Abstract
Bias is ubiquitous in research. The advent of the molecular era provides a unique opportunity to study the consequences of bias with large-scale empirical evidence accumulated in the massive data produced by the current discovery-oriented scientific effort, rather than just with theoretical speculations and constructs. Here I discuss some empirical evidence about manifestations of bias in molecular epidemiology. Bias may manifest as either heterogeneity or as deviation from the true estimates. The failure to translate molecular knowledge and the failure to replicate information are some typical hallmarks of bias at action. The acquired knowledge about the behaviour and manifestations of bias in molecular fields can be transferred back also to more traditional fields of epidemiology and medical research. Getting rid of false claims of the past is at least as important as producing new scientific discoveries. In many fields, the observed effects sizes that circulate as established knowledge are practically estimating only the net bias that has operated in the field all along. Issues of plausibility (in particular biological plausibility), replication, and credibility that form the theoretical basis of epidemiology and etiological inference can now be approached with large-scale empirical data.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
DL Sackett (1979) ArticleTitleBias in analytic research J Chronic Dis 32 51–63 Occurrence Handle10.1016/0021-9681(79)90012-2 Occurrence Handle447779
I Olkin (1995) ArticleTitleMeta-analysis: Reconciling the results of independent studies Stat Med 14 457–472 Occurrence Handle7792440
J Lau JP Ioannidis CH Schmid (1997) ArticleTitleQuantitative synthesis in systematic reviews Ann Intern Med 127 820–826 Occurrence Handle9382404
DG Contopoulos-Ioannidis E Ntzani JP Ioannidis (2003) ArticleTitleTranslation of highly promising basic science research into clinical applications Am J Med 114 477–484 Occurrence Handle10.1016/S0002-9343(03)00013-5 Occurrence Handle12731504
JP Ioannidis (2004) ArticleTitleMaterializing research promises: Opportunities, priorities and conflicts in translational medicine J Transl Med 2 IssueID1 5 Occurrence Handle10.1186/1479-5876-2-5 Occurrence Handle14754464
DF Ransohoff (2005) ArticleTitleBias as a threat to the validity of cancer molecular-marker research Nat Rev Cancer 5 142–149 Occurrence Handle10.1038/nrc1550 Occurrence Handle15685197
DF Ransohoff (2004) ArticleTitleRules of evidence for cancer molecular-marker discovery and validation Nat Rev Cancer 4 309–314 Occurrence Handle10.1038/nrc1322 Occurrence Handle15057290
JP Ioannidis EE Ntzani TA Trikalinos DG Contopoulos-Ioannidis (2001) ArticleTitleReplication validity of genetic association studies Nat Genet 29 306–309 Occurrence Handle10.1038/ng749 Occurrence Handle11600885
MJ Khoury J Little (2000) ArticleTitleHuman genome epidemiologic reviews: The beginning of something HuGE Am J Epidemiol 151 2–3 Occurrence Handle10625169
JP Ioannidis (2003) ArticleTitleGenetic associations: False or true? Trends Mol Med 9 135–138 Occurrence Handle10.1016/S1471-4914(03)00030-3 Occurrence Handle12727138
TA Trikalinos EE Ntzani DG Contopoulos-Ioannidis JP Ioannidis (2004) ArticleTitleEstablishment of genetic associations for complex diseases is independent of early study findings Eur J Hum Genet 12 762–769 Occurrence Handle10.1038/sj.ejhg.5201227 Occurrence Handle15213707
TA Trikalinos R Churchill M Ferri et al. (2004) ArticleTitleEffect sizes in cumulative meta-analyses of mental health randomized trials evolved over time J Clin Epidemiol. 57 1124–1130 Occurrence Handle10.1016/j.jclinepi.2004.02.018 Occurrence Handle15612138
JP Ioannidis (2005) ArticleTitleContradicted and initially stronger effects in highly cited clinical research JAMA 294 218–228 Occurrence Handle10.1001/jama.294.2.218 Occurrence Handle16014596
DA Lawlor G Davey Smith D Kundu KR Bruckdorfer S Ebrahim (2004) ArticleTitleThose confounded vitamins: What can we learn from the differences between observational versus randomised trial evidence? Lancet 363 1724–1727 Occurrence Handle10.1016/S0140-6736(04)16260-0 Occurrence Handle15158637
JE Rossouw GL Anderson RL Prentice et al. (2002) ArticleTitleRisks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results From the Women’s Health Initiative randomized controlled trial JAMA 288 321–333 Occurrence Handle12117397
S Wacholder S Chanock M Garcia-Closas L El Ghormli N Rothman (2004) ArticleTitleAssessing the probability that a positive report is false: An approach for molecular epidemiology studies J Natl Cancer Inst 96 434–442 Occurrence Handle15026468
TR Rebbeck M Spitz X Wu (2004) ArticleTitleAssessing the function of genetic variants in candidate gene association studies Nat Rev Genet 5 589–597 Occurrence Handle10.1038/nrg1403 Occurrence Handle15266341
J Lau JP Ioannidis CH Schmid (1998) ArticleTitleSumming up evidence: One answer is not always enough Lancet 351 123–127 Occurrence Handle10.1016/S0140-6736(97)08468-7 Occurrence Handle9439507
Ioannidis JPA. Differentiating biases from genuine heterogeneity: Distinguishing artifactual from substantive effects. In: Rothstein HR, Sutton AJ, Borenstein M (eds), Publication bias in meta-analysis: Prevention, assessment and adjustments. John Wiley and Sons, New York: 2005.
