Evaluation of a Web-Based, 'Purchase Event' Intensive Monitoring Method for Pharmacovigilance of Natural Health Products: Lessons and Insights from Development Work in New Zealand.

INTRODUCTION: Intensive monitoring methods are used in pharmacovigilance for prescription medicines but have not yet been implemented for natural health products (NHPs). OBJECTIVES: Our objective was to assess feasibility issues with a new 'purchase event' intensive monitoring method for pharmacovigilance of NHPs, including pharmacy and NHP purchaser recruitment rates, collection of NHP purchaser key patient identifier information for data linkage and quality and completeness of data. METHODS: For the Ginkgo study, 213 community pharmacies in the Auckland (Aotearoa New Zealand) District Health Board area were invited to participate. Staff in participating pharmacies (n = 3 [1.4%]) recorded ginkgo product sales and gave purchasers a study invitation card (October 2015-January 2016). Ginkgo purchaser participants were emailed links to web-based baseline and follow-up questionnaires about adverse events occurring during/after taking ginkgo. Participating pharmacists and consumers were invited to provide qualitative feedback about the study. For the NHP-Lite study, all NHPs were included for monitoring. Community pharmacies in the Green Cross Health network were invited to participate. Participating pharmacy staff gave all NHP purchasers a study invitation card over a 2-week period (May 2016). NHP purchaser participants were emailed links to web-based baseline, follow-up and feedback questionnaires. RESULTS: Few community pharmacists (Ginkgo study, n = 3; NHP-Lite study, n = 18) and NHP purchasers (Ginkgo study, n = 0; NHP-Lite study, n = 4) participated. Pharmacists (Ginkgo study, 3/3; NHP-Lite study, 11/18) described several reasons for participating and suggested ways to increase consumer recruitment, including simplifying study procedures. CONCLUSIONS: These web-based, purchase event, intensive monitoring studies, with cohorts built through NHP purchases in pharmacies, identified substantial issues with recruiting pharmacists/pharmacies and NHP purchasers that, at present, render such studies unfeasible. Future studies need to consider other methods of recruiting NHP purchasers and develop a simple method for recording NHP purchases.

Pregnancies associated with etonogestrel implants in the UK: comparison of two 5-year reporting periods.

OBJECTIVES: (1) To identify pregnancies associated with the use of the contraceptive implants Implanon and Nexplanon in the UK during two 5-year reporting periods. (2) To classify the possible reasons for device failure in cases reported for each implant. (3) To examine any differences between reasons for pregnancies associated with these products. STUDY DESIGN: Extraction of data from the UK spontaneous reporting system for adverse drug reactions in relation to etonogestrel implants. Reports indicating pregnancy were identified for the periods 2005-2009 (Implanon) and 2012-2016 (Nexplanon). Possible reasons for failure of the method in each reported case were assigned to one of eight predetermined categories. RESULTS: After exclusions, 229 Implanon and 234 Nexplanon cases contained sufficient information for analysis. True method failures accounted for a majority of the pregnancies in those using contraceptive implants (58%); the next most common cause was missing implants (26% of pregnancies). In all categories of cases, there was no difference in frequency of pregnancy when the two time periods were compared. CONCLUSIONS: There is still potential for greater avoidance of pregnancies associated with etonogestrel implant use. IMPLICATIONS: This study underscores the continuing need for taking a full drug history, timing the insertion on days 1-5 or according to recommended quick starting routines and palpating the arm after implant insertion.

The role and strategy of ISoP in global pharmacovigilance.

Applying the WHO definition of pharmacovigilance, the International Society of Pharmacovigilance, (ISoP) is concerned with all aspects of medicine safety. The safety of patients exposed to medicines depends on a wide variety of factors, where the understanding of each factor is associated with its own professional competence and skillset. For pharmacovigilance systems to work efficiently, a broad understanding of the necessary contribution of each of the different scientific competence areas and professional skills is required. ISoP is an independent, not-for-profit international professional organization, concerned with the best interest of patients exposed to pharmaceutical interventions in all healthcare systems in the world. ISoP offers an open platform for professionals from around the world with different expertise and skillsets, to network and exchange information and knowledge in a friendly environment. The society wishes to become a stronger global voice, speaking up in favour of patient safety and to be at the frontline of the global patient safety movement.

