title: Health-related quality of life assessment in contemporary phase III trials in advanced colorectal cancer.
abstract: BACKGROUND
  Health-related quality of life (HRQOL) is often used as an endpoint in cancer clinical trials. We assessed the frequency and correlates of HRQOL use in phase III trials in advanced colorectal cancer.
  
  
  METHODS
  We searched PubMed for phase III trials published between January 1998 and December 2014, as well as for companion papers reporting on HRQOL separately. We excluded papers reporting on correlative biology or prognostic factors in isolation from the main trial results, as well as trials on supportive care and on local therapy.
  
  
  RESULTS
  We retrieved 111 trials that enrolled a total of 61,531 patients in 241 trial arms. HRQOL was reportedly used as an endpoint in 40 trials (36%), in all but two as a secondary endpoint. There was a significant decrease in the use of HRQOL, with frequencies of 46% in trials published between 1998 and 2006, and 27% between 2007 and 2014 (P=0.04). Trials with HRQOL as endpoint were significantly larger than trials without such endpoint. Formal statistical comparisons involving HRQOL parameters were reported in 36 of 40 trials (90%) with HRQOL assessment, with a significant difference between arms found in 14 (39%), six of which favoring the experimental arm. HRQOL gains were usually accompanied by improvements in efficacy endpoints, but were not related to the number of patients or chemotherapy line.
  
  
  CONCLUSIONS
  HRQOL has been formally assessed in about one-third of recent phase III trials in advanced colorectal cancer, with a significant gain in HRQOL in about 40% of cases. It is questionable whether HRQOL results may largely help select between competing treatments. This assumption may be one of the reasons for the apparent decreased use of HRQOL as an endpoint in phase III trials in this disease.
authors.affiliation: Regional Hospital, Wejherowo, Poland. Electronic address: krzys.adamowicz@gmail.com.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Adamowicz
authors.affiliation: Dendrix Research, Sao Paulo, Brazil; International Drug Development Institute, Louvain-la-Neuve, Belgium.
authors.forename: Everardo D
authors.initials: ED
authors.lastname: Saad
authors.affiliation: Medical University of Gdansk, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D006304:Health Status; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D017063:Outcome Assessment, Health Care; D010166:Palliative Care; D011788:Quality of Life
chemical_list: D000970:Antineoplastic Agents; D007155:Immunologic Factors
keywords: Advanced colorectal cancer; Chemotherapy; Quality of life; Treatment outcomes