patient centricity in : new directions and new horizons for transformation

Supriya Desai

he importance of Patient-centric innovation will be at the heart pharmacovigilance (PV) as a of the transformation of PV over the next science, critical to both effective couple of decades and this will likely forever change PV as we know it today. But are we patient care in clinical practice and public T really prepared to implement patient-centric is growing. Patient-centeredness approaches in PV? What steps are required to and have emerged as core bring safety to patients, as opposed to elements in today’s interactive and bringing patients to safety? responsive healthcare systems. As patients take more interest in their Patient-centred health and healthcare, they support the implementation in PV maxim of ‘‘Nothing about me, without In Europe, the EU Directive 2010/84/EU and EU me’’ and expect caregivers to engage in Regulation No. 1235/2010 provide shared decision making, so that the recommendations, developed by the patients’ voice is always included. European Patients’ Forum, for patient-centred implementation for PV. These recommendations are intended to lead to a Patients usually report adverse drug reactions strong, open and transparent PV system that (ADRs) to their doctors. However, since only ensures the confidence of patients, healthcare 5% of doctors are estimated to participate in PV, traditional mechanisms may not be professionals (HCPs) and regulators alike and represents a step forward for safe, high efficient in ensuring adequate safety 3,4 reporting. Data from studies indicate that quality and patient-centred healthcare . systems which enable direct recording of patient concerns may identify new drug safety The Directive 2010/84/EU amends the signals earlier than professional reporting definition of ADRs to include medication 1 errors and misuse as part of ADR reporting to systems alone . This emphasises that the Supriya Desai MD, PGDBM is a patients’ role in actively reporting ADRs is key help collect more information on the real-life Clinical Research and to building a better PV ecosystem. working of medicines, when used in different Pharmacovigilance (PV) circumstances by different people. Products, Executive with over 16 years of experience in clinical practice programmes and responsible subject to additional monitoring (e.g. products and in various leadership roles in media coverage aimed at increasing access to with new active substances, biologics) need to the healthcare industry including clinical research, drug safety and drug information has led patients in many be identified by a black symbol with a PV. In her current role as Medical countries to take greater responsibility for standard explanatory sentence on the Director and Practice Head at packaging indicating that the medicine is Sciformix, she provides scientific their own health. This is reflected in the and operational leadership to a creation of patient charters, patients’ bills of under additional monitoring, what such global medical team (across rights 2 and patient advocacy groups. For monitoring means and the reasons behind it, India, Philippines and US); without creating unwarranted alarm so that involved in medical review example, patients with HIV/AIDS have been activities across instrumental in creating international patients do not stop their treatment pharmacovigilance, safety awareness of disease impact, improving unnecessarily. This transparency is paramount , signal management and allied safety surveillance access to therapies and of to ensure patients’ trust in the functioning of activities, spanning diverse associated medication risks. the PV system. therapeutic areas.

