The limitations of evidence: increasing data and increasing doubt in the treatment of cardiac arrest.

PURPOSE OF REVIEW Cardiac arrest is one of the most challenging disease processes to study with clinical trials due to the emergent and unpredictable nature of these events and complexity of the patient population. In recent years, there has been a major push to complete more large, multicentre trials. In many cases, however, there remains little certainty on what treatments are most efficacious, in spite of the recent increase in evidence. This review was undertaken to address some of the unique barriers to address answering research questions in cardiac arrest with clinical trials. RECENT FINDINGS Multiple examples of trials that have failed to reach definitive conclusions, and potential reasons for this, are discussed. SUMMARY Trials on multiple major cardiac arrest interventions, including temperature management, drugs during cardiopulmonary resuscitation (CPR) and airway management, now have high-quality randomized trials, but significant questions on efficacy and best practices remain. Common pitfalls and reasons for this are explored, including heterogeneity of patients and providers, variability in exact interventions studied, delay in starting research interventions and lack of consistency across systems in decision making around appropriateness for resuscitation.