The patient (or their legal representative) is capable of giving, and gives, fully informed consent. The patient may request conventional treatment at any stage, or may be placed on such treatment by the treating physician. The key item in this list, is clearly the first, one because the other items apply more generally to all HTS clinical trial procedures. If the line of argument advanced in the first point is accepted, then it becomes
important to have a clear understanding of what constitutes serious or irreversible harm in Inhibitors,research,lifescience,medical each specific medical situation. Secondly, it is argued that the use of placebo is scientifically necessary under those circumstances where activecontrolled trials are unreliable Inhibitors,research,lifescience,medical and where their use would increase the proportion of erroneous clinical and regulatory decisions. This topic is thoroughly discussed in the ICH E10 regulatory guideline
on the choice of control.12 In some areas of medicine, the sensitivity of a specific trial is an uncertain matter. For example, in the field of depression, there are plenty of examples of apparently goodquality, placebo-controlled trials of established and licensed agents that failed to detect a difference.13 Such trials are scientifically awkward and expensive, but clearly cannot and do not form the basis of regulatory CHIR99021 CT99021 approvals; they lead to delays and further research. However, Inhibitors,research,lifescience,medical in an area of medicine where the paradoxical failure of a placebo-controlled trial was a real possibility, a trial that used a licensed treatment, as the sole
comparator arm would also run the risk of failing to Inhibitors,research,lifescience,medical detect, a real difference. That is, it might, fail to pick up the inferiority of a test agent to a standard agent. The lack of difference from the standard agent could be equally paradoxical, but in this case it could lead to a positive licensing decision. Thirdly, some alternative (and regularly used) design strategies using placebo avoid the apparent, ethical dilemma, for example, the addition of a new medication or placebo Inhibitors,research,lifescience,medical on top of standard treatment, (the “add-on” design). Following widespread critical comment, the World Medical Association (WMA) took the unusual step of issuing a statement on their website that modifies the Cilengitide position in the Declaration with respect, to section 29.3 This states that: “… 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.