Concordance of randomized and nonrandomized studies was unrelated to translational patterns of two nutrient-disease associations

J Clin Epidemiol. 2012 Jan;65(1):16-29. doi: 10.1016/j.jclinepi.2011.07.006. Epub 2011 Nov 1.


Objective: There are several examples in nutrition of discordance between the results of observational studies and randomized controlled trials (RCTs). We hypothesized that this discordance is attributable to differences in the translational paths of nutrient-disease associations. Translational paths can be assessed using citation analysis.

Study design and setting: We compared the characteristics of citation networks using examples, where RCTs and observational studies agreed (long-chain n-3 polyunsaturated fatty acids [n-3 PUFA]) or disagreed (vitamin E). We performed systematic reviews in each example, constructed citation networks, and compared them with respect to the number of articles and citation relationships between them, as well as the distribution of articles' hub and authority scores.

Results: For n-3 PUFA, meta-analyses of 14 RCTs and 10 observational studies both suggested that higher intake was associated with lower cardiovascular mortality. For vitamin E, the meta-analysis of 14 RCTs excluded a clinically significant effect, whereas 14 observational studies reported a significant inverse association. The respective citation networks consisted of 392 (n-3 PUFA) and 351 (vitamin E) articles. No differences between the characteristics of the two networks were identified. There was no evidence that the observational studies predated RCTs in the translational process in either example.

Conclusion: In the two examples, citation network characteristics do not predict concordance in the results of observational studies and RCTs.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antioxidants / administration & dosage
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control*
  • Clinical Trials as Topic
  • Data Interpretation, Statistical
  • Docosahexaenoic Acids / administration & dosage
  • Eicosapentaenoic Acid / administration & dosage
  • Evidence-Based Medicine
  • Fatty Acids, Omega-3 / administration & dosage
  • Food*
  • Humans
  • Meta-Analysis as Topic
  • Randomized Controlled Trials as Topic*
  • Risk Assessment
  • Translational Medical Research*
  • Treatment Outcome
  • Vitamin E / administration & dosage


  • Antioxidants
  • Fatty Acids, Omega-3
  • Vitamin E
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid