FormalPara Key Points

During the 18-month pharmacovigilance enhancement project that aimed to increase adverse event reporting in the Abidjan region of Côte d’Ivoire, 1427 health care professionals at 91 facilities were trained and mentored in adverse event reporting.

Thirty-three adverse event reports were received in the 8-month period (January to August 2018) before implementation versus 85 after 3 months and 361 after 18 months of project implementation.

This enhanced adverse event reporting was achieved with the support and partnership of national pharmacovigilance experts from the Ministry of Health, regulatory authority, academia, and public health programmes, as well as technical and financial partners.

1 Introduction

Spontaneous adverse event (AE) reporting to a competent authority, such as a national regulatory authority, has been the conventional approach to pharmacovigilance (PV) surveillance of medicines and vaccines since the early 1960s [1, 2]. Most low- and middle-income countries (LMICs), including those in sub-Saharan Africa (SSA), rely on passive surveillance models that are generally easy to implement and inexpensive, but underreporting has been a major challenge [3, 4]. Low rates of spontaneous AE reporting are often due to suboptimal PV systems for reporting AEs, a lack of awareness among health care professionals (HCPs), limited financial resources, high workload, unclear policies, and incomplete legal or regulatory frameworks [4,5,6]. Consequently, up to 2015, less than 1% of all individual case safety reports (ICSRs) in the World Health Organization (WHO) global safety database, VigiBase, were submitted by African countries, with 55% of these originating from Morocco, Nigeria, and South Africa [7].

In passive surveillance systems, HCPs have primary responsibility for overseeing the spontaneous identification and reporting of AEs. As the frontline contact with patients, the HCP is the cornerstone for spontaneous reporting of suspected AEs, assuring the accuracy and completeness of reports, with a critical role in providing information that enables rare and unexpected safety signals to be detected [8]. The efficiency of passive surveillance could therefore be enhanced through additional training of HCPs [4, 6, 9].

The main objective of the PV enhancement project that started in 2016 in selected SSA countries (Malawi, Côte d'Ivoire, and the Democratic Republic of Congo) was to raise awareness of safety surveillance and improve routine reporting of suspected AEs through PV training and mentoring of HCPs, thereby aiding the detection of emerging safety signals in these countries [10, 11]. This was achieved via in-country engagement, PV training, and mentoring of HCPs at their facilities, and financial support for the project. Planning and implementation of the PV enhancement project were built on a principle of partnership between GlaxoSmithKline (GSK), the non-governmental organisation PATH, and the Ministry of Health, national health authority, and the PV department (national PV centre) of each country [11].

Results from the pilot project in Malawi showed that regular PV training and mentoring were effective in enhancing passive safety surveillance, but transmission of reports to the national PV centre required further improvement [10]. Here, we present findings from the PV enhancement project in Côte d’Ivoire. PV activities, which began in this country in 1988, were initially limited to academia but evolved into institutional activities, managed by the Vigilance Unit within Department of Pharmacy, Medicine and Laboratories (DPML) in the 2000s. In 2010, the national PV system was created and the country joined the WHO Programme for International Drug Monitoring [12], obtaining access to the global safety database, VigiBase [13]. In April 2014, the country adopted a national PV policy [14].

PV activities in Côte d’Ivoire are now coordinated by the Vigilance Unit of the Ivorian Pharmaceutical and Regulatory Authority (AIRP; previously DPML). The AIRP collaborates with the Clinical Pharmacology Department of University Félix Houphouet-Boigny (U-FHB), which is the reference centre of the National Committee of Pharmacovigilance (NCP). The NCP was created in 1988 to oversee the collection of AE reports from 20 regional committees; this has since increased to 33 regional committees, one in each health region. Each committee is responsible for organising PV activities within their respective regions, performing the investigations decided by the NCP and preparing information to be shared with HCPs and the general population. However, none of the regional committees is currently functional in Côte d’Ivoire and all PV activities are therefore limited to the central level coordinated by the AIRP. Understaffing at the AIRP has been a limiting factor for nationwide PV training.

