Pharmacovigilance
Encyclopedia
Pharmacovigilance is the pharmacological
science
relating to the detection, assessment, understanding and prevention of adverse effects
, particularly long term and short term side effects of medicines. Generally speaking, pharmacovigilance is the science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medication
s, biological products, herbalism
and traditional medicine
s with a view to:
The process of collection of such information about a drug begins in phase I of the clinical trial, before approval of the drug, and continues even after approval; several post-market safety studies are conducted, with many made mandatory by drug regulatory agencies around the world.
The etymological roots are: pharmakon (Greek), “drug;” and vigilare (Latin), “to keep awake or alert, to keep watch.”
Pharmacovigilance is particularly concerned with adverse drug reaction
s, or ADRs, which are officially described as: "A response to a drug which is noxious and unintended, and which occurs at doses normally used… for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological function."
Pharmacovigilance is gaining importance for doctor
s and scientists as the number of stories in the mass media
of drug recalls increases.
Because clinical trials involve several thousand patients at most; less common side effects and ADRs are often unknown at the time a drug enters the market. Even very severe ADRs such as liver damage are often undetected because study populations are small. Postmarketing surveillance
uses tools such as data mining
of spontaneous reporting systems and patient registries, and investigation of case reports to identify the relationships between drugs and ADRs.
The purpose of clinical trials is to discover:
Clinical trials do, in general, tell us a good deal about how well a drug works and what potential harm it may cause. They provide information which should be reliable for larger populations with the same characteristics as the trial group - age, gender, state of health, ethnic origin, and so on.
The variables in a clinical trial are specified and controlled and the results relate only to the population of which the trial group is a representative sample. A clinical trial can never tell you the whole story of the effects of a drug in all situations. In fact, there is nothing that could tell you the whole story, but a clinical trial must tell you enough; "enough" being determined by legislation and by contemporary judgements about the acceptable balance of benefit and harm.
to their national pharmacovigilance center or to the manufacturer. Spontaneous reports are almost always submitted voluntarily. In many parts of the world these are submitted electronically using a defined message standard.
One of this system’s major weaknesses is under-reporting, though the figures vary greatly between countries and in relation to minor and serious ADRs (also referred to as ICSRs, individual case safety reports).
Another problem is that overworked medical personnel do not always see reporting as a priority. If the symptoms are not serious, they may not notice them at all. And even if the symptoms are serious, they may not be recognised as the effect of a particular drug.
Even so, spontaneous reports are a crucial element in the worldwide enterprise of pharmacovigilance and form the core of the World Health Organization
Database, which includes around 4.6 million reports (January 2009), growing annually by about 250,000.
(QPPV), all the reports they receive from healthcare providers to the national authority. Others have intensive, focused programmes concentrating on new drugs, or on controversial drugs, or on the prescribing habits of groups of doctors, or involving pharmacists in reporting. All of these generate potentially useful information. Such intensive schemes, however, tend to be the exception.
Member countries send their reports to the Uppsala Monitoring Centre
where they are processed, evaluated and entered into the WHO International Database. When there are several reports of adverse reactions to a particular drug this process may lead to the detection of a signal – an alert about a possible hazard communicated to members countries. This happens only after detailed evaluation and expert review.
(EMA) and conducted by the national competent authorities (NCAs). The main responsibility of the EMA is to maintain and develop the pharmacovigilance database consisting of all suspected serious adverse reactions to medicines observed in the European Community. The system is called EudraVigilance
and contains separate but similar databases of human and veterinary reactions.
EMA requires the individual marketing authorisation holders (drug companies), to submit all received adverse reactions in electronic form (save in exceptional circumstances). The reporting obligations of the various stakeholders are defined in the Community legislation, in particular:
Reporting can be performed with software developed for the purpose or with a web utility called EVWEB accessible through the EudraVigilance homepage. Registration for use of EVWEB is necessary.
In 2002 Heads of Medicines Agencies agreed on a mandate for an ad hoc Working Group on establishing a European risk management strategy. The Working Group considered the conduct of a high level survey of EU pharmacovigilance resources to promote the utilisation of expertise and encourage collaborative working.
and Public Citizen
).
