Hostname: page-component-586b7cd67f-dlnhk Total loading time: 0 Render date: 2024-11-20T07:38:21.346Z Has data issue: false hasContentIssue false
  • English
  • Français

Ethical Concerns About Relapse Studies

Published online by Cambridge University Press:  29 July 2009

Adil E. Shamoo  and
Timothy J. Keay
Adil E. Shamoo
Affiliation:
Professor of Biological Chemistry, University of Maryland School of Medicine, Baltimore, Maryland. He is Editor-in-Chief of the journal Accountability in Research and a Board member of the National Alliance for the Mentally Ill (NAMI).
Timothy J. Keay
Affiliation:
Assistant Professor in the Department of Family Medicine, University of Maryland at Baltimore, Maryland.
Get access Rights & Permissions [Opens in a new window]

Extract

It is universally accepted that informed consent to participate in medical research should be given by subjects. People have the fundamental human right to freely choose, without coercion or withholding of information necessary to make a reasonable choice, whether they will undergo any risks associated with a research project. United States researchers have known for some time that they have the duty to inform potential subjects of the nature of proposed research and the risks and possible benefits, and to seek consent. Investigators also have the duty to design the research so that it will be scientifically valid while minimizing foreseeable and avoidable harms.

Type
Special Section: Rejuvenating Research Ethics
Information
Cambridge Quarterly of Healthcare Ethics , Volume 5 , Issue 3 , Summer 1996 , pp. 373 - 386
Copyright
Copyright © Cambridge University Press 1996

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Notes

1. Levine, RJ. Ethics and the Regulation of Clinical Research. Baltimore, Maryland: Urban and Schwarzenberg, 1981:69–95.Google ScholarPubMed

2. Shamoo, AE. Our responsibilities towards persons with mental illness as a human subject in research. The Journal 1994;5:14–6.Google Scholar

3. Willwerth, J. Tinkering with madness. Time 1993; 08 30:40–2Google Scholar; Hilts, PJ. New York Times 1984;03 10:A1, B10.Google Scholar

4. [Editorial]. New York Times 1994;03 14:A16.Google ScholarPubMed

5. Shamoo, AE, Ed. The Baltimore Conference on Ethics: Ethics in Neurobiological Research With Human Subjects. Proceedings of the Conference held January 7–9,1995,Google ScholarBaltimore, Maryland. New York: Gordon & Breech Science Publishers [In Press].Google ScholarPubMed

6. Andreasen, NC, Carpenter, WT. Diagnosis and classification of schizophrenia. Schizophrenia Bulletin 1993;19:25–40.CrossRefGoogle ScholarPubMed

7. Shore, D. Non-technical summaries of articles. Schizophrenia Bulletin 1993;19:1–24.Google Scholar

8. Kane, JM, Marder, SR. Psychopharmacologic treatment of schizophrenia. Schizophrenia Bulletin 1993;19:113–28.CrossRefGoogle ScholarPubMed

9. See note 7. Shore.

10. Davis, JM. Overview: Maintenance therapy in psychiatry: I. Schizophrenia. American Journal of Psychiatry 1975;132:1237–45Google ScholarPubMed; Davis, JM. Maintenance therapy and the natural course of schizophrenia. Journal of Clinical Psychiatry 1985;11:18–21Google Scholar; Schooler, NR, Levine, J. Strategies for enhancing drug therapy of schizophrenia. American Journal of Psychotherapy 1983;37:521–32Google ScholarPubMed; Kissling, W. Ideal and reality of neuroleptic relapse prevention. British Journal of Psychiatry 1992;161:133–9.Google Scholar

