14 Improtant Aspects of Pharmacovigilance

Adverse Drug Reactions (ADRs) are among the top ten leading causes of death in most of the countries. Drug safety monitoring is a risk mitigation exercise in which the ADRs caused by therapeutic drugs, biologicals or devices can explored, prevented or minimized.

It is very important to monitor the safety of a drug. Pharmacovigilance has many important aspects, they are as follows:

    Pharmacovigilance in Drug Regulation

    Sound drug regulatory arrangements provide the foundation for a national ethos of drug safety, and for public confidence in medicines. The issues with which drug regulatory authorities have to contend besides the approval of new medicines, include:

    • Clinical trials
    • Safety of complementary and traditional medicines, vaccines and biological medicines
    • Developing lines of communication between all parties with an interest in drug safety and ensuring that they are open and able to function efficiently, particularly at times of crisis.

    Pharmacovigilance programmes need strong links with regulators to ensure that authorities are well briefed on safety issues in everyday practice that may be relevant to future regulatory action. Regulators understand that Pharmacovigilance plays a specialized and pivotal role in ensuring ongoing safety of medicinal products. Pharmacovigilance programmes need to be adequately supported to achieve their objectives.

    A new medicine must pass three hurdles before its approval by the national drug regulatory authority. Sufficient evidence is required to show the new drug to be:

    • Of good quality,
    • Effective, and
    • Safe for the purpose or purposes for which it is proposed.

    Whereas the first two criteria must be met before any consideration can be given to approval, the issue of safety is less certain. Safety is not absolute, and it can be judged only in relation to efficacy, requiring judgement on the part of the regulators in deciding on acceptable limits of safety.

    There is a possibility that rare yet serious adverse events (such as those occurring with a frequency of, say, one in five thousand) will not be detected in the pre-registration development of the drug. For example, fatal blood dyscrasia occurring in 1 in 5,000 patients treated with a new drug is only likely to be recognized after 15,000 patients have been treated and observed, provided that the background incidence of such a reaction is zero or a causal association with the drug is clear.

    This arbitrary ‘rule of three’ is based on the experience that for any given adverse effect approximately threefold the number of patients need to be treated and observed for the side effect to become manifest and reliably linked with the drug assuming a background incidence of zero of the effect being observed.

    Clinical Trial Regulation

    In recent years there has been a substantial increase in the number of clinical trials in developed and developing countries.

    For drug regulators, the changing trends over recent years in the conduct of clinical trials present special and urgent challenges, particularly in ensuring that the rights and health of patients and their communities are protected.

    In their approval of clinical trials, regulatory bodies look at safety and efficacy of new products under investigation. They must also pay attention to the general standards of care and safety of study subjects, in conjunction with the appropriate institutional review boards (IRBs).

    RELATED: History and Development of Pharmacovigilance

    Safety monitoring during clinical trials is now recognized as one of the major concerns for new drug development. This is currently being addressed by a CIOMS working group. Three main topics are being addressed:

    • The collection of adverse experience information.
    • Assessment/monitoring of clinical data.
    • Reporting/communication of clinical data.

    Once research into new drugs is in the post-marketing stage (Phase IV studies) safety may be monitored to comply with the conditions of registration, particularly when there are unresolved concerns.

    This may lead to improved and more rapid changes in labelling or even withdrawal of a new drug from the market. Routine application of principles of good clinical practice that ensure patient safety and strict compliance with prescribed regulatory requirements would substantially improve standards of clinical trials. 

    Post-Marketing Safety Monitoring

    It is now generally accepted that part of the process of evaluating drug safety needs to happen in the post-marketing (approval) phase, if important innovations are not to be lost in an unduly restrictive regulatory net. Judgement as to whether and how this might happen lies with the regulators.

    The stronger the national system of Pharmacovigilance and ADR reporting, the more likely it is that reasonable regulatory decisions will be made for the early release of new drugs with the promise of therapeutic advances. Legislation governing the regulatory process in most countries allows for conditions to be placed on approvals, such as a requirement that there should be detailed Pharmacovigilance in the early years after a drug’s release.

    Careful safety monitoring is not confined, however, to new drugs or to significant therapeutic advances. It has an important role to play in the introduction of generic medicines, and in review of the safety profile of older medicines already available, where new safety issues may have arisen. In a developing country, these latter considerations are likely to be more important than the benefits a novel therapeutic entity might bring to an already pressed health service.

    While spontaneous reporting remains a cornerstone of Pharmacovigilance in the regulatory environment, and is indispensable for signal detection, the need for more active surveillance has also become increasingly clear. Without information on utilization and on the extent of consumption, spontaneous reports do not make it possible to determine the frequency of an ADR attributable to a product, or its safety in relation to a comparator.

