Challenges posed by non-random missing quality of life data in an advanced-stage colorectal cancer clinical trial

Effects of variations in agent, dose, and route of treatment administration on patient reported quality of life (QOL) were examined for 279 patients e nrolled on a seven-arm randomized clinical trial (S8905) of 5-FU and its mo dulation for advanced colorectal cancer. Patients completed QOL questionnai res at randomization and weeks 6, 11, and 21 post-randomization with five Q OL endpoints considered primary: three treatment-specific symptoms (stomati tis, diarrhea, and hand/foot sensitivity); physical functioning; and emotio nal functioning. Patient compliance with the QOL assessment schedule was go od, supporting the feasibility of including QOL measures in cooperative gro up trials. However, death and deteriorating health produced substantial mis sing data. Cross-sectional analyses indicated that the seven therapeutic ar ms did not differ in their impact on QOL. Unfortunately, longitudinal analy ses of the QOL data were inappropriate given non-random missing data. Graph ical presentation of non-random missing data identified the seriousness of this problem and its effect on potential conclusions about QOL during treat ment. This problem appears to be particularly challenging in the context of advanced-stage disease. Failure to recognize the presence of non-random mi ssing data can lead to serious overestimates of patient QOL over time. Copy right (C) 2000 John Wiley & Sons, Ltd.