Md. Akter Hossain
Assistant Director, DGDA
Focal Point, National PV Centre, Bangladesh
Pharmacovigilance (PV) is - “The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems”- World Health Organization (WHO, 2002). It is concerned with Adverse Drug Reactions or ADR, which is also described by WHO as “a response to a drug which is noxious and unintended, and which occurs at doses normally used for prophylaxis, diagnosis or therapy of disease, or for the modification of physiological function” (Suke et al., 2015). Searching of harms or risks in approved drugs and to take right measures for protection is the main goal pharmacovigilance. It is one of the nine WHO requires for a functional National Drug regulatory Authority (NRA) of a country.
Aims and scope of PV
Partners in Pharmacovigilance
The management of the risks associated with the use of medicines demands close and effective collaboration between the key players in the field of pharmacovigilance. Sustained commitment to such collaboration is vital if the future challenges in pharmacovigilance are to be met, and if the discipline is to continue to develop and flourish. Those responsible must jointly anticipate, describe and respond to the continually increasing demands and expectations of the public, health administrators, policy officials, politicians and health professionals. However, there is little prospect of this happening in the absence of sound and comprehensive systems which make such collaboration possible. The constraints typically include lack of training, resources, political support, and especially scientific infrastructure. Understanding and tackling these are an essential prerequisite for future development of the science and practice of pharmacovigilance.
Key partners for monitoring the safety of medicines:
Limitations of Clinical development of drugs.
50% of the approved drugs have serious adverse effects not detected prior to approved (US Dept. of HHS, FDA : May-1999). The process involved in the clinical development of medicines are illustrated in Figure 1.
Once put onto the market, a medicine leaves the secure and protected scientific environment of clinical trials and is legally set free for consumption by the general population. At this point, most medicines will only have been tested for short-term safety and efficacy on a limited number of carefully selected individuals. In some cases as few as 500 subjects, and rarely more than 5000, will have received the product prior to its release.
For good reason, therefore, it is essential that new and medically still evolving treatments are monitored for their effectiveness and safety under real-life conditions post release. More information is generally needed about use in specific population groups, notably children, pregnant women and the elderly, and about the efficacy and safety of chronic use, especially in combination with other medicines.
The information collected during the pre-marketing phase of a medical drug is inevitably incomplete with regard to possible adverse reactions (for definition see Glossary):
Even very severe ADRs, such as liver damage, are often undetected because study populations are small. Post market surveillance uses tools such as data mining and investigation of case report to identify the relationships between drugs and ADRs (Suke et al., 2015; Yao et al., 2013).
Experience has shown that many adverse effects, interactions (i.e. with foods or other medicines) and risk factors come to light only during the years after the release of a medicine (Table 1).
PV is needed in every country
Pharmacovigilance is needed in every country, because there are differences between countries (and even regions within countries) in the occurrence of adverse drug reactions and other drug-related problems. This may be because of differences in:
Data derived from within the country or region may have greater relevance and educational value and may encourage national regulatory decision-making. Information obtained in a certain country (e.g. the country of origin of the drug) may not be relevant to other parts of the world, where circumstances may be different. When information from a region itself is not available, it may take longer before a problem becomes known to drug regulatory authorities, physicians, pharmacists, patients and pharmaceutical companies.
On the other hand, international monitoring such as the WHO International Drug Monitoring Programme may provide information on possible safety issues which may not yet have emerged within the country’s data. So, pharmacovigilance activities and related studies are needed for prevention of drug-induced human sufferings.
Current position of PV in Bangladesh
Pharmacovigilance has been started in Bangladesh at Directorate General of Drug Administration (DGDA) in 1996 with the support of WHO. Then adverse drug reaction monitoring (ADRM) Cell was established and some steps were taken to build awareness & communication. But the initiatives became dormant due to lack of adequate support, legislation, funding, knowledge and attitude of the stakeholders.
ADRM Cell at DGDA has been re-started in 2013 with technical support of USAID funded MSH/SIAPS program and functioning well now. It is doing as a National PV Center in Bangladesh. DGDA is receiving suspected ADE reports from the primarily selected top selling 30 pharmaceuticals industries and 32 different types of government & private hospitals in the country. The Cell is also receiving reports from a Public Health Program (Kala-azar) & some other health facilities of the country. For PV activities Bangladesh has achieved the 120th full membership of WHO–Uppsala Monitoring Centre (UMC), Sweden.
Fig-2.Total 1577 Suspected ADE Reports received at National PV Centre
(ADRM Cell) from 2014 to 2017 (Up to Sept)
Total 517 reports have been reviewed by ADRAC up to March, 2017.
and uploaded to WHO-UMC database.
Table-2 : Sources of Reports received
Number of Reports
Pharmaceutical Industries & Importers
Suspected ADE Reporting form is available in DGDA web site. Easily one can download, fill-up and send it through mail or post to the ADRM Cell. On-line reporting system is also going to be launched very soon. ADRM Cell and ADR Advisory Committee (ADRAC) are performing as well. Number of received reports are going up gradually, but the figure is not yet up to the standard as per WHO.
