1 Introduction

The importance of pharmacovigilance (PV) for safe medicines and their safe use has increasingly been recognised during the last few years [1]. PV has been subject of intense research and regulation. In particular, it has earned more and more importance and attention in low-resource countries. This is largely due to the globalisation of trade and the availability of new, highly effective but potentially harmful chemical medicinal products in those parts of the world where traditional treatments, in particular herbal or other complementary remedies, used to prevail. A plethora of publications, guidelines and information about newly observed or further investigated adverse drug reactions (ADRs) from all over the world creates a growing burden for people working with medicines or patients to keep abreast of this development. Largely due to the global availability of information through the Internet, patients are nowadays more and more critical and often concerned about, or even frightened of, potential ADRs of their medicines. This poses an additional demand on the up-to-date capacities of their doctors and other healthcare professionals (HCPs). A particular challenge is the multidisciplinary character of PV which requires know-how in topics as different as molecular mechanisms of ADRs, clinical medicine, pharmacoepidemiology, information technology, pharmaceutical manufacturing, legal aspects, public health situations on various levels, and traditions in different regions of the world. Also, theoretical knowledge needs supplementing with experience and practical skills.

There are various stakeholders with specific and different interests requiring PV training, particularly industry, HCPs and their organisations, local health workers, regulators, policy makers, healthcare-related non-governmental organisations (NGOs), researchers in pharmacology or other healthcare disciplines, and teachers at universities and hospitals, both in industrialised and in developing countries. In this complex situation there is a growing need for PV capacity building, particularly by professional training through a broad range of high-quality PV courses with different focuses and different levels of detailing.

Several PV seminars and educational programmes have already been offered for many years by a range of institutions, societies and commercial entrepreneurs. Information about such courses can be readily obtained via the advertising flyers or the Internet. Such material typically outlines about 10–15 main topics and provides a few paragraphs addressing hands-on exercises, if any, together with information about the lecturers and their qualification, the duration of the course, logistic and financial aspects and the issue of homework, exams and certificates. Although there is a substantial overlap in the main topics covered by those PV courses, there are also significant differences between them. Furthermore, the descriptions of the topics, e.g. ‘signal detection’, are very broad. They have to be filled with detailed substance by the lecturers, reflecting their opinion of what is important, but also according to their individual expertise, preference or even personal purposes. Consequently, courses not only about PV as a whole but also about specific topics can be designed extremely differently.

For this reason, people working in public health or other fields related to drug safety, and who are responsible for teaching and who feel a need for widespread and in-depth education in this area, will often be unsure about the topics that should most importantly be covered by a course. Also, they may appreciate advice on how much time, which educational material and what kind of specific expertise of the trainers are needed so that the participants can achieve relevant knowledge and skills on defined levels. Even trainers with indisputable competence in specific areas of PV may not always present their topic within the wider context of PV, i.e. with explanation how other areas adjoin their field and how the topics relate to each other.

It is with this background that experts working in various fields of medicine safety around the world took the initiative and have co-operated to create a comprehensive, detailed and balanced curriculum of PV. Some are appointed members in PV committees associated with the World Health Organization (WHO) or work at its collaborating centres. Others are members of the Executive Committee of the International Society of Pharmacovigilance (ISoP) or its Education and Training Project (ETP) group, or work in institutions dedicated to PV. Our purpose was to provide an inventory and overview of the scope of PV, including relatively new topics such as pharmacogenomics, consumer reporting of ADRs, risk management and WHO-led international projects at several levels of specificity. It was also intended to propose a range of tasks for practical training to reinforce theoretical knowledge acquired. This paper presents the result of this work.

2 Development of the Curriculum

The curriculum makes use of several relevant, already existing packages of topics and concepts of PV teaching. There are already well-established courses, such as those organised by the WHO collaborating centres in Uppsala [2], Rabat and Accra, the University of Hertfordshire [3], the Drug Safety Research Unit (DSRU) [4] or the London School of Hygiene and Tropical Medicine (LSHTM) [5]. Also, a teaching programme ‘EU2P’ is now available in the EU [6]. Furthermore, courses of general interest or with a focus on specific methods, have been offered by ISoP and the International Society of Pharmacoepidemiology (ISPE) during their annual or mid-year meetings. WHO, often in collaboration with the Uppsala Monitoring Centre (UMC) or other collaborating centres, have conducted several training courses in low- and middle-income countries in Africa, Asia and Latin America where the focus was on safety of medicines used for the treatment of important infectious diseases or on setting up new PV centres. Topics of specific relevance for industry and regulators in industrialised countries have usually been covered by the Drug Information Association (DIA) [7] and other commercial conference organisers.

