Role of three-dimensional echocardiography in drug trials

There are two main typologies of clinical trials in whom echocardiography may be used. The first one is represented by studies in which echocardiography is used as part of the assessment, but does not contribute substantially to the end-points. This is the case of trials using echo parameters to define a given study population, a use accepted and supported also by the regulatory authorities. The second one, more ambitious for echocardiography, corresponds to studies involving echocardiographic measurements (e.g., chamber volume and/or shape and LV mass) as primary or secondary efficacy and safety end-points. This second use of echocardiography is debated, at least when the effect of a therapy is concerned. In fact, for phase II trials echo parameters are considered acceptable to prove a concept of a treatment, while the use of echo measures as primary end-points in phase III (purpose of registering a drug) remains controversial. In this case it is necessary to demonstrate that a given echo measure is a real surrogate of clinical events. In this view, the prognostic value alone is not sufficient and should be combined with the demonstration that modifications of the echo measures correspond (better if proportionally) to changes in outcome events. By analyzing the existing notes for guidance of regulatory authorities, echo parameters are not established end-points of pivotal trials designed in order to approve new drugs in conditions like heart failure, post-myocardial infarction dysfunction and arterial hypertension.