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Background Lung-volume–reduction surgery has been proposed as a palliative treatment for severe emphysema. Effects on mortality, the magnitude and durability of benefits, and criteria for the selection of patients have not been established.
Methods A total of 1218 patients with severe emphysema underwent pulmonary rehabilitation and were randomly assigned to undergo lung-volume–reduction surgery or to receive continued medical treatment.
Results Overall mortality was 0.11 death per person-year in both treatment groups (risk ratio for death in the surgery group, 1.01; P=0.90). After 24 months, exercise capacity had improved by more than 10 W in 15 percent of the patients in the surgery group, as compared with 3 percent of patients in the medical-therapy group (P<0.001). With the exclusion of a subgroup of 140 patients at high risk for death from surgery according to an interim analysis, overall mortality in the surgery group was 0.09 death per person-year, as compared with 0.10 death per person-year in the medical-therapy group (risk ratio, 0.89; P=0.31); exercise capacity after 24 months had improved by more than 10 W in 16 percent of patients in the surgery group, as compared with 3 percent of patients in the medical-therapy group (P<0.001). Among patients with predominantly upper-lobe emphysema and low exercise capacity, mortality was lower in the surgery group than in the medical-therapy group (risk ratio for death, 0.47; P=0.005). Among patients with non–upper-lobe emphysema and high exercise capacity, mortality was higher in the surgery group than in the medical-therapy group (risk ratio, 2.06; P=0.02).
Conclusions Overall, lung-volume–reduction surgery increases the chance of improved exercise capacity but does not confer a survival advantage over medical therapy. It does yield a survival advantage for patients with both predominantly upper-lobe emphysema and low base-line exercise capacity. Patients previously reported to be at high risk and those with non–upper-lobe emphysema and high base-line exercise capacity are poor candidates for lung-volume–reduction surgery, because of increased mortality and negligible functional gain.
Methods
The design and methods of the trial have been described previously.9 We summarize them below.
Population of Patients and Assessments
At 17 clinics, patients with severe emphysema underwent comprehensive medical evaluation to ensure compliance with usual medical therapy and to rule out clinically significant coexisting conditions.9 Base-line measurements were completed after pulmonary rehabilitation but before randomization, and patients underwent complete evaluations at 6 months, 12 months, and yearly thereafter. Overall mortality and maximal exercise capacity (on cycle ergometry with an increment of 5 or 10 W per minute after three minutes of pedaling with the ergometer set at 0 W and the patient breathing 30 percent oxygen) were the primary outcome measures. Secondary outcome measures included pulmonary function,10,11 the distance walked in six minutes,12,13 and the results on a self-administered questionnaire about health-related quality of life (St. George's Respiratory Questionnaire),14 a general quality-of-life questionnaire (the Quality of Well-Being scale),15 and a dyspnea questionnaire (the University of California, San Diego, Shortness of Breath Questionnaire16).
The distribution of emphysema was classified as heterogeneous or homogeneous on the basis of high-resolution computed tomography (CT) with the use of a visual scoring system.17 In addition, the radiologist classified the craniocaudal distribution of emphysema as predominantly affecting the upper lobes, predominantly affecting the lower lobes, diffuse, or predominantly affecting the superior segments of the lower lobes; the latter three categories were grouped together as predominantly non–upper-lobe emphysema for the purposes of our analysis. The ratio of perfusion in the upper regions of the lungs to that in the lower regions was quantified on the basis of radionuclide scans of the lungs that were interpreted at each center.
Before randomization, eligible patients completed 6 to 10 weeks of pulmonary rehabilitation supervised by study personnel. All patients provided written informed consent, and the study was approved by the institutional review board at each clinic. In May 2001, patients with a forced expiratory volume in one second (FEV1) that was 20 percent or less of the predicted value and either a homogeneous distribution of emphysema or a carbon monoxide diffusing capacity that was 20 percent or less of the predicted value were determined to be at high risk for death after lung-volume–reduction surgery, with a low probability of functional benefit,17 and were no longer eligible for randomization. Detailed criteria for inclusion in and exclusion from the trial are listed in Supplementary Appendix 1 (available with the full text of this article at http://www.nejm.org).
