Pharmacovigilance plays an important role in detecting, assessing, understanding, and preventing the Adverse Effects of medications, ultimately ensuring patient safety. Although strict regulatory guidelines exist for drug safety and efficacy before a drug is approved for market, information about its adverse effects only becomes available once it is released into a larger population.

The timely detection and intervention of adverse effects/adverse drug reactions (ADRs) is essential, as delayed detection can significantly burden public health. For example, over 2,000,000 serious ADRs are estimated to occur among hospitalized patients in the U.S.

This article will explore pharmacovigilance and its role in early detection and intervention of adverse effects.

Pharmacovigilance Overview

What is pharmacovigilance?

Pharmacovigilance is defined as the “science and activities relating to the detection, assessment, understanding, and prevention of adverse effects of medicines.” Its primary objective is to enhance patient safety by identifying and managing the risks associated with pharmaceutical products.

The aim of pharmacovigilance is to:

• Help identify any safety concerns associated with medications.
• Improve public health and safety concerning the use of medicines.
• Contribute to evaluating the benefits, harm, effectiveness, and risks of medicines. In turn, it encourages their rational, safe, and effective use.3
• Help regulatory agencies or manufacturers make decisions regarding restrictions on use, withdrawal, or labeling changes for medications.
• Promote education, clinical training, and understanding of pharmacovigilance and its communication to the public.

Every country has its own pharmacovigilance program due to differences in factors such as prescribing practices, predominant diseases, people’s traditions, and the population’s genetic makeup. These factors can influence the presentation, incidence, and pattern of ADRs.

The history of pharmacovigilance

Pharmacovigilance was implemented roughly 170 years ago. The roots of pharmacovigilance trace back to a few notable drug disasters in the mid-20th century, such as the thalidomide tragedy, which led to severe birth defects in thousands of infants. Incidents like the thalidomide and sulfanilamide tragedies spurred the need for a systematic approach to monitor and regulate pharmaceuticals after they reach the market. Consequently, pharmacovigilance practices began to evolve globally, with various countries and organizations establishing regulatory bodies to oversee drug safety.

One of the most prominent organizations in the field of pharmacovigilance is the World Health Organization (WHO), which initiated the Program for International Drug Monitoring (PIDM) in 1968. The PIDM established the framework for collecting and analyzing data on adverse drug reactions (ADRs) from around the world, laying the foundation for international collaboration in pharmacovigilance.

The scope of pharmacovigilance

Pharmacovigilance extends its reach to all stages of a drug’s life cycle, from pre-marketing clinical trials to post-marketing surveillance. Its primary functions include:

1. Detection: Identifying new and previously unknown adverse effects associated with a drug.
2. Assessment: Evaluating the severity and causality of reported adverse events.
3. Understanding: Investigating the mechanisms underlying adverse effects and their risk factors.
4. Prevention: Developing strategies to mitigate risks and improve patient safety.
5. Communication: Disseminating information to healthcare professionals, regulatory authorities, and the public to ensure informed decision-making.

Clinical trials and beyond

Before a drug is authorized for use by regulatory authorities such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), there needs to be evidence that the benefits of the medicine outweigh the risks. The evidence of safety and efficacy is only limited to the data generated from the clinical trials. However, the clinical trial process only involves a small population for a short period of time.

When the new drug is approved to enter the market, it is now exposed to a large population for a longer period of time and, often, combined with other medications. Due to this, side effects that were not observed during the clinical trials may occur. Therefore, it is vital that safety and risk assessment monitoring continue after the drug has received regulatory approval.

Methods of Pharmacovigilance- Detecting Adverse Effects

The prime objective of pharmacovigilance is to detect undiscovered ADRs. Data can be utilized from various methods to monitor the safety and efficacy of medications. A functioning pharmacovigilance system collects information from healthcare professionals, patients, and marketing authorization holders.

The most common types of post-marking surveillance include:

1. Spontaneous reporting

Spontaneous reporting is a passive approach as it relies on individuals to voluntarily report any suspected ADRs to a local or national pharmacovigilance center. Spontaneous reporting methods include case reports, case series, and spontaneous reports. Spontaneous reporting can be electronic or paper-based.

