| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 2001;72:649-657
© 2001 The Society of Thoracic Surgeons
a The Overholt-BlueCross Emphysema Surgery Study Trial (OBEST), and the Clinical Services affiliated with the medical schools of Boston University, Harvard, Tufts, and University of Massachusetts, Boston and Worcester, Massachusetts, USA
Address reprint requests to Dr Berger, 824 Boylston St, Suite 101, Chestnut Hill, MA 02167
e-mail: robert_berger{at}hms.harvard.edu
Abstract
Although unanswered questions remain, scores of observational studies and several small randomized clinical trials (RCTs) indicate that lung volume reduction surgery (LVRS) offers safe and effective palliation for a relatively well defined subset of patients with advanced emphysema. Nonetheless, Medicare and other insurers stopped reimbursement for the procedure. Subsequently, two multicenter RCTs on LVRS, the National Emphysema Treatment Trial (NETT) and the Overholt-BlueCross Emphysema Surgery Trial (OBEST), were launched with the stipulation that the procedure would not be paid for outside these trials. Thus access to LVRS has been denied to patients who could benefit but do not wish to participate in an RCT. Emerging operations, unlike new drugs or devices, pass through evolutionary changes and frequently fail to produce data that meet the scientific rigor required by randomized studies. In such a setting, the observational approach is more appropriate. Indeed, almost all operations in the present surgical armamentarium have been evaluated and have evolved through observational studies without the use of RCTs. By the time new operations are standardized and qualify for RCTs, benefits for certain patients may be demonstrated and randomization could involve unacceptable health hazards. Patients from this population should be offered the choice between participating in RCTs and having the operation outside the study. Imposition of financial restrictions that bars access to a therapy with known benefit is a questionable practice.
Almost all operations in the contemporary surgical repertoire have been evaluated through retrospective analysis of observational data obtained from case series. It has been suggested in recent decades that new operations, like new drugs, should be routinely evaluated through randomized clinical trials (RCTs) [1–3]. The history of the evaluation of lung volume reduction surgery (LVRS), a recently rediscovered operation for treating far advanced emphysema, raises questions about the wisdom of evaluating all new operations through a randomized strategy. We shall summarize that history here, and on the basis of that history, we shall explore the merits of various methods of assessing the effectiveness of emerging surgeries [4, 5].
The LVRS story
Pulmonary emphysema affects approximately 2 million adults in the United States and three to four times that number worldwide. Medical treatment offers only limited palliation and does not slow or halt progression of the disease. Of the many operations introduced during the past century to remedy the consequences of advanced emphysema, almost all failed to achieve the desired objectives and were abandoned [5]. One of the exceptions, lung transplantation, is of limited value because of the scarcity of donor organs. The second promising surgical approach, lung volume reduction surgery, entails resection of 20% to 30% of the most diseased portion of each lung. Introduced by Brantigan and Mueller [6] in the late 1950s, the operation was based on the theory that reducing lung size restores elastic recoil and circumferential pull on small bronchioles, leading to improved pulmonary function, chest wall mechanics, and exercise tolerance. By 1961, Brantigan had performed LVRS on 56 patients [7]. Although nearly 90% of the surviving patients experienced symptomatic improvement, LVRS was abandoned because of the high operative mortality (18%) and failure to document the subjective improvements with objective measurements.
In 1994, after an almost 40-year hiatus, Cooper and associates [8] reintroduced LVRS and reproduced the gratifying symptomatic response reported by Brantigan. The operative mortality was approximately 5%. Objective assessment showed improved pulmonary function, exercise tolerance, and quality of life indices [8]. Following Cooper’s lead, other surgical teams produced similar results and LVRS gained increasing acceptance [9, 10]. A 1996 editorial in the New England Journal of Medicine noted: "Whatever the physiologic mechanism, surgery to reduce lung volume in properly selected patients can lead to substantial relief of suffering with acceptable rates of mortality and morbidity" [11]. Thoracic specialty groups endorsed the short-term effectiveness of lung volume reduction. The operation was assigned a CPT code [12, 13]. LVRS also received extensive media attention [14–16]. From the rapidly growing collective experience, a subset of patients with advanced emphysema was identified, in whom the operation produced impressive subjective and objective improvements in 75% to 85% of patients [18]. Criteria for patient selection are shown in Table 1. Only about 15% of the patients referred to Cooper’s group were judged to be suitable candidates for LVRS [17].
