Pharmacovigilance: opportunities for active surveillance and other fanciful stuff Dodoo ANO, Pal S (WHO-HQ), Olsson S, Lindquist, M., Edward IR (all of UMC) Director, WHO Collaborating Centre for Advocacy and Training in Pharmacovigilance, University of Ghana Medical School, Accra, Ghana // With some diagrams/illustrations from Geraldine Hill, CARM/IMMP New Zealand

The issues There is the need to collect real-life safety information on all medicines used in all countries Because – Pre-licensure clinical studies are of short-duration, limited in extent and exclude several groups of people including typically the elderly, children, pregnant women, lactating mothers – Global health initiatives have helped to expand access to life saving medicines for conditions like HIV/AIDS, malaria, TB; BUT These medicines are being used in countries with little or no systems for safety monitoring Some of these medicines or combinations are new and are being used for the first time ever – no experience of use anywhere else Safety issues can compromise public health programmes and interventions

In short.... The global community has very little information on the safety profiles of medicines deployed for priority conditions Genetics (pharmacogenetics), differences in healthcare practices, endemic diseases and other considerations e.g. malnutrition can all have an effect on medicine safety Countries could rely on the classical method of pharmacovigilance in most countries - spontaneous reporting Or countries can develop and/or utilise newer methods to address national safety issues bearing in mind the well known limitations of spontaneous reporting

Spontaneous Reporting Spontaneous report (ICSR - individual case safety report ) ‘an unsolicited communication by healthcare professionals or consumers that describes one or more adverse drug reactions in a patient who was given one or more medicinal products and that does not derive from a study or any organised data collection scheme’ Adverse drug reaction ‘a response to a medicine which is noxious and unintended, and which occurs at doses normally used in man’ (WHO)

Spontaneous Reporting                       ADR report

Spontaneous Reporting ProsCons Detection of signals of new, rare or serious ADRs Most commonly used method Easiest method to establish Relatively inexpensive Least labour intensive Continual safety monitoring of a product Covers all medicines Only suspected ADRs reported Under-reporting* so data incomplete Reporting bias** Lack of denominator† Unable to accurately assess risk, risk factors or between drug comparisons‡ § Poor at detecting delayed ADRs Deaths poorly reported

Targeted Spontaneous Reporting Targeted spontaneous report (‘targeted ICSR’) ‘a spontaneous report from a healthcare professional or consumer within a defined cohort that describes one or more adverse drug reactions in a patient who was given one or more medicinal products’

Targetted Spontaneous Reports (of adverse events and reactions)

Targeted Spontaneous Reporting ProsCons Still relatively inexpensive, simpler and less labour intensive c.f. CEM Principles similar to SR, hence familiarity Higher reporting rates than SR* Denominator known so incidence of known or suspected ADRs may be determined May encourage spontaneous reporting Only suspected ADRs reported Some reporting bias remains, but less than SR Reporting incomplete so numerator incomplete; assessment of risk not reliable

Active Surveillance e.g. Cohort Event Monitoring “Hot pursuit” Identify, recruit and follow-up cohort of patients who receive specified medicines e.g. antimalarials, anti-retrovirals – Document demographic & drug information, mode of diagnosis – Solicit information on adverse events during follow-up visits Usually once for anti-malarials and continuously for anti-retrovirals Phone follow-up where possible Provides rapid safety information and denominator

Cohort Event Monitoring Adverse event report ‘a solicited communication by healthcare professionals for a patient within a defined cohort that describes one or more adverse events in a patient who was given one or more actively monitored medicines’ (G. Hill) Adverse event Any new clinical experience (favourable or unfavourable) that is worthy of a record in the patient’s file, regardless of its severity and without judgement on its causality (D. Coulter)

Spontaneous Reporting Targeted Spontaneous Reporting                                              CEM  ADR report

Cohort Event Monitoring ProsCons Early detection of signals of unsuspected ADRs Denominator information allows incidence rates of ADRs to be calculated Near complete profile of AEs/ADRs for medicine of interest Assessment of risk; characterises risk factors; between drug comparisons Pregnancy outcomes Deaths recorded More labour intensive than SR or TSR More costly Much data collected most of which represents ‘background noise’ New to health professionals and PV Centres Training required LTFU may be substantial and needs to be actively managed

Several mechanisms for collecting information during follow-up Home visits Diary cards Telephones Cell phones SMS

Collecting event information?

Diary/AE Card – Outer Fold

Diary/AE Card – Inner Fold Injection Site Abscess Date:

Social Media and SMS for Pharmacovigilance

“Hello. My name is John twitter. I have an ADR that I intend to report to pharmacist or that failing to Dr You. …” Tube facebook

Conventional social media

Usage and Impact In the US, 22% of all online time or one in every 4.5 minutes is spent on social networking; with 74% of internet consumers using social networks ( al-media-accounts-for-22-percent-of-time- online/) al-media-accounts-for-22-percent-of-time- online/ One in four people aged 65yrs and above now join social networking ( ational/main shtml) ational/main shtml

Usage and Impact Facebook recorded 750 million users in June 2011 and would be the largest third if it were a country ( million-users/, million-users/ In the US facebook tops Google for weekly traffic ( 93% of business use social media for marketing. (

Guidance to industry and pharmacovigilance (EMA Vol. 9a) Information on Adverse Reactions from the Internet The Marketing Authorization Holder should regularly screen websites under their management or responsibility, for potential reports on adverse reactions. The Marketing Authorization Holder is not expected to screen external websites for information of adverse reactions. However if a Marketing Authorization Holder becomes aware of an adverse reaction on any other website the Marketing Authorization Holder should review the case and determine whether it should be reported in expedited manner in accordance with Chapter I.4, Sections 3.1 and 3.5

Vol. 9a (continued) The Marketing Authorization Holder should consider utilizing their websites to facilitate adverse reaction collection, e.g. by providing adverse reaction forms for reporting or by providing appropriate contact details for direct communication. In relation to such reported adverse reactions, identifiability of the reporter and Patient refers to the existence of actual

New EC PV regulation (2010/84/EU) Article 102 The Member States shall: (a) take all appropriate measures to encourage patients, doctors, pharmacists and other healthcare professionals to report suspected adverse reactions to the national competent authority; for these tasks, organizations representing consumers, patients and healthcare professionals may be involved as appropriate; (b) facilitate patient reporting through the provision of alternative reporting formats in addition to web-based formats; (c) take all appropriate measures to obtain accurate and verifiable data for the scientific evaluation of suspected adverse reaction reports;

WHO-CC Ghana and Tigo Collaboration Simple SMS system for ADR collection – Patient gets enrolled at point of dispensing Demographics, initials, gender, medicine (name, dose, route) taken SMS to server and to patient (serves as carrot: personal patient medication record) – Second carrot: patient gets reminders to take medicine if patient so requests PV centre able to use the data in the server to either request manually ADR information or to send SMS soliciting for ADRs System finalised and roll out just starting.....

Conclusions Mechanisms exist for collecting safety information in all countries including resource limited countries Active surveillance is key when new products are deployed Newer technologies hold great promise