A  Comparative Study of Pharmacovigilance System in Nigeria and Ghana using Indicator Based Pharmacovigilance Assessment Tools ( IPAT).

doi:10.21203/rs.3.rs-3601971/v1

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A Comparative Study of Pharmacovigilance System in Nigeria and Ghana using Indicator Based Pharmacovigilance Assessment Tools ( IPAT).

https://doi.org/10.21203/rs.3.rs-3601971/v1

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Introduction: Nigeria and Ghana are both members of the World Health Organization (WHO) Program for International Drug Monitoring (PIDM) operated by the Uppsala Monitoring Centre (UMC) in Sweden. The requirements to join the WHO PIDM include submission of 20 reports in the internationally accepted E2B format to UMC and a formal letter from the ministry of health requesting to join the program. Even though the two countries are members of the WHO PIDM, they have different capacities.

Aim: To assess and determine the functionality, scope of operation, strengths and limitations of the national pharmacovigilance systems in Nigeria and Ghana using IPAT indicators as standard.

Method: National PV documents backed by law and other statutory documents governing the PV systems of both Nigeria and Ghana were examined using the WHO indicators. Indicator–based Pharmacovigilance Assessment (IPAT) was developed by WHO to assess PV systems, PV in the two countries were compared by reviewing the government policies on PV. The staff of the pharmacovigilance unit of the National Medicines Regulatory Authorities (NMRAs) were interviewed using WHO Pharmacovigilance Indicators tool. The responses were recorded, and data collected were analyzed.

Results: The PV systems in Nigeria and Ghana were supported by law and regulations in line with international standards. The Standard operating procedures for reporting, processing, and communicating suspected adverse event reports from stakeholders of PV were in place in both countries, but reporting of suspected medicine-related harm from stakeholders was not reported countries. The number of Physician density per 1000 population in Nigeria and Ghana is 0.38 and 0.10. The two countries did not meet the 200 number of reports of suspected ADRs report by 1 million of the population in 2020. The national pharmacovigilance systems in the two countries did not have access to data on drug utilization. The national PV unit in NAFDAC and Ghana FDA scored 69% and 72% respectively using IPAT indicators measuring standard and both met the standard requirements of PV by scoring greater than 60%. The lack of relevant PV regulations and legislation coupled with absence of implementation could be accounted for low scores under some sub headings in IPAT indicators

Conclusion: The national pharmacovigilance systems in the two countries have policy and legal frameworks defined by law and regulation to conduct pharmacovigilance activities. However, the two national PV systems are at different levels of dimension and performance with respect to conducting PV activities. In other to have an effective PV system in both countries, there is a need to formulate and implement strategic PV interventions that will involve all relevant stakeholders, including public health programs, healthcare facilities and professionals, academic institutions, and patients, to build a standard national PV systems.

Medications and Vaccines have benefits and are also considered harmful even when administered within therapeutic doses. Though preventable, these harmful effects are termed adverse drug reactions (ADRs), which are among the significant causes of death in recent times. (WHO, 2021). Pharmacovigilance (PV) is considered an essential instrument to reduce medicines' ADRs in public health and medical practice. (WHO, 2010)

Despite the increase in access to medications in Nigeria and Ghana, there has not been a direct proportion of development in Pharmacovigilance (PV) practices in these two countries; this may be partly due to various challenges in ensuring the safety of medicines and the licensing of newer molecules to be added to essential drug list by the regulatory bodies. (Opadeyi et al., 2018). Other reasons may include inappropriate use of medication, inappropriate prescribing, overwhelmed healthcare institutions and healthcare workers, weak or fragmented drug control/legislation, unlicensed drug markets (at which harmful pharmaceuticals are often sold), inadequate record-keeping of medication exposures and outcomes, including lack of adequate recording of adverse events.

The World Health Organization (WHO) Program for International Drug Monitoring (otherwise known as the WHO Pharmacovigilance Program) has as its primary goal to adopt strategic global pharmacovigilance principles which address these challenges and meet the health needs of low- and middle-income countries.

