Advertisement

Archives of Toxicology

, Volume 81, Issue 9, pp 605–617 | Cite as

Bias in toxicology

  • Birgitte Wandall
  • Sven Ove Hansson
  • Christina Rudén
Regulatory Toxicology

Abstract

The potential for bias, i.e., influences that cause results to deviate systematically from the truth is substantial both in toxicological research and in the performance of standardized toxicological testing. In this contribution, major potential sources of bias in toxicological research and testing are identified. Due to the lack of empirical studies of bias in toxicology, very little is known about its prevalence and impact. Areas to consider for such studies are pointed out, and it is suggested that such investigations should be given priority.

Keywords

Bias Systematic errors Toxicity testing Chemicals control Guideline tests 

Notes

Acknowledgements

This work was funded by the Swedish Research Council for Environment, Agricultural Sciences and Spatial planning (FORMAS), and the Swedish Foundation for Strategic Environmental Research (MISTRA). An earlier version of this paper was presented at a seminar hosted by professor Helen Håkansson at the Institute for Environmental Medicine, Karolinska Institutet. The authors wish to thank participants in that seminar for helpful comments.

References

  1. Barnes DE, Bero LA (1998) Why review articles on the health effects of passive smoking reach different conclustions. JAMA 279(19):1566–1570PubMedCrossRefGoogle Scholar
  2. Bekelman JE, Li Y, Gross CP (2003) Scope and impact of financial conflicts of interest in biomedical research. JAMA 289(4):454–464PubMedCrossRefGoogle Scholar
  3. Bero LA, Rennie D (1996) Influences on the quality of published drug studies. Int J Technol Assess Health Care 12(2):209–237PubMedCrossRefGoogle Scholar
  4. Boorman GA, Haseman JK, Waters MD, Hardisty JF, Sills RC (2002) Quality review procedures necessary for rodent pathology databases and toxicogenomic studies: The National Toxicology Program Experience. Toxicol Pathol 30(1):88–92.  doi: 10.1080/01926230252824752 PubMedCrossRefGoogle Scholar
  5. Commission Directive 2003/63/EC on Community code relating to medicinal products for human use. Official Journal no. L 159, 27/06/2003, pp 46–94Google Scholar
  6. Correspondence about publication ethics and regulatory toxicology and pharmacology (2003). Int J Occup Environ Health 9(4):386–391 http://www.ijoeh.com/pfds/0904_Correspondence.pdf Google Scholar
  7. Council Directive 76/768/EEC (1976) on the approximation of the laws of the Member States relating to cosmetic products. Official Journal no-.L 262, 27/09/1976 pp. 169–200Google Scholar
  8. Council Directive 89/107/EEC (1988) on the approximation of the laws of the Member States concerning food additives authorized for use in foodstuffs intended for human consumption Official Journal no. L 40, 11/02/1989, pp 27–33Google Scholar
  9. Council Directive 91/414/EEC concerning the placing of plant protection products on the market (1991) Official Journal no. L 230, 19/08/1991, pp 1–32Google Scholar
  10. Council Directive 92/32/EEC (1992) Amending for the seventh time Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances. Official Journal, no. L 154, 05/06/1992, pp. 1–29Google Scholar
  11. Council of the European Union (2006) Presidency Proposal for a regulation of the European Parliament and of the council concerning the Registration, Evaluation, Authorisation and Restrictions of Chemicals (REACH), establishing a European Chemicals Agency and amending Directive 1999/45/EC and Regulation (EC) on Persistent Organic Pollutants. 15921/1/05 REV 1, Brussels, 9 March 2006, available at http://www.register.consilium.eu.int
  12. Council Regulation (EEC), no. 793/93 (1993) on the evaluation and control of the risks of existing substances. Official Journal, no L 84, 05/04/1993, pp 1–75Google Scholar
  13. Council Directive 67/548/EEC on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances (1967) Official Journal no. 196, 16/08/1967, pp 1–98Google Scholar
  14. Crissman JW, Bus JR, Miller RR(1999) Toxicology: judge data or dollars? Environ Health Perspect 107(10): A489–491PubMedCrossRefGoogle Scholar
  15. Crissman JW, Goodman DG, Hildebrandt PK, Maronpot RR, Prater DA, Riley JH, Seaman WJ, Thake DC (2004) Best practices guideline: toxicologic histopathology. Toxicol Pathol 32:126–131.  doi: 10.1080/01926230490268756 PubMedCrossRefGoogle Scholar
