Identifying Methodological Gaps in Treatment Guidelines and Advancing Evidence Synthesis for Empiric Treatment of Hospital- and Community-Acquired Pneumonia

Abstract

Clinical practice guidelines provide recommendations to help clinicians, patients, and other relevant stakeholders make appropriate healthcare-related decisions. The Institute of Medicine (IOM) in 2011 proposed standards for developing trustworthy guidelines. Whether the trustworthiness of guidelines has improved since the release of IOM remains uncertain. In this thesis to address this question, we conducted a systematic survey comparing trustworthiness of guidelines released before versus after the introduction of IOM. We faced important challenges in assessing trustworthiness of guidelines in this study, as the available instrument – the National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards (NEATS) – to evaluate adherence of guidelines to the IOM trustworthiness standards has limitations in addressing methodological quality of the guideline development process and lacks explicit instruction for reproducible assessments. To overcome these limitations, we developed modifications to the instrument and applied the modified NEATS instrument to assess trustworthiness of guidelines in our systematic survey. The findings of our systematic survey revealed that adherence of post-IOM guidelines to the standards of systematic review of evidence, which is a crucial step in informing guideline recommendations, is suboptimal. This departure from the trustworthiness standards can be a source of conflicting guideline recommendations which is evident among guidelines developed to guide antibiotic selection for empiric management of non-ventilator-associated hospital-acquired pneumonia (HAP) and moderate to severe community-acquired pneumonia (CAP). Therefore, in subsequent chapters of this thesis, we present two systematic reviews with network meta-analyses that adhere to the trustworthiness standards and address limitations in the existing evidence synthesis for antibiotics used in the empiric treatment of HAP and moderate to severe CAP.