Abstract

The pharmaceutical science field of pharmacovigilance (pv) is notable for its work on the identification, assessment, mitigation, and prevention of adverse medication responses and issues associated with them, such as allergic reactions. The assessment of the risk vs. Benefit medication profile for improved potency with more safety to use various pharmaceuticals in patients suffering from various illnesses is the primary issue of pharmacovigilance. Pharmacovigilance, the process of gathering information and disseminating reports on diverse adverse medication responses among various users, plays a critical role in the healthcare sector in the responsible use of pharmaceuticals in society. India's pharmaceutical business, in terms of capability and ethics, is able to position third globally. In india, a top choice for research and development, new therapeutic compounds, including synthetic and natural ingredients, particular dosage forms, and pharmaceuticals are produced on a big scale. However, for improved safety studies in the pharmaceutical sector, we need a worldwide standardised pharmacovigilance system. This review paper clarifies the significance of excellent or effectual communication in the health maintenance and function in pharmacovigilance.(1)

Keywords

Pharmacovigilance, Adverse Drug Reactions (ADR), WHO, Drug safety, Pharmcovigilance steps Social networking sites (SNS).

Introduction

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(Figure 1)The WHO International Drug Monitoring network, membership as of 2004

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Safety signal detection and management

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Principles of Good Pharmacovigilance Communication:-

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Post market Surveillance

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(Figure 3). Pharmacovigilance at different stages of Drug Development & Registration

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Premarket Surveillance:-

During the pre-marketing phase, pharmacovigilance has been devout to speculate potential ADRs in the early stages of drug development process. Safety Pharmacology Profiling (SPP) is one of the basic methods most commonly employed in preclinical in-vitro assessment of compounds with the help of biochemical and tissue culture techniques at laboratory scale. This method works on the principle that in order for appearance of any ADR in human beings, a chemical moiety will bind to a specific target the result of which may produce any reported adverse effect. However, in economic and effective terms , an experimental reports of ADRs are not always acceptable.. By using the preclinical characteristics of the compounds using SPP models, a wide range of research activities have been implemented to speculate most possible ADRs. The categorization of the current research is based on the protein targetting and chemical structural related approaches.(13)

Post-marketing surveillance :-

A drug undergoes a substantial clinical screening prior to its acceptance by the Food and Drug Administration (FDA), still there are chances to skip several ADRs as unnoticed due to small biased clinical trials by non-involvement of the patients suffering from concurrent diseases like insomnia, diabetes, anxiety anddepression. One cannot rely on Premarketing clinical trials as they do not provide actual information for varied community, therefore the continuation of the post-market surveillance is essential. Pharmacovigilenceplays a great role in evaluating post-marketing of newly developed drugs. The competition among the different pharmaceutical industries along with the rigorous regulatory evaluation procedures allows a research and development process prior to the launch of a new drug into the market.(14)

PHARMACOVIGILANCE STEPS :-

The primary steps involved in pharmacovigilance are: 

 Management of safety data.

• • Detection of Signal.
  • Signal evaluation and decisions in accord to safety measures.
  • Regulatory Actions to protect health of the community.
  • Providing Information.

MANAGEMENT OF SAFETY DATA:-

Any therapeutic molecule can result in a serious adverse event, either during the pre- or post-marketing monitoring phases. Any member of the medical team, including a doctor, chemist, nurse, patient, family member, neighbour, or paramedical personnel, may report a major adverse reaction. It takes time to effectively monitor and manage the drug safety data since these undesirable medication effects might happen at any point during the drug molecule's lifespan.

The steps involved in management of safety data are: 

• Collection and verification of data 
• Adverse drug reactions coding
• Drugs coding
• Assessment of causalities 
• Reporting to authorities.(15)

COLLECTION AND VERIFICATION OF DATA :-

ACKNOWLEDGEMENT

All genuine instances must be appropriately recognised by providing an acknowledgement number in order to obtain more information from the reporter if needed.

 Duplicate search:-

Many safety database software programmes can look for and distinguish between duplicate reports. Basic techniques to identify any duplication include parameters like patient age, patient sex, date of drug exposure, country, etc.

