Strategies and interventions to strengthen pharmacovigilance systems in low- and middle-income countries: A scoping review

Objectives
The slow progress of pharmacovigilance (PV) in low-and-middle-income countries (LMIC) raises questions about core challenges on the growth of PV, and the appropriateness of strategies used so far to develop PV. Therefore, this scoping review aims to describe strategies and interventions to strengthen PV in LMIC and to propose recommendations for future investments in PV capacity building.

Inclusion criteria
Publications included were primary studies, articles, and policy and guideline papers, describing interventions to strengthen PV in LMIC. 

Methods
The review was conducted following the Joanna Briggs Institute (JBI) guidelines on conducting scoping reviews. Literature searches were performed in MEDLINE, EMBASE, Web of Science, PDQ-evidence, CINAHL and relevant websites from 1990 to January 2021. Two reviewers independently screened titles, abstracts and full-texts. One reviewer performed data extraction and descriptive analysis, which were reviewed by two other reviewers.

Results
10,922 unique titles were screened and 152 were eligible for full text review. Of these, 57 and an additional 13 reports from grey literature fulfilled eligibility criteria for inclusion in the review. These were grouped into two categories: i) Interventions aimed at increasing PV knowledge and adverse drug reactions (ADR) reporting (45 papers), primarily education of healthcare professionals (HCP), alone or in combination with other interventions such as mobile and electronic reporting; ii) Interventions aimed at strengthening various components of the national PV system (25 papers), describing strategies or mixed interventions implemented at the national level, targeting different components of the national PV system.

Conclusions
Results of this review suggest that educating HCP on ADR reporting is the most common approach to build PV capacity in LMIC. Though important, education alone is insufficient and should ideally be organised within the holistic framework of strengthening national PV systems, with a focus on building capacity for advanced activities such as signal detection.
Methods
This scoping review included primary research, both qualitative and quantitative, that described interventions or strategies to strengthen pharmacovigilance (PV) capacity, as well as policy and guideline papers from national regulatory authorities (NRA). An initial limited search of MEDLINE, EMBASE, Epistemonikos, Joanna Briggs Institute (JBI) Database of Systematic Reviews and Implementation Reports and Web of Science was undertaken to identify articles of interest. This search strategy was defined in MEDLINE and was adapted for each database above using the Polyglot Search Translator. The search was performed on 25 Jan 2021 in the following databases: Ovid Medline, Ovid Embase, CINAHL via Ebsco, Web of Science core Collection, PDQ Evidence. Sources of grey literature included Google Scholar, websites of technical agencies such as WHO, and websites of selected NRA. A simpler search strategy was defined.

Identified citations from the searches were collated and uploaded into EndNote X9.3 (Clarivate Analytics, PA, USA) and duplicates removed. Three batches of 100 titles and abstracts were tested until two reviewers agreed on the selection. Two batches of 10 full-text articles were tested until agreement on article selection. The results of the search and the study inclusion process were reported in full and presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review (PRISMA-ScR) flow diagram (Figure 1: Prisma flow diagram – selection of relevant records).

Abstracts of articles were selected if they met the following inclusion criteria:

Peer-reviewed papers, and policy papers within the last 30 years (1990 to 2021) that described strategies and intervention to establish or strengthen national PV systems in LMIC
 Papers describing the capacity of national PV systems if these included interventions to develop PV
 Articles that described national PV systems and governance

Data were extracted using a data extraction tool developed for the purpose by the reviewers. Extraction parameters included the author, country, year of publication, objective of the research, nature and description of the intervention, the outcome, the challenges encountered and the lessons learnt. The extracted data were presented in a descriptive summary aligned with the objectives of the review. 

Articles were further divided into two categories:

1) Articles describing interventions aimed at increasing pharmacovigilance knowledge and reporting of adverse events.

2) Articles that described interventions aimed at building or strengthening various components of the national PV system.