Pharmacovigillance: Drug Safety Monitoring

 

Archana B. Chavhan*, Dipali M. Bhoi

Shellino Education Society’s, Arunamai College of Pharmacy, Mamurabad, Jalagaon-425001 [M.S.] India.

 

ABSTRACT:

The safety concern of drug is now becoming the priority area. The thalidomide disaster of 1960’s opened the eyes of medication controllers as well as other concern body to establish a way to ensure drug safety; previously the issue was in shadow. The drug safety issues werestrengthen and systemized after the establishment of WHO programmed for international drug monitoring in 1968. Each medication is connected with gainful and undesirable or antagonist effect or adverse reaction (ADR). ADR is the common clinical problem, the number of ADRs reported have also resulted in an increase in the volume of data handled. Pharmacovigillance supports safe and appropriate use of drugs. Spontaneous reporting of ADRs is an essential component of pharmacovigillance. Adverse drug reactions are a common, frequently preventable cause of illness, disability and death. To understand the pharmacovigillance a high level of expertise is required to rapidly detect drug risk as well as to defend the product against an inappropriate removal. Safety and efficacy are the two major predominant considerations about any drug. Proactive pharmacovigillance throughout the product life cycle is the way formed and the future direction for drug safety. Thus, significance of pharmacovigillance is developing and became very important part of clinical research.

 

 

 

INTRODUCTION:

Pharmacovigillance has been defined as: The science and activities relating to the detection, assessment, understandings and prevention of adverse effects or any other drug relation problem (WHO).^1-3

 

Pharmacovigillance is majorly known as drug safety. It is main integral part of clinical research, both clinical trials safety and post marketing. Pharmacovigillance are critical throughout the product life cycle.

 

 

 

 

With a high number of recent high-profile drug withdrawal, both the pharmaceutical industry as well as various regulatory agencies across the globe have raised in the bar. It is now well understand the limitations of clinical trials, which cannot generate enough safety information to safeguard the public health. To ensure the safety of new product after marketing authorization, there are provisions to continuously monitor the safety of a drug as a part of regulatory requirements. Pharmacovigillance emerged after much in area of drug safety, which resulted tragic event of thalidomide 1960’s. After that there has been lots of process in the drug safety issues.^4-6

 

Starting from spontaneous reporting system (SRS) to the latest concept of risk management plans, they all are instrumented to ensure drug use safer and safer. Pharmacovigillance is the ongoing process to monitor drug safety and to make available new information and knowledge about ADRs. Drug regulators and other stakeholders are always vigilant to drug safety issues.⁷ There are lots of examples of restriction and withdraw of drug product based on safety concern. for example, Cisapride, Phenyl propanolamine, Refocoxib, Cerivastine were withdrawn because of safety concerns. So there is an immerse role of drug safety monitoring that is pharmacovigillance.⁸

 

List of withdrawal drugs:

Brand name	Reason of withdrawal	Year of manufacture	Year of withdrawal
Practolol	Blindness	1970	1975
Encainamide	Excessive mortality	1982	1991
Bromfenac	Hepatotoxic effects	1997	1998
Benoxaprofen	Liver necrosis	1982	1982
Terfenadine	Fatal cardiac arrhythmia	1985	1998
Temafloxacin	Haemolytic Anemia	1992	1992
Mibefradil	Multiple drug interaction	1997	1998
Flosequinan	Excessive mortality	1992	1993
Cisapride	Adverse cardiac events	1993	2000

 

Historical Background:

In the 1960 at least two serious drug reactions were observed in many patient thalidomide causes limb deformities (Phocomelia). It was observed in Japan, the optic nerve damage (Subacute Myelooptic- neuropathy). The PMA, senator Edward Kennedy suggested that a better system was need for monitoring the use and effects of prescription drug after they are marketed. As a result, the joint commission prescription drugs use was established in 1976, funded largely by the drug industry with the Mandale to design a post marketing surveillance (PMS) system to detect, quantify and describe the unanticipated effects of marketed drugs. The delayed discovery of the practolol adverse effects spurred effects to improve PMS.⁶

 

Aims of Pharmacovigillance:

1.    To improve patient care and safety in relation to the use of medicines and all medical and paramedical interventions.

2.    To improve public health and safety in relation to the use of medicines.

3.    To contribute to the assessment of benefit, effectiveness and risk of medicines, leading to the prevention of harm and maximization of benefit.

4.    To encourage the safe, rational and more effective use of medicines.

5.    To promote education and clinical training.

6.    To identification of signals of serious ADRs following the introduction of new drug.

7.    To diagnose or therapy of disease or for the modification of physiological functions.

8.    To identify patient related factors of ADRs such as dose, age, gender etc.^9-11

 

Pharmacovigillance and drug safety monitoring:

Adverse Drug Reactions (ADRs):

Every drug is associated with desirable as well as undesirable effects. ADR as defined by WHO is “Noxious or unintended response to a drug occurs at a usual dose”.¹⁰

 

ADR is broadly classified as Type A and Type B. Type A (augmented) ADRs are the result of an augmented pharmacological action of a drug which given in usual therapeutic doses. This type of ADrs are predictable and dose dependent. Their incidence of morbidity id often high, but mortality is low.

