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Background  Evidence on the relative costs and effects of interventions that do not consider ‘real-world’ constraints on implementation may be misleading. However, in many low- and middle-income countries, time and data scarcity mean that incorporating health system constraints in priority setting can be challenging.    Methods  We developed a ‘proof of concept’ method to empirically estimate health system constraints for inclusion in model-based economic evaluations, using intensified case-finding strategies (ICF) for tuberculosis (TB) in South Africa as an example. As part of a strategic planning process, we quantified the resources (fiscal and human) needed to scale up different ICF strategies (cough triage and WHO symptom screening). We identified and characterised three constraints through discussions with local stakeholders: (1) financial constraint: potential maximum increase in public TB financing available for new TB interventions; (2) human resource constraint: maximum current and future capacity among public sector nurses that could be dedicated to TB services; and (3) diagnostic supplies constraint: maximum ratio of Xpert MTB/RIF tests to TB notifications. We assessed the impact of these constraints on the costs of different ICF strategies.    Results  It would not be possible to reach the target coverage of ICF (as defined by policy makers) without addressing financial, human resource and diagnostic supplies constraints. The costs of addressing human resource constraints is substantial, increasing total TB programme costs during the period 2016–2035 by between 7% and 37% compared to assuming the expansion of ICF is unconstrained, depending on the ICF strategy chosen.    Conclusions  Failure to include the costs of relaxing constraints may provide misleading estimates of costs, and therefore cost-effectiveness. In turn, these could impact the local relevance and credibility of analyses, thereby increasing the risk of sub-optimal investments.    Electronic supplementary material  The online version of this article (10.1186/s12962-018-0113-z) contains supplementary material, which is available to authorized users.

Empirical estimation of resource constraints for use in model-based economic evaluation: an example of TB services in South Africa