The use of continuous data versus binary data in MTC models: A case study in rheumatoid arthritis

BMC Medical Research Methodology

Cathal Walsh¹  Roisin Adams¹  Susanne Schmitz² 

[1] National Centre for Pharmacoeconomics, , Dublin, Ireland;Department of Statistics, Trinity College Dublin, Dublin, Ireland

关键词: Anti-TNF agents;    Rheumatoid arthritis;    Bayesian mixed treatment comparison models;   

Others  :  1126526
DOI  :  10.1186/1471-2288-12-167

 received in 2012-05-23, accepted in 2012-10-30,  发布年份 2012

【 摘 要 】

Background

Estimates of relative efficacy between alternative treatments are crucial for decision making in health care. When sufficient head to head evidence is not available Bayesian mixed treatment comparison models provide a powerful methodology to obtain such estimates. While models can be fit to a broad range of efficacy measures, this paper illustrates the advantages of using continuous outcome measures compared to binary outcome measures.

Methods

Using a case study in rheumatoid arthritis a Bayesian mixed treatment comparison model is fit to estimate the relative efficacy of five anti-TNF agents currently licensed in Europe. The model is fit for the continuous HAQ improvement outcome measure and a binary version thereof as well as for the binary ACR response measure and the underlying continuous effect. Results are compared regarding their power to detect differences between treatments.

Results

Sixteen randomized controlled trials were included for the analysis. For both analyses, based on the HAQ improvement as well as based on the ACR response, differences between treatments detected by the binary outcome measures are subsets of the differences detected by the underlying continuous effects.

Conclusions

The information lost when transforming continuous data into a binary response measure translates into a loss of power to detect differences between treatments in mixed treatment comparison models. Binary outcome measures are therefore less sensitive to change than continuous measures. Furthermore the choice of cut-off point to construct the binary measure also impacts the relative efficacy estimates.

