Analysis Of Adverse Event Reports Research Articles

The Safety of Niacin in the US Food and Drug Administration Adverse Event Reporting Database

Of currently approved drugs, niacin is the most effective in raising high-density lipoprotein cholesterol levels, either as monotherapy or in combination with other agents. The US Food and Drug Administration's (FDA) Adverse Event Reporting System provides 1 mechanism to evaluate the safety of niacin as it is used in common clinical practice. In this report, the authors review recent analyses of adverse events reported to the FDA demonstrating that the extended-release formulation of niacin (niacin-ER) has a significantly better safety profile compared with other niacin formulations and compares favorably with other commonly used lipid-altering drugs, including 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and fibrates. In addition, analyses of FDA adverse event reports of the pill combining lovastatin and niacin-ER suggest that the safety of combination therapy with niacin-ER and a statin is comparable with the safety of each of the drugs alone. These analyses should encourage the use of niacin-ER in patients at high risk for cardiovascular disease, as recommended by current national guidelines for cardiovascular prevention.

Improving global monitoring of vaccine safety: A quantitative analysis of adverse event reports in the WHO Adverse Reactions Database

The World Health Organization (WHO) Programme for International Drug Monitoring (PIDM) was initially developed for chemical rather than biological products. The PIDM made considerable achievements in analysing drug-related adverse event reports, progress was more limited for vaccine-related reports. In 2005, the Global Advisory Committee on Vaccine Safety, called for a global consultation to address the need for improved monitoring and analysis of vaccine-related adverse event reports on an international level. In preparation for this consultation, the WHO Adverse Reactions Database was quantitatively assessed and results of this analysis are presented in this paper. Three countries contributed 82% of vaccine-related reports in the database. The mean difference between onset date and report date was 2.4 years. Several issues of concern were identified, such as the fact that many member countries do not forward any or all reports of adverse events following immunization to the PIDM, and the poor timeliness and regularity of reporting, which could prevent timely generation of safety signals.

TZDs and Bone: A Review of the Recent Clinical Evidence

Over the past two years, evidence has emerged that the currently available thiazolidinediones (TZDs), rosiglitazone, and pioglitazone have negative skeletal consequences, at least in women, which are clinically important. Increased fracture risk in women, but not men, was reported for both TZDs, based on analyses of adverse event reports from clinical trials. In short-term clinical trials in women, both TZDs caused more rapid bone loss. In these trials, changes in bone turnover markers suggest a pattern of reduced bone formation without a change in resorption. Although limited, these results support the hypothesis based on rodent and in vitro models that reduced bone formation resulting from activation of peroxisome proliferator-activated receptor-γ (PPARγ) is a central mechanism for TZDs' effect on bone. Research is needed to better understand the mechanisms of bone loss with TZDs, to identify factors that influence susceptibility to TZD-induced osteoporosis, and to test treatments for its prevention.

Automated support for pharmacovigilance: a proposed system.

Governments, manufacturers, and other entities are interested in adverse event surveillance of marketed medical products. FDA's Center for Drug Evaluation and Research redesigned the post-marketing adverse reaction surveillance process to use the advantages of new technology. As part of this effort, a 'Pharmacovigilance Working Group' designed a new strategy for the review and analyses of adverse event reports received by FDA. It created requirements which divided signal detection into five tiers: (1) Single 'urgent' reports would be sent to reviewers' workstations nightly for immediate attention. Reviewers would be able to customize definitions of 'urgent' (events that should not wait for aggregate review). (2) Single urgent reports would be placed in a context matrix containing historical counts of similar events to aid in initial interpretation. (3) In this first level of aggregate review, graphical displays would highlight patterns within all the reports, both urgent and non-urgent, and (4) periodic drug-specific tabled-based reports would display the newly received reports across a pre-defined variety of displays. These four tiers would produce passive and criteria-based results which would be presented to safety reviewers' electronic workstations. (5) Active query capabilities (routine, such as age, sex, and year distributions, as well as ad hoc) would be available for exploring alerted issues. The historical database would be migrated into the new format. All historical and new reaction data would be coded with the new MedDRA (Medical Dictionary for Regulatory Activities) scheme. The strategy was to design a full data capture system which effectively exploits current computing advances and technical performance to automate many aspects of initial adverse event review, supporting more efficient and effective clinical assessment of safety signals.