- Email: [email protected]
What does it all mean? Using health-related quality-of-life data to interpret treatment outcomes
CLINICAL THERAPEUTICS”
dian change, 10 to 40). Patients who completed the trimodal treatment had significantly better baseline physical function (93 vs 80; P = 0.005) and significantly fewer problems with dysphagia (22 vs 38; P = 0.009) than did those not completing the treatment course. CONCLUSIONS: This exploratory study shows that neoadjuvant treatment for esophageal cancer has a negative impact on generic functional QOL scores and some symptoms. Disease-specific QOL issues, however, may improve during treatment. All aspects of QOL deteriorate dramatically after major surgery. QLQ-C30 score changes of 210 appear to represent clinically significant changes.
#29 What Does It All Mean? Using Health-Related Quality-ofLife Data to Interpret Treatment Outcomes Nancy K. L.etiy, PhD,’ Deborah Jonas,’ Cheryl Silberman, PhD,2 Mary Kay Margolis,’ and Anne Heyes, BSc2 ‘MEDTAP International, Inc., Bethesda, Maryland, and 2AstraZeneca Le Wilmington, Delaware
Pharmaceuticals,
INTRODUCTION: The primary goals of treatment for patients with chronic symptomatic conditions and those requiring palliative care are to contain the underlying disease and control symptoms to improve or maintain health-related quality of life (QOL). Thus, QOL data not only can, but should play a key role in interpreting the success of treatment. This implies that there is another perspective to the QOL interpretation issue: How are disease containment and symptom outcomes interpreted? What constitutes symptom distress, tolerance, and relief? What changes in the more traditional efficacy end points are meaningful to patients-that is, what changes translate into improvements or maintenance in QOL? OBJECTIVE: This theoretical paper discusses the clinical significance of QOL data in oncology research by examining the relationships between disease control, symptoms, and QOL in this population. Specifically, the paper discusses the meaning of successful treatment in patients with terminal conditions such as non-small-cell lung cancer by proposing a framework in which QOL data are used to interpret traditional efficacy end points, such as tumor size and symptoms. RESULTS: The framework draws a distinction between the underlying pathologic condition or process, symptom occurrence (ie, frequency, intensity, duration), impact (distress, tolerance), and outcomes (relief and control). This permits the researcher to model and test the extent to which the underlying disease process and each attribute of a given symptom or symptom cluster are distressing to patients and which dimensions of QOL are affected. The nature of the relationships among these variables, including the extent to which symptoms serve as mediating or moderating variables in the relationship between the underlying pathologic condition and QOL, also can be examined. Finally, terms such as symptom distress, tolerance, relieA and control can be operationalized in terms of patient QOL. CONCLUSION: The use of QOL data to operationalize the true meaning of treatment success offers an-
39
CLINICAL THERAPEUTICS”
other perspective on the issue of clinical significance and the challenge of interpreting QOL outcomes in oncology research. ACKNOWLEDGMENT: Funding for this study was provided by AstraZeneca Pharmaceuticals, LP, Wilmington, Delaware.
#30 Interpretation of Quality-of-Life Data from a Clinician’s Point of View: Getting to the Clinical Part of Clinically Meaningful Change Cheryl R. Dennison, PhD, CRNP,’ Nancy K. Leidy, PhD,’ Cheryl Silberman, PhD,2 and Anne Heyes, BSc2 ‘MEDTAP International, Inc., Bethesda, Maryland, and 2AstraZeneca Pharmaceuticals, Le Wilmington, Delaware
INTRODUCTION: The purpose of assessing the impact of cancer diagnosis and treatments on quality of life (QOL) in clinical trials is to help clinicians assist their patients in making informed treatment decisions. This is particularly pertinent when multiple treatment options exist or when survival gains from treatment are modest and treatment toxicity is considerable. Although clinicians are proficient in evaluating physiologic outcomes based on established “norms” and their own clinical experience, most have little or no experience in evaluating QOL. Moreover, it is challenging to clinicians to relate the quantitative measurement of QOL reported in the literature to their clinical practice. For QOL outcomes to be applied in treatment-related decision-making in the clinical setting, we must bridge the gap between research and clinical practice. OBJECTIVE: The aim of this paper is to offer a clinically oriented framework to guide clinicians in selecting pertinent QOL literature, interpreting QOL change scores, and determining the utility of results. METHODOLOGY: The framework is as follows: (1) Determine overall interest in the specific topic of the report. Is the therapeutic area of interest to the clinician? Are clinicians familiar with the QOL instrument used? (2) Determine whether the disease and treatment characteristics of the study population reflect the characteristics of the patients that the clinician is treating. (3) Examine the quality of the research, including study design, methods, and analytic approach. Was a generic or disease-specific instrument used? Were data on instrument reliability and validity provided? Were the specific items in the QOL instrument relevant to the clinician’s patient population? Were the timing and frequency of QOL assessments appropriate given the treatment schedule and the expected clinical effects of treatment? Did the authors report information regarding the amount of individual variation in treatment response (eg, CIs, SDS, and subgroup data)? Were potential confounding variables included in analyses to account for changes that may have been unrelated to treatment? (4) Determine what the results mean from a clinical perspective. Were the QOL scores consistent with clinical indicators? Did the authors provide interpretation of the clinical significance of changes in QOL scores, and is the interpretation comprehensible? If distribution- or anchor-based methods were used, were
40
dian change, 10 to 40). Patients who completed the trimodal treatment had significantly better baseline physical function (93 vs 80; P = 0.005) and significantly fewer problems with dysphagia (22 vs 38; P = 0.009) than did those not completing the treatment course. CONCLUSIONS: This exploratory study shows that neoadjuvant treatment for esophageal cancer has a negative impact on generic functional QOL scores and some symptoms. Disease-specific QOL issues, however, may improve during treatment. All aspects of QOL deteriorate dramatically after major surgery. QLQ-C30 score changes of 210 appear to represent clinically significant changes.
