Encyclopedia
Please note this is a comparison between Version 1 by Hamza Garashi and Version 2 by Jason Zhu.
Pharmacovigilance (PV) is defined by the World Health Organisation (WHO) as “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem" and represents an important element of a country’s public health policies’ portfolio. Like other developing countries, PV systems in Arab countries are at different stages of maturity, with many still in the early stages of development. Recently, however, the importance of having a strong PV system in place has gained increased attention.
- pharmacovigilance
- adverse drug reactions
- Arab world
- postmarketing surveillance
- developing countries
- Middle East
1. Introduction
Pharmacovigilance (PV) is defined by the World Health Organisation (WHO) as “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem” [1] (p. 7) and represents an important element of a country’s public health policies’ portfolio. PV has four main objectives, namely, (a) the identification and quantification of previously unknown drug safety hazards; (b) the elucidation of predisposing factors to drug safety hazards, which if avoided could improve drug safety; (c) obtaining safety evidence on approved drugs to widen their usage; and (d) refuting false-positive adverse drug reaction (ADR) signals [2].
Increased efforts towards addressing public health concerns have led to an unprecedented expansion in global access to healthcare and medicines over the past decades [3]. However, these efforts have not been met by a proportionate improvement in PV systems in developing countries. A systematic review of developing countries’ PV systems found that overall system performance was poor and varied widely from one country to another [4]. This means that these systems are unable to benefit from local data identifying ADR signals to support regulatory decisions regarding drug safety in the populations they serve [3].
Like other developing countries, PV systems in Arab countries are at different stages of maturity, with many still in the early stages of development [5][6][7]. Recently, however, the importance of having a strong PV system in place has gained increased attention [8]. Recognising the importance of PV as a part of public health, the Arab League developed the “Guideline on Good Pharmacovigilance Practices (GVP) for Arab Countries” in 2014 with the aim of harmonising practices in the region [6][8][9]. However, effective implementation of these guidelines requires improvement in the existing PV systems in these countries. Literature on PV systems in the Arab World has mainly focused on surveying these countries’ systems and providing a descriptive overview of their characteristics [5][7][10]. However, no studies have been conducted that set out to provide an in-depth exploration of the PV situation within the individual countries.
21. Core Indicators
21.1. Core Structural Indicators
The World Health Organisation (WHO) indicates that a prerequisite of a functional Pharmacovigilance (PV) system is the presence of a dedicated space (i.e., a centre, department, or unit) for PV activity, which is officially recognised and/or accredited by the country’s Ministry of Health (MOH). Only in Kuwait was the national PV centres (NPVCs) not officially recognised by the country’s MOH and hence operated as an unofficial unit (sub-section) of the NMRA’s Drug Registration Department. Some NPVC and PI participants from Kuwait believed that their system’s lack of a dedicated and officially recognised NPVC represented a weakness because it resulted in a lack of authority and autonomy and prevented the system from being operational. In contrast, a few NPVC and PI participants in Jordan and Oman pointed to their countries’ PV centres’ official recognition as a strength since it provided it with increased visibility and significance.
“This [the establishment of an official PV department as a strength] is because it was a section of a department before, therefore was not that much importance placed on the section in terms of the reports received and increasing their numbers.”(Participant 1, NPVC, Oman)
“The lack of a dedicated PV department is a weakness… the dedicated department is very important to act on a legal basis with proper staff, with proper infrastructure, with proper independent decisions, to have the full structure, full capacity to work with a proper PV system.”(Participant 17, NPVC, Kuwait)
A few members of Jordan’s NPVC believed that the NPVC’s affiliation with the NMRA was also a point of strength due to the NMRA’s extended reach and authority.