Medicines, vaccines, and cosmetics have been used to diagnose, prevent, and treat diseases. (WHO. 2019). In addition to their benefits, medicinal products also elicit side effects in humans; these side effects present as unexpected and harmful. Regulatory Authorities (RAs) were bounded by national policies to safeguard the people’s health and the general welfare in their countries. The primary objective of RAs is to protect the public from unsafe medicinal products (SIAPS, 2013, WHO 2019). They are also saddled with the responsibilities of preventing the irrational use of medications and reducing to the barest minimum the availability of fake, substandard, and adulterated medicinal products (Ndomondo-sigola et al., 2017). Availability of drugs for various diseases of public health interest is improving in Africa mainly due to the commitment of national governments through the National regulatory agencies, which were established to manage conditions of public health concern like human immunodeficiency virus (HIV), tuberculosis, and other tropical diseases affecting humans. (Olsson et al., 2015). However, the pace at which medicinal product is being made available in Africa is not on par with the ability of the RAs to ascertain the safety of medicines (Isah et al., 2012). There are 54 RAs in Africa, and each has a varying capacity in terms of PV activities, yet most of them are incapable of performing critical functions expected of RAs (WHO, 2018). There are 54 countries in Africa, and out of these, only 25 had minimal or no pharmacovigilance capacity. Only four of the 54 countries had pharmacovigilance systems with the capability to detect, evaluate, and prevent safety issues, indicating the limited abilities of these countries to monitor medicines’ safety. (David, 2015). It should, however, be noted that the concept of pharmacovigilance covers such areas as product quality, medication errors, and therapeutic ineffectiveness, as well as adverse drug reactions ADRs (WHO, 2018). These areas are essential to the drug regulatory authorities, consumers, and clinicians. Performance metrics such as IPAT are necessary to monitor and evaluate pharmacovigilance and medicine safety systems in countries (WHO, 2015). Efforts to assess and compare PV activities in countries promote the safety of the patients and improve efforts to strengthen PV operations in such countries. (EMA.2022). PV assessment in countries can also help to define the elements of a sustainable PV strategy and suggest areas for improvements as the basis to plan for improved public health and safety of medicines (Radecka et al., 2018). PV evaluation will equally help establish the current capacity for medication safety in a country and allow longitudinal measurement of progress after various intervention programs to improve PV activities in the concerned countries are implemented. (Babigumira et al., 2014)

Nigeria and Ghana are current members of the Program for International Drug Monitoring (PIDM), an arm of WHO operated by the Uppsala Monitoring Centre (UMC) in Sweden. Members of The PIDM are currently more than 150 countries. This made PIDM to have an increasing influence on public health decisions and the development and implementation of (PV) systems. Avorn (2018) submitted that The National Regulatory Authorities (NRAs) that house the PV centers have been created in various countries and they are responsible for developing PV activities and ensuring that ADRs reporting systems work correctly either manually or via the Internet. These reports will be collated and transferred to WHO (UMC) in Sweden and stored in the VigiBase™ global database.

Ghana Food Drug Authority(FDA) joined the WHO PV program as the 65th member in 2001 and as the first country in West- Africa, while Nigeria National Agency for Food Drug Administration and Control (NAFDAC) joined in 2004 (WHO, 2021). The conditions for joining the WHO PIDM include submitting 20 reports in the internationally accepted E2B format to UMC and a formal letter from the ministry of health requesting to join the program (WHO, 2018). Even though the two countries are members of the WHO PIDM, they have different PV capacities.

The Internet has enabled medication regulatory bodies in various countries to connect and cooperate more effectively in reporting ADRs and accessing information. It has equally helped to make prompt decisions on the use of medicines at the national and local levels. Moreover, it also helps make information available on PV, and specific information about medicinal products is made accessible and available to professionals and members of the public through RA’s websites. Hence, ADR reporting and RA’s operations and responsibilities have become more visible.

This paper aims to determine and assess how the PV system operates in Nigeria and what its areas of responsibility are, compared with Ghana, using IPAT PV indicators as standard. The study, therefore, analyses and assesses the PV systems in these two countries through their RAs: the National Agency for Food and Drugs Administration and Control (NAFDAC) in Nigeria and the Food and Drugs Agency (FDA) in Ghana, to identify gaps between the two and suggests the area of improvement.

This was a cross-sectional descriptive study aimed at comparing the PV systems in Nigeria and Ghana using the WHO indicators, Indicator–based Pharmacovigilance Assessment Tool (IPAT). IPAT was a tool developed by WHO to assess PV systems. PV in the two countries was compared by reviewing the government policies on PV and interviewing stakeholders in the National PV directorate/center in NAFDAC, Nigeria, and FDA, Ghana, respectively.