Triage:-

According to documented fatalities, life-threatening adverse responses within 7 days, and non-severe adverse reactions within 15 days, triage is used to assign priority to the case for reporting to authorities.

DATA ENTRY:-

It is important to thoroughly report the real cases. The utmost caution and secrecy should be used while storing patient information. The ADR reporter's information should be sufficiently clearand thorough to enable easy contact should it be necessary. The brand name, generic name, dosage form, and dose for each drug must be precisely noted. To determine the cause of a negative medication reaction, all side effects must be meticulously documented. This would contain the events' chronology, type, severity, features, findings from investigations and tests, the start date, the course of therapy, its results, and any further medications that could have been used in conjunction with them.

CASE NARRATIVES:-

Case summaries comprise a synopsis of a submitted case that contains all pertinent details, such as the medicine and its ADRS. Case reviewers assess and use case narratives to determine the significance of adverse occurrences during the management of safety data.

DRUGS CODING:-

It is necessary to code both the suspected drug and the related substances. The World Health Organization's medication lexicon, which is updated three to four times annually by the organization's pharmacovigilance monitoring unit, is frequently used for coding purposes. The WHO lexicon also includes a variety of biotechnological terms, such as special goods, blood products, and diagnostic compounds. For chemical and therapeutic categories, the ATC classifications and the WHO drug record number system are utilised, respectively.

Causality assessment:-

In practically every situation, a causality analysis must be carried out, particularly when the severity of the adverse response cannot be proven owing to the delivery of the drug moiety. Several methods are used to evaluate the link between drug exposure and adverse events precisely.(16)

1. The case history between drug administration and adverse events
2. Possibility based on signs and symptoms, lab tests, MOA& Other information
3. Knowledge of pharmacology and frequency of adverse reactions occurring due to the suspected drug
4. Exclusion of the disease condition or concurrent medicines for similar adverse reactions.

Reporting to authorities:-

The reporting to the concerned authorities or stakeholders should be done at right time in order to fulfill the role and responsibilities of a pharmacovigilance agent. This will help in timely update of ADRs and issuance of safety guidelines of any pharmaceutical product post marketing surveillance.

Pharmacovigilance in clinical practice:-

Safety monitoring of medicines in common use should be an integral part of clinical practice. The degree to which clinicians are informed about the principles of pharmacovigilance, and practise according to them, has a large impact on the quality of health care. Education and training of health professionals in medicine safety, exchange of information between national pharmacovigilance centres, the coordination of such exchange, and the linking of clinical experience of medicine safety with research and health policy, all serve to enhance effective patient care. A regular flow and exchange of information in this way means that national pharmacovigilance programmes are ideally placed to identify gaps in our understanding of medicine-induced diseases.

 

Communication, Training and Information Sharing:-

With a vast territorial area and a large population, mutualcommunication and learning must be facilitated betweenmonitoring institutions through training, experience sharing and research collaborations to improve the overall level of pharmacovigilance capability in China. The CFDA organises training and workshops in various ways, including training courses for staff at all levels, compiling pharmacovigilance manuals, organising nationwide pharmacovigilance seminars and meetings with directors from provincial and municipal ADR centres, and encouraging pharmacovigilance research. The national pharmacovigilance annual meeting has invited specialists from the US Food and Drug Administration, UK Medicines and Healthcare products Regulatory Agency and European Medicines Agency to present the pharmacovigilance systems in different countries and regions. Manufacturers, academic researchers, stafffrom all levels of ADR centres and government officials also attend these events. Still, systematic training programmesare needed to help staff to better understand the methods and gain updates on international pharmacovigilance work.  Therefore, it is important to fully engage with international and domestic resources, including the professional platform offered by the WHO-UMC, International Society of Pharmacovigilance (ISoP) and ISPE to establish a systematic pharmacovigilance training programme.The CFDA also submits unexpected and serious ADR case reports to the UMC, which promotes the understanding of medication safety issues worldwide. Further exploration of information sharing is another important issue to consider in the future. Since the CADRMS was developed in Chinese language may pose a challenge at different stages of pharmacovigilance in China in terms of global information communication. Nevertheless, there are solutions to this issue. The Chinese versions of the WHO Adverse Reaction Terms (WHO-ART) and WHO-Drug Dictionary are being developed by UMC, which might overcome the language challenge, and thus improve the exchange of information with other national and international institutions.(17)

