OBJECTIVES: To use a database of previous National Institute for Health and Clinical Excellence (NICE) health technology assessment (HTA) decisions (HTA inSite)1to understand the impact of four clinical evidence scenarios on the outcome of NICE technology appraisals (TAs). METHODS: We identified published NICE TAs containing evidence applicable to the following scenarios: 1) Efficacy data with a non-significant but positive trend; 2) Surrogate endpoints used in place of real endpoints; 3) Composite endpoints where statistical significance was driven by some, but not all, of the individual components; and 4) Efficacy data from observational studies. For each scenario, multiple submissions and re-submissions were identified using HTA inSite. The analysis focused on the evidence submitted, the final decision and critique by NICE, and any changes in approach by the manufacturer at re-submission. RESULTS: Clear patterns emerged for each scenario. For example NICE accepted data from surrogate endpoints (scenario 2) in all of the 4 submissions analysed. This was due to support by clinical experts and a clear rationale for the surrogates as established markers of efficacy. Observational data (scenario 4) were accepted in the absence of randomised controlled trials (RCTs), or in addition to RCTs where long-term or country-specific evidence was required. However, it was important to acknowledge and report any potential bias associated with the design of observational studies. CONCLUSIONS: An evaluated database can be used to understand the impact of any clinical evidence scenario on NICE decisions. The results can be used to inform submission strategy and assess decision outcome risk.