OBJECTIVES: In this analysis we are going to investigate the influence of the orphan drugs’ (OD) study type (RCT vs non-RCT) on the assessment of the additional benefit in the German early benefit assessment. In addition, a possible correlation between additional benefit and negotiated reimbursement price is assessed. METHODS: We included any OD assessment that was completed by 15 Nov 2015 and for which a final reimbursement price was available (only correlation additional benefit>price). It was investigated whether the presence of only non-RCTs resulted in a different extent of additional benefit. The possible correlation between additional benefit and reimbursement price was assessed by comparison of the initial price at market launch in Germany to the negotiated final price. RESULTS: We identified 30 OD assessments, 20 of those had a final reimbursement price. In 9 assessments only non-RCTs were available which lead to a non-quantifiable additional benefit in 8 cases and a minor benefit in 1 case. In contrast, from 21 assessments based on at least one RCT, only 5 resulted in a non-quantifiable benefit while in 16 assessments either a minor (14) or a considerable (2) additional benefit was granted. The negotiated final discounts ranged from 14-33% for drugs with a non-quantifiable additional benefit (8) while it was 16-30% for drugs with minor additional benefit (10) and 19-24% for assessments with considerable additional benefit (2). CONCLUSIONS: The results clearly show a strong relationship between the presence of a RCT and a quantifiable additional benefit (minor, considerable or major) in the assessment of ODs. Without a RCT a non-quantifiable additional benefit is most likely. In contrast there seems to be no obvious correlation between the additional benefit and the final reimbursement price. However, the additional benefit is only one of the components with a possible influence on the final reimbursement price.