Correspondence
Erythropoietin on cycling performance In a recent study published in The Lancet Haematology, Jules Heuberger and colleagues¹ suggested that the use of recombinant human erythropoietin (rHuEPO) did not affect road race performance in a sample of amateur cyclists. This finding was surprising, since it is generally assumed that increased red blood cell mass would benefit endurance sports.2,3 Their study used a double-blind, randomised, placebo-controlled design and measured exercise performance in maximal, submaximal, and road race tests, finding significant differences between groups only during the maximal exercise test. The authors conclude that the effect of rHuEPO is undetectable in a real-life cycling race, and suggest that other potential performance-enhancing drugs (PEDs) should be tested using a similar study design. Although we welcome the initiative of Heuberger and colleagues¹ to use a randomised clinical trial in sports doping research, we argue that their conclusion should be met with caution. In this Correspondence, we bring philosophical and practical issues that may be worth considering in further studies. Two fundamental questions are (1) how much gain in performance is required for a drug to be considered a PED? and (2) how much statistical power a study should use to add (or clear) a drug from a list of banned substances? Heuberger and colleagues’ study¹ aimed at 80% power to detect a difference in maximal oxygen consumption (VO2 max) of 1·7 mL/min per kg. Is this enough? Given the ethical damage to sports caused by doped athletes,4,5 we argue that clinical trials on (potential) PEDs should be high powered (perhaps >95%) to detect small differences in relevant physiological parameters, as minimal differences in race times (or other performance outcomes) may determine the
winners. Unavoidably, sample sizes should be large. There may be other confounding factors as well. Can results based on amateur athletes be extrapolated to elite athletes? Do all individuals respond similarly to the PED under study? It seems plausible that differences among individuals may result from distinct genetic backgrounds, individual differences in training programmes, race strategy, and experience. In the study by Heuberger and colleagues,¹ several outcomes in both maximal and submaximal tests showed a trend towards an improved performance in the rHuEPO group, which may suggest that a similar study with larger sampling would be able to show statistical differences in a submaximal or even a race test. The relevance of clinical trials in PEDs research is undeniable, but planning such studies should consider several still unresolved issues. We declare no competing interests.
*Nelson J R Fagundes, Juliano Boquett, Fernanda S L Vianna
[email protected] Post-Graduation Program in Genetics and Molecular Biology, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre, RS 91501-970, Brazil (NJRF, JB, FSLV); and Laboratório de Medicina Genômica and Laboratório de Pesquisa em Bioética e Ética na Ciência (LAPEBEC), Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil (FSLV) 1
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www.thelancet.com/haematology Vol 4 October 2017
Heuberger JAAC, Rotmans JI, Gal P, et al. Effects of erythropoietin on cycling performance of well trained cyclists: a double-blind, randomised, placebo-controlled trial. Lancet Haematol 2017; 4: e374–86. Citartan M, Gopinath SC, Chen Y, Lakshmipriya T, Tang TH. Monitoring recombinant human erythropoietin abuse among athletes. Biosens Bioelectron 2015; 63: 86–98. de la Chapelle A, Träskelin AL, Juvonen E. Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis. Proc Natl Acad Sci USA 1993; 90: 4495–99. Solberg HA, Hanstad DV, Thoring TA. Doping in elite sport—do the fans care? Public opinion on the consequences of doping scandals. Int J Sports Marketing Sponsor 2010; 11: 2–16. Cisyk J, Courty P. Do fans care about compliance to doping regulations in sports? the impact of PED suspension in baseball. J Sports Econ 2017; 18: 323–50.
The Lancet Haematology Article by Heuberger and colleagues1 claim that repeated injections of recombinant human erythropoietin (rHuEPO) does not improve real-world cycling performance. However, it is important to carefully consider the methods of the study and the conclusions drawn, so to not hamper scientific rHuEPO anti-doping efforts.2 It would be a concern if athletes who have been found misusing rHuEPO use the study to claim that the performanceenhancing effect of their misconduct is minimal, which is not substantiated by the data. It is laudable that the authors aim at evaluating ecological performance, but the outcome of road race performance was only assessed post intervention. Possible differences between groups in initial performance as well as in pacing or drafting strategies were not controlled for. Together with the lack of test-retest variability data, it is impossible to interpret the result and draw robust conclusions applicable to the real world. The physiological measurements demonstrate marked improvements in cycling peak power and maximal oxygen consumption in accordance with several double-blind placebo-controlled studies. 3,4 This finding clearly demonstrates that rHuEPO causes enhanced capacity for aerobic metabolism. Thus, the study seems to demonstrate that a 5% increase in maximal oxygen uptake does not translate into improved performance, which is highly unlikely.5 We remind the reader that rHuEPO treatment has been demonstrated repeatedly to improve maximal oxygen consumption and peak power by 6–12%. Moreover, rHuEPO treatment increases total haemoglobin mass (Hbmass), and autologous blood transfusion (another strategy to increase Hb mass) clearly improves exercise performance.4 Therefore, the lack of Hbmass determination confounds interpretation on the effectiveness of the treatment. e459
