Comparative Effectiveness and Practice Variation in Neonatal Care Joanne Lagatta, MD, MSa, *, Michael Uhing, MDa , Julie Panepinto, MD, MSPHa,b INTRODUCTION There is increasing discussion in medical literature and among grant funding agencies about the need for comparative effectiveness research (CER). CER is defined by the Institute of Medicine as “the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care.”1 At first glance, this definition is broad enough that it potentially encompasses all types of clinical research, because the prevention, diagnosis, and treatment of illness is the ultimate goal of any clinical research team. In fact, neonatal clinical research literature already contains many examples of research that fit into the broad framework of CER. This article describes the main types of CER research methods using recent examples from existing neonatology literature, and highlights challenges in conducting CER specific to neonatal research. Disclosures: None. a Department of Pediatrics, Medical College of Wisconsin, 999 North 92nd Street, Suite C410, Milwaukee, WI 53226, USA; b Center for Clinical Effectiveness Research, Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA * Corresponding author. E-mail address: jlagatta@mcw.edu KEYWORDS Comparative effectiveness Neonatology Clinical research methods KEY POINTS Components of comparative effectiveness research (CER) include comparisons of alternative standards of care, evaluating outcomes important to individuals, and incorporating varied settings and participants. Neonatal clinical research contains examples of CER with strengths in clinical trials and metaanalyses comparing alternative standards of care. Future work in neonatal CER could focus on patient-centered outcomes in both prospective and retrospective studies. Clin Perinatol 41 (2014) 833–845 perinatology.theclinics.com 0095-5108/14/$ – see front matter 2014 Elsevier Inc. All rights reserved. WHAT IS COMPARATIVE EFFECTIVENESS RESEARCH? The focus of CER is to assist patients, clinicians, and policymakers in making informed decisions to improve health care. Although a variety of research methods can be used to accomplish these goals, 4 key elements of CER have been identified. Direct Comparison of Potential Alternative Standards of Care In contrast with an efficacy trial of a novel intervention versus a placebo, an effectiveness study compares the outcome of at least 2 existing interventions that a patient or clinician could reasonably choose in day-to-day clinical practice. Specifically, an effectiveness study aims to determine if an intervention does work, whereas a traditional efficacy study aims to determine if it can work.2 Evaluating a Broad Array of Health-related Outcomes that Are Important to Individuals Although there is often overlap, CER targets individual decision making by the patient or clinician, whereas public health decision making focuses on a population. CER studies assess both benefits and harms of interventions, and the measurement of clinical outcomes (as opposed to surrogate markers) that are important to decisionmakers such as survival, daily functioning, symptoms, and health-related quality of life. Incorporating a Wide Variety of Settings and Participants In contrast with carefully controlled clinical trials evaluating a select group of patients, CER is meant to focus on a typical patient in a typical practice setting. In addition to estimating an average treatment effect across an entire study population, a goal of CER is to study heterogeneous effects within clinically relevant subgroups to help predict which individuals most benefit from treatment.3 Prioritizing Topics of Interest to Stakeholders Involvement from patients, clinicians, policymakers, and other relevant participants in health care delivery is seen as key to guiding investment in research that reflects the priorities of the public. HOW DOES COMPARATIVE EFFECTIVENESS RESEARCH RELATE TO QUALITY IMPROVEMENT? Neonatal research has documented numerous examples of variation in neonatal care practices, such as use of inotropic agents,4 use of home oxygen and diuretics for infants with bronchopulmonary dysplasia,5,6 and antenatal counseling for preterm infants.7 Likewise, there are numerous examples of variation in important clinical outcomes, such as mortality for extremely preterm infants,8 bronchopulmonary dysplasia,9 and length of hospital stay.10 Quality improvement efforts focus on reducing variation in care and implementing best process and practice within individual neonatal intensive care units (NICUs) via education, monitoring changes in care and outcome, and benchmarking of outcomes against national