LAUSR

Carrying out clinical trials and reporting on these studies are essential requisites for drug development and approval. Phase IV studies are essential for the continuing monitoring of drugs. The differences are fundamental: the efficacy of a drug is measured in an idealized clinical environment during Phase III studies, while in Phase IV effectiveness occurs in a real-life context. There is a boundary zone in the passage from Phase III to Phase IV trials, that is, from experimental to marketing and free use phases; in this zone, patients can be treated with unapproved drugs by means of named patient programme (NPP), compassionate and off-label use and, in Italy, under request based on a local disposition of the Italian Drug Agency issued according to a national law (Law 648/96: “medicinal products that are provided free of charge on the national health service”). In the development of a new drug, several established steps must be done prior to the final approval by the regulatory authorities worldwide for use in daily clinical practice. In the phase III of the drug development, randomized double blind studies are often conducted to evaluate risks and benefits of the drug. After this pivotal step the drug may be approved for marketing. In the phase IV or post-marketing studies that follow, further investigation on the drug is conducted in routine clinical practice. It is evident that data from phase III studies may not be sufficient to determine the whole description of a drug in routine use: the assessment of drugs during daily clinical practice may reveal evidence of additional side effects or change in efficacy, results trigging sometimes withdrawal or changing indication. We have a ten-year experience in treating patients with NPP or under national law 648/96 and we started to collect retrospectively data of this experience with observational studies as we registered new benefits but new adverse events too [1–4]. The majority of studies are investigatorsponsored, sometime are company-sponsored. We firstly began with monocentric study and, then, we conducted and still conduct multicenter national studies reporting on significant sample size (four investigator-sponsored studies are ongoing). Many our colleagues ask for participating in these researches as co-investigators to report on their experience too, judging the results of this kind of studies very