How could employing the patient perspective transform pharmacovigilance?

KEYWORDS:

• Patient involvement
• pharmacovigilance
• adverse drug reactions
• voluntary reporting

1. Patient involvement: development over the years

The concept of involving patients in pharmacovigilance started in the 1970s [1], with the first studies exploring the value of direct patient reporting published in the 1980s [2]. The reasons to initiate such studies were based on the inherent limitations of available methods of pharmacovigilance, which mostly relied on spontaneous reporting by healthcare professionals. While reporting by physicians was the norm in pharmacovigilance for a long time, an increasing number of pharmacovigilance centers saw the value of involving other groups of reporters such as pharmacists and nurses [3–6]. However, despite these new groups of reporters, limitations of spontaneous reporting remained. Especially underreporting and relatively late detection of new adverse drug reactions were reasons to explore the value of patient reporting.

One of the methods used to collect adverse drug reaction reports directly from patients, was a pharmacy-based approach. A cohort of patients for which antibiotics were dispensed in 11 clinical pharmacies received a questionnaire with questions regarding health events resulting in hospitalization or death. Both the inclusion rate in the pharmacy and the response rate were high, respectively, 71% of the eligible patients and 93% of the participants [7]. Interviewing patients was explored as another method and was shown to complement voluntary physician reporting [8]. This conclusion was confirmed by a validation study [9]. These first studies mainly showed that the number of reports could increase, by adding patient reports as a source. In 1996, Egberts et al. reported that adverse drug reactions can be detected earlier when patient reports (from a telephone medicines information service) would be used as a source in addition to physician reports. In their opinion, relying solely on patient reports would result in too many false alarms due to the quality of the reports [10].

Studies continued to be performed on the value of patient reporting, which were summarized in a systematic review published in 2017 [11]. A comprehensive search in several databases, resulted in 34 studies eligible for inclusion: 2 systematic reviews and 3 other reviews, 14 retrospective observational studies, 9 surveys and 6 mixed method studies. The studies described several advantages of patient reporting: a more detailed description of adverse drug reactions, patients report to other drugs and report other adverse drug reactions than physicians, and supply information on the severity and impact on daily life. Potential drawbacks described were the identification and accuracy of the reported symptoms, the seriousness of the reactions and the costs to the system, meaning that assessment of the reports requires a substantial time investment. Based on the included studies, the 1980s studies’ conclusion that patient reports can complement physician reports was confirmed. In contrast to the opinion expressed by Egberts et al. [10], studies on the quality of patient reports increasingly revealed that the quality is actually sufficient for use in signal detection [12]. More research was recommended on topics such as the value of active programs (explicitly asking patients to report adverse drug reactions to certain drugs) versus passive programs (using spontaneous patient reporting) and the value of social media-generated safety surveillance information [11]. Many countries allow patients to report [13], but most studies on patient reporting were performed in the Netherlands, UK and Denmark [11]. Therefore, additional studies from other countries are needed, in particular from middle and low income countries.

2. Value of patient reporting

Although one of the advantages of patient reporting is the increase in the number of reports, underreporting is still common, like it is in healthcare professional reporting. Healthcare professional underreporting is a major limitation of voluntary reporting and its causes have been well described in literature. Main causes mentioned are ignorance (only serious adverse drug reactions need to be reported), lethargy (for example lack of interest), complacency (believing that only well tolerated drugs are marketed), diffidence (fear of appearing stupid when a reported reaction is only suspected) and insecurity (about the drug being the cause of the reaction) [14]. In addition, high workload and a large administrative burden are likely reasons for underreporting.

Two recent systematic reviews explored the issue of patient underreporting [15,16]. Costa et al. explored factors associated with underreporting by patients in 13 studies. Underreporting was associated with younger age and lower levels of education. The most common reasons for not reporting were comparable to those mentioned in healthcare professional reporting but: ignorance (regarding recognition of adverse drug reactions, not knowing the reason and importance to report, and not knowing how to report), complacency (marketed drugs are perceived as safe and all adverse reactions are well known) and lethargy (reporting is time consuming and difficult) [15]. The other review aimed to summarize reported behavioral determinants, that influence patient and public adverse drug reaction reporting, using the theoretical domains framework. The included 26 studies revealed that knowledge, social or professional role and identity, beliefs about consequences and environmental context and resources were the most important framework domains associated with reporting. Strategies to improve patient reporting should therefore focus on education, training and facilitating feedback and follow-up on submitted reports [16].

Several good examples for such strategies aiming to overcome underreporting in patients are described by Van Hoof et al., such as involving expert patients who are trained in dedicated programs. Expert patients may subsequently be employed by patient organizations to educate patients on the importance of adverse drug reaction reporting [17].

But reduction of underreporting may be less relevant, as the value of patient reporting lies more in the type of information patients can add to reports of adverse drug reactions [11].

