A framework for assessing health-related quality of life among children with cancer (1999)

<-pick;f1;0;0>There is a critical need for the development of valid and useful measures of health-related quality of life (HRQL) for children with cancer. The ever-increasing survival rates in pediatric oncology, presently approximating 70% overall, demand that our priorities be modified to not only seek cure but to focus close attention also on the costs of cure. Key elements of the costs of cure include the morbidity burdens associated with short-term and long-term toxicities and the morbidity associated with sequelae of the treatment and of the disease itself. A critical issue in designing new therapies for childhood cancer is how to reduce the morbidity of treatment without compromising survival rates. These morbidities can be quantified objectively with measures of HRQL. Measuring HRQL during the process of treatment would provide information crucial to patients, families and health-care providers when faced with difficult decisions concerning treatment alternatives. Similarly, HRQL information collected from survivors would be useful in decision making. However, further substantive progress requires the identification, acceptance and use of standard HRQL measures (Osoba, 1994; Reaman and Haase, 1996). Most of the existing publications have focused on HRQL in adult populations. There is a need for measures that deal with the problems faced by children1. Because cognitive capacity for self-evaluation changes with the process of normal maturation, designing and validating instruments for children below the age of 3 years is particularly challenging (Bradlyn et al., 1996). In addition, there is a dearth of instruments for children 3 through 8 years of age. The spectrum of morbidities in many other illnesses of children is encompassed by the morbidities among children with cancer. Therefore, a focus on HRQL in pediatric oncology affords a context within which to build a prototype strategy for the assessment of HRQL among all children. In fact, several approaches developed originally in the context of childhood cancer have been applied already in other areas of pediatrics, such as follow-up studies among survivors of extremely low birthweight and population health surveys of children (Saigal et al., 1994,b, 1996; Feeny et al., 1996a). The original primary aim of this document was to provide a structure for the scientific agenda of the International Workshop on Assessing Health-Related Quality of Life among Children with Cancer. The objective was to provide a common language and a set of definitions for concepts to facilitate communication among workshop participants from diverse backgrounds (the intention was not to limit the scope of the workshop to particular approaches or methodologies). Now that the workshop has been held, this document provides an outline and the necessary background information for the publication of the reports presented at the event. A discussion of critical topics follows. These topics include the basic concepts of quality of life and HRQL, the purposes of HRQL measures and measurement, a taxonomy of measures of HRQL and a variety of methodological standards for assessing the performance of HRQL measures. Finally, key objectives for the workshop agenda, around which the program was organized, are delineated. “Quality of life” is a broad, multi-dimensional concept applied to an individual's status that includes economic welfare; characteristics of the community, such as crime rate and cultural and recreational amenities; characteristics of the environment, such as air and water quality; and health status. All of these dimensions are important for an overall sense of positive well-being (Patrick and Erickson, 1993). In the context of health care, most treatments are focused narrowly on medical complaints and may not affect overall quality of life importantly. Therefore, the publications on outcomes in health and health care have developed a specially defined concept of quality of life: HRQL. HRQL is concerned with the opportunities that a person's health status affords, the constraints that it places upon the person and the value that a person places on his or her health status. There is a wide variety of definitions of health status (e.g., Patrick and Erickson, 1993; McDowell and Newell, 1996). Some, like the World Health Organization definition, include overall well-being and therefore overlap with more global quality-of-life definitions. Others are more narrow and correspond more closely to the concept of HRQL. There are a number of key dimensions of health status found in virtually all definitions, including (i) physical function (mobility and fitness), (ii) sensation (vision, hearing, speech, taste, smell, touch), (iii) self-care and dexterity, (iv) cognition, (v) pain and discomfort and (vi) emotional and psychological well-being. The definitions of health status based on this list of dimensions have been described as “narrow–within the skin” definitions because of the focus on the health status of the person and the capacity for living afforded by that health status (Ware et al., 1981). Some definitions of health status expand on this list to include social interactions. Each of these approaches has its advantages and disadvantages, depending on the purpose of measurement. What is important is that investigators be explicit about the underlying conceptualization of HRQL to be used and select HRQL measures that are consistent with that conceptualization and the objectives of their study. An important rationale for using an HRQL measure is that a goal of medical treatment is to make patients feel better, i.e., to enhance their HRQL. If the enhancement of HRQL is