PharmacoVigilance Revıew • Volume 8 Number 4 • November 2015 7 The shift from pure safety analysis to benefit– centres. Medical concepts need to be risk evaluation and thereby the overall comprehensively communicated in an implementation approach for an effective understandable and accessible format to patient-centric PV model is entrenched in four patients. Involvement of patient organisations main steps; namely to educate, encourage, as experts for development of safety engage and enable patients, as outlined in information as well as for set-up and Figure 1 . development of the national web portals on medicines is critical. Step 1: Education and encouragement The growing commercial relevance of emerging markets coupled with lower levels One of the key approaches in patient-centric of patient awareness in these regions poses a PV is raising patient awareness regarding the specific challenge and would likely limit the importance of reporting ADRs and continually success of patient-centric measures in a global highlighting the critical role they can play in PV environment. In this context, involving PV, right from safety reporting through risk HCPs like pharmacists, nurses or communication. builds upon existing relationships between Targeted educational initiatives include providers and patients and helps activate their training programmes to directly train patients to participate in safety reporting consumers and patients regarding adverse activities. Reported information can be acted event (AE) reporting systems, as well as train upon by the HCP or reported to other HCPs, investigator site teams, patient organisations as appropriate and provides a mechanism for and HCPs. Dissemination of product safety providers to report complementary clinical summaries, benefit–risk data and risk information or enable linkage to a medical management plan summaries for public record. Direct appreciation and recognition for consumption on a real-time basis is important patient efforts to report AEs with possible and can be through company websites, provision of some incentives (non-monetary) national web portals and patient information to patients and consumers would further encourage ADR reporting. Step 2: Engage purposefully and enable proactively ADRs are estimated as the fifth largest cause ()*+"&$' of deaths in hospitals 4, yet only around 10% to 25% of all ADRs are reported. Underreporting of ADRs is a serious issue, which undermines the evaluation of safety of medicines. Direct in reporting drug-related problems can increase the efficiency of the PV system and compensate for some of the shortcomings of systems based on HCP reports only 5. (%0"0$' !"#$%&'' (%",-$' The Directive 2010/84/EU [Article 102(b)] proposes guidance encouraging direct patient reporting of ADRs, via appropriate measures including web-based and alternative formats to the national competent authorities (NCAs). Studies show that patient reports are more valuable compared to HCP reports as patients often report earlier, perceive the impact and (%+.*/"0$' severity of reactions differently and give more detailed descriptions, including specific circumstances in which the reaction occurred. In certain situations, like ADRs resulting from Figure 1: Implementation model for patient- prescribing errors or off-label use of centric pharmacovigilance. medications and ADRs of intimate nature,

8 PharmacoVigilance Revıew • Volume 8 Number 4 • November 2015 direct reporting by patients would enable practice records and pharmacy registries collection of such crucial safety data to ensure within national health systems (containing better medication safety 6. confirmed patient-level health and treatment information) would provide the ability to link Patient-reported outcomes (PROs) are data validated patient information (around elements directly reported by patients about diagnosis, co-morbidities, allergies and other experiences with healthcare, symptoms, treatments) for analysis of aggregated safety functional status, or quality of life 7. The Patient data, and help better understand the etiology Reported Outcomes Safety Event Reporting of rare reactions and possible correlation of (PROSPER) Consortium comprises of industry, patient-related genomic data with specific regulatory authority, academic, private sector safety issues 10 . and patient representatives interested in the area of patient reported outcomes of adverse offers another novel channel for events (PRO-AEs). This consortium has put driving patient-centric PV. Most social media forth specific guidance for improved safety activities for PV by companies are focused on reporting by better incorporation of the screening of social media sites to ensure patient’s ‘voice’ and perspectives into adequate safety reporting. Easy, convenient collection of safety data, so that the safety reporting of AEs via simple patient-friendly profile and benefit–risk balance of new and mobile applications (deployed on mobiles, existing medicines is better defined 8. smartphones), monitoring of company- managed websites, health forums and Effective involvement of patients in the AE monitoring of safety data reported on social reporting process is possible by use of novel media sites like Facebook and Twitter are ADR reporting tools and processes like ADR useful in this context 11 . online forms, mobile applications and through local pharmacies. Further, patient involvement Patient engagement in the PV process can in set-up and user-testing of the reporting only be considered truly complete when the systems ensures that the system is fit-for- patients and the public are involved in the purpose and user-friendly. Developing risk management and communication guidelines for the follow-up procedure for process. The industry, regulators and HCPs reports in consultation with patient and HCP must build public trust through effective risk organisations enables collection of high- communication by proactively publishing quality data, conveys feedback to patients on required safety information as per EU how the information will be used and provides guidance. High-quality information patients with further information or where empowers patients to play their role in the information is available (e.g. the publicly- PV system, to drive better patient safety and accessible part of the EudraVigilance high quality of care 5,6 . database 3). EU Directive 2010/84/EU [Chapter 2 of title Engaging patients as partners in the data IX] contains crucial provisions from the collection enterprise would enable systematic patients’ perspective concerning collection of information and provide a more transparency and communication regarding comprehensive picture within a population. medicines, while Articles 21 and 106 list This can be achieved in limited populations via information that NCAs should make publicly patient registries, or in a wider population available through national web portals. This using existing infrastructure to engage includes marketing authorisation, patients, e.g. community pharmacies and assessment reports, package leaflets, pharmacists 9. summary of product characteristics, risk management plan summaries, list of Additional patient-centred PV initiatives medicinal products subject to additional include real-time monitoring of clinical trial monitoring, and information on different safety data with targeted back-up data ways of reporting ADRs to the NCA by HCPs collection methods to reduce missing data for and patients. Further, involvement of non-compliant patients (e.g. electronic patients and patient organisations in testing reminders, email, telephone or a human call). of patient information leaflets and other Collection of patient reports via approaches safety information prior to release per linked to electronic health records, clinical mandatory () user testing in the

