OBJECTIVES: If the cost-effectiveness and appropriate use of a drug in the Netherlands cannot yet be determined during the initial reimbursement assessment (T=0), this will be done at the re-evaluation 4 years later (T=4) using RWD. Outcome research is an essential part of the re-evaluation of conditionally reimbursed drugs. The objective was to assess the reasons for accepting or rejecting outcome research results to confirm cost-effectiveness and appropriate use of a drug at T=4. METHODS: The website of Zorginstituut Nederland (ZiNL) was searched for re-evaluations of drugs published between January 2006 and May 2014. ZiNL’s assessments of the outcome research were compared. RESULTS: ZiNL published the outcome research results for four drugs. The outcome research results for agalsidase alfa & beta were accepted for demonstrating cost-effectiveness and appropriate use in Fabry’s disease. The T=4 results for omalizumab for the treatment of asthma were not accepted due to comments about population and model input, lack of statistical calculations and size of the incremental effects. Ranibizumab’s results for age-related macular degeneration were not accepted because of a wrong comparator, lack of long term data, assumptions on risks and mortality, and uncertainties around healthcare costs and ICER sensitivity. Finally, ZiNL considered the appropriate use of alglucosidase alfa for Pompe’s disease to be unsubstantiated because of the population choice for the ICER calculation and the use of a higher dose than the registered dose which was not supported by scientific data. The outcome results of alglucosidase alfa for cost-effectiveness were accepted, however. CONCLUSIONS: Although at T=0 ZiNL provided feedback regarding the design of the outcome research study, most of ZiNL’s comments were on the final methodology used. The outcome research studies were considered to be of mixed quality and the results could often not substantiate the claim of cost-effectiveness and appropriate use.