A. SPONSOR

Blue Cross Blue Shield of Massachusetts (Tel. No. 1 800 214 0019)

B. PARTICIPATING HEALTH PLAN

Blue Cross Blue Shield of Massachusetts
Harvard Pilgrim Health Plan
Others: being negotiated

C. SUPPORTERS

U.S. Surgical Corp., BioVascular Co. GlaxoWellcome and The Thoracic Foundation granted the funds for the research component of OBEST.

D. PARTICIPATING CLINICAL SITES

1. Medical-Surgical Centers. Medical-Surgical Centers are designated to perform all screening and diagnostic procedures, pulmonary rehabilitation, LVRS, and follow-up studies.

   Medical-Surgical Center	Telephone Number
   Beth Israel-Deaconess Medical Center, Boston	617 632 8383
   Brigham and Women's Hospital, Boston	1 888 BWH LUNG
   Lahey-Hitchcock Clinic, Burlington	781 744 2777
   Massachusetts General Hospital, Boston	617 726 5801
   U. Mass-Memorial Hospitals, Worcester	508 793 6678

2. Satellite Consortium Centers. The Satellite Consortium Centers are designated to provide all screening and diagnostic procedures, pulmonary rehabilitation and follow-up studies but will not perform LVRS. It is anticipated that by participating in the activities of OBEST, the Consortium Center staff will gain sufficient expertise to perform LVRS independently and set up second generation OBEST Medical Surgical Centers, if and when the demand for LVRS increases. The following hospitals were selected as Satellite Consortium Centers:

   Satellite Consortium Center	Telephone Number
   Bay State Medical Center, Springfield	413 784 4470
   Boston Medical Center, Boston	617 638 7487
   North Shore Medical Center, Salem	978 741 1215 Ext. 4285
   St. Elizabeth's Medical Center, Boston.	617 789 3065

3. Satellite Pulmonary Rehabilitation Centers. In order to accommodate patients, who reside at an inconvenient distance from OBEST clinical sites, seven additional Pulmonary Rehabilitation facilities have been selected throughout the Commonwealth of Massachusetts. The staffs at these facilities received formal training in a pulmonary rehabilitation program standardized by OBEST.

E. STUDY OBJECTIVES

a. Primary Objectives.

1. To establish in selected patients with severe emphysema, whether six months after LVRS there is

   i. Improvement in Health-Related Quality of Life (HRQOL), when compared to the medical arm receiving only optimal medical management, as measured by the Chronic Respiratory Questionnaire (CRQ).

   ii. Improvement in functional capacity when compared to the medical arm receiving only optimal medical management, as measured by the six-minute walk test (6MWT).
   

2. To establish in selected patients with severe emphysema, whether the observed improvements, if any, following LVRS in HRQOL (as measured by he CRQ) and functional capacity (as measured by the 6MWT) persist for at least 3 years.

b. Secondary Objectives

1. To establish in selected patients with severe emphysema, whether compared to the medical arm receiving only optimal medical management, LVRS results in:

   i. improved physiologic measures of lung function, including arterial blood gases (ABG), FEV1, TLC, RV, and maximal inspiratory (Pi_max) and expiratory (Pe_max) pressures.

   ii. a reduction in dyspnea, as measured by the Baseline Dyspnea Index/ Transitional Dyspnea Index (BDI/TDI), the MRC Dyspnea Scale (MRC), and the Borg Visual Analog Scale (VAS).

   iii. improved overall quality of life, as measured by the Medical Outcomes Study Short Form-36 (SF-36).

2. To establish whether the observed improvements, if any, in physiologic measures of lung function, dyspnea and overall quality of life will persist for at least 3 years following randomization.
3. To establish whether radiographic assessment of lung heterogeneity correlate with benefits obtained from LVRS.

F. STUDY DESIGN

a. Randomized Clinical Trial. OBEST study design is based on a six-month randomization period between LVRS combined with the best available medical treatment versus the best available medical treatment alone. Six months after randomization both cohorts will be evaluated and patients in the medical arm will be permitted to crossover to surgery, if they so desire. The design affords access to LVRS by all suitable candidates and randomization merely determines the timing of the operation. As emphysema is a slowly progressing disease, the six-month wait for patients in the medical treatment arm is not fraught with undue risk of sudden or major untoward medical event. A total of 219 individuals will be randomized either to LVRS plus medical therapy or to medical therapy alone in a 2:1 ratio. Patients will be followed for 36 months after randomization. This period may be extended if warranted by study results.

b. Registry. OBEST Emphysema Registry (OER) will be used to observe the natural history of emphysema of the lung. It will enroll 160 patients, found ineligible for randomization by the OBEST screening process. For controls, 30 non-smoking and 30 smoking healthy adults will be recruited. This relatively uniform, closely monitored population will represent a unique resource for prospective longitudinal study of the natural history of emphysema.

G. ELIGIBILITY FOR THE RANDOMIZED CLINICAL TRIAL

Non-smoking individuals under the age of 75 with symptomatic emphysema and appropriate insurance coverage are screened for the randomized clinical trial. Those meeting eligibility criteria for the study will undergo six weeks of intensive pulmonary rehabilitation and then will be randomized between LVRS combined with optimal medical therapy and optimal medical therapy alone without LVRS.

H. DATA COORDINATING CENTER (DCC)

The DCC has collaborated on developing OBEST study design and study plan. The DCC also has primary role in data collection, storage and analysis, as well as training of On-site Research Coordinators. The group is staffed by scientists from Abt Associates and CareStat, Inc. Abt Associates is one of the largest economics, biostatistics and epidemiology research groups in the U.S. employing 800 professionals. The firm has had extensive experience with design and analysis of clinical trials and has collaborated with research organizations, academia, private industry and Government. CareStat, Inc, is a research firm specializing in clinical trials.