Patient-assessed Health Outcomes in Chronic Lung Disease
What are They, How Do They Help Us, and Where Do We Go From Here?

J. RANDALL CURTIS, DIANE P. MARTIN, and THOMAS R. MARTIN

Division of Pulmonary and Critical Care Medicine, Department of Medicine; Department of Health Services, University of Washington; and Medical Research Service, Seattle Department of Veterans' Affairs Medical Center, Seattle, Washington

	INTRODUCTION

TOP INTRODUCTION CONCLUSION REFERENCES

During the last 10 to 15 yr there has been an exponential increase in the development and use of instruments to measure the outcomes of health care from the patient's perspective. These instruments have appeared in the pulmonary literature, first in the assessment of COPD (1, 2) and more recently with asthma (3), cystic fibrosis (7, 8), and primary pulmonary hypertension (9). In March of 1996, the American Thoracic Society sponsored a meeting to summarize the state of the art in measuring patient-assessed health outcomes for patients with chronic obstructive lung diseases. The conference was followed by a round table discussion attended by major "stakeholders" in the assessment of patient-assessed outcomes in chronic lung disease, including academic investigators who have developed and used the instruments, representatives of the pharmaceutical industry interested in health outcomes in pharmaceutical research, representatives of managed care interested in health outcomes of the populations for whom they provide care, and representatives of a federal regulatory agency confronted with health outcomes in requests for the approval of pharmaceutical products. The purpose of this report is to review, from the perspective of the authors, some of the major points raised during the conference and the accompanying workshop. We will summarize what outcome measures are and some of the major instruments that have been used to assess outcomes of chronic lung disease. We will emphasize how patient-assessed clinical outcomes differ from traditional outcomes and the information they provide about care of patients with chronic airflow obstruction. Finally, we will summarize the current unresolved issues in this field and important future directions.

	HEALTH OUTCOMES: WHAT ARE THEY AND WHY ARE THEY IMPORTANT?

Chronic pulmonary diseases such as asthma and COPD are incurable and, for many patients, progressive. Consequently, health care providers work to minimize patients' symptoms and improve their ability to function in day-to-day life. Although improved survival time is an important goal of therapy, there is growing recognition that improving the quantity of a person's life may not be the only goal; for some, especially those with debilitating, chronic disease, improving the quality of life may be more important. Because increasing function and improving the quality of life are central therapeutic goals for many chronic diseases, it is important for researchers and clinicians to develop a common understanding of what functional status and quality of life mean and the settings in which it is useful to measure them.

There is a growing literature about the measurement of health outcomes in patients with chronic pulmonary diseases (10). For example, these measures have been used in patients with COPD to assess bronchodilators (13, 14), home respiratory nursing care (15), and pulmonary rehabilitation programs (16). Similarly, these types of measures have been used in patients with asthma to assess bronchodilator therapy (3) and asthma self-management (17). Health outcome measures are now being used as primary end points in clinical trials and outcomes research in chronic pulmonary diseases. Clinicians must be able to understand and critically assess these measures in order to help decide whether a new therapy should be applied to their patients.

Terms and Definitions

Patient-assessed health outcomes can be divided into three major categories: health status (encompassing health-related quality of life and functional status); health utilities (patients' values for a particular state of health); and patient satisfaction. In addition, other innovative measures of patient outcomes in chronic lung disease include work disability (18, 19), daily symptom diaries (20), and activity monitoring devices (21). For simplicity, we will focus on health status measurement. The relationships between the terms used to describe health status and quality of life are shown in Figure 1. This figure shows the overlap in the operational definitions of these terms; a useful conceptual model of the interactions between these terms and clinical variables has been constructed by Wilson and Cleary (22).

View larger version (52K): [in this window] [in a new window]   Figure 1.   Conceptual model of the overlapping realms of common terms describing patient-assessed health outcomes. Shaded area represents heath-related quality of life.

The term "quality of life" is widely used in clinical research and clinical care, but it is rarely defined. In its broadest definition, the quality of a person's life is a holistic, self-determined evaluation of satisfaction with issues important to the person. Quality of life is influenced by many factors, including financial status, housing, employment, spirituality, social support network, and health. Consequently, many investigators use the more restrictive term "health-related quality of life" (HRQL) for quality of life as it is affected by health and health care. The term "functional status" is used to describe a person's ability to function in such diverse realms as physical, social, and emotional. As functional status (or performance) on a day-to-day basis is a subset of a person's functional capacity, they will vary in how closely their daily performance approaches their maximal functional capacity (23). These two terms, HRQL and functional status, are often used interchangeably, but they represent different concepts. Functional status reflects the ability to perform the tasks of daily life, whereas HRQL connotes the subjective experience of the impact of health status on the quality of life. Operationally, many of the instruments designed to measure HRQL or functional status encompass both, which makes it difficult to distinguish these concepts.

In its most general definition, "health status" assesses the effect of a person's health on the ability to perform and enjoy the activities of daily life. This term encompasses functional status and health-related quality of life. Health status instruments range from disease-specific to generic measures. Disease-specific measures assess the severity of particular pulmonary symptoms such as dyspnea, wheezing, and cough and the effect that these symptoms have on a patient's life (24, 25). Generic instruments assess many facets of health status, often including such diverse realms as emotional functioning (mood changes and other psychologic symptoms), social role functioning (employment, home management, and social/family relationships), activities of daily living (self-care skills and mobility), and the ability to engage in enjoyable activities (hobbies and recreation) (2).

Although we will not focus on specific utility measures, these measures deserve some description. Utility measures allow researchers to use the values of patients to combine the additional life years gained from an intervention with a judgment of the quality of life in those years. This approach produces a composite indicator of outcome (the quality-adjusted life year or QALY) that can be used to compare different treatments on the same metric (26). The major application of QALYs lies in comparing different interventions rather than evaluating the health status of individual patients; QALYs are often used in policy analyses to compare the merits of devoting resources to one intervention versus another (27).

Use of Generic and Disease-specific Instruments in Chronic Lung Disease

Disease-specific and generic instruments each have advantages (28). The optimal choice of the type of instrument depends in part on the specific study question. It is often appropriate to use both a generic and a disease-specific instrument in the same study. Disease-specific instruments are likely to be more sensitive to small changes. For instance, an instrument including a measure of dyspnea is more likely to show a benefit of bronchodilators than a generic health status instrument.

Generic instruments are broader than disease-specific instruments and have the advantage that they have often been more thoroughly tested in a variety of clinical settings and populations. Because of this breadth, they may reveal important, but unexpected, effects of a treatment. In addition, they are more likely to appropriately weigh diverse side effects of treatment and establish an overall assessment of the effect of treatment on a patient's life. This may be particularly important, for example, in the evaluation of chemotherapy for nonoperable lung cancer, as diverse (nonpulmonary) side effects of treatment may have important effects on health status (29, 30). Generic instruments also allow investigators to compare health status across different diseases (31).

A list of some of the health status instruments that have been used in patients with COPD and asthma is shown in Table 1. The table shows the components (or domains) of each instrument. The components of an instrument are the basic units of health status used by the instrument developers and differ slightly from instrument to instrument.

Assessment of Health Status Instruments

Reliability and validity are the most important features of any instrument used to measure health outcomes. An instrument is reliable if it gives the same answer on repeated testings when the outcome has not changed (test-retest reliability) and when different observers use the instrument (interobserver reliability). The term reliability also includes an assessment of whether different parts of the instrument give consistent results (internal consistency). The reliability of an instrument is not necessarily reexamined with each study using the instrument, but investigators need to be convinced that reliability has been established and that the instrument will be reliable in their research setting.

Validity is a more difficult issue to assess, yet it is the primary issue in development of a health status instrument. The validity of an instrument is the extent to which it actually measures a patient's health-related quality of life or functional status. There is no gold standard against which to measure the validity of a health status instrument. Consequently, validity must be assessed indirectly. One method is to examine correlations between the health status instrument and other clinical indicators of disease severity such as FEV₁ and exercise tolerance. An instrument should correlate in the expected direction with clinical markers of disease severity and with other health status instruments. This process is known as "construct validation," and is an ongoing process since no single critical observation can definitively establish validity. Some of these correlations should be provided with each use of an instrument in a clinical trial so that the reader can be reassured that the instrument is valid in the population under study.

For clinical trials or other longitudinal evaluations, "responsiveness" is a key feature of a health status instrument. Responsiveness reflects whether an instrument can distinguish small, but clinically important, changes in health status over time. Understanding the minimal clinically important difference may be less difficult with traditional clinical measures, e.g., a clinician would interpret a statistically significant improvement of 50 ml in FEV₁ in a large study as clinically unimportant. With health status measures, however, the minimal clinically important difference is usually not apparent to clinicians and must be defined by the investigators (32).

