Clinical hyperthermia trials: design principles and practice.

The initial development of a significant risk device is predicated upon demonstrable medical need and an adequate biophysical rationale. Although microwave and radiofrequency thermotherapy systems strongly meet these requirements, their clinical evaluation has often suffered from inadequate or inappropriate preclinical laboratory experimentation. It is suggested that devices be tested in animals rather than phantoms and that thermal profiles, cooling curves, power vs. temperature studies et al be carried out in the organ or organs of interest. Clinical trials can then be designed in which an attempt is made to replicate laboratory measurements in humans in order to develop physical dose-response relationships and toxicity data (i.e. a phase-I or feasibility study). The experimental paradigm for clinical drug testing can also be applied, with some modifications, to the further evaluation of devices for the determination of therapeutic response rates (phase-II) and for controlled evaluation against available treatments in a homogeneous patient population (phase-III). It is extremely important that early clinical trials not be contaminated by the possible effects of other concurrent therapies and that sophisticated statistical design be employed to protect human subjects from unnecessary exposure to experimental treatments. The ethical issues involved are best dealt with by good scientific design.