【 授权许可】

   
2012 Schmitz et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Sutton A, Higgins JPT: Recent developments in meta-analysis. Stat Med 2008, 27:625-650.
• [2]Lu G, Ades AE: Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med 2004, 23:3105-3124.
• [3]Spiegelhalter DJ, Abrams KR, Jonathan PM: Bayesian Approaches to Clinical Trials and Health-Care Evaluation. Wiley: NewYork; 2004.
• [4]Royston P, Altman D, Sauerbrei W: Dichotomizing continuous predictors in multiple regression: a bad idea. Stat Med 2006, 25:127-141.
• [5]Austin P, Brunner L: Inflation of the type I error rate when a continuous confounding variable is categorized in logistic regression analyses. Stat Med 2004, 23:1159-1178.
• [6]Chen H, Cohen P, Chen S: Biased odds ratios from dichotomization of age. Stat Med 2007, 26:2487-3497.
• [7]Sauerbrei W, Royston P, Zapien K: Detecting an interaction between treatment and a continuous covariate: A comparison of two approaches. Comput Stat Data Anal 2007, 51:4054-4063.
• [8]Breitling L, Brenner H: Odd odds interactions introduced through dichotomisation of continuous outcomes. J Epidemiol Community Health 2010, 64:300-303.
• [9]Dawson N, Weiss R: Dichotomizing continuous variables in statistical analysis: a practice to avoid. Med Decision Making 2012, 32:225-226.
• [10]Senn S, Julious S: Measurement in clinical trials: A neglected issue for statisticians? Stat Med 2009, 28:3189-3209.
• [11]Julious S, George S, Machin D, Stephens R: Sample sizes for randomized trials measuring quality of life in cancer patients. Qual Life Res 1997, 6:109-117.
• [12]Hutton J, McGrath C, Frybourg J, Tremblay M, Bramley-Harker E, Henshall C: Framework for describing and classifying decision-making systems using technology asesessment to determine the reimbursement of health technologies (fourth hurdle systems). Int J Technol Assess Health Care 2006, 22:10-18.
• [13]Klareskog L, Catrina A, Paget S: Rheumatoid arthritis. The Lancet 2009, 979:659-672.
• [14]Sutton A, Abrams KR: Bayesian methods in meta-analysis and evidence synthesis. Stat Methods Med Res 2001, 10:277-303.
• [15]Nixon R, Bansback N, Brennan A: Using mixed treatment comparisons and meta-regression to perform indirect comparisons to estimate the efficacy of biologic treatments in rheumatoid arthritis. Stat Med 2007, 26:1237-1254.
• [16]Jansen J, Crawford B, Bergman G, Stam W: Bayesian meta-analysis of multiple treatment comparisons: an introduction to mixed treatment comparisons. Value in Health 2008, 11:956-964.
• [17]Saag K, Teng G, Patkar N, Anuntiyo J, Finney C, Curtis J, Paulus H, Mudano A, Piso M, Outman R, Allison J, Suarez Almazor M, Bridges A, Chatham W, Hochberg M, Maclea C, Mikuls T, Moreland L, O’Dell J, Turkiewicz A, Furst D, Elkins-Melton M: American College of Rheumatology 2008 Recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis & Rheumatism 2008, 59:762-784.
• [18]Felson D, Anderson J, Boers M, Combarier C, Furst D, Goldsmith C, Katz L, Lightfoot R, Paulus H, Strand V, Tugwell P, Weinblatt M, Williams H, Wolfe F, Kieszak S: American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis & Rheumatism 1995, 38:727-735.
• [19]Van Riel P, van Gelstel A: Clinical outcome measures in rheumatoid arthritis. Ann Rheumatic Diseases 2000, 59:128-131.
• [20]American College of Rheumatology: A proposed revision to the ACR20: The hybrid measure of american college of rheumatology response. Arthritis & Rheumatism 2007, 57:193-202.
• [21]Prevoo M, van’t Hof M, Kuper H, van Leeuwen M, van de Putte L, van Riel P: Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis & Rheumatism 1995, 38:44-48.
• [22]Moher D, Liberati A, Tetzlaff J, Altman D, PRISMA Group: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Medicine 2009, 6:e1000097.
• [23]Schmitz S, Adams R, Walsh C, Barry M, FitzGerald O: A mixed treatment comparison of the efficacy of anti-TNF agents in rheumatoid arthritis for methotrexate non-responders demonstrates differences between treatments: a Bayesian approach. Ann rheumatic diseases 2012, 71:225-230.
• [24]Dias S, Welton N, Caldwell D, Ades A: Checking consistency in mixed treatment comparison meta-analysis. Stat Med 2010, 29:932-944.
• [25]Bucher HC, Guyatt GH, Griffith LE, Walter SD: The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997, 50:683-691.
• [26]Lumley T: Network meta-analyis for indirect treatment comparisons. Stat Med 2002, 21:2313-2324.
• [27]Hyrich K, Watson K, Silman A, Symmons D The BSR Biologics Register: Predictors of response to anti-TNF-α therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology 2006, 45:1558-1565.
• [28]Warn D, Thompson D, Spiegelhalter D: Bayesian random effects meta-analysis of trials with binary outcomes: methods forthe absolute risk difference and relative risk scales. Stat Med 2002, 21:1601-1623.
• [29]Gelman A: Prior distributions for variance parameters in hierarchical models. Bayesian analysis 2006, 1:133-151.
• [30]Lunn D, Thomas A, Best N, Spiegelhalter D: WinBUGS – a Bayesian modelling framework: concepts, structure, and extensibility. Stat Comput 2000, 10:325-337.