Patients randomly assigned to lung-volume–reduction surgery underwent bilateral stapled wedge resection through a median sternotomy or video-assisted thoracic surgery; the goal was to resect 20 to 35 percent of each lung, targeting the most diseased portions. Eight centers performed lung-volume reduction by median sternotomy alone, three centers by video-assisted thoracic surgery alone, and six by median sternotomy or video-assisted thoracic surgery selected randomly. Patients' adherence to medical regimens, abstinence from tobacco use, and pulmonary-rehabilitation treatment at home were monitored through regular telephone calls and clinic visits.
Definition of Outcomes
Vital status, ascertained as of December 2002, was determined by reports from the clinical centers and review of the Social Security Administration's December 2002 Death Master File.18,19 Total, 30-day, and 90-day mortality from all causes were measured from the day of randomization for both treatment groups. On the basis of previous experience, we defined improvement in maximal exercise capacity as an increase in the maximal workload of more than 10 W from the postrehabilitation base-line level. Improvement in health-related quality of life was defined as a decrease in the score on the St. George's Respiratory Questionnaire of more than 8 points (on a 100-point scale) from the base-line level (measured after rehabilitation). These thresholds are higher than those typically used to define minimal clinically important differences (e.g., a four-point change on the respiratory questionnaire is usually used20) but were selected to represent a degree of improvement that would be appropriate to justify the high risks associated with surgery in patients with severe emphysema. Patients who died or were missing data required for the assessment were considered not to have had improvement.
Statistical Analysis
All analyses were performed according to the intention-to-treat principle. Fisher's exact test was used to compare the proportions of patients in each group who died.21 The trial protocol specified that the primary comparison would be between the proportions of patients in the two groups who died rather than a comparison with the use of a typical rank-based test (e.g., a log-rank or Wilcoxon test) for differences in mortality, because the hazard functions for death were expected to cross, resulting in nonproportional hazards. This crossing of hazards was anticipated as a consequence of the expected perioperative mortality, potentially followed by lower mortality in the surgery group after six months.22 The risk ratio for death was estimated on the basis of the overall mortality in each group after a mean of 29.2 months of follow-up.21
Despite randomization, differential early mortality makes survivors in the surgery group appear healthier than their counterparts in the medical-therapy group. This imbalance confounds the interpretation of outcomes measured only in survivors, such as exercise capacity, pulmonary function, and quality of life. Therefore, we used classifications derived from measured outcomes defined for all patients, such as improvement versus no improvement, with the latter category also including patients who were unable to complete the evaluation or who had died. The cutoff point used for a derived variable — for example, the definition of improvement — is necessarily somewhat arbitrary.
Histograms were used to compare the surgery group and the medical-therapy group in terms of the distributions of categories of change from base line in the outcome measures; all patients who were followed for 6, 12, and 24 months were included in these analyses. The histograms included 8 or 10 categories of the change measured in survivors (scored from 2 to 12, with higher scores indicating more improvement), a category for patients who died (scored as 0), and a category for patients who missed or were unable to complete the evaluation (scored as 1). For cycle ergometry, patients who could pedal only with the ergometer set at 0 W were also given a score of 1. For the Quality of Well-Being scale, patients who died were assigned a score of 0 on the questionnaire for that visit, and patients who did not complete the questionnaire were assigned a score equal to half of the lowest score observed for that visit. P values for the comparisons of the two groups in terms of the distribution of scores were derived by the Wilcoxon rank-sum test.23
Subgroups of patients with differential risks or benefits were identified with the use of a series of logistic-regression analyses that included as the outcome death, improvement in exercise capacity, or improvement in health-related quality of life at 6, 12, or 24 months. For each outcome, the model included terms for the treatment-group assignment, a base-line prognostic factor, and the interaction between the treatment group and the prognostic factor, to test whether or not the factor was associated with differential outcome. P values for the interaction terms were determined by exact-score tests for logistic regression,24 and factors with statistically significant interactions were also examined in logistic models including pairwise combinations of the factors with corresponding interaction terms.
Most prognostic factors were identified by a hypothesis specified in the trial protocol (age, percentage of the predicted value for the FEV1, partial pressure of arterial carbon dioxide, percentage of the predicted value for the residual volume, distribution of perfusion on radionuclide scanning of the lungs, homogeneity or heterogeneity of the distribution of emphysema on CT, and presence or absence of hyperinflation on chest radiography).17 Other base-line prognostic factors were added by the data and safety monitoring board or the investigators after the initiation of the trial but well before the completion of data collection (percentage of predicted value for carbon monoxide diffusing capacity, maximal exercise capacity, ratio of residual volume to total lung capacity, ratio of expired ventilation in one minute to carbon dioxide excretion in one minute, presence or absence of upper-lobe predominance of emphysema, degree of dyspnea, quality of life, race or ethnic group, and sex). Measured prognostic factors were categorized into approximate quartiles, and patients in the quartile with the worst prognosis were compared with all other patients. The prognostic factors were analyzed quarterly as part of ongoing monitoring of the study to meet the a priori objective of identifying characteristics of patients who might have a differential risk of harm or differential benefit from lung-volume–reduction surgery.
