Abstract
Accepted outcome measures in randomized controlled trials (RCTs) in osteoarthritis (OA) include patient-reported assessments of physical function and health-related quality of life (HRQOL). Available data can inform treatment decisions when statistically significant changes are viewed in terms of clinically important improvements. Patient-reported outcomes validated in OA include global assessments of pain, disease activity, and disease-specific and generic measures of physical function and HRQOL. Definitions of minimum clinically important differences (MCID) have been derived from RCTs with physical therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 selective agents. Definitions of MCID should serve only as guidelines based on mean changes in a treatment group, and do not necessarily reflect clinically meaningful improvements for an individual patient. They help to interpret data across treatments and patient populations. Definitions of MCID may differ for the type of intervention assessed; additional methodologic issues must be addressed when evaluating nonpharmacologic treatments. Based on RCTs in OA evaluating physical therapy, cyclooxygenase-2 agents, and NSAIDs, the Western Ontario and McMaster Osteoarthritis Index is valid, reliable, sensitive to change, and correlates closely with the generic Medical Outcomes Survey Short-Form 36 measure of HRQOL. When evaluating RCT data, understanding derivation and MCID values of outcome measures facilitates informed therapeutic decisions regarding therapeutic interventions.
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References and Recommended Reading
Beaton DE, Schemitsch E: Measures of health-related quality of life and physical function. Clin Orth Rel Res 2003, 413:90–105. A thorough review of patient-reported outcome measures developed for musculoskeletal research.
Bellamy N, Kirwan J, Boers M, et al.: Recommendations for a core set of outcome measures for future Phase III clinical trials in knee, hip, and hand osteoarthritis. Consensus development at OMERACT III. J Rheumatol 1997, 24:799–802. Summarizes the recommended domains to be assessed in RCTs in OA.
Altman R, Brandt K, Hochberg M, Moskowitz R: Design and conduct of clinical trails in patients with osteoarthritis: recommendations from a task force of the osteoarthritis research society. Osteoarthritis Cartilage 1996, 4:217–243.
US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Devices and Radiologic Health: Guidance for industry: clinical development programs for drugs, devices and biological products intended for the treatment of osteoarthritis. Washington, DC: US Department of Health and Human Services; 1999.
European Agency for the Evaluation of Medicinal Products, Human Medicines Evaluation Unit, Committee for Proprietary Medicinal Products: Points to Consider on Clinical Investigation of Medicinal Products Used in the Treatment of Osteoarthritis. London: EMEA; 1998.
Boers M, Brooks P, Strand V, Tugwell P: The OMERACT filter for outcome measures in rheumatology [editorial]. J Rheumatol 1998, 25:198–199.
Bolognese JA, Schnitzer TJ, Ehrich EW: Response relationship of VAS and Likert scales in osteoarthritis efficacy measurement. Osteoarthritis Cartilage 2003, 11:499–507.
Von Korff M, Jensen MP, Karoly P: Assessing global pain severity by self-report in clinical and health services research. Spine 2000, 25:3140–3151. Excellent review of available instruments to assess chronic pain
Bellamy N, Buchanan WW, Goldsmith CH, et al.: Validation of the WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in osteoarthritis of the hip or knee. J Rheumatol 1988, 15:1833–1840.
Bellamy N, Buchanan WW, Goldsmith CH, et al.: Validation of the WOMAC: a health status instrument for measuring clinically important patient relavent outcomes following total hip or knee arthroplasty in Osteoarthritis. J Ortho Rheumatol 1988, 1:95–108.
Brazier JE, Harper R, Munro J, et al.: Generic and condition specific outcome measures for people with osteoarthritis of the knee. Rheumatology 1999, 38:870–877. Excellent summary of available outcome measures for RCTs in knee OA.
McConnell S, Kolopack R, Davis AM: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC): a review of its utility and measurement properties. Arth Care Res 2001, 45:453–461.
