OBJECTIVES: The purpose of this study was to identify factors leading to unfavourable reviews of cost-effectiveness analyses (CEAs) for oncology products by comparing recent summary reports from multiple HTA agencies. METHODS: We utilised reports issued by HTA agencies of the United Kingdom (NICE), Scotland (SMC), Canada (pCODR), and Australia (PBAC) for this study due to their detailed and publicly available evaluations of CEA submissions. We examined the factors driving unfavourable appraisals by comparing recent reports of 13 selected oncology drugs launched between January 2012 and December 2013. The following factors were examined and compared as predictors for negative decisions: (1) nature of the modelled patient population, (2) comparator selection, (3) survival analysis approach, and (4) sensitivity analyses performed. RESULTS: Issues related to one or more of these factors were often cited as leading to higher and more uncertain ICER values that HTA bodies viewed unfavourably. The SMC and NICE frequently took issue whether the patient populations sourced as inputs into the CEAs were representative of the intended indication in each respective country. All HTA agencies took issue with survival analysis methods that assumed a carry-over of benefit into post-treatment states. Similarly, HTA bodies typically critically examined the extrapolation methodology of studies with immature survival data. Although various combinations of these identified factors were likely to lead to negative HTA decisions, robust sensitivity analyses (especially regarding extrapolation methods and input sources) that clearly identified the factors driving ICER values were cited favourably by HTA agencies. CONCLUSIONS: Manufacturers must carefully select the survival analysis approach that is suitable for their asset given the clinical data available, such that the benefit of their product is not overstated; performing robust sensitivity analyses to account for uncertainty may help to maximise favourable HTA appraisal outcomes in CEA markets.