S. S. Shuka1*, Bina Gidwani1, R. Pandey1, S. P. Rao1, V. Singh1, Amber Vyas2
1Columbia Institute of Pharmacy, Raipur (C.G.)
Institute of Pharmacy,
*Corresponding Author E-mail: firstname.lastname@example.org
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.
It is the science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medications, biological products, herbalism and traditional medicines with a view to:
Identifying new information about hazards associated with medicines
Preventing harm to patients.
Phase IV of the evaluation of a drug starts when the marketing license is granted and extends over many years. It consists of pharmacoepidemiological studies to evaluate the effectiveness, safety, and utilization of the drug in large populations, under real-life conditions. The results confirm or disprove the effectiveness of the drug in clinical practice (confirmation of the therapeutic effect), determine whether approved uses should be expanded or restricted, any untoward interactions (pharmacovigilance) and pharmacoeconomics of the drugs.
The challenge of maximizing drug safety and maintaining public confidence has become increasingly complex. Pharmaceutical and biotechnology companies must not only monitor, but also proactively assess and manage drug risk throughout a product’s lifecycle, from development to post-market.1
The word Vigilance simply means ‘to watch’ and it basically refers to:
· Alert watchfulness
· Forbearance of sleep; wakefulness
· watchfulness in respect of danger; care, caution, circumspection
· The process of paying close and continuous attention.
Pharmacovigilance (abbreviated PV or PhV) 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.2
Generally, pharmacovigilance is the science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medications, biological products, herbalism and traditional medicines with a view to:
· Identifying new information about hazards associated with medicines
· Preventing harm to patients.
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 reactions, 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."3
Recently, its concerns have been widened to include:
• Traditional and complementary medicines
• Blood products
• Medical devices
Continuous monitoring of their effects, side effects, contraindications and outright harmful effects which can result in a high degree of morbidity and in some cases, even mortality, is essential to maximize benefits and minimize risks. No degree of care and caution at the pre-clinical and clinical testing stages can guarantee absolute safety, when a drug is marketed and prescribed to large populations across the Country and outside. Because clinical trials involve several thousand patients at most; less common side effects and adverse drug reactions are often unknown at the time a drug enters the market. Even very severe adverse drug reactions, such as liver damage, are often undetected because study populations are small. Post marketing pharmacovigilance uses tools such as data mining and investigation of case reports to identify the relationships between drugs and adverse drug reactions. The drug regulatory agencies have the responsibility of having a well-established pharmacovigilance system to monitor adverse reactions of drugs. During the drug development phase and later during the life time of a marketed drug.3
AIMS OF PHARMACOVIGILANCE
The aims of pharmacovigilance are 4
1. The identification and quantification of previously unrecognized adverse drug reactions (ADR).
2. The identification of sub-groups of patients at particular risk of ADRs (the risk relating to dose, age, gender and underlying disease).
3. The continued monitoring of the safety of a product, throughout the duration of its use, to ensure that its risks and benefits remain acceptable. This includes safety monitoring following significant newly approved indications.
4. The comparative adverse drug reaction profile of products within the same therapeutic class.
5. The detection of inappropriate prescription and administration.
6. The further elucidation of a product’s pharmacological/toxicological properties and the mechanism by which it produces adverse drug reactions.
7. The detection of significant drug–drug interactions between new products and co therapy with agents already established on the market, which may only be detected during widespread use.
In Short, pharmacovigilance aims to improve patient care and safety, public health, assessment of benefit, harm, effectiveness and risk of medicines, promotes understanding, education and clinical training
IMPORTANCE OF PHARMACOVIGILANCE:
When a pharmaceutical drug is introduced in the market there are still a lot of things that are unknown about the safety of the new drugs. These medicines are used by various patients for different diseases. These people might be using several other drugs and must be following different traditions and diets which may adversely affect the impact of medicine in them. Also the different brands of same medicine might differ in the manner of their production and ingredients. Additionally, adverse drug reactions might also occur when drugs are taken along with traditional and herbal medicines that have also to be monitored through pharmacovigilance. In some cases, adverse drug reaction of certain medicines might occur only in one country's or region's citizens. To prevent all undue physical, mental and financial suffering by patients, pharmacovigilance proves to be an important monitoring system for the safety of medicines in a country with the support of doctors, pharmacists, nurses and other health professionals of the country.
