A hypothetical case study about return to work was used to explore the process of translating research into practice. The method involved constructing a case study derived from the characteristics of a typical, sick-listed employee with non-specific low back pain in Norway. Next, the five-step evidence-based process, including the Patient, Intervention, Co-Interventions and Outcome framework (PICO), was applied to the case study. An inductive analysis produced 10 technical and more fundamental challenges to incorporate research into intervention decisions for an individual with comorbidity. A more dynamic, interactive approach to the evidence-based practice process is proposed. It is recommended that this plus the 10 challenges are validated with real life cases, as the hypothetical case study may not be replicable.