Using information on adverse drug reactions shared on social media may also be an effective strategy to gain more insight into patient experiences on adverse drug reactions. Several recent studies on retrieving such information from social media have been performed [18–21]. Artificial intelligence methods such as natural language processing are needed to retrieve analyzable information from social media. These studies concluded that information collected this way may be valuable for both active adverse drug reaction surveillance and pharmacovigilance research. Another option for the deployment of artificial intelligence technology is the analysis of free text fields of patient reports (which tend to be longer than the free text fields in reports of healthcare professionals) to pharmacovigilance centers [22].

3. Active patient participation in pharmacovigilance

Yet, all these efforts focus on rather passive patient participation in pharmacovigilance, namely as a potential source of adverse drug reaction reports. But patients can add much more perspective to pharmacovigilance, in more active forms. Potential activities patients can be involved in, are communication of safety information, development of disease and care management, education, development and implementation of guidelines and the design and conduct of pharmacovigilance research [17]. Based on interviews with 20 stakeholders (patient representatives, pharmaceutical industry staff, regulators), several factors contributing to best practices for patient involvement in pharmacovigilance were identified. Engagement from the start, face-to-face communication, full feedback circle, same-level partners and establishing common goals are among these factors [17]. This information can be used to boost the active patient involvement in pharmacovigilance. The International Society of Pharmacovigilance (ISoP) has founded a Special Interest Group (SIG) on patient engagement: the ISoP PatEG-SIG, which aims to do just so [23]. The ambitions of the SIG are, among others, to help shape the future of patient engagement in safety surveillance and safe use of medicines, to share examples among stakeholders and to support knowledge.

3.1. Patient involvement in risk communication

One of the important challenges of pharmacovigilance is effective risk communication, or in other words to change the behavior of prescribers and patients toward a safer use of medication, based on the information from adverse drug reaction reporting systems. In an invited commentary Arlett and colleagues cite the sometimes disappointing results of regulatory actions [24,25]. Better involvement of patients may improve the effect of regulatory interventions and thus start to transform pharmacovigilance. But perhaps pharmacovigilance will only be truly transformed, when we manage to implement a bottom-up pharmacovigilance culture in healthcare. We will illustrate this by sketching a patient's journey through the hospital of the future, including active follow-up after hospital discharge.

4. Future scenario of patient involvement: the new hospital and beyond

On hospital admission, the patient will verify his or her medication, in order to clarify which medicines are still used and in which dosages. In addition, the patient’s experiences with the medicines will be added, in terms of experienced efficacy and adverse drug reactions, and in terms of medication self-management problems. The reported adverse drug reactions are directly transferred to the pharmacovigilance center, where they will be used to describe on a continuous basis, characteristics like time to onset, course and outcome and for the identification of potential risk factors. Information that can be used by future patients to optimize their pharmacotherapy. When capable, the patient will self-administer his or her medication while hospitalized and will be coached in doing so. This coaching will include the implementation of important advices from regulatory risk communications. In non-capable patients, the informal caregivers will be involved in this coaching.

When new medication is started, the patient (or informal caregiver) will answer a short daily questionnaire on his or her bedside computer regarding the effect and adverse drug reactions. Again, any reported adverse drug reactions are directly transferred to the pharmacovigilance center, but are also used in the evaluation of the therapy and may lead to adaptation of the medication. At discharge all experiences are summarized in a pharmaceutical discharge summary, which will be shared with the next healthcare providers such as the general practitioner and the community pharmacist. In shared decision-making with the patient (and informal caregiver), they will decide which level of pharmaceutical care will be applied for how long in order to continue to monitor therapy. Pharmacovigilance centers generating knowledge from all this information, will directly use this knowledge to improve individual patient care. Of course, pharmacovigilance centers will still perform their oldest task, namely the detection of hitherto unknown adverse drug reactions. But in the future hospital, these reports are enriched by the information from patients or their informal caregivers.

In case informal caregivers are not available and the patient is incapable of such an active role due to dementia, healthcare literacy problems, language difficulties or digital poverty, healthcare professionals will step in and take over the role, as will be the case when informal caregivers are themselves unable to assist (e.g. due to healthcare literacy problems).

For patients not being able to perform this active role due to sickness while in hospital, active follow-up will be provided after hospital discharge for example, by the general practice nurse or by the community pharmacist. An additional advantage of this follow-up is that it accounts for the time needed to develop adverse drug reactions and enables professionals to act upon these reactions swiftly. This may prevent problems such as prescribing cascades [26].

Future studies should explore whether this new hospital including active follow-up is indeed feasible for patients and will add value to pharmacovigilance.

5. Conclusion

This future hospital is just an example to illustrate that what pharmacovigilance really needs is bridging of the gap between regulatory bodies and pharmaceutical industries on the one hand, and everyday healthcare practice centered around the patient on the other hand [27]. If we manage to build that bridge in the coming years, we can be sure that pharmacovigilance is transformed in a positive way.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.