|
In November 1995, the Agency for Health Care Policy Research (AHCPR), an arm of the Health and Human Services, invited submission of data from clinical centers "regarding the risks, benefits and costs associated with this treatment" for a nationwide survey on the results of LVRS [20]. However, weeks before the February 13, 1996, deadline for submissions, Medicare tagged LVRS investigational and discontinued reimbursement for the operation effective January 1, 1996. Many other health insurers also adopted a nonpayment policy. The number of lung volume reduction operations performed fell precipitously [21]. The experience at four hospitals in Massachusetts reflects the pattern of LVRS utilization in the United States (Fig 1).
|
The results of the AHCPR survey on LVRS were published in September 1996, 9 months after Medicare instituted a nonpayment policy for the operation [20]. The unstructured request for information elicited responses from 27 institutions covering more than 3,000 LVR operations. Selection criteria, operative technique, and outcome in the various reporting centers differed widely. Moreover, data obtained from volume reduction by laser ablation, discarded by most surgeons, were incorporated into the analysis. The submitted data were incomplete, lacked the uniformity essential for meaningful analysis, and allowed only fragmentary interpretation of a limited number of variables but not global assessment of the effectiveness of the operation. Indeed, the AHCPR report noted that, "Given the heterogeneity of patient selection and institutional practices and the limited number of institutions that provided detailed information, there are obvious hazards inherent in combining the data from the various sources, and one cannot assume that such a process would necessarily provide a reliable illustration of the current state of LVRS." The report went on to conclude that "... the data suggest that an as yet undefinable proportion of patients with severe COPD may have realized some benefits from the procedure. If the surgery could be accomplished without undue morbidity or mortality, a prospective trial of LVRS ... is both ethically suitable and scientifically essential" [20]. The statement did not specify the type of trial envisioned.
By early 1996, the focus of the LVRS debate shifted to a dialogue about the optimal approach of getting answers to outstanding questions about the operation. Some clinicians believed that, given the demonstrated effectiveness of LVRS, a randomized clinical trial (RCT) would be ethically troublesome and a multicenter prospective nonrandomized controlled trial (registry) would be the best strategy for generating data and for promoting high quality of patient care [24]. Others maintained that an RCT represented the optimal approach for getting credible data about the value of LVRS [19]. With the controversy in the background, HCFA and the National Institutes of Health joined forces to sponsor a clinical trial on the operation.
Methods for evaluating new operations
At the time HCFA and the National Institutes of Health began to organize a clinical trial on LVRS, indications for the operation, the basics of operative technique, and details of perioperative management had been moderately well standardized. Operative mortality in different centers varied widely but most surgeons reported figures between 5% and 8%. Observational studies provided impressive evidence about the short-term effectiveness of the operation in a relatively well defined subset of patients. The same experience also indicated that bilateral reduction was superior to a unilateral procedure [25]. An RCT from a single clinical site confirmed the impression that resection of pulmonary tissue produced better results than laser ablation [26]. The choice for access, between midsternotomy and video-assisted thoracoscopy, and the impact of homogeneous versus heterogeneous distribution of the disease on outcome were still debated. It was also acknowledged that more information was needed for refining indications, surgical techniques, and patient management issues as well as for determining duration of benefits, the impact on longevity, and cost effectiveness.
The wide variation in morbidity and mortality reported from different clinical centers signaled the wisdom for incorporating patient care quality control measures in any trial on LVRS. The options for advanced evaluation of LVRS and other new complex operations at a comparable stage of development are presented below.