Creamer P, Lethbridge-Cejku M, Hochberg MC: Determinants of pain severity in knee osteoarthritis: the effect of demographic and psychosocial variables using three different pain measures. J Rheumatol 1999, 26:1785–1792.
Guidelines for the clinical investigation of drugs used in rheumatic diseases: European drug guideline series 5. Copenhagen: World Health Organization, Regional Office for Europe; 1985.
LeQuesne MG, Mery C, Samsson M, Gerard P: Indices of severity for osteoarthritis of the hip and knee: validationvalue in comparison with other assessment tests. Scand J Rheumatol 1987, 65:S85-S89.
LeQuesne MG: The algofunctional indices for hip and knee osteoarthritis. J Rheumatol 1997, 24:779–781.
Theiller R, Sangha O, Schaeren S, et al.: Superior responsiveness of the pain and physical function sections of the WOMAC as compared to the LeQuesne-algofunctional index in patients with osteoarthritis of the lower extremities. Osteoarthritis Cartilage 1999, 7:515–519.
Bellamy N, Campbell J, Haraoui R, et al.: Dimensionality and clinical importance of pain and disability in hand osteoarthritis: development of the Australian/Canadian (AUSCAN) osteoarthritis hand index. Osteoarthritis Cartilage 2002, 10:855–862.
Bellamy N, Campbell J, Haraoui R, et al.: Clinimetric properties of the AUSCAN osteoarthritis hand index: an evaluation of reliability, validity, and responsiveness. Osteoarthritis Cartilage 2002, 10:863–869.
Solway S, Beaton DE, McConnell S, et al.: The DASH Outcome Measure User’s Manual. Toronto: Institute for Work and Health; 2002.
Hudak PL, Amadio PC, Bombardier C, et al.: Development of an upper extremity outcome measure: the DASH (disabilities of the arm, shoulder, and hand) [corrected]. Am J Ind Med 1996, 29:602–608.
Beaton DE, Katz JN, Fossel AH, et al.: Measuring the whole or the parts? Validity, reliability, and responsiveness of the Disabilities of the Arm, Shoulder and Hand outcome measure in different regions of the upper extremity. J Hand Ther 2001, 14:128–146.
Gummesson C, Atroshi I, Ekdahl C: The disabilities of the arm, shoulder and hand questionnaire: longitudinal construct validity and measuring self-rated health change after surgery. BMC Musculoskelet Disord 2003, 4:11–21.
Dreiser RL, Maheu E, Guillou GB, et al.: Validation of an algofunctional index for osteoarthritis of the hand. Rev Rheum 1995, 62:S43-S53.
Dreiser RL, Maheu E, Guillou GB: Sensitivity to change of the functional index for hand osteoarthritis. Osteoarthritis Cartilage 2000, 8(suppl):S25-S28.
Duruoz MT, Poiraudeau S, Fermanian J, et al.: Development and validation of a rheumatoid hand functional disability scale that assesses functional handicap. J Rheumatol 1996, 23:1167–1172.
Poiraudeau S, Chevalier X, Conrozier T, et al.: Reliability, validity, and sensitivity to change of the Cochin hand functional disability scale in hand osteoarthritis. Osteoarthritis Cartilage 2001, 9:570–577.
Roland M, Morris R: A study of the natural history of low back pain: Part 1. Development of a reliable and sensitive measure of disability in low back pain. Spine 1983, 8:141–144.
Fairbank J, Couper J, Davies J, et al.: The Oswestry low back pain questionnaire. Physiotherapy 1980, 66:271–273.
Roland M, Fairbank J: The Roland-Morris Disability Questionnaire and the Oswestry Disability Questionnaire. Spine 2000, 25:3115–3124.
Fries JF, Spitz P, Kraines RG, et al.: Measurement of patient outcome in arthritis. Arthritis Rheum 1980, 23:137–145.
Bruce B, Fries JF: The Stanford Health Assessment Questionnaire: a review of its history, issues progress and documentation. J Rheumatol 2003, 30:167–178.