Benefits and risks of pharmacovigilance technologies:-

The idea that randomized clinical trials can establish product safety and effectiveness is a core principle of the pharmaceutical industry. Neither the clinical trials process nor the approval procedures of the US Food and Drug Administration (FDA) provide a perfect guarantee of safety for all potential consumers under all circumstances. Despite this fact, there are viable pharmacovigilance technology solutions that biopharmaceutical companies can implement to systematically detect, assess, understand, and prevent adverse drug reactions. When built into clinical research and development practices, pharmacovigilance technologies assist biopharmaceutical firms in enhancing patient safety while reducing or even preventing costly safety-related withdrawals. It is recognized that clinical data mining and signal detection associated with pharmacovigilance technology contribute to potential benefits in providing.(18)

• Systematic, automated and practical means of screening large datasets
• Better utilization of the large safety databases maintained by the FDA, the World Health Organization (WHO) and other organizations
• Improved efficiency by focusing pharmacovigilance efforts on key reporting associations
• Positive contributions to public health by identifying potential safety issues more quickly and/or more accurately than traditional pharmacovigilance methods

• Better decision support for the pharmaceutical industry and regulators
• Potential to clarify the many complex interdependent factors (eg, concomitant drugs and/or diseases) that can play a role in the development of adverse events in a clinical setting
• Value by detecting disproportionalities involving multiple drugs or multiple events that would be too difficult to detect by traditional methods.

Social networking sites and their relevance to pharmacovigilance:-

 Social networking sites (SNS) and applications allow for the exchange of user-generated content whereby people talk/communicate, share information, network and participate in community activities. Boyd and Ellison describe SNS as a web-based service that allow individuals to construct a public or semi-public profile within a bounded system, articulate a list of other users with whom they share a connection and  view and traverse their list of connections and those made by others within the system. The nature and nomenclature of these connections may vary from site to site.More and more individuals are making use of SNS to communicate and stay in contact with family and friends,to engage in professional networking or to connect around shared interests and ideas . There currently exists a rich and diverse ecology of SNS, which vary in terms of their scope and functionality, and include: general purpose and specialised community sites (e.g. Facebook and LinkedIn); media sharing sites (e.g. YouTube and Flickr);weblogs (blogs); micro-blogging sites (e.g. Twitter); and question/answer discussion forums, which have continued to be around for decades with undiminished popularity despite relentless Internet evolution. Social media user base has undergone a nearly tenfold increase in the past decade: 65% of adults now use social networking sites.(19)

 

social media is creating real-world data at an unprecedented rate, with people using social media to discuss their everyday lives,including their health and their illnesses. The motivation to connect and learn about one another has given rise to niche SNS. Recent years have seen the emergence and proliferation of SNS dedicated to healthcare communities (usually consisting of health professionals and/or consumers/patients), which have become particularly popular among patients,with the most common intended use being self-care ,i.e. social media serving as a platform that allows patients to exchange information about their health condition with others who are battling with the same health issues, and receive peer-to-peer support (online patient communities).Social support is deemed extremely beneficial in combating health concerns like depression and mental illness.(20)

“Role of pharmacovigilance” in medicines regulation :-

Robust regulatory arrangements provide the foundation for a national method of medicine safety, and for public confidence in medicines. To be effective the remit of drug regulatory authorities needs to go further than the approval of new medicines, to encompass a wider range of issues relating to the safety of medicines, namely:

• Clinical trials;
• The safety of complementary and traditional medicines, vaccines and biological medicines;
• The development of lines of communication between all parties which have an interest in medicine safety, ensuring that they are able to function efficiently and ethically, particularly at times of crisis.In order to achieve their respective objectives pharmacovigilance programmes and drug regulatory authorities must be mutually supporting. On the one hand, pharmacovigilance programmes need to maintain strong links with the drug regulatory authorities to ensure that the latter are well briefed on safety issues in everyday clinical practice, whether these issues are relevant to future regulatory action or to concerns that emerge in the public domain. On the other, regulators need to understand the specialized and pivotal role that pharmacovigilance plays in ensuring the ongoing safety of medicinal products.(21) Healthcare professionals play a crucial role in the pharmacovigilance system. ?e  require considerable knowledge and expertise in the field of medication safety which will successfully contribute to this area through early recognition, management, and reporting of the medicine safety issues. Furthermore, the healthcare professionals should be well educated about the necessity and procedure of adverse event reporting. ?e  should possess a combination of training and research skills in this area. Despite global concerns against medication safety, there is a lack of awareness and knowledge of pharmacovigilance and ADR reporting among healthcare professionals yet. Moreover, recent studies have indicated that ADRs are poorly reported by healthcare providers, especially in developing countries. It has been reported that only 2-4% of all adverse reactions and 10% of serious ADRs are reported worldwide. It is highly recommended that healthcare professionals including physicians,pharmacists, and nurses report any suspected adverse reaction particularly those suspected reactions to newly authorized medicines and serious events. ?erefore the medicine safety assessment must be considered an inseparable part of everyday clinical practice for healthcare professionals.(22)Careful study of adverse drug events may identify diagnostic features, syndromes or pathogenic mechanisms. Moreover, clinical, pathological and epidemiological information relating to adverse reactions is necessary for a full understanding of the nature of an adverse reaction and for identifying patients at risk. Although spontaneous reporting is the mainstay of passive surveillance, the information obtained is inherently limited and likely to be insufficient for regulatory and clinical decisions. Active or intensive surveillance programmes  for addressing serious safety concerns have had success in identifying and quantifying drug safety issues, using: 
• case control networks
• hospital-based intensive monitoring systems
• record linkage systems
• epidemiological studies.(23)

Promoting communication in the field of drug safety :-

Society has a great concern about coping with the dangers of modern life. Medicinal products are among the technological advances that have provided society with great benefits and added risks. Knowledge of the public perception of these risks is essential if they are to be managed effectively. How safe is safe enough? Which risks are acceptable? These are two critical questions that providers of medicines need to consider when communicating with patients and the public. Recognizing that there is variance between expert views of risk and public perception, there is a need to analyse and understand the differences much more thoroughly. It is not sufficient for the experts to be satisfied with the evidence for safety. The pharmaceutical industry, governments and healthcare providers must build public trust through effective risk communications.(24) Some regulatory authorities are increasing the transparency with which they conduct their affairs. However, many authorities continue to be constrained by real or notional secrecy provisions, intended to protect the intellectual property rights of pharmaceutical manufacturers. The problem with secrecy is that it creates an environment of distrust and misunderstanding. It is now expected of regulators that they should deal with drug regulation, including drug safety issues, with a new commitment to openness, including patients and their representatives in the process.(25)

CONCLUSION :-

The scientific field of pharmacovigilance is notable for its work on the accumulation, assessment, control, and prevention of adverse drug responses and issues that are connected to them, such as allergic reactions. In order to prevent harmful and life-threatening effects of the drug moieties on the community, PV analyst plays a significant role in gathering information from healthcare professionals and patients on the adverse effects of medicines, including biological products like vaccines, toxoids, anticoagulants, herbs, medical devices, and traditional and synthetic medicines. As the pharmaceutical industry in our nation expands daily, we need a solid pharmacovigilance system to monitor medication side effects and guarantee patient safety. Despite all the efforts made by CDSCO to establish a national global pharmacovigilance system, there are still many obstacles to be overcome before pharmacovigilance  To motivate doctors, chemists, and nurses to report adverse drug reactions (ADRs) that occur in patients, education is urgently needed. An international system for drug safety monitoring will be established thanks to standard pharmacovigilance recommendations for India that were inspired by the EMA's good pharmacovigilance practices.(26)

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