Background: The National Emphysema Treatment Trial, a randomized clinical trial of lung volume reduction surgery (LVRS) vs medical therapy for severe emphysema, included a prospective economic analysis. We present an updated analysis of cost-effectiveness with 1-year additional follow-up data.
Methods: Following pulmonary rehabilitation, 1,218 patients at 17 medical centers were randomized to receive LVRS or continued medical treatment. The cost-effectiveness of LVRS vs medical therapy was calculated over the duration of the trial (January 1998 to December 2003) and estimated at 10 years using modeling based on observed trends in survival, cost, and quality of life.
Results: The cost-effectiveness of LVRS vs medical therapy was $140,000 per quality-adjusted life-year (QALY) gained (95% confidence interval, $40,155 to $239,359) at 5 years, and was projected to be $54,000 per QALY gained at 10 years. In subgroup analysis, the cost-effectiveness of LVRS in patients with upper-lobe emphysema and low exercise capacity was $77,000 per QALY gained at 5 years, and was projected to be $48,000 per QALY at 10 years. Compared to the initial results, the updated results are similar for the overall cohort but vary substantially for the subgroups.
Conclusions: LVRS is costly relative to other health-care programs during the time horizon when costs and outcomes are known. The extended follow-up period offers more certainty regarding the long-term value and economic impact of this procedure.
In May of 2003, investigators from the National Emphysema Treatment Trial (NETT)1–—a federally sponsored, multicenter, randomized controlled trial of lung volume reduction surgery (LVRS) vs medical therapy for patients with severe emphysema—reported the outcomes for 1,218 trial participants over a mean duration of 2.4 years of follow-up. Because the potential clinical impact of LVRS was thought to be substantial, the NETT also included a parallel, prospective, economic analysis as part of the clinical trial.2 LVRS was found to confer improvements in survival, exercise capacity, and quality of life for patients with predominantly upper-lobe emphysema combined with low baseline exercise capacity. Patients with upper-lobe emphysema and high exercise capacity benefited from LVRS in exercise capacity and quality of life but had no survival improvement compared to medical therapy. Patients with non–upper-lobe emphysema and low exercise capacity had significant improvements only in quality of life measures, while patients with non–upper-lobe emphysema and high exercise capacity had no evidence of clinical improvement and had a higher mortality.
In a parallel economic analysis, the cost-effectiveness of LVRS compared to medical therapy was $190,000 per quality-adjusted life-year (QALY) gained at 3 years. Using modeling to extrapolate trends in costs and outcomes, the cost-effectiveness of LVRS at 10 years was estimated at $53,000 per QALY overall and $21,000 per QALY for the upper-lobe, low exercise capacity subgroup. Because there was great uncertainty regarding the duration of benefit for LVRS, the cost-effectiveness analysis showed substantial uncertainty for the 10-year estimates.
In January of 2004, the Centers for Medicare and Medicaid Services (CMS) approved LVRS for coverage, based on the results of the trial.3 Specifically, CMS approved three of the four original subgroups: upper-lobe predominant emphysema and low exercise capacity (defined as maximal exercise of ≤ 40 W for men and ≤ 25 W for women on a bicycle ergometer); upper-lobe-predominant emphysema and high exercise capacity; and non–upper-lobe-predominant and low exercise capacity.
In this article, we report the cost-effectiveness of LVRS using an extended follow-up period for NETT enrollees from January 1998 through December 2003. We include a within-trial analysis using follow-up data up to 5 years and new 10-year projections based on the extended follow-up period. Our findings are in some cases substantially different from the previously published results, and thus offer a cautionary tale to those estimating cost-effectiveness of new technologies from clinical trials of limited duration.
The design and methods of the NETT and the cost-effectiveness component of the trial have been described previously.1–2,4–5 The trial design and economic analysis are summarized below.
The NETT was a multicenter, randomized controlled trial of LVRS vs medical therapy for patients with severe emphysema. Between January 1998 and July 2002, 17 centers randomly assigned 1,218 patients with severe emphysema to LVRS or medical therapy. Prior to randomization, all patients underwent pulmonary rehabilitation. Outcome measures included mortality, maximal exercise capacity, pulmonary function, and measures of disease-specific and general health-related quality of life, including the quality of well-being (QWB) scale. Scheduled evaluations for quality of life assessment were at 6 months and annually for years 1 to 5 following randomization. Vital status was determined by clinical center report and the Social Security Master Death File. Interim analysis of the NETT identified a subgroup of patients (n = 140) with high risk of mortality and little chance of improved function following surgery.6 This subgroup was excluded from future enrollment and is omitted from the cost-effectiveness analysis.
