Pharmacovigilance

Pharmacovigilance, also known as drug safety, is the discipline within pharmaceutical science that addresses the identification, evaluation, and mitigation of adverse effects and other drug-related problems associated with pharmaceutical products.
The etymological roots for the word "pharmacovigilance" are: and vigilare. A central concern in pharmacovigilance is adverse drug reactions, defined as harmful and unintended responses to a medicinal product. That definition includes lack of efficacy: that means that the doses normally used for prevention, diagnosis, or treatment of a disease—or for the modification of physiological disorder function. In 2010, the European Union expanded the definition to include lack of efficacy and medication errors, recognizing that adverse outcomes extend beyond harmful responses to therapeutic failures and misuse. The U.S. Food and Drug Administration adopted similar expanded criteria for its pharmacovigilance framework, which includes medication errors, overdose, misuse, abuse, and exposure during pregnancy or breastfeeding. Patient and healthcare provider reports, as well as other sources such as cases reported in medical literature, play a critical role in providing the data necessary for pharmacovigilance to take place. In order to market or to test a pharmaceutical product in most countries, adverse event data received by the license holder must be submitted to the national drug regulatory authority. ''
Pharmacovigilance aims to identify safety signals in medicinal use and implement measures to reduce risk of harm to patients from medicinal products. Companies must conduct a comprehensive drug safety and pharmacovigilance audit to assess their compliance with local, regional, national, or international laws and regulations. This includes ongoing collection of safety data after a product is approved for marketing.

Terms commonly used in drug safety

Pharmacovigilance uses unique terminology. The terms used in this article are specific to drug safety, although some are used by other disciplines within the pharmaceutical sciences as well.
The European Medicines Agency defines terms in its Guideline on good pharmacovigilance practices :

Adverse drug reaction is any unintended, harmful, or unpleasant response to a drug that is reported to have occurred at doses normally used in humans for prevention, diagnosis, or treatment of disease; such reactions may be pharmacologically mediated, immunologically mediated, or idiosyncratic to the individual, and are considered adverse when a causal relationship between the drug and the event is at least suspected or established.
Adverse event is a side effect occurring with a drug. By definition, the causal relationship between the AE and the drug is unknown. An investigator must establish causality and severity and then report it, especially during clinical trials.
Benefits are the therapeutic good of a medicine or device, and benefits also include the patient's subjective response.
Causal relationship is said to exist when a drug causes or contributes to the occurrence of an adverse drug reaction.
Clinical trial refers to an organised program to determine the safety and/or efficacy of a drug in patients. The design of a clinical trial will depend on the drug and the phase of its development. Some clinical trials are conducted after a device or drug is approved to follow for safety.
Control group is a group of individual patients that is used as a standard of comparison within a clinical trial. The control group may be taking a placebo or may be given the standard treatment as the comparator.
Dechallenge and rechallenge refer to a drug being stopped and restarted in a patient, respectively. A positive dechallenge has occurred, for example, when an adverse event abates or resolves completely following the drug's discontinuation. A positive rechallenge has occurred when the adverse event re-occurs after the drug is restarted. Dechallenge and rechallenge play an important role in determining whether a causal relationship between an event and a drug exists.
Effectiveness is the extent to which a drug works under real world circumstances, i.e., clinical practice.
Efficacy is the extent to which a drug works under ideal circumstances, i.e., in clinical trials.
Event refers to an adverse event.
Harm is the nature and extent of the actual damage that could be or has been caused.
Implied causality is a regulatory convention in spontaneous reporting systems where adverse events are assumed to be related to the suspect drug unless the reporter explicitly indicates otherwise. This approach prioritizes signal sensitivity over specificity, recognizing that reporters who select a particular drug as suspect have observed a temporal relationship they deemed noteworthy. Actual causality determination occurs during subsequent pharmacovigilance evaluation.
Individual Case Safety Report is an adverse event report for an individual patient.
Life-threatening refers to an adverse event that places a patient at the immediate risk of death.
Phase refers to the four phases of clinical research and development: I – small safety trials early on in a drug's development; II – medium-sized trials for both safety and efficacy; III – large trials, which includes key trials; IV – large, post-marketing trials, typically for safety reasons. There are also intermediate phases designated by an "a" or "b", e.g. Phase IIb.
Risk is the probability of harm being caused, usually expressed as a percent or ratio of the treated population.
Risk factor is an attribute of a patient that may predispose, or increase the risk, of that patient developing an event that may or may not be drug-related. For instance, obesity is considered a risk factor for a number of different diseases and, potentially, adverse drug reactions. Others would be high blood pressure, diabetes, possessing a specific mutated gene, for example, mutations in the BRCA1 and BRCA2 genes increase propensity to develop breast cancer.
Signal is a new safety finding within safety data that requires further investigation. There are three categories of signals: confirmed signals where the data indicate that there is a causal relationship between the drug and the AE; refuted signals where after investigation the data indicate that no causal relationship exists; and unconfirmed signals which require further investigation such as the conducting of a post-marketing trial to study the issue.
Temporal relationship is said to exist when an adverse event occurs when a patient is taking a given drug. Although a temporal relationship is absolutely necessary in order to establish a causal relationship between the drug and the AE, a temporal relationship does not necessarily in and of itself prove that the event was caused by the drug.
Triage refers to the process of placing a potential adverse event report into one of three categories: 1) non-serious case; 2) serious case; or 3) no case.
Adverse event reporting

