Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.

We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release.

[The transition of amino acid drug development for 50 years in Japan (1)--amino acid parenteral fluid].

Twenty kinds of alpha-amino acids that form the constituents of proteins in mammalian tissues are all L-form with the exception of glycine. These proteins consist of both dispensable and indispensable alpha-amino acids, and play an important role as nutrients. The artificial mixtures of these alpha-amino acids are also important as ethical drugs. The history of alpha-amino acid parenteral fluid is not as long as one might think in terms of its clinical applications. The first publication of clinical data on the subject only appeared in 1944. In Japan, the first product using alpha-amino acid solution made from casein protein entered the market in 1950. In 1959, an alpha-amino acid solution produced from optically pure L-form was launched in Japan and became a pioneer in the field of artificial mixture solutions worldwide. From the 1960s, the amino acid industry has developed remarkably in Japan by means of chemically synthetic, enzymatic and microbial methodologies. Since then, most of the optically active alpha-amino acids have been easily obtainable, and the clinical uses of a-amino acid solutions using a variety of combinations have developed tremendously. From the 1950s to the 1970s, most of the mixture solutions containing a large number of a-amino acids were clinically developed for nutritional supplements. However, from the 1990s, amino acid solutions targeting diseases such as hepato-nephricpathy have increased, while new pediatric a-amino acid solutions are still being launched today. Since the year 2000, amino acid kit formulations with vitamins have been developed for convenient use in hospitals.