The IPAT tool utilizes evidence-based options analysis and development of relevant and appropriate recommendations which reflects each of the two countries’ local realities, existing regulatory capacity, and priorities, identifying system gaps, and resource availability. Additionally, this indicator-based approach allows longitudinal progress measurement after the recommended interventions are implemented.

IPAT is embedded with a performance system that monitors and evaluates drug safety and PV activities. IPAT functions with 43 indicators subdivided into 26 core and 17 supplementary indicators. The core and additional indicators collectively consider these Medicine safety and PV components five: (i) policy, law, and regulation; (ii) systems, structures, and stakeholder coordination; (iii) signal generation and data management; (iv) risk assessment and evaluation; and (v) risk management and communication. These WHO PV indicators are responded to using the National Policy on Pharmacovigilance and other official handbooks from national regulatory bodies, as well as interviews with the stakeholders of PV at the National PV center in Nigeria and Ghana.

The reviewed policies included the Federal government of Nigeria, National Pharmacovigilance Policy and Implementation framework, 2011& 2012. National Drug Policy 2005, National Quality Assurance Policy for Medicine and Other Health Products 2015, National Agency for Food and Drugs Administration, and Control Act. Ghana National Drug Policy 2004. FDA, Guidelines for Qualified Person for Pharmacovigilance 2012, 2015 and PV System in Ghana, 2016.

An interview with stakeholders having a sizeable responsibility and in-depth knowledge of each country's national pharmacovigilance system. In both cases, the stakeholders are the director of PV centers and the Pharmacists in charge of PV who have given their informed consent. Two person each from NAFDAC and Ghana FDA, making a total of four respondents. They were requested to share the legal and statutory documents and other relevant information as it relates to the PV system in Ghana and Nigeria. They shared sensitive information about safety medication actions taken from 2016 to 2020 in both countries, which are not readily available to the public. The core and additional indicators served as a standard on which the interviews were based. The data from the PV assessment of Ghana and Nigeria were collected and entered into a template designed for the study. This template was designed to accommodate the five pharmacovigilance sections of the IPAT indicators. A comparison of the performance indicators of Ghana and Nigeria is presented using the tables below.

Data analysis

The data analysis was both quantitative and qualitative. The scoring of the IPAT indicators was done with a core indicator recorded as ‘Yes’ and was allocated a score of 2; while a supplementary indicator was recorded as ‘Yes’ and allocated a score of 1. Any core or supplementary indicator recorded as ‘No’ was given a score of 0. These numerical values assigned are in line with the IPAT tool scoring system. This result in a total score of 52 for core indicators and 17 for the supplementary indicators. The score attained by the indicators will be divided by the total score of all the indicators and multiplied by 100. If this value is greater than 60% for each component of health system level, the component is said to meet the standard PV requirements for that health system level (SPS 2011). Results were presented as tables and were used to compare performance of indicators with the same component in the two counties.

Results are based on the five significant indicators from which other indicators stem. These five major indicators are highlighted below:

1 Governance, Policy, Law, and regulation

2 Systems, Structure, and Stakeholder Coordination.

3 Signal generation and Data Management

4 Risk assessment and Evaluation

5 Risk Management and communication

These summarized the core indicators and complementary indicators

Governance, Policy, Law, and Regulation

The PV programs of Nigeria and Ghana were supported by legal instruments such as acts, regulations, and policies (Table 1). These legal documents defined the role of the NAFDAC and Ghana FDA and their mandate to monitor the quality, safety, and efficacy of medicinal products and appliances. The two regulatory bodies are compared in relation to policy, law and regulations governing PV in the two countries.

