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Estimating clinically significant differences in quality of life outcomes

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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.

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Abbreviations

CTT:

classical test theory

MID:

minimal important difference

NNT:

number needed to treat

QOL:

quality of life

SEM:

standard error of measurement

References

  • J Sloan D Cella M Frost et al. (2002) ArticleTitleAssessing 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 

  • D Cella M Bullinger C Scott et al. (2002) ArticleTitleGroup vs. individual approaches to understanding the clinical significance of differences or changes in quality of life. Mayo Clinic Proc 77 384–392

    Google Scholar 

  • M Frost A Bonomi C Ferrans et al. (2002) ArticleTitlePatient, clinician, and population perspectives on determining the clinical significance of quality-of-life scores. Mayo Clinic Proc 77 488–494

    Google Scholar 

  • G Guyatt D Osoba A Wu et al. (2002) ArticleTitleMethods to explain the clinical significance of health status measures. Mayo Clinic Proc 77 371–383

    Google Scholar 

  • M Sprangers C Moinpour T Moynihan et al. (2002) ArticleTitleAssessing meaningful change in quality of life over time: A users’ guide for clinicians. Mayo Clinic Proc 77 561–571

    Google Scholar 

  • T Symonds R Berzon P Marquis et al. (2002) ArticleTitleThe clinical significance of quality-of-life results: Practical considerations for specific audiences. Mayo Clinic Proc 77 572–583

    Google Scholar 

  • D. Osoba (2002) ArticleTitleTaxonomy 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 

  • K Wyrwich F Wolinsky (2000) ArticleTitleIdentifying meaningful intra-individual change standards for health-related quality of life measures. J Eval Clin Practice 6 IssueID1 39–49

    Google Scholar 

  • E Lydick R Epstein (1993) ArticleTitleInterpretation of quality of life changes. Qual Life Res 2 221–226 Occurrence Handle10.1007/BF00435226 Occurrence Handle1:STN:280:ByuD3cvotV0%3D Occurrence Handle8401458

    Article  CAS  PubMed  Google Scholar 

  • JJ Ware S Keller (1996) Interpreting general health measures. B Spilker (Eds) Quality of Life and Pharmacoeconomics in Clinical Trials. Lippincott-Raven Publishers Philadelphia, PA 445–460

    Google Scholar 

  • R Kravitz S Greenfield W Rogers et al. (1992) ArticleTitleDifferences 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 

  • M King (1996) ArticleTitleThe interpretation of scores from the EORTC quality of life questionnaire QLQ-C30. Qual Life Res 5 555–567 Occurrence Handle1:STN:280:ByiC2cnhvVU%3D Occurrence Handle8993101

    CAS  PubMed  Google Scholar 

  • AK Nilsdotter LS Lohmander (2003) ArticleTitlePatient relevant outcomes after total hip replacement. A comparison between different surgical techniques. Health Qual Life Outcomes 1 IssueID1 21

    Google Scholar 

  • D Patrick M Martin D Bushnell et al. (1999) ArticleTitleQuality 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 

  • S Jowett C Seal R Barton et al. (2001) ArticleTitleThe Short Inflammatory Bowel Disease Questionnaire is reliable and responsive to clinically important change in ulcerative colitis. Am J Gasteroenterol 96 IssueID10 2921–2928

    Google Scholar 

  • D Patrick D Gagnon M Zagari et al. (2003) ArticleTitleAssessing the clinical significance of health-related quality of life (HrQOL) improvements in anaemic cancer patients receiving epoetin alfa. Eur J Cancer 39 335–345 Occurrence Handle10.1016/S0959-8049(02)00628-7 Occurrence Handle1:CAS:528:DC%2BD3sXotlCrtA%3D%3D Occurrence Handle12565986

    Article  CAS  PubMed  Google Scholar 

  • D Cella D Eton D Fairclough et al. (2002) ArticleTitleWhat 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 

  • M Kosinski et al. (2000) ArticleTitleDetermining 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 Occurrence Handle10.1002/1529-0131(200007)43:7<1478::AID-ANR10>3.0.CO;2-M Occurrence Handle1:STN:280:DC%2BD3czptVOmsw%3D%3D Occurrence Handle10902749

