Pharmacovigilance

Pharmacovigilance

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  Pharmacovigilance Dr. Ashishkumar Baheti MDPharmacology
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  2 Pharmacovigilan ce The etymological rootsare: pharmakon (Greek) means drug and vigilare (Latin) means to keep watch.
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  3 Definition WHO Definition The scienceand activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug related problems.
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  4 Side Effect Any unintendedeffect of a pharmaceutical product occurring at doses normally used in man which is related to the pharmacological properties of the drug. e.g. sedation with antihistaminics
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  5 Adverse Event /Adverse Experience Any untoward medical occurrence that may present during treatment with a pharmaceutical product at the same time, does not necessarily have a causal relationship with this treatment
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  6 Adverse Reaction A responseto a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function
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  7 Unexpected Adverse Reaction Anadverse reaction nature and severity of which is not consistent with domestic labelling or market authorisation, or expected from characteristics of drug action.
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  8 Why Pharmacovigilance ? •Limited value of animal experiments • Clinical trials are limited in time and number of patients • Patients are selected • Rare or delayed serious reactions are likely to remain unnoticed
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  9 Disasters • Sulfanilamide in1937 • Thalidomide in 1962 • Practolol in 1974 • Rofecoxib-Voluntary withdrawal (Sept 2004)
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  10 Aims of thePharmacovigilance • 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
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  11 WHO Programme forInternational Drug Monitoring WHO Drug Monitoring Programme was established in 1968 As of October 2008, 89 countries had joined the WHO Drug Monitoring Programme.
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  12 It consists ofa network of the 1.National Centres, 2.WHO Headquarters and 3.Uppsala Monitoring Centre which is WHO Collaborating Centre for International Drug Monitoring, in Uppsala, Sweden.
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  13 Functions • Identification andanalysis of new adverse reaction signal • Provision of the WHO database • Information exchange between WHO and National Centres mainly through Vigimed • Publication of periodical newsletters, guidelines and books • Provision of training and consultancy support to National Centres
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  14 Contd.. • Annual meetingsfor representatives of National Centres • Producing WHO Drug Dictionary and the WHO Adverse Reaction Terminology • Development of pharmacovigilance as a science
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  15 Status of India •India joined the WHO Programme in 1998 • The Central Drugs Standard Control Organization(CDSCO) launched the National Pharmacovigilance Programme in November 2004. • Basic purpose of this programme is to collate, analyze and archive adverse drug reaction data for making regulatory decisions regarding drugs marketed in India.
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  16 National Pharmacovigilance Program •The program has a three-tier structure with 1) 2 Zonal Centers 2) 5 Regional Centers 3) 26 peripheral centers and • National Pharmacovigilance Advisory Committee • National Pharmacovigilance Center at CDCSO
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  19 Noteworthy Features ofNPP • Foster a culture of notification amongst doctors, pharmacists and nurses. • The reporting forms maintain patient confidentiality • Now even practicing doctors and pharmacists can establish Peripheral Pharmacovigilance Centers and get involved in pharmacovigilance
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  20 Pharmacovigilance Process 1. Datacollection & Data management 2. Signal detection 3. Risk assessment and quantification 4. Benefit/ Risk assessment 5. Actions to reduce risk or increase benefit 6. Communication of risks or interventions 7. Audit
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  21 Data collection &Data management 1.Passive surveillance a) Spontaneous reporting b) Case series c) Large linked administrative database d) Electronic medical records 2.Intensified reporting 3.Active Surveillance 4.Comparative Observational Studies 5.Targeted Clinical Investigations 6.Descriptive studies
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  22 1.Passive surveillance a) Spontaneousreporting • play a major role in the identification of safety signals once a drug is marketed • Is voluntary for health professionals in most countries E.g. UK Yellow Card Scheme, • Most useful 1.Where reaction is unusual and unexpected 2.Where ADRs occur in close temporal relation with start of treatment or increase in dose
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  23 Contd.. • Provide importantinformation on at-risk groups, risk factors, and clinical features of known serious adverse drug reactions. • ADRs are less likely to be suspected if they have insidious onset • Underreporting is an important limitation; causes are lack of awareness, time, report forms, misconception that absolute confidence that the medicine caused the event is needed for reporting • Reporting rates cannot be used to reliably estimate incidence rates
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  24 Reports for regulatoryauthorities are in form of • Expedited adverse drug reaction (ADR) reports • Periodic Safety Update Reports (PSURs)
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  25 b) Case series •Provide evidence of an association between a drug and an adverse event • More useful for generating hypotheses than for verifying an association between drug exposure and outcome • Reports of events like TEN, SJS, Anaphylaxis should undergo detail and rapid follow up
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  26 c) Large linkedadministrative database • Large linked health administrative databases, such as Medicaid in the USA and the Ontario provincial databases • contain data on millions of subjects • the completeness of details, such as diagnoses, are questionable in many circumstances • may not be representative of the whole population.