“Being part of the regulatory body is good for PV in that you have the tools, you have the law, you can go see patient files, do further investigations within the hospitals. That’s why I think it’s our strength to be part of the regulatory body.”(Participant 7, NPVC, Jordan)
An important element of a PV system is the existence of an authoritative instrument, e.g., a national policy document or a legislative provision enacted by the appropriate arm of government to support PV activities. Only Jordan’s system possessed legislation for PV. A few participants from the Jordanian NPVC referred to the presence of a legal statute for PV as a strength of the system, which provided them with the necessary tools to monitor and enforce the implementation process across all stakeholders. A few participants from Kuwait’s NPVC and PI believed that the lack of a PV legal framework was a shortcoming as it meant that PV activities were undertaken without legal backing, thus preventing members of the NPVC from ensuring that pharmaceutical companies complied with decisions on PV, e.g., performing a leaflet change. Interestingly, none of Oman’s participants mentioned the absence of a statutory provision as a weakness as part of the discussion on system strengths and weaknesses.
“…we feel tied up with the fact that we haven’t got a legal framework, so that’s a big weakness… the activities are being carried out, but the activities are being carried out with no umbrella, there’s nothing that protects them.”(Participant 11, NPVC, Kuwait)
A country’s medicines regulatory authority or agency acts as an important stakeholder and focal point for promoting PV. Jordan’s NMRA was the only one that was independent of the country’s MOH. A few participants from the PI in Jordan cited the NMRA’s autonomy in decision making and authority in dealing with pharmaceutical companies as a strength of the PV system.
“The fact that the drug authority and the PV centre are separate from the MOH is, in my opinion, a strength. . A drug authority, which is an entity that gives and takes back the marketing authorisation, are controlling the industry through this, so if you don’t report, and you don’t have a system, and you are not compliant with regulations, we have the authority to withdraw your marketing licence. The MOH does not have this authority.”(Participant 14, PI, Jordan)
Availability of a regular and sustained funding source is necessary for running a PV system. All three countries lacked a dedicated PV budget, and thus financial resources were obtained through the NMRA’s (Jordan) or the MOH’s (Oman and Kuwait) budgets. However, only a few participants from the NPVC, regional PV centres, and PI in Jordan commented on this issue as hindering activities such as training workshops for healthcare providers (HCPs) or awareness-raising campaigns. Hence, there was a reliance on obtaining funding from outside sources.
“…we don’t have a budget for things like printing materials, conducting training outside. When you perform training outside you need coverage to sponsor the event, to provide meals for those attending. We don’t have a budget here at the Jordan Food and Drug Administration (JFDA) for our department for these activities. So, you need sponsors from outside to implement these things.”(Participant 2, NPVC, Jordan)
A PV system needs trained staff according to the expected total full-time equivalents required to enable the PV centre to fulfil all its essential duties and responsibilities. All three countries’ PV systems were similar in terms of the number of staff working at the NPVC. The three countries’ NPVC members and a few industry participants, as well as a few participants from Jordan’s regional PV centres, agreed that staff shortages were a weakness. This caused delays in work that must be done regularly or on a scheduled basis, e.g., entering ADR reports in the national database; review of PV reports, i.e., periodic safety update report (PSUR) and risk management plan (RMP); or publication of a bulletin/newsletter for PV information dissemination.
“It’s [the lack of staff] affecting our work in that we have many PV activities to do, for example, we have to enter reports onto the VigiFlow, which should be done regularly, but is not. So, once we have time then we are entering our reports into VigiFlow. So, this is affecting our implementation, for example, we should by now have completed the inspection on all companies and all drug stores, but we have not. There is also training and awareness campaigns, which is not being done according to the scheduled program.”(Participant 2, NPVC, Jordan)
“This [staff shortage] is the major factor, because for example when you want to study a PSUR you need teamwork to be able to do this quickly. The files for the PSUR are large. One person cannot review every file for every medicine. Also, we are receiving PSURs every six months for every medicine.”(Participant 1, NPVC, Oman)
A few of Jordan’s and Oman’s NPVC and industry participants pointed to the scarcity of individuals with PV expertise and staff turnover due to the large workload that came with working in PV which exacerbated this problem. This, in turn, meant a loss of continuity in terms of the team members working in the department in addition to the loss of time and effort spent in training them.
