Two randomized control trials (RCTs), CREATE and CHOIR, recently published in the New England Journal of Medicine, have received intense attention and discussion by the nephrology community [1,2]. Anaemia and its treatment have been the focus of multiple randomized control studies in the recent past, most small and relatively short, so why this amount of discussion now [3–7]? These two new studies by Drueke et al. [1] and Singh et al. [2] represent the largest studies in nondialysis patients published to date; they both tested the hypothesis that higher haemoglobin would lead to improved patient outcomes, and both were negative. The purpose of this editorial is to critically review the two studies, with special attention to the methodology and analysis of both, and by so doing to understand what we can and cannot conclude from them. Importantly, the readership should be informed as to the specific issues related to analysis of randomized control trials, issues of dropout, bias and the impact of censoring, so that interpretation of these trials can be appropriately applied to clinical care. Of note, both are open label, randomized control trials, in non-dialysed CKD patients with primary endpoints that were composite CVD event endpoints. They are similar in many respects, but differ in some: mostly in the authors’ conclusions and applicability of the results. The CREATE study was conducted in Europe, Asia and Mexico, enrolled 600þ patients, and tested the specific hypothesis that treatment of Hgb values to prevent anaemia (defined as <11 g/dl) would lead to improved CVD outcomes. This is a well-conducted RCT, using Erythropoietin (EPO) beta, in patients with stage 4 CKD. Those assigned to the high and low Hgb groups were not statistically significantly different on any parameters at baseline. The separation between Hgb values in the two groups was achieved, 13.5 vs 11.5 g/dl median Hgb in high vs low groups, respectively. The majority of patients completed the study, and there were few protocol violations. There were no differences in primary outcomes, nor was there any difference in left ventricular mass index (LVMI) change over time. The mean GFR of 25ml/min was the same in both groups, as was the mean decline in GFR (3.4ml/min vs 3.1ml/min) over the 3-year period. The authors do point out that the number of patients who went onto dialysis was greater in the higher Hgb group. Because of the non-protocolized nature of dialysis start, and the fact that there were no differences in rate of decline of GFR, or actual GFR at the time of dialysis, this finding should not be overinterpreted. It is possible that the physicians caring for the patients who knew their Hgb values, would decide to commence dialysis when symptoms worsened, in the absence of other explanations for the symptoms, while those in the lower Hgb group, who complained of symptoms, might have delayed dialysis because the symptoms were attributed to anaemia rather than uraemia. The dose of EPO beta in CREATE averaged 5000 IU/per patient; in keeping with all other studies reported previously. The key ‘issue’ with CREATE was that the annual event rate was much lower than expected (6% vs 15%). The sample size calculation was based on observational studies reported from a Canadian cohort assembled almost a decade ago, in 1993, which described left ventricular hypertrophy (LVH) and LVMI differences in those with and without anaemia, and CVD events as well [8]. At that time, the use of ACEi and ARB was not common in the population, target blood pressures were not as low as current levels and treatment of phosphate, PTH and other parameters were not commonplace. The study was a noninterventional, observational study in referred CKD patients across Canada. In CREATE, patients enrolled may be either different than those who were in an original observational cohort, or are treated differently in the course of the study. As the effect of interest was Hgb, all other parameters (such as BP, mineral metabolism abnormalities, etc.) were managed in Correspondence and offprint requests to: Dr A. Levin, Nephrology, Education and Research, 1081 Burrad Street, Room 6010, Vancouver, BC V6Z 1Y6, Canada. Nephrol Dial Transplant (2007) 22: 309–312