Correspondence

Lung-Volume–Reduction Surgery

N Engl J Med 2003; 349:999-1000September 4, 2003

Article

To the Editor:

The report on the National Emphysema Treatment Trial (May 22 issue)1 states that in the subgroup of patients with predominantly upper-lobe disease and low base-line exercise capacity, lung-volume–reduction surgery, as compared with medical therapy, resulted in a significant improvement in exercise capacity and a lower risk of death. However, there were strikingly high proportions of subjects with missing data at 6, 12, and 24 months, especially in the medical-therapy group (Figure 3 of the article).

In our experience, follow-up according to the protocol is extremely difficult in such seriously ill subjects because of the frequent occurrence of acute exacerbations of disease, difficulty traveling to the research center, weather conditions, and so forth.2 The authors mention the missing data in a single sentence: “Patients who died or were missing data required for the assessment were considered not to have had improvement,” adding to the questionable validity of the conclusion, which is already based on post hoc analysis. Surprisingly, neither the authors nor the editorialists mention anything about the effect of the missing data, which certainly have a major effect on the conclusion that surgery was beneficial in the subgroup with predominantly upper-lobe disease and low exercise capacity. Hence, we do not believe that these results should be applied to this subgroup of patients in clinical practice, which would burden already exhausted health care budgets.

Smita S. Pakhale, M.D.
St. Boniface General Hospital, Winnipeg, MB R2H 2A6, Canada
smita.pakhale@utoronto.ca

Carlos Gutierrez, M.D.
Toronto General Hospital, Toronto, ON M5G 2C4, Canada

2 References

1
National Emphysema Treatment Trial Research Group. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003;348:2059-2073
Full Text | Web of Science | Medline

2
Goldstein RS, Todd TR, Guyatt G, et al. Influence of lung volume reduction surgery (LVRS) on health related quality of life in patients with chronic obstructive pulmonary disease. Thorax 2003;58:405-410
CrossRef | Web of Science | Medline

Author/Editor Response

The subgroups in our study were identified with the use of intention-to-treat analyses of our primary outcome measures: survival and exercise capacity at two years. The survival analyses had no missing data. With respect to data on exercise capacity, to avoid bias resulting from simply excluding patients in the medical-therapy and surgery groups who died or for whom data on exercise capacity at two years were missing, we assigned a “worst-rank score”1 to patients who died and a rank just above that to patients with missing data. This approach is supported by a study of patients with emphysema in which the patients who failed to return for visits had higher mortality than those who returned for visits.2 Since sensitivity analyses in which we assigned the median and 75th percentile of the nonmissing measures to the missing measures at two years yielded results similar to those reported (i.e., P<0.001 for the difference between the treatment groups), it is unlikely that any other reasonable assumptions about the missing data would change the conclusions in our report.

Steven Piantadosi, M.D., Ph.D.
Johns Hopkins University, Baltimore, MD 21205

Alfred Fishman, M.D.
University of Pennsylvania, Philadelphia, PA 19104

for the National Emphysema Treatment Trial Research Group

2 References

1
Lachin JM. Worst-rank score analysis with informatively missing observations in clinical trials. Control Clin Trials 1999;20:408-422
CrossRef | Medline

2
Butler CW, Snyder M, Wood DE, Curtis JR, Albert RK, Benditt JO. Underestimation of mortality following lung volume reduction surgery resulting from incomplete follow-up. Chest 2001;119:1056-1060
CrossRef | Web of Science | Medline

Citing Articles (1)