“…the turnover of staff between the departments also, it is a weakness that we spend time and money to do training for [a] certain individual and then he will go to another department.”(Participant 7, NPVC, Jordan)
Oman was the only country where PV was incorporated into the national curriculum of HCPs (pharmacists and nurses), however none of the country’s participants commented on this issue as part of the discussion on system strengths and weaknesses. Contrastingly, a few industry participants from Jordan and Kuwait believed that PV’s lack of incorporation into HCPs curriculums was contributing to a lack of knowledge and awareness regarding ADR reporting among health workers and as such was a shortcoming of their respective countries’ PV systems.
“…in other countries, HCPs’ awareness is very high. It is part of their education in the universities. Here, it’s not implemented yet, so the HCPs, they are shaky, shall we inform or not? How to report? When to report? What to report? Still, their awareness and the level of education… [has] not reached the level of other people [in other countries], so it’s still not high. The awareness level is not high.”(Participant 13, PI, Kuwait)
The WHO PV indicators include the existence of a qualified committee that can provide advice and technical assistance as an important component of the PV system. Only Jordan had a PV advisory committee consisting of HCPs representing different sectors. A few members of Jordan’s NPVC and regional PV centres viewed the presence of this committee, which provided advice to the NPVC on the basis of its members’ varied expertise as a strength. In comparison, a few members of Oman’s NPVC viewed the absence of such an advisory committee from their system as a weakness.
“Another positive is the presence of the Health Hazard Committee, which has benefitted us a lot since it is composed of individuals representing different sectors and from different healthcare professions.”(Participant 6, NPVC, Jordan)
“…I always think that we [the NPVC] are sitting in a remote position and we are not in the practising side… we are not able to find out whether it is the prejudice among the healthcare professionals or the patients that they say it is ineffectiveness, or whether it is actual ineffectiveness which is happening.”(Participant 5, NPVC, Oman)
21.2. Core Process Indicators
The WHO identifies the number of ADR reports received annually as one of the measures of the PV system’s activity. The volume of reports generated within the population in Oman was higher than in Kuwait (31.88 versus 16.58 reports/100,000 population, respectively). Similarly, the WHO’s guidance refers to the number of cumulative reports in the national ADR database since its inception as another measure of system activity. Oman’s NPVC had collected more ADR reports since the PV systems’ inception than that of Kuwait (19,731 versus 890 reports, respectively). A few NPVC and regional centre participants in Jordan and the NPVC in Kuwait, in addition to some industry participants from Jordan, all cited low ADR-reporting rates as a weakness in their PV systems. Interestingly, a few industry participants from Oman mentioned that this was a problem mainly within the private healthcare sector. Low ADR reporting rates prevented the NPVCs from obtaining a clear view of ADR prevalence in the country and hindered making locally relevant drug safety decisions. Participants cited multiple reasons for the low ADR reporting, including poor knowledge, awareness, and/or attitude of reporters towards PV, as well as lack of mandatory HCP reporting legislation.
“Although HCPs may encounter patients with ADRs, some of them don’t know that [they have encountered an ADR], or some of them don’t know that they have to report it, or that it’s important to report it. So, I think that one weakness is that not all HCPs report ADRs.”(Participant 3, peripheral PV centre, Jordan)
Oman had a higher percentage of satisfactorily completed ADR reports submitted to their NPVC compared to Kuwait (84.3% versus 58.9% respectively), and unlike in Kuwait, these reports were submitted to WHO’s VigiBase. When asked about their views on the strengths and weaknesses of the PV system, a few members of Jordan’s regional PV centres and Kuwait’s NPVC cited poor quality of ADR reports as a weakness and thus a high percentage of the ADR reports received were of little value.