. It is a form of pharmacovigilance which deals specifically with those pharmacological agents that have impact on the environment via elimination through living organisms subsequent to pharmacotherapy
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
science
Science
Science is a systematic enterprise that builds and organizes knowledge in the form of testable explanations and predictions about the universe...
relating to the detection, assessment, understanding and prevention of adverse effects
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
, particularly long term and short term side effects of medicines. Generally speaking, pharmacovigilance is the science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
s, biological products, herbalism
Herbalism
Herbalism is a traditional medicinal or folk medicine practice based on the use of plants and plant extracts. Herbalism is also known as botanical medicine, medical herbalism, herbal medicine, herbology, herblore, and phytotherapy...
and traditional medicine
Traditional medicine
Traditional medicine comprises unscientific knowledge systems that developed over generations within various societies before the era of modern medicine...
s with a view to:
- identifying new information about hazards associated with medicines
- preventing harm to patients.
The process of collection of such information about a drug begins in phase I of the clinical trial, before approval of the drug, and continues even after approval; several post-market safety studies are conducted, with many made mandatory by drug regulatory agencies around the world.
The etymological roots are: pharmakon (Greek), “drug;” and vigilare (Latin), “to keep awake or alert, to keep watch.”
Pharmacovigilance is particularly concerned with adverse drug reaction
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s, or ADRs, which are officially described as: "A response to a drug which is noxious and unintended, and which occurs at doses normally used… for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological function."
Pharmacovigilance is gaining importance for doctor
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
s and scientists as the number of stories in the mass media
Mass media
Mass media refers collectively to all media technologies which are intended to reach a large audience via mass communication. Broadcast media transmit their information electronically and comprise of television, film and radio, movies, CDs, DVDs and some other gadgets like cameras or video consoles...
of drug recalls increases.
Because clinical trials involve several thousand patients at most; less common side effects and ADRs are often unknown at the time a drug enters the market. Even very severe ADRs such as liver damage are often undetected because study populations are small. Postmarketing surveillance
Postmarketing surveillance
Postmarketing surveillance is the practice of monitoring the safety of a pharmaceutical drug or device after it has been released on the market and is an important part of the science of pharmacovigilance...
uses tools such as data mining
Data mining
Data mining , a relatively young and interdisciplinary field of computer science is the process of discovering new patterns from large data sets involving methods at the intersection of artificial intelligence, machine learning, statistics and database systems...
of spontaneous reporting systems and patient registries, and investigation of case reports to identify the relationships between drugs and ADRs.
Risks of medical treatment
- While medicines have led to major improvement in the treatment and control of diseases, they also produce adverse effects on the human body from time to time.
- While many drugs are precisely targeted to the causes and mechanisms of disease, they may also have minor or distressing effects on other parts of the body, or interact negatively with the systems of the particular individual or with other drugs or substances they are taking, or not work well or at all for some, many or all of those who take them for illness.
- There are risks in any intrusion into the human body, whether chemical or surgical. Nothing in this field is entirely predictable as the interaction between chemicals and the human body may produce surprises.
Terms commonly used in drug safety
- Benefits are commonly expressed as the proven therapeutic good of a product, but should also include the patient’s subjective assessment of its effects.
- RiskRiskRisk is the potential that a chosen action or activity will lead to a loss . The notion implies that a choice having an influence on the outcome exists . Potential losses themselves may also be called "risks"...
is the probability of harm being caused, usually expressed as a percent or ratio of the treated population; the probability of an occurrence. - HarmHARMHARM or H.A.R.M. may refer to:* AGM-88 HARM, a high-speed anti-radiation missile* Historic Aircraft Restoration Museum, a museum in Creve Coeur, Missouri, United States...
is the nature and extent of the actual damage that could be caused. It should not be confused with risk. - EffectivenessEffectivenessEffectiveness is the capability of producing a desired result. When something is deemed effective, it means it has an intended or expected outcome, or produces a deep, vivid impression.-Etymology:...
is used to express the extent to which a drug works under real world circumstances, i.e., clinical practice (not clinical trials). - EfficacyEfficacyEfficacy is the capacity to produce an effect. It has different specific meanings in different fields. In medicine, it is the ability of an intervention or drug to reproduce a desired effect in expert hands and under ideal circumstances.- Healthcare :...
is used to express the extent to which a drug works under ideal circumstances (i.e., in clinical trials).
