Theoretical Medicine and Bioethics

, Volume 34, Issue 3, pp 189–206 | Cite as

The perils of protection: vulnerability and women in clinical research

Article

Abstract

Subpart B of 45 Code of Federal Regulations Part 46 (CFR) identifies the criteria according to which research involving pregnant women, human fetuses, and neonates can be conducted ethically in the United States. As such, pregnant women and fetuses fall into a category requiring “additional protections,” often referred to as “vulnerable populations.” The CFR does not define vulnerability, but merely gives examples of vulnerable groups by pointing to different categories of potential research subjects needing additional protections. In this paper, I assess critically the role of this categorization of pregnant women involved in research as “vulnerable,” both as separate entities and in combination with the fetuses they carry. In particular, I do three things: (1) demonstrate that pregnant women qua pregnancy are either not “vulnerable” according to any meaningful definition of that term or that such vulnerability is irrelevant to her status as a research participant; (2) argue that while a fetus may be vulnerable in terms of dependency, this categorization does not equate to the vulnerability of the pregnant woman; and (3) suggest that any vulnerability that appends to women is precisely the result of federal regulations and dubious public perceptions about pregnant women. I conclude by demonstrating how this erroneous characterization of pregnant women as “vulnerable” and its associated protections have not only impeded vital research for pregnant women and their fetuses, but have also negatively affected the inclusion of all women in clinical research.

