B. Number of trials among the 111 presented in panel A … The HKI-272 research buy pragmatism movement is materialized through research, but the driving power is the health-care policy makers and the societies in general. In 2009 the USA Congress passed the American Recovery and Reinvestment Act (ARRA), a multi-billion dollar stimulus package, which included $1.1 billion for Comparative Effectiveness Research (CER). 15 The two main objectives of the CER Initiative were “to evaluate the relative effectiveness of different health care services and treatment options” and “to encourage the development and use of clinical registries, clinical data networks, and other forms of electronic data to generate outcomes

data.” Inhibitors,research,lifescience,medical The Initiative has already published a report in which 100 national health priorities are described, eg, “Compare the Inhibitors,research,lifescience,medical effectiveness of pharmacologic and non-pharmacologic treatments in managing behavioral disorders in people with Alzheimer’s disease and other dementias in home and institutional settings.” Limitations

and criticism The cornerstone of a pragmatic trial is the ability to evaluate an intervention’s effectiveness in real life and achieve maximum external validity, ie, be able to generalize results to many settings. But what is the definition of “real life” when it comes to health sciences? Will the results Inhibitors,research,lifescience,medical of a pragmatic trial that tests a treatment in the primary care setting in UK be applicable in an East-Asian country, or even another European country? Rothwell16 illustrates such a case in the European Carotid Surgery Trial (ECST),17 a RCT of endarterectomy for recent carotid stenosis. The differences in the clinical Inhibitors,research,lifescience,medical settings between

countries resulted in heterogeneity Inhibitors,research,lifescience,medical in the investigation time of a new stroke, thus affecting the overall effectiveness of the endarterectomy. Furthermore, even within the same country’s health system it is unknown whether similar clinical settings are indeed comparable. Evidence of a treatment’s effectiveness in a given setting does not guarantee that it will also be effective in another one, and vice versa. Empirical evidence on the topic is limited. The little systematic evidence Rolziracetam available so far has indicated only the lack of external validity in trials,16 not how comparable different clinical settings are or how easy it is to transfer results from one to another. Moreover, there is no hard evidence that an increase of a trial’s “within-study” heterogeneity, eg, variability of practitioners, patient and health care delivery, will indeed increase the external validity by lowering the “between-study” heterogeneity among different trials. A well-studied intervention, with high-quality evidence from robustly designed and performed explanatory trials, which is effective in a specific combination of practitioners/patients, will probably be less effective in extended populations.