OBJECTIVES: Where standard of care (SoC) is not clearly defined, incremental benefit/cost uncertainty for new treatments can be a challenge for reimbursement decision making. The aim of this work is to demonstrate the variability in SoC options for the management of complex peri-anal fistulas (CPAF) in Crohn’s Disease (CD), their effectiveness, and associated costs and to explore the role of performance-based risk-sharing agreements (PBRSA). METHODS: MEDLINE, Embase, MEDLINE In-Process, and COCHRANE were searched for the timeframe 2000 to 22^nd January 2018 to retrieve relevant publications regarding management patterns and guidelines, economic and humanistic burden of CPAF. Following systematic literature review (SLR), 5 semi-structured interviews with current and former European payers were conducted to understand usefulness of PBRSAs in CPAF treatment. RESULTS: The SLR identified six European treatment guidelines, three treatment pattern studies, two studies assessing economic burden, and 12 studies reporting humanistic burden of CPAF. Current SoC for patients with CPAF is globally heterogeneous and representative of the unmet need for a consistently effective therapeutic approach, with limited existing high-quality evidence and no standardised treatment approach. Only one study from Spain (2009) explored direct costs per patient per year, amounting to €8,289; however, authors and interviewed payers perceived this cost to be potentially under-representative versus current European costs. Interviewees suggest that CPAF treatment would benefit from PBRSAs, although depending on country, different models might be adopted. CONCLUSIONS: here is no standardised SoC in CPAF. Treatment is determined on a patient-by-patient basis, leading to variation in clinical outcomes and costs. Additionally, there is inadequate quantification of medical costs associated with CPAF management. These circumstances generate uncertainty in cost estimation for payers, for lack of consistent comparative figures. Therefore, CPAF treatment represents an excellent candidate for PBRSAs. PBRSAs can enable access to novel therapies with unproven long-term effect.