Definitive clinical efficacy

A monograph (1) covers the pioneering period of sulfa dmg development and describes over 5000 sulfanilamide derivatives, their preparation, properties, trade names, and biological testing. This review is remarkably complete through 1944. Several thousand additional derivatives have been made since, but no comparable coverage is available. A definitive account of medical appHcations up to 1960 has been pubHshed (2), and a review of experimental antibacterial aspects has been made (3). Chapters on general aspects of sulfonamides and sulfones have appeared (4,5). A review of the clinical efficacy of trimethoprim—sulfamethoxazole has been pubHshed (6). 

Phase III studies represent the confirmatory phase of drug development, which takes several years and usually involves several thousand patients at multiple trial centers. Large patient numbers are required in these trials to provide convincing documentation of clinical efficacy and safety, a more complete adverse event profile and covariates and estimates of variability in dose response relationship due to individual differences in pharmacokinetics and pharmacodynamics. They are aimed at definitively determining a drug s effectiveness and side-effect profile. Most of these studies are double-blind and placebo-controlled, sometimes with the option of open-label long-term extensions. 

In conclusion, there is a clear need for a better understanding of AF, in all its manifestations, as well as for proof of concept molecules with better Kvl.5 selectivity, to address in a more definitive manner questions of clinical efficacy and safety with this type of agent. 

Dier and sudden unforeseen emotional crisis invariably create such clinical situations that exceptionally demand the essential use of sedatives and hypnotics. A plethora of insomnia (sleeplessness) inadvertently caused due to short-term situational stress is usually regarded as the most suitable and ideal circmnstantial condition(s) which necessiates drug-treatment not only to facilitate but also to augment sleep. After a vigorous and intensive research the introduction of rather newer yet safer and definitely more efficacious sedative and hypnotic drug has always been greeted with great fervour and optimism. 

The overall objective of clinical trials is to establish a drug therapy that is safe and effective in humans, to the extent that the risk-benefit relationship is acceptable. The ICH process has developed an internationally accepted definition of a clinical trial as Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) with the object of ascertaining its (their) safety and/or efficacy. ... 

Laboratory data are most often associated with safety analyses, but they may play a part in efficacy analyses as well, especially if the laboratory data are part of the clinical endpoint definition. From a CDISC perspective, laboratory data are a finding, as they are a planned assessment. 

Tables 2A and B summarize the results of clinical studies that assessed the efficacy of rifaximin in the treatment of bacterial diarrhea. Many of the studies suffer from small numbers and not uniform definitions of diarrhea. In the studies of DuPont et al. [6, 13], acute diarrhea was defined as three or more unformed stools passed in a 24-hour period accompanied by at least one symptom of...

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. 

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