Data from VigiBase indicate that only 28 ICSRs (0.28 ICSRs per million person-years) were submitted from Côte d’Ivoire from 2010 to 2015 [7]. In a 2006 survey of 157 randomly selected HCPs in Côte d’Ivoire [15], only 11% had received PV training and 8% had reported AEs, with none of them knowing that adverse drug reaction (ADR) reporting was compulsory according to national regulations. The HCPs recommended an improved reporting system, with easier access to reporting forms and telephones, PV training, feedback to HCPs, involvement of the health districts in the AE reporting procedure, and communication of PV legislation or policy to HCPs [15]. Following these recommendations, the DPML (subsequently AIRP) has collaborated in various projects and initiatives funded by different partners to strengthen the national PV system in Côte d’Ivoire and improve AE reporting.

Here, we describe the conceptual approach, or roadmap, for the PV activities implemented as part of the PV enhancement project in Côte d’Ivoire, as well as the achievements, challenges, and lessons learned from this collaborative project.

2 Methods

2.1 The Côte d’Ivoire Health Care System

The health care system in Côte d'Ivoire is under the responsibility of the Ministry of Health and Public Hygiene (MHPH) and constitutes the public sector, private sector, and traditional medicine. The public sector comprises administrative and medical components, each with three levels. The administrative component contains a central level that includes, among others, the Ministerial Cabinet and related services, an intermediate level currently made up of 33 regional offices, and a peripheral or operational level composed of 86 health districts responsible for the implementation of primary health care. The medical component of the public sector is primarily supported by the state and classified according to primary (urban and rural health care centres), secondary (regional and general hospitals), and tertiary care. The tertiary health care facilities (HCFs) include four university teaching hospitals (Centre Hospitalier Universitaire, CHU), five specialised national institutes, and four other national public institutions [16]. The private sector includes clinics, hospitals, specialist practitioners, infirmaries, and pharmacies.

2.2 The PV Enhancement Project in Côte d’Ivoire

The objectives of the project in Côte d’Ivoire were to improve post-marketing safety monitoring of medicinal products through PV training and mentoring of HCPs, and increase AE reporting in selected HCFs in the Abidjan region. Ethical approval was therefore not required. The national PV stakeholders agreed to implement the project in the Abidjan region, which has a population of five million inhabitants. This region was identified as lacking both PV focal point training and trained HCPs.

The project was implemented from the end of August 2018 to February 2020. The main stages of the project are presented in Fig. 1.

Fig. 1
figure 1

Project roadmap showing the main phases of the PV enhancement project in Côte d’Ivoire. AE adverse event, HCF health care facility, HCP health care provider, KPI key performance indicator, PV pharmacovigilance

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2.3 Project Initiation and Planning

After submitting a letter of intent to the MHPH in September 2016, an initiation meeting was held from 28 November to 1 December 2016 to endorse the project. This brought together representatives from GSK, PATH, MHPH, WHO country office, Expanded Programme on Immunisation (EPI), national PV experts, and the DPML (currently known as AIRP, but referred to in this manuscript as the DPML because the Vigilance Unit was under the DPML at the time of project implementation).

The initiation meeting was followed by a planning meeting on 22 February 2017 with the national PV stakeholders, GSK, and PATH to discuss project implementation and to define key performance indicators (KPIs) for monitoring and evaluating progress. A collaboration agreement was signed between the Côte d’Ivoire DPML and GSK before the start of project implementation on 27 August 2018.

2.3.1 Selection of HCFs

The HCFs selected for this project were district referral hospitals (general hospitals) and other HCFs, based on patient consultation rates. Ninety-one HCFs were selected within the two health care regions of Abidjan: Abidjan 1 Grands Ponts (37 HCFs) and Abidjan 2 (54 HCFs). In Abidjan 1 Grands Ponts, there were 29 HCFs in six health districts, six general hospitals, one private clinic, and one private pharmacy, and in the Abidjan 2 region, 44 HCFs in six health districts, seven general hospitals, and three private clinics (Table 1; Supplementary Table S1).

