Pharmacovigilance

Pharmacovigilance is “defined as the pharmacological science relating to the detection, assessment, understanding and prevention of adverse effects, particularly long term and short term adverse effects of medicines.
Pharmacovigilance is an important and integral part of clinical research1. Both clinical trials safety and post marketing pharmacovigilance are critical throughout the product lifecycle. Pharmacovigilance is “defined as the pharmacological science relating to the detection, assessment, understanding and prevention of adverse effects, particularly long term and short term adverse effects of medicines.”
The goals of PV are to bolster patient safety concerning medicine use by providing a system to collect, assess, and distribute drug safety data. PV activities involve monitoring approved drugs and investigational medicinal products (IMPs) to:
  • Identify previously unknown adverse effects
  • Recognize changes in the frequency or severity of known adverse effects
  • Assess a drugs risk/benefit to determine if action is required to improve safety
  • Ensure the accuracy of information communicated to healthcare professionals and patients, and to ensure information contained in patient information leaflets (PILs) is up to date
Pharmacovigilance in clinical research
Pharmacovigilance begins with clinical trials that provide data on the benefits and risks of a drug. The aim of pharmacovigilance in clinical research is to determine if the benefits outweigh the risks; if they do, drug manufacturers take steps to gain approval to market the new drug.
Phase I, II, and III clinical trials are needed before a drug company can apply for a new medicine’s market authorization. In these studies, the principle investigator is the main point of contact at the trial site. They are responsible for the conduct of the research and then feed it back to the sponsor (the pharma company).
During clinical trials, the investigator collects and analyzes data on serious adverse events (SAEs), determining whether the drug in question caused the SAEs. If they conclude that the negative side effects were causal, they are categorized as adverse drug reactions (ADRs).
The investigator shares this data with the pharmaceutical company responsible for the drug’s R&D (research and development). This is assessed by the pharmaceutical company’s in-house PV team and the patient files undergo medical review. The PV team determines if the drug is sufficiently safe and effective to progress to the next phase of clinical research or to submit an application to the regulatory authority for approval to go to market.
These regulatory authorities have the final word as to whether the drug’s safety and efficacy profile is acceptable.
If approved, Phase IV clinical trials may be conducted by the drug company to provide additional data on the safety profile and efficacy of a drug. These studies are beneficial as they provide data in a less controlled environment, representative of how patients are using the drug.
Pharmacovigilance outside of clinical research
Pharmacovigilance data from clinical research is limited due to study restrictions. PV data from clinical research poorly identifies:
  • Potential drug interactions
  • Long-term risks
  • Risks that come from higher doses
  • Dangers that come from drug misuse or abuse
For this reason, ongoing PV from healthcare professionals and consumers is necessary to update the potential risks of medications. The drug company may facilitate post marketing drug safety surveillance (a specific type of Phase IV study) to monitor the “real world” effectiveness and safety of the product as it is not possible to anticipate all possible adverse effects of a drug based on preapproval studies. Numerous approaches can be adopted such as; spontaneous reporting systems, drug registries, electronic health records.
Importance of Pharmacovigilance
Pharmacovigilance is central to drug safety. PV analysis conducted in Phase I, Phase II, and Phase III clinical trials gives drug companies data on the safety profile of the drug. This data can be used for further R&D if necessary or can be submitted to regulatory authorities to allow new markets to be accessed.
Both PV practices in clinical research and those done through medical professionals and consumers offer valuable insights into the safety profile of pharmaceutical medications.
When a new adverse reaction is identified, the list of side effects on the label must be updated. At times, PV data can lead to the removal of a drug from the market (drug recall) due to dangerous side effects.
Pharmacovigilance terms/definitions
Adverse drug events (ADEs): Any “untoward medical occurrence” that occurs alongside a drug that has not been conclusively attributed to the use of the drug itself. ADEs encompass side effects and laboratory results.

Adverse drug reactions (ADRs): Any “noxious and unintended responses” attributed to a drug. ADRs are side effects that are directly caused by the use or discontinuation of a medicine.

Serious adverse events (SAEs): Adverse drug events that are particularly serious, including those that are life-threatening, lead to congenital abnormalities, result in extended or unexpected inpatient hospitalization, or cause disability. Newly discovered SAEs for drugs on the market require expedited reporting by pharma companies to regulatory authorities.

Suspected adverse drug reactions: An adverse event that is suspected to be caused by a drug. If research confirms the correlation, it would become a confirmed adverse drug reaction.

Suspected unexpected serious adverse reactions (SUSARs): Adverse reactions that occur which do not line up with the adverse reactions currently outlined in the investigator brochure (before marketing) or product information including the SmPC and PIL (after marketing). Also called unexpected drug reactions.

Good pharmacovigilance practice
The goal of good pharmaceutical practices for pharmaceutical companies is to prevent harm to humans caused by adverse drug reactions from approved pharmaceutical drugs.

Good pharmacovigilance practices (GVP) vary slightly from one country to the next and are determined by the country’s regulatory authorities.

Regulatory authorities worldwide

There are a variety of drug authorities that oversee pharmacovigilance. These vary by country and include:

Multiple organizations oversee international collaboration for pharmacovigilance. The World Health Organization (WHO) is one of the primary groups that facilitate the sharing of data between countries around the world.