Background

Detecting, assessing and preventing adverse events and other medicine-related issues necessitate a functional pharmacovigilance system. In many low- and middle-income countries (LMIC), key elements of functional pharmacovigilance, such as effective organisation and procedures for vigilance activities are missing. With increased access to essential and novel medicines in LMIC, and taking into consideration other factors that can influence medicine use and the safety profile of medicines such as the healthcare system, socio-political and genetic factors, LMIC must establish and maintain functional pharmacovigilance systems to ensure adequate safety surveillance of authorised medicines.

Objectives

This research aims to analyse the development of pharmacovigilance systems across high-, middle- and low-income countries and to carve out essential elements for functionality and sustainability of pharmacovigilance systems in LMIC.

Design

A convergent parallel mixed methods design, combining qualitative and quantitative methods.

Methods

Qualitative and quantitative research consisted of semi-structured interviews and an online survey, respectively.

Results

Twelve key informants from ten countries were interviewed and 52 respondents from 36 countries completed the online survey. From the qualitative and quantitative data, we identified nine essential elements for sustainable pharmacovigilance development in LMIC: understanding the drivers of pharmacovigilance development; adequately resolving core system challenges; implementing an efficient organisational structure and good governance; establishing procedures for pharmacovigilance activities; ensuring availability of qualified and trained staff; identifying alternate sources of financing; having a strategic development plan; adequately leveraging the health system; and effectively integrating the pharmaceutical sector in the national pharmacovigilance system.

Conclusions

Findings from this research revealed progress in pharmacovigilance systems in LMIC in the last decade, though significant efforts are still needed to develop these systems to meet global standards. Developing the different areas emerging from this research, within the framework of a holistic, fit-for-purpose pharmacovigilance system strengthening, would enable a comprehensive progression from basic to functional and thus sustainable pharmacovigilance systems in LMIC.

Study design

The study had a convergent parallel mixed methods design, consisting of qualitative and quantitative methods. Qualitative research contained semi-structured interviews. To expand the breadth and range of the study, a quantitative survey was conducted, focusing on the same thematic questions as the semi-structured interviews.

Sampling, setting and study population

To ensure adequate representation of national and global PV stakeholders, study participants included representatives from the NRA, National Immunisation Programmes (NIP), and global technical and donor agencies (hereafter referred to as Technical and Financial Partners [TFP]).

For the interviews, countries were selected based on the publicly available information corresponding to their PV maturity levels, such that all PV maturity levels were adequately represented. Potential participants were contacted via email addresses provided by their organisations, or via regional PV mailing lists. In addition, authors of articles included in a scoping review of strategies to build PV in LMIC, conducted within the context of this research, were contacted by provided email addresses . At least one LMIC from each WHO Region was identified. Sampling was purposive, based on informants’ knowledge and expertise in PV and their decision-making position within the national and global PV organisations concerned. It was deemed sufficient to interview eight to twelve key informants, based on evidence suggesting that saturation can be achieved in a narrow range of interviews particularly in studies with relatively homogenous study populations and narrowly defined objectives.

For the survey, the identification of countries and participants was the same as for the interview. The number of participants was determined based on full membership of the WHO Programme for International Drug Monitoring (PIDM) at the start of the research (i.e., approx. 90 out of 131 LMIC), indicating that at least the minimum requirements for a functional PV system were present.

For both qualitative and quantitative research, the definite sample was determined by the willingness of potential informants to participate in the research. For this study, the countries were categorised according to World Bank Group country classifications.

Data collection

Qualitative data were collected through semi-structured interviews built around the topic ‘Strategies to build functional and sustainable pharmacovigilance systems – an analysis of pharmacovigilance implementation in high-, middle- and low-income countries’. An interview guide (Supplemental File 1) was developed based on the study’s objective and on the previously performed scoping review (21). The interview guide was divided into five sections with a total of 30 questions: 1) key informant’s role in the national PV system; 2) organisation of the national PV system; 3) PV and health system development; 4) PV and pharmaceutical development; and 5) ensuring functional and sustainable PV systems. The interview guide was reviewed by the co-authors for clarity and validity of questions, then pilot-tested by a PV expert not directly involved in the research. Sixteen key informants were invited by email to participate in the interviews and were provided with an overview of the research. Verbal informed consent to record the interview and to use of the information provided by the key informant in the research was obtained at the start of each interview. The interviews were conducted by the first author using Zoom videoconferencing (Zoom Video Communications Inc.) over a nine-month period (November 2021 to July 2022). The duration of the interviews ranged from 60 to 90 minutes.

Quantitative data were collected using a standardised questionnaire (Supplemental File 2), informed by the interview questions. The questionnaire was set up in ODK (https://opendatakit.org) and pilot-tested by a PV expert not directly involved in the research. The questionnaire, in both English and French, was distributed to 80 persons by email and WhatsApp Messenger (WhatsApp Inc.) between November 2022 and February 2023; three reminders were sent to non-respondents.

Data analysis and interpretation

The Framework Method was used for the thematic analysis of qualitative data. The respondents’ statements from the interviews were verbatim transcribed by the first author and deductive coding was used to code the transcript. For this purpose, a codebook was developed with the predefined codes organized into corresponding categories based on the research objectives (Supplemental File 3). The codes were assigned to the transcribed data, line by line, and related sub-codes were created to improve the accuracy of the analysis. The codes were then clustered into categories. Using Microsoft Excel (Microsoft Corporation, 2016) each transcript was summarized and the data were ‘charted’ into a matrix consisting of sub-codes, codes and categories (Supplemental File 4). The data were interpreted, with the identification of patterns, relationships, differences and similarities leading to new thematic groups.

Quantitative data collected in ODK were exported into Microsoft Excel 2016 for analysis using a PivotTable. Data analysis consisted of descriptive statistics, primarily frequencies and percentages for categorical variables.

The Checklist for Mixed Methods Search (MMR) Manuscript Preparation and Review was consulted when preparing the manuscript (see Supplemental File 5 for the completed checklist).