Safety surveillance trials

Phase IV Post Marketing Surveillance Trial. Determines ongoing safety of the medication after the medication is being prescribed by healthcare providers. 

As discussed in the chapter on Drug Surveillance, the safety surveillance mission is to implement the systematic review of spontaneous post-marketing data for proactive risk identification and assessment. In general, signal generation is done using clinical trials data, the medical literature, knowledge of class effects and spontaneous reports. 

S ee color insert.) Example of patient profile interactive graph, in Spotfire. (This is discussed in detail in Section 11.4.) (Courtesy of Jones, D., Timely safety surveillance of clinical study safety data, Tibco Software, Atlanta, GA Pfizer, La JoUa, CA, http //www.tibco.com/company/news/ releases/2012/tibco-spotfire-to-showcase-graphical-representation-of-safety-data-for-timely-safety-surveillance-during-clinical-trials.)... 

The excellent safety profile observed in clinical trials has been confirmed by the postmarketing surveillance program [117]. More than 8.5 million patients have been treated in Italy and abroad with rifaximin since its introduction to the market. During the overall postmarketing... 

Phase IV. Studies or trials conducted after a medicine is marketed to provide additional details about the medicine s efficacy or safety profile. Different formulations, dosages, durations of treatment, medicine interactions, and other medicine comparisons may be evaluated. New age groups, races, and other types of patients can be studied. Detection and definition of previously unknown or inadequately quantified adverse reactions and related risk factors are an important aspect of many Phase IV studies. If a marketed medicine is to be evaluated for another (i.e., new) indication, then those clinical trials are considered Phase II clinical trials. The term postmarketing surveillance is frequently used to describe those clinical studies in Phase IV (i.e., the period following marketing) that are primarily observational or nonexperimental in nature, to distinguish them from well-controlled Phase IV clinical trials or marketing studies. 

The Food Additives Amendment to the Federal Food, Drag, and Cosmetic Act of 1938, which was adopted in 1958, requires that proof of safety of a new food additive be furnished by the manufacturer based on extensive scientific research. Since it is impossible to conclusively prove the safety of a new food additive through animal and clinical trials, manufacturers routinely conduct postmarketing surveillance and long-term follow-up studies to monitor adverse events. 

Phase III Extended large-scale trials to obtain additional evidence of efficacy and safety, and definition of adverse effects. Humans exposed several hundred to several thousand Phase IV Post-marketing surveillance occurs after the chnical trials programme is complete. It is used to collect adverse event data from a large patient population. Humans exposed 10 000+... 

Phase IV. post-licensing studies in the target population, with widening of entry criteria to broaden experience in clinical practice study objectives are typically surveillance for safety or further comparisons with other therapies. The results of such trials are more likely to be used for marketing purposes than in support of applications to regulatory authorities. 

The pharmaceutical industry presents many new challenges to such a person which include the interface with pharmacy and pharmacology, toxicological research, human volunteer studies, clinical trials and post-marketing surveillance to name just a few. Product safety is a factor which impacts on all of those endeavours and the pharmaceutical physician will be expected to work and provide advice within that framework. It will be clear to anyone that evidence of lack of safety in a medical product is not good news for the company concerned and that some level of protective action will often be required which in extreme circumstances may involve product withdrawal. It is, therefore, essential that the pharmaceutical physician should be absolutely clear what constitutes lack of safety in relation to the intended use of the product. 

PDUFA III allows the FDA to spend some user fees to increase surveillance of the safety of medicines during their first two years on the market, or three years for potentially dangerous medications. It is during this initial period, when new medicines enter into wide use, that the agency is best able to identify and counter adverse side effects that did not appear during the clinical trials. 

---