JNCI Monographs - current issue

Introduction

Minasian, L., O'Mara, A. — 2007-10-18

Translating the Science of Patient-Reported Outcomes Assessment Into Clinical Practice

Osoba, D. — 2007-10-18

Patient-reported outcomes (PROs) are based on direct reporting by patients without the intervention of an observer. They include the self-assessment of functional status, symptoms, and other concerns such as needs and satisfaction with care. Health-related quality of life (HRQOL) assessment is a form of PRO and often includes both functional status and symptoms. The science underlying the assessment of HRQOL in clinical practice requires an understanding of the relationships between symptoms, functional status, and HRQOL, as well as instrument selection, and analysis and interpretation of the data. A modification of the Wilson and Cleary model is proposed to show the likelihood of bidirectional relationships between symptoms, functions, and HRQOL. Instrument selection should be based on the measurement properties of the instruments and patient populations in which they will be used. Analyses of data that allow a calculation of the proportion of patients who benefit from an intervention are preferred to analyses that show only the mean change in scores from baseline. HRQOL assessment in clinical practice has been shown to lead to a better understanding of patients' concerns with improvement in counseling and referral for required services. Potentially, HRQOL assessment should also be used to monitor the progress of a patient's disease and benefit from treatment.

Outcomes Research in Cancer Symptom Management Trials: The Radiation Therapy Oncology Group (RTOG) Conceptual Model

Bruner, D. W. — 2007-10-18

The Radiation Therapy Oncology Group (RTOG) Health Services Research and Outcomes (HSRO) Committee aims to guide the study of the interactions among clinical, humanistic, and economic variables that optimize patient outcomes on clinical trials. To guide this work, the RTOG Outcomes Model was developed. Within this framework, measurement focuses primarily on patient-reported outcomes (PROs). In the examples presented, these outcomes have served to better quantify the benefit of one therapy over alternative therapies, as in the example of multimodality therapy for lung cancer, and to add evidence to clinical outcomes when clinical outcomes alone have not been strong enough to change clinical practice, as in the example of palliative radiotherapy for painful bone metastasis. The unique contribution to the RTOG of the HSRO Committee is the selection and use of PRO measures that give "voice" to the patient in clinical trials as well as provide data to better manage symptoms.

Symptom Burden: Multiple Symptoms and Their Impact as Patient-Reported Outcomes

Cleeland, C. S. — 2007-10-18

Cancer and its treatment produce multiple symptoms that significantly distress patients and impair function. Symptoms caused by treatment may delay treatment or lead to premature treatment termination, and residual treatment-related symptoms often complicate posttreatment rehabilitation. When treatment is no longer possible, symptom control becomes the focus of cancer care. Patient ratings of symptom severity and impact are important patient-reported outcomes (PROs) in cancer clinical trials and comprise a subset of a larger domain of PROs generally referred to as health-related quality of life (HRQOL). Symptoms rarely occur in isolation; rather, there is now ample evidence that symptoms frequently occur in clusters. The impact of these multiple symptoms upon the patient can be described as "symptom burden," a concept that encompasses both the severity of the symptoms and the patient's perception of the impact of the symptoms. The distress caused by symptoms is a subject of much investigation, and several validated measures of the severity and impact of multiple symptoms are now available. Symptom measures are generally brief, thereby reducing respondent burden, and can be administered repeatedly during a trial to give a relatively fine-grained picture of the patient's status across time. In many instances, information on trial-related changes in symptom burden, or comparison of symptom burden between arms in a clinical trial, may provide sufficient self-report data for clinical trial consumers (patients, clinicians, and regulators) to make treatment choices or to evaluate new therapies, without measuring other HRQOL domains.

Differences in What Quality-of-Life Instruments Measure

Ferrans, C. E. — 2007-10-18

To address the question of what value is added by assessing quality of life (QOL) in symptom management trials in cancer, we used the model of Wilson and Cleary to identify what is measured by the most commonly used QOL instruments. Examples of clinical trials are presented demonstrating the contributions of these broad-based QOL instruments in terms of symptoms, functioning, general health perceptions, and overall QOL. The examples show that QOL instruments can provide valuable information about side effects and impact on other aspects of life, which would not be captured by a more narrowly focused measure of the target symptom. A better understanding is needed of the differences in what QOL instruments measure, since conclusions regarding the effectiveness of treatment may differ depending on which one is used to assess outcomes. Head-to-head comparisons of instruments within the same studies would increase precision for selecting QOL instruments for symptom management trials.

Challenges to Use of Health-Related Quality of Life for Food and Drug Administration Approval of Anticancer Products

2007-10-18

The U.S. Food and Drug Administration (FDA) approves labeling claims of drug efficacy based on substantial evidence of clinical benefit demonstrated in adequate and well-controlled investigations. Patient-reported outcomes (PROs) may support marketing claims of clinical benefit, either alone or with other study endpoints. Health-related quality of life (HRQL) is a PRO that comprehensively measures patients' reported health status. We present an overview of why HRQL-based efficacy claims have not to date been accepted by the FDA for inclusion in anticancer product labels. Persistent challenges to allowance of such claims include shortcomings in randomization and blinding of clinical trials, missing data, statistical multiplicity, and unclear intrinsic meaning of selected HRQL findings.