PharmacoVigilance Revıew • Volume 8 Number 4 • November 2015 9 EU and use of the US Food and Drug Medicine estimates that at least 1.5 million Administration’s (FDA’s) new preventable ADRs, including medication misuse Labelling Rule format for display of occur within the healthcare system each year 12 . important risk information for patients are The goal of the US FDA Safe Use Initiative is to required. Another recommendation [Section create and facilitate public and private 4, Chapter 3 of the Pharmacovigilance title collaborations within the healthcare (Article 107i to k)] requires Member States to community to reduce preventable harm by involve and consult patient organisations and identifying specific, preventable medication HCPs as appropriate to provide the right risks and developing, implementing and messages, advice in case of urgent safety evaluating cross-sector interventions with measures such as suspensions or recalls, and partners who are committed to safe employ appropriate temporary measures 3,4 . medication use 13,14 .

Social media can also serve as an effective The label is the patient’s best, and often only, digital tool for risk management and source of information. It is the safety net to communication for PV teams within prevent medication errors. While written companies to directly connect and engage information and oral consultations may with patients, consumers and HCPs to sometimes be available, the prescription improve awareness about product safety, container label must be able to fulfil the leading to improved health amongst professional obligations of physicians and consumers and patients, as shown in pharmacists to give the patient all the Figure 2 11 . information needed to understand how to safely use the medication. The Today, patients in the US depend on recommendations made by the US prescription and over-the-counter medications Pharmacopeia Health Literacy and Prescription to sustain their health, with 3 billion Container Labelling Advisory Panel in prescriptions written annually. The Institute of November 2009 14 outline multiple patient-

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Figure 2: Using social media to engage patients and improve awareness about product safety.

