RCTs aims to avoid biased assessment of clinical interventions through the even distribution of both known and unknown factors that may influence outcomes. However, not all RCTs are well designed, conducted or reported. As such, the clinician needs to critically appraise RCTs in order to determine their strengths and weaknesses. This paper aims to explain how to approach critical appraisal, by highlighting and illustrating important 5-Fluoracil questions that help determine the

reliability of results from randomized trials. In previous papers in this series we have discussed how to formulate an answerable question and how to search the literature effectively to find answers. In this paper we outline a framework for critical appraisal of literature that investigates the effects of a healthcare intervention. Randomized

controlled trials (RCTs), along with systematic reviews and meta-analyses that combine the results of several randomized trials, offer the strongest scientific design for investigating the effects of an intervention. When well conducted and reported RCTs will give Venetoclax datasheet the least biased estimates of both benefits and harms of a treatment. Non-randomized studies can produce results that can be wrong in terms of both the magnitude of effect (i.e. exaggerating potential benefits), but more importantly also the direction of effect for an intervention (suggesting a benefit when in truth either no benefit exists, or worse, the intervention is harmful). In recognition of this, guideline bodies are Leukotriene-A4 hydrolase increasingly providing

treatment recommendations solely based on RCTs, or systematic reviews and meta-analyses of these trials. However, not all randomized trials are well designed and even when well designed, not all are well reported. Appropriately incorporating the results of a RCT into ones clinical practice requires an understanding of the strength of evidence provided by the trial and its relevance to an individual patient. It is thus essential for clinicians to be able to read RCT reports critically. Below, we explore ways in which this can be done. A 53-year-old man on haemodialysis with an elevated serum phosphate (1.8 mmol/L) returns to you, his nephrologist, for review. You are concerned about his elevated phosphate level and plan to control it using phosphate binders. The patient has done some research on the Internet and asks whether sevelamer would provide better long-term outcomes than a calcium-based phosphate binder. You search the literature for relevant trials and discover a RCT assessing the effects of sevelamer, compared with calcium-based phosphate binders, on mortality in haemodialysis patients.1 You wonder if the results of this study should impact your recommendations, so you proceed to read the report asking a few simple but important questions about the trial.