Public Aspirations for ‘Drug Safety’

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Chapter: Pharmacovigilance: Teaching and Learning Pharmacovigilance

The second major current that has energized the field of pharmacovigilance derives from efforts of both drug regulators and the pharmaceutical industry to meet increasingly insistent public demand for new pharmaceuticals to be proven ‘safe’.


The second major current that has energized the field of pharmacovigilance derives from efforts of both drug regulators and the pharmaceutical industry to meet increasingly insistent public demand for new pharmaceuticals to be proven ‘safe’.

In recent years, the highly publicized withdrawal from sale of many extensively used drugs has elicited wide but shallow public debate about risks and benefits associated with use of pharmaceuticals. Regrettably, this discussion has been confounded by increasingly prevalent perceptions of an unsupport-able rapacity of the global pharmaceutical industry. In addition, in some countries such as the United States, there has been a growing belief that existing regulatory systems designed to evaluate relative risks and benefits of individual products, both before and after licensure for sale, have been compromised by inappropriately structured public administration.

Most of the public discussion has been predicated on the assumption that effective new drugs need to be ‘safe’ to a level that is almost entirely unachievable. Certainly there is a marked contrast in relative levels of ‘safety’ between newer drugs that have recently been withdrawn and older drugs that have been gener-ally available for many years. Drugs such as warfarin, digoxin or aspirin are increasingly widely used and yet are known to produce very significant morbidity and mortality.

However, whether the public’s perception of levels of exemplary pharmaceutical ‘safety’ are ever achievable, it is clear that far too little has been done in the past to systematically eval-uate positive and negative drug effects beyond the point of licensure. The implications of past failure to make such post-marketing assessments has been analysed, and the need for decisive action has been comprehensively justified by Dr Jerry Avorn (2004) in his pivotal book: ‘Powerful medicines – the benefits, risks and costs of prescrip-tion drugs’.

The first day a new drug is on the market should mark the start of a systematic ongoing evaluation of how wisely doctors are prescribing it, how thoroughly patients are taking it, what adverse events it causes in routine care, and (eventually) whether its promised benefits are actually being realized with routine use (p. 383).

Additionally, beyond licensure for marketing, there is also a need for comparative studies assessing both pharmaceutical risks and benefits at different dosing levels between drugs of the same class (or drugs used for the same purpose) across broad end-user populations.

This has been perhaps a key conclusion after recent controversies surrounding negative cardiovas-cular effects associated with the non-steroidal anti-inflammatory class of drugs. It has been the failure to recognize differential levels of benefits and adverse effects amongst members of this class that has resulted in precipitate drug withdrawals (Edwards, 2005). Why retain relatively more hazardous forms of these drugs on the market, when beneficial effects can be achieved from other members of the class with lower levels of negative cardiovascular effects? This is a question that is increasingly being asked. Regrettably the information that might allow some degree of certainty about these relative bene-fits and risks in actual practice is not currently available.

Failure to require such post-marketing studies remains therefore perhaps the single biggest defi-ciency in public regulation of drug ‘safety’ at present.

Global movements are now starting to at least partially address these deficiencies in contemporary systems of pharmaceutical regulation. These move-ments are highlighting and deepening the field of pharmacovigilance and leading to learning needs far from traditional pharmacovigilance activities of past decades. The study and classification of ADRs remains a core activity for pharmacovigilance, but study of and communication about risks as well as benefits of pharmaceuticals in whole user populations is now confronting pharmacovigilance educators as a further key contemporary challenge.

Recent important work has been done by the Inter-national Conference on Harmonization of technical requirements for registration of pharmaceuticals for human use (ICH). This body consists of pharmaceu-tical industry and drug regulators from the European Union, Japan and the United States. The ICH has developed significant new guidelines for pharma-covigilance planning that are currently under active consideration for adoption in each of the major devel-oped world jurisdictions of the pharmaceutical market (ICH, 2004). These guidelines suggest that market-ing licensure might become conditional upon pharma-covigilance planning.

Actions in these pharmacovigilance plans are foreshadowed as extending well into, if not throughout the period of patent protection for pharmaceutical proprietors. Mandatory surveillance of individual products in whole-population use, using compara-tive observational studies, targeted clinical inves-tigations and descriptive drug utilization studies are all suggested as possible components of such pharmacovigilance plans.

It is to be hoped that these moves will be followed with steps to incorporate collection of the needed intra-class drug hazard/effectiveness data that will assist in colouring a more complete picture of key issues in pharmacovigilance.

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