11. See note 10. Schooler, Levine.

12. Ravaris, CL, Weaver, LA, Brooks, GW. Further studies with fluphenazine enanthate: II. Relapse rate in patients deprived of medication. American Journal of Psychiatry 1967; 124-248–9CrossRefGoogle ScholarPubMed; Prien, RF, Cole, JO, Belkin, NF. Relapse in chronic schizophrenics following abrupt withdrawal of tranquilizing medication. British Journal of Psychiatry 1968;115:679–86CrossRefGoogle Scholar; Gallant, DM, Mielke, D, Bishop, G et al. Pipotiazine palmitate: an evaluation of a new long acting intramuscular antipsychotic agent in severely ill schizophrenic patients. Disease of the Nervous System 1975;36:193–6Google ScholarPubMed; Quitkin, F, Rifkin, A, Kane, J et al. , Long-acting oral vs injectable antipsychotic drugs in schizophrenics. A one-year double-blind comparison in multiple episode schizophrenics. Archives of General Psychiatry 1978;35:889–92CrossRefGoogle ScholarPubMed; Lonowski, DJ, Sterling, FE, Kennedy, JC. Gradual reduction of neuroleptic drugs among chronic schizophrenics: a double blind controlled study. Acta Psychiatry Scandinavia 1978;57:97–102CrossRefGoogle ScholarPubMed; Prang, AJ, Loosen, PT, Wilson, IC et al. , Behavioral and endocrine responses of schizophrenic patients to TRH (protirelin), Archives of General Psychiatry 1979;36:1086–93CrossRefGoogle Scholar; Rifkin, A, Quitkin, F, Kane, J et al. , The effect of fluphenazine upon social and vocational functioning in remitted schizophrenics. Biological Psychiatry 1979;14:499–508Google ScholarPubMed; Kane, JM, Rifkin, A, Quitkin, F et al. , Low dose fluphenazine decanoate in maintenance treatment of schizophrenia, Psychiatry Research 1979;1:341–8CrossRefGoogle ScholarPubMed; Schooler, NR, Levine, J, Severe, JB, NIMH-PRB Collaborative Fluphenazine Study Group. Depot fluphenazine in the prevention of relapse in schizophrenia: evaluation of a treatment regimen. Psychopharmacology Bulletin 1979;15:44–7Google Scholar; Brown, WA, Laughren, T. Low serum prolactin and early relapse following neuroleptic withdrawal. American Journal of Psychiatry 1981;138:237–9Google ScholarPubMed; Branchey, MH, Branchey, LB, Richardson, MA. Effects of neuroleptic adjustment on clinical condition and tardive dyskinesia in schizophrenic patients. American Journal of Psychiatry 1981;138:608–12Google ScholarPubMed; Shenoy, RS, Sadler, AG, Goldberg, SC et al. , Effects of a six week drug holiday on symptom status, relapse, and tardive dyskinesia in chronic schizophrenics. Journal of Clinical Psychopharmacology 1981;1:141–5CrossRefGoogle ScholarPubMed; Goldberg, SC, Shenoy, RS, Sadler, A et al. , The effects of a drug holiday on relapse and tardive dyskinesia in chronic schizophrenics. Psychopharmacology Bulletin 1981;17:116–7Google ScholarPubMed; Herz, MI, Szymanski, HV, Simon, J. Intermittent medication for stable schizophrenic outpatients: an alternative to maintenance medication. American Journal of Psychiatry 1982; 139:918–22;Google ScholarPubMedVan Kammen, DP, Docherty, JP, Bunney, WE. Prediction of early relapse after pimozide discontinuation by response to d-amphetamine during pimozide treatment. Biological Psychiatry 1982;17:233–42Google ScholarPubMed; Brown, WA, Laughren, T, Chisholm, E, Williams, BW. Low serum neuroleptic levels predict relapse in schizophrenic patients. Archives of General Psychiatry 1982;39:998–1000CrossRefGoogle ScholarPubMed; Kane, JM, Rifkin, A, Quitkin, F et al. , Fluphenazine vs placebo in patients with remitted, acute first-episode schizophrenia. Archives of General Psychiatry 1982;39:70–3CrossRefGoogle ScholarPubMed; Mandel, MR, Severe, JB, Schooler, NR et al. , Development and prediction of postpsychotic depression in neuroleptic treated schizophrenics. Archives of General Psychiatry 1982;39:197–203CrossRefGoogle ScholarPubMed; Glazer, WM, Sheard, MH. Relapse in patients with shifting RDC diagnoses treated with lithium alone. Journal of Clinical Psychiatry 1982;43:134–6Google ScholarPubMed; Lehmann, HE, Wilson, WH, Deutsch, M. Minimal maintenance medication: effects of three dose schedules on relapse rates and symptoms in chronic schizophrenic outpatients. Comprehensive Psychiatry 1983;24:293–303CrossRefGoogle