In all countries (low, middle or high income), national PV systems rely heavily on spontaneous (or voluntary) reporting in which suspected adverse drug reactions (ADRs) are reported to a national coordinating centre by health professionals, manufacturers or directly by patients. Of all the sources of data for drug safety monitoring, the spontaneous reporting systems provide the highest volume of information at the lowest maintenance cost [3
], and have proven their value in the early detection of patient safety issues related either to the products themselves or to their use [4
]. The most important function of spontaneous reporting systems is the early identification of signals [5
] and formulation of hypotheses, leading to further confirmatory investigations or sometimes regulatory warnings and changes of product information leaflets. In some instances, withdrawals of marketing authorizations are also based on ICSRs [6
]. For example, in the case of cerivastatin, an association (a ‘signal’) between cerivastatin, myopathy and rhabdomyolysis was published, based on ICSRs, by the Uppsala Monitoring Centre (UMC) in 1999; various regulatory decisions were announced between 1999 and 2001 in different countries [7
In spontaneous reporting, the most common form of PV, no measures are taken to systematically follow-up patients to record ADRs that they may have experienced. Reporting is dependent on the initiative and motivation of the reporters. This leads to underreporting [8
] compared with actual incidence of ADRs. The absence of an effective PV system with clear protocols, tools and a PV mandate can also act as a barrier to ADR reporting [9
]. Under these circumstances it is difficult to determine the actual number of individuals experiencing an adverse reaction to the medicine. This, together with the uncertainties around the number of patients exposed to the medicine in question, makes it difficult to estimate rates and frequencies of ADRs through spontaneous reporting. Methods of greater scientific rigour are needed to establish quantitative aspects of medicine safety, to better identify specific risk factors and high-risk groups, and to provide valid clinical characteristics of problems associated with specific medicines.
Public health programmes may treat a large population, in an organized and structured fashion, and record the number of patients treated, drugs used, doses given, etc. These programmes thus provide good platforms for capturing the quantitative aspects (rates and frequencies) of ADRs and adverse events with the medicines used [10
]. In the management of HIV and tuberculosis (TB) patients, short- and long-term toxicity data play a critical role in informing treatment choices [11
]. In adopting a public health approach to the delivery of HIV and TB services, it is important to quantify and characterize treatment-related risks, as early as possible, to minimize the harm to public health as well as to sustain public confidence in the programme [14
]. For example, it is important to know what ADRs may be expected with certain treatment and how many will experience this ADR. Such quantitative information will have a direct impact on treatment guidelines, policies and practices. While spontaneous reporting remains the bedrock of safety monitoring, additional methods are needed to quantify the frequency and severity of expected and unanticipated ADRs occurring in patients receiving long-term treatment. In the context of HIV programmes which provide life-long therapy, a simple, inexpensive but robust methodology is needed to capture both known and unknown ADRs. In addition, we need to monitor adverse events that, instead of being directly attributed to the ‘active’ substance, could be attributed more to aspects such as inappropriate use, medication errors, poor quality products or drug-drug interactions. The Global Fund urges countries to invest in PV programmes that monitor the quality, usage and efficacy of the HIV, TB and malaria medicines that it helps countries to buy [15
]. An effective PV programme is one that monitors medicines used in all public health programmes, to improve patient safety, and to improve the credibility and public perception of these programmes.