We estimated the cost per QALY gained from a societal perspective. Costs included the following: (1) medical goods and services; (2) transportation to and from health-care facilities; (3) time spent by family and friends caring for the patient; and (4) time spent in treatment. QALYs were derived by adjusting survival by health-state preferences, also known as utilities, which range from 0 (death) to 1.0 (optimum quality of life). Utility weights were obtained from the QWB scale, a comprehensive multiattribute survey measure of health-related quality of life covering acute and chronic symptoms, self care, mobility, physical activity and functioning, and social activity, using a previously published algorithm to convert questionnaire responses to utility weights.7Medical care utilization was based on Medicare claims for trial participants. Outpatient medications for emphysema (not covered by Medicare) were recorded on clinical trial reporting forms. Travel distances to NETT-affiliated facilities and patient time spent seeking medical care were recorded and valued. Costs and benefits after year 1 were discounted at 3% per annum, as is recommended for economic studies.8
Results were analyzed using intention to treat. Survivors with missing QWB data were assigned a value equal to one half of the lowest score of all subjects at a corresponding visit.1 Patients who did not have Medicare as their primary insurer and those enrolled in Medicare+Choice plans were excluded from the analysis, as no health-care claims were available for these individuals. Average total costs, QALYs, and associated 95% confidence intervals (CIs) were determined using the Kaplan-Meier sample average estimator.9–10 The estimator sums over follow-up time intervals either mean costs (for total costs) or mean utility weights (for QALYs) for patients alive at the beginning of the interval weighted by the Kaplan-Meier probability of surviving to the beginning of the interval. Cost-effectiveness was calculated as a ratio of the difference in costs divided by the difference in QALYs for LVRS vs medical groups. Cost-effectiveness ratios were computed for the trial observation period through December 31, 2003, and then projected for 10 years.
We fit a log-logistic model using survival data from only those subjects who survived at least 1 year. Several models were tried; the log logistic provided the best fit to the observed data. Survival and censoring information was then regressed on treatment assignment to get parameter estimates for the model. Monthly survival was extrapolated beyond the observation period using the scale and regression parameters for the log-logistic model.
Separate models were constructed for each subgroup to predict outcomes under alternate assumptions of the duration of the relative survival benefit. Point estimates for the relative survival advantage were first set at observed levels (for example, all patients excluding high-risk subgroup risk ratio = 0.89, p = 0.31). To estimate long-term survival, log-logistic models were fit using data from patients who survived at least 1 year. The relative hazard rate for survival for surgery vs medical therapy was set at observed levels through year 5, and then assumed to change to 1 (no survival benefit) thereafter. Survival was modeled with Weibull distributions. QWB scores for years 6 to 10 were estimated based on values observed in year 5. Costs were estimated by fitting regression lines to monthly values for both groups averaged over the fourth and fifth years of follow-up. Model coefficients and summary statistics are available on request.
The bias-corrected nonparametric bootstrap method was used to derive a 95% CI. Cost-effectiveness acceptability curves were constructed to characterize uncertainty.11 We received patient consent from all participants, as well as approval from internal review boards for this study.
Excluding the high-risk subgroup that was identified and excluded mid-trial, a total of 538 patients were randomized to LVRS and 540 were randomized to medical care. Twelve of these participants were excluded from the cost-effectiveness analysis (7 in the surgery group and 5 in the medical therapy group) because they were not enrolled in Medicare, because they were enrolled in Medicare+Choice plans at the time of randomization, or because the Medicare claims could not be located. Table 1
shows baseline characteristics of the remaining individuals. Median follow-up was 4.3 years. Mean (± SD) QWB scores before randomization were 0.58 ± 0.12 in the surgery group and 0.57 ± 0.11 in the medical therapy group.
At 5 years, overall Kaplan-Meier survival was 62.2% in the LVRS group and 56.1% in the medical therapy group (Table 2
). Mean QWB scores for patients alive at 5 years were 0.472 (SD 0.212, n = 11) for the LVRS group and 0.444 (SD 0.251, n = 14) for the medical therapy group. Mean total costs per person over 5 years (future years not discounted) were $141,300 (95% CI, $131,647 to $150,953) in the surgery group and $105,822 (95% CI, $96,895 to $114,749) in the medical therapy group (p < 0.001). The mean number of QALYs (future years not discounted) was higher in the surgery group than in the medical therapy group (1.99 vs 1.71, p < 0.001). After discounting future costs and QALYs by 3% per annum, the cost-effectiveness of LVRS vs medical therapy over 5 years was $140,000 per QALY gained (95% CI, $40,000 to $239,000 per QALY gained).
