OBJECTIVES: Vandetanib, approved in 2012 in Canada, is indicated for the treatment of advanced medullary thyroid cancer. QTc-prolongation or torsade de pointes is considered in the risk management plan as an identified risk. To minimize this risk a restricted distribution program (RDP) has been implemented. Although shown effective, there are limited data on its associated burden to patients, health care professionals and the healthcare system. The objectives of the present study are to evaluate qualitatively and quantitatively the burden associated with the different components of the vandetanib RDP and, to determine the economic impact of the program for the healthcare system. METHODS: A mixed method evaluation has been used. Burden was determined by comparing prescribing and monitoring practices under the RDP with those that would have been observed in the absence of the RDP. Data on healthcare usage were collected through interviews conducted in convenient samples of HCPs (prescribers, pharmacists and nurses) either exposed to the RDP or not yet certified for the vandetanib RDP (i.e., unexposed) but familiar with the treatment of medullary thyroid cancer. A mapping of patient journeys, with and without the RDP, was developed to identify major components of the program. An economic evaluation, considering the perspective of the third party payers completed this analysis. Avoidable costs corresponded to those associated with activities deemed redundant with routine oncology care. RESULTS: Major components of the vandetanib RDP have been identified as well as areas of redundancies with standard oncology care. For each component, the qualitative burden for HCPs and ultimately patients was determined along with its associated costs considering the third party payers perspective. CONCLUSIONS: Risk minimisation measures should avoid duplication of efforts and loss of economic resources. Evaluation of burden, key to optimize the effectiveness of risk management plans, should be conducted systematically.