Variability and Sample Size Requirements of Quality-of-Life Measures: A Randomized Study of Three Major Questionnaires Yin-Bun Cheung, Cynthia Goh, Julian Thumboo, Kei-Siong Khoo, and Joseph Wee A B S T R A C T Purpose To compare the variability and sample size requirements of the global quality-of-life (QOL) scores of the following three major QOL instruments: the Functional Assessment of Cancer Therapy–General (FACT-G), Functional Living Index–Cancer (FLIC), and Euro- pean Organisation for Research and Treatment of Cancer Core Quality of Life Question- naire C30 (EORTC QLQ-C30). Patients and Methods Cancer patients were randomly assigned to answer two of the three instruments using an incomplete block design (n = 1,268). The instruments were compared in terms of coefficient of variation, effect size in detecting a difference between patients with different perfor- mance status, and correlation coefficient between scores at baseline and follow-up. Results The FACT-G and FLIC had significantly smaller coefficients of variation than the EORTC QLQ-C30 (both P  .05). The FLIC also had significantly larger correlation coefficients between scores at baseline and follow-up than the EORTC QLQ-C30 (P  .05). The FACT-G and the FLIC had a larger effect size in a cross-sectional and longitudinal setting, respectively, than the EORTC QLQ-C30 in differentiating patients with different perfor- mance status (both P  .05). Conclusion In some aspects, the FACT-G and FLIC global QOL scores had smaller variability and larger discriminative ability than the EORTC QLQ-C30. Further research using other criteria to compare the three instruments is recommended. J Clin Oncol 23:4936-4944. © 2005 by American Society of Clinical Oncology INTRODUCTION A major challenge in conducting clinical trials is to recruit enough subjects for the trials to have a sufficient power. Sample size depends on the variability of the primary outcome measure. Other factors being equal, the larger the variability is, the larger the sample size required for a given purpose. In the context of questionnaire-based in- struments, the level of variability may be affected by the clarity of questions and the precision of response scales, and so on. In the past, health-related quality of life (HRQOL) was usually regarded as a minor end point. However, other researchers have advocated the use of HRQOL as a primary end point in some cancer clinical trials. 1,2 Therefore, it is useful to examine the variability of HRQOL scores of differ- ent measures and compare their sample size requirements. This will facilitate re- searchers to make informed choices on HRQOL instruments in clinical trials and to ensure studies are performed as effi- ciently as possible. From the Division of Clinical Trials and Epidemiological Sciences and Depart- ments of Palliative Medicine and Medical Oncology, National Cancer Centre; and Department of Rheuma- tology and Immunology, Singapore General Hospital, Singapore. Submitted July 27, 2004; accepted March 31, 2005. Supported by research grant No. NMRC/0743/2003 from the National Medical Research Council of Singapore. Authors’ disclosures of potential con- flicts of interest are found at the end of this article. Address reprint requests to Yin-Bun Cheung, PhD, Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre, 11 Hospital Dr, Singa- pore 169610; e-mail: cheungyb@ graduate.hku.hk. © 2005 by American Society of Clinical Oncology 0732-183X/05/2322-4936/$20.00 DOI: 10.1200/JCO.2005.07.141 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 23  NUMBER 22  AUGUST 1 2005 4936 Downloaded from jco.ascopubs.org on January 27, 2016. For personal use only. No other uses without permission. Copyright © 2005 American Society of Clinical Oncology. All rights reserved.