BACKGROUND: The global economic crisis imposes severe restrictions on budgets allocated to healthcare. Innovative technologies in medicine may improve patient outcomes but such improvements come at a substantial cost, thus limiting the number of patients that may benefit from them. According to current cost-effectiveness analyses (CEA), most innovative interventions are associated with a higher efficacy and higher costs compared with the standard of care. These analyses do not account for the budget impact associated with implementing the interventions on all eligible patients. Even when a new intervention is highly cost-effective, healthcare systems may not be able to adopt it due to substantial budgetary impacts. Implementing a substantially lower-cost intervention to a substantially wider population, accepting inferior per-patient outcomes, may improve overall health outcomes under a restricted budget. OBJECTIVES: Develop an innovative health technology assessment (HTA) model that combines CEA and budget-impact analyses, thus enabling to compare the impact of intervention alternatives on the entire intended use population, under a pre-specified budget constraint. METHODS: We identified the following steps to be included in the model formulation: 1) Define the intended use and the target population. 2) Define two or more interventions, one of them at higher cost and better per-patient outcome, and the second with lower cost and inferior per-patient outcome. 3) Forecast the diffusion of the alternatives into the entire intended use population, under a pre-defined budget, in order to estimate the treated and untreated populations. 4) Calculate the clinical impact of each alternative on the treated population. 5) Calculate the clinical impact of no therapy on the untreated population 6) Compare the aggregated clinical impact of each alternative on the entire intended use population – both treated and untreated. POLICY IMPLICATIONS: Using the proposed population-based model may result in improved healthcare outcomes, especially in times of economic downturn and austerity.