Estimating clinically significant differences in quality of life outcomes Article DOI:
Cite this article as: Wyrwich, K.W., Bullinger, M., Aaronson, N. et al. Qual Life Res (2005) 14: 285. doi:10.1007/s11136-004-0705-2 Abstract Objective: This report extracts important considerations for determining and applying clinically significant differences in quality of life (QOL) measures from six published articles written by 30 international experts in the field of QOL assessment and evaluation. The original six articles were presented at the Symposium on Clinical Significance of Quality of Life Measures in Cancer Patients at the Mayo Clinic in April 2002 and subsequently were published in Mayo Clinic Proceedings. Principal findings: Specific examples and formulas are given for anchor-based methods, as well as distribution-based methods that correspond to known or relevant anchors to determine important differences in QOL measures. Important prerequisites for clinical significance associated with instrument selection, responsiveness, and the reporting of QOL trial results are provided. We also discuss estimating the number needed to treat (NNT) relative to clinically significant thresholds. Finally, we provide a rationale for applying group-derived standards to individual assessments. Conclusions: While no single method for determining clinical significance is unilaterally endorsed, the investigation and full reporting of multiple methods for establishing clinically significant change levels for a QOL measure, and greater direct involvement of clinicians in clinical significance studies are strongly encouraged. Keywords Clinically important change Clinical significance Minimally important difference Quality of life Abbreviations CTT
classical test theory
minimal important difference
number needed to treat
quality of life
standard error of measurement
The Clinical Significance Consensus Meeting Group - See listing of members at the end of this article
References Sloan, J, Cella, D, Frost, M, et al. 2002 Assessing clinical significance in measuring oncology patient quality of life: Introduction to the symposium, content overview, and definition of terms. Mayo Clinic Proc 77 367 370 Google Scholar Cella, D, Bullinger, M, Scott, C, et al. 2002 Group vs. individual approaches to understanding the clinical significance of differences or changes in quality of life. Mayo Clinic Proc 77 384 392 Google Scholar Frost, M, Bonomi, A, Ferrans, C, et al. 2002 Patient, clinician, and population perspectives on determining the clinical significance of quality-of-life scores. Mayo Clinic Proc 77 488 494 Google Scholar Guyatt, G, Osoba, D, Wu, A, et al. 2002 Methods to explain the clinical significance of health status measures. Mayo Clinic Proc 77 371 383 Google Scholar Sprangers, M, Moinpour, C, Moynihan, T, et al. 2002 Assessing meaningful change in quality of life over time: A users’ guide for clinicians. Mayo Clinic Proc 77 561 571 Google Scholar Symonds, T, Berzon, R, Marquis, P, et al. 2002 The clinical significance of quality-of-life results: Practical considerations for specific audiences. Mayo Clinic Proc 77 572 583 Google Scholar Osoba, D. 2002 Taxonomy of the uses of health-related quality-of-life instruments in cancer care and the clinical meaningfulness of the results. Med Care 40(6 suppl) III-31 III-38 Google Scholar Wyrwich, K, Wolinsky, F 2000 Identifying meaningful intra-individual change standards for health-related quality of life measures. J Eval Clin Practice 6 39 49 Google Scholar Lydick, E, Epstein, R 1993 Interpretation of quality of life changes. Qual Life Res 2 221 226 CrossRef PubMed Google Scholar Ware, JJ, Keller, S 1996 Interpreting general health measures. Spilker, B eds. Quality of Life and Pharmacoeconomics in Clinical Trials. Lippincott-Raven Publishers Philadelphia, PA 445 460 Google Scholar Kravitz, R, Greenfield, S, Rogers, W, et al. 1992 Differences in the mix of patients among