Substituting proxy ratings for patient ratings in cancer clinical trials: an analysis based on a Southwest Oncology Group trial in patients with brain metastases.

In studies of the effect of cancer treatment in the advanced disease setting, researchers have attempted to avoid missing data for quality of life (QOL) assessments by either substituting proxy for patient assessments from the outset or by interspersing proxy measures when patients are unable to respond. Although poor agreement between patient and proxy assessments has been amply demonstrated in the literature, interest in using proxy measures persists. Completion of the Spitzer QL-Index by a small sample of patients with brain metastases and family member proxies provided data for evaluating the ability to substitute proxy for patient QOL assessments. These data cannot address treatment efficacy due to the modest sample size. Rather, the analyses serve to alert researchers to the important distinction (in a clinical trial setting) between agreement and the use of the proxy as a surrogate. We present several methods for evaluating the accuracy of proxy measures and for identifying other sources of error and bias that may vary with time or with treatment arm. Lin's concordance correlation coefficient suggests that proxies are generally a poor substitute for capturing a patient's perspective of his/her QOL. A longitudinal analysis suggests that the use of proxy rather than patient responses could lead to different conclusions concerning radiation therapy's effect on QOL.