The Importance of Pharmacovigilance are as follows:5
1. Safety monitoring of medicinal products
2. Drug monitoring
3. Pharmaceutical preparations - adverse effects
4. Adverse drug reaction reporting
5. Product surveillance, Post marketing
STEPS IN PHARMACOVIGILANCE PROGRAMME
1. Finding the risk of drug
2. Clinical trials
3. Pharmaco epidemiological study
4. Case report
5. Developing case series
6. Analysis of case series
7. Use of data mining to identify product – event combination
8. Spontaneous reporting
PARTNERS IN PHARMACOVIGILANCE
A complex and vital relationship exists between wide ranges of partners in the practice of drug safety monitoring. Sustained collaboration and commitment are vital if future challenges in pharmacovigilance are to be met in order to develop and flourish.
• Hospitals and academia6
• Medical and pharmaceutical associations
• Poisons information centres
• Health professionals7,8
PHARMACOVIGILANCE IN INDIA
It is related to the surveillance of drugs once they are released for use in the community (post marketing surveillance) and relies on voluntary reporting, prescription monitoring, medical records and statistical studies in the population.
Since very few new drugs were discovered in India and hardly any new drug was launched for the first time in India in the past, there was no major compulsion to have a strong Pharmacovigilance system to detect adverse reactions of marketed drugs. The experience from the markets where the drug was in use for several years before introduction in India, was used by the Companies and the Regulatory Agencies to assess the safety parameters and take corrective actions , such as the withdrawal or banning of the drug in question. With the Indian Companies'' capacity to develop and market new drugs out of their own research efforts, it is important that adequate Pharmacovigilance standards are introduced to monitor adverse reactions of products, first launched in India.
Continuous monitoring of their effects, side effects, contraindications and outright harmful effects which can result in a high degree of morbidity and in some cases, even mortality, is essential to maximize benefits and minimize risks. No degree of care and caution at the pre-clinical and clinical testing stages can guarantee absolute safety, when a drug is marketed and prescribed to large populations across the Country and outside. Because clinical trials involve several thousand patients at most; less common side effects and adverse drug reactions are often unknown at the time a drug enters the market. Even very severe adverse drug reactions, such as liver damage, are often undetected because study populations are small. Post marketing pharmacovigilance uses tools such as data mining and investigation of case reports to identify the relationships between drugs and adverse drug reactions. The drug regulatory agencies have the responsibility of having a well-established pharmacovigilance system to monitor adverse reactions of drugs. During the drug development phase and later during the life time of a marketed drug.7
Pharmacovigilance is fastest emerging as an important approach for the early detection of unwanted effects of the drugs and to take appropriate regulatory actions if necessary. This may ensure the safer use of drugs.8
Historically, Indian market has always, except in very few cases, seen the launch of only products, which have been earlier approved and marketed in U.S.A., Western Europe or Japan. Until now, the time lag between the first marketing of a new drug in a foreign country and India has been on an average around 4 years, and hardly any new drug was introduced for the first time in India. In that kind of scenario, it was not too critical that there was in place a system of pharmacovigilance in India, since reports of side-effects from outside India would have helped our regulatory agencies to assess the rationale of continuing the drug in the Indian market. Thus in the past, action on marketed drugs has been triggered on the basis of reports on the harmful effects of drugs marketed abroad. In a few cases, drugs, which have been banned or withdrawn in foreign markets, were allowed to be kept in the market in India. For example, Chloramphenicol, Phenyl Butazone, Clioquinol, Phenformin, Cisapride, all continue to be prescribed in India on the basis of a conscious decision by the Regulatory Agency that the benefit to risk ratio is in favour of the former.8
