Journal of Clinical Epidemiology
Volume 58, Issue 6 , Pages 543-549 , June 2005

Early extreme contradictory estimates may appear in published research: The Proteus phenomenon in molecular genetics research and randomized trials

  • John P.A. Ioannidis

      Affiliations

    • Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA
    • Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece
    • Biomedical Research Institute, Foundation for Research and Technology-Hellas, Ioannina 45110, Greece
    • Corresponding Author InformationCorresponding author: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. Tel.: +3026510-97807; fax: +3026510-97867.
  • ,
  • Thomas A. Trikalinos

      Affiliations

    • Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA
    • Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece

,Accepted 8 October 2004.

References 

  1. Dickersin K, Min YI. Publication bias: the problem that won't go away. Ann N Y Acad Sci. 1993;703:135–146
  2. Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR. Publication bias in clinical research. Lancet. 1991;337:867–872
  3. Ioannidis JP. Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials. JAMA. 1998;279:281–286
  4. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG. Replication validity of genetic association studies. Nat Genet. 2001;29:306–309
  5. Hirschhorn JN, Lohmueller K, Byrne E, Hirschhorn K. A comprehensive review of genetic association studies. Genet Med. 2002;4:45–61
  6. Siegmund D. Upward bias in estimation of genetic effects. Am J Hum Genet. 2002;71:1183–1188
  7. In:  Cooper H,  Hedges LV editor. The handbook of research synthesis. New York: Russell Sage Foundation; 1993;
  8. Lau J, Antman EM, Jimenez-Silva J, Kupelnick B, Mosteller F, Chalmers TC. Cumulative meta-analysis of therapeutic trials for myocardial infarction. N Engl J Med. 1992;327:248–254
  9. Ioannidis J, Lau J. Evolution of treatment effects over time: empirical insight from recursive cumulative metaanalyses. Proc Natl Acad Sci USA. 2001;98:831–836
  10. Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science. 1996;273:1516–1517
  11. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet. 2003;33:177–182
  12. Zhao Z, Boerwinkle E. Neighboring-nucleotide effects on single nucleotide polymorphisms: a study of 2.6 million polymorphisms across the human genome. Genome Res. 2002;12:1679–1686
  13. Sachidanandam R, Weissman D, Schmidt SC, et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature. 2001;409:928–933
  14. Ioannidis JP. Genetic associations: false or true?. Trends Mol Med. 2003;9:135–138
  15. Piantadosi S. Clinical trials: A methodological perspective. New York: John Wiley and Sons; 1997;
  16. Jadad AR, Rennie D. The randomized controlled trial gets a middle-aged checkup. JAMA. 1998;279:319–320
  17. Ioannidis JP, Trikalinos TA, Ntzani EE, Contopoulos-Ioannidis DG. Genetic associations in large versus small studies: an empirical assessment. Lancet. 2003;361:567–571
  18. The Cochrane Library. Issue 4, available at: http://www.update-software.com. Last accessed on 04/11/2003.
  19. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188
  20. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127:820–826
  21. van der Put NM, Steegers-Theunissen RP, Frosst P, et al. Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet. 1995;346:1070–1071
  22. Papapetrou C, Lynch SA, Burn J, Edwards YH. Methylenetetrahydrofolate reductase and neural tube defects. Lancet. 1996;348:58
  23. Yoshida H, Mitarai T, Kawamura T, et al. Role of the deletion of polymorphism of the angiotensin converting enzyme gene in the progression and therapeutic responsiveness of IgA nephropathy. J Clin Invest. 1995;96:2162–2169
  24. Rosenthal R. The file drawer problem and tolerance for null results. Psychol Bull. 1979;86:638–641
  25. Palmer AR. Detecting publication bias in meta-analyses: a case study of fluctuating asymmetry and sexual selection. Am Nat. 1999;154:299–332
  26. Palmer AR. Quasireplication and the contrast of error: lessons from sex ratios, heritabilities and fluctuating asymmetry. Ann Rev Ecol Syst. 2000;31:441–480
  27. Hedges LV, Vevea JL. Estimating effect size under publication bias: small sample properties and robustness of a random effects selection model. J Educ Behav Stat. 1996;21:299–332
  28. Schena M. Microarray analysis. Hoboken, NJ: Wiley-Liss; 2003;
  29. Ioannidis JP, Cappelleri JC, Lau J. Issues in comparisons between meta-analyses and large trials. JAMA. 1998;279:1089–1093
  30. Vieland VJ. The replication requirement. Nat Genet. 2001;29:244–245
  31. Attia J, Thakkinstian A, D'Este C. Meta-analyses of molecular association studies: methodologic lessons for genetic epidemiology. J Clin Epidemiol. 2003;56:297–303

PII: S0895-4356(05)00023-5

doi: 10.1016/j.jclinepi.2004.10.019

Journal of Clinical Epidemiology
Volume 58, Issue 6 , Pages 543-549 , June 2005