As noted, post hoc analyses suggested differential benefits from LVRS based on the presence or absence of upper-lobe predominance in the distribution of emphysema on CT and low or high maximal exercise capacity after pulmonary rehabilitation. Patients with predominantly upper-lobe emphysema and low exercise capacity had the most favorable cost-effectiveness ratio for surgery ($77,000 per QALY gained). The other subgroups had far less favorable cost-effectiveness (Table 3
). The cost-effectiveness acceptability curves revealed moderate uncertainty for the overall group and the upper-lobe plus low exercise capacity subgroup but high levels of uncertainty for the other two subgroups (Fig 1
Projected Results at 10 Years
Based on extrapolations for survival and cost, the projected overall cost-effectiveness of LVRS at 10 years was $54,000 per QALY gained. The cost-effectiveness ratios were more favorable for each subgroup (Table 3), but uncertainty analysis (as displayed by the cost-effectiveness acceptability curves) revealed high degrees of uncertainty around the point estimates (Fig 2
Comparison of Initial and Final Observed and Projected Results
Comparison of actual and projected results using the earlier and most recent data reveals some important differences in the cost-effectiveness analysis of LVRS that emphasize the limitations of interim analysis and projections of shorter-term follow-up. Our previous analysis2 showed an overall cost-effectiveness ratio of $190,000 per QALY at 3 years for LVRS vs medical therapy, and a projected ratio of $58,000 per QALY at 10 years. Using the extended follow-up period, the observed cost-effectiveness of LVRS improved, consistent with the trend toward improvement over time observed in the projections (Table 3). Compared to the 10-year projections using 3 years of follow-up data, the projected results using the extended follow-up data revealed similar results for the overall cohort but markedly different results for the subgroups. The 10-year projected outcome for one subgroup—non–upper-lobe-predominant emphysema and low exercise capacity—changed dramatically from initially suggesting lower costs and better outcomes for surgery to now showing $80,000 per QALY gained when 5-year data are available. Uncertainty remained high for both analyses.
Using follow-up data from the NETT, we reestimated the cost-effectiveness of LVRS vs maximal medical therapy for patients with severe emphysema. Within-trial evaluation of costs and outcomes suggests that LVRS continues to be relatively less cost-effective compared to other common therapies applied to persons of this age group. Projecting trends in costs and outcomes observed at 5 years to a 10-year time horizon yields more favorable cost-effectiveness estimates, yet with considerable uncertainty, largely due to difficulties estimating long-term survival and quality of life for the surgical cohort.
Post hoc analysis identified three subgroups with differential benefit favoring LVRS. We find that the cost-effectiveness of the upper-lobe, low-exercise cohort at 5 years is substantially better than that of the entire cohort, largely due to the better survival and quality of life observed over time for the LVRS group among all patients meeting these criteria. Because the sample sizes are necessarily much smaller for these subgroups, the degree of uncertainty is much higher, both for the within-trial evaluation and particularly for the 10-year projections.
The cost-effectiveness of LVRS for the overall group was better at follow-up than what we observed initially. This was anticipated, since LVRS patients who survived at least 90 days beyond their surgery had improved quality of life and a trend toward improved survival compared to medical therapy patients, while costs for both groups in the extended follow-up period were generally similar. The 10-year projections suggest that one should expect this trend to continue over time. Nevertheless, this was a severely ill cohort at the onset, and those who survive 5 years are likely to have very high variability in both costs and quality of life. For example, if only a modest excess number of patients in either cohort have a COPD exacerbation requiring hospitalization and a prolonged recovery, this will have a substantial impact on costs and outcomes for the entire cohort. In essence, this is the reason that it is so difficult to predict the long-term cost-effectiveness of LVRS.
Our analysis highlights the difficulties in predicting cost-effectiveness for time horizons extending beyond a clinical trial. The predicted 10-year cost-effectiveness results for the upper-lobe, low exercise capacity and non–upper-lobe, low exercise capacity groups are much less favorable using the extended follow-up data than they were using the initial data. In contrast, the results for the upper-lobe, high exercise capacity group are substantially more favorable than originally predicted. Extrapolations of clinical trial results are common and accepted in cost-effectiveness analysis, but our analysis suggests that researchers must be quite cautious when faced with multiple sources of uncertainty. In our case, the uncertainties include the post hoc analysis, small sample sizes, and lack of information about duration of benefit in the longer term.
At the same time that the trial results were published, the CMS released a national coverage memorandum stating that LVRS would be covered for patients with upper-lobe or non–upper-lobe-predominant emphysema with low exercise capacity, or upper-lobe emphysema with high exercise capacity. The CMS originally specified that LVRS would be performed at NETT facilities and sites that have been approved by Medicare as lung transplant facilities.12More recently, the CMS has delegated to the Joint Commission on Accreditation of Healthcare Organizations a process for certifying additional LVRS centers.13The CMS implemented its final coverage policy on January 5, 2004. Some private health insurance plans have agreed to cover LVRS for persons < 65 years old since the CMS coverage policy was implemented.14–15 Notably, the private health plans that cover LVRS do not appear to have facility restrictions similar to the CMS policy.
We originally estimated that 10,000 persons may meet eligibility criteria for LVRS annually, with a resulting impact on national health expenditures of $100 million to $300 million per year, depending on patients’ interest in the procedure and their suitability after pulmonary rehabilitation. Others16 have estimated the impact as high as $1.2 billion annually. Based on Medicare claims for LVRS since the coverage was implemented, the actual budget impact has been substantially less. Between January 2004 and September 2005, the CMS has paid 258 claims for LVRS. Furthermore, there has been no upward trend in procedure volume over time (Fig 3
). This very modest use suggests that there is relatively limited demand for the LVRS, despite the relatively open CMS coverage policy. Annualizing these claims and using our 5-year evaluation of costs, we now project 5-year LVRS-related expenditures in excess of the costs of medical therapy to range from $8.2 to $21 million for those receiving the procedure over a 12-month period.
