Pharmacovigilance, a French term, which refers to identifying side effects of drugs, their treatment, documentation, reportage and regulatory decisions based on them, is a well-established science in the developed world. Adverse drug reactions (ADRs) are negative consequences of drug therapy.
India is a country with over 6 billion population. Each individual in the country has at one time or the other taken a drug. In many instances, a person takes more than one drug and that too for a period of time. To complicate matters, the people of India utilize various systems of medicine such as allopathy, homeopathy, ayurveda, siddha etc. In such a scenario, the pharmacovigilance programme initiated by drugs control department of Indian government promises to maintain a close watch over the use of drugs and their effects on people.
If this monitoring and reviewing process is absent, the pharmacological effects of drugs, their adverse effects, interactions and misuse can play havoc with the health system in this country. A few examples are needed to drive home the point. In 1930's, the marketing of elixir of sulphanilamide dissolved in diethylene glycol resulted in the death of over 100 children. In the 1960's, pregnant ladies who ingested thalidomide gave birth to children with deformities. In the last two decades, several drugs have been withdrawn from the market because of serious ADRs. In India, very recent example of drug being banned due to severe cardiovascular side effects include the withdrawal of COX-II inhibitor and anti-inflammatory drug Rofecoxib, which has reportedly caused 93000 heart attacks in users.
The World Health Organisation (WHO) sponsored and World Bank funded National Pharmacovigilance Programme for India became operational from 1st January 2005. This programme was launched on November 23, 2004 in Delhi. It will be overseen by the National Pharmacovigilance Advisory Committee based at the Central Drugs Standard Control Organization (CDSCO), New Delhi. The Central ministry has announced formation of a National Pharmacovigilance Advisory Committee (NPAC) under the chairmanship of Director General of Health Services in October 2004. The Drug Controller General of India will function as the member secretary of the Committee. NPAC has been given the sole responsibility of putting in place machinery for monitoring of the pharmacovigilance programme throughout the country.
Two zonal centres, the South-West zonal centre (located at the Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai) and the North-East zonal centre (located at the Department of Pharmacology, AIIMS, New Delhi), will collate information from all over the country and send it to the committee as well as to the Uppsala Monitoring centre in Sweden. Three regional centres will report to the Mumbai centre, and two to the New Delhi one. Each regional centre in turn will have several peripheral centres reporting to it. Presently, there are 24 peripheral centers. The Central Drugs Standard Control Organisation (CDSCO), is now planning to appoint a team of about 100 clinical pharmacologists across the country, on a contract basis, to collect adverse drug reaction reports and patient complaints from hospitals, clinics and practising clinicians.
Though US FDA frequently publishes drug reviews and follow-up actions (recalls or restricted-use notifications) on its website, such moves are still unheard of in India. CDER's PMS system monitors the ongoing safety of marketed drugs. This is accomplished by reassessing drug risks based on new data learned after the drug is marketed and recommending ways of trying to most appropriately manage that risk. This is done through a variety of activities and tools, including:
● PMS information sources chart - It provides an overview of various drug experience and epidemiologic sources available to CDER in conducting surveillance and risk assessment of marketed drugs
● MEDWatch - a description of FDA's medical product reporting programme
● Spontaneous reporting system - For monitoring adverse drug reaction reports
● Pharmacoepidemiology- Efforts of CDER's epidemiology staff in monitoring drug safety
● Contracts/cooperative agreements- These provide important drug safety data on a national level
This work is accomplished primarily through CDER's division of pharmacovigilance and epidemiology (DPE).
MEDWatch: In addition, to promote and facilitate voluntary reporting of serious adverse events and product problems with drugs by health care practitioners, FDA initiated a new medical products reporting programme called "MEDWatch." MEDWatch has been in effect since June 1993.
MEDWatch has four goals. They are:
● Make it easier for healthcare providers to report serious events
● Make it clearer to healthcare providers what types of adverse events FDA is interested in receiving
● More widely disseminate information about FDA's actions that have resulted from adverse event and product problem reporting
● Increase healthcare providers' understanding and awareness of drug and device-induced disease
The MEDWatch programme makes it easy for healthcare professionals to report serious adverse events to FDA. It requires a single form that may be sent via postage-prepaid mail, fax or computer modem or uses a special call in phone number to verbally report.
FDA is interested in learning of serious events that follow drug use. Serious events are generally defined as those that involve death, a life-threatening condition, hospitalization, disability, a congenital anomaly or intervention to one of these serious outcomes.
In return, FDA keeps healthcare professionals informed about new safety discoveries.
Spontaneous Reporting System (SRS): It contains the adverse drug reaction reports from hospitals, health care providers and lay persons that are sent either directly to the agency (via MEDWatch) or first to the drug manufacturer, and then, by regulation, to the agency by the manufacturer.
Pharmacoepidemiology: CDER's DPE also carries out an epidemiological function in the monitoring of drug safety. This function is performed by a multi-disciplinary professional staff of physicians and Ph.D. epidemiologists, pharmacists and program/project managers. The primary work is directed towards the evaluation and risk assessment of drugs in the post marketing environment, using the tools of epidemiology. Epidemiologists integrate the medical/clinical details of the underlying disease being treated with the influence of patient factors, concomitant diseases and medications, as well as the clinical pharmacology of the specific product under study.
Contracts/Cooperative Agreements: Externally, US FDA uses a mix of contracts and cooperative agreements (an interactive form of a grant) to address a variety of drug exposure and risk issues. Each of these cooperative agreements and contracts has a distinct purpose that is vital to the surveillance and evaluation of drug safety issues on a national level. The contracts are used to gain access to databases to help obtain answers to questions that the FDA has regarding particular drugs. FDA defines a specific need, generates a request or a protocol and the contractor makes a delivery of data or a report. CDER's division of pharmacovigilance and epidemiology (DPE) has several contracts used for pharmacoepidemiologic and drug safety evaluation. One such contract is a drug marketing database used for describing and estimating use of many drugs. The database also provides various patient demographics.
Thus, can we resolve to establish the US FDA-CDER model of post marketing surveillance in India, to benefit both manufacturers and end user of medicines? It is high time to look at patient safety very seriously and political will can only make it happen once for all. The transition from clinical development of a new drug to marketplace introduction is critical to the success of any pharmaceutical, biotechnological or medical device product. Post marketing surveillance programmes can give manufacturers the valuable information they need to optimize the product's potential and gain competitive advantage.
I think the first step towards this goal can be the trained man power recruitment in our CDSCO, which is central regulatory agency and then inducting proactive agencies to monitor the PMS in each state. Our drug information centre can definitely take up such national cause to start with in Maharashtra.
(The author is director of DIC, MSPC)