Griffiths G, Bellamy N, Bailey WH, et al.: A comparative study of the relative efficiency of the WOMAC, AIMS, and HAQ instruments in evaluating the outcome of total knee arthroplasty. Inflammopharmacology 1995, 3:1–6.
Bruce B, Fries JF: Longitudinal comparison of the health assessment questionnaire and the Western Ontario McMasters University Osteoarthritis Index. Arthritis Rheum 2003, 48:S640.
Meenan RF, Gertman PM, Mason JH: Measuring health status in arthritis: the arthritis impact measurement scales. Arthritis Rheum 1980, 23:146–152.
Meenan RF, Mason JH, Anderson JJ, et al.: The content and properties of a revised and expanded arthritis impact measurement scales health status questionnaire. Arthritis Rheum 1992, 35:1–10.
Ware JE, Kosinski M, Bayliss MS, et al.: Comparisons of methods for the scoring and statistical analysis of SF-36 health profile and summary measures: summary of results from the Medical Outcomes Study. Med Care 1995, 33:AS264-AS279.
Kantz ME, Harris WJ, Levitsky K, et al.: Methods for assessing condition-specific and generic functional status outcomes after total knee replacement. Med Care 1992, 30:MS240-MS252.
Ware JE, Kosinski M, Hatoum HT, et al.: Is the SF-36 health survey a valid measure of osteoarthritis and rheumatoid arthritis? Arthritis Rheum 1996, 39:S258.
Strand V, Aranow C, Cardiel M, et al.: Improvement in healthrelated quality of life in SLE patients enrolled in a randomized clinical trial comparing LJP 394 treatment with placebo. Lupus 2003, 12:677–686.
Brazier JE, Harper R, Jones NMB, et al.: Validating the SF-36 health survey questionnaire: new outcome measure for primary care. BMJ 1992, 305:160–164.
Damiano AM: The sickness impact profile. In Quality of Life and Pharmacoeconomics in Clinical Trials, edn 2. Edited by Spilker B. Philadelphia: Lippincott-Raven; 1996:347–354.
Coons SJ, Rao S, Keininger DL, et al.: A comparative review of generic quality-of-life instruments. Pharmacoeconomics 2000, 1:13–35.
Ware JE Jr: SF-36 health survey update. Spine 2000, 25:3130–3139. Summarizes properties of SF-36 and its widespread use across medical conditions and in RCTs, with validated translations in German, Italian, Spanish, Swedish and adaptations for use in Australia, Canada, New Zealand and the UK.
Ehrich E, Bolognese J, Kong S, et al.: Improvements in SF-36 mental health domains with treatment of OA: a result of decreased pain and disability or independent mechanisms? Arthritis Rheum 1998, 41:S221.
Brazier JE, Roberts J, Deverill M: The estimation of a preference-based measure of health from the SF-36. J Health Econ 2002, 21:271–292.
Wright JG, Young NL: A comparison of different indices of responsiveness. J Clin Epidemiol 1998, 50:239–246.
Brooks P, Oh E-S, Cross M, et al.: A comparison of WOMAC and MOS SF-36 in OA patients undergoing joint replacement. Arthritis Rheum 1996, 39:S90.
Lerner D, Amick BC, Rogers WH, et al.: The Work Limitations Questionnaire. Med Care 2001, 39:72–85.
Lerner D, Reed JI, Massarotti E, et al.: The Work Limitations Questionnaire’s validity and reliability among patients with osteoarthritis. J Clin Epidemiol 2002, 55:197–208.
Goldsmith C, Boers M, Bombardier C, Tugwell P: Criteria for clinically important changes in outcomes: development, scoring and evaluation of rheumatoid arthritis patient and trial profiles. J Rheumatol 1993, 20:561–565.
Wells GA, Tugwell P, Kraag GR, et al.: Minimum important differences between patients with rheumatoid arthritis: the patient’s perspective. J Rheumatol 1993, 20:557–560.