Our analysis has limitations. Administrative and facility costs associated with the maintenance of a center that performs LVRS were not included. We also excluded medical and nonmedical costs that patients incurred as part of their screening and pulmonary rehabilitation before randomization, as these were similar between groups in the trial. These services have no impact on the incremental analysis but do affect total expenditures for LVRS patients. Medicare copayments and deductibles paid by patients for NETT-related services were not included in the analysis. These out-of-pocket payments varied from center to center and from service to service and thus were extremely difficult to quantify. Finally, all clinical trials necessarily involved inclusion and exclusion criteria that resulted in a more homogeneous patient population and closer monitoring than typical clinical practice. Thus, these results may not reflect patterns of care that will be observed in a nonresearch environment.
Optimally, health insurers weigh data from cost-effectiveness analyses alongside clinical evidence when making coverage decisions regarding new medical technologies. In the case of LVRS, the CMS weighted clinical evidence heavily and discounted economic evidence in its final coverage decision. Some have noted that relatively generous coverage of CMS for LVRS seems disproportionate to the weight of the evidence, the degree of clinical benefit, and relatively unfavorable cost-effectiveness that was shown from the trial.17–18 However, the vast majority of medical therapies covered by Medicare have not been subjected to similar clinical investigation of efficacy or to rigorous cost-effectiveness analysis. Furthermore, Medicare has not generally used cost-effectiveness in determining coverage policy when there is evidence or consensus regarding medical effectiveness. Compared to our original report,2 this update does not change the essential message regarding the relatively poor cost-effectiveness of LVRS overall, at least over the duration of time of which benefits and costs have been measured. The upper-lobe, low exercise capacity subgroup appears to have the highest probability of achieving rates of cost-effectiveness that would be considered a good value for the level of expenditure required. Continued follow-up of the LVRS and medical therapy arms would provide more precise estimates of the true clinical and economic value for LVRS. Few patients in the medical therapy arm are still eligible or have chosen LVRS since announcement of the results, thus facilitating the value of continued follow-up. The value of this information is likely to exceed the cost of obtaining it.19
Members of the NETT Research Group and Clinical Centers
Office of the Chair of the Steering Committee, University of Pennsylvania, Philadelphia, PA:
Alfred P. Fishman, MD (Chair); Betsy Ann Bozzarello; Ameena Al-Amin.
Baylor College of Medicine, Houston, TX:
Marcia Katz, MD (Principal Investigator); Carolyn Wheeler, RN, BSN (Principal Clinic Coordinator); Elaine Baker, RRT, RPFT; Peter Barnard, PhD, RPFT; Phil Cagle, MD; James Carter, MD; Sophia Chatziioannou, MD; Karla Conejo-Gonzales; Kimberly Dubose, RRT; John Haddad, MD; David Hicks, RRT, RPFT; Neal Kleiman, MD; Mary Milburn-Barnes, CRTT; Chinh Nguyen, RPFT; Michael Reardon, MD; Joseph Reeves-Viets, MD; Steven Sax, MD; Amir Sharafkhaneh, MD; Owen Wilson, PhD; Christine Young PT; Rafael Espada, MD (Principal Investigator 1996–2002); Rose Butanda (1999–2001); Minnie Ellisor (2002); Pamela Fox, MD (1999–2001); Katherine Hale, MD (1998–2000); Everett Hood, RPFT (1998–2000); Amy Jahn (1998–2000); Satish Jhingran, MD (1998–2001); Karen King, RPFT (1998–1999); Charles Miller III, PhD (1996–1999); Imran Nizami, MD (Co-Principal Investigator, 2000–2001); Todd Officer (1998–2000); Jeannie Ricketts (1998 -2000); Joe Rodarte, MD (Co-Principal Investigator 1996–2000); Robert Teague, MD (Co-Principal Investigator 1999–2000); Kedren Williams (1998–1999).
Brigham and Women’s Hospital, Boston, MA:
John Reilly, MD (Principal Investigator); David Sugarbaker, MD (Co-Principal Investigator); Carol Fanning, RRT (Principal Clinic Coordinator); Simon Body, MD; Sabine Duffy, MD; Vladmir Formanek, MD; Anne Fuhlbrigge, MD; Philip Hartigan, MD; Sarah Hooper, EP; Andetta Hunsaker, MD; Francine Jacobson, MD; Marilyn Moy, MD; Susan Peterson, RRT; Roger Russell, MD; Diane Saunders; Scott Swanson, MD (Co-Principal Investigator, 1996–2001).