A base-line maximal exercise capacity in the lowest quartile (
25 W) was one of the two prognostic factors that identified patients with a differential risk of death. Recognizing that there are differences between men and women in exercise capacity, we refined the cutoff point for base-line maximal exercise capacity by examining a range of sex-specific cutoff points, and we found that the sex-specific 40th percentile (25 W for women and 40 W for men) was the best cutoff point for the classification of patients with a differential risk of death from lung-volume–reduction surgery (see Supplementary Appendix 2, available with the full text of this article at http://www.nejm.org).
All reported P values are based on two-sided tests. P values were not corrected for multiple comparisons. The primary and secondary objectives of the trial were identified by hypothesis before the study began and specifically included the identification of subgroups associated with differential harm or benefit from lung-volume–reduction surgery. Although a large number of statistical tests were possible, we limited the number through planning and an orderly analysis of the data. The prognostic factors identified have a plausible clinical rationale and were associated with large, statistically significant risk ratios.
The study protocol specified that recruitment would end by July 2002, with an accrual of 2500 patients and study completion in December 2002. This design was based on a primary survival comparison allowing for 8 percent mortality in the group assigned to medical therapy and for a rate of unplanned crossover of 30 percent among those assigned to medical therapy.9 The trial was ended on the planned date despite accrual that was lower than expected. Had the study been designed with the assumptions of the higher mortality rate and the lower crossover rate that were actually observed (0.11 death per person-year and 5.4 percent, respectively), the recruitment goal would have been 1190 patients.
Results
Study Patients
Between January 1998 and July 2002, 3777 patients were evaluated, and 1218 patients underwent randomization — 608 to surgery and 610 to medical therapy. The groups had similar base-line characteristics after rehabilitation, except that there was a higher proportion of men in the medical-therapy group (Table 1) (Results for subgroups are given in Supplementary Appendix 3 [available with the full text of this article at http://www.nejm.org]). As of December 2002, 99 percent of surviving patients continued to complete quarterly telephone interviews or annual clinic visits.
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Of the 608 patients assigned to lung-volume–reduction surgery, 580 (95.4 percent) underwent surgery (406 [70.0 percent] of them by median sternotomy and 174 [30.0 percent] by video-assisted thoracic surgery), 21 (3.5 percent) declined to undergo surgery, and 7 (1.2 percent) were deemed to be unsuitable for surgery after randomization. The median time from randomization to surgery was 10 days; 74 of the patients assigned to lung-volume–reduction surgery (12.2 percent) underwent surgery more than 14 days after randomization. Deviations from the surgical protocol (unilateral surgery or bilateral surgery performed in two sessions) occurred in 12 patients (2.0 percent) because of intraoperative factors; 4 patients in the surgery group (0.7 percent) received lung transplants after undergoing lung-volume–reduction surgery. Among the 610 patients assigned to medical therapy, 33 (5.4 percent) underwent lung-volume–reduction surgery outside the study, and 15 (2.5 percent) received lung transplants during follow-up.
Outcomes for All 1218 Patients
The 90-day mortality rate in the surgery group was 7.9 percent (95 percent confidence interval, 5.9 to 10.3) and was significantly higher than that in the medical-therapy group (1.3 percent [95 percent confidence interval, 0.6 to 2.6], P<0.001) (Table 2). The 90-day mortality rate was similar among patients who underwent video-assisted thoracic surgery and among those who underwent median sternotomy (6.1 percent and 8.6 percent, respectively; P=0.33). All clinics reported similar rates of mortality, morbidity, and common intraoperative and postoperative complications. During follow-up (mean duration, 29.2 months), 157 patients assigned to lung-volume–reduction surgery and 160 assigned to medical therapy died. The total mortality rate was 0.11 death per person-year in both groups (risk ratio for death in the surgery group, 1.01; P=0.90) (Table 2). There was no significant difference in overall mortality despite a higher early mortality rate in the surgery group (Figure 1A).
