Introduction

The World Health Organization (WHO) defines pharmacovigilance as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any drug-related problems [1]. Broadly speaking, this definition relates to a system used for adverse drug reaction (ADR) reporting and, having detected a potential problem, minimize its impact in the population. This is done using the spontaneous reporting system (SRS), in which a healthcare professional (HCP) or patient sends an unsolicited communication to competent authorities or pharmaceutical companies describing one or more ADRs [2]. However, pharmacovigilance is much more than just spontaneous reporting (SR) [2]. Its scope has grown considerably in the past few decades, encompassing not only ADR reporting but as well medication errors (ME), counterfeit or substandard medicines, lack of efficacy or drug–drug interactions [1]. Currently, pharmacovigilance covers the life-cycle of a medicinal product with concerns to its safety and quality. As such, it needs the active involvement of responsible stakeholders, such as HCPs, patients, regulatory authorities and industry.

Since the creation of the SRS that reporting was mostly restricted to HCPs [1]. Patient reporting (PR) was accepted in some countries, but its value to produce quality information on ADRs was questioned [3]. The accumulation of evidence on PR has allowed to dissipate the fears that patient reports might not be useful [4]. In the European Union (EU), the new pharmacovigilance legislation introduced several changes such as the formal implementation of PR, updated the definition of ADR (now including MEs, misuse and abuse, off-label use and overdose), additional monitoring measures such as the introduction of the black triangle, or a higher level of transparency [5]. Many other countries have followed with the implementation of a PR system [6]. The introduction of PR is part of a wider trend towards an active involvement of patients in decision-making in pharmacovigilance. As defined by Peter Arlett, excellence in pharmacovigilance is based on a patient-focused, proactive, proportionate, multidisciplinary benefit-risk balancing, transparent and science-based approach [7].

The value of patient reporting: where do we stand?

PR has the potential to add new information and perspectives about ADRs in a way otherwise unavailable [8]. Table 1 summarizes the impact and value of PR. Evidence points to the complementarity of PR with HCP reporting, adding more detailed descriptions on previously known ADRs and enabling to establish stronger causality. Patients have contributed to identify new signals and helped in strengthening the supporting evidence for many others [8,9,10]. The added value from PR also lies in the narratives describing their subjective views and experiences such as impact ADRs have or quality issues [10,11,12,13]. Patients have distinct reasons to report and denote an altruistic attitude [8, 14]. Overall, PR continues to increase both in the EU and in many other countries worldwide [4, 6].

Table 1 Patient contribution to pharmacovigilance
Full size table

Despite the positive input from patients, there are several challenges in enabling and placing PR within pharmacovigilance.

Challenges in integrating patient reporting

Recent systematic reviews have looked into the value and the factors that influence PR (REFS) [8, 14]. Patients face barriers to reporting similar to the ones experienced by HCPs, such as low awareness, uncertainty about responsibility for reporting and lack of feedback for submitted reports [8, 14]. Raising awareness to reporting is especially important. Public awareness-raising campaigns have been done in Europe [15]. Despite positive results, as demonstrated by a 13% increase of reports for the period the campaign ran, there needs to exists repetition of such events [15]. Competent authorities should promote a culture of simplicity and eliminating barriers to report. Providing continuous educational activities and cooperate with other organizations such as HCP or consumer organizations to disseminate information about ADRs and pharmacotherapy in accessible language should be aimed [16].

Many countries have their pharmacovigilance system organized around regional centres. In some countries, these centres’ play an important role in gathering missing information from both patients and HCPs [17,18,19]. Regional pharmacovigilance centres can become more involved with patient and consumer organizations in providing training and raising awareness. These centres could also help healthcare institutions to streamline mechanisms of reporting both ADRs and MEs, or have patient-specific webpages with clear language. Considering that healthcare-investment factors can help explain a higher propensity to report, more financial autonomy should be sought for these centres, as this was identified to be a major obstacle to further their current activities [6, 20].

Another topic is the origin of evidence about patient reporting. Most of the studies come from a limited number of countries, largely in Europe [8, 14]. In general, evidence from these countries has been very positive towards PR. Despite the proven benefit of patient reporting, there is a lack of qualitative studies focusing on the perception of HCPs regarding patient reporting, the role and involvement of HCP professional associations or a critical evaluation of patient reporting in other geographies [20]. Currently, PR is accepted in 107 countries [6].

Healthcare professionals’ engagement

Despite the positive contribution from patients, reporting of ADRs by HCPs is fundamental to pharmacovigilance. It is important to not to lose sight of HCP input [9]. It’s important to engage HCPs in identifying ADRs especially in more vulnerable groups. The role of pharmacists has undergone profound changes in recent years, with greater emphasis in pharmacotherapy outcomes through the provision of comprehensive medication review services [21]. This should encourage pharmacists to become more active stakeholders in the detection and reporting of ADRs. In Italy, pharmacist-led interventions to facilitate PR has been done, with encouraging results [22, 23]. Similarly, nurses’ direct contact with patients puts them in a privileged position regarding not only the detection of ADRs, but as well education of patients to report ADRs [24]. Overall, a cultural shift needs to happen to promote the cooperation of HCPs with patients to autonomously report ADRs.

Methodological developments

Spontaneous reporting remains the cornerstone of pharmacovigilance. However, this method has limitations, especially under-reporting of ADRs [18]. PR brings complementary information on ADRs not covered by HCPs, but also presents methodological challenges. Concerns have been expressed that the data richness provided by patients is not being fully utilized in the regulatory process [10, 13]. Recent projects in Europe have highlighted some of the methodological difficulties with the use of patient-reported information [15]. To take full advantage of PR, there needs to be research in different methods for data collection, signal detection, benefit-risk assessment and the ability make use of registries and other forms of direct data capture from patients [10, 20]. Other methods to complement PR have shown their worth, such as the intensive monitoring methodology using patients used in the Netherlands [25]. Such approaches should be more encouraged in other geographies.

Social media has been recognized as a potential source to gather data on patients’ experiences with medicines. However, the usefulness of social media data for pharmacovigilance has not been fully assessed [26]. Questions remain about how social media can supplement routine pharmacovigilance [26]. An interesting route of research has been focusing on mobile apps [27]. Further studies in this area should be encouraged.

Conclusion

Pharmacovigilance has evolved considerably over the decades and currently involves the systematic life-cycle monitoring of medicines. For it to be effective, all stakeholders needs to be involved. PR has been an important development. Overall, PR brings a new depth of information about ADRs and promotes the engagement of patients in their own treatment.

However, there are several interrelated challenges facing pharmacovigilance. PR is not independent from HCP engagement. For both patients and HCPs it is important to raise the awareness for reporting. New methods of data collection, further evaluation of patient-reported data and methods able to better incorporate PR requires further research. The position of HCPs in pharmacovigilance should not be forgotten. Due to their contact with patients, they should rely more on patients to report ADRs. The changing nature of healthcare professions and it’s interaction with pharmacovigilance requires exploration as well.

There is still a long way to go in assuring PR is recognised as a robust sources of information in pharmacovigilance. In order to enable the early detection of ADRs and have a proactive pharmacovigilance system, more needs to be done with and for patients.