indeed a goal of therapy, then it is imperative to measure HRQL directly and objectively. Another reason to measure HRQL is that these data may provide useful information that is unavailable from other, often qualitative and subjective, clinical measures. HRQL measures will complement traditional clinical and physiological measures. In a number of situations in medicine, physiological measures of treatment efficacy may improve without people feeling better as a result. For example, the ejection fraction of a patient with cardiac problems may change, but there may be no corresponding change in activities of daily living or vitality. In other cases, such as the result of a pain intervention, patients may feel better but there may be no corresponding change in physiological functioning. HRQL measures also help to identify the most appropriate choices among alternatives that involve tradeoffs of therapeutic and adverse effects. For example, reduction in the number of painful and swollen joints is important in the treatment of patients with arthritis but, in some cases, the treatment benefit may be offset completely by the side effects of nausea and abdominal discomfort that accompany anti-inflammatory or analgesic therapy. HRQL measures allow one to assess the net effects of interventions. Broadly speaking, we may identify 3 primary purposes for measures of health status and HRQL: discrimination, evaluation and prediction (Kirshner and Guyatt, 1985; Guyatt et al., 1993, 1996). When one uses an HRQL measure for discrimination, the purpose is to distinguish the burden of morbidity among groups or individuals at a point in time2. Thus, HRQL measures that emphasize discrimination are useful for cross-sectional analyses. For a discriminatory measure to be useful, it is desirable that it have a large, stable between-subject variation. Evaluation involves the assessment of change in HRQL within individuals over time. Evaluative measures are used in longitudinal/prospective studies such as clinical trials. Therefore, items in an evaluative measure need to be modifiable. Small within-subject variation in stable patients and responsiveness to change are desirable properties for evaluative measures. Prediction may involve the use of an HRQL measure to predict the score on another measure at the same point in time. In this case, one might be interested in using a simpler and less invasive test as a substitute for a more burdensome one or a short form as a substitute for a long form of a questionnaire. Alternatively, one might be interested in how well a measure taken at time t predicts outcome at time t + 1. Indeed, there is evidence that baseline HRQL measures have independent prognostic value for predicting survival in lung cancer, breast cancer and metastatic malignant melanoma (Mossey and Shapiro, 1982; Ganz et al., 1991; Coates et al., 1992; Clinch, 1996) and in other circumstances (Mossey and Shapiro, 1982; Gold et al., 1996). Both of these uses of predictive measures are relevant in the context of pediatric oncology. More specifically, the routine clinical use of HRQL (and other measures) to identify patients and families at risk for adverse effects may provide clinicians the opportunity to reduce sequelae by modifying treatment or intervening in some other manner in a more timely fashion3. The use of HRQL measures may permit the identification of groups susceptible to adverse medical or psychological sequelae who might benefit from such intervention or even prophylaxis (Lauria et al., 1996). Baseline HRQL scores might be used also to stratify patients in clinical trials. It is important to keep the purpose of the HRQL measure in mind during the design and development of the measure because there are tradeoffs among these 3 primary purposes. Measures designed for one purpose may be less than ideal for another purpose. For instance, an item may be very useful for discriminating the degree of impairment among individuals but, because the item is not readily modifiable, not very useful for evaluative purposes. Many standard psycho-social measures were developed originally for discrimination; their usefulness for evaluative purposes often remains to be established. In addition to these 3 major purposes of HRQL measures, Osoba (1995) identifies a complementary list of purposes for HRQL measurement. The purposes he identifies include screening, describing health status, assisting in the management of individual patients, assisting in the formulation of clinical policy and assisting in making resource allocation decisions. A wide variety of HRQL measures have emerged. Some diversity is both inevitable and appropriate. HRQL is a broad, multi-dimensional concept, and different measures examine different domains. Many investigators have a variety of objectives and thus require a battery of HRQL measures for different research questions, situations and purposes. In addition, a wide variety of intellectual disciplines have contributed to the development of measures of HRQL. As a result, measures often differ in terms of the underlying conceptual foundations upon which they are based4. There are a number of ways to classify HRQL measures. One classification scheme is presented below in Table I. Specific instruments have been developed for application to particular populations5. Typically, these measures focus on the dimensions of HRQL that are relevant to a particular disease or health problem and its treatment. By including only those elements that are most important in the particular clinical situation, these measures can be constructed to include a wide range of effects. For instance, components of physical function and emotional function and items that are of special concern to individual patients