Keywords

Pregnant women Clinical research Vulnerability Research subjects 

References

  1. 1.
    US Code of Federal Regulations. 2009. Protection of human subjects. 45 CFR 46. http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html. Accessed 2 May 2013.
  2. 2.
    Coleman, C.H. 2009. Vulnerability as a regulatory category in human subject research. Journal of Law, Medicine and Ethics 37(1): 12–18.CrossRefGoogle Scholar
  3. 3.
    Macklin, R. 2003. Bioethics, vulnerability, and protection. Bioethics 17(5–6): 472–486.CrossRefGoogle Scholar
  4. 4.
    Hurst, S.A. 2008. Vulnerability in research and health care; describing the elephant in the room? Bioethics 22(4): 191–202.CrossRefGoogle Scholar
  5. 5.
    Schroeder, D., and E. Gefenas. 2009. Vulnerability: Too vague and too broad? Cambridge Quarterly of Healthcare Ethics 18(2): 113–121.CrossRefGoogle Scholar
  6. 6.
    Levine, C., R. Faden, C. Grady, D. Hammerschmidt, L. Eckenwiler, and J. Sugarman. 2004. The limitations of “vulnerability” as a protection for human research participants. American Journal of Bioethics 4(3): 44–49.CrossRefGoogle Scholar
  7. 7.
    Kipnis, K. 2001. Vulnerability in research subjects: A bioethical taxonomy. In Ethical and policy issues in research involving human participants, vol. 2, G1–G13. Bethesda, MD: National Bioethics Advisory Commission. http://bioethics.georgetown.edu/nbac/human/overvol2.html. Accessed 9 May 2013.
  8. 8.
    Kipnis, K. 2003. Seven vulnerabilities in the pediatric research subject. Theoretical Medicine and Bioethics 24(2): 107–120.CrossRefGoogle Scholar
  9. 9.
    Swan, H.D., and D.C. Borshoff. 1994. Informed consent—Recall of risk information following epidural analgesia in labour. Anaesthesia and Intensive Care 22(2): 139–141.Google Scholar
  10. 10.
    Frohlich, S., T. Tan, A. Walsh, and M. Carey. 2011. Epidural analgesia for labour: Maternal knowledge, preferences and informed consent. Irish Medical Journal 104(10): 300–302.Google Scholar
  11. 11.
    Pattee, C., M. Ballantyne, and B. Milne. 1997. Epidural analgesia for labour and delivery: Informed consent issues. Canadian Journal of Anaesthesia 44(9): 918–923.CrossRefGoogle Scholar
  12. 12.
    Broaddus, B.M., and S. Chandrasekhar. 2011. Informed consent in obstetric anesthesia. Anesthesia and Analgesia 112(4): 912–915.CrossRefGoogle Scholar
  13. 13.
    Kalish, R.B., L.B. McCullough, and F.A. Chervenak. 2008. Patient choice cesarean delivery: Ethical issues. Current Opinion in Obstetrics and Gynecology 20(2): 116–119.CrossRefGoogle Scholar
  14. 14.
    Little, M.O., A.D. Lyerly, L.M. Mitchell, E.M. Armstrong, L.H. Harris, and R. Kukla. 2008. Mode of delivery: Toward responsible inclusion of patient preferences. Obstetrics and Gynecology 112(4): 913–918.CrossRefGoogle Scholar
  15. 15.
    American College of Obstetricians and Gynecologists. 2008. Surgery and patient choice. ACOG committee opinion no. 395. Obstetrics and Gynecology 111: 243–247.CrossRefGoogle Scholar
  16. 16.
    Cantor, J.D. 2012. Court-ordered care—A complication of pregnancy to avoid. New England Journal of Medicine 366(24): 2237–2240.CrossRefGoogle Scholar
  17. 17.
    Lyerly, A.D., M.O. Little, and R. Faden. 2008. The second wave: Toward responsible inclusion of pregnant women in research. International Journal of Feminist Approaches to Bioethics 1(2): 5–22.CrossRefGoogle Scholar
  18. 18.
    Merton, V. 1993. The exclusion of pregnant, pregnable, and once-pregnable people (aka women) from biomedical research. American Journal of Law and Medicine 19(4): 369–451.Google Scholar
  19. 19.
    Shahin, I., and A. Einarson. 2011. Knowledge transfer and translation: Examining how teratogen information is disseminated. Birth Defects Research, Part A: Clinical and Molecular Teratology 91(11): 956–961.CrossRefGoogle Scholar
  20. 20.
    Walfisch, A. 2012. Maternal depression and perception of teratogenicity. Journal of population therapeutics and clinical pharmacology 19(3): e376–e379.Google Scholar
  21. 21.
    Widnes, S.F., J. Schjott, and A.G. Granas. 2012. Risk perception and medicines information needs in pregnant women with epilepsy—A qualitative study. Seizure 21(8): 597–602.CrossRefGoogle Scholar
  22. 22.
    Byatt, N., K.M. Deligiannidis, and M.P. Freeman. 2013. Antidepressant use in pregnancy: A critical review focused on risks and controversies. Acta Psychiatrica Scandinavica 127(2): 94–114.CrossRefGoogle Scholar
  23. 23.
    Mendola, P., S.K. Laughon, T.I. Mannisto, K. Leishear, U.M. Reddy, Z. Chen, and J. Zhang. 2013. Obstetric complications among US women with asthma. American Journal of Obstetrics and Gynecology 208(2): 127.e1–127.e8.CrossRefGoogle Scholar
  24. 24.
    Baylis, F. 2010. Pregnant women deserve better. Nature 465(7299): 689–690.CrossRefGoogle Scholar
  25. 25.
    Andrade, S.E., J.H. Gurwitz, R.L. Davis, et al. 2004. Prescription drug use in pregnancy. American Journal of Obstetrics and Gynecology 191(2): 398–407.CrossRefGoogle Scholar
  26. 26.
    Daw, J.R., B. Mintzes, M.R. Law, G.E. Hanley, and S.G. Morgan. 2012. Prescription drug use in pregnancy: A retrospective, population-based study in British Columbia, Canada (2001–2006). Clinical therapeutics 34(1): 239–249e2.CrossRefGoogle Scholar
  27. 27.
    Yang, T., M.C. Walker, D. Krewski, et al. 2008. Maternal characteristics associated with pregnancy exposure to FDA category C, D, and X drugs in a Canadian population. Pharmacoepidemiology and Drug Safety 17(3): 270–277.CrossRefGoogle Scholar
  28. 28.
    Guttmacher Institute. 2012. Facts on unintended pregnancy in the United States. In Brief: Fact sheet. http://www.guttmacher.org/pubs/FB-Unintended-Pregnancy-US.html. Accessed 2 May 2013.
  29. 29.
    Lyerly, A.D., L.M. Mitchell, E.M. Armstrong, L.H. Harris, R. Kukla, and M. Kuppermann. 2009. RISK and the pregnant body. Hastings Center Report 39(6): 34–42.CrossRefGoogle Scholar
