Pharmacogovernance in Low- and Middle-Income Countries: a case study of Brazil and Kenya by Kathy Moscou A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Department of Pharmaceutical Sciences University of Toronto © Copyright by Kathy Moscou 2016 Pharmacogovernance in Low- and Middle-Income Countries: a case study of Brazil and Kenya Kathy Moscou Doctor of Philosophy Department of Pharmaceutical Sciences University of Toronto 2016 Abstract Adverse drug reactions (ADRs) are a global public health threat leading to illness, disability and death. Yet, few countries have a framework to guide postmarket drug safety policy despite increasing access to pharmaceuticals worldwide and the growing trend of gathering information about medicines in the postmarket (rather than the premarket) period. This gap is addressed by ‘pharmacogovernance’, a new theoretical concept that is introduced in this thesis. Pharmacogovernance is defined as the manner in which governing structures; policy instruments; and institutional authority (e.g., ability to act, implement and enforce norms, policies and processes) are managed to promote societal interests for patient safety and protection from ADRs. An analytic framework for examining pharmacogovernance is presented that clarifies the relationship between governance and pharmacovigilance in order to explain how pharmacogovernance influences pharmacovigilance. The research investigates how and why the State (at all levels), global actors and the pharmaceutical industry interact to affect pharmacogovernance and ultimately postmarket drug safety in a low and upper-middle income country (Kenya and Brazil); and how patterns of governance (e.g., devolved and decentralized) affect pharmacovigilance. A new application for ii Network Governance Theory is presented to explain state and non-state actors’ interactions regarding pharmacovigilance. Qualitative research methods that included key informant interviews, document analyses and a scoping review were conducted. Key findings show that the pharmacogovernance framework can guide policy making for postmarket drug safety. Policy, law and regulations are important for advancing pharmacovigilance and ensuring enforcement however gaps in other pharmacogovernance domains may impede pharmacovigilance in areas such as risk communication and regional equity in postmarket surveillance. The current funding model for pharmacovigilance in Brazil and Kenya is inadequate leading to ad hoc investment in pharmacovigilance and fluctuating priorities. Positive interdependency between pharmacogovernance structure, institutions and networks comprised of global actors can enhance pharmacogovernance and pharmacovigilance. Research results illuminate how in Brazil and Kenya investments in pharmacogovernance processes, institutions and network engagement may further improve pharmacovigilance. Investments include: strengthening medicines regulatory authorities; establishing a sustainable funding model for pharmacovigilance; strengthening social participation and inclusion in regulatory decisions pertaining to pharmacovigilance; and increasing interdependency amongst pharmacogovernance structure, institutions, and networks. iii Acknowledgments The journey to completing a doctorate is an arduous one made easier by a league of mentors, family and friends. I have many people to thank for the guidance and assistance they provided along my journey. First, I would like to thank my PhD supervisor Dr. Jillian C. Kohler, Advisory Committee members Dr. Joel Lexchin, Dr. Anita McGahan and Dr. Suzanne Cadarette who provided the mentorship and guidance that contributed to my success. I would also like to thank Dr. Barbara Mintzes, the external appraiser of my thesis for her thoughtful comments and Dr. Diana Menya, my research supervisor at Moi University, for enabling my research in Kenya. Next, I would like to thank my family for encouraging me throughout my journey. A special thank you goes to my husband Dr. Gervan Fearon who was instrumental in encouraging me to pursue a doctoral degree. He supported me in many ways during the past five years by accompanying me to late night study and writing sessions at coffee shops, reading numerous drafts of my thesis and providing constructive feedback. I would like to thank my sister Dr. Susan Moscou. Susie is the first person in my family to earn a PhD. She has been a fabulous mentor and role model. She set the bar for my family that we can pursue and achieve a doctoral degree. I am extremely proud of my daughter Dr. Gyasi Moscou-Jackson who received her PhD in nursing this past year. Gyasi and I enrolled in doctoral studies simultaneously. It has been an incredible mother-daughter bonding experience to walk this path together. While encouraging her and advising her through roadblocks in her doctoral journey, I have on occasion found that my words of advice were invaluable to me in overcoming similar setbacks. I would also like to thank my parents for encouraging their children to think about how to make a contribution to the betterment of society at large, thus influencing my decision to conduct research on pharmacogovernance. Lastly, I would like to that Dr. Paola Casalvina and João Batista Da Silva Junior for their contribution to the scoping review. iv Table of Contents Acknowledgments.......................................................................................................................... iv Table of Contents ...........................................................................................................................v List of Tables ...................................................................................................................................x List of Figures ................................................................................................................................ xi List of Appendices ........................................................................................................................ xii List of Abbreviations ................................................................................................................... xiv Chapter One: Introduction ...............................................................................................................1 1.1 Context .................................................................................................................................1 1.2 Background ..........................................................................................................................1 1.2.1 Postmarket drug safety issues in LMI countries ......................................................2 1.2.2 Pharmacovigilance in LMI countries .......................................................................5 1.2.3 Governance and postmarket drug safety ..................................................................6 1.2.4 Global actors and the spread of pharmacovigilance policy norms ..........................9 1.3 Statement of the problem ...................................................................................................10 1.3.1 Rationale for Examining Pharmacogovernance in LMI countries ........................10 1.3.2 Rationale for Investigating Pharmacogovernance in Brazil and Kenya ................11 1.3.3 Decentralization and devolved governance ...........................................................13 1.4 Rationale for the research ..................................................................................................13 1.5 Purpose of the research ......................................................................................................15 1.6 Theoretical Framework ......................................................................................................16 1.7 Overview of thesis chapters ...............................................................................................22 Chapter Two: Methods .................................................................................................................26 v 2.1 Preamble ............................................................................................................................26 2.2 Research Methods ..............................................................................................................26 2.2.1 Case Study .............................................................................................................27 2.3 Data Sources and Methods of Data Collection ..................................................................29 2.3.1 Semi-structured interviews ....................................................................................30 2.3.2 Documentary Evidence ..........................................................................................37 2.3.3 Scoping Review .....................................................................................................38 2.4 Data Analysis .....................................................................................................................40 2.4.1 Thematic Analysis .................................................................................................40 2.4.2 Semantic Analysis ..................................................................................................41 2.5 Validity and Reliability ......................................................................................................41