• [31]Weinblatt M, Keystone E, Furst D, Moreland L, Weisman M, Birbara C, Teoh L, Fischkoff S, Chartash E: Adalimumab, a fully human anti-tumour necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthitis & Rheumatism 2003, 48:35-45.
• [32]Keystone E, Kavanaugh A, Sharp J, Tannenbaum H, Hua Y, Teoh L, Fischkoff S, Chartash E: Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: A randomized, placebo-controlled, 52-week trial. Arthritis & Rheumatism 2004, 50:1400-1411.
• [33]Van De Putte L, Atkins C, Malaise M, Sany J, Russell A, van Riel P, Settas L, Bijlsma J, Todesco A, Dougados M, Nash P, Emery P, Walter N, Kaul M, Fischkoff A, Kupper H: Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheumatic Diseases 2004, 63:508-516.
• [34]Miyasaka N: Clinical investigation in highly disease-affected rheumatoid arthritis patients in Japan with adalimumab applying standard and general evaluation: the CHANGE study. Modern Rheumatology 2008, 18:252-262.
• [35]Kim H, Lee K, Song Y, Dae-Hyun Y, Koh E, Yoo B, Luo A: A randomized, double-blind, placebo-controlled, phase III study of the human anti-tumor necrosis factor antibody adalimumab administered as subcutaneous injections in Korean rheumatoid arthritis patients treated with methotrexate. APLAR J Rheumatology 2007, 10:9-16.
• [36]Maini R, St Clair E, Breedveld F, Furst D, Kalden J, Weisman M, Smolen J, Emery P, Harriman G, Feldmann M, Lipsky P: Infliximab (chimeric anti-tumour necrosis factor [alpha] monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. The Lancet 1999, 353:1932-1939.
• [37]Westhovens R, Yocum D, Han J, Berman A, Strusberg I, Geusens P, Rahman M: The safety of infl iximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: a large, randomized, placebo-controlled trial. Arthritis & Rheumatism 2006, 54:1075-1086.
• [38]Zhang F, Hou Y, Huang F, Wu D, Bao C, Ni L, Yao C: Infliximab versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: A preliminary study from China. APLAR J Rheumatology 2006, 9:127-130.
• [39]Schiff M, Keiserman M, Codding C, Songcharoen A, Berman A, Nayiager S, Saldate C, Li T, Aranda R, Becker J, Lin C, Cornet P, Dougados M: Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann rheumatic diseases 2008, 67:1096-1103.
• [40]Moreland L, Schiff M, Baumgartner A, Tindall E, Fleischmann R, Bulpitt K, Weaver A, Keystone E, Furst D, Mease P, Ruderman E, Horwitz D, Arkfeld D, Garrison L, Burge D, Blosch C, Lange M, McDonnell N, Weinblatt M: Etanercept therapy in rheumatoid arthritis: A randomized, controlled trial. Ann Internal Med 1999, 130:478-486.
• [41]Weinblatt M, Kremer J, Bankhurst A, Bulpitt K, Fleischmann R, Fox R, Jackson C, Lange M, Burge D: A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. New England J Med 1999, 340:253-259.
• [42]Keystone E, Genovese M, Klareskog L, Hsia E, Hall A, Miranda P, Pazdur J, Bae S, Palmer W, Zrubek J, Wiekowski M, Visvanathan S, Wu Z, Rahman M: Golimumab, a human antibody to tumour necrosis factor (alpha) given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: The GO-FORWARD Study. Ann Rheumatic Diseases 2009, 68:769-289.
• [43]Kay J, Matteson E, Dasgupta B, Nash P, Durez P, Hall A, Hsia E, Han J, Wagner C, Xu Z, Visvanathan S, Rahman M: Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, doubleblind, placebo-controlled, dose-ranging study. Arthritis & Rheumatism 2008, 58:964-975.
• [44]Keystone E, Van Der Heijde D, Mason D, Landewe R, van Vollenhoven R, Combe B, Emery P, Strand V, Mease P, Desai C, Pavelka K: Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: Findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis & Rheumatism 2009, 58:3319-3329.
• [45]Smolen J, Landewe R, Mease P, Brzezicki J, Mason D, Luijtens K, van Vollenhoven R, Kavanaugh A, Schiff M, Burmester G, Strand V, Vencovsky J, van der Heijde D: Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial. Ann rheumatic diseases 2008, 68:797-804.
• [46]Fleischmann R, Vencovsky J, Van Vollenhoven R, Borenstein D, Box J, Coteur G, Goel N, Brezinschek H, Innes A, Strand V: Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study. Ann rheumatic diseases 2009, 68:805-8011.
• [47]Adams R, Walsh C, Veale D, Bresnihan B, FitzGerald O, Barry M: Understanding the relationship between the EQ-5D, SF-6D, HAQ and disease activity in inflammatory arthritis. Pharmacoeconomics 2010, 28:477-487.
• [48]Bennette C, Vickers A: Against quantiles: categorization of continuous variables in epidemiologic research, and its discontents. BMC Med Res Methodology 2012, 12:21. BioMed Central Full Text
• [49]Hasselblad V, Hedges L: Meta-analyses of screening and diagnostic tests. Quant Methods Psychology 1995, 117:167-178.
• [50]Caldwell D, Welton N, Dias S, Ades A: Selecting the best scale for measuring treatment effect in a network meta-analysis: a case study in childhood nocturnal enuresis. Res Synth Methods 2012, 3:126-141.
• [51]O’Rourke K, Walsh C, Hutchinson M: Outcome of beta-interferon treatment in relapsing-remitting multiple sclerosis: a Bayesian analysis. J Neurology 2007, 254:1547-1554.