The committee noted that the evidence of clinical effectiveness was based mainly on a single unpublished randomised controlled trial (the CLL-8 trial), which compared rituximab in combination with fludarabine and cyclophosphamide with fludarabine and cyclophosphamide. The committee accepted that the CLL-8 trial demonstrated a benefit in progression-free survival, and increased overall and complete response rates for rituximab. The committee heard from clinical specialists that the CLL-8 trial population was younger and fitter than the population of people with chronic lymphocytic leukaemia seen in routine practice within the NHS in England and Wales. However, for the study population fludarabine in combination with cyclophosphamide was the appropriate comparator, and these people reflected the group who would receive fludarabine in combination with cyclophosphamide in clinical practice. The committee noted that an interim analysis of the clinical trial results had demonstrated a statistically significant gain in overall survival but this gain had not been maintained during longer follow-up. The committee accepted that crossover and subsequent lines of treatment in the trial made the overall survival benefit difficult to prove. The committee heard expert opinion that the degree of response to treatment and the duration of progression-free survival were generally accepted as surrogates for overall survival. In addition, the committee heard that cohort studies using historical controls had also shown survival benefits for people treated with rituximab-containing regimens, although results may have been influenced by changing clinical management, such as earlier identification of people with chronic lymphocytic leukaemia. On balance, the committee was persuaded that the benefits observed in progression-free survival and response rate were likely to lead to a gain in overall survival, although currently this would be difficult to quantify.