Finding the risks of drugs
Pharmaceutical companies are required by law in all countries to perform clinical trials, testing new drugs on people before they are made generally available. The manufacturers or their agents usually select a representative sample of patients for whom the drug is designed – at most a few thousand – along with a comparable control group. The control group may receive a placebo and/or another drug that is already marketed for the disease.The purpose of clinical trials is to discover:
- if a drug works and how well
- if it has any harmful effects, and
- its benefit-harm-risk profile - does it do more good than harm, and how much more? If it has a potential for harm, how probable and how serious is the harm?
Clinical trials do, in general, tell us a good deal about how well a drug works and what potential harm it may cause. They provide information which should be reliable for larger populations with the same characteristics as the trial group - age, gender, state of health, ethnic origin, and so on.
The variables in a clinical trial are specified and controlled and the results relate only to the population of which the trial group is a representative sample. A clinical trial can never tell you the whole story of the effects of a drug in all situations. In fact, there is nothing that could tell you the whole story, but a clinical trial must tell you enough; "enough" being determined by legislation and by contemporary judgements about the acceptable balance of benefit and harm.
Spontaneous reporting
Spontaneous reporting is the core data-generating system of international pharmacovigilance, relying on healthcare professionals (and in some places consumers) to identify and report any suspected adverse drug reactionAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
to their national pharmacovigilance center or to the manufacturer. Spontaneous reports are almost always submitted voluntarily. In many parts of the world these are submitted electronically using a defined message standard.
One of this system’s major weaknesses is under-reporting, though the figures vary greatly between countries and in relation to minor and serious ADRs (also referred to as ICSRs, individual case safety reports).
Another problem is that overworked medical personnel do not always see reporting as a priority. If the symptoms are not serious, they may not notice them at all. And even if the symptoms are serious, they may not be recognised as the effect of a particular drug.
Even so, spontaneous reports are a crucial element in the worldwide enterprise of pharmacovigilance and form the core of the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
Database, which includes around 4.6 million reports (January 2009), growing annually by about 250,000.
Other reporting methods
Some countries legally oblige spontaneous reporting by physicians. In most countries, manufacturers are required to submit,through its Qualified Person for PharmacovigilanceQualified Person for Pharmacovigilance
The Qualified Person Responsible for Pharmacovigilance, or QPPV, is an individual named by a pharmaceutical company as the main person responsible for ensuring that the company meets its legal obligations for the monitoring of the safety of the product on the market.When a company submits an...
(QPPV), all the reports they receive from healthcare providers to the national authority. Others have intensive, focused programmes concentrating on new drugs, or on controversial drugs, or on the prescribing habits of groups of doctors, or involving pharmacists in reporting. All of these generate potentially useful information. Such intensive schemes, however, tend to be the exception.
International collaboration
The principle of international collaboration in the field of pharmacovigilance is the principal basis for the WHO International Drug Monitoring Programme, through which over 100 member nations have systems in place which encourage healthcare personnel to record and report adverse effects of drugs in their patients. These reports are assessed locally and may lead to action within the country. Through membership of the WHO Programme one country can know if similar reports are being made elsewhere (see below for other schemes.)Member countries send their reports to the Uppsala Monitoring Centre
Uppsala Monitoring Centre
The Uppsala Monitoring Centre , located in Uppsala, Sweden, is the field name for the World Health Organization Collaborating Centre for International Drug Monitoring...
where they are processed, evaluated and entered into the WHO International Database. When there are several reports of adverse reactions to a particular drug this process may lead to the detection of a signal – an alert about a possible hazard communicated to members countries. This happens only after detailed evaluation and expert review.
European Union
The pharmacovigilance effort in the European Union is coordinated by the European Medicines AgencyEuropean Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
(EMA) and conducted by the national competent authorities (NCAs). The main responsibility of the EMA is to maintain and develop the pharmacovigilance database consisting of all suspected serious adverse reactions to medicines observed in the European Community. The system is called EudraVigilance
EudraVigilance
EudraVigilance is the European data processing network and management system for reporting and evaluation of suspected adverse reactions during the development of new drugs and for following the marketing authorisation of medicinal products in the European Economic Area .The European...
and contains separate but similar databases of human and veterinary reactions.
