Drug use could lead to better outcome’ is undoubtly accepted by all but favourable outcome is hardly seen with increased number of problems like irrationality, resistance, medication errors and lack of root cause analysis. The other side of the story is equally dangerous. The delayed reflexes were picked up way back in 1960s with Thalidomide tragedy and then origin of international drug monitoring activities in 1968 making it mandate for manufacturers, stakeholders, regulators, drug authorities and healthcare professionals to vigilantly monitor drug use. No wonder “Pills for ill” concept adopted as “Pills make ill”.
Regulations for drugs are proposed by authorities but execution delay interrupted the whole network. Pharmacovigilance network is well sustained in developed countries but still on its way to progress in developing countries. With increased number of new chemical entities (NCE), pharmacovigilance has become mandatory requirement for pharmaceutical companies. With this view, phase IV studies are critically analyzed and executed with the aim to monitor and capture long term safety outcomes and report ongoing safety review to regulatory authorities in terms of periodic safety update reports (PSUR). It also insists manufacturers to update safety information in product leaflet or summary of product characteristics (SPC) within stipulated time period.
Regulatory authorities are concerned about drug safety and implementing risk minimization plan to: improve patient outcome, prevent drug associated injury or hazard, minimize healthcare associated cost especially cost attributed to ADRs, create awareness among consumers, healthcare professionals, stakeholders, third party payers and managed care organizations (MCOs), frame prevention strategies for highly vulnerable population, plan management strategies for effective care, disseminate safety information via communication network, develop guidelines for effective management of drug safety issues and execution and implementation of well framed guidelines based on recent information and ongoing safety review.
Regulatory authorities are constantly working to promote effective management strategies and risk minimization plan. Some of the responsibilities delegated to triage cover healthcare professionals, stakeholders and the consumers.
Good reporting practices
Good reporting practices (GRP) could improve the quality of ADR reports and also minimize the subsequent occurrence of ADRs. Adverse drug reactions once notified should be subjected to analysis to establish causality. For analysis of ADR, standard scales are used to assess causality, severity and preventability aspects. Clinical interpretation of ADRs is of clinical importance to attribute the causality link between drug and reaction. In many clinical situations causality link is difficult to establish due to contradictory information or lack of proper data. Certain parameters which must be included for analysis are previous history, demographics, date of onset of reaction, onset time, time temporal relationship, suspected drug, description of the reaction, dechallenge, rechallenge, management and outcome of the reaction.
The scales commonly preferred for analysis are causality analysis as per WHO probability scale, Naranjo’s algorithm, French imputation method, European ABO method etc.). Severity analysis based on Hartwig et al scale. Preventability analysis as per the Modified Schumock and Thornton scale.
In order to improve the patient outcome, constant efforts are required to build up a strong pharmacovigilance network. In India, we do not have robust structure which could in turn compromise the safety and lead to adverse outcome. We still remember the Rofecoxib story of devastation. Drugs are meant to treat not to harm but practically speaking drugs could alter the normal physiology of patients despite targeting the affected organ which in turn could lead to adverse effects. Adverse effects could be avoided by vigilant monitoring and reporting.
In developing countries like India, the pharmacovigilance programme was initiated by Central Drugs Standard Control Organization (CDSCO) in Nov 2004 under the aegis of ministry of health and family welfare based on the recommendations made in the WHO document entitled “Safety monitoring of medicinal products-guidelines for setting up and running a pharmacovigilance centre” with the objective to monitor ADRs and report through hierarchy of pharmacovigilance network and disseminate the information with global healthcare community through WHO-Uppsala Monitoring Centre. Under this programme, 26 peripheral centres, 5 regional centres and 2 zonal centres were established. The National Pharmacovigilance Advisory Committee (NPAC) was constituted to assess the performance and recommend possible regulatory measures based on the data received from various centres.
Due to lack of sufficient information and under reporting, the programme has been modified as Pharmacovigilance Programme of India (PvPI) and reinitiated in June 2010 with the aim to expand the existing structure and proactively report ADRs. The purpose of PvPI is to collect, collate and analyze data to recommend regulatory interventions and communicating risks to healthcare professionals and consumers. The National Coordinating Centre (NCC) i.e. Indian Pharmacopeia Commission, Ghaziabad will operate under the supervision of a Steering Committee which would consist of DCGI, New Delhi as chairman and other govt officials as constituent members. The following programme will be executed and monitored by Steering Committee and Strategic Advisory Committee. Technical support for the programme will be provided under different panels: Signal Review Panel, Core Training Panel and Quality Review Panel.
The five year PvPI has been scheduled under five phases covering the Initiation phase (2010-11), Expansion and consolidation phase (2011-12), Expansion and maintenance phase (2012-13), Expansion and optimization phase (2013-14) and the Excellence phase (2014-15)
As per proposed plan under Phase 1, 40 ADR monitoring centres will be enrolled. An additional 60, 100 and 100 centres will be enrolled under respective Phase 2, Phase 3 and Phase 4 comprises of 300 centres overall.
Adverse drug reaction information will be entered in safety database ‘Vigiflow’ programmed by WHO-Uppsala Monitoring Centre. The performance of individual centre will be continuously monitored and evaluated based on quality parameters and indicators.
The prevention strategies cover intensive monitoring and timely reporting of ADRs, prophylactic treatment for known reactions, ADR database for safety information and history of known allergy, patient education, dissemination of safety information.
Adverse drug reactions could be effectively managed by strong build up of causality link, discontinuation of drug therapy, reintroduction of drug therapy, if necessary. Introduction of definitive therapy in case of certain or probable reactions, intensive monitoring and reporting of ADRs, and follow-up plan for patients who experienced ADRs.
Strategies to enhance ADR reporting can include creation of reporting culture, awareness about monitoring, sensitize healthcare professionals for enhancing ADR reporting, training sessions, reminders, reporting aids such as ADR drop box, ADR posters, ADR newsletter, fax and web reporting, periodic meeting, scientific newsletters and appreciation to reporter.
Pharmacovigilance network will be expanded further to cover broader region. There is a need for proactive monitoring and reporting. Quality control system should be installed to constantly monitor the quality of ADR reports generated and authenticate the channel of network. Adoption of good pharmacovigilance practices (GPP) could create good reporting environment for healthcare professionals. Drug utilization may improve with strapping evidence based clinical practice and could lead to better patient outcome.
Source: PB
by
Akshaya Srikanth*, Tarun Wadhwa, Prof. MS Ganachari
Hyderabad, India
