OBJECTIVES: To identify the extent to which current approaches to clinical development, regulatory assessment, and economic evaluation of personalised healthcare drugs in oncology are aligned with real world clinical practice at product launch.  To identify and critically evaluate alternative approaches that should be factored into future clinical development and health technology assessment (HTA) planning. METHODS: Structured interviews were undertaken with physicians and payers (n=50) to identify the key issues surrounding the phased development and early use of personalised healthcare drugs in oncology. Analogue analyses were undertaken, based on “treatment tracking”, to develop a comparison between theoretical RCT (randomised control trial) evidence based, licensure aligned, utilisation and that observed in real world clinical practice Gap Analyses identified drivers of differences. The utility and limitations of retrospective and prospective observational registries in addressing these were explored.  RESULTS: Early results indicate that the level of unmet need, the magnitude of incremental clinical benefit, the timing of biomarker testing in the treatment algorithm and, increasingly, the number and prioritisation of diagnostic tests for an increasing number of different biomarkers are drivers of real world utilisation. Differences exist between countries. The greatest differences between theoretical and real world utilisation are in markets where decisions are driven by considerations of relative clinical effectiveness rather than cost effectiveness. Comparative SWOT analyses were developed of current and alternative clinical development, regulatory and health technology assessment systems.  These highlight areas where improvements in approach would be beneficial.  CONCLUSIONS: Additional evidence sources should be used to reinforce the regulatory and health technology assessment of PHC products in oncology with the aim of bringing closer alignment between the RCT approach to drug development and assessment - and the utilisation and outcomes (economic, clinical, and humanistic)  seen in real-world clinical practice.