Retrospective analysis of observational data
Almost all operations in contemporary surgical armamentarium have been evaluated through retrospective analysis of observational data. The method fails to deal with confounding bias and frequently fails to exercise adequate oversight over the quality of clinical services. The lure of accolades associated with introduction of new operations can lead to premature enthusiasm about a procedure, exaggerated optimism about the results, and questionable clinical practices. History is replete with surgical therapies that had been widely used but were abandoned after lack of effectiveness was demonstrated. In spite of the disadvantages, however, retrospective analysis of observational data has been essentially the sole vehicle for evaluating the remarkable array of currently employed sophisticated surgical procedures, from hemorrhoidectomy to heart transplant. Routine use of RCTs for evaluating these operations would have produced a therapeutic wasteland. The ratio of patients helped to those harmed in the course of evaluating new operations through the observational approach is difficult to assess. Because of shortcomings in scientific rigor, the observational method should be complemented, whenever possible, with randomized studies.
Observational studies are especially useful during the developmental phase of complex operations, when patient care protocols and surgical techniques change frequently and the data generated are not sufficiently uniform to meet the rigorous standards required for a randomized clinical trial. However, by the time a surgical procedure is standardized, effectiveness in specific patient subsets may be established and the use of RCT could involve withholding known health benefits from the nonsurgical arm of the study.
Registry
Registries range from simple data repositories to prospective, controlled, nonrandomized clinical trials. Introduction of bias is far greater with registries than with RCTs. Limiting selection to a well defined cohort and standardizing the clinical protocol can facilitate the formation of homogeneous study populations for prospective, controlled, nonrandomized clinical trials. This structure can discourage performing operations for inappropriate indications, encourage implementation of standardized care, and generate reliable data. Selection of clinical sites with expertise and experience is conducive to optimization of the quality of patient services. Multicenter registries facilitate comparison of results obtained at various participating clinical sites and attenuate bias attributed to the "surgical skill" factor. Patient accrual is usually easier through a registry than through an RCT. A Registry on LVRS is in place in Australia and New Zealand (ANZ LVRS Database) and has already reported on enrollment of 309 patients at 12 clinical sites [27].
Randomized clinical trial
A randomized clinical trial represents the scientific gold standard for evaluating new therapies. Assignment of treatment through randomization reduces known and unknown bias. Quality of clinical care measures can be incorporated into the trial protocol. However, a basic rule requires that random assignment of treatment can be used only "whenever it is not known whether the patient who receives the new therapy will, on the average, fare better or worse than the one from whom it is withheld" [28]. Randomizing patients to evaluate therapies with known influence raises ethical concerns, as patients assigned to the control arm could be deprived of health benefits.
RCTs are most suitable for treatment modalities with fixed character and uniform action. Well-tested drugs and medical devices, standardized operations, and adjuvant therapies exhibit these features and are best evaluated by RCTs. However, new operations before standardization are frequently modified and do not produce sufficiently uniform data to qualify for randomized studies. Cardiac surgery is a case in point. During the early developmental phase of most heart operations, surgical techniques and patient care protocols were repeatedly modified and the data produced lacked uniformity and consistency. Operative morbidity and mortality were high and functional results marginal but improved with increasing experience. Evaluation of emerging heart operations through RCTs could have resulted in unreliable and misleading conclusions. Scores of operations in the current cardiac surgical armamentarium could have been rejected. The list of discarded operations might have included heart transplantation, mechanical circulatory assist devices, cardiac valvular procedures, coronary artery bypass grafting, and repair of congenital lesions. Progress in cardiac surgery would have been slowed, if not arrested, and the large array of presently employed heart operations would not have been developed. The repeated appeals that all new operations should be tested in the same manner as new drugs disregard fundamental differences between stable pharmacological agents and ever-changing complex new operations, especially in the early developmental phases [1, 2, 3].
Unduly long randomization periods in RCT protocols designed to evaluate standardized operations with known benefits may expose control patients to serious health risks. A projected annual mortality of 10% to 12%, suggested by available information on the natural history of severe emphysema, places limits on the duration of acceptable randomization period for studies evaluating the efficacy of LVRS [29, 30].
