Reports of Lactic Acidosis Attributed to Metformin, 2015-2018.

OBJECTIVE: In 2016, the U.S. Food and Drug Administration (FDA) revised metformin's label to permit use in patients with mild-moderate chronic kidney disease. We sought to determine whether this change was associated with increased reports of metformin-associated lactic acidosis (MALA) to the FDA's Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS: Publicly available FAERS reports were analyzed. RESULTS: MALA reports increased from 521 in 2015 to 1,939 in 2018. After restriction to U.S. reports, absolute and relative increase in MALA reports was less, from 111 to 243. The proportionate reporting ratio (PRR), a measure adjusted for rates of other adverse event reports, was stable. CONCLUSIONS: The increased reports deserve attention, but the PRR's stability and FAERS's known limitations, including lack of a denominator or control group, do not permit the conclusion that U.S. MALA rates have increased. Further study with more robust data sources is needed.

Drug Safety Evaluation in China.

PURPOSE OF REVIEW: This review aimed to introduce the regulations management and current situations of drug safety evaluation in China. RECENT FINDINGS: The nationwide implementation of good laboratory practice and good clinical practice guarantees the quality of pre-marketing drug safety evaluation. In recent years, post-marketing drug safety monitoring is changing from passive mode to the combination of active and passive monitoring. A national adverse drug reaction monitoring sentinel alliance has been created to actively identify, report, and evaluate adverse reactions, with more than 1.4 million cases reported in 2017. But the quality of the reports is not optimal, with few reports from drug manufacturers, low rate of severe reports, and trend of lag reporting. Drug safety evaluation in China is transitioning from passive monitoring to a combination mode. Drug pharmacovigilance is a powerful tool for active monitoring, but participation by drug manufacturers would be essential to an effective drug safety evaluation system.

An historical overview over Pharmacovigilance.

Pharmacovigilance started about 170 years ago, although it was not yet named as such at that time. It is structured activity in the professional health field, with important social and commercial implications aimed at monitoring the risk/benefit ratio of drugs, improving patient's safety and the quality of life. In this commentary we report the milestones of pharmacovigilance up to the present day, in order to understand all the steps that have characterized the historical evolution; from the first reports, which were essentially letters or warnings sent by clinicians to publishers of important and famous scientific journals, up to today's modern and ultra-structured electronic registries. The historical phases also help us to understand why pharmacovigilance helped us to achieve such important results for man's health and for pharmacology itself, and to identify the challenges that await Pharmacovigilance in future years.

Historical aspects of immunization and vaccine safety communication.

It has been a long journey starting from the beginnings of variolation [3] leading up to the greatest success in the history of immunization: the eradication of smallpox [39]. Today, vaccines are an acknowledged important medical advance [40]. Nevertheless, immunization has been the subject of public controversy on several occasions [15, 24, 31]. This article shall provide a short overview of some aspects of the early stages of immunization in Western countries, including some examples of vaccine safety controversies in the past.

The role of the Immunisation Adverse Events Clinic at The Children's Hospital at Westmead.

Specialist immunisation clinics review and manage children who have experienced an adverse event following immunisation and provide advice to parents and health care providers regarding the revaccination of these children. Information collected by these clinics supplement passive surveillance data and allow the investigation of suspected safety signals associated with the delivery of immunisation programs. This paper reviews the role and experience of the Immunisation Adverse Events Clinic at The Children's Hospital at Westmead and identifies areas for development.

The history of anaesthetic mortality reporting.

Anaesthetists are acutely aware of the legal constraint of reporting to the coroner deaths in association with anaesthesia. The evolution of the office of the coroner in England is presented and the relationship with the discovery and evolution of anaesthesia is examined. The legal and medical climate in the 19th century is described, with some of the key participants named and their roles explained. The 19th century was an age of questioning and exploration, which led to the elucidation of the problems with chloroform and set the path for progress in monitoring in anaesthesia. Comments are made on the development of anaesthetic mortality reporting into its current system and some of the benefits flowing from it. The collaboration of the various state mortality committees in producing a triennial national report is an important way to ensure that the lessons of the past are kept in mind in the present. The author believes that mortality reporting, the analysis of data and the dissemination of information is a valuable field of research, monitoring and educational tool. Primum non nocere is particularly pertinent in anaesthesia.

Adverse drug reactions: keeping up to date.

The amount of published literature on adverse drug reactions is overwhelming; for example, the serial publication Side Effects of Drugs Annual lists and critically discusses over 3000 references each year. As a group, pharmacotherapeutics journals publish more papers on adverse drug reactions than journals that cover other fields, but even so they publish a minority of the total number of papers, and no single journal or group of journals can be highlighted as being a frequent source of primary information. Non-specialists must therefore rely on secondary literature (reviews) and tertiary literature (critical summaries) for information. Most of the primary published literature is in the form of anecdotal reports (30%) and formal studies or randomized controlled trials (35%). The anecdotal reports vary in quality; a new serial publication devoted to this type of article would bring some of the literature together and would improve the quality of reporting. Although many of the randomized controlled trials are of good quality and large enough to reveal benefit, most are too small to provide robust information about adverse drug reactions. Systematic reviews are too few in number (only 1.25% of publications on adverse drug reactions cited in Side Effects of Drugs Annual); more are needed.