Association between serum 25(OH)D and hematological markers of erythropoiesis: the curse of large numbers, the treachery of p value

European Journal of Pediatrics, Dec 2018

Daniel Virella, Ana Luísa Papoila, Luís Pereira-da-Silva

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Association between serum 25(OH)D and hematological markers of erythropoiesis: the curse of large numbers, the treachery of p value

European Journal of Pediatrics pp 1–1 | Cite as Association between serum 25(OH)D and hematological markers of erythropoiesis: the curse of large numbers, the treachery of p value AuthorsAuthors and affiliations Daniel VirellaAna Luísa PapoilaLuís Pereira-da-Silva Correspondence First Online: 05 December 2018 5 Shares 155 Downloads Abbreviations 25(OH)D 25-hydroxyvitamin D Communicated by Mario Bianchetti The study by Doudin et al. [2], exploring the association between serum 25(OH)D and hematological indices in adolescents, stands out for the wise use of cross-sectional data from a German cohort to explore a novel issue related to vitamin D. The authors’ interpretation of the findings is misled by the use of p value. Applying it to assess associations whose underlying plausibility is ignored and is not suggested by the correlation coefficients, easily leads to false-positive findings. In fact, p values are strongly related to sample size [6], “sometimes attracting attention to very small effects that have little real-world importance” [1]. The authors acknowledge that “the correlation coefficients and the effect sizes are very small” [2]. Indeed, the correlation coefficient estimates range from r = −0.04 to r = 0.08 (very close to r = 0, i.e., absence of correlation), and the differences on hematological indices by levels of serum 25(OH)D are minimal (e.g., Hb [g/dl] 1st tertile: 13.7 ± 1.2; 2nd tertile: 13.5 ± 1.1; 3rd tertile 13.6 ± 1.1), in spite of the low estimated p values. None of the “statistically significant” differences found have a clear “clinical relevance” [3]. This frequent methodological error prompted methodologists and editors to discourage the widespread use of p values and to promote the use of alternative measures, with scarce success [4]. “False positive findings are detrimental to science and society, as once published, they accumulate persistent untrue evidence” [5]. Notes Authors’ contributions Daniel Virella: critical reading of the article by Doudin et al., review of the statistical analysis, review of the literature, and writing this manuscript. Ana Luisa Papoila: critical reading of the article by Doudin et al., review of the statistical analysis, and writing this manuscript. Luis Pereira-da-Silva: critical reading of the article by Doudin et al., and contributed to the final manuscript. All authors read and approved the final manuscript. Compliance with ethical standards Conflict of interest The authors declare that they do not have a financial relationship with the organization that sponsored the research. References 1. Boyd JC, Annesley TM (2014) To P or not to P: that is the question. Clin Chem 60:909–910CrossRefPubMedGoogle Scholar 2. Doudin A, Becker A, Rothenberger A, Meyer T (2018) Relationship between serum 25-hydroxyvitamin D and red blood cell indices in German adolescents. Eur J Pediatr 177:583–591CrossRefPubMedGoogle Scholar 3. Goodman S (2008) A dirty dozen: twelve p-value misconceptions. Semin Hematol 45:135–140CrossRefPubMedGoogle Scholar 4. Ludwig DA (2005) Use and misuse of p-values in designed and observational studies: guide for researchers and reviewers. Aviat Space Environ Med 76:675–680PubMedGoogle Scholar 5. Lytsy P (2017) Creating falseness - how to establish statistical evidence of the untrue. J Eval Clin Pract 23:923–927CrossRefPubMedPubMedCentralGoogle Scholar 6. Wellek S (2017) A critical evaluation of the current “p-value controversy”. Biom J 59:854–872CrossRefPubMedGoogle Scholar Copyright information © Springer-Verlag GmbH Germany, part of Springer Nature 2018 Authors and Affiliations Daniel Virella1Email authorView author's OrcID profileAna Luísa Papoila123Luís Pereira-da-Silva121.Epidemiology and Statistics Office, Research UnitCentro Hospitalar de Lisboa CentralLisbonPortugal2.NOVA Medical SchoolUniversidade Nova de LisboaLisbonPortugal3.Centre of Statistics and its Applications, Faculty of Sciences (CEAUL)University of LisbonLisbonPortugal


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Daniel Virella, Ana Luísa Papoila, Luís Pereira-da-Silva. Association between serum 25(OH)D and hematological markers of erythropoiesis: the curse of large numbers, the treachery of p value, European Journal of Pediatrics, 2018, 1-1, DOI: 10.1007/s00431-018-3296-6