<< Previous Section | < Previous Page | Next Page > | Next Section >> Appropriate Risk to Benefit Ratio (page 3 of 3) Equipoise The concept behind equipoise is that in order for a therapeutic trial to be ethical there has to be genuine uncertainty as to the relative efficacy or safety of the treatment arms. Is this new drug better than placebo? Is drug A more efficacious or safer than drug B? In theory, if we knew the answer, there would be no reason to do the trial. In order for a clinical trial to be ethical, then either The individual investigator has genuine uncertainty regarding the comparative therapeutic merits of each arm, or The medical community has genuine uncertainty regarding the comparative therapeutic merits of each arm. Arguments have been made that true equipoise rarely exists because previous research, whether it be in cells or animals or in small groups of humans, usually suggests that the proposed treatment has a better than 50% chance of being effective. In fact, those sponsoring clinical trials have to invest so much money and effort that they would hardly take the risk of such an undertaking unless they felt that the evidence supporting the efficacy of the intervention was reasonably strong. The FDA would not permit a Phase 3 trial unless the preliminary evidence was promising. Use of Placebos A placebo is an inactive version of a treatment identical in appearance to the real thing. Sometimes part of the treatment consists of active medications and part is placebo. Once you recognize the need for controls then the question of whether placebo controls are desirable or acceptable must be answered. This has become a major issue because of international research (see below), in which it became apparent that placebos were being used when, in the developed world standard therapies were available and routinely utilized. The most recent version of the Declaration of Helsinki states: The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists. See footnote: Footnote: The WMA hereby reaffirms its position that extreme care must be taken in making use of a placebo-controlled trial and that in general this methodology should only be used in the absence of existing proven therapy. However, a placebo-controlled trial may be ethically acceptable, even if proven therapy is available, under the following circumstances: Where for compelling and scientifically sound methodological reasons its use is necessary to determine the efficacy or safety of a prophylactic, diagnostic or therapeutic method; or Where a prophylactic, diagnostic or therapeutic method is being investigated for a minor condition and the patients who receive placebo will not be subject to any additional risk of serious or irreversible harm. All other provisions of the Declaration of Helsinki must be adhered to, especially the need for appropriate ethical and scientific review. The issue of placebo controls also applies to studies in developed countries where the cost of studies using standard therapy in the controls is much greater and the end points much less definitive than in the use of placebo controls. Standard of Care: This term applies to the expected care in the medical community as a whole. Often, standard of care can be defined on the basis of practice guidelines, which are being developed by all medical specialties, element by element. The issue of standard of care becomes problematic when a study is to be performed in a developing country where it is impossible to provide medical care at anywhere near the level available in the developed world. The current expectation is that controls will be treated at the level of the Western standard of care, not the indigenous standard. << Previous Section | < Previous Page | Next Page > | Next Section >> Chapter 3 Quick Links Ethics and Study Design Introductory Ethics Design Appropriate Risk to Benefit Ratio Selection of Subject Populations Cases Bibliography Chapter 3 Download (PDF)