QoL Measurement in RCTs in Breast Cancer
QoL Measurement in RCTs in Breast Cancer
Background Quality-of-life (QOL) measurement is often incorporated into randomized clinical trials in breast cancer. The objectives of this systematic review were to assess the incremental effect of QOL measurement in addition to traditional endpoints (such as disease-free survival or toxic effects) on clinical decision making and to describe the extent of QOL reporting in randomized clinical trials of breast cancer.
Methods We conducted a search of MEDLINE for English-language articles published between May–June 2001 and October 2009 that reported: 1) a randomized clinical trial of breast cancer treatment (excluding prevention trials), including surgery, chemotherapy, hormone therapy, symptom control, follow-up, and psychosocial intervention; 2) the use of a patient self-report measure that examined general QOL, cancer-specific or breast cancer–specific QOL or psychosocial variables; and 3) documentation of QOL outcomes. All selected trials were evaluated by two reviewers, and data were extracted using a standardized form for each variable. Data are presented in descriptive table formats.
Results A total of 190 randomized clinical trials were included in this review. The two most commonly used questionnaires were the European Organization for Research and Treatment of Cancer QOL Questionnaire and the Functional Assessment of Cancer Therapy/Functional Assessment of Chronic Illness Therapy. More than 80% of the included trials reported the name(s) of the instrument(s), trial and QOL sample sizes, the timing of QOL assessment, and the statistical method. Statistical power for QOL was reported in 19.4% of the biomedical intervention trials and in 29.9% of the nonbiomedical intervention trials. The percentage of trials in which QOL findings influenced clinical decision making increased from 15.2% in the previous review to 30.1% in this updated review for trials of biomedical interventions but decreased from 95.0% to 63.2% for trials of nonbiomedical interventions. Discordance between reviewers ranged from 1.1% for description of the statistical method (yes vs no) to 19.9% for the sample size for QOL.
Conclusion Reporting of QOL methodology could be improved.
Health-related quality of life (QOL) is now commonly incorporated into the design of clinical trials as a primary or secondary outcome. In 1993, QOL was defined broadly by the World Health Organization as an "individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. It is a broad-ranging concept affected in a complex way by the persons' physical health, psychological state, level of independence, social relationships, and their relationship to salient features of their environment". In 1989, Moinpour et al. suggested that QOL be included as an endpoint in randomized phase III clinical trials in the following circumstances: "protocols using adjuvant therapy for patients at risk of recurrence, disease sites with an extremely poor prognosis, protocols in which different modalities are compared, protocols in which treatment of different intensities and/or durations are compared and protocols in which survival is expected to be equivalent but QOL is expected to show difference." Data derived from QOL measured in clinical trials can be used to select the optimal intervention, describe a patient's experience, or provide prognostic information. Previous studies have shown that measuring QOL provides more information about symptoms than measuring adverse events alone.
In 2006, the Food and Drug Administration (FDA) introduced the term "patient-reported outcomes" as "a measurement of any aspect of a patient's health status that comes directly from the patient". The FDA proposed a series of criteria for selecting patient-reported outcome instruments when the effectiveness criteria for approval of medical product labeling claims are based on patient-reported outcomes. QOL is measured by patient-reported outcomes.
In breast cancer, patient-reported outcomes are rarely used for approval of a medical product. Most interventions are approved based on disease-free, progression-free, or overall survival outcomes. The incremental contribution of QOL measurement to clinical decision making beyond these traditional medical outcomes is unclear. However, for patients and clinicians, the effect of an intervention on QOL is of major interest.
The drawbacks of incorporating QOL outcomes into clinical trials include the additional resources needed to perform data collection and the challenges encountered in analyzing the data. Administering QOL questionnaires is labor intensive for the research team, and they take time and energy for patients to complete, which may be particularly precious when QOL assessment is conducted at the end of life. Administering and analyzing QOL questionnaires is also costly. Data analysis is a challenge because multiple questionnaires are often used, and missing data are frequently encountered. In addition, data analyses need to take into account the complexity of multiple assessments at different points in time with different questionnaires. Moreover, QOL data need to be presented so that the clinical significance of the results is clear. Ultimately, these results should also be made comprehensible for patients. Although QOL questionnaires are rarely included in the publications that describe their development and validity, many are accessible from the authors or from Web sites free of charge. Finally, QOL data are often reported either very briefly in the main publication or as a separate publication in a different journal and at a different time, potentially reducing the impact of these data on treatment decision making.
