ILAE Report Principles of Health-related Quality of Life: Assessment in Clinical Trials *Joyce A. Cramer for the ILAE Subcommission on Outcome Measurement in Epilepsy (Carol Camfield, Hans Carpay, Christopher Helmstaedter, John Langfitt, Kristina Malmgren, and Samuel Wiebe) *Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, U.S.A. The importance of health-related quality of life (HRQOL) is increasingly leading to inclusion of HRQOL instruments in clinical trials. The purpose of these assessments is to demonstrate a change over time that is related to an intervention (e.g., medication, device, surgery, other services). Although the number of HRQOL instruments developed for epilepsy populations is increasing, most of the information currently available relates to instrument validation. Few data are available about the instruments in practical use. Thus it is difficult to plan a clinical trial with an HRQOL instrument as the primary outcome because of the paucity of information on which to base expected change for sample size. The use of HRQOL instruments in trials will be as secondary outcomes, additional data on which to evaluate patient outcomes, until there is a well-established basis from which to draw clinical conclusions. This report is an overview of the principles of HRQOL assessment in clinical trials. It is designed to serve as a guide to the inclusion of patient-reported outcomes in research planning and implementation. Selected refer- ences are given for general resources. The Appendix is a listing of instruments used in studies of epilepsy with details and references to sources of additional informa- tion. DEFINITIONS Definition of outcomes Outcomes are the clinical results of treatments. Detec- tion or estimation of the improvement or decline in pa- tient outcome after a treatment change is best measured in a controlled clinical trial. HRQOL scales may be cor- related to such clinical measures and reflect different degrees of impairment in various domains. Definition of HRQOL HRQOL instruments usually assess the patient’s sub- jective perception of the impact of disease and treatment on multiple dimensions of health status, based on the patient’s report. Instruments are composed of the follow- ing general domains: physical, psychological, and social functioning, as well as some disease- and treatment- related symptoms or other domains. At times, a subjec- tive assessment is made for children, disabled subjects, or subjects with neurologic disorders by a surrogate (e.g., parent, caregiver, observer). HRQOL instruments are not diagnostic scales or disease/symptom severity scales. Scales that measure only performance, handicap or dis- ability, anxiety, depression, fatigue, pain, or other symp- toms are not HRQOL scales. SELECTION OF AN HRQOL INSTRUMENT Measure selection Choice of the measure is determined by the actual question posed by the investigator. The purposes for which an instrument is used must be clearly stated to assure that the questionnaire is used as designed by the developers, unless they have been restandardized for the setting or population for which the current study is planned. This would include a similar application of methodology in the disease, population, function, or con- dition. Examples of differences in settings or populations that can affect whether a measure is appropriate or not include 1. Age, education range, or developmental level of population studied. 2. Setting in which administered—telephone, home, or clinic setting, etc. 3. Respondent or caregiver: mother, father, patient, foster parent, nurse, etc. Accepted November 23, 2001. Address correspondence and reprint requests to J. A. Cramer at Yale-VA Medical Center, 950 Campbell Avenue (G7E), West Haven, CT 06516-2770, U.S.A. E-mail: Joyce.Cramer@Yale.Edu Epilepsia, 43(9):1084–1095, 2002 Blackwell Publishing, Inc. © International League Against Epilepsy 1084