Int J Clin Pharm (2014) 36:859–862 DOI 10.1007/s11096-014-0004-0
Pharmacovigilance: empowering healthcare professionals and patients Stephane Steurbaut • Yolande Hanssens
Received: 25 February 2013 / Accepted: 12 August 2014 / Published online: 5 September 2014 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2014
Abstract The European Union has thoroughly reformed its pharmacovigilance legislation in July 2012. Despite the changes, underreporting of adverse drug reactions remains a concern. This underreporting seems to be partially associated with incorrect customs and beliefs by healthcare professionals. Therefore, strengthening teaching and training in drug safety monitoring and reporting are essential. Sustained campaigns and education on pharmacovigilance are key elements to enhance its performance and effectiveness. In general, all healthcare professionals as well as patients should be more sensitized and empowered to contribute to pharmacovigilance programmes in order to improve drug safety. Keywords Adverse drug reaction Drug safety Health care professional Patient Pharmacovigilance Spontaneous reporting
Introduction In July 2012, the concept of pharmacovigilance in the European Union (EU) underwent a major reform affecting various aspects of drug safety reporting and monitoring as well as defining updated and/or new responsibilities for the various stakeholders . Important fundamental changes include: 1.
Impact of findings on practice •
Although pharmacovigilance programmes have been expanded, as is the case in the European Union, they still suffer from underreporting.
S. Steurbaut (&) Department of Clinical Pharmacology and Pharmacotherapy, UZ Brussel and Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Jette, Brussels, Belgium Y. Hanssens Department of Pharmacy, Hamad General Hospital, P.O. Box 3050, Doha, Qatar e-mail: [email protected]
Underreporting by healthcare professionals seems to be associated with certain customs and beliefs that are (partially) incorrect. Adverse drug reaction reporting by patients and healthcare professionals can be complementary. Healthcare professionals need more education and training in pharmacovigilance.
the definition of an adverse drug reaction (ADR). This was formerly restricted to any response to a medicinal product which is noxious and unintended under normal use of the medicine. Within the new legislation, the definition has been extended to include reactions resulting from misuse (situations where the medicinal product is intentionally and inappropriately used not in accordance with the authorised product information), abuse (persistent or sporadic, intentional excessive use of medicinal products which is accompanied by harmful physical or psychological effects) and medication errors; the introduction of the legal right for individual European citizens to report suspected ADRs directly to the competent authorities of each EU Member State, and the harmonisation of the concept of medicinal products subjected to additional monitoring such as those
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containing a new active substance as well as all biological medicinal products. In addition, EU national competent authorities may also require this additional monitoring status for older medicines, e.g. to conduct a post-authorisation safety study (PASS). These changes were introduced to collect more information about a drug’s safety profile and hence to increase its safe use by patients. But were these expectations met and if so, to what extent? Besides the legal obligation of the marketing authorisation holder (MAH) to report any ADR to the competent authorities and to elaborate additional risk minimisation activities when deemed necessary, the EU pharmacovigilance programme continues to rely mostly on spontaneous reporting by healthcare professionals (HCPs). Since the new legislation also allows reporting by patients, it is of interest to discern how both categories perform in this regard.
Spontaneous reporting by HCPs It is apparent from literature as well as from personal experience that the major weakness of ADR reporting by HCPs (physicians, pharmacists, dentists and nurses) is its reliance on the willingness and/or ability to report. Each ADR that occurs and is not appropriately reported contributes to the phenomenon of underreporting . This underreporting dilutes and delays the quantity of signals that are needed to introduce a label change or to suspend or revoke a drug’s marketing authorization, thereby compromising patient safety. To overcome the problem, it is important to understand what drives underreporting by HCPs. Several factors relating to customs and beliefs by HCPs have been identified as determinants of underreporting such as ignorance (only severe ADRs need to be reported whether or not in combination with the belief that a causal relationship between the ADR and the drug needs to be ascertained), lethargy (comprising lack of interest and/or time as well as forgetting to report the ADR), diffidence (fear of appearing ridiculous when reporting merely suspected ADRs), judgement bias (the ADR is too trivial to report or is already too well known), perspective bias (the one case that a particular HCP sees cannot contribute to medical knowledge), and complacency (only safe drugs are allowed on the market) [3–7]. In a small survey conducted at the occasion of a workshop on ADRs with 30 participants during the 41st Symposium on Clinical Pharmacy organized by the European Society of Clinical Pharmacy (ESCP) in Barcelona (October 28-31, 2012), the respondents, mostly European hospital pharmacists, indicated that the number of
pharmacovigilance reports transmitted from their institution to the competent authorities underrepresented the real prevalence of ADRs. Although not generalizable due to the small sample size, this indicates that even in a cohort interested in pharmacovigilance, underreporting remains an issue. The main perceived barriers for ADR reporting were uncertainty of a causal link between the ADR and the drug (81 %), time restrictions (70 %) and insufficient clinical background regarding the case (44 %). When asked what actions could be undertaken to overcome this ADR underreporting, enhanced sensitization, promotion and education on pharmacovigilance were most mentioned. In addition, respondents emphasized the need for a simple and efficient ADR detection and registration tool to increase patient safety and decrease the time needed to report the ADR. Moreover, this should be embedded in a culture that is not stigmatizing towards the HCP confronted with an incident to overcome fear for blaming or negative reactions. This latter aspect is especially important because the new legislation also expects medication errors to be reported . Given the fact that medication errors are preventable, it remains to be seen how many HCPs are willing to admit that they have made an error since they may fear medico-legal consequences. Moreover, a medication error does not necessarily points towards a safety issue with the drug as such, e.g. when a hypoglycaemic drug was given to a non-diabetic patient this may trigger an ADR (hypoglycaemia) in this patient whereas it probably wouldn’t in the diabetic patient for which the drug was intended. For these reasons, medication errors might be least of all reported to the authorities and thus most affected by underreporting, despite the fact that such reports may provide useful information.