In spite of a strong scientific appeal, RCTs have been used infrequently in surgical research. Fewer than 1% of all patients treated for lung cancer with a variety of experimental regimens are enrolled in randomized trials [31]. A survey of the journals Surgery, Diseases of the Colon and Rectum, and the British Journal of Surgery, for the years of 1980 and1990, revealed that RCTs accounted for only 7% of 1,060 reports on clinical studies [32]. Another review of nine surgical journals focusing on the first month of 1996 produced similar results [3].
Combined RCT and registry
Under this arrangement the small subset of patients for whom the outcome from LVRS is known are placed into a registry while patients with unknown results can be enrolled into an RCT. The Coronary Artery Surgery Study (CASS), a National Institutes of Health-sponsored clinical trial, serves as a relevant model [33]. CASS was organized after coronary bypass grafting (CABG) had been standardized and observational data demonstrated that the operation offered benefits in patients with severe symptoms (Canadian class 3 and 4) but not in the subset with milder (Canadian class 1 and 2) presentation. CASS assigned Canadian class 3 and 4 patients to a registry, while those in Canadian class 1 and 2 were enrolled in an RCT. Approximately 25,000 patients were studied in the registry but fewer than 800 could be recruited for the RCT. Remarkably, only 4% of contemporary CABG practice derives from the category of patients who would have been appropriate for the RCT, while the bulk of cardiac revascularization procedures are performed for indications that qualified for the CASS registry [34]. Far more information has been generated by the registry than by its companion RCT. Had the value of CABG been studied indiscriminately in all classes of patients through an RCT, many patients would have been deprived of an effective therapy, and the evolution of sound CABG utilization could have been placed in jeopardy.
Choice of studies for advanced evaluation of LVRS
In May of 1996 HCFA and the National Institutes of Health announced joint sponsorship of the National Emphysema Treatment Trial (NETT) on LVRS. The study was designed to randomize 4,700 Medicare patients between LVRS and the best available medical treatment for 5 years at 18 clinical sites throughout the United States. Patient eligibility criteria for NETT resembles the characteristics of the population in which the short-term effectiveness of LVRS had already been established. The duration of the randomization period precludes access to LVRS for 5 years by patients in the medical arm [35]. This cohort faces a 5-year mortality that may reach 50% to 60% [29, 30]. Seventeen clinical sites joined NETT. However, the Institutional Review Board of one designated center found the ground rules ethically unacceptable and withdrew from the study [36].
Medicare also established a nonpayment policy for LVRS outside the aegis of NETT. This move has imposed a financial barrier to an operation that many experts believe offers predictable benefits.
Stirred by the desire to offer a more patient-friendly clinical trial, Blue Cross Blue Shield of Massachusetts (BCBSMA), in conjunction with 11 community and academic hospitals, affiliated with four medical schools in the Commonwealth of Massachusetts, organized the Overholt-BlueCross Emphysema Surgery Trial (OBEST). This second multicenter RCT on LVRS in the United States randomizes patients between LVRS and the best available medical treatment for 6 months followed by a crossover option to surgery for those in the medical arm [37]. The eligibility criteria of OBEST are similar to those of NETT. Comparison of the results in the medical and surgical groups 6 months after institution of the randomly selected treatment is expected to provide credible information about the short-term palliative influence of LVRS but not about its impact on longevity. The crossover option provides access to LVRS by all qualified candidates and merely postpones the operation for the medical arm by 6 months. This delay does not expose patients to undue health risks, as emphysema progresses relatively slowly and is not usually associated with sudden death. Longitudinal follow-up studies are expected to provide information about the duration of benefits obtained from LVRS. Emphasis on the palliative influence of LVRS is consistent with the basic tenets of medicine that improvement in quality of life is as important a measure of the value of a therapeutic intervention as is its power to extend life. Indeed, many widely used operations, such as joint replacement and a host of others, palliate and do not add to longevity. Only 6 of the 11 OBEST clinical sites are designated to both screen and perform LVRS while 5 hospitals provide only screening services. One of the OBEST clinical sites also serves as a NETT center. Pulmonary rehabilitation has been standardized at a network of centers across the Commonwealth of Massachusetts in order to provide uniform therapy and geographic convenience for patients. Harvard Pilgrim Health Care (an HMO) joined the trial after its Committee on Ethics concluded that the 6-month randomization period protects patients in the medical arm from the adverse health consequences of a lengthy delay. Harvard Pilgrim Health Care patients may also elect to have LVRS outside OBEST.