can be included without imposing a large burden of irrelevant questions on respondents. Many specific instruments were constructed to maximize their responsiveness to change, i.e., designed for evaluative purposes. A good example of such a specific instrument is the Pediatric Asthma Quality of Life Scale (Townsend et al., 1991; Juniper et al., 1996a,b, 1997; Guyatt et al., 1997; Feeny et al., 1998b). In the context of cancer in childhood, the Pediatric Oncology Quality of Life Scale (POQOLS) focuses on health-related quality-of-life concerns of patients undergoing therapy (Boggs et al., 1991; Goodwin and Boggs, 1994). A number of specific instruments developed for use in pediatric oncology settings were discussed at the International Workshop and are described in the reports that follow. Generic instruments are suitable for use with virtually any population. Therefore, generic measures typically cover a number of dimensions of HRQL, including physical function, social and emotional function, pain and self-care. It is useful to distinguish at least 2 major subcategories of generic instrument: health profiles and preference-based measures. Health profiles provide separate scores for a number of categories or dimensions of HRQL. The profile may or may not allow for aggregation into a single summary score. The Sickness Impact Profile developed by Bergner et al. (1981) is a good example of a health profile measure which allows for a single summary score. The Nottingham Health Profile does not yield a summary score (McEwen and McKenna, 1996). Preference-based measures, like health profiles, are widely applicable. Preference-based instruments give scores on a conventional, 0.00 (dead) to 1.00 (perfect health), scale, thus facilitating broad comparisons between the effects of alternative health-care interventions. Preference-based measures can be subdivided into 2 approaches. The first approach involves the direct assessment of preferences for health states, e.g., the health states experienced by patients in a particular study. The second approach involves the use of multi-attribute health-status classification systems and their corresponding HRQL scoring systems. The first (direct) approach some characteristics with health profiles as well as with specific measures are designed for specific the to as with specific items of particular in that used with instruments typically include of hearing, speech, cognition, and was included in a of HRQL in pediatric et al., Feeny et al., and in a of the HRQL experienced by long-term survivors of extremely low birthweight (Saigal et al., 1996). The direct approach has an to the specific in that patients can be to provide global of the net of treatment on their HRQL. Thus, HRQL by the patients their of the positive treatment effects and the side effects. specific these effects are and or no information is on the of the of therapeutic and treatment side effects (the same to instruments for which no single summary score is In the second preference-based the health status of a patient is described using a multi-attribute health status classification and then using an HRQL scoring HRQL scoring are often based on surveys of A good example of the application of a multi-attribute approach to is found in the evaluation of care by et al. which the Health The multi-attribute approach has been applied also in a number of clinical studies in pediatric characteristics that the for measures of HRQL include (i) (ii) (iii) and (iv) (v) (vi) and The is to the set of concepts which were to a common for purposes of discussion at the International Workshop and for the reports from The is not to methodological standards (the will discussion of concerning of the properties of HRQL These performance characteristics for the most from and methodological used for the assessment of HRQL in adult populations. HRQL is more in pediatric settings (Bradlyn et al., 1996; et al., and 1996). There are age on the of normal maturation, the language and of children change with age. more is normal health for children is a of is need to be in and pediatric HRQL measures. In addition, for very or very one has to often on (e.g., in pediatric settings and The to which into the assessment of HRQL is to the degree to which interested the measure to be In the context of pediatric HRQL, can be from a variety of including those of the patients, of the patient and health-care the burden of on is A number of be when assessing including the time necessary for degree of or degree of and degree of or A issue is the burden on investigators and clinical to the of a measure to distinguish people to an underlying A measure is and has low of There are a number of concepts to responsiveness and to the degree of when the same a may be in such to the to which 2 provide the same scores when are at the same point in time. using among items in a is another often used in the context of to the among items at the same point in time. If a includes many items on a particular or of health status, the information by some of may be However, only a items on a are important information may be to the to which a measure provides the same score when there has been no underlying The concept with as described or to change, to the of a measure to change over time. Some investigators this concept as of the to changes or in HRQL and 1996). Others to it as responsiveness et al., 1991; Guyatt et al., 1993). A measure be it can be useful as an outcome measure in a clinical The to an important and the to a or large change or in the population will be in to the responsiveness of the and Guyatt 2 for assessing that the scores improve with application of a treatment of efficacy and use of the measure in a clinical by of change scores in