OBJECTIVES: Payer expectations for reimbursement from novel drugs are constantly increasing. Understanding these is crucial during evidence generation. Expectations in terms of clinical outcomes vary across EU countries. This study compared payer awareness and expectations in two disease areas with contrasting prevalence and subsequent impact on healthcare budgets, and thus their impact on reimbursement. METHODS: The study was conducted in EU5 markets. Opinions of 36 stakeholders were collected via telephone interviews. Value drivers for new drugs were tested including unmet need, clinical data – safety and efficacy, cost effectiveness, budget impact, price, price against comparator and innovation. The results in the two disease areas were separately analysed and then compared with each other qualitatively on the basis depth of the responses. RESULTS: Awareness about the evidence expectations were seen to vary substantially between the disease areas. Payers were seen to be far more conscious in the high burden disease area. Of the 12 stakeholders interviewed for the high burden disease area (cardiovascular disease used as an example), all of them could provide an in-depth understanding of the value drivers for a new drug. On the other hand, of the stakeholders interviewed from a low-burden disease area within urology, a very small part of the sample (n=2) was able to provide details about necessary expectations for the indication. CONCLUSIONS: The variation in awareness amongst payers in disease areas tends to affect the clinical outcomes that are presented by the drug manufacturer for a novel drug for the indication. The low awareness regarding evidence expectations in disease areas with low budgetary impact may lead to lower quality of evidence being accepted for reimbursement. This needs to be further investigated.