Table 1

Showing regulation, law and policies governing PV in the two countries.
Country	Act	Regulation	Policy	Guidelines
Nigeria	Poison and Pharmacy Act ,Cap 360 of 1970, NAFDAC Act (CAP.N1 LFN), 2004. Food and Drugs Act Cap 150 of 1990, Counterfeit and fake drugs (miscellaneous provisions) Act, Cap 73 of 1990. Pharmacists Council of Nigeria, Act 91 of 1992.	Good Pharmacovigilance Practice Regulations,2021	Nigerian National Pharmacovigilance Policy and Implementation Framework first revision 2020.	NAFDAC Good Pharmacovigilance Practice Guidelines 2021.
Ghana	Food and Drugs Law 1992 (PNDCL 305B) and the Pharmacy Act, 1994 (Act 489), Traditional Medical Practice Act 2000 (Act 575) National Drug Policy in August 1999 Food & Drugs Law (PNDCL 305B) 1992, as amended by the Food & Drugs (Amendment Act), Act 523, 1996	X	Ghana National Drug Policy 2004	Guidelines for qualified person for Pharmacovigilance 2020.
X missing/not available

Comparison of Pharmacovigilance Performance of NAFDAC and Ghana FDA (Policy, Law, and Regulations)

The IPAT indicators were classified according to their relevance to health system levels and where they could be collected. 39 indicators were used to determine the performance of NAFDAC and Ghana FDA. These 39 indicators for NMRAs are as follows (1.1–1.4, 2.1–2.15, 3.1–3.6, 4.1–4.5, 5.1–5.7 and 5.9–5.10). (23 core and 16 supplementary) and (19 structure, 11 process and 9 outcome) were employed to assess both countries NRAs up to a maximum score of 62 score.

Table 2

Shows the summary of PV performance of both countries at National level using IPAT indicators
PV components	Score (%) Ghana FDA	Score (%) NAFDAC	Outcome Ghana FDA	Outcome NAFDAC
Policy, law and regulations	67 (4/6)	83 (5/6)	Achieved	Achieved
Systems, structure and stakeholders coordination	81 (21/26)	88 (23/26)	Achieved	Achieved
Signal generation and data management	67 (8/12)	50 (6/12)	Achieved	Not Achieved
Risk assessment and evaluation	57 (4/7)	42 (3/7)	Not Achieved	Not Achieved
Risk management and communication	73 (8/11)	56 (6/11)	Achieved	Not Achieved
Overall score	72 (45/62)	(69)43/62	Achieved	Achieved

Table 3

Summary of Pharmaceutical Market in Nigeria and Ghana. This table compares information about the scope of Pharmaceuticals in the two countries under review (Nigeria and Ghana) ,including the Gross Domestic Product (GDP) and health status indicators like the Number of Physicians and Midwives per 1000 population.
Parameters	Country(Nigeria)	Country(Ghana)
Population (July 2020 estimate)	191.000 Million	31.07 million
Gross national income per capita (PPP international 2013)	$ 5,360.000	$ 5,480.000
Physician density per 1000 population (2019)	0.380	0.100
Nursing & Midwifery Personnel density (Per 1000 Population) 2019	1.589	2.700
G.D.P per Capital (2019)	2,028.200	2,275.77
Market size Pharmaceuticals (USD 2019)	607.000 Million	589.000 Million
Number of Medicine registered in (2019)	58,016.000	61,515,000
Total Expenditure on healthcare per capita $ (2019)	217	78

Figure 4.2: Showing Population and Pharmaceutical markets of the two countries in millions

Table 4

Pharmacovigilance Governance at National Levels This table summarizes and compares the PV activities in the two countries using the IPAT indicators as the yardstick. How PV signals are generated, managed, and transmitted, PV systems, and how risks are assessed, evaluated, organized, and communicated in the two countries are highlighted.
Indicators	Nigeria	Ghana
Regulatory Register	Present	Present
Industry reporting of Serious Adverse drug effects (ADE, S) is mandated. (expedite reporting required)	Yes	Yes
Reporting timeline for marketed products ( serious)	7 Calendar days	15 calendar days
Reporting timeline for marketed products (nonserious)	28 Calendar days	60 calendar days
Periodic safety update reports required (PSUR)	Yes (Every 28 days)	Yes (Every six months)
Reporting timeline for Clinical trials (SUSAR)	Seven days	Three days
Monitoring period of new medicine required.	Six months	Two years

Table 5

Showing regulatory framework of PV in Nigeria and Ghana
Indicators	Nigeria	Ghana
PV/Medicine Safety Policy	Available	Available (but not in the public domain)
PV/Medicine Safety in National medicine legislation	Yes	Yes
PV/Medicine Safety in National medicine legislation	Yes	Yes
MAH is mandated by law to report severe adverse drug reactions to the National Regulatory Authority. (NRA)	No	No
MAH is required to conduct post-market Surveillance per stringent regulatory authority Standards	Yes	Yes
Legal provisions for Product quality assurance	Available	Available
Legal provision for Promotion and advertisement.	Available	Available
Regulatory framework	Yes	Limited