Cedars-Sinai Medical Center, Los Angeles, CA:
Rob McKenna, MD (Principal Investigator); Zab Mohsenifar, MD (Co-Principal Investigator); Carol Geaga, RN (Principal Clinic Coordinator); Manmohan Biring, MD; Susan Clark, RN, MN; Jennifer Cutler, MD; Robert Frantz, MD; Peter Julien, MD; Michael Lewis, MD; Jennifer Minkoff-Rau, MSW; Valentina Yegyan, BS, CPFT; Milton Joyner, BA (1996–2002).
Cleveland Clinic Foundation, Cleveland, OH:
Malcolm DeCamp, MD (Principal Investigator); James Stoller, MD (Co-Principal Investigator); Yvonne Meli, RN,C (Principal Clinic Coordinator); John Apostolakis, MD; Darryl Atwell, MD; Jeffrey Chapman, MD; Pierre DeVilliers, MD; Raed Dweik, MD; Erik Kraenzler, MD; Rosemary Lann, LISW; Nancy Kurokawa, RRT, CPFT; Scott Marlow, RRT; Kevin McCarthy, RCPT; Pricilla McCreight, RRT, CPFT; Atul Mehta, MD; Moulay Meziane, MD; Omar Minai, MD; Mindi Steiger, RRT; Kenneth White, RPFT; Janet Maurer, MD (Principal Investigator, 1996–2001); Terri Durr, RN (2000–2001); Charles Hearn, DO (1998–2001); Susan Lubell, PA-C (1999–2000); Peter O’Donovan, MD (1998–2003); Robert Schilz, DO (1998–2002).
Columbia University, New York, NY, in consortium with Long Island Jewish Medical Center, New Hyde Park, NY:
Mark Ginsburg, MD (Principal Investigator); Byron Thomashow, MD (Co-Principal Investigator); Patricia Jellen, MSN, RN (Principal Clinic Coordinator); John Austin, MD; Matthew Bartels, MD; Yahya Berkmen, MD; Patricia Berkoski, MS, RRT (Site coordinator, LIJ); Frances Brogan, MSN, RN; Amy Chong, BS, CRT; Glenda DeMercado, BSN; Angela DiMango, MD; Sandy Do, MS, PT; Bessie Kachulis, MD; Arfa Khan, MD; Berend Mets, MD; Mitchell O’Shea, BS, RT, CPFT; Gregory Pearson, MD; Leonard Rossoff, MD; Steven Scharf, MD, PhD (Co-Principal Investigator, 1998–2002); Maria Shiau, MD; Paul Simonelli, MD; Kim Stavrolakes, MS, PT; Donna Tsang, BS; Denise Vilotijevic, MS, PT; Chun Yip, MD; Mike Mantinaos, MD (1998–2001); Kerri McKeon, BS, RRT, RN (1998–1999); Jacqueline Pfeffer, MPH, PT (1997–2002).
Duke University Medical Center, Durham, NC:
Neil MacIntyre, MD (Principal Investigator); R. Duane Davis, MD (Co-Principal Investigator); John Howe, RN (Principal Clinic Coordinator); R. Edward Coleman, MD; Rebecca Crouch, RPT; Dora Greene; Katherine Grichnik, MD; David Harpole, Jr., MD; Abby Krichman, RRT; Brian Lawlor, RRT; Holman McAdams, MD; John Plankeel, MD; Susan Rinaldo-Gallo, MED; Sheila Shearer, RRT; Jeanne Smith, ACSW; Mark Stafford-Smith, MD; Victor Tapson, MD; Mark Steele, MD (1998–1999); Jennifer Norten, MD (1998–1999).
Mayo Foundation, Rochester, MN:
James Utz, MD (Principal Investigator); Claude Deschamps, MD (Co-Principal Investigator); Kathy Mieras, CCRP (Principal Clinic Coordinator); Martin Abel, MD; Mark Allen, MD; Deb Andrist, RN; Gregory Aughenbaugh, MD; Sharon Bendel, RN; Eric Edell, MD; Marlene Edgar; Bonnie Edwards; Beth Elliot, MD; James Garrett, RRT; Delmar Gillespie, MD; Judd Gurney, MD; Boleyn Hammel; Karen Hanson, RRT; Lori Hanson, RRT; Gordon Harms, MD; June Hart; Thomas Hartman, MD; Robert Hyatt, MD; Eric Jensen, MD; Nicole Jenson, RRT; Sanjay Kalra, MD; Philip Karsell, MD; Jennifer Lamb; David Midthun, MD; Carl Mottram, RRT; Stephen Swensen, MD; Anne-Marie Sykes, MD; Karen Taylor; Norman Torres, MD; Rolf Hubmayr, MD (1998–2000); Daniel Miller, MD (1999–2002); Sara Bartling, RN (1998–2000); Kris Bradt (1998–2002).