The development of a core curriculum was also inspired by comprehensive overviews and textbooks, which provided ideas and information material about the broad scope of PV. For specific themes and sections, many suggestions have been retrieved from textbooks with specific focuses. Standard sources of information about specific drug-related risks include various reference books. For practical issues concerning PV within the pharmaceutical industry and their relation to drug regulatory authorities, a couple of guidelines were used as reference sources. Also, sets of specific guidance documents were consulted. Single review articles with a wide scope which seemed useful for didactical purposes, were mainly identified in the journals Drug Safety and Pharmacoepidemiology and Drug Safety. An overview of these primarily-used literature sources is given in Table 1.

Table 1 Tabulated overview of primarily-used literature sources

For the purpose of supporting trainers and participants, a more extensive list of references has also been compiled. Many of these references are chapters of comprehensive books [8, 9], and provide overviews of the respective topic. Among journal articles, emphasis is put on systematic reviews. Guidelines and recommendations are preferably cited if they were developed by worldwide acting organisations, such as the Council for International Organizations of Medical Sciences (CIOMS) and the International Conference on Harmonisation (ICH). Considering public health issues relevant to low- and middle-income countries, several guidelines and recommendations are also drawn from printed material issued by the WHO and related organisations. Another selection criterion was freely available information from the Internet, particularly guidelines that are updated from time to time.

The development of the PV curriculum has been a continued effort, started by a few of us some years ago, with several additional experts subsequently contributing to the project. There was no formal procedure for reaching a consensus, such as the Delphi method; however, as many proposals as possible were taken into account.

3 Results

The curriculum presented here includes a main component consisting of modules for theoretical lecture-based training and a minor component with suggestions for hands-on exercises. The theoretical component has a hierarchical and modular structure with evenly divided tiers, and outlined in Table 2. There are 15 chapters of about equal length (hierarchy level I) with four sections each of about equal length again, making a total of 60 sections (hierarchy level II). All sections are composed of four to six subsections, i.e. approximately 300 subsections altogether (hierarchy level III).

Table 2 Core elements of the modular pharmacovigilance curriculum for lecture-based teaching

The practical part consists of 12 times three or four proposals for hands-on exercises. These are related to, and meant to illustrate and provide actual application of, know-how obtained from lectures about those theoretical topics for which skills and experience seem helpful or even necessary. This applies to the fields covered by chapters 4–15. Proposals for practical tasks related to chapters 1–3 are intentionally not included because it was felt that learning of these parts is almost entirely based on the acquirement of theoretical knowledge. The practical part is described in Table 3.

Table 3 List of suggested practical tasks for hands-on exercises as part of the pharmacovigilance curriculum

The comprehensive list of references is available in the electronic supplementary material.

4 Discussion

4.1 Contents and Structure of the Curriculum and its Relation to Established Pharmacovigilance Courses

Our curriculum provides comprehensive coverage of almost all areas of PV, i.e. biochemical, clinical, regulatory and methodological aspects. It also addresses issues relevant for highly industralised and low industrialised countries, including their different healthcare structures and issues. Thus, there are topics as heterogeneous as genetic testing, risks related to monoclonal antibodies, adverse events following immunisation (AEFIs), counterfeiting, record linkage, periodic safety update reports and communication to HCPs.

The curriculum as such is neither ready-for-use teaching material nor the description of a course. It just reflects the current status of the rapidly evolving science in PV. Accordingly, it needs continuous updating and, therefore, regular consideration of new or updated information and guidelines is essential. The theoretical part formulates headings and key terms of topics which a trainer should address in order to cover the essential scope of PV, and provides a harmonised structure for the material. It remains up to the lecturer to develop details, texts and slides, real-life cases or scenarios, and other didactic materials. Likewise, the proposals for hands-on exercises are frameworks that would need to be filled with concrete teaching material and explicitly formulated tasks, selected to be of relevance to the audience, e.g. in a particular geographical region. Trainers may find help in the detailed background information provided in the complete reference list. The selected literature (see electronic supplementary material) provides more information than just the basics of PV, and explains in detail most of the important topics.

Even though some of the broad headings of chapters are similar to those of the well-established courses mentioned previously, our curriculum appears to be rather unique in its granularity of key topics, detailed at a three-level hierarchy, for advanced, medium and basic ‘knowledge’ modules, as well as for hands-on exercises. Another advantage of our curriculum resides in its broad and impartial basis of competence through the involvement of many PV experts from international non-governmental not-for-profit organisations which we consider representative for all major fields of PV.

