The public social policy and programme decisions that are made in low-income countries have critical effects on human social and development outcomes. Unfortunately, it would appear that inadequate attention is paid to analysing, understanding and factoring into attempts to reshape or change policy, the complex historical, social, cultural, economic, political, organizational and institutional context; actor interests, experiences, positions and agendas; and policy development processes that influence policy and programme choices. Yet these can be just as critical as the availability of research or other evidence in influencing decision making on policies and their accompanying programmes and the resulting degree of success or failure in achieving the original objectives. Ghana, a low-income developing country in sub-Saharan Africa, embarked on a national policy process of replacing out-of-pocket fees at point of service use with national health insurance in 2001. This paper uses a case study approach to describe and reflect on the complex interactions of context with actors and processes including political power play; and the effects on agenda setting, decision making and policy and programme content. This case study supports observations from the literature that although availability of evidence is critical, major public social policy and programme content can be heavily influenced by factors other than the availability or non-availability of evidence to inform content decision making. In the low-income developing country context there can be imbalances of policy decision-making power related to strong and dominant political actors combined with weak civil society engagement, accountability systems and technical analyst power and position. Efforts at major reform need to consider and address these issues alongside efforts to provide evidence for content decision-making. Without an analysis and understanding of the politics of reform and how to work within it, researchers and other technical actors may find their information to support reform is not applied effectively. Similarly, without an appreciation of the need for critical technical analysis to support decision making rather than an indiscriminate use of political approaches, political actors may find that even with the best of intentions, desired policy objectives may not be attained.