those who or as by some other effects when patients the score with a particular Similarly, effects when patients who already the score The of or effects will limit the responsiveness and of measures of HRQL and 1996). has been defined as an of the degree to which a measures it to measure also and et al., 1993; McDowell and Newell, 1996). In other a instrument is in the context of the purpose for which it is to be used There are several relevant of discussed to the to which and of the measure the items described in the measure to be i.e., the to which the measure sense to to the with which a measure the important areas of the which it is to (Kirshner and Guyatt, 1985; and 1996). and 3 for a valid (i) of the of that is relevant to the particular situation, (ii) identification and of dimensions and from the of dimensions for in the measure and (iii) of items that the associated with can be in the set of relevant dimensions or in assessing the of a is concerned with the to which a particular measure to other measures in a manner that is consistent with concerning the concepts or that are The of evidence of is necessary there is no or standard that is as to the concept to be and In for the purposes of assessing the and evaluative properties of HRQL measures, there is no standard the assessment of on involves 3 (i) of the between (ii) of the between measures of the concepts and (iii) of the evidence in terms of how it the of the in the of a measure with a of consistent different a number of different studies and The rationale of that the between of a concept, and relevant be in terms of and For the most or of the of an evaluative its to other measures be in a in which change over time is (Kirshner and Guyatt, involves assessing the between the test measure and the is by the of the and have usefulness in the of health status for some of the dimensions (e.g., and concepts (e.g., health status and there are no which the measures can be The is the assessment of predictive one measure is to a of how of and differ because of the purpose of HRQL are presented in Table to the to which one can to the qualitative information and scores afforded by the measure et al., and 1993; and 1996). involves the of and data on using the measure in a variety of the is one useful of information on how to Similarly, information on how individuals with particular or health problems score and how their scores to scores for the population is Both and comparisons can be on how scores in the of important changes in health circumstances is in change scores et al., The underlying of the scoring including its also and the of the scoring When assessing the of any HRQL scoring the underlying about the of preferences and the that they on items or will affect to how a measure of HRQL might be used to affect clinical management and can the to which the measure in communication among patients, families and health-care providers et al., HRQL measures can be useful also in to clinical policy and resource allocation (Patrick and Erickson, Feeny et al., 1997; Osoba et al., The primary aim of the workshop was the and of information on the of HRQL in the context of cancer during this the workshop was around 1. more evidence on the performance characteristics of HRQL measures in the context of pediatric oncology and closely areas of Because there is we are interested in both studies in which HRQL measures to have and to have valid and studies in in of care and a measure not in that particular examine the of and among about the HRQL of an individual at a point in time and changes in HRQL over time. The questions be of and children by health-care with by patients and the degree of with the age of the there important of among health-care the degree of by of HRQL measure or over If virtually all then the HRQL effects of a therapy or assessing the burden of morbidity will not on there are important among which therapies or among burdens of morbidity more the of children to HRQL Many children and may require to HRQL More of concept can children at and of development be to of such as and may these can HRQL measures be to is appropriate for children at evidence the performance of different HRQL measures at the same in in terms of their purposes and and some measures better than in some measures more some measures to of A objective is the of evidence on the of measures in different cultural and settings and in assessing the and of cultural of evidence to in HRQL data for include information on and to test need to evidence also on the of of and large changes (and in HRQL. is is What of change are to What of change are to their families or to health-care evidence on the usefulness of HRQL measures in pediatric oncology on a variety of includes clinical management at the individual formulation of clinical development of treatment and formulation of resource allocation from in which HRQL have been will be in assessing the for HRQL measures as a for the clinical management of patients and their If HRQL measures are useful in predicting those who will burdens of morbidity or families for the will be particularly then their routine use may provide a for to reduce those HRQL measures be used also in this context to assess the of such interventions. The International Workshop focused on these from a broad of with the to make an important to the of HRQL in pediatric oncology, were and to The workshop was also designed to a critical of investigators to the of assessing HRQL in children with cancer. that the time was to make major concerning the underlying and in the use of HRQL in methodological in HRQL in pediatric oncology will also to the assessment of HRQL among children in The reports that are evidence of progress these The Guyatt for on an of the