National Jewish Medical and Research Center, Denver, CO:
Barry Make, MD (Principal Investigator); Marvin Pomerantz, MD (Co-Principal Investigator); Mary Gilmartin, RN, RRT (Principal Clinic Coordinator); Joyce Canterbury; Martin Carlos; Phyllis Dibbern, PT; Enrique Fernandez, MD; Lisa Geyman, MSPT; Connie Hudson; David Lynch, MD; John Newell, MD; Robert Quaife, MD; Jennifer Propst, RN; Cynthia Raymond, MS; Jane Whalen-Price, PT; Kathy Winner, OTR; Martin Zamora, MD; Reuben Cherniack, MD (Principal Investigator, 1997–2000).
Ohio State University, Columbus, OH:
Philip Diaz, MD (Principal Investigator); Patrick Ross, MD (Co-Principal Investigator); Tina Bees (Principal Clinic Coordinator); Jan Drake; Charles Emery, PhD; Mark Gerhardt, MD, PhD; Mark King, MD; David Rittinger; Mahasti Rittinger.
Saint Louis University, Saint Louis, MO:
Keith Naunheim, MD (Principal Investigator); Robert Gerber, MD (Co-Principal Investigator); Joan Osterloh, RN, MSN (Principal Clinic Coordinator); Susan Borosh; Willard Chamberlain, DO; Sally Frese; Alan Hibbit; Mary Ellen Kleinhenz, MD; Gregg Ruppel; Cary Stolar, MD; Janice Willey; Francisco Alvarez, MD (Co-Principal Investigator, 1999–2002); Cesar Keller, MD (Co-Principal Investigator, 1996–2000).
Temple University, Philadelphia, PA:
Gerard Criner, MD (Principal Investigator); Satoshi Furukawa, MD (Co-Principal Investigator); Anne Marie Kuzma, RN, MSN (Principal Clinic Coordinator); Roger Barnette, MD; Neil Brister, MD; Kevin Carney, RN, CCTC; Wissam Chatila, MD; Francis Cordova, MD; Gilbert D’Alonzo, DO; Michael Keresztury, MD; Karen Kirsch; Chul Kwak, MD; Kathy Lautensack, RN, BSN; Madelina Lorenzon, CPFT; Ubaldo Martin, MD; Peter Rising, MS; Scott Schartel, MD; John Travaline, MD; Gwendolyn Vance, RN, CCTC; Phillip Boiselle, MD (1997–2000); Gerald O’Brien, MD (1997–2000).
University of California, San Diego, San Diego, CA:
Andrew Ries, MD, MPH (Principal Investigator); Robert Kaplan, PhD (Co-Principal Investigator); Catherine Ramirez, BS, RCP (Principal Clinic Coordinator); David Frankville, MD; Paul Friedman, MD; James Harrell, MD; Jeffery Johnson; David Kapelanski, MD; David Kupferberg, MD, MPH; Catherine Larsen, MPH; Trina Limberg, RRT; Michael Magliocca, RN, CNP; Frank J. Papatheofanis, MD, PhD; Dawn Sassi-Dambron, RN; Melissa Weeks.
University of Maryland at Baltimore, Baltimore, MD, in consortium with Johns Hopkins Hospital, Baltimore, MD:
Mark Krasna, MD (Principal Investigator); Henry Fessler, MD (Co-Principal Investigator); Iris Moskowitz (Principal Clinic Coordinator); Timothy Gilbert, MD; Jonathan Orens, MD; Steven Scharf, MD, PhD; David Shade; Stanley Siegelman, MD; Kenneth Silver, MD; Clarence Weir; Charles White, MD.
University of Michigan, Ann Arbor, MI:
Fernando Martinez, MD (Principal Investigator); Mark Iannettoni, MD (Co-Principal Investigator); Catherine Meldrum, BSN, RN, CCRN (Principal Clinic Coordinator); William Bria, MD; Kelly Campbell; Paul Christensen, MD; Kevin Flaherty, MD; Steven Gay, MD; Paramjit Gill, RN; Paul Kazanjian, MD; Ella Kazerooni, MD; Vivian Knieper; Tammy Ojo, MD; Lewis Poole; Leslie Quint, MD; Paul Rysso; Thomas Sisson, MD; Mercedes True; Brian Woodcock, MD; Lori Zaremba, RN.
University of Pennsylvania, Philadelphia, PA:
Larry Kaiser, MD (Principal Investigator); John Hansen-Flaschen, MD (Co-Principal Investigator); Mary Louise Dempsey, BSN, RN (Principal Clinic Coordinator); Abass Alavi, MD; Theresa Alcorn, Selim Arcasoy, MD; Judith Aronchick, MD; Stanley Aukberg, MD; Bryan Benedict, RRT; Susan Craemer, BS, RRT, CPFT; Ron Daniele, MD; Jeffrey Edelman, MD; Warren Gefter, MD; Laura Kotler-Klein, MSS; Robert Kotloff, MD; David Lipson, MD; Wallace Miller, Jr., MD; Richard O’Connell, RPFT; Staci Opelman, MSW; Harold Palevsky, MD; William Russell, RPFT; Heather Sheaffer, MSW; Rodney Simcox, BSRT, RRT; Susanne Snedeker, RRT, CPFT; Jennifer Stone-Wynne, MSW; Gregory Tino, MD; Peter Wahl; James Walter, RPFT; Patricia Ward; David Zisman, MD; James Mendez, MSN, CRNP (1997–2001); Angela Wurster, MSN, CRNP (1997–1999).