medical specialities and systems of care: Results from the medical outcomes study. J Am Med Assoc 267 1617 1623 Google Scholar King, M 1996 The interpretation of scores from the EORTC quality of life questionnaire QLQ-C30. Qual Life Res 5 555 567 PubMed Google Scholar Nilsdotter, AK, Lohmander, LS 2003 Patient relevant outcomes after total hip replacement. A comparison between different surgical techniques. Health Qual Life Outcomes 1 21 Google Scholar Patrick, D, Martin, M, Bushnell, D, et al. 1999 Quality of life of women with urinary incontinence: Further development of the incontinence quality of life instrument (I-QOL). Uro-logy 53 71 76 Google Scholar Jowett, S, Seal, C, Barton, R, et al. 2001 The Short Inflammatory Bowel Disease Questionnaire is reliable and responsive to clinically important change in ulcerative colitis. Am J Gasteroenterol 96 2921 2928 Google Scholar Patrick, D, Gagnon, D, Zagari, M, et al. 2003 Assessing the clinical significance of health-related quality of life (HrQOL) improvements in anaemic cancer patients receiving epoetin alfa. Eur J Cancer 39 335 345 CrossRef PubMed Google Scholar Cella, D, Eton, D, Fairclough, D, et al. 2002 What is clinically meaningful change (CMC) on the Functional Assessment of Cancer Therapy–Lung (FACT-L) questionnaire?. An analysis of data from ECOG 5592. J Clin Epidemiol 55 286 295 Google Scholar Kosinski, M, et al. 2000 Determining minimally important changes in generic and disease-specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis. Arthritis Rheum 43 1478 1487 CrossRef PubMed Google Scholar Barber, B, Santanello, N, Epstein, R 1996 Impact of the global on patient perceivable change in an asthma-specific QOL instrument. Qual Life Res 5 115 122 Google Scholar Jaeschke, R, Singer, J, Guyatt, G 1989 Measurement of health status: Ascertaining the minimal clinically important difference. Control Clin Trials 10 407 415 Google Scholar Osoba, D, Rodriques, G, Myles, J, et al. 1998 Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol 16 139 144 PubMed Google Scholar Redelmeier, D, Guyatt, G, Goldstein, R 1996 Assessing the minimal important difference in symptoms: A comparison of two techniques. J Clin Epidemiol 49 1215 1219 Google Scholar Redelmeier, D, Goldstein, R, Min, S, et al. 1996 Spirometry and dyspnea in patients with COPD. Chest 109 1163 1168 Google Scholar Norman, G, Stratford, P, Regehr, G 1997 Methodological problems in the retrospective computation of responsiveness to change: The lessons of Cronbach. J Clin Epidemiol 50 869 879 Google Scholar Wyrwich, K 2002 Statistical interpretation of HRQoL changes in COPD: Development of the MCID standards and related approaches. Eur Respir Rev 12 94 103 Google Scholar Sloan, J, et al. 2003 Practical guidelines for assessing the clinical significance of health-related quality of life changes within clinical trials. Drug Inf J 37 23 31 Google Scholar Cohen, J 1977Statistical Power Analysis for the Behavioral Sciences Academic Press New York Google Scholar Cohen, J 1988Statistical Power Analysis for the Behavioral Sciences. Lawrence Erlbaum Associates Hillsdale Google Scholar Anastasi, A, Urbina, S 1997Psychological Testing7 Prentice-Hall Upper Saddle River, NJ Google Scholar Nunnally, J, Bernstein, I 1994Psychometric Theory McGraw Hill New York Google Scholar Wyrwich, K, Nienaber, N, Tierney, W, et al. 1999 Linking clinical relevance and statistical significance in evaluating intra-individual changes in health-related quality of life. Med Care 37 469 478 Google Scholar Wyrwich, K, Tierney, W, Wolinsky, F 1999 Further evidence supporting a SEM-based criterion for identifying meaningful intra-individual changes in health-related quality of life. J Clin Epidemiol 52 861 873 Google Scholar Wyrwich, K, Tierney, W, Wolinsky, F 2002 Using the standard error of measurement to identify important intra-individual change on the Asthma Quality of Life Questionnaire. Qual Life Res 11 1 7 Google