Table 1 Summary of PV trainings provided to HCPs in Abidjan, Côte d’Ivoire, and numbers of AE reports received centrally by the Vigilance Unit
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2.3.2 Critical PV Personnel

Personnel important for project delivery included PV focal points, the national PV coordinator, and the PV data manager. No new positions were created; instead, existing infrastructure and personnel were engaged for sustainability. Forty focal points (20 per health care region) were identified, trained and engaged in training HCPs at their facilities: 12 for the 12 health districts, 13 for the 13 general hospitals, and two for the five private facilities, as well as 11 focal points for monitoring AEs following immunisation (AEFI) for each district (apart from the Marcory-Treichville district, which had instead a focal point at each of the two district general hospitals), and one for each of the two Abidjan health care regions in order to establish two regional PV hubs. Of the 40 focal points, 26 were pharmacists, 10 were clinicians, and four were pharmacy assistants. The EPI and health district focal points were based at the health district offices and were responsible for the HCFs within their district, while the focal points for the general hospitals and private facilities were based within their respective facilities.

A pharmacist from the Vigilance Unit of the DPML was designated as PV coordinator to lead and coordinate PV activities as part of this project and nationally. The PV coordinator had prior experience in national PV initiatives and partnerships, including PV training in conjunction with AEFI monitoring associated with vaccination programmes. To support effective data management, a dedicated data manager role was established at the Vigilance Unit, with responsibility for data entry into the Vigilance Unit’s PV database (Excel spreadsheet) and the global PV database (VigiBase). However, VigiBase data entry did not occur until the end of 2019.

2.3.3 Key Performance Indicators

Various KPIs were discussed and validated by the national PV experts to ensure systematic evaluation of the project’s performance in the Abidjan region. No baseline AE reporting data were available specifically from this region, only national data showing 20 and 74 AE reports were received at the Vigilance Unit in 2015 and 2016, respectively, and 10% of identified AEs underwent causality assessment by the Vigilance Unit in 2016. Four categories of KPIs were proposed: (A) volume of AE reports; (B) efficiency of AE report transmission and data entry; (C) quality of the AE reports; and (D) quality of the central response to the AE reports received. Expected proportions were set for each KPI where possible, based partly on experience from the pilot project in Malawi [10].

  1. A.

    Volume of AE reports

  1. KPI 1.

    The number of AE reports received at the Vigilance Unit.

  2. KPI 2.

    Proportion of AE reports received at the Vigilance Unit, calculated as the number of AE notifications drawn up and sent by HCPs, and received centrally by the Vigilance Unit, divided by the number of notifications expected to be received centrally during the implementation period (since it was expected that all AE reports that were made by HCPs would be received by the Vigilance Unit eventually, the expected proportion was 100%).

  3. KPI 3.

    Proportion of serious AEs, as identified from all AE reports received and reviewed at the Vigilance Unit (no expected proportion set because of lack of previous data from Côte d’Ivoire). A serious AE was defined as standard, i.e., as an AE that results in death, is life-threatening, requires hospitalisation or prolongation of hospitalisation, or results in persistent or significant disability or a birth defect.

  1. B

    Efficiency of AE report transmission and data entry

  1. KPI 4.

    Proportion of AE reports delivered to the Vigilance Unit within 72 h, calculated as the number of reports transmitted by the focal point or HCP within 72 h of when the HCP completed the AE notification divided by the total number of AE reports received centrally at the Vigilance Unit (expected proportion, 50%). Proportion of AE reports delivered to the Vigilance Unit within 30 days (expected proportion, 100%) was evaluated as a supplementary analysis.

  2. KPI 5.

    Proportion of AE reports received, examined, and entered into the Vigilance Unit’s PV database (Excel spreadsheet) within 48 h (expected proportion, 100%).

  3. KPI 6.

    Proportion of AE reports received, examined, and entered into VigiBase (expected proportion, 90%).

  1. C

    Quality of AE reports

  1. KPI 7.

    Proportion of AE reports received that were complete, i.e., contained information considered mandatory for a valid AE case report: the reporter, event, patient, and suspected medicinal product (expected proportion, 80%).

  1. D.

    Quality of central response to AE reports received

  1. KPI 8.

    Proportion of AE reports for which causality assessment was performed for identified AEs by the Vigilance Unit (no expected proportion set because of few previous data from Côte d’Ivoire).