Table 6

Showing system, structure, and Stakeholder’s Coordination of PV in Nigeria and Ghana
Indicators Dedicated Budget available for PV activities or PV-Centers	Nigeria Limited	Ghana Available
The annual budgetary allocation for PV activities or PV Centers	Limited	Available
Funds provided by MOH or donors towards PV activities in 2018	Yes	Information not available
The global fund for PV	Yes	Yes
Existence of a quality control lab/unit with a clear Mandate, structure & function	Yes (PQRST)	Yes (PQRST)

Key

Testing of Pharmaceuticals. (Non-biodegradable products) / Q - Testing of biological products such as Vaccines / R- Participation in registration activities / S- Inspection of Industry Quality Control laboratories / T- Collaboration with the Inspectorate to test Samples

Table 7

Showing Risk Assessment and Evaluation (Quality Control Laboratories and PV information Centers in Nigeria and Ghana
Indicators	Nigeria	Ghana
Quality Control lab under the National Regulatory Agency functions of QC lab.	Yes	Yes
QC lab has a documented Quality Management System	Yes	Yes
The WHO prequalifies QC	No	No
PV center has a clear mandate, lab structures, and function	Available	Available
PV information center	Available	Available
Dedicated Staff for PV	Limited	Available
Budget for PV	Non	Limited
National guidelines for PV	Available	Available
SOPs for PV and Quality Control	Available	Available
Medicine Safety advisory committee	Absent	Absent
Quality control committee	Absent	Present

Table 8

Showing PV Stakeholders Coordination in Nigeria and Ghana
Core PV reference materials in PV centers	Available	Available
Core PV topics present in Pre-service training Curricula	No	Yes
Health workers trained in PV & Medicine	Yes	Yes
PV stakeholders Coordination mechanism	Available	Available
WHO program for international drug monitoring membership	Available	Available
Quality Management System for PV & Quality assurance	Available	Available

Table 9

Showing Data Management, Risk Management, and Communication
Presence of a system for Coordination and collation of PV data from all Sources in the Country	Available (Not functional)	Yes
Presence of a local database system for collating PV data from all sources	Post, & Electronics/ in Person	By Post, Electronics
Methods by which reporting forms are typically collected and transmitted to the PV Center / Unit	In Person	Electronics &in-person
PV data transmission complies with the E2B format	Yes	Yes
The data method used	Not specified	Reporting Odd Ratio.

Key

BCPNN - Bayesian Confidence Propagation neural network / ROR -Reporting Odds ratio / RRR - Relative Risk ratio

Table 10

Showing Risk Management and Communication in Nigeria and Ghana.
Presence of a consumer reporting form	Present	Present
Presence of suspected ADR reporting form	Available	Not available
Product quality reporting form	Not Available	Not Available
Medication error reporting form	Not Available	Not Available
Treatment failure reporting form.	Not Available	Not Available

Table 11

Medicine Safety Regulation Action taken beside ADR Reporting, Between January 2019 and September 2019. This table contains information besides ADR reporting but is not readily available to the general public on the websites. Most of the information from interviews with the PV stakeholders in the two countries is also presented here.
Indicators	Nigeria	Ghana
Product Recalls	54	36
Withdrawal of Product License	Nil	Nil
Suspension of Marketing authorization	Nil	Nil
MOH memo/Circular referencing Safety data.	Yes	Yes
Medicine Safety information addressed	Yes	Yes
Regularly published medicine safety bulletins.	Yes ( NAFDAC website)	Yes (Online)
Unregistered products/medicine in the Pharmaceutical market less than 3%	No	No
Medicine safety issues identified from external sources and acted on	Yes	Yes
The time from ADR signal generation to communication to healthcare workers and the public is less than three weeks.	Yes	Yes
Public/community education activities on PV	No	Yes
Medicine safety action was taken other than ADR reporting	Yes	Yes

