Signal Selection and Follow-Up in Pharmacovigilance

Abstract

The detection of unknown and unexpected connections between drug exposure and adverse events is one of the major challenges of pharmacovigilance. For the identification of possible connections in large databases, automated statistical systems have been introduced with promising results. From the large numbers of associations so produced, the human mind has to identify signals that are likely to be important, in need of further assessment and follow-up and that may require regulatory action. Such decisions are based on a variety of clinical, epidemiological, pharmacological and regulatory criteria. Likewise, there are a number of criteria that underlie the subsequent evaluation of such signals. A good understanding of the logic underlying these processes fosters rational pharmacovigilance and efficient drug regulation. In the future a combination of quantitative and qualitative criteria may be incorporated in automated signal detection.

Bruising associated with sibutramine: results from postmarketing surveillance in New Zealand

“…Causality assessment was performed for each case to determine the relationship with the medicine. 9 A request was made to the World Health Organisation Uppsala Collaborating Centre for International Drug Monitoring 10 (WHO-UMC) to search for all platelet, bleeding and clotting disorder (system organ class 1230) reports associated with sibutramine. The reports in the WHO-UMC international database are derived from spontaneous reports from each national reporting centre.…”

“…For all reports of purpura (the high-level term which includes bruising/ ecchymosis), case reports submitted to WHO were obtained and causality assessments were again performed. 9 …”

Signal Detection for Cyclophosphamide: Canadian Adverse Reaction Monitoring Program (CADRMP)

“…From now on the human mind has to decide whether the association is likely or not to represent a true signal and needs further examination. 1 Cyclophosphamide is an inactive pro-drug that requires enzymatic and chemical activation; the resultant nitrogen mustard produces the interstrand and intrastrand DNA cross links that account for its cytotoxic properties. The major mechanism of cyclophosphamide detoxification involves aldehyde dehydrogenase; cells with high proliferative potential express high levels of aldehyde dehydrogenase and as a consequence are relatively resistant to cyclophosphamide.…”

Tracking Vaccine-Safety Inquiries to Detect Signals and Monitor Public Concerns

“…Failure to fully capture cases can cause potential indications of previously unknown side effects to be missed. 8,9 In addition, more common AEs may be undercounted. Serious AEs are more likely to be reported than those that are less serious, but reporting of any AE depends, in large part, on alert health care providers.…”

“…Serious AEs are more likely to be reported than those that are less serious, but reporting of any AE depends, in large part, on alert health care providers. 7,9 Serious AEs are defined by the Food and Drug Administration as those that result in death, life-threatening illness, hospitalization, prolongation of an existing hospitalization, or permanent disability.…”