title: Challenges posed by non-random missing quality of life data in an advanced-stage colorectal cancer clinical trial.
abstract: Effects of variations in agent, dose, and route of treatment administration on patient reported quality of life (QOL) were examined for 279 patients enrolled on a seven-arm randomized clinical trial (S8905) of 5-FU and its modulation for advanced colorectal cancer. Patients completed QOL questionnaires at randomization and weeks 6, 11, and 21 post-randomization with five QOL endpoints considered primary: three treatment-specific symptoms (stomatitis, diarrhea, and hand/foot sensitivity); physical functioning; and emotional functioning. Patient compliance with the QOL assessment schedule was good, supporting the feasibility of including QOL measures in cooperative group trials. However, death and deteriorating health produced substantial missing data. Cross-sectional analyses indicated that the seven therapeutic arms did not differ in their impact on QOL. Unfortunately, longitudinal analyses of the QOL data were inappropriate given non-random missing data. Graphical presentation of non-random missing data identified the seriousness of this problem and its effect on potential conclusions about QOL during treatment. This problem appears to be particularly challenging in the context of advanced-stage disease. Failure to recognize the presence of non-random missing data can lead to serious overestimates of patient QOL over time.
authors.affiliation: Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. carolm@swog.fhcrc.org
authors.forename: C M
authors.initials: CM
authors.lastname: Moinpour
authors.forename: J
authors.initials: J
authors.lastname: Sawyers Triplett
authors.forename: B
authors.initials: B
authors.lastname: McKnight
authors.forename: L C
authors.initials: LC
authors.lastname: Lovato
authors.forename: C
authors.initials: C
authors.lastname: Upchurch
authors.forename: C G
authors.initials: CG
authors.lastname: Leichman
authors.forename: F M
authors.initials: FM
authors.lastname: Muggia
authors.forename: L
authors.initials: L
authors.lastname: Tanaka
authors.forename: W A
authors.initials: WA
authors.lastname: James
authors.forename: M
authors.initials: M
authors.lastname: Lennard
authors.forename: F L
authors.initials: FL
authors.lastname: Meyskens
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D015982:Bias; D017322:Clinical Trials, Phase II as Topic / Q000523:psychology*; D017326:Clinical Trials, Phase III as Topic / Q000523:psychology*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000523:psychology*; D003430:Cross-Sectional Studies; D003625:Data Collection / Q000592:standards*; D003627:Data Interpretation, Statistical; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011788:Quality of Life / Q000523:psychology*; D016032:Randomized Controlled Trials as Topic / Q000523:psychology*; D015203:Reproducibility of Results; D012107:Research Design / Q000592:standards*; D011795:Surveys and Questionnaires
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil