OBJECTIVES: Haemophilia B (HB), a rare disease, occurs in approximately 1:30,000 males and requires individualized therapy with factor IX (FIX) concentrate. Payers in European countries request studies with high levels of evidence for decision making. The objective was to determine the status quo of current studies concerning HB, new FIX products and new therapeutic modalities regarding clinical and real-life evidence. METHODS: A systematic literature research was conducted in EMBASE and MEDLINE, search terms ‚hemophilia B‘ and ‚FIX‘. Inclusion criteria: journal articles (JA), conference abstracts (CA), English language, published between January 2009 and March 2013, studies only. Screening of titles, abstracts and full texts was performed subsequently. Registered trials (RT) concerning HB or FIX were identified in ClinicalTrials.gov. Analysis comprised age group, sponsor, research topic, recruitment status, and study design. RESULTS: Screening of 1,639 hits yielded 31 JA describing 35 studies, and 62 CA. FIX was the topic of 21 studies (60.0%) and 29 CA (46.8%). A total of 7 studies focused on various aspects of HB, 6 on haemophilia studies with separate data on HB. Gene therapy was the main focus of 2 JA and 11 CA (17.7%). Screening of 173 hits from ClinicalTrials.gov yielded 47 RT, 42 unpublished. Overall 32 unpublished RT (76.2%) concerned FIX, and 4 (9.5%) gene therapy. Randomized study design was described in one study (2.9%) and 4 RT (9.5%), and 3 studies (8.6%) and 7 RT (16.7%) were prospective observational comparative. CONCLUSIONS: Randomized study design or comparator arms were uncommon, and payers` requirements for evidence were not met. Therefore, randomization, comparison to standard of care and documentation of outcome should be discussed. Development of refined statistical methods and exploitation of complementary data like real-life data may help to fill actual evidence gaps in rare diseases.