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  27 d) Electronic medicalrecord (EMR) • Large number and detail of the variables are available like use of tobacco products and nonprescription drugs, symptoms and signs, laboratory data and social circumstances etc. • can be combined to generate new diagnoses or adverse events, • Hypotheses which are not restricted to existing diagnoses, can be explored
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  28 2.Intensified reporting To encourageand facilitate reporting for new products or for limited time periods methods used are - on-line reporting of adverse events - systematic stimulation of reporting of adverse events based on a pre-designed method
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  29 3. Active monitoring Drugevent monitoring • Patients might be identified from electronic prescription data or automated health insurance claims. • A follow-up questionnaire can then be sent to each prescribing physician or patient at pre-specified intervals to obtain outcome information. • More detailed information can be collected • Limitation - poor response rates
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  30 Registries • A registryis a list of patients presenting with the same characteristic(s) • Used as information gathering and hypothesis generating tool, particularly on drug exposure during pregnancy and for orphan drugs • Can act as population basis for linkage studies
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  31 4.Comparative Observational Studies •Are key component in the evaluation of adverse events. • Cross- sectional studies- primarily used to gather data for surveys or for ecological analyses • Case-control studies- used to investigate whether there is an association between a drug (or drugs) and one specific rare adverse event, as well as to identify risk factors for adverse events • Cohort studies- incidence rates of adverse events in addition to the relative risks of adverse events are calculated
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  32 5.Targeted Clinical Investigations •to evaluate the mechanism of action for the adverse reaction • pharmacodynamic and pharmacokinetic studies • to investigate potential drug-drug interactions and food-drug interactions
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  33 6. Descriptive studies •These studies are primarily used to obtain the background rate of outcome events • and/or establish the prevalence of the use of drugs in specified populations.
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  34 Pharmacovigilance Process steps •Data collection & Data management • Signal detection • Risk assessment and quantification • Benefit/ Risk assessment • Actions to reduce risk or increase benefit • Communication of risks or interventions • Audit
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  35 Signal detection Signal • Reportedinformation on a possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously. • Usually more than a single report is required to generate a signal, depending upon the seriousness of the event and the quality of the information
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  36 Contd.. • describes thefirst alert of a problem with a drug • cannot be regarded as definitive • indicates the need for further enquiry or action • The automated systems used to generate signal is called as data mining
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  37 Data mining is theapplication of statistical techniques, e.g. predictive modelling, clustering, link analysis, deviation detection and disproportionality measures, to databases to generate signal.
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  38 • Signal detectionpattern may be affected by coding systems and retrieval • For coding adverse events and reactions Medical dictionary MedDRA was developed • Signal prioritization is needed as detailed evaluation using all relevant data is complex and resource intensive • Potential impact of a safety issue on public health is major determinant for prioritization
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  39 Contd.. • SNIP criteria Strongsignals that are judged to be New, clinically Important, and have potential for Prevention will be given priority for further evaluation
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  40 Aim of statisticalaids To provide the means of comparing the frequency of a medicine – event combination with all other such combinations in the database under consideration , with potential for early detection of signals of possible medicine – event association.
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  41 Measures of disproportionality are thecommonly used techniques to identify ADEs. It was used to • Identify an association between delay of withdrawal bleeding during concomitant use of oral contraceptives and itraconazole • The association of pericarditis with practolol but not with other b-blockers • The association of captopril and other angiotensin converting enzymes with cough
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  42 Pharmacovigilance Process steps •Data collection & Data management • Signal detection • Risk assessment and quantification • Benefit/ Risk assessment and decision making • Actions to reduce risk or increase benefit • Communication of risks or interventions • Audit
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  43 Risk assessment andquantification Evaluation of drug safety issue 1. Causality assessment 2. Identifying other possible cause 3. Assesing the risk to individual and public
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  44 Pharmacovigilance Process steps •Data collection & Data management • Signal detection • Risk assessment and quantification • Benefit/ Risk assessment and decision making • Actions to reduce risk or increase benefit • Communication of risks or interventions • Audit
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  45 Benefit/ Risk assessmentand decision making • Benefit/ Risk assessment is continued throughout life of a drug • Guidelines to assess risk/ benefit differ from country to country E.g. Trovafloxacin was withdrawn from but in US its use was initially restricted and monitored • CIOMS has set working group to produce guidelines on standardized Benefit/ Risk assessment
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  46 Key elements ofBenefit/ Risk assessment • Description of target disease, populations being treated, purpose of intervention • Degree of efficacy, presence of alternative therapy • Type of risk and identification of risk factors • Consideration of all benefits and risks by indication and population
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  47 Pharmacovigilance Process steps •Data collection & Data management • Signal detection • Risk assessment and quantification • Benefit/ Risk assessment and decision making • Actions to reduce risk or increase benefit • Communication of risks or interventions • Audit
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  48 Actions to reducerisk or increase benefit and Communication • Contraindicate use of drug in specific group • Reducing maximum authorized dose • contraindicating concomitant use of interacting drug • Monitoring early warning signs • Educating practitioners and consumers • Withdrawal of drug
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  49 Communication • To preventthe ADRs effective communication is essential • Communications need to planned, if possible communication team should be employed • different but compatible messages may be essential for health care professionals, patients, and the media • The messages should be informative, targeted, clear, balanced
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  50 Pharmacovigilance Process steps •Data collection & Data management • Signal detection • Risk assessment and quantification • Benefit/ Risk assessment and decision making • Actions to reduce risk or increase benefit • Communication of risks or interventions • Audit
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  51 Audit • To evaluatethe outcomes of the interventions • To plan future activities
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  52 Considerations for future •Involve professional organizations of healthcare providers like IMA, IPA. • Address clinicians’ concerns • Collect adverse drug reaction data involving drugs of alternative medicine and their interactions with drugs of modern medicine. • Consider including reports of “lack of efficacy”
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  53 Contd.. • Environmental implicationsneed to be addressed
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  THANK YOU!