Guyatt G, Juniper E, Walter S, et al.: Interpreting treatment effects in randomized trials. BMJ 1998, 316:690–693.
Sloan J, Symonds T, Vargas-Chanes D, Fridley B: Practical guidelines for assessing the clinical significance of healthrelated quality of life changes within clinical trials. Drug Inf J 2003, 37:23–31.
Samsa G, Edelman D, Rothman M, et al.: Determining clinically important differences in health status measures. Pharmacoeconomics 1999, 2:141–155. An informative discussion of methods for determining MCID.
Zhao SZ, McMillen JI, Markenson JA, et al.: Evaluation of the functional status aspects of health-related quality of life of patients with osteoarthritis treated with celecoxib. Pharmacotherapy 1999, 19:1269–1278. Derivation of MCID for WOMAC in OA RCTs with a COX-2 agent.
Ehrich EW, Davies GM, Watson DJ, et al.: Minimal perceptible clinical improvement with the Western Ontario and McMaster University Osteoarthritis Index questionnaire and global assessments in patients with osteoarthritis. J Rheumatol 2000, 27:2635–2641. Derivation of MCID for WOMAC in OA RCTs with a COX-2 agent.
Bolognese JA, Ehrich EW, Schnitzer TJ: Precision of composite measures of osteoarthritis efficacy in comparison to that of individual endpoints. J Rheumatol 2001, 28:2700–2704.
Angst F, Aeschlimann A, Stucki G: Smallest detectable and minimal clinically important differences of rehabilitation intervention with their implications for required sample sizes using WOMAC and SF-36 quality of life measurement instruments in patients with osteoarthritis of the lower extremities. Arth Care Res 2001, 45:384–391. Derivation of MCID for WOMAC and SF-36 for a physical therapy intervention in OA.
Tubach F, Baron G, Ravaud P, et al.: Evaluation of clinically relevant changes and states in symptomatic outcome variables in osteoarthritis. Arth Rheum 2003, 48:S292.
Bensen WG, Fiechtner JJ, McMillen JI, et al.: Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial. Mayo Clin Proc 1999, 74:1095–1105.
Williams GW, Ettlinger RE, Ruderman EM, et al.: Treatment of osteoarthritis with a once-daily dosing regimen of celecoxib. J Clin Rheumatol 2000, 6:65–74.
Day R, Morrison B, Luza A, et al.: A randomized trial of the efficacy and tolerability of the cox-2 inhibitor rofecoxib vs ibuprofen in patients with osteoarthritis. Arch Int Med 2000, 160:1781–1787.
Cannon GW, Caldwell JR, Holt P, et al.: Rofecoxib, a specific inhibitor of cyclooxygenase 2, with clinical efficacy comparable with that of diclofenac sodium. Arthritis Rheum 2000, 43:978–987.
Pincus T, Koch GG, Sokka T, et al.: A randomized doubleblind, crossover clinical trial of diclofenac plus misoprostal versus acetaminophen in patients with osteoarthritis of the hip or knee. Arthritis Rheum 2001, 44:1587–1598.
Case JP, Balunias AG, Block JA: Lack of efficacy of acetaminophen in treating symptomatic knee osteoarthritis. Arch Intern Med 2003, 163:169–178.
Bradley JD, Brandt KD, Katz BP, et al.: Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee. N Engl J Med 1991, 325:87–91.
Williams HJ, Ward JR, Egger MJ, et al.: Comparison of naproxen and acetaminophen in a two-year study of treatment of osteoarthritis of the knee. Arthritis Rheum 1993, 36:1196–1206.
Richy F, Bruyere O, Ethgen O, et al.: Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis. Arch Intern Med 2003, 163:1514–1522.
Buckland-Wright JC, Macfarlane DG, Williams SA, et al.: Accuracy and precision of joint space width measurements in standard and macroradiographs of osteoarthritic knees. Ann Rheum Dis 1995, 54:872–880.
