The Evolving Role of Pharmacovigilance

Ketan Zota
Director
Zota Healthcare

Pharmacovigilance is a critical component for determining the benefit to risk ratio of treatment. The potential for drug toxicity is determined throughout the lifetime of use of a drug or biological agent, including the development cycle. This includes both the preclinical as well as clinical data. This article defines the science of pharmacovigilance and the process of adverse event reporting and reviews the new directions that pharmacovigilance has taken.

The World Health Organization (WHO) defines Pharmacovigilance as "The science and activities relating to the detection, evaluation, understanding, and prevention of adverse reactions to medicines or any other medicine-related problems".

Pharmacovigilance, shortened to PV, is the scientific and detailed study of collecting, monitoring, researching, assessing and evaluating pharmaceutical products. The word Pharmacovigilance comes from Greek and Latin words; Pharmakon (Greek) which means Medical Substances and Vigilia (Latin) which means To keep watch. All the information given by the healthcare providers and patients, are the main key to perform the Pharmacovigilance process.

The main purpose of this in Pharma industry is to improvise patient's care and safety in relation to the use of medicines. It is very important to understand all the paramedical and medical interventions in order to serve good and safe public health. Pharmacovigilance assesses the beneficial and harmful attributes of the medicines that further indicate about their rational and safe use. It also promotes the clinical training and education involved in it. Thus, it helps in communicating effectively to the public and health professionals.

Developed countries are actively involved in using the concept of Pharmacovigilance and the statistics by these countries have indeed focused on the issues and highlighted the benefits incurred. But under developed or lower income countries have major health issues that aren't being rectified because of their major setback. Such countries are in complete need of Pharmacovigilance. Indulging this concept into the health infrastructure of such countries will help them generate reliable supply and quality of medicines, trained essential healthcare staff and proper access to its education, communication and technology.

Pharmacovigilance is very important for every healthcare professional to have an acute knowledge of every drug. Proper data documentation, drug benefits/risk profile, and other practices should be incorporated well in the Pharmaceutical industry. Hence knowing about every step of the Pharmacovigilance Management cycle will be an advantage for every health organization to educate every patient clearly about every drug.

To understand the topic in a well manner, there are certain terminologies used and are further categorised according to the health situation.

1. Harm Occurred.
Terms and its definitions:
Adverse Drug Event (ADE)-Harm caused by the use of drug.
Adverse Drug Reaction (ADR)-An unintended reaction to a drug taken as a normal dose.
Serious Adverse Event (SAE)-An event which is fatal or life threatening.
2. Harm may have occurred.
Terms and its definitions:
Medication Error-A preventable event that may cause harm to the patient.
3. Harm did not occur.
Terms and its definitions:
Potential Adverse Drug Event - Situations that may cause harm by using the drug but does not harm the patient.

The above mentioned terms are frequently used to explain and understand the concept of Pharmacovigilance. It is very essential to deeply understand these terminologies Pharma Bio World February 2017 27 in order to avoid misconceptions. But the main three are ADE, ADR, and Medication Error that sums up the core elements of Pharmacovigilance.

What is Adverse Drug Event (ADE) in Pharmacovigilance and how is it important?

as the harm caused by the overdose or overconsumption of drug. It may also be caused from the use of drug for discontinuing or reducing the dose of any drug therapy. It is precisely defined as an "injury caused by using a drug". This can also be a result of a medication error, but such scenarios hold a rare chance. The study of ADEs in patients during clinical trials must be recorded with the education sponsor or can willingly be given to the local ethics committee as well.

There are types of ADEs:
Serious
Non-Serious
Expected
Unexpected
Study-related
Possibly study-related
Non study -related

Reporting all the types of ADEs plays a major role in Pharmacovigilance. Without these reports it becomes a difficult scenario to conclude the situation. The reporting of ADE involves data entering, triage, assessment, receipt, distribution, and archiving all ADE documentation.

After ADE, it is Adverse Drug Reaction (ADR) that educates about how reactions are caused during the process of Pharmacovigilance.