	HEALTH OUTCOME MEASURES: WHAT DO WE KNOW ABOUT THEM AND HOW DO THEY HELP?

If one is interested in understanding the patient's perception of quality of life or functional status, it follows that the most accurate approach is to ask the patient. Clinicians do this regularly in routine clinical care, but health status questionnaires provide this assessment in a standardized way that can be summarized and used to compare the outcomes of groups of patients at one time or over time. Can instruments designed to reliably, accurately, and "objectively" measure the patient's perspective provide useful information about chronic lung disease and its treatment? There is a substantial body of literature that has attempted to answer this question from three different approaches: (1) cross-sectional studies comparing health status with physiologic measures; (2) cross-sectional and longitudinal studies describing the effect of chronic lung disease on patients' health status; and (3) randomized, controlled trials using health status to determine the efficacy of therapy for patients with chronic lung disease.

  (1) Cross-sectional studies: Comparing health status with traditional clinical measures. Clinical research has established the efficacy of many treatments using traditional clinical outcomes such as mortality and physiologic measures. If health status measures are to be believable, they should correlate with traditional outcome measures; that is, if a therapy significantly improves FEV₁ or peak flow rates and doesn't have important side effects, it should improve health status. Correlation can be assessed in the statistical sense using the correlation coefficient to determine the degree to which two continuous variables are related. A measure of correlation, r², can range from 0 (no correlation) to 1.0 (perfect correlation) and can be interpreted as the proportion of one variable that is explained by a second variable. In general, summary statistics of correlation from different studies should only be compared with caution since studies often have different entry criteria, different outcome measures, and different statistical techniques. Nonetheless, the correlation coefficients between health status and physiologic measures in studies of patients with COPD have shown some homogeneity across studies. The correlation between health status and selected physiologic measures is shown in Table 2. The "correct" degree of correlation is difficult to assess, as perfect agreement would suggest that these measures are redundant. Because patients with the same FEV₁ can have very different health status, clinical experience suggests that these different outcomes should not correlate perfectly.

In general, health status should be directly related to physiologic measures of the severity of chronic lung disease. In other words, as the lung function (such as FEV₁ or FVC) decreases, the health status should decrease. Many studies have compared physiologic measures of COPD severity with health status measures. These studies have shown moderate to weak correlations between these measures (r² values from 0.01 to 0.41) (1, 2, 24, 33). More recently, several studies of patients with asthma have shown moderate to low correlations between health status and airflow obstruction (r² from 0.01 to 0.33) (3, 5, 36). Even studies showing moderate correlation have found that airflow (FEV₁) is less strongly correlated with health status than are emotional dysfunction (1, 33), dyspnea (33, 37), and symptoms (3, 5, 36). Similarly, measures of oxygenation such as Pa_O2 and Sa_O2 are either weakly correlated with health status (35) or not significantly correlated (1, 2, 38).

Exercise tolerance correlates more strongly with health status than either FEV₁ or oxygenation among patients with chronic lung disease (1, 2, 33, 35, 38). Exercise tolerance also correlates with many dyspnea measures better than do the pulmonary function parameters (24, 39, 40). Jones and colleagues (33) found that the correlation between pulmonary function and health status could be completed accounted for by exercise tolerance in patients with COPD, suggesting that pulmonary function influences health status mostly through its effect on exercise tolerance.

In summary, several studies have shown that health status measures correlate with physiologic measures of chronic lung disease and that they correlate in the expected direction. The correlation is not strong, suggesting that the physiologic parameters do not accurately predict health status (and vice versa). These studies also suggest that dyspnea ratings and exercise tolerance are better predictors of health status than FEV₁ or oxygenation.

  (2) Cross-sectional or longitudinal studies: Describing the effect of lung disease on health status. COPD is the chronic pulmonary disease for which the most extensive health status data are available. These data provide insights about the value of health status measurement. Studies of health status in COPD have included patients with varying severity of disease, ranging from patients eligible for continuous oxygen therapy with a mean FEV₁ of 0.75 L (30% of predicted) (2) to patients in a family practice clinic with a mean FEV₁ of 1.86 L (70% predicted) (41). Despite this heterogeneity, a clear picture emerges showing that patients with COPD have markedly decreased health status. Stewart and colleagues (31), using a Medical Outcomes Study instrument (the SF-20), showed that patients with COPD had decreased health status in all five domains of this instrument: physical functioning, role functioning, social functioning, mental health, health perceptions, and bodily pain. Furthermore, patients with COPD consistently scored worse on all domains that did patients with hypertension, arthritis, and diabetes, and worse than patients with chronic back pain in all domains except bodily pain. Similarly, McSweeny and colleagues (2) showed that patients with severe COPD had diminished health status in all domains of the Sickness Impact Profile (SIP) except employment and had severe decrements in the domains of emotional disturbances (primarily depression), recreational activities, home management, and sleep and rest.

