Do effectiveness ("real world") studies on antipsychotics tell us the real truth?

Abstract

In recent years, so-called "effectiveness studies" have gained increasing importance in the context of evidence-based medicine. These studies supposedly follow less restrictive methodological standards than phase III studies in terms of patient selection, co-medication and other design issues, and their results should therefore be better generalisable than those of phase III studies. Effectiveness studies, like other types of phase IV studies, can therefore contribute to the knowledge about antipsychotics or other psychopharmaceuticals and supply relevant information in addition to that gained from phase III trials. However, the less restrictive design and inherent methodological problems of phase IV studies mean that their results cannot falsify the results of phase III studies. The greater complexity of phase IV studies, for example the greater variance caused by the different kinds of confounders, means that their results have to be interpreted with great care and especially with a high degree of awareness of problematic design issues, such as insensitive primary outcome criteria, biased randomisation, unblinded treatment conditions, inclusion of chronic refractory patients, etc. Some recently published effectiveness studies on antipsychotic treatment of schizophrenia will be discussed under these methodological aspects. The main conclusions of these trials will be questioned on the basis of their severe methodological pitfalls.