Postmarketing Safety Events Relating to New Drugs Approved in Brazil Between 2003 and 2013: A Retrospective Cohort Study

Abstract

This study investigated postmarketing safety events (PMSEs) for new drugs approved in Brazil and evaluated whether a range of drug characteristics influenced the time between approval and the first PMSE. This retrospective study included new drugs registered between 2003 and 2013 by the National Health Surveillance Agency (ANVISA), which is responsible for medicines approval in Brazil. PMSEs were defined as any drug safety alert or drug withdrawal from the market. The existence of risk evaluation and mitigation strategies (REMS) by the US Food and Drug Administration (FDA) and Brazil were recorded. A Kaplan-Meier survival curve of the period between the date of ANVISA registration and the PMSE was calculated. We found a statistically significant difference between the time to PMSE for drugs with an FDA REMS compared with those without a REMS, with a log rank value (Mantel Cox) of 0.002. There was no association between the time to PMSE and the other drug characteristics investigated. This study demonstrated that the frequency of PMSEs for new drugs approved by ANVISA was statistically associated with the existence of an FDA REMS. The time between approval and first PMSE was shorter for drugs with an FDA REMS, and this finding may contribute to improved awareness of the risk/benefit balance required to ensure continued safe and effective use of new drugs.

Thirteen years of medication alerts issued by the Brazilian Health Regulatory Agency (ANVISA): What is the profile?

“…Only 3.79% of the alerts belonged to the antineoplastic class. This result differs from another study that investigated postmarketing safety events of new medication between 2003 and 2013 in Brazil, the result of which indicates that antineoplastic and immunomodulatory medications are twice as likely to have safety alerts compared to other therapeutic classes . This difference can be justified by the fact that the study by Botelho and collaborators contemplate only new medication in the market.…”

New drugs registered in Brazil from 2003 to 2013: analysis from the perspective of child health

“…The frequency of drugs that were important therapeutic inovation and first-in-class in the cohort investigated was reduced. There was a predominance of pharmacological innovations, an aspect also identified in the evaluations of new adult-specific drugs (Botelho et al, 2017) that is an international trend (Ward et al, 2014;Vitry, Shin, Vitre, 2013). The small molecule ratio also showed the same pattern detected in studies on adults.…”

“…This retrospective cohort study included new drugs registered from January 2003 to December 2013 by Anvisa, the authority responsible for drug approval in Brazil. The definition of the cohort investigated was detailed in a previous study (Botelho et al, 2017). The cohort was defined after the identification of new drugs launched in other countries during the period of the research and which were concurrently approved by Anvisa.…”

“…The register of new drugs in Anvisa were surveyed in site of Brazilian government responsible for official publications. The drugs were surveyed using the drug names adopted in Brazilian Portuguese from international non-proprietary names (Botelho et al, 2017). Drugs that were still marketed in Brazil were identified in the January 2016 list of medicines prices published by Anvisa (ANVISA, 2016a).…”

“…Drugs were classified according to the third pharmacological therapeutic level of the Anatomical Therapeutic Chemical (ATC) Classification of the World Health Organization (WHO, 2018). The following drug characteristics were also identified: first-in -class, orphan drug, small molecule or biological drug, referring to the Food and Drug Administration (FDA) database and the "To Market, To Market" review articles (Botelho et al, 2017).…”