DOI: 10.5061/dryad.2547d7wzs
title: Building functional and sustainable pharmacovigilance systems - an analysis of pharmacovigilance development across high-, middle- and low-income countries

description: 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.
description: 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).
description: # Building functional and sustainable pharmacovigilance systems - an
 analysis of pharmacovigilance development across high-, middle- and
 low-income countries
 [https://doi.org/10.5061/dryad.2547d7wzs](https://doi.org/10.5061/dryad.2547d7wzs) ## Description of the data and file structure ## 1.     Interview guide - presented as Supplemental File 1 (.docx) Qualitative data were collected through semi-structured interviews built around the theme ‘Strategies to build functional and sustainable pharmacovigilance systems – an analysis of pharmacovigilance implementation in high-, middle- and low-income countries’. An interview guide (Additional file 1) was developed based on the study’s objective and on the previously performed scoping review(1). The interview guide was divided into five sections with a total of 30 questions: 1.     Key informant’s role in the national pharmacovigilance (PV) system 2.     Organization of the national PV system 3.     PV and health system development 4.     PV and pharmaceutical development 5.     The way forward in building 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. Verbal informed consent for the use of information provided in the research and for the interview recording was obtained at the start of each interview. The interviews were conducted by the first author via Zoom videoconferencing (Zoom Video Communications Inc.) over a nine-month period, from November 2021 to July 2022. ## 2.     Codebook - presented as Supplemental File 3 (.docx) The Framework Method was used for the thematic analysis of qualitative data (2). The respondents’ statements from the interviews were transcribed verbatim by the first author and deductive coding was used to code the transcript. For this purpose, a codebook was developed. The codebook outlined the categories, codes, and subcodes with the corresponding description of the codes and assumptions or rationales for collecting the data. ## 3.     Qualitative data framework matrix - presented as Supplemental File 4 (.xlsx) The Framework Method was used for the thematic analysis of qualitative data (2). The respondents’ statements from the interviews were transcribed verbatim by the first author, and deductive coding was used to code the transcript. The codes were clustered into categories and Microsoft Excel (Microsoft Corporation, 2016) was used to summarize and ‘chart’ each transcript into a matrix consisting of subcodes, codes and categories. Twelve categories, clustered into four themes based on the objectives of the interviews emerged from the qualitative study. The analytical level used for the analysis of the interviews was the categories: 1.     Triggers and motivation for PV 2.     Core PV challenges 3.     Organisation and structure for PV 4.     Stakeholder coordination 5.     Procedures for PV activities 6.     PV system financing 7.     Focus of capacity building 8.     Strategic plan for systematic approach 9.     Influence of healthcare systems on PV growth 10.  Leveraging the health system for PV in LMIC 11.  The influence of the pharmaceutical development 12.  Engaging marketing authorisation holders (MAH) in PV To avoid the possibility of identifying the respondent through their job title and the organisation for which they worked, the respondents’ countries, organisations and job titles are not included in the framework matric. Furthermore, any responses that could provide a hint for possibly identifying the respondents were  edited such that the text is completely anonymised. ## 4.     Online survey questionnaire - presented as Supplemental File 2 (.docx) Quantitative data were collected using a standardised questionnaire (Additional file 2), informed by the interview questions. The questionnaire was set up in ODK ([https://opendatakit.org](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 by email and WhatsApp Messenger (WhatsApp Inc.) between November 2022 and February 2023 and three reminders were sent to non-respondents. ## 5.     Checklist for Mixed Methods Research - presented as Supplemental File 5 (.docx) The Checklist for Mixed Methods Search (MMR) Manuscript Preparation and Review was consulted when preparing the manuscript. ## 6.     Survey data PivotTable (.xlsx) Quantitative data collected in ODK will be extracted as CSV (comma-separated values) file and cleaned. There were initially 31 variables, representing each question in the online questionnaire. After cleaning, variable B3 and B4 were merged. To avoid the possibility of identifying the respondent through their, job title and the organisation for which they worked, the respondents’ countries, organisations and job titles are not included in the survey data table provided (variables A1 to A3). Text fields were restructured and standardised to facilitate analysis. Twenty-seven variables were included in the analysis: 1.     Years of PV experience 2.     Influence on PV system 3.     Assessment with WHO-GBT 4.     Maturity level 5.     Other assessment 6.     Competent staff 7.     Health system influences PV 8.     Health system levels 9.     PV integrated at each level 10.  Opinion on integrating PV at each level 11.  Pharmaceutical development influencing PV 12.  Legal provisions for industry 13.  Industry involved in PV 14.  Industry fees used for PV 15.  Opinion on using industry fees for PV 16.  Strategic PV plan 17.  Other plan 18.  Stakeholder coordination 19.  PV system financing 20.  Is there PV without external financing 21.  Donor alignment 22.  PV priority area 23.  Proportion of advanced activities 24.  Vaccine contribution 25.  PV tools contribution 26.  PV approach adequate 27.  PV recommendation ## Sharing/Access information All data sources used in the submission have been appropriately cited and referenced in the publication. Data were derived from the following sources: ·  Qualitative data were collected through semi-structured interviews with key informants representing national and global PV stakeholders (National Regulatory Authorities, National Immunization Programs, Non-Governmental Organisations, technical and donor agencies) ·  Quantitative data were collected using a standardised questionnaire provided by key informants representing national and global PV stakeholders