One of the most striking and consistent findings of the studies describing the health status in patients with COPD is the prominent role that depression and emotional dysfunction play in this disease. In the study by Stewart and colleagues (31), patients with COPD scored lower on the mental health domain than did patients with hypertension, diabetes, congestive heart failure, myocardial infarction, angina, arthritis, and chronic back pain. Only patients with chronic gastrointestinal disorders scored lower in mental health than those with COPD.

  (3) Clinical trials: Using health status to evaluate the efficacy of treatment. Health status instruments have been used in many clinical trials of pharmaceutical agents, pulmonary rehabilitation, and oxygen and noninvasive ventilation. These trials provide insight about the benefit of assessing health status in clinical trials.

There have been many trials in which all outcomes demonstrate the benefit of treatment. The Nocturnal Oxygen Therapy Trial demonstrated improved health status (using the SIP) and decreased mortality with continuous oxygen therapy (42). Guyatt and colleagues (13) used the Chronic Respiratory Questionnaire (CRQ) to assess inhaled salbutamol and oral theophylline in patients with COPD. They showed that both agents individually improved health status, FEV₁, exercise tolerance, and peak flow. Two studies have compared the effect of salmeterol and salbutamol on health status and clinical outcomes in patients with asthma (using the Asthma Quality of Life Questionnaire and other instruments) (3, 5). Both studies found statistically significant improvement in health status, symptom scores, FEV₁, and peak flow rates with salmeterol compared with salbutamol. Jones and colleagues (6) have shown improvement in health status, clinician assessment, FEV₁, and peak flow rates with nedocromil sodium inhalation therapy in asthmatics (using the Saint Georges Respiratory Questionnaire). Noonan and colleagues (4) demonstrated improved health status, symptom scores, and asthma control in asthmatics receiving fluticasone propionate (using the SF-36). Each of these studies showed improvement in clinical and physiologic measures as well as health status, showing that these treatments are effective at improving physiology, symptoms, and health status.

There have been several trials demonstrating a benefit in health status while showing no change in physiologic or other outcomes. Mahler and colleagues (14) used the Baseline Dyspnea Index (BDI) in a crossover, double-blind trial of theophylline in patients with COPD. In this study the dyspnea scale showed a benefit of theophylline, whereas spirometry, arterial blood gases, and exercise tolerance were not affected. Borson and colleagues (43) examined the effect of antidepressant therapy on depression, health status (using the Sickness Impact Profile), spirometry, and exercise tolerance in patients with COPD and depression. They found that therapy improved not only anxiety and depression, but also health status. There was, however, no significant change in FEV₁, arterial blood gases, or exercise tolerance. These studies showed significant improvement in health status when traditional clinical outcomes did not show improvement. If health status had not been assessed, these therapies might have been judged ineffective.

van Schayck and colleagues (44) found that physiologic measures can change without a change in health status. These investigators examined the effect of routine versus symptomatic inhaled salbutamol and ipratroprium therapy on health status (using the Nottingham Health Profile) and spirometry in patients with COPD and/or asthma. Although they found no difference between salbutamol and ipratroprium in either health status or spirometry, there was a significantly greater decline in FEV₁ in the group receiving continuous therapy than in those receiving symptomatic therapy. The more rapid decline in FEV₁ was not associated with a decline in health status. This trial suggests that if investigators are concerned about health status, they must measure it rather than assuming that it will change with a physiologic parameter such as FEV₁.

Finally, the use of health status to assess pulmonary rehabilitation provides insight into generic and disease-specific measures. Ries and colleagues (16) compared an 8-wk comprehensive pulmonary rehabilitation program with an education-only program and showed that exercise capacity and symptoms improved with pulmonary rehabilitation, but there was no difference in health status (using the Quality of Well Being). Similarly, other studies have found no benefit of pulmonary rehabilitation in health status as measured by generic instruments (45, 46). However, using the disease-specific Chronic Respiratory Questionnaire, Wijkstra and colleagues (47) found that health status and exercise tolerance improved in a randomized, controlled trial of home pulmonary rehabilitation and that there was long-term benefit in health status from a follow-up home respiratory therapy program (15). This difference in outcome may be because the generic instruments are less responsive to changes caused by treatment (48).