The evolution of a new Patent regime in the Indian Pharmaceutical Industry (the Post-2005 scenario) as a consequence of India being a founder member of WTO, and her obligations under Trade Related Intellectual Property Rights and Services (TRIPS), makes it incumbent that India can no longer copy patented products and market them without license from the innovator company. The leading Indian companies realizing the compulsions of the new regime have already initiated investments of substantial resources for the discovery and development of new drugs needed for both Indian and International markets. This in turn means that during the coming years Research and Development by the Indian Pharmaceutical companies will hopefully lead to new drugs based on pre-clinical and clinical data generated mostly in India. In such cases, the Indian regulatory agencies cannot count on the experience of other markets to assess the incidence and prevalence of adverse reactions from drug usage, and therein lies the importance of a properly designed pharmacovigilance system in India. For an effective Pharmacovigilance system to be functional and efficient all the stakeholders need to be alert and attentive throughout the lifetime of the drug in the market.9
At present, post – marketing survillence of medicines is mainly coordinated by National Pharmacovigilance Centres. The Central Drugs Standard Control Organization (CDSCO) has initiated a country-wide Pharmacovigilance programme under the aegis of DGHS, Ministry of Health and Family Welfare Government of India.
The programme is coordinated by the National Pharmacovigilance Centre at the Central Drugs Standard Control Organization (CDSCO). The National Centre is operating under the supervision of the National Pharmacovigilance Advisory Committee to recommend procedures and guidelines for regulatory interventions.9
National Pharmacovigilance Programme
The National Pharmacovigilance Programme was officially inaugurated by the Honorable Health Minister Dr.Anbumani Ramadoss on 23 November, 2004 at New Delhi. The National Pharmacovigilance Programme for India, sponsored by the World Health Organization (WHO) and funded by the World Bank, became fully operational in January 2005.9
The Programme aims to foster the culture of adverse drug reactions notification in its first year of operation and subsequently aims to generate broad based Adverse drug reactions data on the Indian population and share the information with global health-care community through WHO-UMC.
The nationwide programme, sponsored and coordinated by the country’s central drug regulatory agency – Central Drugs Standard Control Organization (CDSCO) – to establish and manage a data base of Adverse Drug Reactions (ADR) for making informed regulatory decisions regarding marketing authorization of drugs in India for ensuring safety of drugs.
Under the program 26 peripheral centers, 5 Regional Centers and 2 Zonal Centers were established. The Peripheral centers will record the Adverse Events (AE) and send to the Regional Centers. They in turn collate and scrutinize the data received from the Peripheral Centers and submit to the Zonal Centers. The Zonal Centers will analyze the data and submit consolidated information to the National Pharmacovigilance Centre. The Zonal Centre will also provide training, general support and coordinate the functioning of the Regional Center.
Primary pharmacovigilance centers. Relatively smaller medical institutions including individual medical practitioners’ clinics, private hospitals, nursing homes, pharmacies etc. First contact Adverse drug reaction data collection unit at a health care facility. They would be identified and coordinated by Regional pharmacovigilance centre or Zonal pharmacovigilance centre in consultation with Central Drugs Standard Control Organization (CDSCO) .10
Secondary pharmacovigilance centers. Relatively larger healthcare facilities attached with medical colleges. They would act as second level centers in the administrative structure of the NPPI. They will function as first contact Adverse Drug Reactions data collection units also. They would be identified and coordinated by Zonal Pharmacovigilance Centers in consultation with the Central Drugs Standard Control Organization (CDSCO). 10
Tertiary pharmacovigilance centers. Large healthcare facilities attached with medical colleges in metro cities identified by the Central Drugs Standard Control Organization (CDSCO) for the purpose. They would act as third level centers in the administrative structure of the NPPI. They will function as First contact Adverse drug effect data collection units also.10
Oversee the performance of various Zonal, Regional and Peripheral Pharmacovigilance centers as well as recommend possible regulatory measures based on the data received from various centers. It also oversees data collection and assessment, interpretation of data as well as publication of adverse drug reactions monitoring data. The Committee also periodically evaluates their protocol compliance levels to ensure that the data received is homogenous and can be scientifically pooled for informed regulatory decisions. Wherever necessary, National Pharmacovigilance Advisory Committee also seeks the opinion of experts in various specializations. 10 The specific aims of the Pharmacovigilance Programme are to:
· Contribute to the regulatory assessment of benefit, harm, effectiveness and risk of medicines, encouraging their safe, rational and more effective (including cost effective) use.