The biostatisticians from the data coordinating center of OBEST determined that randomization of 219 patients would provide sufficient power for obtaining statistically significant information about the palliative influence of LVRS. With an estimated 47,000 emphysema patients in the Commonwealth of Massachusetts, no difficulties were anticipated with recruitment ("Estimated prevalence and incidence of lung disease by lung association territory." Epidemiology and Statistics Unit, American Lung Association, April 1999). Completion of patient enrollment phase was expected within 2 years.
Progress of the clinical trials and utilization of LVRS
Fewer than one third of the anticipated number of patients have entered NETT and OBEST. As there appears to be no prospect for a change in the pace of enrollment in the foreseeable future, the recruitment phase of the two ongoing randomized trials may not be completed for another 6 to 10 years. NETT has already cut back its original enrollment goal from 4,700 to 2,500 patients [38]. OBEST has joined forces with the Canadian Lung Volume Reduction Trial in an attempt to obtain statistically meaningful 6-month outcome data.
NETT’s recruiting problems appear to be due in large part to patient and physician reluctance to accept a 50% chance of having to wait 5 years for an operation that promises impressive palliation from a disease that has a 50% to 60% 5-year mortality. Indeed, investigators from a British RCT on LVRS reported that many patients refused randomization and elected to have surgery outside the trial [39]. NETT’s geographic structure may also be problematic for some patients.
We believe that the low enrollment in OBEST has been due in large part to the noncoverage policy of Medicare and other insurers resulting in reduction of the size of patient pool with health plan benefits to pay for the operation. Another randomized study, the Canadian Lung Volume Reduction Trial, has also fallen short of its recruitment goal. A major cause of the shortage is attributed to budgetary constraints limiting the number of LVR operations at the participating hospitals [40].
The decrease in LVRS utilization outside randomized trials is most likely due to (1) the nonpayment policy by Medicare and other insurers, (2) loss of confidence in the effectiveness of LVRS owing to the "experimental" categorization, and (3) the relatively small percentage of patients from the total emphysema pool who qualify for LVRS under recommended indications. The collective experience indicates that the population that could benefit from LVRS is larger than the current level of utilization but much smaller than the 1.35 million operations projected by Make and Fein [20]. The importance of an economic factor behind the declining utilization is suggested by the rapid rise in the number of LVR surgeries during the period when insurance coverage was available and the precipitous fall after payment was stopped. Indeed, recent telephone screening of 165 responders to an OBEST recruiting effort revealed that a substantial number of these patients would qualify for LVRS but were not eligible because of lack of appropriate insurance coverage (Berger RL, unpublished information).
The ambiguity surrounding the interpretation of data on LVRS to guide evidence based decisions is illustrated by the deliberations of the Technology Evaluation Center (TEC), a research program that evaluates scientific evidence on new treatment modalities for the independent Blue Cross Blue Shield plans, Kaiser Permanente, and other health insurers. In 1995, TEC advised that the available evidence supported the effectiveness of LVRS. Four years later, after a second survey of peer-reviewed literature, TEC reversed the earlier opinion, and concluded that "... it is not possible to determine whether the procedure improved net health outcome" [41]. Although the publications reviewed by TEC suggested that LVRS afforded statistically significant improvements in short-term measurements of pulmonary function and other variables (Tables 2 and 3), the validity of these observations as surrogates for clinically significant improvement in functioning or quality of life was questioned. TEC determined that conclusions about clinical benefits of LVRS should await the results of the NETT trial.
