Introduction

Traditionally, clinical trials have focused on endpoints that are physical or laboratory measures of response. For example, therapies for cancer are evaluated on the basis of disease progression and survival. The efficacy of a treatment for anemia is evaluated by hemoglobin levels or number of transfusions required. Although traditional biomedical measures are often the primary endpoints in clinical trials, they do not reflect how the patient feels and functions in daily activities, yet these perceptions reflect whether or not the patient believes he or she has benefited from the treatment. In certain diseases, the patient’s perception of his or her well-being may be the most important health outcome [144]. More recently, clinical trials are including endpoints that reflect the patient’s perception of his or her well-being and satisfaction with therapy. Sometimes clinical investigators assume that a certain change in therapy or a traditional biomedical outcome will improve the patient’s quality of life. While in many cases this may be true, sometimes surprising results are obtained when the patient is asked directly. One classic example of this occurred with a study by Sugarbaker et al. [148] comparing two therapeutic approaches for soft-tissue sarcoma. The initial study compared two therapeutic options. The first was limb-sparing surgery followed by radiation therapy. The second treatment approach was full amputation of the affected limb. The investigator hypothesized, “Sparing a limb, as opposed to amputating it, offers a quality of life advantage.” As a result of the study, the hypothesis was rejected; subjects receiving the limb-sparing procedures reported limitations in mobility and sexual functioning. These observations were confirmed with physical assessments of mobility and endocrine function. Radiation therapy was modified and physical rehabilitation was added to the limb-sparing therapeutic approach [65].