	WHERE DO WE GO FROM HERE?

Although available instruments provide reliable and valid measures of health status in patients with chronic lung disease, the utility of health status measures is not widely accepted. For example, the Food and Drug Administration does not accept health status as a primary measure of efficacy in clinical trials of new treatments for pulmonary diseases. Consequently, major clinical trials sponsored by the pharmaceutical industry do not use health status as the primary outcome measures.

Areas of Disagreement

In the American Thoracic Society's conference on health outcomes in chronic lung disease, a group of colleagues from diverse backgrounds gathered to discuss the following question: what prevents health status measures from being used as the primary outcome measure in major clinical trials? The group included academic investigators and developers of health status instruments, clinicians and managed care representatives, industry representatives, and representatives of regulatory agencies. There were differing opinions about the current state of the art of health status assessment. Many of the industry and regulatory agency representatives were not convinced that the current experience allowed these instruments to be used as the primary end point of clinical trials. One view was that there are dozens of health status instruments available and that it is difficult to determine which instruments are reliable and valid. On the other hand, instrument developers were convinced that published data identify a small group of instruments with sufficient reliability and validity for use in clinical trials.

Industry and regulatory agency representatives also raised some technical issues about health status instruments. One issue identified was that the relative lack of experience with health status measures makes it difficult to assess the minimum amount of change in a health status score that represents a clinically significant change (the minimal clinically significant difference). Although some investigators have developed methods to determine this value (49, 50), there is no generally accepted method. Another issue is that health status measures with multiple subscores are particularly prone to the statistical problem of multiple comparisons. Finally, there was concern that measures assessing a patient's subjective experience may be particularly prone to the "placebo effect" or to showing artifactual improvement because of mood-altering side effects of drugs such as corticosteroids, beta-agonists, or antidepressants. Investigators with experience in the use and development of these instruments felt that each of these issues reflected a lack of widely accepted standards rather than an insurmountable problem inherent to health status measures.

Needs for the Future of Health Status Assessment in Chronic Lung Disease

Five groups are major stakeholders for the future of health status measurement in chronic lung disease. These groups are clinicians and managed care organizations, academic investigators, industry, regulatory agencies, and patients with chronic lung disease. Each of these groups has a slightly different perspective about the future needs in health status assessment; these perspectives provide insight into the potential roles for health status measurement in chronic lung disease.

For clinicians and managed care, the major potential for health status assessment is to identify patients and groups at risk for poor outcomes and target services to prevent these poor outcomes. Other potential goals for providers and managed care organizations are to use health status measures to evaluate the effect of specific therapies and medical care approaches on the patients under their care and to use these instruments to provide a valid assessment of the effect that individual providers have on improving the health status of their patients. Finally, providers are interested in exploring and developing the use of health status assessment of an individual patient to improve the quality of care provided to that patient.

The primary short-term goal for academic investigators is to develop a standardized set of methodologies to advance health status research. Areas in need of standardization include terms, methods for determining the minimal clinically significant difference, and criteria for evaluating and comparing health status instruments. Academic investigators also identified a need to perform head-to-head comparisons of different instruments to identify the best instruments, encourage a standardized approach to health status measurement, and enhance understanding of the field. Other important areas of need include incorporating diverse perspectives into health status assessments such as those of patients, physicians, nurses, respiratory therapists, and administrators and providing education and training for investigators and clinicians in the use and interpretation of health status measurement. Finally, specific methods need to be developed to enhance the interpretability of health status measures for clinicians.

For the pharmaceutical industry, a major area of need is for specific health status instruments to be widely accepted, limited in number, easy to administer and score, and generalizable to different patient populations. Emphasis should also be placed on the importance of a standardized method of using health status measurement in statistical and cost-effectiveness analyses. Finally, two unique needs for industry are to develop a standardized way to report the results of a clinical trial in the product label and promotional material and for these instruments to be accepted by the regulatory agencies for use as a primary end point in clinical trials.