International studies show that-
ADRs constitute the top ten leading causes of death (WHO, pharmacovigilance: ensuring the safe use of medicines, Geneva, 2004) . Reports from GPs are the backbone of ADR reporting with total reporting from doctors contributing to almost 50% (UK-MHRA 2014). 3.19% of patients were admitted to hospital because of an adverse drug reaction. (Pouyanne et al.1998). A review of 17 studies show that overall incidence of ADRs among hospitalized children of 9.53% when compared with Le et al. (2006) with severe reactions accounting for 12.29% of the total. The overall rate of pediatric admissions due to ADRs was 2.09% with 39.3% of the ADRs being severe reactions. Functional PV (ADR monitoring) systems can improve these situations. ‘…and more importantly 30.7% of admissions due to ADRs were preventable, providing a potential savings of 175 million Euro’ (Goettler et al. 1997
Studies in Bangladesh
Author conducted a questionnaire based study on Pharmacovigilance in 2016 among 496 educated (66.9% Masters and above degree) populations to find out the main components require immediate action for sustainable PV in Bangladesh. Respondents were Academicians, Doctors, Pharmacists, Medicine Manufacturers and DGDA inspectors. Area of study was Dhaka, Rajshahi and Khulna division.
Figure 3: Components of the PV require immediate action for sustainable PV
(Multiple response up to 3)
Result shows that the top most prioritized component is Education for Knowledge (71.4%) in this regard. Then the others are strengthening the laboratory service (64.3%) and recruitment of Graduate Pharmacists in all the Hospitals & Pharmacies (45.5%).
Another study has been conducted from December 2009 to December 2010 to find out response of reporting ADRs in one teaching hospital and 10 private chambers revealed that response of reporting of ADR from private chamber was very poor (29%) whereas response from teaching hospital was more (55%) (Nahar et al., 2011) (Table-3)
Table 3. General ADR practices of respondent
Findings of the study is shown in table 1 (Amin et al., 2015). From this study it is clear that more than half of them were not familiar with the existence of ADR reporting body of Bangladesh though they were experienced ADRs. Many did not even know how to report, some were afraid of legal liabilities associated with reporting to ADRs. So it is very urgent to strengthen the pharmacovigilance practice and reporting system in our country for the safety of medication system, especially in case of self medication which is very common in our country.
Challenges of PV activities in Bangladesh
Importance of PV education and awareness
The first day a new drug is on the market should mark the start of a systematic ongoing evaluation of how wisely doctors are prescribing it, how thoroughly patients are taking it, what adverse events it causes in routine care, and (eventually) whether its promised benefits are actually being realized with routine use. Additionally, beyond licensure for marketing, there is also a need for comparative studies assessing both pharmaceutical risks and benefits at different dosing levels between drugs of the same class (or drugs used for the same purpose) across broad end-user populations. Failure to require such post-marketing studies remains therefore perhaps the single biggest deficiency in public regulation of drug ‘safety’ at present.
Conventional methods of communication of pharmacovigilance knowledge such as letter writing, label wording and package insert warnings have very limited success in achieving the goal of an informed prescriber ready to apply pharmacovigilance intelligence in their everyday practice (Belton et al., 1995; Smalley et al., 2000). Similarly with the general public, largely ineffective communication has been observed using these conventional tools (Berryet al., 2002).
When does a side effect of a drug become an adverse event, an ADR or a medication-related error? Clearly different players in the healthcare system will have different perceptions on this point. The relationship between medication errors and adverse drug events is complex, with medication errors being generally more common than adverse drug events. It has been estimated that about a third to a half of adverse drug events are typically associated with medication errors: however, of course, not all adverse drug events necessarily spring from medication errors (Morimoto et al., 2004).
For a clinician management of an adverse drug effect and filling the ADR report represents an important opportunity for learning. Local institutional settings, discussion of, and interaction about ADR reports may become a matter of routine. Such arrangements need to be purposefully fostered. Multi-disciplinary hospital drug and therapeutics advisory committees can be a useful forum for such learning.
Necessity of more study on PV in Bangladesh
Bangladesh is an underdeveloped country. Bangladesh is now exporting wide range of products to 140 countries of the world. It includes all major therapeutic class & dosage forms along with high-tech products like inhalers, nasal sprays, suppositories, IV fluids, injectables etc. (Mustansir et al., 2013). On the other hand, a major portion of the people of Bangladesh are unconscious about the health and the drug they intake during diseases. They have limited ideas about their health and medicines. They face many serious health hazard (several drug induced diseases like- kidney damage, liver disease etc.). Due to these reasons pharmacovigilance study must be required for the safety of the people. It is very urgent to strengthen the pharmacovigilance practice and reporting system in our country for the safety of medication system, especially in case of self medication which is very common in our country. (Jahan et al.,2017).Education for PV knowledge of the stakeholders and building awareness can improve the present situation resulting sustainable & effective Pharmacovigilance system in Bangladesh.
Pharmacovigilance is very much crucial and important to ensure safety of marketed drug products. DGDA is working to ensure safe, quality and effective medicines for safeguarding the human and animal health. So, nationwide Good PV Practice is essential. Basics of PV may be introduced in course-curriculum for healthcare professionals (Doctor, Pharmacist & Nurse) in Bangladesh. All stakeholders should be aware about PV-activities. WHO definition of PV has evolved considerably during the period 1961– 2000 and includes, through the term ‘prevention’, a clear call for knowledge gained through pharmacovigilance activities to be influencing and improving outcomes from use of medicines. This call is reflected in contemporary expert commentary on the importance of surveillance and drug safety (Edwards, Faich and Tilson, 2005): A general effort to improve risk communication both in particular instances and in the general education of the public, should be a high priority. For the individual healthcare professional to reliably learn and incorporate pharmacovigilance in their routine patient care is now a key challenge.
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