Keynote Clinical Lessons from Pharmacovigilance

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Chapter: Pharmacovigilance: Keynote Clinical Lessons from Pharmacovigilance

The history of predicting the future in medical sciences is fraught with difficulty.

Keynote Clinical Lessons from Pharmacovigilance


The history of predicting the future in medical sciences is fraught with difficulty. Almost invariably, major new developments lie just round the corner and are unforeseen by those working in the field. That said, we have always regarded the best guides to the future to be the lessons gained from mistakes made in the past.

Unfortunately, the public perception of drug safety is not one of the triumphs of science over disease. Rather it is one of vague unease and concern often aggravated by exaggerated and markedly adverse media publicity. Adverse drug effects are again being trum-peted as a major cause of admissions to hospital. This is being emphasised with no regard to separating out those adverse reactions that are predictable (due to pharmacological effects and thus reflect inappropriate prescribing or inadequate adherence to clinical advice by patients), from those that are idiosyncratic and thus unpredicted (due to intrinsic problems with medicines whether documented or as yet undiscovered). Nor is due attention directed towards the underlying disorders for which the medicines were prescribed and which them-selves may have major consequences if left untreated. For example, more and more patients are subjected to heroic chemotherapy with the objective of prolonging existence in advanced neoplasia. The therapy may be effective in one or more accepted sense, but may also be associated with undesired, possibly severe side effects, these being entirely predictable and accepted as a risk by the prescriber (and hopefully the patient) at the time of initiating therapy. At the outset, the potential benefits may appear to be worth the risks. For many patients this turns out not to be so.

Similarly, the increasingly widespread use of prophylactic anticoagulation in patients with unsta-ble rhythms with the objective of preventing life-threatening embolic phenomena is associated with a predictable burden of haemorrhagic complications, some of which are undoubtedly life-threatening. Were the media to address the reasons for the drug exposure as well as the consequences thereof, perhaps a more balanced approach to the subject could be undertaken. Unfortunately this is likely to be asking too much in our litigation-conscious society.

Occasional sudden death from torsade de pointes in young individual recipients of antihistamine ther-apy has been another pressing cause for concern over the years. Despite this, there are little in the way of systematic efforts directed towards quantitating the frequency of such deaths. Identifying such patients and reviewing their treatment in the days and weeks preceding death could add valuable knowledge to our portfolio of information on this topic.

Another area of major current concern is the great parental anxiety about the potential hazards of the combined measles, mumps and rubella (MMR) vaccine. Clearly this is a problematic area. Vaccina-tion is used to prevent illness, and the perception of risk in the ‘treatment’ of healthy individuals is differ-ent from the perception of risk in those suffering from disease. Some of those vaccinated may experience minor (local) side effects, while non-vaccinated chil-dren do not suffer any problems at the time when their peers are vaccinated. The reported associations between MMR vaccines, inflammatory bowel disease and autism have caused greatly increased concern about all vaccines in parents who have rarely seen the effects of mumps, measles, whooping cough or indeed most other contagious diseases in the raw. The over-whelming balance of evidence available at present indicates that this problem arises from a causal inter-pretation being placed erroneously onto an apparently random association. Such wrongful interpretations can cause enormous distress. They also cannot easily be rejected or proven wrong by the very nature of the information available to pharmacovigilators  one cannot prove that a drug or intervention is safe, only that there is a risk. One key feature of most of these recent pharmacovigilance problems is the substantial rarity with which they occur. This is because events occur as a consequence of the intrinsic properties of the medicine itself, rather than the way in which it is used. We shall return to this topic in the concluding section of this chapter.

Finally, recurrent headline-grabbing, but false, claims by the media of collusion between the phar-maceutical industry, drug regulators and advisory committees serve greatly to heighten public concern in an area where the echoes of the thalidomide disaster are still audible (House of Commons Health Commit-tee: The Influence of the Pharmaceutical Industry. The Stationery Office, London: 2005).

If one then adds to the above concerns the epidemic of drug abuse that is hitting mainly the youth in west-ern countries at the present time, the scene is set for a major lack of understanding of the true benefits and risks of modern therapeutic medicines. Patients at present seem to have high expectations for the effi-cacy of new medicines, together with expectations of low, or zero, risk. This balance is now unrealistic, and at the very least would contribute to major delays in licensing new products. The public perception of a ‘pill for every ill’ has been, if anything, stronger over the last 10 years. There is a strong feeling that drugs should be safe. After all, they are tested for years by increasingly sophisticated mechanisms. The fact that at the time of marketing only a few thousand individuals with the disease of interest may have been exposed to the drugs at the dose for which they are licensed is not generally understood by the public. Moreover, individual members of the public have increasing desires to participate in decisions concern-ing their health. People increasingly insist on full information about the risks of the diseases from which they suffer, the benefits of therapy to be obtained and the risks of such therapies. Whilst this is generally understandable and desirable, it often places physi-cians in difficult situations, particularly when patients choose not to fully inform their physicians about all their problems or about alternative therapies that they might be using. Should anything untoward happen, there is an inevitable tendency to blame the prescriber. Thus in the minds of many patients, the European Convention on Human Rights gives them complete justification for seeking information and making judg-ments on their own, independently of their physi-cians. However, should things go wrong, there is no such thing as an equivalent European Convention on Human Responsibility. So, any errors or misfortunes that might arise are not seen as, even partly, the responsibility of the patient, but rather attributed in their entirety to the medicines or the prescriber!

These topics raise an important problem in pharmacovigilance that has only recently begun to be recognised and dealt with. This is the question of acceptance of risk by the public. The former Chief Medical Officer of England (and before that of Scot-land), Sir Kenneth Calman, has emphasised the need to have a public debate about this issue as it is clear that a substantial body of the general public (and possibly even some members of the professions) have at best a very hazy understanding of the concepts and magnitude of risks and benefits as far as they apply to disease and its medical treatment. Clearly pharmacoepidemiologists should be to the fore in supporting the necessary endeavours to initiate and sustain any such efforts aimed at improving this sad state of affairs.

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