|Year : 2015 | Volume
| Issue : 1 | Page : 54-57
Prospects of consumer-initiated adverse drug reaction reporting in cardiovascular pharmacovigilance
Vinu Wilson, Vijayalekshmi Amma
Department of Pharmacology, Sree Gokulam Medical College and Research Foundation, Venjaramoodu, Thiruvananthapuram, Kerala, India
|Date of Web Publication||22-May-2015|
Dr. Vinu Wilson
Department of Pharmacology, Sree Gokulam Medical College and Research Foundation, Venjaramoodu, Thiruvananthapuram - 695 607, Kerala
Source of Support: None, Conflict of Interest: None
Drugs used for the treatment of cardiovascular disorders are frequently reported to cause adverse drug reactions (ADRs), second only to antimicrobials. ADRs strain the patients' health and finances further and could prove fatal too. Pharmacovigilance programs aim to detect, monitor and understand ADRs in order to prevent them. Pharmacovigilance provides vital input to drug regulatory agencies to monitor safety of new as well as old drugs. Spontaneous reporting of suspected ADRs by healthcare professionals forms the backbone of pharmacovigilance programs worldwide including the Pharmacovigilance Program of India (PvPI) launched in 2010. The PvPI has significantly contributed to strengthening pharmacovigilance in India but suffers from under-reporting of ADRs like similar programs worldwide. Consumer-initiated reporting of ADRs incorporated in pharmacovigilance programs of several countries has been found to decrease under-reporting rates besides supplementing traditional pharmacovigilance information. The PvPI has recently introduced the facility for consumers to report ADRs by contacting a hotline (1800-180-3024), through e-mail (email@example.com) or by filling specifically designed ADR reporting forms, either in English language or vernacular translations, and submitting them to the nearest ADR monitoring centre. This is a welcome step in empowering patients as consumers of drugs with the mechanism to monitor their safety. It could potentially fill the huge gap in spontaneous ADR reporting and supplement the indigenous drug safety database with patients' perspectives regarding ADRs e.g. effect on their quality of life. Whether it encourages rational prescription practices by doctors or enhances transparency regarding safety of investigational drugs in clinical trials needs to be seen.
Keywords: Cardiovascular drugs, patient reporting of ADRs, pharmacology, pharmacovigilance, pharmacovigilance program of India
|How to cite this article:|
Wilson V, Amma V. Prospects of consumer-initiated adverse drug reaction reporting in cardiovascular pharmacovigilance. J Pract Cardiovasc Sci 2015;1:54-7
|How to cite this URL:|
Wilson V, Amma V. Prospects of consumer-initiated adverse drug reaction reporting in cardiovascular pharmacovigilance. J Pract Cardiovasc Sci [serial online] 2015 [cited 2020 Sep 18];1:54-7. Available from: http://www.j-pcs.org/text.asp?2015/1/1/54/157570
The therapeutic arsenal for cardiovascular disorders (CVD) has witnessed the introduction of a number of new drugs over the last two decades. Preapproval clinical trials of these drugs conducted in three phases may involve several thousand carefully selected patients studied under controlled clinical settings excluding vulnerable subjects such as children, the elderly, pregnant or lactating women and patients with co-morbidities, e.g., hepatic and/or renal dysfunction. These trials may detect common and rapidly developing adverse effects of the drug but may not reveal rare or delayed effects. Clinical use of such drugs after regulatory approval in large patient population is prone to the occurrence of expected as well as unexpected adverse events (AEs), some of which may be life-threatening. This is true for the widely used older drugs too. When an AE is causally associated with a drug, it is called its adverse drug reaction (ADR). The detection, evaluation, understanding and monitoring of ADRs with the aim to prevent them come under the purview of pharmacovigilance programs.
Pharmacovigilance is indispensable because ADRs are significant causes of potentially preventable morbidity and mortality worldwide.  They are serious in up to 6.7% of hospitalized patients and are the 4 th -6 th leading cause of death in the USA.  According to a recent meta-analysis, ADRs may occur in up to 16.8% of hospitalized patients.  Patients developing ADRs have to stay hospitalized longer and pay higher costs to manage these reactions than those discharged uneventfully.  Pharmacovigilance activities guide regulatory interventions to maintain drug safety in populations and promote informed, rational pharmacotherapy in individual patients.  It is also an important source of hypotheses for pharmacogenomic studies since clustering of similar ADRs in ethnic groups may point to putative genetic susceptibility.  Therefore, it is important to monitor not only serious but common, expected ADRs also as it may identify at-risk population.
