Adverse drug reactions clinical detection

Corrigan, O.P., A risky business tire detection of adverse drug reactions in clinical trials and postmarketing exercises, Soc. Sci. Med., 55, 497, 2002. 

One of the most important aspects of the UK regulatory system is the scheme that provided for the voluntary reporting of adverse reactions to a marketed drug. Because most serious adverse drug reactions (ADRs) are rare events, they are unlikely to be detected in early clinical trials. The problem is essentially one of numbers, as relatively few patients are exposed to a new drug before it is released on to the market. Marketing, therefore, may be the first adequate safety trial. 

An evaluation of the rifaximin tolerability profile observed in almost 1,000 patients from 30 clinical trials was unable to identify a definite pattern of intolerance [33]. Very few adverse events have been reported during short-tem treatment with the drug, the most frequently reported being gastrointestinal in nature (e.g. flatulence, nausea, abdominal pain and vomiting). It is worthwhile to emphasize that the detection of GI adverse reactions could have been difficult in rifaximin trials since the symptoms of the underlying diseases were often similar to the GI complaints observed after drug treatment. 

The data on the adverse reactions of the fluoroquinolones which have received the most extensive clinical evaluation (ciprofloxacin, ofloxacin, pefloxacin, norfloxacin and enoxacin), involving about 30,000 patients, have been the subject of a review [54a], An important point noted in this review involves the difficulty in detecting an important severe adverse reaction if it is of relatively low frequency, until there has been a very large patient exposure (some examples are provided in which at least 150,000-300,000 exposures would be required to observe the importance of side-effects, resulting in an alert, which have been discovered with specific drugs). However, the majority of side-effects observed thus far with the fluoroquinolones have been minor,... 

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