    Article  CAS  PubMed  Google Scholar 

  • B Barber N Santanello R Epstein (1996) ArticleTitleImpact of the global on patient perceivable change in an asthma-specific QOL instrument. Qual Life Res 5 IssueID1 115–122

    Google Scholar 

  • R Jaeschke J Singer G Guyatt (1989) ArticleTitleMeasurement of health status: Ascertaining the minimal clinically important difference. Control Clin Trials 10 407–415

    Google Scholar 

  • D Osoba G Rodriques J Myles et al. (1998) ArticleTitleInterpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol 16 IssueID1 139–144 Occurrence Handle1:STN:280:DyaK1c7gtFKrtw%3D%3D Occurrence Handle9440735

    CAS  PubMed  Google Scholar 

  • D Redelmeier G Guyatt R Goldstein (1996) ArticleTitleAssessing the minimal important difference in symptoms: A comparison of two techniques. J Clin Epidemiol 49 IssueID11 1215–1219

    Google Scholar 

  • D Redelmeier R Goldstein S Min et al. (1996) ArticleTitleSpirometry and dyspnea in patients with COPD. Chest 109 IssueID5 1163–1168

    Google Scholar 

  • G Norman P Stratford G Regehr (1997) ArticleTitleMethodological problems in the retrospective computation of responsiveness to change: The lessons of Cronbach. J Clin Epidemiol 50 IssueID8 869–879

    Google Scholar 

  • K Wyrwich (2002) ArticleTitleStatistical interpretation of HRQoL changes in COPD: Development of the MCID standards and related approaches. Eur Respir Rev 12 IssueID83 94–103

    Google Scholar 

  • J Sloan et al. (2003) ArticleTitlePractical guidelines for assessing the clinical significance of health-related quality of life changes within clinical trials. Drug Inf J 37 23–31

    Google Scholar 

  • J Cohen (1977) Statistical Power Analysis for the Behavioral Sciences Academic Press New York

    Google Scholar 

  • J Cohen (1988) Statistical Power Analysis for the Behavioral Sciences. Lawrence Erlbaum Associates Hillsdale

    Google Scholar 

  • A Anastasi S Urbina (1997) Psychological Testing EditionNumber7 Prentice-Hall Upper Saddle River, NJ

    Google Scholar 

  • J Nunnally I Bernstein (1994) Psychometric Theory McGraw Hill New York

    Google Scholar 

  • K Wyrwich N Nienaber W Tierney et al. (1999) ArticleTitleLinking clinical relevance and statistical significance in evaluating intra-individual changes in health-related quality of life. Med Care 37 IssueID4 469–478

    Google Scholar 

  • K Wyrwich W Tierney F Wolinsky (1999) ArticleTitleFurther evidence supporting a SEM-based criterion for identifying meaningful intra-individual changes in health-related quality of life. J Clin Epidemiol 52 IssueID9 861–873

    Google Scholar 

  • K Wyrwich W Tierney F Wolinsky (2002) ArticleTitleUsing the standard error of measurement to identify important intra-individual change on the Asthma Quality of Life Questionnaire. Qual Life Res 11 IssueID1 1–7

    Google Scholar 

  • G Donaldson C Moinpour (2002) ArticleTitleIndividual differences in quality-of-life treatment response. Med Care 40(6 Suppl) III39–53

    Google Scholar 

  • G Norman J Sloan K Wyrwich (2003) ArticleTitleInterpretation of changes in health-related quality of life: The remarkable universality of half a standard deviation. Med Care 41 582–592

    Google Scholar 

  • G Miller (1956) ArticleTitleThe magic number seven plus or minus two: Some limits on our capacity for processing information. Psycholog Rev 63 81–97

    Google Scholar 

  • C McHorney A Tarlov (1995) ArticleTitleIndividual-patient monitoring in clinical practice: Are available health status surveys adequate? Qual Life Res 4 293–307 Occurrence Handle1:STN:280:BymD2crisFU%3D Occurrence Handle7550178

    CAS  PubMed  Google Scholar 

  • D Revicki D Osoba D Fairclough et al. (2000) ArticleTitleRecommendations on health-related quality of life research to support labeling and promotional claims in the United States. Qual Life Res 9 887–900 Occurrence Handle10.1023/A:1008996223999

