, Volume 1, Issue 3, pp 372–377

Evidence-based ethics for neurology and psychiatry research


American bioethics, historically arising out of theology and philosophy, has been dominated by the method of normative analysis. Ethics as policy, however, requires in addition a solid evidence base. This paper discusses the background conditions that make neurotherapeutics research particularly challenging. Three key ethical issues are discussed within an evidence-based ethics framework: the ethical challenges arising from changes in the financial incentive structures for academic researchers and their institutions, the challenges of risk—benefit analysis for neurotherapeutics protocols testing innovative interventions, and the evolving issues surrounding impaired decision-making capacity and surrogate consent for research. For each of these issues, selected empirical data are reviewed, areas for further inquiry are noted, and the need for development of novel methods for bioethics policy research is discussed.

Key Words

Research ethics conflicts of interest informed consent risk—benefit analysis neurotherapeutics 


  1. 1.
    Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC et al. Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunization.Neurology 61: 46–54, 2003.PubMedGoogle Scholar
  2. 2.
    Silverberg GD, Levinthal E, Sullivan EV, Bloch DA, Chang SD, Leverenz J et al. Assessment of low-flow CSF drainage as a treatment for AD: results of a randomized pilot study.Neurology 59: 1139–1145, 2002.PubMedGoogle Scholar
  3. 3.
    Hock C, Konietzko U, Streffer J, Tracy J, Signorell A, Muller-Tillmanns B et al. Antibodies against β-amyloid slow cognitive decline in Alzheimer’s disease.Neuron 38: 547–554, 2003.PubMedCrossRefGoogle Scholar
  4. 4.
    Kim SYH, Caine ED, Currier GW, Leibovici A, Ryan JM. Assessing the competence of persons with Alzheimer’s disease in providing informed consent for participation in research.Am J Psychiatry 158: 712–717, 2001.PubMedCrossRefGoogle Scholar
  5. 5.
    Carpenter WT Jr, Gold J, Lahti A, Queern C, Conley R, Bartko J et al. Decisional capacity for informed consent in schizophrenia research.Arch Gen Psychiatry 57: 533–538, 2000.PubMedCrossRefGoogle Scholar
  6. 6.
    National Bioethics Advisory Commission. Research involving persons with mental disorders that may affect decision making capacity, Vol 1, report and recommendations of the National Bioethics Advisory Commission. Rockville, MD: NBAC, 1998.Google Scholar
  7. 7.
    Neuroethics: mapping the field: conference proceedings, May 13–14, 2002, San Franciso, California (Marcus S, ed). New York: The Dana Press, 2002.Google Scholar
  8. 8.
    Jonsen AR. The birth of bioethics. New York: Oxford University Press, 1998.Google Scholar
  9. 9.
    Stolberg SG. The biotech death of Jesse Gelsinger.N Y Times Mag Nov 28: 136–140, 149–150, 1999.Google Scholar
  10. 10.
    Kolata G. Johns Hopkins Death Brings Halt to U.S.-financed human studies.N Y Times Mag Jul 20: A1, A18, 2001.Google Scholar
  11. 11.
    Marshall E. Shutdown of research at Duke sends a message.Science 284:1999.Google Scholar
  12. 12.
    National Institutes of Health. Required education in the protection of human research participants. NOTICE: OD-00-039, June 5, 2000.Google Scholar
  13. 13.
    Association for the Accreditation of Human Research Protection Programs, Inc. AAHRPP website, 2002.Google Scholar
  14. 14.
    Task Force on Financial Conflicts of Interest in Clinical Research. Protecting subjects, preserving trust, promoting progress—policy and guidelines for the oversight of individual financial interest in human subjects research. Association of American Medical Colleges, 2001.Google Scholar
  15. 15.
    Task Force on Research Accountability. Report on individual and institutional financial conflict of interest. Association of American Universities, 2001.Google Scholar
  16. 16.
    Wilson D, Heath D. Class-action suit filed against ‘The Hutch’.Seattle Times Mar 27, 2001.Google Scholar
  17. 17.
    Mello MM, Studdert D, Brennan TA. The rise of litigation in human subjects research.Ann Intern Med 139: 40–45, 2003.PubMedGoogle Scholar
  18. 18.
    Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical?JAMA 283: 2701–2711, 2000.PubMedCrossRefGoogle Scholar
  19. 19.
    Blumenthal D. Ethics issues in academic-industry relationships in the life sciences: the continuing debate.Acad Med 71: 1291–1296, 1996.PubMedCrossRefGoogle Scholar