Table 12

Showing Actual ADR reporting versus expected for NAFDAC and Ghana FDA
Country	Year joined WHO PIDM	Number of ADR reports 2017Dec to Dec.2018	Population Millions (2018)	Expected (200 ADR reports per million population)	Percentage Actual /Expected
Ghana	2001	697.00	27.41	5,482.00	12.71%
Nigeria	2004	130.00	197	39,400	0.32%

Table 13

Spontaneous ICSR per million of Inhabitant submitted 2015–2020
Country	Year joined PIDM	Number of ICSR submitted per million of inhabitants 2015–2020
Ghana	2001	57
Nigeria	2004	2

The WHO Program for International Drug Monitoring recommends that in relation to ADR reporting, the optimal National Pharmacovigilance Centre should send over 200 reports per million inhabitants per year

Limitations of the Study.

All the core and structural indicators developed by the WHO are 63 (Abiri &Johnson, 2019). All were not assessed in this study because some of them are related to health facilities and zonal regulatory offices, but the aim of this study is centered on national regulatory bodies hence the use of IPAT indicators. This meant that the pro data collection process is purely based on the IPAT indicator used as guidelines and information available on Nigeria and Ghana RA’s websites, policy documents made available by the directors and response to interviews granted by the stakeholders of PV in Nigeria and Ghana. A significant limitation of the study is that inferences were made for most of the indicators relying on the information provided by the stakeholders of PV in Nigeria and Ghana. Some other inferences were made for other indicators based on policy documents made available and the information available on the RA’s website for Nigeria and Ghana at the time of data collation and collection.

WHO (1998) defined evaluation as the objective assessment of the relevance, adequacy, progress, efficiency, effectiveness, and impact of a course of action concerning objectives while considering the resources and facilities deployed. Hence the total number of indicators necessary to perform a proper evaluation is likely to vary depending on the aim and objectives of the PV evaluation. Based on the purpose and objectives of this study, addressing the complete set of IPAT indicators that were itemized at the introduction of the article in the study is enough to provide a satisfactory PV evaluation and assessment

The essence of the study is to assess and compare the performance of national PV activities in Nigeria and Ghana. The study is directed to the National medicine regulatory agencies (NMRA) of the two countries to provide a general overview of the current status and performance of the PV systems. In Nigeria and Ghana, the NMRAs possess the policy and legal frameworks authorized by law and regulation to conduct PV activities in their respective countries. The existence of rules, laws, and regulations supporting the PV system is an indication that the countries are committed to maintaining and improving the rational use of medications and access to excellent and standard medicines made available in the pharmaceutical systems. (Barry et al. 2019).

The national PV unit in NAFDAC and Ghana FDA scored 69% and 72% respectively using IPAT indicators measuring standard and both met the standard requirements of PV by scoring greater than 60%. The lack of relevant PV regulations and legislation coupled with absence of implementation could be accounted for low scores under some sub headings in IPAT indicators. The omission of this aspect of legislation in NAFDAC acts limits the capacity of NAFDAC to mandate post-marketing safety commitments of the MAHs. The presence of a legislation, law, policies and guidelines with relevant statements on PV shows that Nigeria and Ghana have demonstrated a high-level commitment to improve medicine safety and hence channel a direction to enhance the PV system of the country. This existence of legislations and regulations also support a strong legal foundation that ensures conformity by relevant stakeholders. There are more PV activities to emulate by Nigeria from Ghana and vice versa in order to enhance PV performance by both countries, these are reiterated in the next chapter.

The measure of the health status as indicated by the Physician per 1000 of the population is 0.380 and 0.100, respectively, for Nigeria and Ghana. (WHO 2019). This figure is far below the standard as stipulated by WHO. World Bank data (2019) which is one physician per 1000 population. Countries like Cuba and Canada have 8.4 and 2.4 respectively. It is saddening to note that most physicians trained in Nigeria and Ghana migrate to the United States and the United Kingdom after graduation, these countries already had 2.8 and 5.6 Physicians per 1000 population in 2019, yet Physicians migrate to these countries for better reward packages and greener pastures.(Opadeyi et al.2018)

