The field of guideline development has made considerable progress in the past twenty years, particularly after the introduction of GRADE in 2004. However, there are many shortcomings in current guideline development including failure to use GRADE, low quality systematic reviews, and excessive delays from the publication of practice changing evidence to new recommendations. The objective of this thesis is to describe the development of evidence-based recommendations, to document methodological issues that arose and describe how the research team addressed the questions, and to document how the ultimate guidelines contributed to optimization of treatment in clinical practice. The relevant guidelines address the issues of gastrointestinal bleeding prophylaxis and coronavirus disease 2019 (COVID-19). The thesis begins by presenting three methodological issues that arose during the planning and implementation of the guideline process and the initial process of how the research team addressed the challenges. The thesis subsequently presents a published paper that documents recommendations regarding gastrointestinal bleeding prophylaxis in critically ill patients. Then, this thesis presents a published systematic review and meta-analysis addressing efficacy and safety of corticosteroids in COVID-19 based on direct evidence from patients with COVID-19, and indirect evidence from acute respiratory distress syndrome, community-acquired pneumonia, severe acute respiratory syndrome, middle east respiratory syndrome and influenza. Further, the thesis includes a published paper describing recommendations regarding corticosteroids, convalescent plasma and antiviral drugs in COVID-19 on the basis of evidence available very early during the pandemic. This thesis ends by presenting how the methodological issues were ultimately addressed in the relevant guidelines, the importance of the guidelines themselves, and presents perspectives on future research and opportunities in guideline development. / Thesis / Candidate in Philosophy