 

Type B (Bizarre) ADRs are totally abnormal and are not expected on the basis of known pharmacology of the drug often given in usual therapeutic doses. They are unpredictable and dose independent. Their incidence and morbidity is low, but mortality is high. High index of ADRs are to be diagnosed successfully by clinicians, it is the high level of awareness about the drug being used. Events that occurs when a particular drug is administered are recorded in the patient by drug monitoring then an ADR of drug and activity of drug being monitored, these study aims to detect ADRs of drugs.^12-15

 

Reporting of ADRs of drugs after marketing must be actively encouraged and should involve all those concerned including Doctors, Pharmacists, Nurses and pharmaceutical companies. In the process of development of new drug there are preclinical trials, then clinical trials this includes four phases. In this the first three phases helps in the determination of safety, efficacy and side effects of the developed drug product respectively. Whereas in case of fourth phase post marketing studies are uplifting the knowledge of pharmacovigillance.¹⁶

 

Post marketing surveillance (PMS):

Post marketing surveillance (PMS) is the identification and collection of information regarding themedications after their approval by the U.S.FDA. Systematic PMS of the drugs began in the early 1970’s and has increased substantially since then. The monitoring of drugs after their approval has became necessary for many reasons. In the 1950s and 1960s, there was fewer drugs to monitor. PMS is conducted by various types of organizations, government agencies, private companies and consumer advocacy groups. The purpose of conducting PMS may differ, depending of the perspective of the individuals conducting the surveillance. Since the drug approval process involves phase I, II and III trials, post marketing trials are sometimes referred to as phase IV trials. PMS involves systematic monitoring of medications as they are used in real life scenarios, as opposed to the controlled settings of 3pre marketing trials.PMS provides valuable information on the use of drugs in special patient populations, which is information not easily obtained from the pre-marketing studies.¹⁷

 

OBJECTIVE:

Primary objective of PMS studies is to develop information about drug effects under customary condition of drug use.

 

Sources of PMS information:

The following may be considered as a source of information, some are proactive and some are reactive.

·      Expert user groups

·      Customer surveys

·      Customer complaints and warranty claims

·      Post-CE market clinical trials

·      Literature reviews

·      Device tracking/Implant registries

·      User reactions during training programmes

·      The media

 

PMS uses a number of approaches to monitor drugs and devices safety, including spontaneous reporting database, prescription event monitoring, electronic health records, patient registries and record linkage between health databases.¹⁸

 

Spontaneous Adverse Reaction Reporting (SRS)/Voluntary Reporting:

SRS is the best and most widely used method since decades to report ADRs. A spontaneous reporting is an unsolicited communication by health care professionals or consumers that describes one or more ADRs in a patient who was given one or more medicinal products and that does not derived from the study or any organized data collection scheme. It is the easiest method to establish and the cheap to run, but reporting rates are generally very low and subject to strong biases and there is no database of all users or information on overall drug utilization. These problems prevent the accurate assessment of risks, risk factors or comparison between drugs.

 

Pharmacovigillance surveillance using a SRS is designed to detect ADRs not previously observed in preclinical or clinical studies. Spontaneous reporting is dependent on the clinicians other health professionals who need to trained and encouraged to report details of suspected ADRS in patient on ARV treatment. Pharmaceutical manufacturers have to communicate with the doctors at the clinical level regarding the ADRs by,^19-20

·      Changing medication formula if necessary

·      Implenting new prescribing procedure

·      Implenting new dispensing procedures

·      Educating the professional staffs

·      Educating the patients.

 

Prescription Event Monitoring:

A non international cohort technique, which involves health professionals submitting data on all clinical events reported by a patient subrequest to the prescribing of a new drug.

 

It is the method of studying the safety of new medications that are used by general practioners. The aims of prescription event monitoring includes,

·      Provides incidence rates for adverse events as a measure of risk

·      Detect signals of unrecognized reactions

·      Identify risk factors and thus, provide evidence on which to base effective risk management

·      Provides measure of comparative risks between medicines.

 

Here patients being prescribed maintained drugs. The criteria for safety drugs are,

·      5000-18000 prescriptions for that drugs are obtained.

·      Prescribers are contacted with a questionnaire to determine subsequent events or clinical outcomes.0

·      Experiences with the drug can then be examined and the incidence of various events can be estimated.

·      Comparisons are made between periods before and after drug use.

 

Electronic Health Records:

These are the important source of data for detection of ADRs. It is computer stored collection of health about the patient linked by a person identifier, it represents the basis for health care information system development.^21-22

 

Patient Registers:

To bring together patient records, it is time consuming and less expensive.

 

CONCLUSION:

Pharmacovigillance is the only way to ensure the safety of drugs throughout the life cycle. It plays an important role in identifying and measuring the effects and uses of drugs in clinical practice. The knowledge and information available regarding safety of drug is very important to take appropriate decision by drug regulators to safeguard the public health. Reporting of ADRs after marketing should be actively encouraged and should involve all those concerned including doctors, pharmacists, nurses, patients, and pharmaceutical companies. To enhance facillates this, a culture of learning about pharmacovigillance should start early in the professional training of health care students. This will help healthcare professional to understand subject and also create awareness by giving adequate information to patient at the start of any treatment about the potential benefits and risk of therapy. There are significant efforts on the pharmacovigillance to make it more functional and day by day we are closer to the destination.

 

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Received on 14.11.2018                Accepted on 24.01.2019               

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