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The subgroup of 140 patients with a value for FEV1 that was 20 percent or less of the predicted value and either homogeneous emphysema or a carbon monoxide diffusing capacity that was 20 percent or less of the predicted value was previously reported to be at high risk for death after lung-volume–reduction surgery, with little chance of functional benefit.17 The updated analyses of mortality and functional improvement in this subgroup support the previous findings (Table 2 and Table 3 and Figure 1B).
Outcomes for Patients without High Risk
Among the 1078 patients who were not at high risk, the 30-day mortality rate was 2.2 percent in the surgery group, as compared with 0.2 percent in the medical-therapy group (P<0.001), and the 90-day mortality rate was 5.2 percent in the surgery group, as compared with 1.5 percent in the medical-therapy group (P=0.001) (Table 2). One month after randomization, 28.1 percent of the patients in the surgery group, as compared with 2.2 percent of the patients in the medical-therapy group, were hospitalized, living in a nursing or rehabilitation facility, or unavailable for interview but not known to be dead (P<0.001 for the comparison between groups); at two months, the percentages were 14.3 percent and 3.3 percent, respectively (P<0.001); at four months, 6.7 percent and 3.2 percent, respectively (P=0.007); and at eight months, 3.3 percent and 3.7 percent, respectively (P=0.87) (see Supplementary Appendix 5 [available with the full text of this article at http://www.nejm.org]).
Total mortality among patients who were not at high risk during the trial was 0.09 death per person-year in the surgery group, as compared with 0.10 death per person-year in the medical-therapy group (risk ratio, 0.89; P=0.31) (Table 2 and Figure 1C). Changes in exercise capacity, distance walked in six minutes, percentage of the predicted value for FEV1, quality of life, and degree of dyspnea at 6, 12, and 24 months all favored the surgery group (Table 3, Figure 2, and Supplementary Appendix 6 [available with the full text of this article at http://www.nejm.org]). When the analysis was limited to survivors who were able to complete the follow-up assessments, the pattern of changes in the outcome measures showed a progressive decline from base line in the medical-therapy group; the surgery group had improvements from base line but also had a gradual decline over the course of 24 months (see Supplementary Appendix 7 [available with the full text of this article at http://www.nejm.org]).
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The only individual base-line factors associated with differences in mortality between the treatment groups were the craniocaudal distribution of emphysema (presence or absence of upper-lobe predominance, P for interaction = 0.02) and base-line exercise capacity (low or high, P for interaction = 0.01). The only individual base-line factor associated with differential improvement in the maximal workload at 24 months was the craniocaudal distribution of emphysema (presence or absence of upper-lobe predominance, P for interaction = 0.005). No base-line factor we considered was predictive of differential improvement in the health-related quality of life.
When patients were divided into four subgroups on the basis of combinations of upper-lobe or non–upper-lobe emphysema and low or high exercise capacity at base line, there was strong evidence of differential effects on the risk of death (P for interaction = 0.004) and on exercise capacity at 24 months (P for interaction = 0.005). Among 290 patients with upper-lobe disease and low exercise capacity, patients in the surgery group had a lower risk of death than patients in the medical-therapy group (risk ratio, 0.47; P=0.005) (Figure 1D and Table 2), were more likely to have an improvement of more than 10 W in the maximal workload at 24 months (30 percent vs. 0 percent, P<0.001) (Table 3), and were more likely to have an eight-point improvement in the St. George's Respiratory Questionnaire score at 24 months (48 percent vs. 10 percent, P<0.001) (Table 3).
Among the 419 patients with upper-lobe disease and high exercise capacity, mortality was similar, regardless of the treatment-group assignment (risk ratio for death in the surgery group, 0.98; P=0.70) (Figure 1E and Table 2). However, patients in the surgery group were more likely than those in the medical-therapy group to have improvement of more than 10 W in the maximal workload at 24 months (15 percent vs. 3 percent, P=0.001) (Table 3) and to have an eight-point improvement in the health-related quality-of-life score at 24 months (41 percent vs. 11 percent, P<0.001) (Table 3).
The 149 patients with non–upper-lobe disease and low exercise capacity had a similar risk of death, regardless of the treatment group (risk ratio for the surgery group, 0.81; P=0.49) (Figure 1F and Table 2), and had similar chances of improvement of more than 10 W in the maximal workload at 24 months, regardless of the treatment group (12 percent vs. 7 percent, P=0.50) (Table 3), but patients in the surgery group had a greater chance than patients in the medical-therapy group of an eight-point improvement in health-related quality of life at 24 months (37 percent vs. 7 percent, P=0.001) (Table 3).