The Nursing and Midwifery population per 1000 in 2019 is 1.589 and 2.700, respectively for Nigeria and Ghana. (World Bank data, 2019). The world health report (2006) concluded that at least an estimated 2.5 medical staff (nurses and midwives) per 1,000 people must be available to provide the minimum health coverage with essential primary. Ghana was able to meet this criterion with 2.7, while Nigeria fell short of the number of Nurses and Midwives per 1000. The implication is that fewer nurses are available to provide healthcare services than the number required to provide adequate healthcare delivery in Nigeria. Nigeria has a slightly higher market size in terms of Pharmaceuticals than Ghana, with an estimate of $ 607 million in 2019 as against $ 589 million in Ghana. (World Bank data, 2019). Still, Ghana registered 61,515 number of medicine between 2016–2019.Nigeria registered 58,016 within the same years. Nigeria had a total healthcare expenditure per capita of $217, while Ghana had $78. (World Bank data, 2019).

The Market Authorization Holders (MAHs) involvement in the activities of national pharmacovigilance systems in the two countries is inadequate. In Nigeria, MAHs are expected to contribute to the pharmacovigilance system to improve compliance in both countries. MAHs are expected to contribute to the pharmacovigilance system. This needs to be strengthened to the level of regulation and implementation rather than based on guidelines alone. Generally speaking, the regulatory activities for pharmacovigilance in Nigeria and Ghana is in line with current international standards, and all the regulatory pharmacovigilance centers had the systems and structures to conduct PV activities.

In 2020, Ghana’s FDA, reached WHO Global Benchmark Tool (GBT) performance maturity level 3, joining the National regulatory authority of Tanzania (TMDA) and got the WHO-GBT in 2018 as the first country in Africa. This means Ghana’s FDA & TMDA are stable institutions and well-functioning, with an integrated regulatory PV system (WHO, 2020).

Olison et al. (2010) submitted that the number of ADR reports received from Africa is not sufficient to identify significant drug-related issues. They further went on to encourage African countries to report more because the safety information sourced from the WHO global database might not always be relevant for local settings in individual countries. This is important because data from countries with similar demographics, genetic background, nutritional status and background, and co-morbidities should be in one data repository, such as the WHO VigiBase database so that analysis of the pooled data can be done to provide relevant solutions( Olison et al., 2010).

The NRAs of both countries are faced with limited financial and human resources. The national PV systems in both countries have a specific budget for pharmacovigilance activities; however, even with allocated budgets for PV activities, the budgets need to be improved so that they are well-matched with the resource requirements for enforcement of the respective PV regulations and guidelines in both countries. Financing and continuous financing of PV activities is essential for maintaining PV activities in both Countries. A situation whereby the budget is not available or small as the case in the two countries will not help PV operation in the two countries. During the study period, Nigeria was in the process of implementing new regulations and guidelines concerning PV policy, the last one was reviewed and implemented in 2012. It is therefore imperative that in the new policy or guidelines, issues related to human resources and budgetary allocation for PV activities be emphasized.

The national PV system in both Countries does not have comprehensive pre-service PV training, even though it is recently included in the Pharm D curriculum in the Nigerian Pharmacy program, the impact of the pre-service pharmacovigilance training is yet to be felt either in Nigeria or Ghana.. Preservice pharmacovigilance education is a sustainable and cost-effective intervention that strengthens health systems (SIAPS, 2013). The pre-service PV training in the two countries needs to be strengthened across different healthcare professional training programs. Trainees for pre-service pharmacovigilance training are future healthcare professionals, and it is important that they understand their role in the safety monitoring and safe use of medicines. As reported by Mirhaba et al., (2015) Lack of knowledge of the reporting processes of suspected AEs is the main cause of underreporting. Hence, Pre-service PV training across different healthcare professional programs (Pharmacy, Nursing, and Medicine) when made to include the ADR reporting process may promote reporting according to Lopez et al., (2009). This inclusion of higher learning institutions that provide training for healthcare professionals as stakeholders in the national pharmacovigilance system is crucial for the sustainability of the programs and it will enhance PV performance in both countries.

WHO recommends an ADRs report of 200 per 1 million population in a particular year. Nigeria and Ghana are perpetually categorized as under-reporting in the years under review because they both generated less than 200 reports per 1 million of their population. Hence, Stakeholder coordination needs to be strengthened to increase reporting. Several ways by which ADRs reporting can increase in the two countries include direct patient reporting, effective electronic reporting systems, and mobile phone reporting applications. All these may increase the number of reports.