|
|
In spite of declining LVRS utilization, a steady stream of data from uncontrolled case series have continued to confirm the short and midterm effectiveness of the operation [42, 43]. Two RCTs from the United States (37 and 49 patients), and one each from the United Kingdom (48 patients), Sweden (38 patients), and Italy (60 patients) compared LVRS with the best available medical treatment. All five studies reported better outcomes in the surgical arms [39, 44–48]. Observational studies indicate that the benefits from LVRS peak at about 12 months and plateau or recede thereafter, but respiratory function remains above baseline for as long as 3 to 5 years in some patients [42, 49–51]. In contrast, medically treated patients continue on a progressive downhill course. Meyers and associates (52) reported that 65 patients maintained symptomatic and physiologic improvements 24 months after LVRS, but 22 comparable patients who did not have the operation because of lack of insurance coverage experienced progressive deterioration. Peer-reviewed publications refer to LVRS as an accepted form of palliative therapy. A 1999 review article from one of the NETT clinical sites lists LVRS as standard treatment for a subgroup of patients suffering from advanced emphysema and occasionally as an alternative to lung transplantation [53]. Although the possibility of bias favoring publication of positive results must be considered, the near total absence of reports on negative outcomes in more than 200 articles listed in Medline is striking.
Reports in the literature describe patients with lung cancer who were judged inoperable because of coexistent severe emphysema but survived resection of the malignancy when LVRS was added to the treatment program [54]. Similarly, LVRS has facilitated coronary artery bypass, cardiac valvular, and aortic aneurysmal operations with gratifying results in patients who were regarded as high or even prohibitive operative risks owing to coexisting advanced emphysema [55–57]. Furthermore, a patient whose respiratory function deteriorated after single lung transplantation for emphysema responded favorably to volume reduction on the hyperinflated native lung [58].
The compelling evidence on the favorable physiologic and symptomatic impact of LVRS raises concerns about randomly assigning therapy with known outcome. Randomization is the appropriate strategy for cohorts in which the impact of LVRS is unknown and may be acceptable for subsets with known benefits but only if the length of randomization does not expose patients to undue health hazards.
Although the randomized strategy ranks at the top in the hierarchy of research methods, it is also recognized that scientific rigor must accommodate practical clinical requirements. Hence in selected situations well-designed observational studies may be preferable to RCTs [34]. This choice is especially applicable to standardized therapies with known outcomes and emerging operations with changing operative and perioperative management practices that are unlikely to produce the uniform data essential for the randomized approach. Although observational studies fail to deal with confounding bias and tend to inflate positive treatment results, data from careful comparative surveys also indicate that well-designed observational and randomized studies frequently arrive at similar conclusions about the value of treatment modalities [59–61].
Some health insurers justify a nonpayment policy by maintaining that available data support only short- to mid-term palliation but not long-term benefits. The question of "how long is long enough" poses a perplexing public health dilemma. Should those who set public policy decide or should patients and their physicians make the choice? We believe the answer should come from a balanced consideration of clinical, ethical, and economic issues, not from arbitrary decisions by insurance companies or government agencies.
The community of physicians dedicated to develop and deliver safe and sound therapies to patients face an LVRS "crisis." The NETT, OBEST, and Canadian LVR trials are at risk of failing to answer critically important questions about the risks and benefits of LVRS, not because the operation does not work but because of differences in opinion about who should be referred, how effective the treatment is, and how long the benefits last. To address these issues, these ongoing RCTs should be supported. Rather than discouraging participation because of theoretical reservations, we should be encouraging appropriate patients to participate for their own benefit and for the good of the public. Simultaneously, we should do our utmost to make LVRS available to patients who desire to have the procedure and whose preoperative profiles suggest that they are likely to benefit from the operation. Medicare and other insurers are invited to participate in this endeavor and cover LVRS for all qualified patients, including those who do not wish to participate in a designated randomized clinical trial. (Appendix)
Acknowledgments
The research component of OBEST is supported by the Thoracic Foundation, United States Surgical Corp and Biovascular Corp.
