Medicines Safety
Modern medicines have changed the way of management and control of disease; however, despite having beneficial effects, they contribute to adverse drug reactions (ADRs) (WHO 2014). In this context, the safe use of medicines is vital as it affects each member of the society (Edwards and Aronson 2000). Despite medicinesâ utility in the treatment and prevention of disease, it sometimes may result into undesirable or even fatal reactions, and in some countries ADRs are listed among the top ten causes of mortality (White et al. 1999).
The World Health Organization (WHO) defines an ADR as "a response to a drug that is noxious and un-intended and occurs at doses normally used in man for prophylaxis, diagnosis or therapy of disease, or for modification of physiological functionâ (WHO 2002). The risk of ADR is associated with the drug use including dose, administration frequency and pharmacodynamic and pharmacokinetic characteristics of population composed of paediatric and geriatric patients or those with hepatic and renal impairment (Sultana et al. 2013). Such conditions require special attention in regard to ADR monitoring, thus making ADRs to cause an additional economic burden on patients, caregivers and healthcare systems.
Hospital Admissions and Adverse Drug Reactions
Since the early 1980s, many studies have reported that the ADRs were the cause of hospital admissions with reporting rate of 2.9 to 6.0 percent. The hospital admissions due to ADRs incidents were found to be 1.5 to 20% and were higher than that to the total admissions to hospitals (Black and Somers 1984; Lazarou et al. 1998; Baker et al. 2004). A study by Classen et al. (1997) reported that during 1990â1993, the ADR incidence-related hospital admissions were 2.43 per 100 admissions (Classen et al. 1997). Similarly, Bates et al. (1995) found that ADR-related admissions were 6.5 ADRs out of 100 admissions (Bates et al. 1995). Pirmohamed et al. (2004) conducted prospective analysis of 18,820 admissions in UK hospitals which accounted to the 1225 ADR-related admissions and found that there was a high burden of ADRs in terms of morbidity, mortality and cost to the National Health Service (NHS) (Pirmohamed et al. 2004). Wu et al. (2010) analysed a ten-year trend of hospital admissions related to ADR in England and found that 557,978 admissions were related to ADR, presenting 0.9% of total patient admissions due to an ADR. During this period, the number of ADR incidents increased from 42,453 to 75,076, and mortality rate also increased from 4.3% to 4.7% (Wu et al. 2010). A prospective study conducted in public hospitals of France in 2006â2007 showed that out of 2692 admissions, about 97 admissions were related to an ADR (BĂŠnard-Laribière et al. 2015). Schneeweiss et al. (2002) conducted a longitudinal population-based study between 1997 and 2000 and found that among 10,000 hospital admissions, 9.4 admissions were drug related in Germany (Schneeweiss et al. 2002). Contrary to this, the data regarding ADR-related hospital admissions are scarce in developing countries (Ramesh et al. 2003).
Pharmacovigilance Systems
There is always a tradeoff between medicinesâ side effects and therapeutic benefits. However, evidence suggests that ADRs are very common and may lead to hospitalization and even deaths (WHO 2014). The thalidomide disaster, which took place half a century ago, is still perceived as a big tragedy in the history of healthcare, that has resulted in the foetus anomalies to thousands of pregnant mothers, who had used the drug to treat morning sickness problems (Nkeng et al. 2012). This incident marked the failure of medicines regulation, weak approval process as well as a hesitant approach by regulatory bodies to take action. It has also highlighted the lack of communication between the patients and the healthcare professionals (HCPs) (Caduff-Janosa 2017).
To address these issues, the WHO established a programme for monitoring of drug safety as a pilot project in 1968. Initially ten countries joined this project; however, as of June 2019, 166 countries are members of the WHO Programme for International Drug Monitoring (PIDM). Moreover, 136 countries are submitting ADR reports to the VigiBase, a WHO global database of ADRs (WHO 2019a, b). In 1971, WHO established its first pharmacovigilance centre in Uppsala, Sweden, known as the Uppsala Monitoring Centre (UMC) (WHO 2015). Now UMC has pharmacovigilance collaborating centres all over the world (UMC 2019a).
Pharmacovigilance (PV) is defined as âthe science and the activities concerning the assessment, detection, understanding and the prevention of the harmful results or any adverse drug-related issuesâ (UMC 2018a). Many developed countries have successfully established strong pharmacovigilance systems in their countries. The system is meant to report suspected ADRs that are encountered by HCPs in their clinical practice. A pharmacovigilance centre collects spontaneous reports on possible drug-related issues to detect the ADRs in the post-marketing phase (Rolfes et al. 2014). This spontaneous reporting is considered as the most important feature of the PV system whereby the reports are submitted to the national reporting agency by healthcare professionals, general public and pharmaceutical manufacturers and are then further communicated to the WHO pharmacovigilance centre (UMC 2018b). The suspected ADR reports from member countries of the WHO Programme for International Drug Monitoring (PIDM) are sent to the WHO international database âVigiBaseâ, which is managed by the WHO Uppsala Monitoring Centre (UMC). The reports are systematically reviewed and analysed and then the evidence-based recommendations are forwarded to the member countries (UMC 2017a).
Organization of Pharmacovigilance Activities
Pharmacovigilance activities in any country are carried out by the help of regional or local centres in these countries which collect ADR reports (serving as alarm signals), design surveys and other pharmacovigilance studies and provide additional information on drugs. Concerns about possible ADRs and requests for information about a drug are directed to the appropriate regional pharmacovigilance centre. In recent years, regional centres have expanded their pharmacoepidemiology activities such as finding associations between specific ADRs and factors such as age, gender, dosage, population phenotype, concomitant use of other medicines as well as environmental factors. The information is further communicated to the national pharmacovigilance centre, which then considers specific measures such as drug withdrawal from the market, modification in drug classification and restricting the approved uses of a drug, evaluation of risk-benefit ratio of medicines, sending additional information to physicians and then submitting the ADR reports to the UMC (Montastruc et al. 2006).
Apart from all the above-discussed pharmacovigilance activities, the main role of the pharmacovigilance system is associated with the signal detection which is a core activity of the UMC. This perhaps aims to find and describe medicines associated with the suspected harm to patients. Signal detection happens through the evidence provided by healthcare professionals in the form of spontaneous reporting of ADRs or reports submitted by pharmaceutical companies and patients. A signal is considered as a hypothesis of a risk associated with a medicine supported by arguments and the data (UMC 2019b). Globally, most of the pharmacovigilance systems depend upon the information about ADRs, which is communicated through the spontaneous reporting systems. The ADR reported from healthcare professionals is entered into the database and is regularly assessed for the signal generation (Edwards and Biriell 1994; Waller and Harrison-Woolrych 2010). During the post-marketing phase of an approved drug, spontaneous adverse drug reaction (SADR) reporting is used for the...