The strict hierarchical and modular structure may seem too rigid to some PV experts; we are well aware of the fact that some people would prefer a different relative weighting of the chapters or sections on their respective level of hierarchy. Others may also criticise the rather homogenous and comprehensive character of the curriculum, arguing that only courses with contents tailored to the interest and need of the specific audience can be useful.

4.2 General Opportunities Offered by the Structure of the Curriculum, and Concrete Options for its Use

Considering these potential criticisms, we believe, however, that they may be counter-balanced by the broad-based and hierarchical structure of the curriculum. This structure allows almost every kind of focusing on specific issues and going into depth as needed, while maintaining the overall context. There are mainly three factors through which this flexibility is achieved:

  1. 1.

    The large number of theoretical modules on different levels of hierarchy and related practical tasks offers an opportunity for the organiser to tailor a course according to the already existing knowledge and experience, as well as the specific situation and need of the trainees and the available time.

  2. 2.

    The evenly developed structure of the theoretical part with chapters and sections of about equal length suggests its use in a way that similar periods of time can be allocated to individual units.

  3. 3.

    Likewise, the proposed 12 sets of practical tasks are designed in a way that it should be possible to formulate specific exercises which can be fulfilled within approximately equal periods of time.

The curriculum can be applied to an intensive course offered over several weeks where a whole day is devoted to each of the 15 theoretical chapters. In this case, the typical four-quarters of a day can easily be allocated to the four sections of every chapter. Also, one day each could additionally be allocated to the proposed 12 sets of exercises, or even to individual practical tasks. At the other end of the options, there may only be an opportunity to give a 1-day course and go over the majority of the contents of the theoretical chapters at a high level within the day, without further delving into the individual sections or even subsections, let alone any inclusion of hands-on training.

Also, there are various opportunities of tailoring a course specifically to the needs of the audience.

For example, the emphasis put on the 15 theoretical chapters and their sections on the one hand, and on the training of practical skills on the other, should be chosen according to the specific training situation. This could be planned in advance or decided upon in specific situations during the actual conduct of a course where a trainer may wish to include some hands-on exercises. These could be expected to enhance active audience participation and to facilitate dialogue and interaction among her- or himself and the course participants.

Using the curriculum for a ‘zooming’ course may be considered on occasion. This would put a specific narrow topic in perspective, i.e. its place within the field of PV. In this case, one would first devote some time for a broad overview of the whole scope of PV on the chapter level, thereafter address a specific chapter with its four sections, and finally focus on one specific section with its set of subsections or even just on a specific subsection, possibly intensified by one or several of the practical tasks.

A further option would be some kind of ‘cluster teaching’, i.e. training in related chapters such as ‘individual case safety reports’ plus ‘spontaneous reporting systems’, ‘signal detection’ plus ‘post-authorisation observational studies’ or ‘communication’ plus ‘sources of information’. Other aspects may specifically apply to the local situation, recent drug regulations, a current safety problem or individual ADR cases reported in the media. These topics might not be part of a standard international curriculum but might be useful supplements as lively illustrations and stimuli for discussion on a case-by-case basis.

4.3 The Way Forward

For some of the theoretical chapters we have started to develop sets of keywords and examples relating to each of the subsections in order to further detail and illustrate their meaning. Such an additional breakdown of the subsections might be considered as the creation of a further level of hierarchy (‘level IV’). Our aim is to complete this work for all 15 chapters. Also, we may add more proposals for practical tasks to choose from. However, such a detailed curriculum would probably be too extensive for publishing in a printed international journal. It is planned, therefore, to make this version available electronically in Drug Safety or on the homepages of WHO and ISoP. An electronic version could be updated relatively easy and as often as necessary in a modular fashion, in line with how PV in scientific, public health and regulatory terms will evolve in the future. Also, online availability would facilitate the use of the curriculum for long-distance courses. An example of a subsection with keywords drawn from an already detailed theoretical chapter is shown in Table 4 to illustrate how it is envisaged the curriculum would look like at the ‘fourth level of hierarchy’.

Table 4 An example of how a subsection of the theoretical chapter 15, with keywords and examples, would look like in the ‘IV levels of hierarchy’ version of the curriculum

For any revision of this curriculum in the future and also for the development of the detailed ‘level IV’ version, we would be grateful for comments and suggestions and for feedback from applying the curriculum, as we hope that it will be used by many organisations and trainers and prove helpful for professional capacity building.