Abstract
Health-related quality of life (HRQOL) assessment is becoming common practice in many clinical trials. There is much debate over how to determine the clinical significance of changes in HRQOL scores. A number of techniques have been used to address this issue. This paper reviews the most popular of these approaches for use in a clinical trial setting. More specifically, the anchor-based “minimal clinically important difference” technique is described and critiqued, as is the more traditional distribution-based effect size technique. A novel application of effect size, which applies a common statistical premise known as the empirical rule, is also presented. The review of these techniques indicates that there is no single, optimal solution to determining clinical significance of changes in HRQOL scores. However, it is encouraging to note that they ail suggest a similar criterion of a half-standard deviation for whether or not a change in HRQOL score is clinically significant. Recommendations are given for reporting the clinical significance of HRQOL assessments in clinical trials.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Wilke RJ. Glick HA, McCarron TJ, et al. Quality of life effects of alprostadil therapy for erectile dysfunction.J Urol. 1996;157:2124–2128.
Juniper EF, Guyatt GH, Willam A. Griffith LE. Determining a minimal important change in a disease-specific Quality of Life Questionnaire. J Clin Epidemiol. 1994;47:81–87.
Juniper EF, The value of quality of life in asthma. Eur Respir Rev. 1997;7:333–337.
Juniper EF. Quality of life questionnaires: does statistically significant = clinically important? J Allergy Clin Immunol. 1998;102:16–17.
Cohen J. Statistical Power Analysis for the Behavioral Sciences. Hillsdale, NJ: Academic Press; 1988.
Jaeschke R, Singer J, Guyatt GH. Measurement of health status. Ascertaining the minimal clinically important difference. Control Clin Trials. 1989; 10:407–415.
Osoba D, Rodrigues G. Myles J. Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998; 16:139–144.
Sloan J, Symonds T. Health related quality of life: When does a statistically significant change become clinically significant? Presented at the ISO-QOL Educational Workshop, Washington, DC, January, 2001.
Guyatt GH, Sullivan MJ, Thompson PJ, et al. The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure. Can Med Assoc J. 1985;132:919–923.
Bittner V, Weiner DH, Yusuf S, et al. Prediction of mortality and morbidity with a 6-minute walk test in patients with left ventricular dysfunction. SOLVD Investigators. JAMA. 1993;270: 1702–1707.
Jones PW, Quirk FH, Baveystock CM. The St George’s Respiratory Questionnaire. Respir Med. 1991;85 Suppl B25-31; Discussion 33–37.
Jones PW. Quality of life, symptoms and pulmonary function in asthma: long-term treatment with nedocromil sodium examined in a controlled multicentre trial. Nedocromil Sodium Quality of Life Study Group. Eur Respir J. 1994;7:55–62.
Jones PW, Bosh TK. Quality of life changes in COPD patients treated with salmeterol. Am J Respir Crit Care Med. 1997; 155:1283–1289.
Pocock SJ. Statistical and ethical issues in monitoring clinical trials. Stat Med. 1993; 12(15–16): 1459–1469.
Senn SJ, Auclair P. The graphical representation of clinical trials with particular reference to measurements over time. Stat Med. 1990; Nov;9 (11): 1287–1302.
Sloan JA. Asking the obvious questions regarding patient burden. J Clin Oncology. 2002;20:4–6.
Kazis LE, Anderson JJ, Meenan RF. Effect sizes for interpreting changes in health status. Med Care. 1989;27:S178–189.
McCorkle R, Young K. Development of a symptom distress scale. Cancer Nurs. 1978;1:373–378.
Norman GR, Stratford P, Regehr G. Methodological problems in the retrospective computation of responsiveness to change: the lesson of Cronbach. J Clin Epidemiol. 1997;50:869–879.
Barber BL, Santanello NC, Epstein RS. Impact of the global on patient perceivable change in an asthma specific QOL questionnaire. Qual Life Res. 1996;5:117–122.
Redelmeier DA, Guyatt GH, Goldstein RS. Assessing the minimal important difference in symptoms: a comparison of two techniques. J Clin Epidemiol. 1996;49:1215–1219.
Cella DF. Quality of life outcomes: measurement and validation. Oncology (Huntingt). 1996;10: 233–246.
Feinstein AR. Indexes of contrast and quantitative significance for comparisons of two groups. Stat Med. 1999;18:2557–2581.
Stucki G, Daltroy L, Katz JN, Johannesson M, Liang MH. Interpretation of change scores in ordinal clinical scales and health status measures: the whole may not equal the sum of the parts. J Clin Epidemiol. 1996;49:711–717
Bellamy N. Anastassiades TP, Buchanan WW, et al. Rheumatoid arthritis antirheumatic drug trials. III. Setting the delta for clinical trials of antirheumatic drugs results of a consensus development (Delphi) exercise. J Rheumatol. 1991; 18:1908–1915.
Bellamy N, Carette S, Ford PM, et al. Osteoarthritis antirheumatic drug trials, III. Setting the delta for clinical trials—Results of a consensus development (Delphi) exercise. J Rheumatol. 1992;19: 451–457.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sloan, J., Symonds, T., Vargas-Chanes, D. et al. Practical Guidelines for Assessing the Clinical Significance of Health-Related Quality of Life Changes within Clinical Trials. Ther Innov Regul Sci 37, 23–31 (2003). https://doi.org/10.1177/009286150303700105
Published:
Issue Date:
DOI: https://doi.org/10.1177/009286150303700105