Ethical issues clinical trial design

The design of randomized clinical trials introduces ethical issues.Usually, study designs prevent the treatment from being modified because of the need to collect sufficient data to allow valid statistical inference. Ethically, clinicians are required to provide their patients with the best available treatment however, the justification for a randomized clinical trial is simply that the best treatment is not yet known. 

Finally, regulatory and policy bioethics is concerned with ethical issues such as clinical trial design, drug approval ethics, use of embryonic tissue in research and clinical treatment, human cloning, organ procurement for transplantation, xenotransplantation, assisted suicide, euthanasia, formulation of brain death policy, allocation of scarce healthcare resources, and so on. 

A basic ethical issue in several areas of psychiatric research is whether participants are able to provide informed consent, particularly for protocols entailing medication washout and/or placebo treatment. The majority of psychiatric patients who are asked to participate in clinical trials have adequate capacity to provide consent. Thus, in a study specifically designed to examine the capacity of schizophrenic patients to give informed consent, cognitive dysfunction and negative symptoms (apathy and avolition). but not psychotic symptoms (hallucinations, delusions), were found to be associated with impaired decisional capacity (Moser et al., 2002). These features are probably not unique to schizophrenia but are likely to apply to many other forms of illness. 

Each study component has an ethical aspect. The ethical aspects of a clinical trial cannot be separated from the scientific objectives. Segregation of ethical issues from the full range of study design components demonstrates a flaw in understanding the fundamental nature of research involving human subjects. Compartmentalization of ethical issues is inconsistent with a well-run trial. Ethical and scientific considerations are intertwined (p. 4). 

B. C. Goh, Design of phase I and II clinical trials in oncology and ethical issues involved. Ann Acad Med Singapore 29 588-597 (2000). 

Grunwald HW. Ethical and design issues of phase I clinical trials in cancer patients. Cancer Invest 2007 25 124-126. 

Ethical considerations must be applied from the design to the completion of a clinical trial. Clear scientific hypotheses and objectives are critical. It is difficult to justify a clinical study if it is not clinically important or relevant. There are added ethical considerations for cancer patients, many of whom have been heavily pretreated with other chemotherapy agents and many of whom are terminally ill and may not derive any direct benefit from the agent being studied, particularly in phase 0 and I trials [23]. Clinical trials are conducted under guidelines issued in the Belmont Report of 1978 that protects human subjects and follows principles of respect for persons, beneficence, and justice. Scientific conduct is also guided by ethical principles in that competent and rigorous analysis is required to prevent compromise of the results [24]. 

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