  2. KPI 9.

    Proportion of AE reports for which feedback was provided to the reporter. Feedback (at the least, acknowledgement of receipt) was expected for all AE reports received (expected proportion, 100%).

The KPIs were to be evaluated by the national stakeholders and GSK/PATH every six months and at the end of the project.

2.4 Project Implementation

2.4.1 PV Trainings

Project implementation began with a “Training of Trainers” workshop for the focal points, held in Grand-Bassam, Côte d’Ivoire, 27–30 August 2018. The sessions included trainings on AEFI and ADR classification, sensitisation on the importance and impact of vaccination, case studies on how to notify an AE, group presentations, and sharing of real-life experiences of the challenges of AE reporting. Interactive sessions encouraged the active participation of all attendees. On Day 2 of the workshop, a roundtable discussion allowed focal points to share what they had learned from the previous day’s training and how they could impart PV sensitisation within their HCFs. All participants received a certificate of attendance, reinforcing the value of the training. The trainers were recognised as country PV experts: a clinical pharmacologist from the University of Bouaké, a vaccinologist from the EPI, and a pharmacist from the Vigilance Unit (also the national PV coordinator).

Trained focal points delivered 1- to 2-h abridged PV trainings to HCPs at the selected HCFs, with the aim of raising awareness among HCPs of the importance of spontaneous AE notification and explaining how to report AEs. The trainings covered topics such as the importance of detecting and reporting suspected AEs to the national PV office, the process of reporting AEs, the minimum and essential information required, and a case study on AE reporting. Trainings were provided every two to three months. The first two rounds of training were provided by the national PV coordinator and subsequent rounds by trained focal points, with new HCPs trained during each session.

2.4.2 PV Mentoring

The national PV coordinator visited the selected HCFs every three months to supervise and mentor the PV activities of the focal points and to participate in the HCP training sessions. Mentoring was done through supervision visits, telephone calls, short message service (SMS) messages, WhatsApp group reminders, email, and hand delivery of material during face-to-face meetings. Additionally, during each sensitisation visit, focal points of selected general hospitals mentored at least seven previously trained HCPs, while the district and AEFI focal points mentored at least five HCPs per HCF. Each focal point received a monthly airtime award, which enabled them to communicate freely with HCPs in the HCFs under their responsibility during the sensitisation and mentoring phases.

2.4.3 AE Report Form Completion, Transmission, and Data Entry

The national AE reporting form was the primary tool for AE notification. The HCPs were encouraged to report ADRs, AEFIs, traditional medicine-suspected AEs, and any incidents in newborns, whether or not medicinal products were prescribed, including information on where the medicinal product was purchased (pharmacy, drug store, or roadside vendor). The original AE reporting form (Supplementary Material S2 and S4) was revised in April 2019 to include essential information facilitating causality assessment, such as information on risk factors, medical history, batch number, etc. (see Supplementary Material S3 and S5).

The AE report transmission scheme in place in Côte d’Ivoire is shown in Fig. 2. However, the focal points and HCPs were encouraged to use all possible means for transmitting completed AE report forms directly to the Vigilance Unit, including email, SMS, postage, and hand delivery, for prompt data entry and assessment of the reports. Because Côte d’Ivoire had no national AE database, an Excel spreadsheet was used to collate the AE data, and this information was entered later into VigiBase.

Fig. 2
figure 2

Official route for flow of information on AEs in Côte d’Ivoire: the transmission pathway for reporting AEs (mostly adverse drug reactions) to the AIRP (previously DPML) Vigilance Unit followed by data entry into the WHO global database (VigiBase). Dotted lines indicate causality assessment by the Clinical Pharmacology Department of University Félix Houphouet-Boigny. E-notification refers to data entry via the Med Safety medical mobile app (used since 2020). AEs adverse events, AIRP Ivorian Pharmaceutical and Regulatory Authority, DPML Department of Pharmacy, Medicine and Laboratories, HCF health care facility, MHPH Ministry of Health and Public Hygiene, UTH University teaching hospital, WHO World Health Organization

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Weekly accountability sessions were to be held internally by the Vigilance Unit to classify the quality of the reports and detect any signal requiring causality assessment for discussion and assessment by the Clinical Pharmacology Department of U-FHB, the reference centre of the NCP.