Exposure to the smoking cessation medicine varenicline during pregnancy: a prospective nationwide cohort study.

PURPOSE: The purpose of this study was to investigate the extent of exposure to varenicline during pregnancy in 'real-life' post-marketing use and follow-up all pregnancy exposures to identify maternal and fetal outcomes. METHODS: This was a prospective observational cohort study conducted in New Zealand using intensive prescription event monitoring methods. A nationwide cohort of patients dispensed varenicline during a 4-year period was established from pharmacy dispensing data. Women of reproductive age were followed up with specific questionnaires to identify exposure to varenicline during pregnancy and maternal and fetal outcomes. RESULTS: Between 1 April 2007 and 31 March 2011, 23,721 patients were dispensed varenicline. Pregnancy questionnaires were sent for 6882 women of reproductive age, representing 29% all patients (54% female/unknown sex patients) in the varenicline cohort. The frequency of pregnancy exposure in women for whom a valid pregnancy questionnaire was returned was 23/2739 = 0.84%. For the 23 reports of pregnancy identified, exposure to varenicline was from the time of conception for 19 cases. Duration of exposure during pregnancy ranged from 1 day to 16 weeks. Adverse outcomes were identified in five of 17 live births: one baby had birth asphyxia and recurrent chest infections, one had gastro-oesophageal reflux, one was diagnosed with ankyloglossia and two had feeding difficulties. CONCLUSIONS: This study suggests that approximately 1% of women of reproductive age prescribed varenicline may be exposed to this medicine during pregnancy. This could result in significant fetal exposure worldwide and indicates the need for a global pregnancy register for varenicline.

How to improve communication for the safe use of medicines?: Discussions on social marketing and patient-tailored approaches at the annual meetings of the WHO Programme for International Drug Monitoring.

Over the past decade, the annual meetings of national centres participating in the WHO Programme for International Drug Monitoring have increasingly included discussions on how to improve communication between national pharmacovigilance centres, patients, healthcare professionals, policy makers and the general public, with the aim of promoting the safe use of medicines. At the most recent meetings, working groups were dedicated to discuss possible applications and implementation of social marketing and patient-tailored approaches. This article provides the history and a summary of the recent discussions and recommendations to support progress in this respect at national and global level. Recommendations are made to investigate and pilot these approaches in small-scale projects at national pharmacovigilance centres. Applying elements from the social marketing and patient-tailored approaches to support behaviours of safe medicines use in patients and healthcare professionals should give the pharmacovigilance community new tools to achieve their goal to minimize risks with medicines and improve patient safety.

Epistaxis and other haemorrhagic events associated with the smoking cessation medicine varenicline: a case series from two national pharmacovigilance centres.

PURPOSE: To present a case series of haemorrhagic events associated with varenicline identified from the New Zealand (NZ) and Netherlands national pharmacovigilance centres and propose a possible mechanism for these adverse events. METHODS: Reports of epistaxis and other haemorrhagic events (in all system organ classes excluding gynaecological) associated with varenicline were identified and assessed in both the NZ Intensive Medicines Monitoring Programme (IMMP) and the Netherlands Pharmacovigilance Centre Lareb (Lareb). Additional reports were identified from the World Health Organisation Uppsala Monitoring Centre (WHO-UMC) datasets, and these also underwent causality assessment. RESULTS: A total of 30 reports of haemorrhagic events were identified by the NZ IMMP (16 reports) and Lareb (14 reports). Six cases of epistaxis were identified, and four patients had a positive dechallenge on withdrawal of varenicline, suggesting a causal association. Another five reports of gingival bleeding were identified, with three patients having a positive dechallenge. Another patient who experienced haemoptysis while taking varenicline had a positive dechallenge and a positive rechallenge. In the WHO datasets, a further 49 reports of epistaxis, 39 reports of haemoptysis and 21 reports of thrombocytopenia were identified. A plausible mechanism for haemorrhagic events associated with varenicline may be a result of interaction with the serotonin (5-HT) receptor system and transporter. CONCLUSIONS: This is the first specific investigation of haemorrhagic events associated with varenicline. The results of our assessment of reports identified by two national pharmacovigilance centres suggest that there may be causal relationship between varenicline and these adverse events.