The primary goal of the regulatory agency is to be certain that a standardized method exists for objectively determining the efficacy of a new product and the validity of the research used to demonstrate efficacy. In order to achieve this goal with health status measures, regulatory agencies must be able to identify the well-characterized, validated, and widely accepted instruments, and there must be standardized methods for using health status instruments in sample size calculations, hypothesis-testing, and prespecified statistical analysis plans.

Finally, from the perspective of patients with chronic lung disease, the burden of completing health status instruments must be minimal. If patients are going to take the time to complete these instruments, there must be some assurance that the instruments will be used in a way that will improve the health of the persons completing the forms.

Recommendations for the Future

1. Establish Standards for Evaluating, Using, and Interpreting Health Status Instruments in Clinical Research Concerning Chronic Lung Diseases.

There is an important need to develop uniform and widely accepted criteria to assess the reliability, validity, and utility of health status instruments for use in patients with chronic lung disease. It would be useful to have an experienced and diverse group charged with developing standards for health status instruments to be used among patients with chronic lung diseases. The standards should be explicit and could, for example, be published as "ATS Standards for Assessing Health Status in Chronic Lung Disease." Similar standards have been developed for the assessment of generic health status instruments (51). In addition, the committee might periodically review instruments submitted by investigators to assess their reliability, validity, and utility in the evaluation of patients with chronic lung disease. The committee could implement the standards by (1) providing investigators, managed care organizations, industry, and regulatory agencies with clear criteria for evaluating and using instruments; (2) assessing available instruments using these criteria; (3) recommending specific instruments that should be used in specific settings.

2. Facilitate Funding for Research on Health Status Measurement in Chronic Lung Disease.

Advancement of this field will require identification of research funding to answer specific questions about health status measurement in chronic lung disease. Important areas of research include head-to-head comparisons of different health status instruments, standardization of critical areas such as the "minimal clinically significant difference," and further elucidating the relationship between health status and traditional clinical measures of outcome and severity of chronic lung disease. Further information is also needed to define the generalizability of health status measures to different populations and subgroups, including different racial and ethnic groups, wide ranges of socioeconomic status, and children. Future areas of research should also include the use of health status measures to assess the role of specialty and subspecialty care in the outcomes of chronic lung disease and to define the costs and cost-effectiveness of different therapeutic approaches.

3. Promote Education and Training Concerning the Measurement of Health Status.

There is a need to promote education and training in the understanding of health status assessment for clinicians, investigators, and trainees. This would include education about the choice and use of health status measures in clinical research and the evaluation and interpretation of these measures in the medical literature. Information about individual health status measures should be accessible to investigators interested in health status in chronic lung disease. For example, the Assembly of Behavioral Science within the American Thoracic Society is developing a webpage which will provide some of this specific information to investigators (http://www.thoracic.org).

	SUMMARY

TOP INTRODUCTION CONCLUSION REFERENCES

Health status measures have become an important part of clinical research concerning chronic lung disease in the past 10 years. Health status can be reliably measured in patients with chronic lung disease. Many investigators believe that these measures provide a valid assessment of the effect that disease and treatment have on patients' lives. These measures are being used increasingly to determine the efficacy (or lack of efficacy) of therapy in improving patients' lives. We believe that health status measures will provide an important supplement to the clinical and physiologic measures traditionally used in clinical research because these different outcomes do not always change to the same degree or in the same direction.

Despite the recent increase in the use of health status measures, there remain considerable challenges before these measures will be widely used as the primary end points in clinical research. There needs to be standardization in the evaluation, use, and interpretation of health status measures for these measures to gain widespread acceptance among clinicians, the pharmaceutical industry, and the regulatory agencies. Existing research has laid the groundwork for this standardization. The challenges will be: (1) direct future research to consolidate, rather than expand, the number of methods and instruments used in health status research; (2) build further evidence supporting the validity and utility of health status measures in clinical research; and (3) continue efforts to forge an alliance among academia, pharmaceutical industry, regulatory agencies, managed care, clinicians, and patients to ensure that health status measures meet each of their diverse needs.

	Footnotes

Correspondence and requests for reprints should be addressed to J. Randall Curtis, M.D., M.P.H, Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, Box 359762, 325 Ninth Avenue, Seattle, WA 98104-2499.

(Received in original form February 5, 1997 and in revised form June 4, 1997).

Acknowledgments: Supported in part by Grant HL-30542 from the National Institutes of Health and by the Medical Research Service of the Department of Veterans Affairs.

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