2.4.4 Project Communication

The PV coordinator regularly communicated project updates to the focal points. Posters were developed by the DPML and displayed in sensitised HCFs and other HCFs across the country to raise awareness and remind patients and HCPs of the importance of spontaneous AE reporting.

National PV stakeholder meetings were organised within 12 months of project implementation to update the PV experts on project progression. Two technical committee meetings were held during the 18-month implementation period to discuss the progress of the project, including successes and challenges. During HCP trainings and mentoring visits, challenges were discussed, along with proposals on how to improve reporting. Due to the COVID-19 pandemic, the end-of-project meeting planned in March 2020 with national stakeholders, GSK, and PATH could not be held.

2.4.5 Funding

GlaxoSmithKline Biologicals SA provided financial support for the PV trainings and mentoring visits, and acquisition of office equipment (such as laptops, hard disks, printers, antivirus software, etc.). Allowances for the PV coordinator and data manager were also funded.

3 Results

3.1 PV Trainings

Forty focal points took part in the “Training of Trainers” workshop. A total of 1427 HCPs from 91 HCFs participated in abridged PV training between September 2018 and December 2019: 611 from the Abidjan 1 Grands Ponts region and 816 from the Abidjan 2 region (Table 1, Supplementary Table S1).

3.2 AE Reports Received Centrally

Between January and August 2018, before project implementation, 33 AE reports were submitted centrally to the DPML Vigilance Unit, with 11 (33.3%) from the Abidjan region, while in the first three months of project implementation (September to December 2018), 85 reports were received, with 71 (83.5%) from the Abidjan region (Fig. 3). Overall, during the 18-month implementation period (September 2018–February 2020), 361 AE reports were received from HCFs nationwide, with 278 (77.0%) from the Abidjan region; 81 from Abidjan 1 Grands Ponts and 197 from Abidjan 2 (Table 1). Of the 278 AE reports from Abidjan, 208 were from the 91 HCFs where PV trainings had been provided as part of this project and 70 were from 28 HCFs where an unknown number of HCPs had been trained by the PV coordinator during AEFI trainings before vaccination campaigns (supplementary Table S1). Pharmacovigilance training was therefore provided to 119 HCFs within the Abidjan region. Most of the AE reports notified to the DPML were ADRs (217; 78.1%) and the remainder (61; 21.9%) were AEFI reports. These AEFI reports were submitted directly by the HCFs; an unknown number of additional AEFI reports was notified to the EPI office and not forwarded to the Vigilance Unit. Most AE reports (236, 84.9%) were submitted by email to the Vigilance Unit. A few reports were delivered in person and the PV coordinator collected some during mentoring visits.

Fig. 3
figure 3

Adverse event (AE) reports received centrally by Vigilance Unit before and following implementation of the pharmacovigilance enhancement project in Abidjan, Côte d’Ivoire

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3.2.1 Categorisation of AE Reports

Categorisation of the data according to the gender and profession of the reporter showed a predominance of female reporters both nationwide (62.0%) and in Abidjan (68.0%), and most reports were submitted by medical doctors (47.6% and 59.7%, respectively) and nurses (17.2% and 21.9%, respectively) (Table 2). In Abidjan, 11.5% of reports were submitted by midwives, compared to 8.9% nationally. Primary level HCFs submitted most AE reports at the national level (52.1%) and in Abidjan (62.9%), followed by secondary level HCFs (27.4% and 22.7%, respectively) (Table 2). Nationally, 32 reports were received from the pharmaceutical industry (none from Abidjan) and few reports were from private facilities (14 reports; 13 from Abidjan).

Table 2 Origin of adverse events reported following implementation of the PV enhancement project in Côte d’Ivoire, nationally and in the Abidjan region
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The most frequent suspected medicinal products specified in the AE reports were anti-retroviral, anti-malarial, and anti-tuberculosis drugs, and vaccines (Table 2).