    There are other aspects of drug safety that have been rather neglected until now, which should be included in monitoring latent and long-term effects of medicines. These include:

    • Detection of drug interactions.
    • Measuring the environmental burden of medicines used in large populations.
    • Assessing the contribution of ‘inactive’ ingredients (excipients) to the safety profile.
    • Systems for comparing safety profiles of similar medicines.
    • Surveillance of the adverse effects on human health of drug residues in animals. E.g. Antibiotics and hormones.

    International Harmonization of Drug Regulatory Requirements

    Harmonization of various elements of drug regulatory activities has been undertaken in the last decade by various intergovernmental organizations at regional and inter-regional levels.

    The driving force of these efforts was the increase of global trade in pharmaceutical products and the growth in complexity of technical regulations related to drug safety and quality.

    Harmonization activities related to drug regulation are being pursued in all WHO regions.

    Promoting Communication in the Field of Drug Safety

    Society has a great concern about coping with the dangers of modern life. Medicinal products are among the technological advances that have provided society with great benefits and added risks. Knowledge of the public perception of these risks is essential if they are to be managed effectively.

    How safe is safe enough? Which risks are acceptable? These are two critical questions that providers of medicines need to consider when communicating with patients and the public.

    Recognizing that there is variance between expert views of risk and public perception, there is a need to analyse and understand the differences much more thoroughly. It is not sufficient for the experts to be satisfied with the evidence for safety.

    The pharmaceutical industry, governments and healthcare providers must build public trust through effective risk communications. This can be achieved only once the public mindset is examined and understood.

    Risk and Crisis Management

    The importance of an efficient system for dealing with drug safety risks and crises has become increasingly evident in recent years. Drug safety issues tend rapidly to take on international significance.

    The speed with which information spreads in the modern world means that drug safety concerns are no longer confined to individual countries. Often the media and general public are informed at the same time as, or even before, the national regulatory authority.

    When crises arise, whether they are real or perceived, local safety issues or concerns arising abroad, regulatory authorities are expected to meet them openly, efficiently, thoroughly and rapidly.

    Many national authorities have identified the need for developing an organizational plan for managing risks and for communication and action during crises.

    Pharmacovigilance and the National Drug Regulatory Authority

    The limitations of pre-marketing drug safety data are well-recognized.

    Pharmacovigilance has become an essential component of drug regulation.

    In many countries Pharmacovigilance and drug regulatory approvals are linked by an ADR advisory committee appointed by, and directly reporting to, the national regulatory authority. 

    The committee consists, amongst others, of independent experts in clinical medicine, epidemiology, paediatrics, toxicology and clinical pharmacology. Such an arrangement inspires confidence amongst health personnel and it can be expected to make a substantial contribution to public health.

    Pharmacovigilance in Clinical Practice

    Safety monitoring of medicines in common use should be an integral part of clinical practice. The degree to which clinicians are informed about the principles of Pharmacovigilance, and practise according to them, has a large impact on health care quality.

    Education and training of health professionals in drug safety, exchange of information between national centres, the co-ordination of such exchange, and linking clinical experience of drug safety with research and health policy, all serve to enhance effective patient care.

    National programmes for Pharmacovigilance are perfectly placed for identifying research necessary for better understanding and treatment of drug-induced diseases.

    Pharmacovigilance in International Health

    Pharmacovigilance is an activity that has international significance. The current global network of Pharmacovigilance centres, co-ordinated by the Uppsala Monitoring Centre, would be strengthened by an independent system of review.

    This would consider contentious and important drug safety issues that have the potential to affect public health adversely beyond national boundaries.

    The Erice Declaration provides a framework of values and practice for collection, analysis and subsequent communication of drug safety issues.

    In providing for this, it asserts scientific and clinical issues on the one hand and the right of the public to be openly and fully informed on the other.

    It is a process that requires the active commitment of all involved - regulators, policy makers, health personnel, journalists, and (not least) pharmaceutical manufacturers. Scrupulous attention is required in the practice of Pharmacovigilance to the issues of patient confidentiality.

    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.

    Broader safety concerns about overcoming the problems resulting from,

    • Irrational drug use.
    • Overdoses.
    • Polypharmacy and interactions.
    • Increasing use of traditional and herbal medicines with other medicines.
    • The illegal sale of medicines and drugs of abuse over the Internet.
    • Increasing self medication practices.
    • Substandard medicines.
    • Medication errors.
    • Lack of efficacy.

    Detection of ADRs

    Improve detection and accurate diagnosis of ADRs by healthcare providers and patients. Encourage active surveillance of specific drug safety concerns through epidemiological methods such as case control studies, record linkage and epidemiological studies.

    Assessment of ADRs

    Further development of automated signal detection systems used in spontaneous monitoring programmes.

    Improvements in assessment of drug safety concerns that are of international relevance.


    Improve access to reliable and unbiased drug information at all levels of health care.


    Improve communication and collaboration between key partners in Pharmacovigilance both locally and internationally.

    This Post Was Modified on 9th June 2021.