#29 What Does It All Mean? Using Health-Related Quality-ofLife Data to Interpret Treatment Outcomes Nancy K. L.etiy, PhD,’ Deborah Jonas,’ Cheryl Silberman, PhD,2 Mary Kay Margolis,’ and Anne Heyes, BSc2 ‘MEDTAP International, Inc., Bethesda, Maryland, and 2AstraZeneca Le Wilmington, Delaware
Pharmaceuticals,
INTRODUCTION: The primary goals of treatment for patients with chronic symptomatic conditions and those requiring palliative care are to contain the underlying disease and control symptoms to improve or maintain health-related quality of life (QOL). Thus, QOL data not only can, but should play a key role in interpreting the success of treatment. This implies that there is another perspective to the QOL interpretation issue: How are disease containment and symptom outcomes interpreted? What constitutes symptom distress, tolerance, and relief? What changes in the more traditional efficacy end points are meaningful to patients-that is, what changes translate into improvements or maintenance in QOL? OBJECTIVE: This theoretical paper discusses the clinical significance of QOL data in oncology research by examining the relationships between disease control, symptoms, and QOL in this population. Specifically, the paper discusses the meaning of successful treatment in patients with terminal conditions such as non-small-cell lung cancer by proposing a framework in which QOL data are used to interpret traditional efficacy end points, such as tumor size and symptoms. RESULTS: The framework draws a distinction between the underlying pathologic condition or process, symptom occurrence (ie, frequency, intensity, duration), impact (distress, tolerance), and outcomes (relief and control). This permits the researcher to model and test the extent to which the underlying disease process and each attribute of a given symptom or symptom cluster are distressing to patients and which dimensions of QOL are affected. The nature of the relationships among these variables, including the extent to which symptoms serve as mediating or moderating variables in the relationship between the underlying pathologic condition and QOL, also can be examined. Finally, terms such as symptom distress, tolerance, relieA and control can be operationalized in terms of patient QOL. CONCLUSION: The use of QOL data to operationalize the true meaning of treatment success offers an-
39
CLINICAL THERAPEUTICS”
other perspective on the issue of clinical significance and the challenge of interpreting QOL outcomes in oncology research. ACKNOWLEDGMENT: Funding for this study was provided by AstraZeneca Pharmaceuticals, LP, Wilmington, Delaware.
#30 Interpretation of Quality-of-Life Data from a Clinician’s Point of View: Getting to the Clinical Part of Clinically Meaningful Change Cheryl R. Dennison, PhD, CRNP,’ Nancy K. Leidy, PhD,’ Cheryl Silberman, PhD,2 and Anne Heyes, BSc2 ‘MEDTAP International, Inc., Bethesda, Maryland, and 2AstraZeneca Pharmaceuticals, Le Wilmington, Delaware
INTRODUCTION: The purpose of assessing the impact of cancer diagnosis and treatments on quality of life (QOL) in clinical trials is to help clinicians assist their patients in making informed treatment decisions. This is particularly pertinent when multiple treatment options exist or when survival gains from treatment are modest and treatment toxicity is considerable. Although clinicians are proficient in evaluating physiologic outcomes based on established “norms” and their own clinical experience, most have little or no experience in evaluating QOL. Moreover, it is challenging to clinicians to relate the quantitative measurement of QOL reported in the literature to their clinical practice. For QOL outcomes to be applied in treatment-related decision-making in the clinical setting, we must bridge the gap between research and clinical practice. OBJECTIVE: The aim of this paper is to offer a clinically oriented framework to guide clinicians in selecting pertinent QOL literature, interpreting QOL change scores, and determining the utility of results. METHODOLOGY: The framework is as follows: (1) Determine overall interest in the specific topic of the report. Is the therapeutic area of interest to the clinician? Are clinicians familiar with the QOL instrument used? (2) Determine whether the disease and treatment characteristics of the study population reflect the characteristics of the patients that the clinician is treating. (3) Examine the quality of the research, including study design, methods, and analytic approach. Was a generic or disease-specific instrument used? Were data on instrument reliability and validity provided? Were the specific items in the QOL instrument relevant to the clinician’s patient population? Were the timing and frequency of QOL assessments appropriate given the treatment schedule and the expected clinical effects of treatment? Did the authors report information regarding the amount of individual variation in treatment response (eg, CIs, SDS, and subgroup data)? Were potential confounding variables included in analyses to account for changes that may have been unrelated to treatment? (4) Determine what the results mean from a clinical perspective. Were the QOL scores consistent with clinical indicators? Did the authors provide interpretation of the clinical significance of changes in QOL scores, and is the interpretation comprehensible? If distribution- or anchor-based methods were used, were
40