Value and Methods of Pharmacovigilance in the Monitoring of Drug Safety in Parkinson’s Disease

Abstract

Pharmacovigilance encompasses the detection, assessment, understanding and prevention of drug-related adverse outcomes. This important discipline plays a key role in evaluating drug safety and efficacy under real-world conditions of use following market authorization. Pharmacovigilance focuses mainly on adverse drug reactions (ADRs), which are unintended adverse medical events caused by an approved drug used at normal human doses for the prophylaxis, diagnosis, or therapy of disease, or for modification of physiological function. Spontaneous reporting of ADRs is a key source of pharmacovigilance data on marketed drugs. Analytic pharmacoepidemiologic studies can also be used to study real world safety and effectiveness (RWSE) of marketed drugs. Evaluation of spontaneous reporting data is often referred to as passive pharmacovigilance, with analytic epidemiological studies based on electronic health records or claims data representing active surveillance.

Pharmacovigilance has contributed substantially to our knowledge of the safety of antiparkinsonian drugs. Though patients on dopamine agonists and/or L-DOPA usually develop diurnal somnolence or impulse-control disorders, because they only occur infrequently, they were only identified in the marketing phase by spontaneous reporting of the adverse events. Tolcapone has been shown to produce fulminant hepatitis with a very low frequency, an adverse effect that was unnoticed during premarketing clinical development. Heart valvular disorders in patients treated with ergolinic dopamine agonists were also identified using spontaneous reporting data and later confirmed by large-scale pharmacoepidemiologic studies. Heart failure has been related to pramipexole use by several pharmacoepidemiological studies, after a signal was detected in phase III clinical trials. In this chapter, the main concepts underlying modern pharmacovigilance are outlined, along with the specific role of pharmacovigilance in assessing the safety of antiparkinsonian drugs.

Appendix

Adverse event or experience: any untoward medical occurrence that may present during treatment with a medicine but which does not necessarily have a causal relationship with this treatment . The basic point here is the coincidence in time without any suspicion of a causal relationship.

Serious adverse event: any event that: is fatal; is life-threatening; is permanently/significantly disabling; requires or prolongs hospitalization; causes a congenital anomaly; or requires intervention to prevent permanent impairment or damage.

Adverse drug reaction (ADR): a response to a medicine which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function. In this description it is of importance that it concerns the response of a patient, in which individual factors may play an important role, and that the phenomenon is noxious (an unexpected therapeutic response, for example, may be a side effect but not an adverse reaction).

Unexpected adverse reaction: an adverse reaction, the nature or severity of which is not consistent with domestic labeling or market authorization, or expected from characteristics of the drug.

Side effect: an unintended pharmacodynamic effect of a pharmaceutical product occurring at doses normally used by a patient which is related to the pharmacological properties of the drug.

Modified from: Safety of Medicines, A guide to detecting and reporting adverse drug reactions . WHO, Geneva, 2002 [1].