Despite these challenges, QOL outcomes are commonly used in oncology research. A systematic review published in 2003 by Goodwin et al. (our group) found 66 randomized clinical trials in breast cancer that included at least one QOL outcome. We found that the contribution of information obtained by measuring QOL to clinical decision making (ie, to selecting the optimal treatment among those being studied) depended on the trial setting. In randomized clinical trials of adjuvant therapy, QOL data did not influence clinical decision making. By contrast, these data had more weight in trials of psychosocial interventions, in which QOL was often the primary outcome.
Other systematic reviews of QOL in oncology have been published since ours. For example, Efficace et al. reviewed 24 randomized clinical trials in prostate cancer. They found that 74% reported some differences in QOL but only one-third had a robust QOL design and provided a "comprehensive picture of the whole treatment." The trials that were considered to have a robust QOL design (ie, they met eight of 11 criteria from a checklist for QOL outcome) were exclusively in the metastatic setting. In 2006, Blazeby et al. reviewed 33 randomized clinical trials in surgical oncology and found that in 22 of them, QOL measurement either influenced treatment recommendation from the authors or provided important information for patients to be fully informed of the impact of treatment on their QOL. In 2007, Joly et al. reviewed trials in metastatic cancer that had a sample size of at least 150 patients. They concluded that reporting of QOL was poor. More recently, Montazeri reviewed studies published from 1974 to 2007 that focused on QOL in breast cancer patients; the conclusions of the studies were summarized, but there was no assessment of the extent of QOL reporting.
Because numerous randomized clinical trials in breast cancer have been published since our review in 2003 (the literature search for that review was terminated in May–June 2001) and the quality and utility of QOL measurement and reporting have likely improved in recent studies, we have updated our review to examine if there has been any change in the effect of QOL on clinical decision making in randomized clinical trials in breast cancer. The objectives of this review were to assess the incremental effect of QOL measurement on clinical decision making over and above that of traditional trial endpoints and to describe the extent of QOL reporting in clinical trials.
Abstract and Introduction
Abstract
Background Quality-of-life (QOL) measurement is often incorporated into randomized clinical trials in breast cancer. The objectives of this systematic review were to assess the incremental effect of QOL measurement in addition to traditional endpoints (such as disease-free survival or toxic effects) on clinical decision making and to describe the extent of QOL reporting in randomized clinical trials of breast cancer.
Methods We conducted a search of MEDLINE for English-language articles published between May–June 2001 and October 2009 that reported: 1) a randomized clinical trial of breast cancer treatment (excluding prevention trials), including surgery, chemotherapy, hormone therapy, symptom control, follow-up, and psychosocial intervention; 2) the use of a patient self-report measure that examined general QOL, cancer-specific or breast cancer–specific QOL or psychosocial variables; and 3) documentation of QOL outcomes. All selected trials were evaluated by two reviewers, and data were extracted using a standardized form for each variable. Data are presented in descriptive table formats.
Results A total of 190 randomized clinical trials were included in this review. The two most commonly used questionnaires were the European Organization for Research and Treatment of Cancer QOL Questionnaire and the Functional Assessment of Cancer Therapy/Functional Assessment of Chronic Illness Therapy. More than 80% of the included trials reported the name(s) of the instrument(s), trial and QOL sample sizes, the timing of QOL assessment, and the statistical method. Statistical power for QOL was reported in 19.4% of the biomedical intervention trials and in 29.9% of the nonbiomedical intervention trials. The percentage of trials in which QOL findings influenced clinical decision making increased from 15.2% in the previous review to 30.1% in this updated review for trials of biomedical interventions but decreased from 95.0% to 63.2% for trials of nonbiomedical interventions. Discordance between reviewers ranged from 1.1% for description of the statistical method (yes vs no) to 19.9% for the sample size for QOL.
Conclusion Reporting of QOL methodology could be improved.
