Ethics of clinical research in schizophrenia
Despite these seeming obstacles, clinical judgment is a critical protection for research subjects (Miller & Weijer, 2006). IRB approval of a research study means that it has determined that the benefits and harms of study participation are acceptable. But in making this determination the IRB can appeal only to population-level evidence. The circumstances of individual research subjects are not in view at the time of IRB approval; hence, such approval does not imply the acceptability of enrollment or continued participation of particular patients. It remains for the clinician to meet his or her obligations to the research subject through the exercise of clinical judgment that takes into account the circumstances of the research subject. If the clinician judges study participation to be medically irresponsible based on evidence that ought to be convincing to colleagues, the clinician is obliged to decline to offer enrollment or to recommend to the patient or to the legal guardian withdrawal of the patient/subject from the study. When may placebo controls be used ethically? Placebo is a nonactive intervention, such as a sugar pill. In standard clinical trials, subjects (and clinicians) are blinded to whether they are receiving placebo or active treatment. The use of placebo controls in psychiatric research has proven controversial. Proponents of the routine use of placebo controls have argued that good science and ethics require their use (Temple & Ellenberg, 2000). Scientifically, the placebo control provides a clinical trial with a “benchmark” according to which investigators may ensure that conclusions derived from study results are sound (i.e., that the new intervention/medication being studied is indeed beneficial). Proponents argue that free and informed consent provides sufficient moral grounds for placebo studies, provided that research subjects are not exposed to a risk of death or permanent disability. Critics of this view point out that the design of the study ought to depend on the scientific question, and not on unsubstantiated claims regarding the special properties of placebo controls (Weijer, 1999). Clinically relevant scientific questions usually regard the comparative effectiveness of treatments and require designs that employ a standard therapy control. Although often permissible ethically, the use of placebo controls is problematic when therapeutic procedures in a study are not consistent with clinical equipoise, as may be the case for schizophrenia, where there are evidence-based beneficial interventions such as various antipsychotic medications. Given the contentious nature of placebo use in clinical research currently, how ought the clinician approach the issue? It is a well accepted maxim in research ethics that the medical care of a patient ought not to be disadvantaged by research participation. In considering decisions to refer, enroll, or continue a patient in a clinical trial, the clinician ought to act accordingly. The use of a placebo control is generally agreed to be unproblematic when there is no treatment for a condition, when nontreatment is consistent with competent medical care, or when all patients receive standard care and the study is concerned with the efficacy of the addition of a treatment to the standard regimen. This may not be the case for clinical research on schizophrenia using placebo-only controls. Hence, such research on subjects with schizophrenia may not be ethically justified. As discussed earlier, clinical judgment must also take into account the circumstances of each patient. KEY POINTS
- Bioethics addresses conflicts of values that arise in health care situations.
- Mental health care such as psychiatric rehabilitation for individuals with schizophrenia is not ethically and conceptually sound if it is (purely) client-centered at all costs.
- A dialogical approach to the mental health care of individuals with schizophrenia may provide an ethically and conceptually sound alternative to a purely client-centered approach when the latter fails ethically or conceptually.
- Research ethics considers the moral principles and rules that govern the conduct of scientific studies on human beings.
- Clinical research is governed by Federal regulations that are implemented through an upfront review of research by IRBs.
- Whereas obligations of the State to protect the research subject are fulfilled by IRB review, clinicians have an obligation to use clinical judgment to protect patients in research from harm.
- Placebo-only controlled clinical research on subjects with schizophrenia may be ethically justified only under special circumstances, such as when evaluating the effects of medications on treatment-refractory patients or the effects of ancillary medications on associated symptoms (e.g., cognitive impairment).
- Anthony, W. A., Cohen, M., Farkas, M., & Gagne, C. (2002). Psychiatric rehabilitation (2nd ed.). Boston: Center for Psychiatric Rehabilitation.
- Beauchamp, T. L., & Childress, J. F. (2001). Principles of biomedical ethics (5th ed.). New York: Oxford University Press.
- Dunn, L. B. (2006). Capacity to consent to research in schizophrenia: The expanding evidence base. Behavioral Sciences and the Law, 24, 431 - 445.
- Emanuel, E. J., Wendler, D., & Grady, C. (2000). What makes clinical research ethical? Journal of the American Medical Association, 283, 2701 - 2711.
- Grisso, T., & Appelbaum, P. S. (1998). Assessing competence to consent to treatment: A guide for physicians and other health professionals. New York: Oxford University Press.
- Hendrickson-Gracie, K., Staley, D., & Morton-Neufeld, I. (1996). When worlds collide: Resolving value differences in psychosocial rehabilitation. Psychiatric Rehabilitation Journal, 20, 25 - 31.
- Karlawish, J. (2006). Alzheimer's disease "clinical trials and the logic of clinical purpose. New England Journal of Medicine, 355, 1604 - 1606.
- Miller, P. B., & Weijer, C. (2006). The trust-based obligations of the state and physician - research to patient - subjects. Journal of Medical Ethics, 32, 542 - 547.
- Moreno, J. D. (2001). Undue risk: Secret state experiments on humans. New York: Routledge.
- Rudnick, A. (2002a). The goals of psychiatric rehabilitation: An ethical analysis. Psychiatric Rehabilitation Journal, 25, 310 - 313.
- Rudnick, A. (2002b). The ground of dialogical bioethics. Health Care Analysis, 10, 391 - 402.
- Rudnick, A. (2007). Processes and pitfalls of dialogical bioethics. Health Care Analysis, 15, 123 - 135.
- Stewart, M., Brown, J. B., Weston, W. W., McWhinney, I. R., McWilliam, C. L., & Freeman, T. R. (2003). Patient-centered medicine: Transforming the clinical method (2nd ed.). Oxon, UK: Radcliffe.
- Temple, R., & Ellenberg, S. S. (2000). Placebo-controlled trials and active-control trials in the evaluation of new treatments: Part 1. Ethical and scientific issues. Annals of Internal Medicine, 133, 455 - 463.
- Twamley, E. W., Jeste, D. V., & Bellack, A. S. (2003). A review of cognitive training in schizophrenia. Schizophrenia Bulletin, 29, 359 - 382.
- Weijer, C. (1999). Placebo-controlled trials in schizophrenia: Are they ethical? Are they necessary? Schizophrenia Research, 35, 211 - 218.
- Weijer, C., & Miller, P. B. (2004). When are research risks reasonable in relation to anticipated benefits? Nature Medicine, 10, 570 - 573.