Clinical trials safety monitoring

Safety evaluation does not cease being an essential element in the success of the pharmaceutical industry once a product is on the market. It is also essential to support marketed products and ensure that their use is not only effective but also safe and unclouded by unfounded perceptions of safety problems. This requires not only that clinical trials be monitored during development (Spector et al., 1988), but also that experience in the marketplace be monitored. 

The sponsor must establish an independent monitoring system in order to conduct an adequate evaluation of progress of the clinical trial, safety information and efficacy end points. This means that Japanese companies will now have to hire medical doctors to handle medical matters. 

Please describe planned study population. Choice of participants should be appropriate for the indication proposed. Subjects should not have enrolled in a clinical trial during the preceding 12 weeks. Please describe how special populations such as women of childbearing age, children and the elderly will be handled in this study. Please comment on the special need for close monitoring due to safety considerations. 

Phase II investigates the compound s efficacy and safety in controlled clinical trials for a specific therapeutic indication. To eliminate as many competing factors as possible, Phase II trials are narrowly controlled. They are characterized as small—several hundred subjects with the indicated disease or symptoms—and are closely monitored. The control may be either a placebo study arm or an active control arm. The endpoint measured may be the clinical outcome of interest or a surrogate. Phase II trials may last for several months or even several years. Early pilot trials to evaluate safety and efficacy are called Phase Ila. Later trials, called Phase lib, are important tests of the compound s efficacy. These trials may constitute the pivotal trials used to establish the drug s safety and efficacy. At least one pivotal trial (most frequently a large, randomized Phase III study) is done. Only about one third of compounds entered into Phase II will begin Phase III studies [61],... 

Because DMPK properties vary among different species, in vitro human and animal data and in vivo animal data cannot always be extrapolated to human in vivo responses. The three main reasons that drugs fail during clinical trials are (1) lack of efficacy, (2) unacceptable adverse effects, and (3) unfavorable ADME properties. Hence, clinical development is necessary to establish solid experiment-based human exposure and safety data through both short- and long-term monitoring. 

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. 

The company requires information in order to establish and monitor the safety profile of a product. At the time a new product is first marketed its efficacy has been well defined. As a relatively small number of patients will have taken part in clinical trials during the development of a new medicine,... 

Card/ac e/fecfs Asymptomatic, nonspecific T-wave inversions were observed in 1 study more often in subjects receiving trospium than in subjects receiving moxifloxacin or placebo following 5 days of treatment. This finding was not observed during routine safety monitoring in 2 other placebo-controlled clinical trials in 591 trospium-treated overactive bladder patients. The clinical significance of T-wave inversion in this study is unknown. 

In addition to possible high therapeutic plasma levels, accumulation in target organs also complicates the side effect picture. Thus, early estimates of safety margins should be approached with a pinch of salt and predicted adverse reactions should be carefully monitored during late phase in vivo studies and clinical trials. 

---