The Role of NETT in Emphysema Research

Abstract

Lung volume reduction surgery (LVRS) is one of a long lineage of surgical approaches to emphysema. The reintroduction of this operation in the mid-1990s led to great controversy over the value of the procedure and its long-term outcomes. The National Emphysema Treatment Trial (NETT) represented an historical scientific collaboration of the National Institutes of Health (NIH), the Centers for Medicare and Medicaid Services (CMS), and the Agency for Health Research and Quality (AHRQ). NETT was designed primarily as a pivotal surgical clinical trial, but also incorporated data collection to inform health policy and cost-benefit analyses. NETT faced challenges that included practical and ethical matters, statistical design and analysis issues, and intense public and political scrutiny. The study design required the development of methods for pulmonary rehabilitation, lung imaging, and exercise testing that have become templates for current clinical and research practice. During the course of the trial, the confidential deliberations of the Data and Safety Monitoring Board (DSMB) played an important role in the ultimate success of the trial and protection of research participants. Because of the importance of the NETT outcomes, the results were disseminated to the medical community and transformed into health policy in a rapid and efficient manner. In many ways, the story of NETT serves as a model for evaluation of new surgical approaches to chronic diseases.Keywords: lung volume reduction surgery; randomized clinical trials; bioethics; clinical trials data monitoring committee; cost-benefit analysis The National Emphysema Treatment Trial (NETT) is a landmark study. The purpose of this article is to put this study into the context of clinical research in general and on emphysema research in particular. Specifically, we will outline how the NETT originated, how challenges and obstacles to the design and conduct of the study were met, and how NETT has contributed to our current approach to emphysema research (Tables 1 and 2).

CT densitometry in emphysema: a systematic review of its clinical utility

“…Over half of the included studies were from larger cohort studies and subsequent retrospective/cross-sectional analysis. The nature of these cohorts introduces heterogeneity in the types of patients recruited, ie, lung cancer screening studies (NELSON), 52 alpha one cohorts, 53 COPD (eg, COPDGene, KOLD 15 , 54 ) and end-stage disease (eg, NETT). 55 The consistency of direction of the relationship between density and lung function across diverse patient groups is reassuring and suggests that density could be a valid surrogate outcome across the spectrum of disease severity.…”

Emphysema Predicts Hospitalisation and Incident Airflow Obstruction among Older Smokers: A Prospective Cohort Study

“…Radiologists did not follow a published protocol such as that of the National Emphysema Treatment Trial (NETT) to grade emphysema. [33] Although this may have reduced precision, reproducibility for moderate or severe emphysema was high and this approach likely increased clinical applicability since the interpretations followed standard academic clinical practice. Moreover, using an identical method this group of radiologists found that mild, moderate and severe emphysema predicted lung cancer and mortality from COPD in older smokers undergoing CT lung cancer screening.…”

Lung volume reduction surgery: an overview

“…Pulmonary rehabilitation provides substantial benefits for patients with severe COPD, including increased exercise capacity and decreased dyspnea. Although many patients never participate in this therapy modality, it is certainly less costly than surgery and associated with less immediate morbidity and mortality 27 .…”