3.3 Key Performance Indicators

The KPIs relating to the 278 AE reports received centrally from the Abidjan region are shown in Table 3 and supplementary Table S2. Several KPIs (proportion of AE reports received; proportion of reports entered into the local PV database; proportion entered into VigiBase) reached or nearly reached the expected proportion (Table 3). Most AE reports were entered into the Vigilance Unit’s PV database (Excel spreadsheet) within 48 h (99.6%) and were entered into the WHO PV database, VigiBase (86.7%). Overall, 69.0% of AE reports contained complete information. The proportion of AE reports that concerned serious AEs was 19.4% (54 serious AEs, of which five were serious AEFIs).

Table 3 Key performance indicators (KPIs) of the PV enhancement project, as indicated by expected proportions and actual proportions achieved (of total 278 AE reports) in Abidjan, Côte d’Ivoire
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Few AE reports (44; 15.8%) were delivered to the Vigilance Unit within 72 h of notification, although further analysis showed that 114 (41.0%) were delivered within 30 days. Both proportions were much lower than the expected proportions (50% and 100%, respectively).

In terms of the quality of the central response to AE reporting, weekly accountability sessions held by the Vigilance Unit led to causality assessments for 41 AEs during the project (supplementary Table S2), which were all ADRs. The bulk of causality assessments was performed only after the end of the project by the Clinical Pharmacology Department of U-FHB, the reference centre of the NCP. Detailed results of the causality assessments will be presented in a separate publication. Feedback on identified AEs was provided by the PV coordinator to focal points or HCPs for only one AE report (an ADR), which concerned a death following medication.

4 Discussion

The GSK PV enhancement project was implemented in the Abidjan region of Côte d’Ivoire with the aim of improving passive safety surveillance by increasing spontaneous reporting of AEs, ultimately aiding the detection of safety signals from the region. This was achieved via in-country engagement of PV stakeholders and training and mentoring of 1427 HCPs in 91 selected HCFs in the Abidjan region over 18 months. The number of AE reports received nationally by the central Vigilance Unit increased from 33 in the eight months before implementation to 361 reports during the 18-month implementation period, with 278 (77%) reports originating from the Abidjan region alone. This confirms the benefits of raising awareness of PV and implementing mechanisms for mentoring HCPs, who are the cornerstone for effective spontaneous AE reporting.

These results are similar to those observed following the implementation of this project in Malawi [10, 11], where 228 and 511 AEs were notified after 18 and 30 months, respectively. With more prolonged support to HCPs, it is expected that PV will become better established in the health care systems of the pilot countries and further progress will be made. This has been observed in Eritrea, where the MHPH has led PV initiatives since 2012, including integration of PV into all public health programmes, assignment of PV focal points to HCFs, and anchoring PV in hospital medicine and therapeutic committees [17]. As a result, over 95% of HCPs are sensitised in PV nationwide [17] and, in 2017, 64% of HCPs reported an ADR at least once [18]. Between 2014 and 2019, the reporting rate to VigiBase reached 646 ICSRs per million inhabitants per year [17], indicating that Eritrea had achieved a functional PV system, with maturity level 3 on the WHO rapid benchmarking assessment [19]. In Côte d’Ivoire, the 1427 trained HCPs reported 208 AEs, representing an AE reporting rate by HCPs of 15% during the 18 months of project implementation. Most of the AE reports notified to the DPML were ADRs, with relatively few AEFI reports. However, the actual number of AEFI reports is likely to be higher because some of those submitted directly to the EPI office were not channelled to the national Vigilance Unit. These undocumented AEFIs were not included in our analysis. We also note that, while most of the AE reports came from the HCFs participating in this project, some AE reports were received from 28 HCFs where HCPs received training on AEFIs before vaccination campaigns. This suggests that sensitisation activities through the PV enhancement project, such as displayed posters, or PV sensitisation activities during the launch of new products, may have enhanced AE reporting in HCFs not selected for this particular project.

One of the reasons identified for failures in reporting AEs during the PV enhancement project, and described previously [11], is the negative perception among HCPs toward AE reporting. Some HCPs failed to report AEs because they believed their occurrence was expected, or they neglected to complete AE report forms because they were unfamiliar with routine PV requirements or PV activities added to their already high workload. Fear of litigation among some HCPs could also have contributed to lower AE reporting rates due to a belief that they would be held responsible for the reported AEs, as highlighted elsewhere [20,21,22,23]. In Côte d’Ivoire, some HCFs that received PV training but did not notify AEs gave the rationale that many more HCPs needed to be trained and mentored for PV to become established in their routine functioning rather than as a short-term project outcome.