“Even though we have 1000 reports, I believe that 70–80% of them are of poor quality. And personally, I know that in one year I provided the PV centre with more than 160 reports, and I later found out that only 40 of them were very useful. …But unfortunately, we never worked on the reports in terms of their quality, we never did statistics on the reports, we don’t know what the gap is, what is the problem with our reports, why are our reports not of good quality.”(Participant 4, regional PV centre, Jordan)
21.3. Core Outcome Indicators
According to the WHO, the PV system’s ability to detect signals indicates its capability of ensuring drug safety. Neither Oman’s nor Kuwait’s NPVC had detected any signals during the past five years. Interestingly, none of the participants in these two countries cited this issue as being a weakness of their respective countries’ PV systems. However, a few participants from Jordan’s NPVC, regional PV centres, and PI pointed out that the inability to detect signals arising from the data obtained through local ADR reporting was a weakness of the system. The lack of signal detection hampered drug safety decision making and was attributed to the low quantity and quality of submitted ADR reports.
“One of the reasons [for the deficiency in signal detection] is that we don’t have enough data, quality data, and the people at the PV centre they focus on collecting the reports without taking it for a further step of analysis and investigation. I think this as well is an issue that our industry has because it is not only the duty of the healthcare system or the health authorities, but also one of the responsibilities of the MAH.”(Participant 4, regional PV centre, Jordan)
The WHO points out that the number of regulatory actions taken by the NPVC provides a measure of regulatory decisions made, on the basis of PV activities, to ensure drug safety. Although regulatory actions exclusively on the basis of local PV data were not taken by the NPVCs in both Oman and Kuwait, it was acknowledged that regulatory actions on the basis of a combination of local and other countries’ data had been taken. A few participants from Kuwait’s NPVC brought up this issue when discussing low ADR reporting rates as a weakness of their PV system.
“…we need more reporting to have our own decision-making process based on our own data in Kuwait. We don’t want to depend on international data. We need to depend on our own data to take into consideration our lifestyle, our raised diet, concurrent medications, morbidity and so on, so that’s why this [i.e., under-reporting] is one of the weaknesses and one of the barriers that we need to overcome.”(Participant 17, NPVC, Kuwait)
32. Complementary Indicators
32.1. Complementary Structural Indicators
Interviewees in Kuwait indicated that the NPVC did not have access to a computerised case-report management system, which hindered their ability to adequately analyse local data. On the other hand, a few NPVC interviewees from Jordan and Oman cited their centres’ use of the WHO-provided case-report management system VigiFlow as a strength because it provided them with a database for report management and storage as well as performing statistical analysis.
“…the IT system [is a weakness], it’s very important for our work to get a proper database and to have a system such as the VigiFlow or the VigiLyze and VigiBase to help get a broader vision of the different cases worldwide. For signal detection, it’s very important to have a system as well, to help get the proper signal as quickly as possible and as efficiently as possible.”(Participant 17, NPVC, Kuwait)
32.2. Complementary Process Indicators
Neither Oman nor Kuwait possessed data on HCPs’ and patients’ awareness levels. Oman’s NPVC had organised more PV training sessions for HCPs and therefore trained more individuals compared that of Kuwait. However, neither country’s NPVC had organised training sessions for the public. A few participants from Oman’s NPVC and PI believed that a strength of their country’s PV system was the increased levels of awareness, particularly among HCPs, which was contributing to improved ADR reporting. This observation was attributed, in part, to the NPVC’s continuous efforts to increase awareness levels. In contrast, some industry participants from the three countries, a few NPVC participants from Jordan and Kuwait, and a few participants from Jordan’s regional PV centres mentioned a lack of awareness regarding PV among both HCPs and the public as a weakness. Participants further believed this to be one of the main reasons for the low ADR reporting rate.
“A point of strength is that there is now awareness. I feel the first step that we took was to increase awareness of HCPs and the general public. This resulted in us receiving many reports.”(Participant 10, NPVC, Oman)
“.the awareness campaigns are still not strong enough. We don’t hear in Kuwait, I didn’t hear that there is a committee for PV or an awareness campaign, to increase awareness of the patients.”(Participant 13, PI, Kuwait)
32.3. Complementary Outcome Indicators
Only in Oman were figures available on the percentage of preventable ADRs and medicine-related birth malformations, and both were low. No information was reported on the remaining eight indicators in this group for either Oman or Kuwait.