ScholarPubMed; Kane, JM, Rifkin, A, Woerner, M et al. , Low dose neuroleptic treatment of outpatient schizophrenics. Archives of General Psychiatry 1983;40:893–6CrossRefGoogle ScholarPubMed; Carpenter, WT, Heinrichs, DW. Early intervention, time limited, targeted pharmacotherapy of schizophrenia. Schizophrenia Bulletin 1983;9:533–42CrossRefGoogle ScholarPubMed; Lieberman, JA, Kane, JM, Gadaleta, D et al. , Methylphenidate challenge as predictor of relapse in schizophrenia. American Journal of Psychiatry 1984;141:633–8Google Scholar; Marder, SR, Van Putten, T, Mintz, J. Costs and benefits of two doses of fluphenazine. Archives of General Psychiatry 1984;41:1025–9CrossRefGoogle ScholarPubMed; Angrist, B, Peselow, E, Rubinstein, M et al. , Amphetamine response and relapse risk after depot neuroleptic discontinuation. Psychopharmacology 1985;85:277–83CrossRefGoogle ScholarPubMed; Jayaram, G, Coyle, J, Tune, L. Relapse in chronic schizophrenics treated with fluphenazine decanoate is associated with low serum neuroleptic levels. Journal of Clinical Psychiatry 1986;47:247–8Google ScholarPubMed; McMillan, DE, Fody, EP, Couch, L et al. , Drug holidays and serum haloperidol levels in schizophrenic patients. Journal ofClinical Psychiatry 1986;47:373–4Google ScholarPubMed; Faraone, SV, Curran, JP, Laughren, T et al. , Neuroleptic bioavailability, psychosocial factors, and clinical status: a 1 year study of schizophrenic outpatients after dose reduction. Psychiatry Research 1986;19:311–22CrossRefGoogle ScholarPubMed; Nuechterlein, KH, Snyder, KS, Dawson, ME et al. , Expressed emotion, fixed dose fluphenazine decanoate maintenance, and relapse in recent onset schizophrenia. Psychopharmacology Bulletin 1986;22:633–9Google ScholarPubMed; Lieberman, JA, Kane, JM, Sarantakos, S et al. , Influences of pharmacologic and psychosocial factors on the course of schizophrenia: prediction of relapse in schizophrenia. Psychopharmacology Bulletin 1986;22:845–53Google Scholar; Davidson, M, Keefe, RSE, Mohs, RC et al. , L-Dopa challenge and relapse in schizophrenia. American Journal of Psychiatry 1987;144:934–8Google Scholar; Faraone, SV, Brown, WA, Laughren, TP. Serum neuroleptic levels, prolactin levels, and relapse: a two year study of schizophrenic outpatients. Journal of Clinical Psychiatry 1987;48:151–4Google ScholarPubMed; Kriesman, D, Blumenthal, R, Borenstein, M et al. , Family attitudes and patient social adjustment in a longitudinal study of outpatient schizophrenics receiving low dose neuroleptics: the family's view. Psychiatry 1988;51:3–13CrossRefGoogle Scholar; Boza, RA, Milanes, F, Starkey, T et al. , Relapse rate and low serum neuroleptic levels in schizophrenics treated with fluphenazine: another view. Journal of Clinical Psychiatry 1988;49:245Google ScholarPubMed; Van Kammen, DP, Peters, J, van Kammen, WB et al. , CSF norepinephrine in schizophrenia is elevated prior to relapse after haloperidol withdrawal. Biological Psychiatry 1989;26:176–88CrossRefGoogle ScholarPubMed; Herz, MI, Glazer, W, Mirza, M et al. , Treating prodromal episodes to prevent relapse in schizophrenia. British Journal of Psychiatry 1989;155:123–7Google Scholar; Glazer, WM, Morgenstern, H, Schooler, N et al. , Predictors of improvement in tardive dyskinesia following discontinuation of neuroleptic medication. British Journal of Psychiatry 1990;157:585–92CrossRefGoogle ScholarPubMed; Buchanan, RW, Kirkpatrick, B, Summerfelt, A et al. , Clinical predictors of relapse following neuroleptic withdrawal. Biological Psychiatry 1992;32:72–8CrossRefGoogle ScholarPubMed; Steinhauer, SR, Van Kammen, DP, Colbert, K et al. , Pupillary constriction during haloperidol treatment as a predictor of relapse following drug withdrawal in schizophrenic patients. Psychiatry Research 1992;43:287–98CrossRefGoogle ScholarPubMed; Ventura, J, Nuechterlein, KH, Hardesty, JP, Gitlin, M. Life events and schizophrenic relapse after withdrawal of medication. British Journal of Psychiatry 1992;161:615–20CrossRefGoogle ScholarPubMed; Barbee, JG, Mancuso, DM, Freed, CR, Todorov, AA. Alprazolam as a neuroleptic adjunct in the emergency treatment of schizophrenia. American Journal of Psychiatry 1992;149:506–10.Google ScholarPubMed