  16. Cunningham AR, Rosenkranz HS (2001) Estimating the extent of the health hazard posed by high-production volume chemicals. Environ Health Perspect 109(9):953–956PubMedCrossRefGoogle Scholar
  17. DeMets DL (1999) Statistics and ethics in medical research. Sci Eng Ethics 5(1):97–117PubMedCrossRefGoogle Scholar
  18. Dickersin K (1990) The existence of publication bias and risk factors for its occurrence. JAMA 268(10):1385–1389CrossRefGoogle Scholar
  19. Dickersin K (1997) How important is publication bias? A synthesis of available data. AIDS Educ Prev 9(suppl A):15–21PubMedGoogle Scholar
  20. Dickersin K, Rennie D (2003) Registering clinical trials. JAMA 290(4):516–523PubMedCrossRefGoogle Scholar
  21. Directive 98/8/EC of the European Parliament and of the Council (1998) concerning the placing of biocidal products on the market. Official Journal of the European Communities, L123, 24/04/1998, pp. 1–63Google Scholar
  22. Directive 2001/20/EC of The European Parliament and of the Council (2001). Official Journal of the European Communities no. L 121, 01/05/2001, pp. 34–44Google Scholar
  23. Directive 2001/83/EC of the European Parliament and of the Council on Community code relating to medicinal products for human use (2001) Official Journal of the European Communities no. L 311, 28/11/2001, pp 67–128Google Scholar
  24. Djulbegovic B, Lacevic M, Cantor A, Fields KK, Bennett CL, Adams JR, Kuderer NM, Lyman GH (2000) The uncertainty principle and industry-sponsored research. Lancet 356:635–638.  doi: 10.1016/S0140-6736(00)02605-2 PubMedCrossRefGoogle Scholar
  25. Doucet MS, Bridge DA, Grimlund RA, Shamoo AE (1994) An application of stratified sampling techniques for research data. Account Res 3:237–247Google Scholar
  26. Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR (1991) Publication bias in clinical research. Lancet 337(8746):867–872PubMedCrossRefGoogle Scholar
  27. European Commission (2003). Technical Guidance Document in support of Commission Directive 93/67/EEC on Risk Assessment for new notified substances, Commission Regulation (EC) No 1488/94 on Risk Assessment for existing substances and Directive 98/8/EC of the European Parliament and of the Council concerning the placing of biocidal products on the market. Part 2Google Scholar
  28. Feinleib M (1987) Biases and weak associations. Prev Med 16:150–164PubMedCrossRefGoogle Scholar
  29. Fletcher RW, Fletcher SW (2005) Clinical epidemiology: the essentials, 4th edn. Lippincott Williams & Wilkins, BaltimoreGoogle Scholar
  30. GAO (2005). Chemical regulation: options exist to improve EPA’s ability to assess health risks and manage its chemical review program. Report to Congressional Requesters, GAO-05-458. (http://www.gao.gov/cgi-bin/getrprt?GAO-05-458)
  31. Godlee F, Dickerson K (2003) Bias, subjectivity, chance and conflict of interest in editorial decisions. In: Godlee F (ed) Peer review in health sciences, 2nd edn. BMJ Publishing Group, London, pp 91–117Google Scholar
  32. Hansson SO, Rudén C (2006a) Evaluating the risk decision process. Toxicology 218(2–3):100–111PubMedCrossRefGoogle Scholar
  33. Hansson SO, Rudén C (2006b) Priority setting in the REACH system. Toxicol Sci 90(2):304–308.  doi: 10.1093/toxsci/kfj071 PubMedCrossRefGoogle Scholar
  34. Hansson SO, Rudén C (2007) Towards a theory of tiered testing. Regul Toxicol Pharmacol (in press)Google Scholar
  35. Holland T (2001) A survey of discriminant methods used in toxicological histopathology. Toxicol Pathol 29(2):269–273PubMedCrossRefGoogle Scholar
  36. Holland T (2005) The comparative power of the discriminant methods used in toxicological pathology. Toxicol Pathol 33:490–494.  doi: 10.1080/01926230590965382 PubMedCrossRefGoogle Scholar
  37. IARC Monographs on the evaluation of carcinogenic risks to humans (1980) Supplement 2Google Scholar
  38. Kaptchuk TJ (2003) Effect of interpretive bias on research evidence. BMJ 326(7404):1453–1455.  doi: 10.1136/bmj.326.7404.1453 PubMedCrossRefGoogle Scholar
  39. Koehler JJ (1993) The influence of prior beliefs on scientific judgments of evidence quality. Organ Behav Hum Decis Process 56:28–55CrossRefGoogle Scholar
  40. Lexchin J, Bero LA, Djulbegovic B, Clark O (2003) Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ 326(7400):1167–1170.  doi: 10.1136/bmj.326.7400.1167 PubMedCrossRefGoogle Scholar
  41. Lynn FM (1986) The interplay of science and values in assesing and regulating environmental risks. Sci Technol Hum Values 11(2):40–50Google Scholar