University of Pittsburgh, Pittsburgh, PA:
Frank Sciurba, MD (Principal Investigator); James Luketich, MD (Co-Principal Investigator); Colleen Witt, MS (Principal Clinic Coordinator); Gerald Ayres; Michael Donahoe, MD; Carl Fuhrman, MD; Robert Hoffman, MD; Joan Lacomis, MD; Joan Sexton; William Slivka; Diane Strollo, MD; Erin Sullivan, MD; Tomeka Simon; Catherine Wrona, RN, BSN; Gerene Bauldoff, RN, MSN (1997–2000); Manuel Brown, MD (1997–2002); Elisabeth George, RN, MSN (Principal Clinic Coordinator 1997–2001); Robert Keenan, MD (Co-Principal Investigator 1997–2000); Theodore Kopp, MS (1997–1999); Laurie Silfies (1997–2001).
University of Washington, Seattle, WA:
Joshua Benditt, MD (Principal Investigator), Douglas Wood, MD (Co-Principal Investigator); Margaret Snyder, MN (Principal Clinic Coordinator); Kymberley Anable; Nancy Battaglia; Louie Boitano; Andrew Bowdle, MD; Leighton Chan, MD; Cindy Chwalik; Bruce Culver, MD; Thurman Gillespy, MD; David Godwin, MD; Jeanne Hoffman; Andra Ibrahim, MD; Diane Lockhart; Stephen Marglin, MD; Kenneth Martay, MD; Patricia McDowell; Donald Oxorn, MD; Liz Roessler; Michelle Toshima; Susan Golden (1998–2000).
Agency for Healthcare Research and Quality, Rockville, MD:
Lynn Bosco, MD, MPH; Yen-Pin Chiang, PhD; Carolyn Clancy, MD; Harry Handelsman, DO.
Centers for Medicare and Medicaid Services, Baltimore, MD:
Steven M Berkowitz, PhD; Tanisha Carino, PhD; Joe Chin, MD; JoAnna Baldwin; Karen McVearry; Anthony Norris; Sarah Shirey; Claudette Sikora; Steven Sheingold, PhD (1997–2004).
Coordinating Center, The Johns Hopkins University, Baltimore, MD:
Steven Piantadosi, MD, PhD (Principal Investigator); James Tonascia, PhD (Co-Principal Investigator); Patricia Belt; Amanda Blackford, ScM; Karen Collins; Betty Collison; Ryan Colvin, MPH; John Dodge; Michele Donithan, MHS; Vera Edmonds; Gregory L. Foster, MA; Julie Fuller; Judith Harle; Rosetta Jackson; Shing Lee, ScM; Charlene Levine; Hope Livingston; Jill Meinert; Jennifer Meyers; Deborah Nowakowski; Kapreena Owens; Shangqian Qi, MD; Michael Smith; Brett Simon, MD; Paul Smith; Alice Sternberg, ScM; Mark Van Natta, MHS; Laura Wilson, ScM; Robert Wise, MD.
Robert M. Kaplan, PhD (Chair); J. Sanford Schwartz, MD (Co-Chair); Yen-Pin Chiang, PhD; Marianne C. Fahs, PhD; A. Mark Fendrick, MD; Alan J. Moskowitz, MD; Dev Pathak, PhD; Scott Ramsey, MD, PhD; Steven Sheingold, PhD; A. Laurie Shroyer, PhD; Judith Wagner, PhD; Roger Yusen, MD.
Cost-effectiveness Data Center, Fred Hutchinson Cancer Research Center, Seattle, WA:
Scott Ramsey, MD, PhD (Principal Investigator); Ruth Etzioni, PhD; Sean Sullivan, PhD; Douglas Wood, MD; Thomas Schroeder, MA; Karma Kreizenbeck; Kristin Berry, MS; Nadia Howlader, MS.
CT Scan Image Storage and Analysis Center, University of Iowa, Iowa City, IA:
Eric Hoffman, PhD (Principal Investigator); Janice Cook-Granroth, BS; Angela Delsing, RT; Junfeng Guo, PhD; Geoffrey McLennan, MD; Brian Mullan, MD; Chris Piker, BS; Joseph Reinhardt, PhD; Blake Robinswood; Jered Sieren, RTR; William Stanford, MD.
Data and Safety Monitoring Board:
John A. Waldhausen, MD (Chair); Gordon Bernard, MD; David DeMets, PhD; Mark Ferguson, MD; Eddie Hoover, MD; Robert Levine, MD; Donald Mahler, MD; A. John McSweeny, PhD; Jeanine Wiener-Kronish, MD; O. Dale Williams, PhD; Magdy Younes, MD.
