The future of pharmacovigilance: a personal view

Abstract

HistoryModern drug safety, in the sense of widespread, routine,post-marketing surveillance of drugs for new safety issuescame into place following the unpredicted teratogenicoutcomes from the use of thalidomide in the mid-1960s.To provide a regularized tool for medical practitioners toreport suspicions of possibly drug related adverse eventswas thought to be a sensible and practical catch-all for drugrelated problems. Then, and now, it was only one possiblemechanism to review the safety of drugs in clinical practice,but reporting of individual case safety reports (ICSRs) hasset the scene for sending information relating to the real lifeuse of drugs. Initially, ICSRs were assessed for the possiblecausal relationship to a drug, singly and in clusters, byclinically trained pharmacologists, and databases around theworld were populated with assessed reports.By the 1980s, there were so many ICSRs sent in to thenational agencies in heavily populated countries, particu-larly in the USA, that clinical assessment of individualreports on input became impractical, and a public healthapproach was adopted: pharmacoepidemiology was born.This change was highly significant. Looked at from anepidemiological aspect, ICSRs are sometimes poor materialto prove a relationship between a drug and an adverseevent. Reporter bias, drug use factors, lack of quantificationof numerator and denominator are a few of the drawbacks.Since then, epidemiological methods have held sway,particularly in the USA, where it was also possible to uselarge health care databases to perform observational studies.Thereafter, very little was heard of the careful clinical andpharmacological assessment of ICSRs, and the developmentof hypotheses.Some countries, France for example, went a different waytomanagethechallengeofincreasingnumbersofreports,andset about developing strong regional centers using agreedmethodologies to assess ICSRs, before pooling them in theirnational database [1, 2]. Those centers have also been verymuch involved in clinical management and advice of drugrelated injuries, thus creating a strong position of healthydialogue with reporters.Most other countries have made progress between thesetwo extremes, and now the collection and evaluation ofICSRs and also observational and large interventionalstudies are used to a greater or lesser extent in all 83countries of the WHO Programme for International DrugMonitoring.So can we say progress has been made towards the goalof safer use of medicines for patients? I will argue that theanswer is doubtful. The doubt is based on several criticalmatters that have not been resolved.– Complete safety is not achievable with therapies: therewill always be some harm from medicines. Our use ofthe term is relative, but there is no agreement as to whatis a satisfactory level of safety, compared with what,from what perspective, agreed by whom, and measuredhow.– Drugs on the market change continuously, their usevaries over time and geographically. Approaches to theconsideration of safety are subject to scientific, polit-ical, and legal influences, which change.