Further review of the AE reports received by the Vigilance Unit during this project showed that approximately 25% of AE reporting occurred within the first three months of the implementation period, implying that training increased awareness of PV, and underlining the need for repeated training until reporting becomes part of the routine practice of HCPs. In Abidjan, 60% and 22% of reports were made by clinicians and nurses, respectively, higher than nationally (48% and 17%, respectively), signifying the positive impact of HCP training and mentoring. Primary care HCFs submitted most reports, probably because these represent the first entry point into the national health system, with sizeable patient populations from both urban and rural areas. The large number of patients seen in primary care reinforces the need to train HCPs in these facilities in AE reporting and to keep focal points motivated, improving their awareness through regular meetings and yearly refresher training. Although there were fewer AE reports from secondary and tertiary HCFs, these have a higher likelihood of consulting serious cases, so PV reinforcement through intensified trainings and mentoring of HCPs in these facilities is also essential. This should be done in collaboration with hospital management and focal points representing each ward or unit in these HCFs, with regular meetings on the challenges and the way forward. The most common suspected medicinal products were anti-retroviral, anti-malarial, or anti-tuberculosis drugs, and different types of vaccines, which was probably due to their widespread use and the organised nature of associated public health programmes [24,25,26,27]. However, much is left to be done to effectively integrate PV sensitisation and AE reporting procedures in conjunction with the launch of new medical products within these programmes.

In terms of KPIs, there was uncertainty in the proportion of AE reports delivered to the Vigilance Unit during the project because of the unknown number of AEFI reports received by the EPI office and not sent to the Vigilance Unit. It is also not guaranteed that all AE reports were sent from HCFs since this project was conducted in the context of passive rather than active surveillance. Consequently, the actual proportion of AE reports made and delivered to the Vigilance Unit is likely to be below 100%. Just over two-thirds (69%) of reports contained mandatory information on the patient, event, suspected medicinal product, and reporter. Although this was below the percentage achieved in Malawi (98%) [10], this is considered a positive outcome in view of the limited budget and the fact that forms were completed by HCF staff rather than PV personnel. In Côte d’Ivoire, a national database was not available, so AE data were reviewed and entered into an Excel spreadsheet database developed by the Vigilance Unit, and this was achieved within 48 h for almost all AE reports received (99.6%). Most of the AE reports (87%) were entered into the global safety database, VigiBase, but this did not occur until the end of 2019 due to lack of personnel. While only 44 (16%) AE reports were delivered to the Vigilance Unit within 72 h, a supplementary analysis showed that 41% were delivered within 30 days. This delay in report transmission was due to a variety of reasons, such as the remoteness of some HCFs, no internet access, a lack of awareness on the importance of immediate transmission for prompt signal detection, and the lack of a simple electronic tool for HCPs to transmit AE forms on a real-time basis.

Efficient feedback has been identified as one of the factors that can motivate HCPs to report AEs [4, 17, 28], reinforcing the importance of reporting medication-related harm and prompting future involvement in PV activities. However, in our project, the proportion of AE reports for which feedback was provided to the reporter was under 1%, with feedback given for only one ADR, which concerned a death following medication. In this case, the Vigilance Unit did the field investigation under the supervision of the Clinical Pharmacology Department of U-FHB, which did the causality assessment. In Côte d’Ivoire, there is no systematic case investigation for serious ADRs, in contrast to serious AEFIs, for which case investigations are performed by the EPI office, but in this project relatively few AEFIs were reported centrally. It is crucial to include feedback mechanisms as a standard operating procedure for the central PV unit.

Another KPI concerned reporting of serious AEs. The proportion of total AE reports that concerned serious AEs was 19.4%. This was higher than the proportion reported in Malawi (5.3%), where 12 of 228 AEs notified over 18 months were serious [10]. However, it is broadly in line with the percentage reported following an analysis of over 3 million ADR reports submitted to VigiBase, which found that 16% were serious, with no differences in distribution across country income groups [29].