The activity that is most commonly associated with pharmacovigilance, and which consumes a significant number of resources for drug regulatory authorities and drug safety departments in pharmaceutical companies, is that of adverse event reporting. Adverse event reporting involves the receipt, triage, data entry, assessment, distribution, reporting, and archiving of AE data and documentation. The source of AE reports may include: spontaneous reports from healthcare professionals or patients ; solicited reports from patient support programs; reports from clinical or post-marketing studies; reports from literature sources; reports from the media ; and reports reported to drug regulatory authorities themselves. For pharmaceutical companies, AE reporting is a regulatory requirement in most countries. AE reporting also provides data to these companies and drug regulatory authorities that play a key role in assessing the risk-benefit profile of a given drug. The following are several facets of AE reporting:

Individual Case Safety Report

One of the fundamental principles of adverse event reporting is the determination of what constitutes an individual case safety report. During the triage phase of a potential adverse event report, it is important to determine if the "four elements" of a valid individual case safety report are present: an identifiable patient, an identifiable reporter, a suspect drug, and an adverse event.
If one or more of these four elements is missing, the case is not a valid individual case safety report. Although there are no exceptions to this rule there may be circumstances that may require a judgment call. For example, the term "identifiable" may not always be clear-cut. For a report to be valid, the patient must be identifiable, meaning the reporter can provide sufficient information to distinguish this case from others and enable follow-up investigation. A reporter may remain anonymous in some jurisdictions under whistleblower protections, but the organization receiving the report must be able to identify the reporter for verification purposes.
The concept of identifiability also applies to the other three elements. Although uncommon, it is not unheard of for fictitious adverse event "cases" to be reported to a company by an anonymous individual trying to damage the company's reputation or a company's product. In these and all other situations, the source of the report should be ascertained. But anonymous reporting is also important, as whistle blower protection is not granted in all countries. In general, the drug must also be specifically named. Note that in different countries and regions of the world, drugs are sold under various tradenames. In addition, there are a large number of generics which may be mistaken for the trade product. Finally, there is the problem of counterfeit drugs producing adverse events. If at all possible, it is best to try to obtain the sample which induced the adverse event, and send it to either the European Medicines Agency, FDA or other government agency responsible for investigating AE reports.
If a reporter can't recall the name of the drug they were taking when they experienced an adverse event, this would not be a valid case. This concept also applies to adverse events. If a patient states that they experienced "symptoms", but cannot be more specific, such a report might technically be considered valid, but will be of very limited value to the pharmacovigilance department of the company or to drug regulatory authorities.