  30. 30.
    Chambers, C.D., J.E. Polifka, and J.M. Friedman. 2008. Drug safety in pregnant women and their babies: Ignorance not bliss. Clinical Pharmacology and Therapeutics 83(1): 181–183.CrossRefGoogle Scholar
  31. 31.
    Macklin, R. 2010. Enrolling pregnant women in biomedical research. Lancet 375(9715): 632–633.CrossRefGoogle Scholar
  32. 32.
    Mastroianni, A.C., R. Faden, and D. Federman. 1994. Women and health research: A report from the institute of medicine. Kennedy Institute of Ethics Journal 4(1): 55–62.CrossRefGoogle Scholar
  33. 33.
    Kass, N.E., H.A. Taylor, and P.A. King. 1996. Harms of excluding pregnant women from clinical research: The case of HIV-infected pregnant women. Journal of Law, Medicine and Ethics 24(1): 36–46.CrossRefGoogle Scholar
  34. 34.
    Lo, W.Y., and J.M. Friedman. 2002. Teratogenicity of recently introduced medications in human pregnancy. Obstetrics and Gynecology 100(3): 465–473.CrossRefGoogle Scholar
  35. 35.
    Adam, M.P., J.E. Polifka, and J.M. Friedman. 2011. Evolving knowledge of the teratogenicity of medications in human pregnancy. American Journal of Medical Genetics Part C, Seminars in Medical Genetics 157(3): 175–182.CrossRefGoogle Scholar
  36. 36.
    Friedman, J.M. 2012. ABCDXXX: The obscenity of postmarketing surveillance for teratogenic effects. Birth Defects Research, Part A: Clinical and Molecular Teratology 94(8): 670–676.CrossRefGoogle Scholar
  37. 37.
    Wilcox, S., S.A. Shumaker, D.J. Bowen, et al. 2001. Promoting adherence and retention to clinical trials in special populations: A women’s health initiative workshop. Controlled Clinical Trials 22(3): 279–289.CrossRefGoogle Scholar
  38. 38.
    Kukla, R. 2005. Mass hysteria: Medicine, culture, and mothers’ bodies. Oxford: Rowman and Littlefield Publishers.Google Scholar
  39. 39.
    Grimes, D.A., and J.F. Peipert. 2010. Electronic fetal monitoring as a public health screening program: The arithmetic of failure. Obstetrics Gynecology 116(6): 1397–1400.CrossRefGoogle Scholar
  40. 40.
    Wong, J.W., M.M. Heller, and J.E. Murase. 2012. Caution advised in interpretation of US FDA risk classification for dermatological medications during pregnancy. Dermatology Online Journal 18(10): 15.Google Scholar
  41. 41.
    Fisk, N.M., and R. Atun. 2008. Market failure and the poverty of new drugs in maternal health. PLoS Medicine 5(1): e22.CrossRefGoogle Scholar
  42. 42.
    Food and Drug Administration. 1993. Guidelines for the study and evaluation of gender differences in the clinical evaluation of drugs. Federal Register 58(139): 39406–39416.Google Scholar
  43. 43.
    Faden, R., N. Kass, and D. McGraw. 1996. Women as vessels and vectors: Lessons from the HIV epidemic. In Feminism and bioethics: Beyond reproduction, ed. S.M. Wolf, 252–281. New York: Oxford University Press.Google Scholar
  44. 44.
    Department of Health and Human Services. 2011. Monitoring adherence to the NIH policy on the inclusion of women and minorities as subjects in clinical research: Fiscal year 2009 and 2010. http://orwh.od.nih.gov/research/inclusion/pdf/Inclusion-ComprehensiveReport-FY-2009-2010.pdf. Accessed 9 May 2013.
  45. 45.
    Geller, S.E., A. Koch, B. Pellettieri, and M. Carnes. 2011. Inclusion, analysis, and reporting of sex and race/ethnicity in clinical trials: Have we made progress? Journal of Women’s Health 20(3): 315–320.CrossRefGoogle Scholar
  46. 46.
    Van Spall, H., A. Toren, A. Kiss, and R.A. Fowler. 2007. Eligibility criteria of randomized controlled trials published in high-impact general medical journals: A systematic sampling review. Journal of the American Medical Association 297: 1233–1240.CrossRefGoogle Scholar
  47. 47.
    Dresser, R. 1992. Single, white male for medical research. Hastings Center Report 22(1): 24–29.CrossRefGoogle Scholar
  48. 48.
    Anderson, J.R., T. Schonfeld, T.K. Kelso, and E.D. Prentice. 2003. An IRB’s deliberations regarding restrictions on women of child-bearing potential as subjects for an early phase clinical trial. IRB 25(4): 7–11.CrossRefGoogle Scholar
  49. 49.
    Schonfeld, T., and B.G. Gordon. 2005. Contraception in research: A policy suggestion. IRB 27(2): 15–20.CrossRefGoogle Scholar
  50. 50.
    Schonfeld, T.L., N.J. Amoura, J.A. Stoner, and B.G. Gordon. 2009. Women and contraception in research: A pilot study. Journal of Women’s Health 18(4): 507–512.CrossRefGoogle Scholar
  51. 51.
    Schonfeld, T., J.S. Brown, N.J. Amoura, and B. Gordon. 2010. Ideal vs. real: Revisiting contraceptive guidelines. IRB 32(6): 13–16.Google Scholar
  52. 52.
    Lyerly, A.D., M.O. Little, and R.R. Faden. 2009. The national children’s study: A golden opportunity to advance the health of pregnant women. American Journal of Public Health 99(10): 1742–1745.CrossRefGoogle Scholar
  53. 53.
    Lyerly, A.D., E.E. Namey, B. Gray, G. Swamy, and R.R. Faden. 2012. Women’s views about participating in research while pregnant. IRB 34(4): 1–8.Google Scholar
  54. 54.
    Wendler, D. 2009. Minimal risk in pediatric research as a function of age. Archives of Pediatrics and Adolescent Medicine 163(2): 115–118.CrossRefGoogle Scholar
  55. 55.
    Wendler, D., L. Belsky, K.M. Thompson, and E.J. Emanuel. 2005. Quantifying the federal minimal risk standard: Implications for pediatric research without a prospect of direct benefit. Journal of the American Medical Association 294(7): 826–832.CrossRefGoogle Scholar
  56. 56.
    Nelson, D.K., D. Skinner, S. Guarda, et al. 2013. Obtaining consent from both parents for pediatric research: What does “reasonably available” mean? Pediatrics 131(1): e223–e229.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Center for EthicsEmory UniversityAtlantaUSA

Personalised recommendations