M Egger G Davey Smith M Schneider C Minder (1997) ArticleTitleBias in meta-analysis detected by a simple, graphical test BMJ 315 629–634 Occurrence Handle9310563
J Ioannidis J Lau (2001) ArticleTitleEvolution of treatment effects over time: Empirical insight from recursive cumulative metaanalyses Proc Natl Acad Sci USA 98 831–836 Occurrence Handle10.1073/pnas.021529998 Occurrence Handle11158556
JP Ioannidis DG Contopoulos-Ioannidis J Lau (1999) ArticleTitleRecursive cumulative meta-analysis: A diagnostic for the evolution of total randomized evidence from group and individual patient data J Clin Epidemiol 52 281–291 Occurrence Handle10.1016/S0895-4356(98)00159-0 Occurrence Handle10235168
JP Ioannidis TA Trikalinos EE Ntzani DG Contopoulos-Ioannidis (2003) ArticleTitleGenetic associations in large versus small studies: An empirical assessment Lancet 361 567–571 Occurrence Handle10.1016/S0140-6736(03)12516-0 Occurrence Handle12598142
JP Ioannidis TA Trikalinos (2005) ArticleTitleEarly extreme contradictory estimates may appear in published research: The Proteus phenomenon in molecular genetics research and randomized trials J Clin Epidemiol 58 543–549 Occurrence Handle10.1016/j.jclinepi.2004.10.019 Occurrence Handle15878467
PA Kyzas KT Loizou JP Ioannidis (2005) ArticleTitleSelective reporting biases in cancer prognostic factor studies J Natl Cancer Inst 97 1043–1055 Occurrence Handle16030302
JP Ioannidis (2005) ArticleTitleWhy most published research findings are false PLoS Med 2 IssueID8 e124 Occurrence Handle10.1371/journal.pmed.0020124 Occurrence Handle16060722
CD Angelis ParticleDe JM Drazen FA Frizelle et al. (2005) ArticleTitleIs this clinical trial fully registered? A statement from the International Committee of Medical Journal Editors Ann Intern Med 143 146–148 Occurrence Handle16027458
R Smith (2005) ArticleTitleMedical journals are an extension of the marketing arm of pharmaceutical companies PLoS Med 2 IssueID5 e138 Occurrence Handle10.1371/journal.pmed.0020138 Occurrence Handle15916457
JP Ioannidis J Bernstein P Boffetta et al. (2005) ArticleTitleA network of investigator networks in human genome epidemiology Am J Epidemiol 162 302–304 Occurrence Handle10.1093/aje/kwi201 Occurrence Handle16014777
JP Ioannidis PS Rosenberg JJ Goedert TR O’Brien (2002) ArticleTitleInternational meta-analysis of HIV host genetics. Commentary: Meta-analysis of individual participants’ data in genetic epidemiology Am J Epidemiol 156 204–210 Occurrence Handle10.1093/aje/kwf031 Occurrence Handle12142254
Ioannidis JPA. Grading the credibility of molecular evidence for complex diseases. Int J Epidemiol 2005 (in press).
S Michiels S Koscielny C Hill (2005) ArticleTitlePrediction of cancer outcome with microarrays: A multiple random validation strategy Lancet 365 488–492 Occurrence Handle15705458
JP Ioannidis (2005) ArticleTitleMicroarrays and molecular research: Noise discovery? Lancet. 365 454–455 Occurrence Handle15705441
EE Ntzani JP Ioannidis (2003) ArticleTitlePredictive ability of DNA microarrays for cancer outcomes and correlates: An empirical assessment Lancet 362 1439–1444 Occurrence Handle10.1016/S0140-6736(03)14686-7 Occurrence Handle14602436
DF Ransohoff (2005) ArticleTitleLessons from controversy: Ovarian cancer screening and serum proteomics J Natl Cancer Inst 97 315–319 Occurrence Handle15713968
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ioannidis, J. Molecular Bias. Eur J Epidemiol 20, 739–745 (2005). https://doi.org/10.1007/s10654-005-2028-1
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10654-005-2028-1