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Cited by 129Meta-analysis and systematic reviewsAcademic Publishing and Open AccessHealth and Medical Research Impacts

Evolution and Translation of Research Findings: From Bench to Where

Open access
Ioannidis, John P. A·2006·PLoS Clinical Trials
DOI 10.1371/journal.pctr.0010036PMC PMC1851723
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Abstract

The credibility and replication of research findings evolve over time, as data accumulate. However, translation of postulated research promises to real-life biomedical applications is uncommon. In some fields of research, we may observe diminishing effects for the strength of research findings and rapid alternations of exaggerated claims and extreme contradictions--the "Proteus Phenomenon." While these phenomena are probably more prominent in the basic sciences, similar manifestations have been documented even in clinical trials and they may undermine the credibility of clinical research. Significance-chasing bias may be in part responsible, but the greatest threat may come from the poor relevance and scientific rationale and thus low pre-study odds of success of research efforts. Given that we currently have too many research findings, often with low credibility, replication and rigorous evaluation become as important as or even more important than discovery. Credibility, replication, and translation are all desirable properties of research findings, but are only modestly correlated. In this essay, I discuss some of the evidence (or lack thereof) for the process of evolution and translation of research findings, with emphasis on the biomedical sciences.

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Research works printed but not linked: 46

  1. Marincola FM 2003 Translational medicine: A two-way road J Transl Med 1 1 14527344 PMC202357
  2. Comroe JH Jr Dripps RD 1976 Scientific basis for the support of biomedical science Science 192 105 111 769161
  3. Smith R 1987 Comroe and Dripps revisited Br Med J (Clin Res Ed) 295 1404 1407 PMC1248552 3690250
  4. O'Collins VE Macleod MR Donnan GA Horky LL van der Worp BH 2006 1,026 experimental treatments in acute stroke Ann Neurol 59 467 477 16453316
  5. Ioannidis JPA Kavvoura FK 2006 Concordance of functional in vitro data and epidemiological associations in complex disease genetics Genet Med 8 583 593 16980815
  6. Jais PH 2005 How frequent is altered gene expression among susceptibility genes to human complex disorders? Genet Med 7 83 96 15714075
  7. Zhu Y Spitz MR Amos CI Lin J Schabath MB 2004 An evolutionary perspective on single-nucleotide polymorphism screening in molecular cancer epidemiology Cancer Res 64 2251 2257 15026370
  8. Marshall JC Deitch E Moldawer LL Opal S Redl H 2005 Preclinical models of shock and sepsis: What can they tell us? Shock 24 S1 S6 16374365
  9. Macleod MR O'Collins T Howells DW Donnan GA 2004 Pooling of animal experimental data reveals influence of study design and publication bias Stroke 35 1203 1208 15060322
  10. Macleod MR O'Collins T Horky LL Howells DW Donnan GA 2005 Systematic review and metaanalysis of the efficacy of FK506 in experimental stroke J Cereb Blood Flow Metab 25 713 721 15703698
  11. Bebarta V Luyten D Heard K 2003 Emergency medicine animal research: Does use of randomization and blinding affect the results? Acad Emerg Med 10 684 687 12782533
  12. Ioannidis J Lau J 2001 Evolution of treatment effects over time: Empirical insight from recursive cumulative metaanalyses Proc Natl Acad Sci U S A 98 831 836 11158556 PMC14669
  13. Ioannidis JP Ntzani EE Trikalinos TA Contopoulos-Ioannidis DG 2001 Replication validity of genetic association studies Nat Genet 29 306 309 11600885
  14. Jennions MD Moeller AP 2002 Relationships fade with time: A meta-analysis of temporal trends in publication in ecology and evolution Proc R Soc Lond Biol Sci 269 43 48 PMC1690867 11788035
  15. Hauben M Reich L Van Puijenbroek EP Gerrits CM Patadia VK 2006 Data mining in pharmacovigilance: Lessons from phantom ships Eur J Clin Pharmacol Aug 3 [Epub ahead of print]. 16896782
  16. Morrison NA Qi JC Tokita A Kelly PJ Crofts L 1994 Prediction of bone density from vitamin D receptor alleles Nature 367 284 287 8161378
  17. Gong G Stern HS Cheng SC Fong N Mordeson J 1999 The association of bone mineral density with vitamin D receptor gene polymorphisms Osteoporos Int 9 55 64 10367030
  18. Thakkinstian A D'Este C Attia J 2004 Haplotype analysis of VDR gene polymorphisms: A meta-analysis Osteoporos Int 15 729 734 15057510
  19. Fang Y van Meurs JB d'Alesio A Jhamai M Zhao H 2005 Promoter and 3'-untranslated-region haplotypes in the vitamin d receptor gene predispose to osteoporotic fracture: The Rotterdam study Am J Hum Genet 77 807 823 16252240 PMC1271389
  20. Uitterlinden AG Ralston SH Brandi ML Carey AH Grinberg D 2006 The association between common vitamin D receptor gene variations and osteoporosis: A participant-level meta-analysis Ann Intern Med 145 255 264 16908916
  21. Ioannidis JP Trikalinos TA 2005 Early extreme contradictory estimates may appear in published research: The Proteus phenomenon in molecular genetics research and randomized trials J Clin Epidemiol 58 543 549 15878467
