Strengthening private-sector medicine systems to tackle the persistence of poor-quality medicines in Africa: a proof-of-concept study Poor-quality medicines, containing little or no active ingredient - whether through deliberate fraud, poor manufacturing practice or post-manufacture deterioration - represent a major public health threat in low/middle-income countries (LMICs): responsible for more than 200,000 under-5 deaths each year in Africa and contributing to antimicrobial drug resistance. Efforts by governments and international agencies to curb the problem through improving detection rates, tightening regulation and public education have been hampered by the economic realities of medicine supply in resource-poor, high-need contexts, but also - we suggest - by a failure to apprehend fully the complex workings of medicine supply systems, particularly beyond the public sector.   Private-sector medicine systems can be characterised as 'complex systems' involving multiple dispersed actors with no central organising authority. Recent developments in the study of complex systems have revealed how the actions of individuals can combine to have non-intuitive effects on the system as whole. This has significant implications for well-intentioned policy interventions based on 'common sense' intuition, which may have unwelcome unanticipated consequences.  Our ultimate goal is to understand - and predict - the workings of complex medicine systems in order to inform effective interventions to minimise the penetration of poor-quality products in LMICs. This will require: mapping complete medicine supply chains; understanding the motivations/behaviours of buyers, sellers and regulators; developing sophisticated computational models to simulate the system; and engaging stake-holders to co-design evidence-based interventions. This is an ambitious project which needs careful groundwork through a proof-of-concept study with the following objectives and activities:  (1) To assess fieldwork feasibility in these contexts and validate research instruments: Very few people have attempted to trace a full medicine supply chain in an under-regulated context. In order to assess feasibility, safety and ethical issues, we will map a limited number of medicine supply chains starting at retail outlets across Ghana and Tanzania and moving upwards to point of manufacture, obtaining as much relevant information as possible at each stage. Research instruments will be validated in each local context, and re-validated across contexts to ensure consistency.  (2) To develop our understandings of the structure and operation of private-sector medicine systems: Geographically weighted analysis will be employed to describe the structure/organization of supply systems (length, number of transaction points, degree/level of vertical 'collapse', etc.) and investigate spatial dependencies in the data. Thematic analysis of ethnographic data and secondary sources will be used to understand actors' decision-making and behaviour at each point.  (3) To build Agent-Based Models (ABMs) simulating medicine systems, based on empirical data: We will build a sequence of ABMs simulating medicine supply systems in Ghana and Tanzania as 'complex systems'. These models will allow us to understand, and ultimately predict, how individual behaviours might affect the system as a whole. We will develop 'user-friendly' models to use with policy-makers, highlighting potential unintended consequences of interventions.  (4) To develop and evaluate strategies for engaging relevant actors (market, regulatory, political) in the research and intervention design:  In each country, we will convene  National Stake-holder Groups (NSGs), with policy, regulatory and high-level market actors and Project Working Groups (PWGs), comprising 'on-the-ground' supply-chain actors (buyers, sellers and regulators). Through a series of collaborative workshops, we will work with 'user-friendly' models to identify potential 'bottlenecks' or problematic behavioural logics that might underpin interventions. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.