  20. 20.
    Emanuel EJ, Steiner D. Institutional conflict of interest.N Engl J Med 332: 262–267, 1995.PubMedCrossRefGoogle Scholar
  21. 21.
    Frankel MS. Perception, reality, and the political context of conflict of interest in university-industry relationships.Acad Med 71: 1297–1304, 1996.PubMedCrossRefGoogle Scholar
  22. 22.
    Munro N. Doctor Who?Washington Monthly Nov 2002.Google Scholar
  23. 23.
    Karlawish J. The search for a coherent language: the science and politics of drug testing and approval. In: Ethics, law, and aging review, Vol 8, Issues in conducting research with and about older persons (Kapp MB, ed), pp 39–56. New York: Springer, 2002.Google Scholar
  24. 24.
    Bekelman JE, Li Y, Gross CP. Scope and impact of financial conflicts of interest in biomedical research: a systematic review.JAMA 289: 454, 2003.PubMedCrossRefGoogle Scholar
  25. 25.
    Nathan DG, Weatherall DJ. Academic freedom in clinical research.N Engl J Med 347: 1368–1371, 2002.PubMedCrossRefGoogle Scholar
  26. 26.
    Shuchman M. Legal issues surrounding privately funded research cause furore in Toronto.CMAJ 159: 983–986, 1998.PubMedGoogle Scholar
  27. 27.
    Rennie D. Thyroid storm.JAMA 277: 1238–1243, 1997.PubMedCrossRefGoogle Scholar
  28. 28.
    Stelfox H, Chua G, O’Rourke K, Detsky A. Conflict of interest in the debate over calcium-channel antagonists.N Engl J Med 338: 101–106, 1998.PubMedCrossRefGoogle Scholar
  29. 29.
    Levine J, Gussow JD, Hastings D, Eccher A. Authors’ financial relationships with the food and beverage industry and their published positions on the fat substitute olestra.Am J Public Health 93: 664, 2003.PubMedCrossRefGoogle Scholar
  30. 30.
    Pieters T. Marketing medicines through randomised controlled trials: the case of interferon.Br Med J 317: 1231–1233, 1998.Google Scholar
  31. 31.
    Blumenthal D. Academic-industry relationships in the life sciences. Extent, consequences, and management.JAMA 268: 3344–3349, 1992.PubMedCrossRefGoogle Scholar
  32. 32.
    Safer DJ. Design and reporting modifications in industry-sponsored comparative psychopharmacology trials.J Nerv Ment Dis 190: 583–592, 2002.PubMedCrossRefGoogle Scholar
  33. 33.
    Baker CB, Johnsrud MT, Crismon ML, Rosenheck RA, Woods SW. Quantitative analysis of sponsorship bias in economic studies of antidepressants.Br J Psychiatry 183: 498–506, 2003.PubMedCrossRefGoogle Scholar
  34. 34.
    Libby R, Bloomfield R, Nelson M. Experimental research in financial accounting.Accounting, Organizations and Society 27: 775–810, 2002.CrossRefGoogle Scholar
  35. 35.
    Bazerman M, Loewenstein G, Moore D. Why good accountants do bad audits.Harv Bus Rev 80: 96–102, 134, 2002.PubMedGoogle Scholar
  36. 36.
    Messick DM, Bazerman MH. Ethical leadership and the psychology of decision making.Sloan Manage Rev 37: 9–22, 1996.Google Scholar
  37. 37.
    Dana J, Loewenstein G. A social science perspective on gifts to physicians from industry.JAMA 290: 252, 2003.PubMedCrossRefGoogle Scholar
  38. 38.
    Sugarman J, Faden R, Weinstein J. A decade of empirical research in medical ethics. In: Methods in medical ethics (Sugarman J, Sulmasy DP, eds), pp 19–28. Washington, DC: Georgetown University Press, 2001.Google Scholar
  39. 39.
    Weijer C. Thinking clearly about research risk: implications of the work of Benjamin Freedman.IRB 21: 1–5, 1999.CrossRefGoogle Scholar
  40. 40.
    Keyserlingk EW. Proposed guidelines for the participation of persons with dementia as research subjects.Perspect Biol Med 38: 319–362, 1995.PubMedGoogle Scholar
  41. 41.
    Meslin E, Lavery J, Sutherland H, Till J. Judging the ethical merit of clinical trials: what criteria do research ethics board members use?IRB 16: 6–10, 1994.PubMedCrossRefGoogle Scholar
  42. 42.
    Sunderland T, Linker G, Mirza N, Putnam KT, Friedman DL, Kimmel LH et al. Decreased β-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease.JAMA 289: 2094–2103, 2003.PubMedCrossRefGoogle Scholar
  43. 43.
    Kim SYH, Appelbaum PS, Jeste DV, Olin J. Proxy and surrogate consent in geriatric neuropsychiatric research: update and recommendations.Am J Psychiatry 161: 797–806, 2004.PubMedCrossRefGoogle Scholar
  44. 44.
    Macklin R. The ethical problems with sham surgery in clinical research.N Engl J Med 341: 992–996, 1999.PubMedCrossRefGoogle Scholar
  45. 45.
