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 first-line 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 fludarabine containing 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 pounds 3244 per additional quality-adjusted life-year.The results were robust to a range of subgroup 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 notcalculated 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 cost effectiveness 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.