10 PharmacoVigilance Revıew • Volume 8 Number 4 • November 2015 centric labelling measures to reduce accept for different medicines. The outcome preventable ADRs. These include the following. of such research would be the creation of better formulated policies within the evolving 1. Organise prescription label in a patient- patient-centric models with the goal to reduce centred manner. patient risk 2. 2. Simplify label language. References 3. Use explicit text to describe 1. Egberts GPG, Smulderes M, De Konig FHP, et al . Can dosage/interval instructions. adverse drug reactions be detected earlier? A comparison of reports by patients and professionals. 4. Include purpose for use on label. British Medical Journal 1996; 313 :530–531. 2. De Vries CS, Duggan CA, Tromp TFJ, de Jong-van den 5. Improve label readability. Berg LTW. Changing prescribing in the light of 6. Provide labelling in patient’s preferred tolerability concerns: how is this best achieved? Drug Safety 1999; 21 (3):153–160. language, include supplemental 3. European Patients’ Forum. Directive 2010/84/EU and information on label and standardise Regulation (EU) No 1235/2010. Amending the EU directions. Pharmacovigilance Legislation Recommendations for a Patient-Centred Implementation . Brussels, Belgium: European Patients’ Forum; April 2012. http://www.eu- Summary patient.eu/globalassets/policy/pharmaceuticalpackag e/pharmacovigilance-recommendations-for-patient- The patient perspective is an essential centred-implementation.pdf. Accessed 28 June 2015. component of the drug safety monitoring and 4. European Commission. Questions & Answers: Pharmacovigilance . Belgium, Brussels: European risk communication process. PV organisations Commission; 31 December 2010. that incorporate the patients’ ‘voice’ in PV http://ec.europa.eu/health/files/pharmacovigilance/qa systems and processes would be better _pharmacovigilance_2011_en.pdf. 5. Consumer reporting of ADRs. WHO Drug Information positioned over the long-term to ensure patient 2000; 14 :211–215. safety and add real value back to the patients 6. Lloyd AJ. The extent of patients’ understanding of by enhancing product benefit–risk profiles. the risk of treatments. Quality in 2001; 10 Supplement 1:14–18. Overall, adopting a patient-centric approach 7. Basch E. New frontiers in patient-reported outcomes: and partnering with patients and public for adverse event reporting, comparative effectiveness reporting, analysis and communication of and quality assessment. Annual Review of Medicine 2014; 65 :307–317. safety data seems to be the way forward. 8. Banerjee AK, Okun S, Edwards IR, et al . Patient- Reported Outcome Measures in Safety Event At the same time, it is critical to remember that Reporting: PROSPER Consortium Guidance. Drug Safety 2013; 36 :1129–1140. patient centricity is more about listening, 9. Leone R, Moretti U, D'Incau P, et al . Effect of communicating and disseminating to the pharmacist involvement on patient reporting of patients, to ultimately empower them to adverse drug reactions: first Italian study. Drug Safety 2013; 36 (4):267–276. participate in the decision-making process and 10. Basch E. Systematic collection of patient-reported not about putting the decision-making solely in adverse drug reactions: a path to patient-centred their hands. The public has increasingly pharmacovigilance. Drug Safety 2013; 36 (4):277–278. 11. Desai S. Social media for drug safety: navigating the influenced HCP prescribing and patterns of evolving, complex global regulatory ecosystem. drug use in recent years due to increased reach PharmaAsia ; 14 August 2015. http://www.pharmaasia.com/article/social-media-for- of the media and internet. Furthermore, direct drug-safety-navigating-the-evolving-complex-global- advertising to consumers of prescription regulatory-ecosystem/11921 medicines has become commonplace in many 12. Institute of Medicine of the National Academies. Preventing Medication Errors . Washington, DC, USA: countries. With this information, patients feel National Academies Press; 2007, p. 124. more empowered to make their own 13. FDA. Safe Use Initiative Fact Sheet . Silver Spring, MD, therapeutic decisions, without assistance from USA: FDA; 5 June 2014. http://www.fda.gov/Drugs/DrugSafety/ucm188760.ht HCPs, resulting in increasing self-medication, m over-prescribing by doctors on patients’ 14. Institute of Medicine of the National Academies. The demand and misuse of medications 15,16 . Safe Use Initiative and Health Literacy – Workshop Summary . Washington, DC, USA: National Academies Press; 1 December 2010. Variations in the way medicines are used can http://www.iom.edu/Reports/2010/The-Safe-Use- potentially alter their safety profiles and these Initiative-and-Health-Literacy-A-Workshop.aspx 15. Schwartz RK, Soumerai SB, Avorn J. Physician need to be investigated further. In addition, it motivation for non-scientific drug prescribing. Social needs to be determined how access to drug Science and Medicine 1997; 44 (4):541–548. information can influence patient safety, 16. Sachs L, Tomson G. Medicines and culture – a double perspective on drug utilization in a developing including patients’ perception of safety and country. Social Science and Medicine 1992; 34 (3):307– the level of harm patients are prepared to 315.

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