EMA requires the individual marketing authorisation holders (drug companies), to submit all received adverse reactions in electronic form (save in exceptional circumstances). The reporting obligations of the various stakeholders are defined in the Community legislation, in particular:
- RegulationRegulationRegulation is administrative legislation that constitutes or constrains rights and allocates responsibilities. It can be distinguished from primary legislation on the one hand and judge-made law on the other...
(EC) No 726/2004 - for human medicines, European UnionEuropean UnionThe European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
Directive 2001/83/ECDirective 2001/83/ECDirective 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use...
as amended and Directive 2001/20/ECDirective 2001/20/ECThe Clinical Trials Directive is a European Union directive that aimed at... - for veterinary medicines, Directive 2001/82/EC as amended.
Reporting can be performed with software developed for the purpose or with a web utility called EVWEB accessible through the EudraVigilance homepage. Registration for use of EVWEB is necessary.
In 2002 Heads of Medicines Agencies agreed on a mandate for an ad hoc Working Group on establishing a European risk management strategy. The Working Group considered the conduct of a high level survey of EU pharmacovigilance resources to promote the utilisation of expertise and encourage collaborative working.
United States
Three primary branches of pharmacovigilance in the U.S. include the FDA, the pharmaceutical manufacturers, and the academic/non-profit organizations (such as RADARResearch on Adverse Drug events And Reports
Research on Adverse Drug events And Reports is a pharmacovigilance team of 25 doctors who receive calls about possible adverse drug reactions and investigate. RADAR is based at Northwestern's Feinberg School of Medicine. RADAR is led by Dennis West...
and Public Citizen
Public Citizen
Public Citizen is a non-profit, consumer rights advocacy group based in Washington, D.C., United States, with a branch in Austin, Texas. Public Citizen was founded by Ralph Nader in 1971, headed for 26 years by Joan Claybrook, and is now headed by Robert Weissman.-Lobbying Efforts:Public Citizen...
).
Pharmacoenvironmentology
Despite receiving attention and necessary action by regulatory agencies like FDA and the European Union, there is a lack of substantial procedures regarding impending monitoring of drug concentrations in the environment and the palpable adverse effects. In 2006 a new concept of pharmacovigilance in environmental pharmacology, entitled as 'Pharmacoenvironmentology' was suggested by Syed Ziaur RahmanSyed Ziaur Rahman
Dr Syed Ziaur Rahman is a faculty member in the discipline of Pharmacology and Chair of the Advisory Council , International Association of Medical Colleges.-Biography:...
. It is a form of pharmacovigilance which deals specifically with those pharmacological agents that have impact on the environment via elimination through living organisms subsequent to pharmacotherapy
Pharmacovigilance of Herbal Medicines
The safety of herbal medicines has become a major concern to both national health authorities and the general public. The use of herbs in Traditional medicines continues to expand rapidly across the world. Many people now take herbal medicines or herbal products for their health care in different national health-care settings. However, mass media reports of adverse events tend to be sensational and give a negative impression regarding the use of Herbal medicines in general rather than identifying the causes of these events, which may relate to a variety of issues.See also
- Adverse drug reactionAdverse drug reactionAn adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
- Adverse effect (medicine)Adverse effect (medicine)In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
- Boston Collaborative Drug Surveillance ProgramBoston Collaborative Drug Surveillance ProgramThe Boston Collaborative Drug Surveillance Program , established in 1966, was a pioneer in the field of drug epidemiology, pharmacoepidemiology . Still active, the group has published over 400 articles and reviews in peer-reviewed journals...
- Consultant pharmacistConsultant pharmacistA consultant pharmacist is a specialized pharmacist. The main principle of consultant pharmacy is Pharmaceutical care term developed by Hepler and Strand in 1990.- United States :...