· Improve patient care and safety in relation to use of medicines and all medical and paramedical interventions.
· Improve public health and safety in relation to use of medicines.
· Promote understanding, education and clinical training in pharmacovigilance and its effective communication to the public.
· Monitoring medicines as used in everyday practice to identify previously
· unrecognized adverse effects or changes in the patterns of their adverse effects
· Assessing the risks and benefits of medicines in order to determine what action,
· if any, is necessary to improve their safe use
· Providing information to users to optimize safe and effective use of medicines
· Monitoring the impact of any action taken
For all medicine there is a tradeoff between the benefits and the potential for harm. To minimize the harm, it is necessary that medicines of good quality, safety and efficacy are used rationally.
Ø Efficacy: evaluated from data obtained from clinical trials
Ø Quality: compliance to established standards, manufacture by Good Manufacruring Practices licensed premise
Ø Safety : toxicology, clinical trials
In all, Pharmacovigilance will promote:
Ø Systematic and rational use of medicines
Ø Boost confidence for safety.
1. www.pwc.com/pharma; drug-safety. Source: The Importance of Pharmacovigilance, WHO 2002
2. Meyboom RHB, Egberts ACG, Gribnau FWJ, Hekster YA. Pharmacovigilance in perspective. Drug Safety 1999; 21(6): 429-447. Abbing HDCR. Legal aspects of medical devices: Study on regulatory mechanisms for safety control. Health Services Research. IOS Press 1993: 358-361. Fracchia GN, Theofilatou M (eds); Mehta U, Milstien JB, Duclos P, and Folb PI. Developing a national system for dealing with adverse events following immunization. Bulletin of the World Health Organization 2000, 78(2), 170-177. Craven BM, Stewart GT, Khan M. Chan TYK. Monitoring the safety of herbal medicines. Drug Safety 1997; 17(4): 209-215.
3. Effective communications in Pharmacovigilance. The Erice Report. InternationalConference on Developing Effective Communications in Pharmacovigilance, Erice, Sicily, 24-27 September 1997, at which a policy statement was drawn up known as The Erice Declaration.
4. Moore N. The role of the clinical pharmacologist in the management of ADRs. Drug Safety 2001; 24(1): 1-7.
5. Hall M, McCormack P, Arthur N, Feely J. The spontaneous reporting of ADRs by nurses. British Journal of Clinical Pharmacology 1995; 40: 173 – 175.
6. Hornbuckle K, Wu H-H, Fung MC. Evaluation of spontaneous adverse event reports by primary reporter - a 15-year review (1983 to 1997). Drug Information Journal 1999; 33: 1117 – 1124.
7. Consumer reporting of ADRs. WHO Drug Information 2000; 14: 211 – 215.
8. Egberts GPG Smulderes M, De Konig FHP et al. Can adverse drug reactions be detected earlier?: a comparison of reports by patients and professionals. British Medical Journal 1996; 313: 530 – 31.
9. National Pharmacovigilance programme, “Indian Journal of Pharmacology” Medknow Publication, Volume 37,issue 6,December 2005.
10. National Pharmacovigilance Protocol, Ministry of Health and Family Welfare, Govt. of India.
Received on 25.10.2011 Accepted on 12.12.2011
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