  42. Maurissen JP, Gilbert SG, Sander M, Beauchamp TL, Johnson S, Schwetz BA, Goozner M, Barrow CS (2005) In: Workshop proceedings: managing conflict of interest in science. A little consensus and a lot of controversy. Toxicol Sci 87(1) 11–14.  doi: 10.1093/toxsci/kfi240
  43. Maxwell C (1981) Clinical trials, reviews, and the journal of negative results. Br J Clin Pharmacol 1:15–18Google Scholar
  44. Murphy EA (1978) The logic of medicine. The John Hopkins University Press, BaltimoreGoogle Scholar
  45. Nordberg A, Rudén C (2007) The usefulness of the bioconcentration factor as a tool for priority setting in chemicals control. Toxicol Lett 168:113–120.  doi: 10.1016/j.toxlet.2006.11.004 PubMedCrossRefGoogle Scholar
  46. OECD guidelines for the testing of chemicals no. 451 carcinogenicity studies (adopted 12 May 1981)Google Scholar
  47. OECD guidelines for the testing of chemicals no. 452 chronic toxicity studies (adopted 12 May 1981)Google Scholar
  48. OECD Guidelines for the testing of chemicals no. 416 two-generation reproduction toxicity study (Updated Guideline, adopted 22 January 2001)Google Scholar
  49. OECD (2003) Managing conflict of interest in the public service. OECD guidelines and country experiencesGoogle Scholar
  50. OECD (2005) Managing conflict of interest in the public sector. A toolkitGoogle Scholar
  51. OECD Series on principles of good laboratory practice and compliance monitoring, no. 2 (1995) Guidance for GLP Monitoring Authorities. OCDE/GD(95)66Google Scholar
  52. OECD series on principles of good laboratory practice and compliance monitoring, no. 1 (1998) OECD principles on good laboratory practice (as revised in 1997). ENV/MC/CHEM(98)17Google Scholar
  53. Prasse K, Hildebrandt P, Dodd D (1986) Letter to the editor. Vet Pathol 23:540–541PubMedCrossRefGoogle Scholar
  54. Purchase IFH (2004) Fraud, errors and gamesmanship in experimental toxicology. Toxicology 202:1–20.  doi: 10.1016/j.tox.2004.06.029 PubMedCrossRefGoogle Scholar
  55. Resnik DB (2000a) Financial interests and research bias. Perspect Sci 8(3):255–285.  doi: 10.1162/106361400750340497 CrossRefGoogle Scholar
  56. Resnik DB (2000b) Statistics, ethics and research: an agenda for education and reform. Account Res 8:163–188CrossRefGoogle Scholar
  57. Rice JM (2005) The carcinogenicity of acrylamide. Mutat Res 580:3–20.  doi: 10.1016/j.mrgentox.2004.09.008 PubMedGoogle Scholar
  58. Roberts I, Kwan I, Evans P, Haig, S (2002) Does animal experimentation inform human healthcare? Observations from a systematic review of international animal experiments on fluid resucitation. BMJ 324:474–476PubMedCrossRefGoogle Scholar
  59. Rothman K.J (1991) The ethics of research sponsorship. J Clin Epidemiol 44(Suppl 1):S25–S28PubMedCrossRefGoogle Scholar
  60. Rudén C (2001) Interpretations of primary carcinogenicity data in 29 trichloroethylene risk assessments. Toxicology 169(3):209–225.  doi: 10.1016/S0300-483X(01)00525-X PubMedCrossRefGoogle Scholar
  61. Sackett DL (1979) Bias in Analytic Research. J Chron Dis 32:51–63PubMedCrossRefGoogle Scholar
  62. Shamoo AE, Resnik DB (2003) Responsible conduct of research. Oxford University Press, New YorkGoogle Scholar
  63. Silman A, MacFarlane GJ (2002) Epidemiological studies. A practical guide, 2nd edn. Cambridge University Press, LondonGoogle Scholar
  64. Sterling TD (1959) Publication decisions and their possible effects on inferences drawn from tests of significance—or vice versa. J Am Stat Assoc 54(285):30–34CrossRefGoogle Scholar
  65. Stern JM, Simes R J (1997) Publication bias: evidence of delayed publication in a cohort study of clinical research projects. BMJ 315(7109):640–645PubMedGoogle Scholar
  66. vom Saal FS, Welshons WV (2006) Large effects from small exposures. II. The importance of positive controls in low-dose research on bisphenol A. Environ Res 100:50–76.  doi: 10.1016/j.envres.2005.09.001sPubMedCrossRefGoogle Scholar
  67. Weinberg AM (1972) Science and trans-science. Minerva 10:208–222.  doi: 10.1007/BF01682418 Google Scholar
  68. Whitbeck C (2004) Trust and the future of research. Phys Today 57(11):48–53CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Birgitte Wandall
    • 1
  • Sven Ove Hansson
    • 1
  • Christina Rudén
    • 1
  1. 1.Department of Philosophy and the History of TechnologyRoyal Institute of Technology (KTH)StockholmSweden

Personalised recommendations