Phase IV clinical studies

Cooperation Group for Phase IV Clinical Study of Levofloxacin. The clinical efficacy and safety of intravenous levofloxacin in the treatment of4888 patients with bacterial infections a multi-center trial. Zhonghua Nei Ke Za Zhi 2009 48(6) 492-6. 

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. 

Phase IV clinical trials and prospective observational cohort studies have been criticised as no more than promotional devices used by aggressive pharmaceutical companies. The fact that misuse has sometimes happened should not be allowed to obscure the greatly more important needs of safety evaluation and the further development of new and improved therapies. A set of guidelines has been published in the United Kingdom which are specifically intended to provide the high standards of study design and methodology necessary for observational cohort studies. It is to be hoped that similar procedures will be adopted internationally. 

Phase IV Postlicensing studies in the target population, with widening of entry criteria to broaden experience in clinical practice study objectives may be marketing, further formal therapeutic and comparator trials and surveillance for safety. 

In summary, the findings of early Phase I and II clinical trials suggest subjective and objective improvements in patients with ischemic lower-extremity or myocardial disease, and merit further investigation in additional Phase II, and pivotal Phase III and IV clinical studies. Issues that need to be addressed in these studies include limitations and safety profiles, definition of the populations that would benefit from this therapy, determination of... 

Phase III and phase IV clinical trials involve larger populations. During phase III trials, which can last two to eight years, a drug is often brought to market. Phase IV studies continue after the drug is being marketed. 

As with other new technologies, it is possible that the first licensed DNA vaccines will receive conditional approval. In this case, postlicensing Phase IV clinical trials may be requested to address and monitor remaining unresolved issues by specific studies or on a larger scale. Furthermore, as for any medicinal product, effective and intensive pharmacovigilance procedures will be used to closely monitor the appearance of any side effects, while the vaccine is applied widely and routinely. 

This section will review the phase III clinical trials of IV thrombolytic agents for acute ischemic stroke, organized by the type of agent and the time window from stroke onset to study drug delivery (Table 3.1). The 1995 National Institute of Neurological Disorders and Stroke (NINDS) rt-PA trial is presented first because it showed that IV rt-PA, given within 3 hours of stroke onset, reduced stroke-related disability. This trial was the basis for the United States Food and Drug Administration (FDA) approval for rt-PA for use in acute ischemic stroke. 

Clinical trials. A subset of those clinical studies that evaluates investigational medicines in Phases I, II, and III. Phase IV evaluations of marketed medicines in formal clinical trials using the same or similar types of protocols to those used in Phases I and III are also referred to as clinical trials. 

Clinical development of NCEs is broadly divided into Phases I, II, III, and then IV (postmarketing) studies. 

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