Pharmacovigilance is especially relevant to cardiovascular therapeutics because patients of CVD are usually on multiple drugs and have co-morbid disorders increasing their susceptibility to ADRs and drug interactions. Unsurprisingly, ADRs to drugs used in CVD are frequently being reported to pharmacovigilance databases, second only to antimicrobials.  Majority of the drug withdrawals or recalls executed worldwide were secondary to reports of ADRs affecting the cardiovascular system, e.g., the antihistamine terfenadine and the selective cyclooxygenase-2 inhibitor rofecoxib. , Moreover, several drugs introduced in recent years have novel mechanisms of action which necessitates monitoring to detect warning signals of dangerous ADRs. For example, the introduction of novel oral anticoagulants has led to several controversies regarding their safety in clinical practice compared to warfarin.  However, it is interesting to note that cardiovascular ADRs are frequently caused by noncardiovascular drugs and drugs used in CVD often cause noncardiovascular ADRs.  Thanks to active pharmacovigilance, several previously unknown ADRs are being reported to cardiovascular drugs, e.g., peripheral neuropathy with statins,  sprue like enteropathy with olmesartan,  corneal perforation with nicorandil,  hepatic dysfunction with aliskiren  and sensorineural hearing loss with phosphodiesterase-5 inhibitors.  Drugs considered relatively safe in patients of CVD may also increase the risk of cardiovascular ADRs, e.g., elevation of asymmetric dimethylarginine levels by proton pump inhibitors. 
The role of pharmacovigilance in guiding drug regulation and in facilitating informed, rational prescribing has been recognized only recently in our country.  Isolated studies report the incidence of ADRs from India based on monitoring of hospitalized patients. , Studies from South India have reported ADRs to be responsible for 0.7−3.4% of hospital admissions, 3.7% of hospital readmissions and 1.3% of deaths. , In one study, cardiovascular drugs were reported to be the second most common group of drugs causing ADRs after antimicrobials.  In North India, a prospective study in inpatients of the cardiology department reported that around 20% of patients developed ADRs, which were potentially preventable in 70% of cases.  However, these small studies from distinct regions of our large country are insufficient to guide the regulatory agency in maintaining drug safety. Consequently, drug regulatory decisions in India are often based on interventions taken in other regions of the world due to paucity of indigenous safety data.  Drugs banned in several countries due to inadequate safety continue to be marketed for several years in India before being recalled.  Scarcity of data also leads to regulatory misadventures like the pioglitazone fiasco.  In June 2013, the Central Drugs Standard Control Organization (CDSCO) banned the insulin sensitizer pioglitazone in India citing risk of bladder cancer reported from other countries. Doctors and patients alike were up in arms against this decision taken without indigenous safety data. The CDSCO had to revoke its ban within a month but not before adding a boxed warning on the drug's label cautioning consumers of reported risk of bladder cancer.  The need for strengthening pharmacovigilance activities in India, therefore, cannot be over-emphasized.
| Pharmacovigilance Program of India|| |
India initiated a concerted World Health Organization (WHO)-sponsored national pharmacovigilance program in 2005 which slackened later due to lack of consistent financial support and political commitment.  It was renamed as pharmacovigilance program of India (PvPI) and reinitiated in 2010 under the aegis of Indian Pharmacopeia Commission (IPC) with ambitious goals and detailed planning.  The program is now in its expansion phase with 150 ADR monitoring centers (AMCs) functioning all over the country and has submitted around 75,000 ADR reports to the global database of ADRs (Vigibase) maintained by the Uppsala Monitoring Centre (UMC), Sweden.  An ADR report completed in the prescribed format is known as an individual case safety report (ICSR) and should be submitted to the nearest AMC. The AMC conducts the causality assessment using WHO-UMC criteria and digitizes the report using proprietary Vigiflow software licensed from UMC.  The software has been developed by Uppsala Monitoring Centre (UMC), Sweden for WHO. UMC provides licence for its use to different countries. The quality of ICSRs is validated by the IPC before committing them to Vigibase.  India ranked 7 th among countries contributing safety data to Vigibase with respect to the number of ICSRs submitted in the year 2013. 