Marketing Center, Temple University, Philadelphia, PA:
Gerard Criner, MD (Principal Investigator); Charles Soltoff, MBA.
Project Office, National Heart, Lung, and Blood Institute, Bethesda, MD:
Gail Weinmann, MD (Project Officer); Joanne Deshler (Contracting Officer); Dean Follmann, PhD; James Kiley, PhD; Margaret Wu, PhD (1996–2001).
Arthur Gelb, MD, Lakewood Regional Medical Center, Lakewood, CA.
Table 1. Characteristics of 1,066 Patients Included in the Cost-effectiveness Analysis From the NETT*
| Save Table
|Characteristics||Surgery Group (n = 531)||Medical Therapy Group (n = 535)|
|Mean age at randomization, yr||67.0 ± 6.2||67.1 ± 5.8|
|Race or ethnic group|
| Non-Hispanic white||506 (95.3)||506 (94.6)|
| Non-Hispanic black||17 (3.2)||18 (3.4)|
| Other||8 (1.5)||11 (2.0)|
| Female||232 (43.7)||196 (36.6)|
| Male||299 (56.3)||339 (63.4)|
|Average daily QWB score†||0.58 ± 0.12||0.57 ± 0.11|
Table 2. Total Health-Care–Related Costs and QALYs With Observation Up to 5 Years After Randomization Overall and Among Subgroups of Patients Defined by Baseline by Distribution of Emphysema and Exercise Capacity
| Save Table
|Variables||LVRS Group||Medical Therapy Group||p Value|
|Mean||95% CI||Mean||95% CI|
| No. of patients||531||535|
| Total costs†||$136,997||$127,329–$146,664||$100,153||$91,199–$109,106||< 0.001|
| QALYs||1.8986||1.8915–1.9057||1.635||1.6286–1.6413||< 0.001|
| Upper-lobe emphysema and low exercise capacity‡|
| No. of patients||137||148|
| Total costs†||$152,368||$132,143–$172,593||$99,023||$84,218–$113,829||< 0.001|
| QALYs||2.0266||2.0127–2.0405||1.3366||1.3256–1.3476||< 0.001|
| Upper-lobe emphysema and high exercise capacity‡|
| No. of patients||204||212|
| Total costs†||$129,582||$111,458–$147,707||$99,894||$85,604–$114,185||0.013|
| QALYs||2.0734||2.0620–2.0848||1.8982||1.8884–1.9081||< 0.001|
| Non–upper-lobe emphysema and low exercise capacity‡|
| No. of patients||82||65|
| Total costs†||$143,154||$122,940–$163,369||$98,429||$77,747–$119,111||0.006|
| QALYs||1.5298||1.5134–1.5462||1.3313||1.3313–1.3313||< 0.001|
Table 3. Projected and Observed Cost-effectiveness Ratios for LVRS vs Maximal Medical Therapy for Observed and Projected Years of Follow-up From Initial Randomization, Using Observations Up to 3 Years and 5 Years After Randomization
| Save Table
|Incremental Cost-effectiveness Ratio*||All Patients†||Subgroups|
|Upper-Lobe Emphysema, Low Exercise Capacity*||Upper-Lobe Emphysema, High Exercise Capacity*||Non–Upper-Lobe Emphysema, Low Exercise Capacity*|
|Observed up to 3 yr||$190,000||$98,000||$240,000||$330,000|
|Observed up to 5 yr||$140,000||$77,000||$170,000||$225,000|
|Projected at 10 yr based on 3 yr of follow-up‡||$58,000||$21,000||$54,000||Dominant§|
|Projected at 10 yr based on 5 yr of follow-up‡||$54,000||$48,000||$40,000||$87,000|
Figure Jump LinkFigure 1. Five-year cost-effectiveness acceptability curves for LVRS vs medical therapy for all patients and for three subgroups with significantly improved clinical outcomes in the LVRS arm (either reduced mortality, improved quality of life, or both). The curve represents the probability that LVRS is associated with a cost per QALY gained that is lower than the corresponding cost-effectiveness ratios displayed on the x-axis. The value of the ceiling ratio at a probability of 0.5 is the median cost per QALY for LVRS. Solid horizontal lines denote 95% confidence limits for the projections.Grahic Jump Location
Figure Jump LinkFigure 2. Ten-year cost-effectiveness acceptability curves for LVRS vs medical therapy for all patients and for three subgroups with significantly improved clinical outcomes in the LVRS arm (either reduced mortality, improved quality of life, or both). The curve represents the probability that LVRS is associated with a cost per QALY gained that is lower than the corresponding cost-effectiveness ratios displayed on the x-axis. The value of the ceiling ratio at a probability of 0.5 is the median cost per QALY for LVRS. Solid horizontal lines denote 95% confidence limits for the projections.Grahic Jump Location
Figure Jump LinkFigure 3. Discharges for LVRS following approval by the CMS for LVRS, January 2004 to September 2005. Source: Calendar year 2004 and 2005 CMS Medicare Provider Analysis and Review files.Grahic Jump Location
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