Clinical trials postmarketing surveillance

Contracting out of activities previously only conducted in-house is already becoming quite common and will probably continue to develop. In the past a so-called full-service pharmaceutical company took direct responsibility for all the activities required for the formulation, manufacture, quality control, and regulatory approval of its drug products. Nowadays the use of specialist contract houses to perform activities such as formulation, analytical methods development, manufacture of clinical trials supplies, supervision of the assembly of an NDA, postmarketing surveillance, and even troubleshooting may be contracted for even by some of the largest companies. 

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. 

To identify a justified risk in a healthy population requires clinical trials and if the risk is very low inordinate numbers of patients are required to identify issues. These become extremely expensive in practice and this is one reason why vaccines are subject to postlicencing and postmarketing surveillance for safety. 

Comments. The clearest lesson from the butorphanol experience is that when a drug is introduced to a new population, it is important to determine whether extant abuse-liability studies will generalize to that population. If not, then clinical trials should be designed to detect signs of abuse in that population, and careful postmarketing surveillance should occur. The goal is not to prevent patient access to necessary medications, but to ensure that providers and patients have adequate information about the risks of such medications. 

The information on safety provided by the controlled trials are of course valuable, but the populations are highly selected and the administration of SLIT is usually supervised this situation is profoundly different from that occurring in the clinical reality. Therefore, more consistent information on the safety should be obtained when SLIT is prescribed and administered in the everyday clinical practice, i.e. in postmarketing surveillance studies. 

As mentioned before, LNIT requires a particular administration technique after premedication, the allergenic extract (aqueous or powdered) has to be sprayed into a nostril while vocalizing. This fact, in addition to the efficacy limited to the nose, reduced the clinical use of LNIT therefore, no postmarketing surveillance studies are available. In conclusion, based on the clinical trials, LNIT appears safe and well tolerated. The EAACI/ESPACI position paper states that side effects do not represent a problem [12],... 

It should also be noted that postapproval clinical trials can be conducted as experimental means of collecting further information about the drug. While these trials can be very informative, the focus of this chapter is on wide-ranging postmarketing surveillance (see Buncher and Tsay, 2006b). 

Lode H, Vogel F, Elies W. Grepafloxacin a review of its safety profile based on clinical trials and postmarketing surveillance. Clin. Then, 1999, 21, 61-74. 

During clinical trials two of 2796 patients (0.08%) developed neutropenia, but both recovered after withdrawal. No other cases were detected in postmarketing surveillance of 13 500 patients in the Netherlands (SEDA-21, 14). 

Spontaneous reports to the FDA and drug manufacturers/ postmarketing surveillance/ and data from ongoing observational studies and clinical trials provide other means for detecting important ADRs that may have not been detected during drug development. 

Not all clinical trials, especially large, multisite, multinational phase III studies and phase IV postmarketing surveillance, pharmacoeconomic, and quality-of-life studies, can be conducted at a CSO facility. These types of studies, and many phase II efficacy studies, are conducted in research- or university-based hospitals or other investigational sites where a sufficient patient population with the disease or disorder to be tested is available. A number of CSOs offer services to support clinical trial studies that are implemented at one or more clinical trial sites. These services can be broken down into relatively broad categories, which are summarized later. 

Preclinical and clinical trial data and data from phase IV studies have shown that levofloxacin, moxifloxacin, and gatifloxacin cause prolongation of the QT interval, but that the potential for torsade de pointes is rare and is influenced by several independent variables (for example concurrent administration of class la and III antidysrhyth-mic agents) (25). There is a moderate increase in the QT interval associated with sparfloxacin, averaging 3%, and the few serious adverse cardiovascular events that have been reported during postmarketing surveillance all occurred in patients with underlying heart disease (26). 

Jungst G, Mohr R. Side effects of ofloxacin in clinical trials and in postmarketing surveillance. Drugs 1987 34(Suppl l) 144-9. 

Clinical trials of sildenafil have not shown increased risks of stroke or myocardial infarction. However, postmarketing drug surveillance programs have mentioned strokes associated with sildenafil, and case reports have been published. 

Whereas priapism has not been reported with sildenafil in controlled clinical trials, it is being mentioned in postmarketing drug surveillance programs, and two case reports have appeared in a healthy young man and a patient with sickle cell trait (29,30). 

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