Nigeria and Ghana do have data on drug importation with NAFDAC and Ghana FDA but none of the two PV systems had a source of data on consumption and prescription of medicines. This suggests that the national PV systems do not have information on the level of drug utilization in the two countries. Drug utilization data at the national level are very important to weigh the potential risk of drug-related harm and assess the public health impact of ADRs. The national PV systems should establish a mechanism to capture medicine utilization data which is the denominator for calculating the rate of reporting ADRs, prioritizing safety signals, and able to assess the impact of regulatory actions.

Generally speaking, most of the information captured in this study was verified using sources of documentation such as legal documents, guidelines, training materials, terms of reference, and national policy papers.

It is pertinent to note that the national PV systems in Nigeria and Ghana are supported by legal instruments and guidelines. Updated regulations or guidelines aiming at complying more with international standards in PV is currently in the pipelines in Ghana and it’s on the verge of being introduced in Nigeria. Despite having legal support and pharmacovigilance systems and structures, limited stakeholder involvement and engagement in the pharmacovigilance systems manifested in very low reporting rates in both countries. In both countries, data collection, management, signal analysis, and decision-making procedures in place.. However, at the time of the assessment, the PV systems did not have the full capacity to systematically identify problems related to pharmaceutical products like Product efficacy and medication error in healthcare delivery systems.

In other to have an effective PV system in both countries, there is a need to formulate and implement strategic PV interventions that will involve all relevant stakeholders, including public health programs, healthcare facilities and professionals, academic institutions, and patients, to build a standard national PV system. The PV systems and structures in Ghana and Nigeria have some similarities still, they also do have some slight differences, and therefore, targeted interventions directed at addressing the immediate needs of the individual countries should be designed.

The researchers are registered pharmacists in South Africa, Ghana, and Nigeria who are also in academia.

Ethical Approval and Informed Consent.

The ethical approval was granted by the Biomedical Research Ethical Committee (BREC) of the University of KwaZulu-Natal on July 30^th, 2020, with protocol reference number: BREC/00001035/2020. The NAFDAC also granted approval on the 24^th of June, 2020, via reference number NAFDAC/PV/PMS/MDG/I/IX to carry out the study. Ghana FDA granted approval to conduct research on PV studies in Ghana on 11^th January 2021 via reference number FDA/HPT/SMC/SMD/VGU/21/0006. Informed consent was sought and given by the stakeholders of PV in Nigeria (NAFDAC) and Ghana (FDA) that granted the interviews.

Consent for Publication

All the authors, give their consent for the publication of the details within the manuscripts to be published in the BMC Health Services Research Journal.

Data Availability Statement

Data sets were generated as shown in the result, but data sharing was not applicable. Data are available from the authors with the permission of BREC, University of KwaZulu-Natal. The data that support the findings of this study are available from the corresponding author, (S.S.Onasanya), upon reasonable request.

Competing Interest

The authors declare that they have no known competing financial or personal interest that could have appeared to influence the work reported in this paper.

Funding

The authors received no funding for this research.

Authors’ Contributions

Author	Role in the study
Onasanya S.S	Data collection and Interpretation of the results. Conduct interviews with PV stakeholders in Ghana and Nigeria. Writing of the manuscript
Yamoah P.	Supervises the manuscript writing Reviews the final draft of the manuscript for submission to the journal
Oosthuizen F	Supervises the manuscript writing Reviews the final draft of the manuscript for submission to the journal

Acknowledgments:

My sincere appreciation goes to the Director General of NAFDAC, The Director of PV and Post-Marketing Directorate, Dr. Fajemirokun , Pharmacist Onu, Pharmacist Seun Adesanya, NAFDAC. The Chief Executive Officer of FDA, Ghana, The Director of PV and Post-Marketing Directorate, and Head of Safety Monitoring Department. Pharm. Tolu Oliyide, my colleague, practicing in Ghana, Pharm. Eric. Of Ghana FDA and Pharm. Funke Sopeinmann, a Pharmacist with the WHO.

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A Comparative Study of Pharmacovigilance System in Nigeria and Ghana using Indicator Based Pharmacovigilance Assessment Tools ( IPAT).

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Results

Governance, Policy, Law, and Regulation

Comparison of Pharmacovigilance Performance of NAFDAC and Ghana FDA (Policy, Law, and Regulations)

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