Reginster JY, Deroisy R, Rovati LC, et al.: Long-term effects of glucosamine sulfate on osteoarthritis progression: a randomized, placebo-controlled clinical trial. Lancet 2001, 357:251–256.
Pavelka K, Gatterova J, Olejarova M, et al.: Glucosamine sulfate use and delay of progression of knee osteoarthritis. Arch Intern Med 2002, 162:2113–2123.
Brandt KD, Mazzuca SA, Katz BP, et al.: Doxycycline slows the rate of joint space narrowing in patients with knee osteoarthritis. Arthritis Rheum 2003, 48:22.
Brandt KD, Mazzuca SA, Katz BP, et al.: The disease-modifying effect of doxycycline includes symptomatic benefit for patients with knee osteoarthritis. Arthritis Rheum 2003, 48:1.
Berman BM, Singh BB, Lao L, et al.: A randomized trial of acupuncture as an adjunctive therapy in osteoarthritis of the knee. Rheumatology 1999, 38:346–354.
Puhl W, Bernau A, Greiling H, et al.: Intra-articular sodium hyaluronate in osteoarthritis of the knee: a multicenter doubleblind study. Osteoarthritis Cartilage 1993, 1:233–241.
Lohmander LS, Dalen N, Englund G, et al.: Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomized, double-blind, placebo controlled, multicenter trial. Ann Rheum Dis 1996, 55:424–431.
Altman RD, Moskowitz R: Intra-articular sodium hyaluronate in the treatment of patients with osteoarthritis of the knee: a randomized clinical trial. J Rheumatol 1998, 25:2203–2212.
Wobig M, Dickhut A, Maier R, Vetter G: Viscosupplementation with hylan G-F 20: a 26-week controlled trial of efficacy and safety in the osteoarthritic knee. Clin Therap 1998, 20:410.
Huskisson EC, Donnelly S: Hyaluronic acid in the treatment of osteoarthritis of the knee. Rheumatology 1999, 38:602–607.
Brandt KD, Black JA, Michalski JP, et al.: Efficacy and safety of intra-articular sodium-hyaluronate in knee osteoarthritis. Clin Orthop 2001, 385:130–143.
Karlsson J, Sjogren S, Lohmander LS: Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis: a controlled, randomized, double-blind, paralleldesign multicenter study. Rheumatology 2002, 41:1240–1248.
Petrella RJ, DiSilvestro MD, Hildebrand C: Effects of hyaluronate sodium on pain and physical functioning in osteoarthritis of the knee. Arch Intern Med 2002, 162:292–298.
Felson DT, Anderson JJ: Hyaluronate sodium injections for osteoarthritis. Arch Intern Med 2002, 162:245–247.
Day R, Brooks P, Conaghan PG, Petersen M: A double-blind, randomized, multi-center, parallel group study of the effectiveness and tolerance of intra-articular hyaluronan in osteoarthritis of the knee. J Rheumatol 2003, in press.
Bellamy N, Campbell J, Gee T, et al.: Hylan G-F20 for knee osteoarthritis: a Cochrane review. Arthritis Rheum 2003, 48:S697.
Raynauld JP, Buckland-Wright C, Ward R, et al.: Safety and efficacy of long-term intra-articular steroid injections in osteoarthritis of the knee. Arthritis Rheum 2003, 48:370–377.
Moseley JB, O’Malley K, Petersen MJ, et al.: A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med 2002, 347:81–88.
Boutron I, Tubach F, Giraudeau P, et al.: Methodological differences in clinical trials evaluating nonpharmacological and pharmacological treatments of hip and knee osteoarthritis. JAMA 2003, 290:1062–1070.
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Strand, V., Kelman, A. Outcome measures in osteoarthritis: Randomized controlled trials. Curr Rheumatol Rep 6, 20–30 (2004). https://doi.org/10.1007/s11926-004-0080-6
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DOI: https://doi.org/10.1007/s11926-004-0080-6