Scholar Donaldson, G, Moinpour, C 2002 Individual differences in quality-of-life treatment response. Med Care 40(6 Suppl) III39 53 Google Scholar Norman, G, Sloan, J, Wyrwich, K 2003 Interpretation of changes in health-related quality of life: The remarkable universality of half a standard deviation. Med Care 41 582 592 Google Scholar Miller, G 1956 The magic number seven plus or minus two: Some limits on our capacity for processing information. Psycholog Rev 63 81 97 Google Scholar McHorney, C, Tarlov, A 1995 Individual-patient monitoring in clinical practice: Are available health status surveys adequate? Qual Life Res 4 293 307 PubMed Google Scholar Revicki, D, Osoba, D, Fairclough, D, et al. 2000 Recommendations on health-related quality of life research to support labeling and promotional claims in the United States. Qual Life Res 9 887 900 CrossRef Google Scholar Hays, R, Hadorn, D 1992 Responsiveness to change: An aspect of validity, not a separate dimension. Qual Life Res 1 73 75 Google Scholar Husted, J, Cook, R, Farewell, V, et al. 2000 Methods for assessing responsiveness: A critical review and recommendations. J Clin Epidemiol 53 459 468 Google Scholar Deyo, R, Centor, R 1986 Assessing the responsiveness of functional scales to clinical change: An analogy to diagnostic test performance. J Chron Dis 1 897 906 Google Scholar Kazis, L, Anderson, J, Meenan, R 1989 Effect sizes for interpreting changes in health status. Med Care 27 S178 S189 Google Scholar Deyo, R, Diehr, P, Patrick, D 1991 Reproducibility and responsiveness of health status measures. Control Clin Trials 12 142S 158S PubMed Google Scholar
Cohen J. Statistical power analysis for the behavioral sciences. Hillsdale, 1998.
Bombardier, C, Raboud, J 1992 A comparison of health-related quality-of-life measures for rheumatoid arthritis research. Control Clin Trials 12 243S 256S Google Scholar Katz, J, et al. 1992 Comparative measurement sensitivity of short and longer health status instruments. Med Care 30 917 925 Google Scholar Guyatt, G, Walter, S, Norman, G 1987 Measuring change over time: Assessing the usefulness of evaluative instruments. J Clin Epidemiol 40 171 178 Google Scholar Guyatt, G, Kirshner, B, Jaeschke, R 1992 Measuring health status: What are the necessary measurement properties? J Clin Epidemiol 45 1341 1345 Google Scholar Liang, M, et al. 1985 Comparative measurement efficiency and sensitivity of five health status instruments for arthritis research. Arthritis Rheum 28 542 547 Google Scholar Baker, D, Hays, R, Brook, R 1997 Understanding changes in health status: Is the floor phenomenon merely the last step of the staircase? Med Care 35 1 15 Google Scholar Liang, M 2000 Longitudinal construct validity: Establishment of clinical meaning in patient evaluative instruments. Med Care 38(9 suppl) II84 II90 Google Scholar Lydick, E 2000 Approaches to the interpretation of quality-of-life scales. Medical Care 38(9 suppl) II180 II183 Google Scholar Bindman, A 1990 The floor phenomenon. Med Care 28 1142 1152 Google Scholar Fayers, P, Machin, D 2000Quality of Life Assessment, Analysis and Interpretation. John Wiley & Sons Chichester, UK Google Scholar Nayfield, S, Ganz, P, Moinpour, C, et al. 1992 Report from a National Cancer Institute (USA) workshop on quality of life assessment in cancer clinical trials. Qual Life Res 1 203 210 Google Scholar Walter, S 2001 Number needed to treat (NNT): Estimation of a measure of clinical benefit. Statist Med 20 3947 3962 Google Scholar Juniper, E, Guyatt, G, Willan, A, et al. 1994 Determining a minimal important change in a disease-specific quality of life questionnaire. J Clin Epidemiol 47 81 87 Google Scholar Guyatt, G, et al. 1998 Interpreting treatment effects in randomised trials. BMJ 316 690 693 Google Scholar
Norman G, Sridhar F, Guyatt G, et al. The relation of distribuation- and anchor-based approaches in interpretation of changes in health related quality of life. Med Care 2001.