Clinical trials observational studies

Determine and document all data sources (e.g., clinical trials, observational studies). 

A systematic review of adverse events in clinical trials, uncontrolled studies, observational studies, and case reports associated with hawthorn leaf and flower monopreparations, including 22 studies with a total of 7080 participants, concluded that hawthorn is generally well tolerated. Adverse events noted in the trials were similar in the hawthorn and placebo groups. The daily doses of hawthorn preparation in the clinical trials ranged from 160 to 1800 mg and the duration of treatment ranged from 3 to 24 weeks (Daniele et al. 2006). 

However, while there are many examples that have addressed clinically important adverse reactions, systematic reviews have a fundamental weakness in their absolute reliance on the availability and quality of primary data. The lack of research activity in several areas of drug safety (as illustrated in Table 1) limits the scope of systematic reviews and hinders the development of comprehensive assessments of specific adverse reactions in a technique described as teleoanalysis [6], which is an exploration that sues data from all available sources, including randomized trials, observational studies, and even case series and case reports. 

Acetyl-i-carnitine (4) is marketed in Italy for dementia as of this writing it is also in Phase III clinical trials in the United States and Europe. In a double-blind, placebo-controUed clinical trial over a one-year period involving 130 patients with clinically diagnosed AD, a slower rate of deterioration in 13 of the 14 outcome measures was observed in the dmg-treated group (28). Earfler smaller scale pilot studies in demented patients had also shown some improvement of various behavioral and cognitive functions (29). 

A clinical trial to evaluate misoprostol as a protector of normal tissue during a course of XRT in cancer patients suggests a reduction in acute normal tissue injury (215). A randomized, prospective, double-blind study indicates that topical misoprostol, administered as an oral rinse 15-20 min before irradiation using conventional 2-Gy (200 rad) fractions, five days a week over 6—7 weeks, significantly protects the oral mucosa from radiomucositis, a frequently observed normal tissue complication during XRT for head and neck cancer (215). 

Selected for clinical trials as a compound to calm agitated patients, imipramine was relatively ineffective. However, it was observed to be effective in the treatment of certain depressed patients (38). Early studies on the mechanism of action showed that imipramine potentiates the effects of the catecholamines, primarily norepinephrine. This finding, along with other evidence, led to the hypothesis that the compound exerts its antidepressant effects by elevating norepinephrine levels at central adrenergic synapses. Subsequent studies have shown that the compound is a potent inhibitor of norepinephrine reuptake and, to a lesser extent, the uptake of serotonin, thus fitting the hypothesis that had been developed to explain the antidepressant actions ofMAOIs. 

The current evidence base for the injection of epinephrine in the initial acute treatment of anaphylaxis includes clinical experience during nearly a century of use, observational studies, epidemiological studies, fatality studies, and randomized controlled trials in people at risk for anaphylaxis although not actually experiencing it at the time of the study. Moreover, the pharmacology of epinephrine has been... 

Data on antidepressant dmgs are available from a number of sources randomized, controlled clinical trials (RCTs) in both hospital and primary-care populations decision analytic models population-based naturalistic observational studies of usual... 

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