| Spontaneous Reporting of Adverse Drug Reactions|| |
The cornerstone of all pharmacovigilance programs is spontaneous reporting of ADRs by doctors, nurses, pharmacists and allied healthcare professionals.  It is done by filling ADR forms which are designed specifically for healthcare professionals. The number of ADR reports received under PvPI has been steadily increasing with a major contribution by physicians especially from government medical institutions, followed by pharmacists and other healthcare professionals.  Spontaneous reports form a major source of data involved in drug withdrawals throughout the world. ,, However, under-reporting of ADRs is a long known limitation of spontaneous reporting programs.  The WHO proposes that functional pharmacovigilance systems should expect to receive a minimum of 200 ADR reports per million population per year.  That translates to a minimum of 2,40,000 ADR reports per year for Indian population of 1.2 billion. According to the latest status report of PvPI, 84,470 ICSRs were received from all over India since program inception.  Though various factors may account for the huge gap between expected and actual ADR reports, neglect of spontaneous ADR reporting by healthcare professionals is thought to be the most pertinent factor. Several studies have revealed that doctors, nurses and pharmacists in India are aware of the need and mechanisms of spontaneous ADR reporting but seldom put them into practice. ,, Spontaneous reporting requires time, care and diligence of the healthcare professional for which she/he is not remunerated. Lack of easy access to functional pharmacovigilance systems, excessive patient care responsibilities, fear of indictment and erosion of professional reputation due to admission of an ADR are some of the factors cited for under-reporting. , The IPC has taken several steps to augment spontaneous reporting practices such as highlighting the issue in conferences, medical journals, meetings of professional bodies and conducting training sessions for healthcare professionals.  Lately, it was realized that spontaneous reporting solely by healthcare providers will not adequately serve the needs of PvPI. Consumer (patient)-initiated spontaneous ADR reporting has been initiated as a potential means to provide a fillip to PvPI.
| Consumer-initiated Adverse Drug Reaction Reporting|| |
Consumer initiated reporting of ADRs was practiced in USA from the start of its pharmacovigilance program in 1960s following the thalidomide tragedy. Other countries have added this service later in their programs, e.g., The Netherlands (2003), Denmark (2003), Australia (2003), Italy (2004), UK (2008), Sweden (2008) and Norway (2013). Studies from The Netherlands and UK have shown that patient-initiated ADR reporting is a reliable source of information for supplementing drug safety monitoring. ,
Patients have been recognized as consumers of the healthcare services under consumer protection laws.  Under their purview, patients consuming drugs for the prevention, diagnosis or cure of a disease have the right to information regarding the known and potential adverse effects of the drug. It should not be the prerogative of the prescriber alone to decide whether a suspected adverse effect should be reported to the regulatory authorities. Patients as consumers should have the right, knowledge of and access to the means to report suspected adverse effects of drugs. Therefore, the PvPI has now introduced the provision of reporting of ADRs by any person including the consumer by contacting a hotline (1800-180-3024), through E-mail (firstname.lastname@example.org) or by filling suspected ADR reporting forms specifically designed for consumers (either in English or vernacular translations) and submitting them to the nearest AMC. However, this feature of the program needs to be widely publicized to the patients and public through mass media before it provides expected results.
| Potential Benefits of Consumer Reporting of Adverse Drug Reactions|| |
Patients may report previously unknown reactions much earlier than their healthcare providers which may include data on over-the-counter drugs, alternative systems of medicine and even food supplements. Their reports may elaborate on how ADRs affected their lives and experiences and may be free of bias due to lack of medical knowledge.  Though cardiovascular symptoms are infrequently reported as ADRs to pharmacovigilance programs, they are usually detected by the patients and are suited for self-reporting. Consumer reporting will provide independence to patients to report ADRs directly to regulatory authorities and to confirm whether they received safe and effective drugs indicated in their disease. It could potentially strengthen accountability of prescribers and reduce irrational prescription patterns. It could ease the responsibility of spontaneous reporting by doctors to some extent, but prudent doctors would continue to report ADRs well ahead of their patients. In the pharmaceutical industry, it could ensure greater accountability and transparency in clinical trials because participants can report ADRs directly to regulatory agencies thereby curtailing any unethical suppression of drug safety information.
| Conclusion|| |
Consumer-initiated reporting of ADRs is a welcome step in PvPI which can potentially fill the huge gap in the current under-reporting of ADRs. It can play a significant role in enhancing the safety data of cardiovascular drugs and devices. It remains to be seen if it could also improve the accountability of prescribers and transparency of clinical trials.
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