• LUNG VOLUME REDUCTION SURGERY FOR EMPHYSEMA: LANDMARK STUDY ENTERS THE HOME STRETCH
  • Andrew L. Ries, MD, MPH
  • Principal Investigator, NETT Clinical Center
  • University of California, San Diego
  • Despite some recent public and professional confusion from misleading news headlines, the National Emphysema Treatment Trial (NETT) continues to go well at the 19 participating centers and will be enrolling patients through Spring with last randomization scheduled for July 2002. This landmark study, sponsored by Medicare, NIH, and AHQR, is designed to systematically evaluate lung volume reductions surgery (LVRS) in patients with advanced emphysema. More than 1,100 patients have been randomized over the past 4 years selected from approximately 15,000 screened individuals and more than 3,400 evaluated at the clinical centers. This represents the largest, well-characterized cohort of patients with advanced COPD to date. The trial has already begun producing important insights about the natural history, physiology, radiology, anatomy, symptoms and quality of life assessment of emphysema. Several publications and abstracts have documented important information from pre-randomization data, such as the benefits of pulmonary rehabilitation. Outcome results of the surgical procedure are still not available, however, because investigators remain blinded while the study is ongoing.
  • One of the important objectives of NETT is to refine selection criteria by identifying particular subgroups of patients who either do-or do not-benefit from LVRS or who are too high risk for the operation. During the study, an independent Data Safety Monitoring Board (DSMB) regularly reviews study results and makes decisions about appropriate protocol changes. It was just such a finding by the NETT DSMB in April, 2001 that led to an important modification of the study, the first major outcome publication, and, unfortunately, some misleading news headlines. In April, the DSMB identified a high-risk subgroup in which 30-day surgical mortality exceeded 8%, previously determined to be an unacceptable threshold. The high-risk group was characterized by a low FEV1 (less than 20% of predicted) AND either 1) homogeneous distribution of emphysema on high resolution CT scan or 2) low DLCO (less than 20% of predicted). Approximately 14% of the NETT subjects were in this high-risk subgroup. Subsequently, selection criteria were modified to exclude patients with these characteristics. In order to publicize these findings as soon as possible, NETT investigators prepared a manuscript accepted by the New England Journal of Medicine for rapid release on its website in the summer before actual publication in October, 2001. After posting on the NEJM website, news releases were distributed widely and all participating NETT subjects were notified individually. As the first major finding from NETT, the press release was picked up by media. Unfortunately, headlines in several newspapers highlighted mortality from LVRS in NETT leading many in the public and professional communities to conclude that the study was being terminated because of the negative findings. Even the ATS communications department, in its rush to notify members, improperly indicated that all patients with severe emphysema were at high risk from LVRS leading to some unfortunate confusion within our own pulmonary community.
  • What are the lessons we can currently draw from NETT-and from the recently published findings?
  • 1. Regardless of the ultimate outcome and future of LVRS, the NETT study is a success and represents an innovative mechanism for systematically evaluating a new surgical procedure through collaboration of the health insurance (Medicare) and medical research (NIH) communities.
  • 2. The large, well-characterized database of more than 1,100 patients with emphysema will produce important information about emphysema and COPD. For instance, in analyzing prerandomization data, NETT has already documented the effectiveness of pulmonary rehabilitation in patients with advanced COPD through data collected at the 19 NETT clinical centers as well as more than 400 satellite rehab centers.
  • 3. The preliminary findings released by the NETT DSMB identifying a high risk subgroup demonstrate why a study like NETT is important-i.e., in a systematic fashion helping to refine appropriate selection criteria to identify patients who are either particularly good or poor candidate for the procedure.
  • NETT is, in fact, still going strong and will be actively enrolling patients through Spring 2002. NETT investigators hope that you will encourage any interested patients to contact one of the NETT centers (Cedars Sinai and UCSD in California) to take advantage of this unique opportunity. Most patients have benefited considerably from the evaluation and rehabilitation activities even before they have made a final decision about randomization. Once NETT concludes randomization in July 2002 and currently scheduled follow-ups through December 2002, data will be analyzed and turned over to Medicare for review and consideration of coverage. Following this analysis, the medical and lay communities will have accurate information about the benefits and risks of LVRS and the appropriate selection of patients.
  • Thank you Dr. Ries!.