[Placebo-controlled trials in schizophrenia].
ABSTRACT Clinical trials involving human subjects give rise to ethical and medico-legal dilemmas. Essential research of new drugs may potentially expose patients to ineffective medications or to placebo. The complexity of the problem increases when dealing with mentally ill patients, for whom, on the one hand there is no known cure for their disease, and on the other hand, it is sometimes questionable whether or not they are able to provide informed consent to participate in clinical trials.
The Israel Psychiatric Association decided to develop a position paper on the subject of placebo-controlled clinical trials in schizophrenia patients.
Discussion groups were established, and the available material in the professional literature was examined, with an emphasis on recent developments. The Declaration of Helsinki and its amendments were analyzed, and experts in the field were consulted.
Clinical drug trials for development of new medications are essential in all fields of medicine, especially in psychiatry. The requirement for a placebo arm in pharmaceutical trials presents ethical and clinical dilemmas that are especially complicated with regard to mentally ill persons whose free choice and ability to provide informed consent may be questionable. However, we do not believe that this predicament justifies unconditional rejection of placebo use in psychiatry, when it may provide substantial benefit for some patients. Simultaneously, it is our duty to provide stringent restrictions that will enable strict supervision over the scientific, clinical and ethical aspects of the trials.
We propose the following criteria for approval of pharmaceutical trials that include a placebo arm: scientific justification; clinical and ethical justification; provision of informed consent; recruitment of patients hospitalized voluntarily; prevention of harm; administration of additional potential therapeutic interventions; benefit to patients participating in the study; control and follow-up procedures for the study as determined by the local Helsinki Committee; and appointment of a supervisory mechanism by the administration of the medical institution where the study is being performed.
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ABSTRACT: Die ethischen Aspekte der Verwendung von Placebos in klinischen Versuchsreihen wurden im letzten Jahrzehnt ausführlich und kontrovers diskutiert. Es fehlt dennoch eine gründliche vergleichende Analyse der verschiedenen internationalen Richtlinien, ihrer Terminologien und ihrer auf Placebo bezogenen Prinzipien. Das zentrale Problem ist die Rechtfertigung von Placebo bei einer nachgewiesen wirksamen Therapie. Alle aktuellen Versionen der untersuchten Richtlinien schlagen solche Rechtfertigungen vor, unterscheiden sich hierbei jedoch beträchtlich. Zunächst werden wir ein formales allgemeines Prinzip herausarbeiten. Dann werden wir drei verschiedene Kategorien von Kriterien darstellen: das Schadensrisiko oder die Belastung, zwingende wissenschaftliche Gründe und die Erhältlichkeit einer nachgewiesen wirksamen Therapie. Die Analyse zeigt bedeutende normative Abweichungen und Widersprüche innerhalb und zwischen den einzelnen Richtlinien. Besonders frappierend ist es, dassmancheRichtlinien es erlauben, Versuchsteilnehmer dem Risiko eines schweren Schadens auszusetzen, während andere gerade dies untersagen. Abschließend versuchen wir zu zeigen, wie sich die normativen Unterschiede bei der Entscheidungsfindung von Forschern und Ethikkommissionen auswirken können. Definition of the Problem: The ethical aspects of placebo control in clinical trials have been extensively and controversially debated in the last decade. However, a thorough analytical comparison of the different existing international regulations, their terminologies and their ethical principles concerning placebo is still missing. The central issue in the ongoing controversy is the justification of placebo-use if proven treatment exists. All present versions of the examined guidelines propose such justifications, but each guideline differs from the others in relevant details. Therefore the conditions justifying placebo-use according to each guideline are in the focus of our attention. Arguments: First, we will first present a formalized general principle that defines the ethical acceptability of placebo use in all regulations. Then we will analyse three categories of conditions put forward by the different documents: the risk of harm or burden, compelling scientific reasons, and the availability of proven treatment. The analysis shows important normative discrepancies and contradictions between the examined guidelines. Especially striking is the fact that some guidelines allow to expose the participants of clinical trials to be exposed to a risk of serious harm, while others do not. Conclusion: The normative difference of each guideline could influence strongly the decision of researchers or IRBs concerning the ethical acceptability of placebo use.Ethik in der Medizin 09/2006; 18(3):223-237. DOI:10.1007/s00481-006-0439-5 · 0.54 Impact Factor
Article: Ethics and research in psychiatry[Show abstract] [Hide abstract]
ABSTRACT: This article reviews the psychiatric research ethics literature of the past year, including papers that cover a broad range of ethical issues arising throughout the research process. Although informed consent is an enduring concern, important issues such as the choice of study design, participant recruitment, and publication are also considered.International Review of Psychiatry 07/2009; 10(4). DOI:10.1080/09540269874691 · 1.80 Impact Factor
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ABSTRACT: The Trial Criteria in Schizophrenia Working Group was convened in November 2007 to define consensus criteria for clinical trials in patients suffering from acute schizophrenia with special focus on placebo-controlled trials and withdrawal conditions. Clinical trials involving patients give rise to ethical and medico-legal dilemmas. Essential research of new drugs may potentially expose patients to ineffective treatment regimens or placebo. The complexity of the problem increases when dealing with mentally ill patients. The Working Group's criteria are thought to cover different aspects important in conducting clinical trials namely to ensure the patient's safety, to present criteria that would allow the ethics committees to agree to the proposed criteria and to enable the possibility to reasonably conduct and ensure comparable quality of clinical studies in acutely ill patients with schizophrenia. To furthermore counteract current inconsistencies, these criteria should be evaluated using standardized rating scales applying established cut-off criteria. The developed trial criteria cover inclusion and exclusion criteria as well as withdrawal criteria due to non-response or worsening of symptoms.European Archives of Psychiatry and Clinical Neuroscience 07/2011; 262(2):151-5. DOI:10.1007/s00406-011-0225-3 · 3.36 Impact Factor