ADR is defined as the side-effect or adverse reaction after drug consumption. It is broadly defined as the unwanted, uncomfortable, or dangerous effects that may be caused after consuming the drug. The toxicity of the drug exceeds than the normal which leads to a situation of ADR. The over-ingestion of any drug reacts first with the blood levels resulting into an adverse reaction. It is very important for every healthcare provider to have knowledge about all possible risks and benefits of every drug. An ADR can be detected by paying attention to the patient's progress graph after consuming the prescribed drug. The types of ADR are classified as:


Type A - Augmented Reactions.
Type B - Bizarre Reactions.
Type C - Continuing Reactions.
Type D - Delayed Reactions.
Type E - 'End-of-use' Reactions.

The intensity of an ADR also depends on patient's characteristics (age, sex, ethnicity, genetic factors) and drug factors (type of drug, composition, dosage, bioavailability, etc)

Apart from ADEs and ADRs, Medication error is another main element of study of Pharmacovigilance. Here the latter is comparatively easier to rectify than the others. The possibility of harm caused is less and can also be prevented at the right time. But a single error can also lead to major harmful situations.

A medication error is further defined as an unorganised prescribing, administration, and dispensing of drugs. It is not an obvious scenario for such errors to cause harm to the patient but the negligence might lead to inappropriate use of the drug by the healthcare provider, and this might cause harm to the patient as well. Following are the causes that lead to a medication error:


Unavailable Drug Information.
Incomplete Information of Patients.
Inaccurate Recording.
Inaccuracy in Transcribing Orders.
Unclear Labelling of Drugs.
Inadequate Knowledge of Drugs.
Deadline Pressure.

It is very important for every drug developer to consider a Pharmacovigilance plan during its first stage itself in order to rectify the errors done and possible errors in time. Where Adverse Drug Event, Adverse Drug Reaction, and Medication Error give detailed insight to Pharmacovigilance, there are few other main elements that are equally important to educate every patient and healthcare provider with. Following are the other main elements that create a complete Pharmacovigilance:

1. Individual Case Safety Report.
A report that gives a detailed description of every doubtful adverse reaction by the administration of one or more drugs to an individual patient. There are four elements of the ICSR - An identifiable patient, An identifiable reporter, A suspect drug, and An adverse event. These four elements are important to be determined during the triage phase of a potential adverse event report.

2. MedRA.
It is the Medical Dictionary for Regular Activities. MedRA is mapped from WHO-ART, the WHO Adverse Reactions Terminology. It is a medical coding dictionary that is used to convert adverse reactions information into terminology that can be easily analyzed and identified.

3. Clinical Trial Reporting.
Clinical Trial Reporting is the safety information about every drug used while performing a clinical trial. This kind of reporting is also known as Serious Adverse Event (SAE) reporting of clinical trials. The drug's effectiveness on human or in simpler terms drug's safety is the main component to consider while deciding the drug's market approval and presence. Every drug authoriser must have a keen eye on the details of every drug.

4. Aggregate Reporting.
Also known as periodic reporting, aggregate reporting plays a very important role in safety assessment of drugs. The records of aggregate reporting are a compilation of the safety drug data. These data's can be of a longer time period such as months or years. The main advantage of Aggregate Reporting is that it gives a broader view of drug safety.

Pharmacovigilance process in simpler words is defined as assessing the benefits and evaluating the risk. The evaluation of risks should begin at the preclinical stage of a medicinal product and it should extend throughout the life cycle. There is now added focus on safety and risk assessment after a product has received regulatory approval, when it is placed on the market and prescribed to large populations. Although there is no international standard that dictates the components of an adequate Pharmacovigilance system or the processes to be engaged in risk management, there is consensus among the major regulators that Pharmacovigilance is necessary and important in the development and commercialization of medicinal products.

Risk management in Pharmacovigilance is the main discipline that is responsible for signal detect and monitoring the risks and benefits of every drug profile. Risk management is a compilation of Risk Management Plans (RMPs) and other aggregate reports such as Development Safety Update Report (DSUR), Periodic Safety Update Report (PSUR), and Periodic Benefit- Risk Evaluation Report (PBRER). Following are the other few elements under Risk Management that play a key role to carry out the process of Pharmacovigilance with an ease:

Causality Assessment.

Signal Detection.

Risk Management Plans.

Risk/Benefit Profile of Drugs.

A drug provider and analyzer should always make the patients and other healthcare providers understand the benefits and risk of every drug. A patient's reaction and effect after consuming any drug should be keenly heard by the drug provider and provide the patient's with solutions that can alter the possibility of the harm.

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