For all medicines there is a trade-off between the benefits and the potential for harm. To minimize the harm, it is necessary that medicines of good quality, safety and efficacy are used rationally, and that the expectations and concerns of the patient are taken into account when therapeutic decisions are made. To achieve this is to serve public health, and to foster a sense of trust in patients in the medicines they use that would extend to confidence in the health service in general.
The discipline of pharmacovigilance has developed considerably since the 1972 WHO technical report, and it remains a dynamic clinical and scientific discipline. It has been essential to meet the challenges of the increasing range and potency of medicines (including vaccines), which carry with them an inevitable and sometimes unpredictable potential for harm.
The risk of harm, however, is less when medicines are used by an informed health profession and by patients who themselves understand and share responsibility for their drugs. When adverse effects and toxicity appear - particularly when previously unknown in association with the medicine - it is essential that they should be analysed and communicated effectively to an audience that has the knowledge to interpret the information. This is the role of pharmacovigilance. Much has already been achieved.
But more is required for the integration of the discipline into clinical practice and public policy.
The following is a summary of some of the serious challenges facing pharmacovigilance programmes in the next ten years, describing in brief the potential implications of such trends on the evolution of the science.
Major challenges are:
1) Globalization. The globalization of drug distribution and the increased exposure of massive populations to large volumes of medicines. These include novel chemical entities used for symptomatic relief and lifestyle modification as well as medicines used in developing countries to curb the prevalence of pandemic diseases such as HIV/AIDS, malaria and tuberculosis. The use of medicines on such a large scale and within such a short period of time calls for a better and more efficient level of international pharmacovigilance.
2) Web-based sales and information. The Internet, in addition to its many benefits, has also facilitated the uncontrolled sale of medicines (including herbal and traditional medicines) across national borders. Drug information in all forms and with varying levels of accuracy is distributed internationally through this medium. Such information covers: prescription drugs, unregistered medicines, highly controlled substances and traditional and herbal medicines with questionable safety, efficacy and quality. Regulatory decisions on drug safety made in distant countries are available to the international public at the same time as national drug regulatory authorities. Aggressive marketing by manufacturers and distributors through the Internet often results in excessive and, probably irrational, use of medicines. All these changes in drug use are likely to have important consequences on public health and safety.
3) Broader safety concerns. The scope of pharmacovigilance continues to broaden as the array of medicinal products grows. There is a realization that drug safety is more than the monitoring, detection and assessment of ADRs occurring under clearly defined conditions and within a specific dose range. Rather, it is closely linked to the patterns of drug use within society.
Problems resulting from:
• irrational drug use
• polypharmacy and interactions
• increasing use of traditional and herbal medicines with other medicines
• illegal sale of medicines and drugs of abuse over the Internet
• increasing self medication practices
• substandard medicines
• medication errors
• lack of efficacy
are all within the domain of pharmacovigilance. Current systems need to evolve in order to address this broad scope adequately.
Another aspect of broadened scope is the lack of clear boundaries between:
• blood products
• medical devices
• food additives
4) Public health versus pharmaceutical industry economic growth. There may be shortcomings and at times conflicting interests within the pharmaceutical industry when dealing with public health concerns arising from drug safety issues. The industry needs to overcome weaknesses in safety monitoring during clinical trials (80) and post-marketing surveillance.(81) Manufacturers should take a more proactive approach to drug safety rather than maintaining defensive tactics. This calls for a heightened level of product stewardship and recognition of responsibility to public and environmental health.
5) Monitoring of established products. The generic sector of the pharmaceutical industry has not fully recognized its responsibility to continuously monitor the safety of its products throughout the world. There is the erroneous belief that generic drugs are inherently safe even when they interact with other medicines. The generic sector is the largest supplier of essential drugs.
6) Developing and emerging countries. Outside the OECD countries, the pharmaceutical industry has not been committed to pharmacovigilance activities, particularly the drug safety issues involving medicines used in communities with overburdened health care systems, different patterns of drug use and different co-morbid conditions. Other problems to be tackled include:
• irrational and potentially unsafe drug donation practices, and
• widespread manufacture and sale of counterfeit and substandard medicines.
7) Attitudes and perceptions to benefit and harm. These trends have dramatically changed the way in which medicines are used by society. Healthcare providers, patients and the public have responded in different ways to these changing trends as has been described in previous chapters. Their perception of benefit and harm and the level of acceptable risk for medicines in the face of these rapid developments have not been considered in a meaningful way. The harm caused by medicines has been shown to be significant. Morbidity and mortality from drug-induced diseases are only recently being recognized as an important item on the public health agenda in developed and developing countries.
