OBJECTIVES: Dutch policy regulations for expensive inpatient drugs require outcomes research for the assessment of appropriate drug use and cost-effectiveness after four years of temporary reimbursement. We investigated whether outcomes research of bortezomib in advanced multiple myeloma reduced decision makers’ uncertainty. METHODS: Our cohort study included 139 patients who were treated for advanced multiple myeloma outside of a clinical study. Detailed data were retrospectively collected from medical records in 38% of all Dutch hospitals. RESULTS: It was possible to develop evidence on types of drug used, dosages, dose modifications and healthcare costs. However, it was impossible to identify a single treatment comparator (>10 drugs in >20 combinations), partly due to rapid developments in treatment for multiple myeloma. Moreover, patients treated with bortezomib (n=72) were not comparable to other patients (n=67) regarding prognostic factors. It was not clear whether physicians used standardised outcome measures (i.e. EBMT response and CTC toxicity criteria) since such information was often not reported in medical records. Although different adjustment techniques were applied to the Cox multivariate regression model to obtain a valid (overall) survival estimate, none succeeded in correcting for the observed confounding. Moreover, the great heterogeneity caused by many treatment arms made it impossible to develop a feasible model to estimate incremental (cost-) effectiveness compared to other treatments. CONCLUSIONS: Outcomes research of bortezomib is complicated by extensive treatment variation and great patient heterogeneity in everyday practice. Although it is possible to generate evidence on appropriate drug use to facilitate informed decision making, much uncertainty remained regarding the incremental (cost-) effectiveness compared to other treatments. Policymakers should carefully consider if outcomes research could potentially lead to an acceptable reduction in decision-making uncertainty or that other options such as financial- or outcomes based risk sharing agreements might be more appropriate to obtain sufficient value for money.