Appendix
Project director: Robert L. Berger, Beth Israel Deaconess Medical Center, Boston, MA.
Principal advisor: Gordon L. Snider, Boston University School of Medicine. Scientific advisor: Bartolome R. Celli, Tufts Medical School. Principal and co-principal investigators of OBEST: G. S. Aldea and O. M. Shapira, Boston Medical Center, Boston, MA; Peter H. Bagley, U Mass/Memorial Health Care, Worcester, MA; D. J. Beer, Newton Wellesley Hospital, Newton, MA; I. Buchwald, Saints Memorial Medical Center, Lowell, MA; B. Celli and J. Stetz, Jr, St. Elizabeth’s Medical Center; Boston, MA; A. W. Gray, C. Williamson, Lahey-Hitchcock Clinic, Burlington, MA; F. M. Hasan and S. Neil, North Shore Medical Center, Salem, MA; E. M. Ingenito and S. J. Mentzer, Brigham & Women’s Hospital, Boston, MA; J. N. Landis, Bay State Medical Center, Springfield, MA; J. LoCicero and R. Silvestri, Beth Israel-Deaconess Medical Center, Boston, MA; C. D. Wright, Massachusetts General Hospital, Boston, MA; T. McLoud, Imaging Center, Massachusetts General Hospital, Boston, MA; Consultant: Evelyn F. Murphy, PhD, Brookline, MA.
Data coordinating center: E. Poggio, D. Amato, D. Danielewski, and K. Brazemore, ABT Associates, Cambridge, MA; T. Colton, H. Golub, C. Hall, S. Hamer, J. Schindler, and S. Brouer, CareStat Inc, Chestnut Hill, MA.
References
This article has been cited by other articles:
|
|
 |
|
  J. D. COOPER, R. V. CLAYMAN, T. M. KRUMMEL, P. R. SCHAUER, C. THOMPSON, and J. D. MORENO Inside the operating room--balancing the risks and benefits of new surgical procedures: A collection of perspectives and panel discussion Cleveland Clinic Journal of Medicine, November 1, 2008; 75(Suppl_6): S37 - S54. [Full Text] [PDF]
|
|
|
|
 |
|
 A R Glanville Ethical and equity issues in lung transplantation and lung volume reduction surgery Chronic Respiratory Disease, January 1, 2006; 3(1): 53 - 58. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Hartling, F. A. McAlister, B. H. Rowe, J. Ezekowitz, C. Friesen, and T. P. Klassen Challenges in Systematic Reviews of Therapeutic Devices and Procedures Ann Intern Med, June 21, 2005; 142(12_Part_2): 1100 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Miller, R. L. Berger, R. A. Malthaner, B. R. Celli, C. H. Goldsmith, E. P. Ingenito, D. Higgins, P. Bagley, G. Cox, and C. D. Wright Lung Volume Reduction Surgery vs Medical Treatment: For Patients With Advanced Emphysema Chest, April 1, 2005; 127(4): 1166 - 1177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Ramsey and S. D. Sullivan Evidence, Economics, And Emphysema: Medicare's Long Journey With Lung Volume Reduction Surgery Health Aff., January 1, 2005; 24(1): 55 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Brenner, N. M. Hanna, R. Mina-Araghi, A. F. Gelb, R. J. McKenna Jr, and H. Colt Innovative Approaches to Lung Volume Reduction for Emphysema Chest, July 1, 2004; 126(1): 238 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Decramer Treatment of chronic respiratory failure: lung volume reduction surgery versus rehabilitation Eur. Respir. J., November 16, 2003; 22(47_suppl): 47s - 56s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Munro, M. J. Bailey, J. A. Smith, and G. I. Snell Lung Volume Reduction Surgery in Australia and New Zealand: Six Years On: Registry Report Chest, October 1, 2003; 124(4): 1443 - 1450. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