    Weijer C. I need a placebo like I need a hole in the head.J Law Med Ethics 30: 69–72, 2002.PubMedCrossRefGoogle Scholar
  46. 46.
    Albin RL. Sham surgery controls: intracerebral grafting of fetal tissue for Parkinson’s disease and proposed criteria for use of sham surgery controls.J Med Ethics 28: 322–325, 2002.PubMedCrossRefGoogle Scholar
  47. 47.
    Grady D, Kolata G. Gene therapy used to treat patients with Parkinson’s.N Y Times Mag Aug 19, 2003.Google Scholar
  48. 48.
    Miller M. Phase I oncology trials. In: Institutional review board: management and function (Amdur R, Bankert E, eds), pp 465–475. Sudbury, Massachusetts: Jones and Bartlett, 2002.Google Scholar
  49. 49.
    Wendler D, Martinez RA, Fairclough D, Sunderland T, Emanuel E. Views of potential subjects toward proposed regulations for clinical research with adults unable to consent.Am J Psychiatry 159: 585–591, 2002.PubMedCrossRefGoogle Scholar
  50. 50.
    Janofsky J, Starfield B. Assessment of risk in research on children.J Pediatr 98: 842–846, 1981.PubMedCrossRefGoogle Scholar
  51. 51.
    Payne J, Bettman J, Schkade D. Measuring constructed preferences: toward a building code.J Risk Uncertain 19: 243–270, 1999.CrossRefGoogle Scholar
  52. 52.
    Fischhoff B. Cognitive processes in stated preference methods. In: Handbook of environmental economics (Mäler K-G, Vincent J, eds). North-Holland: Elsevier, 2002.Google Scholar
  53. 53.
    Abelson J, Forest PG, Eyles J, Smith P, Martin E, Gauvin FP. Deliberations about deliberative methods: issues in the design and evaluation of public participation processes.Soc Sci Med 57: 239–251, 2003.PubMedCrossRefGoogle Scholar
  54. 54.
    Gutmann A, Thompson D. Deliberating about bioethics.Hastings Cent Rep 27: 38–41, 1997.PubMedGoogle Scholar
  55. 55.
    Gutmann A, Thompson D. Democracy and disagreement. Cambridge, MA: Harvard University Press, 1996.Google Scholar
  56. 56.
    Nelson RM. Voluntariness of consent for research: an empirical and conceptual review.Med Care 40[Suppl 9]: V69-V80, 2002.PubMedGoogle Scholar
  57. 57.
    Roberts LW. Informed consent and the capacity for voluntarism.Am J Psychiatry 159: 705–712, 2002.PubMedCrossRefGoogle Scholar
  58. 58.
    Kim SYH, Karlawish JHT, Caine ED. Current state of research on decision-making competence of cognitively impaired elderly persons.Am J Geriatr Psychiatry 10: 151–165, 2002.PubMedGoogle Scholar
  59. 59.
    Appelbaum PS, Grisso T, Frank E, O’Donnell S, Kupfer D. Competence of depressed patients for consent to research.Am J Psychiatry 156: 1380–1384, 1999.PubMedGoogle Scholar
  60. 60.
    Dymek M, Atchison P, Harrell L, Marson DC. Competency to consent to medical treatment in cognitively impaired patients with Parkinson’s disease.Neurology 56: 17–24, 2001.PubMedGoogle Scholar
  61. 61.
    Moser DJ, Schultz SK, Arndt S, Benjamin ML, Fleming FW, Brems CS et al. Capacity to provide informed consent for participation in schizophrenia and HIV research.Am J Psychiatry 159: 1201–1207, 2002.PubMedCrossRefGoogle Scholar
  62. 62.
    Dunn LB, Lindamer LA, Palmer BW, Schneiderman LJ, Jeste DV. Enhancing comprehension of consent for research in older patients with psychosis: a randomized study of a novel consent procedure.Am J Psychiatry 158: 1911–1913, 2001.PubMedCrossRefGoogle Scholar
  63. 63.
    Wirshing DA, Wirshing WC, Marder SR, Liberman RP, Mintz J. Informed consent: assessment of comprehension.Am J Psychiatry 155: 1508–1511, 1998.PubMedGoogle Scholar
  64. 64.
    Marson DC, Ingram KK, Cody HA, Harrell LE. Assessing the competency of patients with Alzheimer’s disease under different legal standards. A prototype instrument.Arch Neurol 52: 949–954, 1995.PubMedGoogle Scholar
  65. 65.
    Kim S, Caine ED. Utility and limits of the mini mental state examination in evaluating consent capacity in Alzheimer’s disease.Psychiatr Serv 53: 1322–1324, 2002.PubMedCrossRefGoogle Scholar
  66. 66.
    Mezey M, Teresi J, Ramsey G, Mitty E, Bobrowitz T. Decision-making capacity to execute a health care proxy: development and testing of guidelines.J Am Geriatr Soc 48: 179–187, 2000.PubMedGoogle Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc 2004

Authors and Affiliations

  1. 1.Department of Psychiatry, Bioethics Program, and Program for Improving Health Care DecisionsUniversity of Michigan Medical SchoolAnn Arbor

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