Among the 220 patients with non–upper-lobe disease and high exercise capacity, patients in the surgery group had a higher risk of death than those in the medical-therapy group (risk ratio, 2.06; P=0.02) (Figure 1G and Table 2), a similarly low chance of improvement of more than 10 W in the maximal workload at 24 months (3 percent in both groups, P=1.00) (Table 3), and a similar chance of an eight-point improvement in health-related quality of life (15 percent vs. 12 percent, P=0.61) (Table 3).
Changes in the maximal workload are shown in Figure 3 for these four subgroups of patients. For patients with either predominantly upper-lobe emphysema or low exercise capacity after rehabilitation, outcomes favored the surgery group at nearly all time points. Similar patterns of outcomes were seen in the changes in the total daily score for health-related quality of life in these subgroups (see Supplementary Appendix 8 [available with the full text of this article at http://www.nejm.org]). Only in the subgroup with both non–upper-lobe emphysema and high maximal workload at base line did patients in the surgery group not have greater functional and symptomatic improvement than patients in the medical-therapy group.
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Our study provides reliable estimates of risk and benefit from lung-volume–reduction surgery because of the size of the sample, the use of randomization, the participation of multiple institutions, the use of well-defined measurements, the long-term follow-up, and the low crossover rates. Overall mortality was similar in the surgery and medical-therapy groups, both for all patients and when the previously identified high-risk patients were excluded. Lung-volume–reduction surgery was associated with a greater chance of improvement in exercise capacity, lung function, quality of life, and dyspnea, but the changes after surgery were highly variable, both among all patients and among those who were not at high risk. After two years, values for the measures of function in survivors in the surgery group had returned nearly to base-line levels, on average, and the values in survivors in the medical-therapy group had continued to deteriorate to levels below base-line values. The functional benefits of lung-volume–reduction surgery came at the price of increased short-term mortality and morbidity.
Because of the broad criteria for inclusion in our study, analysis of prognostic factors allowed us to identify subgroups of patients for whom decisions about lung-volume–reduction surgery are fairly clear-cut. We recognize the pitfalls of subgroup analyses, but we believe that the heterogeneity of the patients and of the outcomes and the considered approach we used make our findings clinically and statistically valid. The subgroup-specific findings were not the result of data mining or the optimization of P values. The candidate prognostic factors we used to identify subgroups were in large part specified in advance on the basis of biologic rationale. The procedures and categorizations for identifying subgroups were carried out under the supervision of the independent data and safety monitoring board.
After high-risk patients had been excluded,17 four additional clinically meaningful subgroups of patients were identified on the basis of the pattern of emphysema on CT scanning and exercise capacity after rehabilitation. Patients with predominantly upper-lobe emphysema and a low maximal workload after rehabilitation had lower mortality, a greater probability of improvement in exercise capacity, and a greater probability of improvement in symptoms if they underwent lung-volume–reduction surgery than if they received medical therapy alone. In contrast, patients with predominantly non–upper-lobe emphysema and a high maximal workload after rehabilitation had higher mortality if they underwent lung-volume–reduction surgery than if they received medical therapy alone, and they had little chance of functional improvement regardless of the treatment they received. In these subgroups, the risks and benefits of surgery as compared with medical treatment are reasonably clear.
Mortality among the remaining patients was largely independent of the treatment-group assignment. For patients with predominantly upper-lobe disease and a high maximal workload, lung-volume–reduction surgery offered a greater chance for improvement in exercise capacity and symptoms than medical therapy, but only a small percentage of patients had an improvement in exercise capacity of more than 10 W from their base-line level. Patients with non–upper-lobe emphysema and a low maximal workload had only a small chance of improvement in exercise capacity, regardless of the treatment group, but had a greater chance of symptomatic improvement after lung-volume–reduction surgery than with medical therapy.
Upper-lobe emphysema has been associated with short-term improvement in pulmonary function after lung-volume–reduction surgery.25,26,27 Our study demonstrates that this pattern of disease is predictive of improved survival in patients who also have low maximal exercise capacity. Upper-lobe predominance, as compared with other patterns, may result in clearer target areas for surgical resection or more accessible areas for excision, or it may indicate that the remaining lung tissue is healthier.