Single reports from patients that are submitted to these centers are called Individual Case Study Reports (ICSRs). Information from multiple ICSRs is then used to detect potential “signals” – casual associations between previously unknown reactions and a medical product.

The advantages of spontaneous reports include:

• Large-scale and cost-effective
• Generates hypotheses, signals, and essential data on risk factors, risk populations, and clinical features of known serious ADRs.
• Rare and unexpected ADRs are documented faster.

2. Active surveillance

The WHO defines active surveillance as a collection of case study information (drug-based, setting-based, and event-based) as a continuous pre-organized process. Active surveillance helps generate comprehensive data on individual adverse event reports. Methods used in active surveillance include registries, sentinel sites, and drug event monitoring.

3. Observational studies

Observational studies include cross-sectional studies, cohort studies, and case-control studies. Organizations may sponsor or set up a cohort-type study as either a generally hypothesis-generating and testing tool that can be used when needed or to answer safety questions that have arisen after marketing.

A comprehensive pharmacovigilance program would also include evaluating other relevant clinical findings from vital signs, laboratory test results, and additional specialized testing.

The different regulatory authorities maintain databases of ADR reports and systematically analyze them for any unusual patterns of adverse events, new safety signals, one striking case report, or a collection of ADR reports that have exceeded the expected level in typical clinical experience.

4. Electronic Health Records (EHRs) and Data Mining

The digital age has brought about significant advancements in pharmacovigilance methodologies. Electronic health records (EHRs) have become a valuable source of real-world data for monitoring drug safety. By analyzing vast databases of patient records, researchers can identify trends and potential safety signals.

Data mining techniques, including natural language processing and machine learning, play a crucial role in sifting through this vast trove of data. These technologies can help identify potential associations between drugs and adverse events more efficiently than manual review.

Reporting ADRs

Reporting of adverse effects is the foundation of pharmacovigilance. An important distinction between clinical trials and post-marketing ADR reporting is that reporting is required in a clinical trial setting but is mostly voluntary in the post-marketing setting. As a result, under-reporting is widespread and a serious challenge for pharmacovigilance.

Under-reporting of ADRs delays the identification and detection of drug-safety problems, making it more difficult for health authorities to take appropriate action and protect public health.

1. Reporting guidelines

Each regulatory authority has different guidelines for reporting ADRs. For example, In the U.S., ADRs must be reported per the requirements of 21 CFR 310.305 and 314.80119, and in the EU, the EMA coordinates the pharmacovigilance system and operates services and processes to support pharmacovigilance.

2. Reporting systems

The EMA operates EudraVigilance, which is a system for analyzing and managing information on suspected ADRs to medicines that have been authorized or studied in clinical trials in the European Economic Area (EEA).

The FDA established its medical product safety reporting program called MedWatch. MedWatch was developed to broaden and speed up voluntary reports of serious ADRs by patients, consumers, manufacturers, and healthcare professionals. MedWatch publishes safety alerts for FDA-regulated products such as medical devices, prescription and over-the-counter medicines, biologics, combination products, food, cosmetics, and special nutritional products when appropriate.

Most recently, the FDA launched the FDA Adverse Event Reporting System (FAERS) Public Dashboard for COVID-19 emergency use authorization (EUA) products. The FAERS dashboard offers stakeholders more ways of searching for and organizing data on ADRs reported to the FDA.

Conclusion

Pharmacovigilance is an ongoing process throughout a drug’s lifecycle. It is essential in detecting, reporting, and documenting adverse events and drug-related problems. A multi-disciplinary approach with healthcare professionals, such as physicians, pharmacists, nurses, etc., is essential for developing an effective pharmacovigilance system.

Vial: A Leading Global, Full-Service CRO

Vial is a trusted CRO partner in navigating the complex landscape of clinical trials and pharmaceutical development. At Vial, we understand the critical role that pharmacovigilance plays in ensuring the safety and efficacy of your investigational products. Our mission is to assist sponsors in this essential aspect of drug development, offering a comprehensive suite of services designed to streamline processes.

As a technology-forward CRO, we leverage our intuitive technology platform, TrialOS, to run faster, more efficient, and affordable clinical trials without sacrificing quality care of patients or quality data.

To learn more about what a global, full-service CRO can do for you, visit our website or connect with a Vial team member today!