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Background: We evaluated 4 different health-related quality of life (HRQL) measures prospectively to determine their ability to detect change over time: the Health Utilities Index Mark 2 and Mark 3, the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core and Cancer Module, the EuroQol EQ-5D visual analogue scale (EuroQol), and the Lansky Play-Performance Scale., Methods: Children with all stages of Hodgkin disease from 12 centers across Canada were asked to complete the 4 measures at 4 time points: 2 weeks after the first course of chemotherapy, on the third day of the second course of chemotherapy, during the third week of radiation, and 1 year after diagnosis., Results: Fifty-one patients were enrolled in the study between May 1, 2002 and March 31, 2005. Two patients were excluded: 1 patient died shortly after the first time point and the other patient failed to complete any of the questionnaires. All measures showed a significant change between Time 1 and Time 4 (<0.05). When the change in child scores was analyzed between the time points using the child's self-reported change in HRQL, the PedsQL and the EuroQol showed significant change at all time points., Conclusions: All of the measures were able to detect change in a diverse group of children with Hodgkin disease. The PedsQL and the EuroQol appeared to be the most sensitive to change.