Measuring the impact of the 2012 European pharmacovigilance legislation on additional risk minimization measures

Aims: Additional risk minimization measures (aRMMs) may be needed to ensure that the benefits continue to outweigh the risks for medicines associated with serious risks. Prior research showed an increasing trend in medicines with aRMMs. We assessed whether the European pharmacovigilance legislation may have impacted the number and type of aRMMs. Methods: We included new active substances approved between 1 January 2010 and 31 December 2015. Information extracted from the summary of the Risk Management Plan at the time of licensing included date and type of marketing authorization, presence and type of aRMMs. We tested for differences using Pearson’s Χ2 test and segmented Poisson regression. Results: We identified 231 medicines approved during the study period, of which 30% had aRMMs at the time of licensing. ARMMs were in place for 38% of medicines before July 2012 and for 28% after (p = 0.16). Segmented Poisson regression did not show changes in trend or level of medicines with aRMMs. Discussion and conclusion: During the study period, no significant differences in the proportion or trend of products with aRMMs at the time of licensing before and after the pharmacovigilance legislation were identified

Measuring the impact of the 2012 European pharmacovigilance legislation on additional risk minimization measures

Aims: Additional risk minimization measures (aRMMs) may be needed to ensure that the benefits continue to outweigh the risks for medicines associated with serious risks. Prior research showed an increasing trend in medicines with aRMMs. We assessed whether the European pharmacovigilance legislation may have impacted the number and type of aRMMs. Methods: We included new active substances approved between 1 January 2010 and 31 December 2015. Information extracted from the summary of the Risk Management Plan at the time of licensing included date and type of marketing authorization, presence and type of aRMMs. We tested for differences using Pearson’s Χ2 test and segmented Poisson regression. Results: We identified 231 medicines approved during the study period, of which 30% had aRMMs at the time of licensing. ARMMs were in place for 38% of medicines before July 2012 and for 28% after (p = 0.16). Segmented Poisson regression did not show changes in trend or level of medicines with aRMMs. Discussion and conclusion: During the study period, no significant differences in the proportion or trend of products with aRMMs at the time of licensing before and after the pharmacovigilance legislation were identified

Inhibition of growth by imadazol(on)e propionic acid: Evidence in vivo for coordination of histidine catabolism with the catabolism of other amino acids

Imidazole propionic acid (ipa), a gratuitous inducer of the histidine-utilization ( hut ) system in Salmonella typhimurium , inhibits the organism's growth on succinate minimal medium. Induction of the hut system is necessary, but not sufficient, to cause inhibition. A study of the ability of single amino acids to relieve ipa-restricted growth suggests that insufficient glutamate is the cause of slow growth. The inhibition of growth by imidazolone propionic acid (iopa), an intermediate in the catabolism of histidine to glutamate, is similar to that by ipa. Studies using 2, 3, 5-triphenyl tetrazolium chloride plates to examine amino acid catabolism suggest that accumulation of ipa or iopa leads to inactivation of aspartate amino-transferase (AAT). This interpretation is supported by studies of an Escherichia coli mutant lacking AAT. The mutant grows poorly on succinate minimal medium, and the poor growth is relieved by the same amino acids that relieve ipa- and iopa-restricted growth. These and other findings are discussed in terms of coordination of the histidine-utilization system with enzymatic activities involved in the catabolism of other amino acids.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47544/1/438_2004_Article_BF00267937.pd