Reforming the innovation system to deliver affordable medicines: a conceptual framework of pharmaceutical innovation as a complex adaptive system (forest) and theory of change.

Background: The current mainstream pharmaceutical innovation system (PIS) is driven by the market-based logic of charging the highest prices societies will bear. Outcomes include unaffordable medicines, restricted access and pressure on health budgets. How can the innovation system change to deliver fairly-priced medicines?

Methods: We inductively developed a novel conceptual framework of the PIS as a complex adaptive system (CAS) analogous to a forest. We constructed a database of 140 pharmaceutical innovation initiatives that sought to address global public interest objectives such as fair pricing or missing innovation. We found a critical mass of initiatives clustered around four areas: pandemic preparedness, neglected diseases, rare diseases and antibiotics, which we conceptualised as niches within the ecosystem. We reviewed the literature on how each niche had emerged and evolved, conducted interviews, and organised workshops with experts on each niche. Finally, we identified from the literature an initial list of 'levers' of change in the PIS, supplemented them with additional levers found in each niche, then compared across niches.

Results: We found that actors created niches in the broader system by purposefully problematising an issue, then pulling on one or more of three levers: mobilising new resources, changing the roles of or creating new actors, and/or changing societal norms or legal rules. A wide range of actors - including governments, funders, R&D practitioners, or civil society groups - could pull these levers, and the order in which they were pulled was not fixed, consistent with a CAS.

Conclusions: Parts of the vast pharmaceutical innovation system have changed to deliver more affordable medicines by design. Such change has occurred largely within specialised niches, responding to evolving societal norms about the purpose of pharmaceutical innovation. Actors can achieve larger-scale change by further expanding and/or solidifying these niches through changes to resources, actor roles, norms and rules.