  22. Kuhn T 1962 The structure of scientific revolutions Chicago University of Chicago Press 226
  23. Ioannidis JP Lau J 1997 The impact of high-risk patients on the results of clinical trials J Clin Epidemiol 50 1089 1098 9368516
  24. Ioannidis JP Cappelleri JC Sacks HS Lau J 1997 The relationship between study design, results, and reporting of randomized clinical trials of HIV infection Control Clin Trials 18 431 444 9315426
  25. Horton R 1996 Surgical research or comic opera: Questions but few answers Lancet 347 984 985 8606606
  26. Gehr BT Weiss C Porzsolt F 2006 The fading of reported effectiveness. A meta-analysis of randomised controlled trials BMC Med Res Methodol 6 25 16689990 PMC1479361
  27. Glenny AM Altman DG Song F Sakarovitch C Deeks JJ 2005 Indirect comparisons of competing interventions Health Technol Assess 9 1 134 iii–iv. 16014203
  28. Heres S Davis J Maino K Jetzinger E Kissling W 2006 Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: An exploratory analysis of head-to-head comparison studies of second-generation antipsychotics Am J Psychiatry 163 185 194 16449469
  29. Gluud LL 2006 Bias in clinical intervention research Am J Epidemiol 163 493 501 16443796
  30. Rothwell PM 2006 Factors that can affect the external validity of randomised controlled trials PLoS Clin Trials 1 e9. doi: 10.1371/journal.pctr.0010009 16871331 PMC1488890 · DOI
  31. Ioannidis JP 2005 Contradicted and initially stronger effects in highly cited clinical research JAMA 294 218 228 16014596
  32. Stephens NG Parsons A Schofield PM Kelly F Cheeseman K 1996 Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS) Lancet 347 781 786 8622332
  33. [No authors listed] 1995 Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial The Writing Group for the PEPI Trial. JAMA 273 199 208 7807658
  34. Chan AW Krleža-Jerić K Schmid I Altman DG 2004 Outcome reporting bias in randomized trials funded by the Canadian Institutes of Health Research CMAJ 171 735 740 15451835 PMC517858
  35. De Vries R Andreson MS Martinson BC 2006 Normal misbehaviour: Scientists talk about the ethics of research J Empir Res Hum Res Ethics 1 43 50 16810336 PMC1483899
  36. Ioannidis JP Polycarpou A Ntais C Pavlidis N 2003 Randomised trials comparing chemotherapy regimens for advanced non-small cell lung cancer: Biases and evolution over time Eur J Cancer 39 2278 2287 14556918
  37. Barbui C Hotopf M Freemantle N Boynton J Churchill R 2000 Selective serotonin reuptake inhibitors versus tricyclic and heterocyclic antidepressants: Comparison of drug adherence Cochrane Database Syst Rev 4 CD002791 11034764
  38. Laheij RJ Rossum LG Jansen JB Straatman H Verbeek AL 1999 Evaluation of treatment regimens to cure Helicobacter pylori infection—A meta-analysis Aliment Pharmacol Ther 13 857 864 10383518
  39. Chan AW Altman DG 2005 Epidemiology and reporting of randomised trials published in PubMed journals Lancet 365 1159 1162 15794971
  40. Pauker SG 2005 The clinical interpretation of research PLoS Med 2 e395. doi: 10.1371/journal.pmed.0020395 16288562 PMC1297552 · DOI
  41. Djulbegovic B Hozo I Schwartz A McMasters KM 1999 Acceptable regret in medical decision making Med Hypotheses 53 253 259 10580533
  42. Smith R Roberts I 2006 Patient safety requires a new way to publish clinical trials PLoS Clin Trials 1 e6. doi: 10.1371/journal.pctr.0010006 16871328 PMC1488891 · DOI
  43. Topol EJ 2004 Failing the public health—Rofecoxib, Merck, and the FDA N Engl J Med 351 1707 1709 15470193
  44. Chalmers I Matthews R 2006 What are the implications of optimism bias in clinical research? Lancet 367 449 450 16473106
  45. Chalmers TC Lau J 1996 Changes in clinical trials mandated by the advent of meta-analysis Stat Med 15 1263 1268 discussion 1269 1272 8817800
  46. Clarke M Alderson P Chalmers I 2002 Discussion sections in reports of controlled trials published in general medical journals JAMA 287 2799 2801 12038916

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Authors
Ioannidis, J. P. A.
Affiliations
University of Ioannina (GR)
Corresponding author
Ioannidis, John P. A
ORCID
Ioannidis, John P. A
Venue
PLoS Clinical Trials
Publisher
Public Library of Science (PLoS)
Published
2006-11-17
Volume
1
Issue
7
Pages
e36
ISSN
1555-5887 (ISSN-L)
DOI
10.1371/journal.pctr.0010036
PMC
PMC1851723
OpenAlex
W1968103573
Cited by
129
References
9
Citations by year
2026: 3 · 2025: 4 · 2024: 6 · 2023: 3 · 2022: 7 · 2021: 11 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 11 · 2016: 13 · 2015: 5 · 2014: 6 · 2013: 5 · 2012: 11
FWCI
4.19
Type
journal article
Language
en
Update notices
correction (2007-02-02)
Open access
Licence
Locations
  • PLoS Clinical Trials (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
  • Social Sciences › Decision Sciences › Information Systems and Management › Academic Publishing and Open Access
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Health and Medical Research Impacts
Keywords
research credibility, replication, translation of research findings, exaggerated claims, biomedical research

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