Low exercise capacity was an unanticipated predictor of a survival benefit after lung-volume–reduction surgery. The better survival among patients with low exercise capacity who underwent surgery appears to be due to the very high mortality and marked progressive functional limitation of the patients with low exercise capacity in the medical-therapy group.
Overall, lung-volume–reduction surgery offered no survival benefit. According to our subgroup analysis, it is likely that patients with certain characteristics will have improved survival and function. The survival benefit was limited to patients with predominantly upper-lobe emphysema and a low base-line exercise capacity, but functional benefits were noted in patients with predominantly upper-lobe emphysema and a high base-line exercise capacity and in patients with non–upper-lobe emphysema and a low base-line exercise capacity. Individual outcomes vary widely, but our study provides reliable estimates of outcomes to guide physicians and patients in making decisions about treatment.
Supported by contracts with the National Heart, Lung, and Blood Institute (N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, and N01HR76119), the Centers for Medicare and Medicaid Services, and the Agency for Healthcare Research and Quality.
Source Information
The writing committee for the National Emphysema Treatment Trial (NETT) (Alfred Fishman, M.D., University of Pennsylvania, Philadelphia; Fernando Martinez, M.D., University of Michigan, Ann Arbor; Keith Naunheim, M.D., Saint Louis University, St. Louis; Steven Piantadosi, M.D., Ph.D., and Robert Wise, M.D., Johns Hopkins University, Baltimore; Andrew Ries, M.D., M.P.H., University of California, San Diego, La Jolla; Gail Weinmann, M.D., National Heart, Lung, and Blood Institute, Bethesda, Md.; and Douglas E. Wood, M.D., University of Washington, Seattle) takes responsibility for the content of this article.
This article was published at www.nejm.org on May 20, 2003.
Address reprint requests to Dr. Piantadosi at the NETT Coordinating Center, 615 N. Wolfe St., Rm. 5010, Baltimore, MD 21205.
References
The members of the National Emphysema Treatment Trial Research Group were as follows: Office of the Chair of the Steering Committee, University of Pennsylvania, Philadelphia: A.P. Fishman, B.A. Bozzarello, A. Al-Amin. Clinical Centers: Baylor College of Medicine, Houston: M. Katz, C. Wheeler, E. Baker, P. Barnard, J. Carter, S. Chatziioannou, K. Conejo-Gonzales, J. Haddad, D. Hicks, N. Kleiman, M. Milburn-Barnes, C. Nguyen, M. Reardon, J. Reeves-Viets, S. Sax, A. Sharafkhaneh, C. Young, R. Espada, R. Butanda, K. Dubose, M. Ellisor, P. Fox, K. Hale, E. Hood, A. Jahn, S. Jhingran, K. King, C. Miller, I. Nizami, T. Officer, J. Ricketts, J. Rodarte, R. Teague, K. Williams; Brigham and Women's Hospital, Boston: J. Reilly, D. Sugarbaker, C. Fanning, S. Body, S. Duffy, V. Formanek, A. Fuhlbrigge, P. Hartigan, S. Hooper, A. Hunsaker, F. Jacobson, M. Moy, S. Peterson, R. Russell, D. Saunders, S. Swanson; Cedars–Sinai Medical Center, Los Angeles: R. McKenna, Z. Mohsenifar, C. Geaga, M. 