The PV enhancement project in Côte d’Ivoire had several strengths (Table 4). Its programme of training and regular mentoring of HCPs was successful in enhancing AE reporting. The experience of the PV coordinator in nationwide PV initiatives and partnerships, and the accuracy of mapped PV interventions in the country, enabling the identification of the Abidjan region as lacking PV training, were also advantages. The engagement of the MHPH and PV experts dedicated to implementing the project and thereby improving the Côte d’Ivoire health care system also facilitated collaboration. Another strength of the project was that most of the focal points were clinicians and pharmacists as opposed to EPI coordinators in Malawi, who were mainly engaged in vaccine campaigns and did not have a strong influence within HCFs [10, 11].

Table 4 Strengths and challenges of the PV enhancement project in Abidjan, Côte d’Ivoire
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Challenges faced by the project (Table 4) included the late start of project implementation activities due to administrative delays in reviewing and signing the legal agreement [11]. The heavy workload of HCPs also prevented some from complying with the training schedule and AE reports were not always transmitted to the Vigilance Unit in a timely manner for reasons already discussed. The absence of a simple communication route for AEs was another drawback, since there were different reporting pathways for suspected ADRs, AEFIs, and AEs from traditional medicines, which was confusing to HCPs, as discussed previously [11]. Another challenge was the lack of dedicated data management personnel and the lack of a national safety database. In terms of the KPIs, calculation of the proportion of AE reports delivered to the Vigilance Unit was limited by the unknown number of undocumented AE reports. Moreover, causality assessment was performed for a minority of AEs identified by the Vigilance Unit, with the remainder performed one year after project implementation by the Clinical Pharmacology Department of U-FHB. The Vigilance Unit lacked the capacity to perform in-depth causality assessments and, although an Expert Review Committee for causality assessment existed in Côte d’Ivoire, it did not meet during the 18-month period due to a lack of funding and coordination. Empowerment of the committee is crucial to enable causality assessment meetings to be held promptly once a signal is detected. Finally, there was no electronic tool for fast transmission of AE data by HCPs. The Med Safety medical mobile app [30, 31], which is compatible with VigiBase, has been used by the Vigilance Unit and the EPI in Côte d’Ivoire to transmit AE data since 2020 [32]. Between June 2021 and March 2022, 3227 AE reports were submitted to VigiBase from Côte d’Ivoire as a result of the availability of this tool and PV training during the COVID-19 pandemic. Once HCPs are trained on the use of Med Safety, the ICSR submission rate is expected to increase even further.

5 Conclusion

The training and mentoring programme in the PV enhancement project in Côte d’Ivoire increased the number of AE reports submitted centrally. This enhanced AE reporting illustrates the benefits of improving the national PV system with the support of national PV experts and technical and financial partners. In particular, collaborative efforts among national and international PV experts were crucial to avoid duplication of activities and to implement PV where gaps were identified. Our experience also emphasises that, for PV to become part of the routine functioning of HCFs, there is a need for reinforcement via repeated trainings and mentoring of HCPs. To achieve this, it is important to have in place PV focal points to coordinate PV activities and hold regular review meetings within their HCFs to discuss challenges, solutions, learnings, and the way forward to improve AE reporting. Yearly refresher training of PV focal points should also be organised for effective and continuous coordination, as well as a prompt feedback mechanism to motivate HCPs, acknowledging and providing outcomes of the notified AEs. An efficient and effective bridge in communication between the central PV unit and the EPI office is important for prompt signal detection; in Côte d’Ivoire, AEFI data were frequently sent via the EPI office. Additionally, for the future development of PV activities in Côte d’Ivoire and other LMICs, the use of electronic tools compatible with VigiBase should be supported to enable prompt AE reporting and faster safety signal detection, as demonstrated during the COVID-19 pandemic.

The outcomes, successes, and challenges of this pilot experience offer lessons for improving the safety surveillance of medicinal products in SSA and other LMICs, through the development of PV activities adapted according to local health care systems. Our experience shows that PV training and mentoring of HCPs, and effective collaboration between public health programmes, the EPI, and the national PV unit, are crucial to ensure all AEs are assembled at the central level, to adequately monitor the safety of medicines.