Spontaneous reporting by patients The first experiences with patient reporting seem to be positive [8–11]. So far, ADR reports by patients showed no major qualitative differences with those generated by HCPs, proving that the quality of patient ADR reporting can be similar to that of HCPs [12, 13]. However, it appears that patients have a higher tendency to report known and non-serious reactions compared to HCPs [13, 14], whereas their aptitude to report serious reactions may be similar [8, 10]. There may also be differences in reporting according to the type of drugs. Patients seem more likely to report ADRs associated with drugs readily used in the community setting and over-the-counter products compared to HCPs . For these reasons, ADR reporting by patients may be
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complementary to that by HCPs and facilitate signal detection resulting from spontaneous reporting systems. Nevertheless, further research is needed to study the full extent by which patients have adopted to report experienced side effects and how this information may contribute to a better understanding of the risk–benefit ratio of any given drug.
Discussion In order to minimize ADRs and to enhance drug safety, the EU has profoundly changed its pharmacovigilance legislation in July 2012. Although these changes contribute to enhanced drug safety, they should be complemented with awareness campaigns directed towards both HCPs and patients to reach their full impact. The prevailing pharmacovigilance legislation and procedures must be made better known to both groups but with a different focus. For HCPs, the emphasis should be on education and training, both at the undergraduate and graduate level, to recognise ADRs and knowing what, how and where to report them, e.g. by practising how to fill out a yellow card form. HCPs also have to stay informed about changing regulations and evolving procedures and/or techniques. In order for a medicine to become registered and allowed on the market, the MAH needs to have established a risk management plan that is sometimes (when deemed necessary by the MAH or when asked for by the regulating authorities) accompanied by risk minimisation activities, mostly comprising of additional information and educational material on the medicinal product for HCPs and/or patients. This certainly is a way to mitigate a drug’s ADR risk on the condition that the HCP is acquainted with this material and remembers to hand it out to each patient when prescribing or delivering the drug. Given that ADR reports by patients can be complementary to those reported by HCPs, it is of importance to stimulate patients to fill out reports when experiencing an ADR. Therefore, the general public needs to know it can file a report to the authorities and the procedures to do so must be patient-friendly, e.g. through a web-based application that guides the patient through the procedure or a smartphone app. In addition, according to Moore (2013)  an important cause of ADRs is due to poor prescribing by physicians and incorrect use by patients. Here also, education is a key element to enhance drug safety by training medical students in proper drug prescribing and by informing patients how to use their drugs correctly . Additional awareness towards HCPs and patients can be created by local and/or national ‘‘active’’pharmacovigilance campaigns. In order to stay effective these efforts
however need to be sustained since self-reporting rates decrease fast after the campaigns were stopped [16, 17]. Other techniques complementing ‘‘traditional’’ spontaneous reporting systems are cohort event monitoring (CEM) and targeted spontaneous reporting (TSR). The first is a prospective, observational, cohort study of adverse events associated with one or more medicines by interviewing patients before and after the start of the treatment to capture problems. The latter is a methodology to sensitise HCPs managing a well-defined group of patients (e.g. patients in HIV treatment programmes) to report all safety concerns or to focus only on specific reactions . Promising techniques with the potential to be of added value to signal detection are analyses of Internet search logs with respect to ADRs and strengthened periodical screening of scientific literature [19, 20]. Last but not least, the launch by the European Medicine Agency (EMA) of its website www.adrreports.eu may improve reporting. One can argue that this may be a blessing and a curse. A blessing due to the vast amount of ADR data that can be retrieved and a curse because that same information may keep the HCP from sending in a report. From that, he/she may conclude that the ADR is already sufficiently known which could decrease the eagerness to report. Nevertheless, in our experience the website helps to overcome doubts about potential drugrelated reactions, thereby stimulating the willingness to report ADRs.
Conclusion Spontaneous or self-reporting of ADRs remains the corner stone of pharmacovigilance systems. To ensure and maintain proper reporting by HCPs, continuous sensitization and education are mandatory. This will increase knowledge and hopefully improve the attitude towards ADR reporting. At the same time, patients must be stimulated to report the ADRs they experience. Pharmacovigilance campaigns addressing both HCPs and patients are a way to raise the general awareness level but need to be maintained in order to sustainably stimulate the engagement and willingness to report ADRs. Acknowledgments We thank the European Society of Clinical Pharmacy (ESCP) for having supported the workshop ‘‘Adverse Drug Reactions—Applying Theory to Practice’’ at the 41st ESCP Symposium in October 2012. We are also grateful to the participants of the workshop for completing the survey. Funding
Conflicts of interest
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