    Article  Google Scholar 

  • R Hays D Hadorn (1992) ArticleTitleResponsiveness to change: An aspect of validity, not a separate dimension. Qual Life Res 1 73–75

    Google Scholar 

  • J Husted R Cook V Farewell et al. (2000) ArticleTitleMethods for assessing responsiveness: A critical review and recommendations. J Clin Epidemiol 53 459–468

    Google Scholar 

  • R Deyo R Centor (1986) ArticleTitleAssessing the responsiveness of functional scales to clinical change: An analogy to diagnostic test performance. J Chron Dis 1 IssueID39 897–906

    Google Scholar 

  • L Kazis J Anderson R Meenan (1989) ArticleTitleEffect sizes for interpreting changes in health status. Med Care 27 IssueID3 S178–S189

    Google Scholar 

  • R Deyo P Diehr D Patrick (1991) ArticleTitleReproducibility and responsiveness of health status measures. Control Clin Trials 12 142S–158S Occurrence Handle1:STN:280:By2C3snotFE%3D Occurrence Handle1663851

    CAS  PubMed  Google Scholar 

  • Cohen J. Statistical power analysis for the behavioral sciences. Hillsdale, 1998.

  • C Bombardier J Raboud (1992) ArticleTitleA comparison of health-related quality-of-life measures for rheumatoid arthritis research. Control Clin Trials 12 243S–256S

    Google Scholar 

  • J Katz et al. (1992) ArticleTitleComparative measurement sensitivity of short and longer health status instruments. Med Care 30 917–925

    Google Scholar 

  • G Guyatt S Walter G Norman (1987) ArticleTitleMeasuring change over time: Assessing the usefulness of evaluative instruments. J Clin Epidemiol 40 171–178

    Google Scholar 

  • G Guyatt B Kirshner R Jaeschke (1992) ArticleTitleMeasuring health status: What are the necessary measurement properties? J Clin Epidemiol 45 1341–1345

    Google Scholar 

  • M Liang et al. (1985) ArticleTitleComparative measurement efficiency and sensitivity of five health status instruments for arthritis research. Arthritis Rheum 28 542–547

    Google Scholar 

  • D Baker R Hays R Brook (1997) ArticleTitleUnderstanding changes in health status: Is the floor phenomenon merely the last step of the staircase? Med Care 35 1–15

    Google Scholar 

  • M Liang (2000) ArticleTitleLongitudinal construct validity: Establishment of clinical meaning in patient evaluative instruments. Med Care 38(9 suppl) II84–II90

    Google Scholar 

  • E Lydick (2000) ArticleTitleApproaches to the interpretation of quality-of-life scales. Medical Care 38(9 suppl) II180–II183

    Google Scholar 

  • A Bindman (1990) ArticleTitleThe floor phenomenon. Med Care 28 IssueID12 1142–1152

    Google Scholar 

  • P Fayers D Machin (2000) Quality of Life Assessment, Analysis and Interpretation. John Wiley & Sons Chichester, UK

    Google Scholar 

  • S Nayfield P Ganz C Moinpour et al. (1992) ArticleTitleReport from a National Cancer Institute (USA) workshop on quality of life assessment in cancer clinical trials. Qual Life Res 1 203–210

    Google Scholar 

  • S Walter (2001) ArticleTitleNumber needed to treat (NNT): Estimation of a measure of clinical benefit. Statist Med 20 IssueID24 3947–3962

    Google Scholar 

  • E Juniper G Guyatt A Willan et al. (1994) ArticleTitleDetermining a minimal important change in a disease-specific quality of life questionnaire. J Clin Epidemiol 47 81–87

    Google Scholar 

  • G Guyatt et al. (1998) ArticleTitleInterpreting treatment effects in randomised trials. BMJ 316 IssueID7132 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.

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Correspondence to Kathleen W. Wyrwich.

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The Clinical Significance Consensus Meeting Group - See listing of members at the end of this article

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Wyrwich, K.W., Bullinger, M., Aaronson, N. et al. Estimating clinically significant differences in quality of life outcomes. Qual Life Res 14, 285–295 (2005). https://doi.org/10.1007/s11136-004-0705-2

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