- COSTARTCOSTARTThe Coding Symbols for a Thesaurus of Adverse Reaction Terms was developed by the United States Food and Drug Administration for the coding, filing and retrieving of post-marketing adverse reaction reports. COSTART provides a method to deal with the variation in vocabulary used by those who...
- Coding Symbols for a Thesaurus of Adverse Reaction Terms - DrugLogicDrugLogicDrugLogic, Inc. is a software company headquartered in Reston, Virginia. It has offices in Boston, Massachusetts; Princeton, New Jersey; San Diego, California; and in Irvine, California....
- European Medicines AgencyEuropean Medicines AgencyThe European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
- EudraVigilanceEudraVigilanceEudraVigilance is the European data processing network and management system for reporting and evaluation of suspected adverse reactions during the development of new drugs and for following the marketing authorisation of medicinal products in the European Economic Area .The European...
- International Society for PharmacoepidemiologyInternational Society for PharmacoepidemiologyThe International Society for Pharmacoepidemiology was launched officially by Stanley A. Edlavitch, David E. Lilienfeld, and Hugh A. Tilson in 1989 during the Fifth International Conference on Pharmacoepidemiology in Minneapolis...
- MedDRAMedDRAMedDRA or Medical Dictionary for Regulatory Activities is a clinically validated international medical terminology used by regulatory authorities and the regulated biopharmaceutical industry throughout the entire regulatory process, from pre-marketing to post-marketing activities, and for data...
- Medical Dictionary for Regulatory Activities - Medical deviceMedical deviceA medical device is a product which is used for medical purposes in patients, in diagnosis, therapy or surgery . Whereas medicinal products achieve their principal action by pharmacological, metabolic or immunological means. Medical devices act by other means like physical, mechanical, thermal,...
- MedWatchMedWatchMedWatch is the Food and Drug Administration’s reporting system for an adverse event or sentinel event, founded in 1993. An adverse event is any undesirable experience associated with the use of a medical product...
- National Drug & Safety LeagueNational Drug & Safety LeagueThe National Drug & Safety League is a charitable organization based in DeSoto, Texas. It received the lowest possible rating from Charity Navigator, being awarded zero stars and a 0.0 rating. 64.3% of its funds went to fundraising activity in the last year of record, with an additional 13.2% going...
- Public healthPublic healthPublic health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals" . It is concerned with threats to health based on population health...
- PharmacoepidemiologyPharmacoepidemiologyPharmacoepidemiology is the study of the use of and the effects of drugs in large numbers of people.To accomplish this study, pharmacoepidemiology borrows from both pharmacology and epidemiology. Thus, pharmacoepidemiology is the bridge between both pharmacology and epidemiology...
- PharmacotherapyPharmacotherapyPharmacotherapy is the treatment of disease through the administration of drugs. As such, it is considered part of the larger category of therapy....
- Pharmaceuticals and personal care products in the environmentPharmaceuticals and personal care products in the environmentThe environmental impact of pharmaceuticals and personal care products is largely speculative. PPCPs are substances used by individuals for personal health or cosmetic reasons and the products used by agribusiness to boost growth or health of livestock. PPCPs have been detected in water bodies...
- The International Society of PharmacovigilanceThe International Society of PharmacovigilanceThe International Society of Pharmacovigilance , previously the European Society of Pharmacovigilance , is an international non-profit scientific organisation, which aims to foster pharmacovigilance both scientifically and educationally, and enhance all aspects of the safe and proper use of...
- Uppsala Monitoring CentreUppsala Monitoring CentreThe Uppsala Monitoring Centre , located in Uppsala, Sweden, is the field name for the World Health Organization Collaborating Centre for International Drug Monitoring...
- WHOARTWHOARTThe WHO Adverse Reactions Terminology is a dictionary meant to serve as a basis for rational coding of adverse reaction terms. The system is maintained by the Uppsala Monitoring Centre , the World Health Organization Collaborating Centre for International Drug Monitoring.-Structure:* 32...
- Yellow Card SchemeYellow Card SchemeThe Yellow Card Scheme is the UK system for collecting information on suspected Adverse Drug Reactions to medicines. The Scheme was founded in 1964 after the thalidomide disaster, and was developed by Dr Bill Inman....
(UK)