Placebo-controlled trials in schizophrenia

Lev-Hasharon Mental Health Center, Pardessiya.
Harefuah 04/2004; 143(3):236-40, 244.
Source: PubMed


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.

1 Read
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ethical issues in the field of schizophrenia research have become a focus of intense debate in the past year. The publication of the final report of the National Bioethics Advisory Commission (NBAC) coupled with recent media reports have catapulted these issues into international view. Major questions have been raised about the capacity of individuals with mental illness to consent to participation in research studies and about the conflicts of interest that psychiatric researchers experience. Questions have also been raised about whether it is ethical to ask patients with schizophrenia to participate in studies that can be expected to lead to an increase in psychotic symptoms.
    Current Psychiatry Reports 11/1999; 1(1):13-9. DOI:10.1007/s11920-999-0005-1 · 3.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Many believe that informed consent makes clinical research ethical. However, informed consent is neither necessary nor sufficient for ethical clinical research. Drawing on the basic philosophies underlying major codes, declarations, and other documents relevant to research with human subjects, we propose 7 requirements that systematically elucidate a coherent framework for evaluating the ethics of clinical research studies: (1) value-enhancements of health or knowledge must be derived from the research; (2) scientific validity-the research must be methodologically rigorous; (3) fair subject selection-scientific objectives, not vulnerability or privilege, and the potential for and distribution of risks and benefits, should determine communities selected as study sites and the inclusion criteria for individual subjects; (4) favorable risk-benefit ratio-within the context of standard clinical practice and the research protocol, risks must be minimized, potential benefits enhanced, and the potential benefits to individuals and knowledge gained for society must outweigh the risks; (5) independent review-unaffiliated individuals must review the research and approve, amend, or terminate it; (6) informed consent-individuals should be informed about the research and provide their voluntary consent; and (7) respect for enrolled subjects-subjects should have their privacy protected, the opportunity to withdraw, and their well-being monitored. Fulfilling all 7 requirements is necessary and sufficient to make clinical research ethical. These requirements are universal, although they must be adapted to the health, economic, cultural, and technological conditions in which clinical research is conducted. JAMA. 2000;283:2701-2711.
    JAMA The Journal of the American Medical Association 05/2000; 283(20):2701-11. · 35.29 Impact Factor

  • The Journal of Law Medicine &amp Ethics 02/2000; 28(4):344-61. DOI:10.1111/j.1748-720X.2000.tb00686.x · 1.10 Impact Factor
Show more