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Rittinger; Saint Louis University, St. Louis: K. Naunheim, F. Alvarez, J. Osterloh, S. Borosh, W. Chamberlain, S. Frese, A. Hibbit, M.E. Kleinhenz, G. Ruppel, C. Stolar, J. Willey, C. Keller; Temple University, Philadelphia: G. Criner, S. Furukawa, A.M. Kuzma, R. Barnette, N. Brister, K. Carney, W. Chatila, F. Cordova, G. D'Alonzo, M. Keresztury, K. Kirsch, C. Kwak, K. Lautensack, M. Lorenzon, U. Martin, P. Rising, S. Schartel, J. Travaline, G. Vance, P. Boiselle, G. O'Brien; University of California, San Diego, San Diego: A. Ries, R. Kaplan, C. Ramirez, D. Frankville, P. Friedman, J. Harrell, J. Johnson, D. Kapelanski, D. Kupferberg, C. Larsen, T. Limberg, M. Magliocca, F.J. Papatheofanis, D. Sassi-Dambron, M. Weeks; University of Maryland at Baltimore, Baltimore, and Johns Hopkins Hospital, Baltimore: M. Krasna, H. Fessler, I. Moskowitz, T. Gilbert, J. Orens, S. Scharf, D. Shade, S. Siegelman, K. Silver, C. Weir, C. White; University of Michigan, Ann Arbor: F. Martinez, M. Iannettoni, C. Meldrum, W. Bria, K. Campbell, P. Christensen, K. Flaherty, S. Gay, P. Gill, P. Kazanjian, E. Kazerooni, V. Knieper, T. Ojo, L. Poole, L. Quint, P. Rysso, T. Sisson, M. True, B. Woodcock, L. Zaremba; University of Pennsylvania, Philadelphia: L. Kaiser, J. Hansen-Flaschen, M.L. Geraghty, A. Alavi, T. Alcorn, J. Aronchick, S. Aukberg, B. Benedict, S. Craemer, R. Daniele, J. Edelman, W. Gefter, L. Kotler-Klein, R. Kotloff, D. Lipson, W. Miller, Jr., R. O'Connell, S. Opelman, W. Russell, H. Sheaffer, R. Simcox, S. Snedeker, J. Stone-Wynne, G. Tino, P. Wahl, J. Walter, P. Ward, D. Zisman, J. Mendez, A. Wurster; University of Pittsburgh, Pittsburgh: F. Sciurba, J. Luketich, C. Witt, G. Ayres, M. Donahoe, C. Fuhrman, R. Hoffman, J. Lacomis, J. Sexton, W. Slivka, D. Strollo, E. Sullivan, T. Simon, C. Wrona, G. Bauldoff, M. Brown, E. George, R. Keenan, T. Kopp, L. Silfies; University of Washington, Seattle: J. Benditt, D. Wood, M. Snyder, K. Anable, N. Battaglia, L. Boitano, A. Bowdle, L. Chan, C. Chwalik, B. Culver, T. Gillespy, D. Godwin, J. Hoffman, A. Ibrahim, D. Lockhart, S. Marglin, K. Martay, P. McDowell, D. Oxorn, L. Roessler, M. Toshima, S. Golden.
Other participants included the following: Agency for Healthcare Research and Quality, Rockville, Md.: L. Bosco, Y.-P. Chiang, C. Clancy, H. Handelsman; Centers for Medicare and Medicaid Services, Baltimore: S. Sheingold, T. Carino, J. Chin, J. Farrell, K. McVearry, A. Norris, S. Shirey, C. Sikora; Coordinating Center, Johns Hopkins University, Baltimore: S. Piantadosi, J. Tonascia, P. Belt, K. Collins, B. Collison, J. Dodge, M. Donithan, V. Edmonds, J. Fuller, J. Harle, R. Jackson, H. Koppelman, S. Lee, C. Levine, H. Livingston, J. Meinert, J. Meyers, D. Nowakowski, K. Owens, S. Qi, M. Smith, B. Simon, P. Smith, A. Sternberg, M. Van Natta, L. Wilson, R. Wise; Cost-Effectiveness Subcommittee: R.M. Kaplan, J.S. Schwartz, Y-P. Chiang, M.C. Fahs, A.M. Fendrick, A.J. Moskowitz, D. Pathak, S. Ramsey, S. Sheingold, A.L. Shroyer, J. Wagner, R. Yusen; Cost-Effectiveness Data Center, Fred Hutchinson Cancer Research Center, Seattle: S. Ramsey, R. Etzioni, S. Sullivan, D. Wood, T. Schroeder, R. Smith, K. Berry, N. Myers; CT Scan Image Storage and Analysis Center, University of Iowa, Iowa City: E. Hoffman, J. Cook-Granroth, A. Delsing, J. Guo, G. McLennan, B. Mullan, C. Piker, J. Reinhardt, J. Sieren, W. Stanford; Data and Safety Monitoring Board: J.A. Waldhausen, G. Bernard, D. DeMets, M. Ferguson, E. Hoover, R. Levine, D. Mahler, A.J. McSweeny, J. Wiener-Kronish, O.D. Williams, M. Younes; Marketing Center, Temple University, Philadelphia: G. Criner, C. Soltoff; Project Office, National Heart, Lung, and Blood Institute, Bethesda, Md.: G. Weinmann, J. Deshler, D. Follmann, J. Kiley, M. Wu.
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N Engl J Med 2003;
349:999-1000, Sep 4, 2003.
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