8) Outcomes and Impact. Along with increased public awareness over safety of medicines, there is an increasing public gaze on the performance of the health professions, industry and regulators. Increased accountability must lead to more research into the effectiveness of pharmacovigilance and its place in improving public perception. A major focus must be to empower health practitioners and patients themselves with useful information that improves individual therapy, aids the diagnosis and management of medicine-induced disease, and generally leads to a reduction of iatrogenic diseases.
Current pharmacovigilance systems need to be reviewed and developed further in the face of these important future challenges. The following summarize some of the priority areas that need to be addressed either at a national or international level:
Detection of ADRs
1) Improve detection and accurate diagnosis of ADRs by healthcare providers and patients.
2) Encourage active surveillance of specific drug safety concerns through epidemiological methods such as case control studies, record linkage and epidemiological studies.
3) Consider special activities and expertise required for the detection of safety concerns related to vaccines, biologicals, veterinary medicines, herbal medicines, biotechnology products and investigational drugs.
4) Improve signal detection systems by facilitating the rapid availability of ADR data that may have international relevance.
5) Revisit the definitions of terms used within the field of pharmacovigilance including the definitions of specific ADRs to ensure reliability and universal understanding of data obtained through ADR reporting systems.
6) Develop and implement ADR detection systems that could benefit populations with restricted access to health care.
Assessment of ADRs
7) Further development of automated signal detection systems used in spontaneous monitoring programmes.
8) Improvements in assessment of drug safety concerns that are of international relevance.
9) Foster collaborative links both at local and international level that could allow countries to assess and respond appropriately to drug safety crises.
10) Consider methods by which information on local patterns of drug use can be integrated with pharmacovigilance information during assessment of benefit and harm at a national level.
11) Improve access to reliable and unbiased drug information at all levels of health care.
12) Improve access to safer and more effective medicines for neglected diseases prevalent in developing communities.
13) Encourage awareness of drug safety and rational drug use among health professionals and the public.
14) Integrate pharmacovigilance activities into national drug policies and the activities arising from these (e.g. standard treatment guidelines, essential drugs lists etc.).
15) Further incorporation of pharmacovigilance principles into clinical practice and academic medicine.
16) Encourage the principles of product stewardship among the various partners in health care.
17) Improve regulation and pharmacovigilance of traditional and herbal medicines.
18) Develop systems which assess the impact of preventive actions taken in response to drug safety problems.
19) Improve communication and collaboration between key partners in pharmacovigilance both locally and internationally.
20) The principles of good communications practice in pharmacovigilance and drug regulation should be encouraged, and the resources and expertise to deliver coopted. Different solutions are likely to be developed in different countries and regions, and the experience should be shared.
21) Develop a better understanding of patients, their expectations of medicines and their perception of risk associated with the use of medicines in order to facilitate programmes that will better inform the public on the benefit and harm associated with medicine.
22) Develop sustained and active relationships with the media in order to facilitate effective and accurate communication of drug information to the public.
23) Encourage harmonization of drug regulatory and pharmacovigilance activities by incorporating the wider international community in the development of harmonization policies.
Outcomes and Impact
24) Conduct on-going research to assess the cost-effectiveness of contemporary pharmacovigilance systems in contributing to patient welfare and public health.
25) Consider the sensitivity and specificity of current signal detection and assessment methods and the extent to which contemporary pharmacovigilance systems have been successful in detecting and preventing potential disasters while avoiding the premature withdrawal of safe and useful medicines from the market.
Taking medicines, and prescribing them, are among the commonest of activities of people who are unwell and of those who care for them. It makes sense that those medicines should be monitored to equally demanding standards as those evident in the development and evaluation of drugs, and that prescribing habits and the extent of rational and cost-effective use should be reviewed.
Responsibility for the holistic approach to drug safety that is encompassed in the science and practice of pharmacovigilance, as reflected in this report, has to be shared if ideal practice is to be achieved. The scientists, clinicians, pharmaceutical manufacturers, drug developers, regulators, public policy makers, patients and the general public all have their own complementary roles in achieving what is envisaged. Among the important issues are information, information sharing and broader communication. What we need is a continuing and dynamic development of modern professional practice. We must recognize that solutions to the challenges will come from those inspired and committed individuals and institutions round the world with a vision of improved public health and patient safety. Most important in this venture, is the need for a new spirit of sharing of information and intelligence in line with the vision and aspirations of the Erice Declaration.