o r i g i n a l a r t i c l e on other HRQOL instruments,23 whereas the other trial found an improvement in Vitality domain scores that persisted for the ﬁrst 72 of the 96 weeks.19 This last trial also reported a higher stroke rate (4% vs. 1%, P ¼ 0.048) with targeting higher Hgb.19 Four lower-quality trials of 253, 35, 14, and 10 patients were also cited, but none used the SF-36; two of these did not use active treatment in one arm, further limiting their utility.7 The workgroup concluded that ‘This evidence supports the conclusion that patients treated to a Hb target greater than 11.0 g/dl likely will experience measurable QOL beneﬁts with little or no increase in AEs compared with treatment at lower Hb levels.’7 The ACTR results greatly undermine this conclusion (see Table 4) and consequently it is likely that the 2006 KDOQI recommenda- tions would have been more conservative, and would certainly not have qualiﬁed as a Clinical Practice Guideline. In retrospect, it is apparent how a guideline group could be misled by the 1998 publication. In the methods, the 1998 publication stated that HRQOL would be assessed as a secondary end point, but the results section provides a description of the association of achieved hematocrit to improved ‘physical function’ within a treatment arm. In describing the association of higher Hgb with higher ‘physical function’, the 1998 publication offers as an example of the magnitude of the improvement a comparison of hematocrit values of 42% and 30%, the two hematocrit values that correspond to the two targets in the study. This gives the incorrect impression that being randomized to a hematocrit of 42%, rather than 30%, increases the ‘physical function’ score by 7.2, and that the P-value (0.03) refers to the comparison between treatment groups. The results from the ACTR presented here show that randomization to the higher target did not improve any parameter of HRQOL. Targeting an intermediate Hgb of 11–12 g/dl in hemodia- lysis patients with cardiac disease, as KDOQI recommended in a 2007 update, would lead to a smaller or insigniﬁcant reduction in transfusion rates than those observed in the NHT. We lack trial data on whether an intermediate target with ESAs mitigates the harm observed with higher targets. The CHOIR trial in patients with Stage 3 and 4 CKD used ESA treatment to target Hgb to 11.3 vs. 13.5 g/dl, and found an increased risk of cardiovascular events and death with the higher target.10 The placebo-controlled TREAT trial reported a signiﬁcant increase in thrombotic events and strokes with ESA use, and case–control studies support the fact that ESA use increases strokes.14,24 Therefore, it is unclear whether lowering the Hgb target while using ESA reduces stroke risk. Consequently, a target above 11 g/dl but below 13 g/dl appears to provide marginal beneﬁts and poses indeterminate risks. Healthier dialysis patients have signiﬁcantly higher baseline vitality scores on the SF-36 than reported in the NHT, and may experience some temporary improvement in vitality with higher Hgb.19,25 In contrast, in the NHT even at 6 months, after a mean 3 g/dl increase in Hgb and before substantial separation of the mortality curves, there was no signiﬁcant improvement in vitality or other HRQOL domains. In 240 DW Coyne: Quality of life in the Normal Hematocrit Trial addition, although KDOQI guideline groups and many in the nephrology community consider the results of trials of higher Hgb targets as indicative of improving quality of life, the FDA considers the results unconvincing, noting that the three largest trials comparing Hgb targets showed that ‘ythe overall quality-of-life effects were small and inconsistent’.26 These HRQOL improvements were seen in trial arms that signiﬁcantly increased the risk of cardiovascular events or death.1,10,14 Consequently, the FDA has stated that ‘Using ESAs to target a Hgb level of greater than 11 g/dl y has not been shown to provide additional patient beneﬁt.’6 Four of the authors of the 1998 publication were Amgen employees, and undoubtedly had access to the ACTR to prepare the article. Four other authors had only academic afﬁliations, and their knowledge of this information is unknown. To assure complete and balanced presentation of industry-funded randomized trial results, all authors should be required to review the complete clinical trial report and conﬁrm in writing that the manuscript reﬂects a complete reporting of the safety and efﬁcacy data. In addition, all clinical trial reports ﬁled with the FDA on all approved drugs should be made freely available within a year or two of trial completion. Alternatively, guideline groups should obtain trial reports on all major studies under review from the FDA via the Freedom of Information Act. To assure impartial review, trial report data should be extracted and conﬁrmed by external expert reviewers who have no connections to the pharmaceutical industry or the guideline organization. On the basis of these complete results on the NHT, in hemodialysis patients with ischemic heart disease or heart failure, there are no compelling beneﬁts from targeting Hgb to above 11 g/dl with ESAs. MATERIALS AND METHODS A Freedom of Information Act request was submitted on January 26, 2008 for the report on the NHT ﬁled by Amgen with the FDA following termination of the trial in 1996. The ACTR was received 1260 days later on July 11, 2011. Statements that are verbatim from the ACTR are in quotes in this publication, followed by the ACTR page number or the ACTR’s unnumbered ﬁve-page synopsis. The ACTR was available to this Journal’s reviewers and editors throughout the review and approval process. Select extracts of the report are available by emailing DCoyne@dom.wustl.edu and placing ‘Amgen NHT Trial Report’ in the subject line. The report may also be obtained through a Freedom Of Information Act request to the FDA for the 1996 Epoetin Alfa clinical study report EPO-930107. I extracted information on the primary and secondary end points of the trial, and the ﬁnal results as reported in the ACTR. Results were compared with the 1998 publication and references to the NHT in the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) anemia guidelines published in 1997, 2001, and 2006. The trial design, baseline characteristics, and treatment goals are outlined in the original publication.1 Brieﬂy, hemodialysis patients with clinical evidence of heart disease (history of heart failure or ischemic heart disease) who were already receiving epoetin and had stable Hgb of 10–11 g/dl (hemocrit 30–33%) were randomized to a higher or lower Hgb target. The higher target (Group A) received a Kidney International (2012) 82, 235–241