Introduction
Health-related quality of life (QOL) is now commonly incorporated into the design of clinical trials as a primary or secondary outcome. In 1993, QOL was defined broadly by the World Health Organization as an "individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. It is a broad-ranging concept affected in a complex way by the persons' physical health, psychological state, level of independence, social relationships, and their relationship to salient features of their environment". In 1989, Moinpour et al. suggested that QOL be included as an endpoint in randomized phase III clinical trials in the following circumstances: "protocols using adjuvant therapy for patients at risk of recurrence, disease sites with an extremely poor prognosis, protocols in which different modalities are compared, protocols in which treatment of different intensities and/or durations are compared and protocols in which survival is expected to be equivalent but QOL is expected to show difference." Data derived from QOL measured in clinical trials can be used to select the optimal intervention, describe a patient's experience, or provide prognostic information. Previous studies have shown that measuring QOL provides more information about symptoms than measuring adverse events alone.
In 2006, the Food and Drug Administration (FDA) introduced the term "patient-reported outcomes" as "a measurement of any aspect of a patient's health status that comes directly from the patient". The FDA proposed a series of criteria for selecting patient-reported outcome instruments when the effectiveness criteria for approval of medical product labeling claims are based on patient-reported outcomes. QOL is measured by patient-reported outcomes.
In breast cancer, patient-reported outcomes are rarely used for approval of a medical product. Most interventions are approved based on disease-free, progression-free, or overall survival outcomes. The incremental contribution of QOL measurement to clinical decision making beyond these traditional medical outcomes is unclear. However, for patients and clinicians, the effect of an intervention on QOL is of major interest.
The drawbacks of incorporating QOL outcomes into clinical trials include the additional resources needed to perform data collection and the challenges encountered in analyzing the data. Administering QOL questionnaires is labor intensive for the research team, and they take time and energy for patients to complete, which may be particularly precious when QOL assessment is conducted at the end of life. Administering and analyzing QOL questionnaires is also costly. Data analysis is a challenge because multiple questionnaires are often used, and missing data are frequently encountered. In addition, data analyses need to take into account the complexity of multiple assessments at different points in time with different questionnaires. Moreover, QOL data need to be presented so that the clinical significance of the results is clear. Ultimately, these results should also be made comprehensible for patients. Although QOL questionnaires are rarely included in the publications that describe their development and validity, many are accessible from the authors or from Web sites free of charge. Finally, QOL data are often reported either very briefly in the main publication or as a separate publication in a different journal and at a different time, potentially reducing the impact of these data on treatment decision making.
Despite these challenges, QOL outcomes are commonly used in oncology research. A systematic review published in 2003 by Goodwin et al. (our group) found 66 randomized clinical trials in breast cancer that included at least one QOL outcome. We found that the contribution of information obtained by measuring QOL to clinical decision making (ie, to selecting the optimal treatment among those being studied) depended on the trial setting. In randomized clinical trials of adjuvant therapy, QOL data did not influence clinical decision making. By contrast, these data had more weight in trials of psychosocial interventions, in which QOL was often the primary outcome.
Other systematic reviews of QOL in oncology have been published since ours. For example, Efficace et al. reviewed 24 randomized clinical trials in prostate cancer. They found that 74% reported some differences in QOL but only one-third had a robust QOL design and provided a "comprehensive picture of the whole treatment." The trials that were considered to have a robust QOL design (ie, they met eight of 11 criteria from a checklist for QOL outcome) were exclusively in the metastatic setting. In 2006, Blazeby et al. reviewed 33 randomized clinical trials in surgical oncology and found that in 22 of them, QOL measurement either influenced treatment recommendation from the authors or provided important information for patients to be fully informed of the impact of treatment on their QOL. In 2007, Joly et al. reviewed trials in metastatic cancer that had a sample size of at least 150 patients. They concluded that reporting of QOL was poor. More recently, Montazeri reviewed studies published from 1974 to 2007 that focused on QOL in breast cancer patients; the conclusions of the studies were summarized, but there was no assessment of the extent of QOL reporting.
Because numerous randomized clinical trials in breast cancer have been published since our review in 2003 (the literature search for that review was terminated in May–June 2001) and the quality and utility of QOL measurement and reporting have likely improved in recent studies, we have updated our review to examine if there has been any change in the effect of QOL on clinical decision making in randomized clinical trials in breast cancer. The objectives of this review were to assess the incremental effect of QOL measurement on clinical decision making over and above that of traditional trial endpoints and to describe the extent of QOL reporting in clinical trials.
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