The knowledge gained from noninterventional (observational) studies (NIS) as well as from single-case studies is only seen as being relevant when it is an addition to such studies or a replacement in indications where empirical studies ol a higher methodological degree are lacking. This view corresponds to the general methodological understanding of empirical research. Evidence graduation is geared to the fact that for methodological reasons certain study designs yield results that are more Inhibitors,research,lifescience,medical likely
to be reliable. This corresponds with the rules of the methodology of empirical research.4,5 Thus, randomized control-group studies have a higher value than nonrandomized or uncontrolled studies.
Do effectiveness studies tell us the truth? There is a general consensus that the results of phase III studies are not fully generalizable: they have a high internal validity Inhibitors,research,lifescience,medical but insufficient external validity. One of the reasons for this is the strict selection of patients according to various clinically relevant characteristics such as the exclusion of suicidally, comorbidity, etc. For this reason it has long been a tradition within clinical psychopharmacology to complement the Inhibitors,research,lifescience,medical phase III trial results with ones more strongly oriented towards everyday clinical practice and conditions, ie, studies in patients who better represent Inhibitors,research,lifescience,medical the “average” patients and treated under conditions as close as possible to “routine” care, eg, phase IV studies ( Figure 1.) However, it has thereby always been stressed that because of many immanent methodological problems, eg, biases due to lack of double-blind conditions or any blinding, such Inhibitors,research,lifescience,medical as phase naturalistic observational studies (NIS), only deliver complementary knowledge and cannot falsify the results of phase III studies. 6 Figure 1. The 4-phase model of clinical psychopharmacology. RCT, randomized controlled trial However, this strict rule can be weakened
if the phase IV studies are performed, like phase III studies, as randomized control-group studies in an unblinded or even in blind or double-blind approach. Some experts seem inclined to attach a greater importance to the results of these studies than to the methodologically stricter phase III studies.7 This might in particular be the result from criticism science arising from the increasingly common practice, especially in the USA, to include, in phase III studies, not “real” patients from care settings, but suitable persons found through advertisements. Of course, rather than this questionable approach, properly performed phase III studies in “real” patients should be advocated. Even so, some experts judge the “real- world approach” of effectiveness studies to be more valuable than phase III trials, at least in terms of clinical relevance.