy analyses specified parametric models (first two lines).…”