Do General Dimensions of Quality of Life Add Clinical Value to Symptom Data?

Moinpour, C. M., Donaldson, G. W., Redman, M. W. — 2007-10-18

Since global health-related quality of life (GHRQL) reflects broad impacts of treatment, its assessment in an advanced-stage disease trial should add valuable clinical information beyond that of a targeted symptom. Using latent trajectory modeling that allowed for individual trends as well as overall relationships, we reanalyzed three repeated assessments of the present pain intensity from the McGill Pain Questionnaire and the European Organization for Research and Treatment of Cancer Quality of life Questionnaire- Core 30 (QLQ-C30) GHRQL score from a hormone-refractory prostate cancer trial. Within- and between-treatment differences not detected in the original S9916 report of pain palliation and GHRQL suggested substantial individual variation in GHRQL level and change after controlling for within-assessment pain. The treatment had a differential effect on the relationship between GHRQL and pain; we observed an approximately threefold stronger association of reported pain with GHRQL in the docetaxel plus estramustine (D + E) arm compared with the mitoxantrone plus prednisone (M + P) arm (P = .02). In addition, the treatment had an effect, on average, on the rate of change in GHRQL, after controlling for pain level. GHRQL for patients on the M + P arm tended to improve over the assessment period while GHRQL tended to deteriorate for patients on the D + E arm (P = .02). Important, interpretable effects and systematic individual variation in GHRQL remain after controlling statistically for the effects of pain, the targeted symptom, in this trial. In addition, identifying the rate at which a person's GHRQL changes or responds to treatment provides clinically relevant information.

Conceptual Issues in Symptom Clusters Research and Their Implications for Quality-of-Life Assessment in Patients With Cancer

Miaskowski, C., Aouizerat, B. E., Dodd, M., Cooper, B. — 2007-10-18

The majority of the research on the various aspects of symptom management has focused on individual symptoms. However, patients with cancer often experience multiple symptoms simultaneously as a result of their disease and treatment. In 2001, symptom management researchers began to study the impact of symptom clusters on patient outcomes. Over the past 6 years, a number of conceptual reviews as well as several research studies have been published on symptom clusters in oncology patients. This paper summarizes the conceptual basis for symptom cluster research, describes two conceptual approaches to symptom cluster research, and discusses the implications of symptom clusters for quality-of-life research. The paper concludes with an enumeration of the critical considerations that need to be addressed if this area of scientific inquiry is to move forward.

Health-Related Quality of Life Measurement in Symptom Management Trials

Ganz, P. A., Goodwin, P. J. — 2007-10-18

There is increasing support for the incorporation of patient-reported outcomes (PROs) into clinical trials in cancer. While the need for inclusion of measures of target symptoms in symptom management trials is clear, arguments can also be made for measurement of a broader range of symptoms, for evaluation of symptom burden, and for evaluation of health-related quality of life (HRQOL) in these trials. What is key to their inclusion is a priori selection of instruments, provision of a theoretic basis for inclusion of instruments, and a clearly described plan of analysis. The federal Food and Drug Administration (FDA) has provided guidance regarding the use of PROs (symptom and HRQOL measures) to support treatment benefit claims in product labeling. Moving forward, research is needed to address methodological issues raised by the FDA and to increase understanding of relationships among symptoms, symptom clusters, HRQOL, and other outcome measures.

Should Health-Related Quality of Life Be Measured in Cancer Symptom Management Clinical Trials? Lessons Learned Using the Functional Assessment of Cancer Therapy

Cella, D., Wagner, L., Cashy, J., Hensing, T. A., Yount, S., Lilenbaum, R. C. — 2007-10-18

There are several advantages to including comprehensive health-related quality of life (HRQL) in symptom trials in oncology. The most obvious is to test the hypothesis that HRQL will be improved in addition to the symptom benefit. We should not "require," however, that a successful symptom intervention also improve other dimensions of HRQL. On the other hand, we should expect that it will not make other dimensions worse through side effects or exacerbation of disease, even if it improves the symptom. HRQL assessment in the trial helps evaluate the competing risks of any therapy. Furthermore, assessment of HRQL is now accomplished with very brief assessment (usually 30 questions or less), and the knowledge gained is valuable. With HRQL, one can compare cancer patients with those with other conditions and can determine the contribution of symptoms and side effects to the more broadly defined HRQL. Examples using the Functional Assessment of Cancer Therapy measurement system will demonstrate how HRQL assessment has contributed to our understanding of common cancer symptoms and their place in the conceptualization of HRQL. The prevalence of clinically significant symptoms is greatest in poor performance status (PS) patients compared with patients with good PS. Symptom improvement trials specifically designed for these patients should be encouraged, particularly with interventions that can provide symptomatic relief and improve multidimensional HRQL.