13. See note 8. Kane, Marder.

14. See note 12. Shhenoy, et al. ; Goldberg, et al. ; Kane, et al. Kriesman, et al. 1983;Google Scholar

15. See note 12. Shenoy, et al. ; Kane, et al. 1983.Google Scholar

16. See note 12. Lieberman, et al. ; Lieberman, et al. Google Scholar

17. See note 12. Gallant, et al. ; Prange, et al. ; Branchey, et al. Google Scholar

18. See note 12. Quitkin, et al. Google Scholar

19. See note 8. Kane, Marder.

20. See note 10. Schooler, Levine.

21. See note 2; see also Shamoo, AE, Irving, DN. Accountability in research using persons with mental illness. Accountability in Research 1993;3:1–17.Google ScholarPubMed

22. Cournos, F. Do psychiatric patients need greater protection than medical patients when they consent to treatment? Psychiatric Quarterly 1993;64:319–28.CrossRefGoogle ScholarPubMed

23. See note 12. Barbee, et al. Google Scholar

24. See note 10. All Authors.

25. See note 10. Schooler, Levine.

26. Wyatt, RJ. Neuroleptics and the natural course of schizophrenia. Schizophrenia Bulletin 1991; 17:325–51CrossRefGoogle ScholarPubMed; Miller, R. Schizophrenia as a progressive disorder: relations to EEG, CT, neuropathological and other evidence. Progress in Neurobiology 1989;33:17–44CrossRefGoogle ScholarPubMed; Katz, J. Human experimentation and human rights. St Louis University Law Journal 1993;38:7–54.Google ScholarPubMed

27. See note 12. Branchey, et al. Google Scholar

28. See note 8. Kane, Marder.

29. Germany (Territory Under Allied Occupation, 1945–1955. United States Zone). Military Tribunal. Trials of War Criminals Before the Nuremberg Military Tribunals Under Control Council Law No. 10: Nuremberg, October 1946-April 1949, Vol II. Washington, DC:Government Printing Office, 1946–1949:181–2.Google Scholar

30. World Medical Association. Declaration of Helsinki: recommendations guiding physicians in biomedical research involving human subjects. In: Bulger, RE, Heitman, E, Reiser, SJ, Eds. The Ethical Dimensions of the Biological Sciences. Cambridge; United Kingdom: Cambridge University Press, 1993:159–61, quote at p. 160.Google Scholar

31. Beecher, HK. Ethics and clinical research. New England Journal of Medicine 1966;274:1354–60.CrossRefGoogle ScholarPubMed

32. Dahan, R, Caulin, C, Figea, L et al. , Does informed consent influence therapeutic outcome? A clinical trial of the hypnotic activity of placebo in patients admitted to hospital. British Medical Journal 1986;293:363–4CrossRefGoogle ScholarPubMed; Edlund, MJ, Craig, TJ, Richardson, MA. Informed consent as a form of volunteer bias. American Journal of Psychiatry 1985;142:624–7Google ScholarPubMed; Myers, MG, Cairns, JA, Singer, J. The consent form as a possible cause of side effects. Clinical Pharmacology and Therapeutics 1987;42:250–3.CrossRefGoogle ScholarPubMed

33. See note 26. Katz.

34. See note 12. Kane, et al. 1983.Google Scholar

35. Candilis, PJ, Wessley, RW, Wichman, A. A survey of researchers using a consent policy for cognitively impaired human research subjects. Institutional Review Board 1993;15:1–5.Google ScholarPubMed

36. See note 12. Lieberman, et al. ; Lieberman, et al. Google Scholar

37. See note 12. Van Kammen, et al. ; Lieberman, et al. Angrist, et al. 1986;Google Scholar

38. See note 12. Davidson, et al. Google Scholar

39. Pellegrino, ED. Beneficence, scientific autonomy, and self-interest: ethical dilemmas in clinical research. Cambridge Quarterly of Healthcare Ethics 1992;1:361–9, quote at p. 368.CrossRefGoogle ScholarPubMed

40. See note 2. Shamoo.

41. See note 10. Kissling.

42. Wing, J. Ethics and psychiatric research. In: Bloch, S, Chodoff, P, Eds. Psychiatric Ethics. Oxford, United Kingdom: Oxford University Press, 1984:277–94, quote at p. 280.Google Scholar

43. Goldner, JA. An overview of legal controls on human experimentation and the regulatory implications of taking Professor Katz seriously. Saint Louis University Law Journal 1993;38:63–134.Google ScholarPubMed

44. See note 21. Shamoo, Irving.

45. See note 21. Shamoo, Irving.

46. Office for Protection From Research Risks (OPRR), Division of Human Subject Protections. Evaluation of Human Subject Protections in Schizophrenia Research Conducted by the University of California Los Angeles. Washington, DC:OPRR, 1994;05 11:21.Google Scholar

47. See note 21. All Authors.

48. See note 42. Wing.

49. See note 26. Katz.

50. Bamberg, M, Budwig, N. Therapeutic misconceptions: when voices of caring and research are misconstrued as the voice of curing. Ethics and Behavior 1992;2:165–84.CrossRefGoogle ScholarPubMed

51. Appelbaum, PS, Roth, LH, Lidz, CW et al. , False hopes and best data: consent to research and the therapeutic misconception. Hastings Center Report 1987; 17(04):20–4.CrossRefGoogle ScholarPubMed