CINeMA: An approach for assessing confidence in the results of a network meta-analysis

Autoři: Adriani Nikolakopoulou aff001;  Julian P. T. Higgins aff002;  Theodoros Papakonstantinou aff001;  Anna Chaimani aff003;  Cinzia Del Giovane aff005;  Matthias Egger aff001;  Georgia Salanti aff001
Působiště autorů: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland aff001;  Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom aff002;  Université de Paris, Research Center of Epidemiology and Statistics Sorbonne Paris Cité (CRESS UMR1153), INSERM, INRA, Paris, France aff003;  Cochrane France, Paris, France aff004;  Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland aff005
Vyšlo v časopise: CINeMA: An approach for assessing confidence in the results of a network meta-analysis. PLoS Med 17(4): e32767. doi:10.1371/journal.pmed.1003082
Kategorie: Guidelines and Guidance
doi: 10.1371/journal.pmed.1003082



The evaluation of the credibility of results from a meta-analysis has become an important part of the evidence synthesis process. We present a methodological framework to evaluate confidence in the results from network meta-analyses, Confidence in Network Meta-Analysis (CINeMA), when multiple interventions are compared.


CINeMA considers 6 domains: (i) within-study bias, (ii) reporting bias, (iii) indirectness, (iv) imprecision, (v) heterogeneity, and (vi) incoherence. Key to judgments about within-study bias and indirectness is the percentage contribution matrix, which shows how much information each study contributes to the results from network meta-analysis. The contribution matrix can easily be computed using a freely available web application. In evaluating imprecision, heterogeneity, and incoherence, we consider the impact of these components of variability in forming clinical decisions.


Via 3 examples, we show that CINeMA improves transparency and avoids the selective use of evidence when forming judgments, thus limiting subjectivity in the process. CINeMA is easy to apply even in large and complicated networks.

Klíčová slova:

Adverse events – Coronary heart disease – Diagnostic medicine – Electrocardiography – Magnetic resonance imaging – Metaanalysis – Network analysis – Statins


1. Zarin W, Veroniki AA, Nincic V, Vafaei A, Reynen E, Motiwala SS, et al. Characteristics and knowledge synthesis approach for 456 network meta-analyses: a scoping review. BMC Med. 2017;15:3. doi: 10.1186/s12916-016-0764-6 28052774

2. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924–6. doi: 10.1136/bmj.39489.470347.AD 18436948

3. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction—GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64:383–94. doi: 10.1016/j.jclinepi.2010.04.026 21195583

4. Puhan MA, Schünemann HJ, Murad MH, Li T, Brignardello-Petersen R, Singh JA, et al. A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis. BMJ. 2014;349:g5630. doi: 10.1136/bmj.g5630 25252733

5. Salanti G, Del Giovane C, Chaimani A, Caldwell DM, Higgins JPT. Evaluating the quality of evidence from a network meta-analysis. PLoS ONE. 2014;9(7):e99682. doi: 10.1371/journal.pone.0099682 24992266

6. Jansen JP, Trikalinos T, Cappelleri JC, Daw J, Andes S, Eldessouki R, et al. Indirect treatment comparison/network meta-analysis study questionnaire to assess relevance and credibility to inform health care decision making: an ISPOR-AMCP-NPC Good Practice Task Force report. Value Health. 2014;17:157–73. doi: 10.1016/j.jval.2014.01.004 24636374

7. Hoaglin DC, Hawkins N, Jansen JP, Scott DA, Itzler R, Cappelleri JC, et al. Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2. Value Health. 2011;14:429–37. doi: 10.1016/j.jval.2011.01.011 21669367

8. Ades AE, Caldwell DM, Reken S, Welton NJ, Sutton AJ, Dias S. Evidence synthesis for decision making 7: a reviewer’s checklist. Med Decis Making. 2013;33:679–91. doi: 10.1177/0272989X13485156 23804511

9. Dias S, Sutton AJ, Ades AE, Welton NJ. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Making. 2013;33:607–17. doi: 10.1177/0272989X12458724 23104435

10. Siontis GC, Mavridis D, Greenwood JP, Coles B, Nikolakopoulou A, Jüni P, et al. Outcomes of non-invasive diagnostic modalities for the detection of coronary artery disease: network meta-analysis of diagnostic randomised controlled trials. BMJ. 2018;360:k504. doi: 10.1136/bmj.k504 29467161

11. Naci H, Brugts J, Ades T. Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circ Cardiovasc Qual Outcomes. 2013;6:390–9. doi: 10.1161/CIRCOUTCOMES.111.000071 23838105

12. Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391:1357–66. doi: 10.1016/S0140-6736(17)32802-7 29477251

13. CINeMA: Confidence in Network Meta-Analysis. Bern: Institute of Social and Preventive Medicine; 2017 [cited 2020 Mar 6]. Available from:

14. Rücker G, Krahn U, König J, Efthimiou O, Schwarzer G. netmeta: network meta-analysis using frequentist methods. GitHub. 2020 [cited 2020 Mar 12]. Available from:

15. Papakonstantinou T. flow_contribution: R package to calculate contribution of studies in network meta-analysis. GitHub; 2020 [cited 2020 Mar 6]. Available from:

16. Dumville JC, Soares MO, O’Meara S, Cullum N. Systematic review and mixed treatment comparison: dressings to heal diabetic foot ulcers. Diabetologia. 2012;55:1902–10. doi: 10.1007/s00125-012-2558-5 22544222

17. Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162:777–84. doi: 10.7326/M14-2385 26030634

18. Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi: 10.1136/bmj.d5928 22008217

19. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi: 10.1136/bmj.l4898 31462531

20. Guyatt GH, Oxman AD, Vist G, Kunz R, Brozek J, Alonso-Coello P, et al. GRADE guidelines: 4. Rating the quality of evidence—study limitations (risk of bias). J Clin Epidemiol. 2011;64:407–15. doi: 10.1016/j.jclinepi.2010.07.017 21247734

21. Brignardello-Petersen R, Bonner A, Alexander PE, Siemieniuk RA, Furukawa TA, Rochwerg B, et al. Advances in the GRADE approach to rate the certainty in estimates from a network meta-analysis. J Clin Epidemiol. 2018;93:36–44. doi: 10.1016/j.jclinepi.2017.10.005 29051107

22. Papakonstantinou T, Nikolakopoulou A, Rücker G, Chaimani A, Schwarzer G, Egger M, et al. Estimating the contribution of studies in network meta-analysis: paths, flows and streams. F1000Res. 2018;7:610. doi: 10.12688/f1000research.14770.3 30338058

23. Page MJ, McKenzie JE, Kirkham J, Dwan K, Kramer S, Green S, et al. Bias due to selective inclusion and reporting of outcomes and analyses in systematic reviews of randomised trials of healthcare interventions. Cochrane Database Syst Rev. 2014;(10):MR000035. doi: 10.1002/14651858.MR000035.pub2 25271098

24. Dwan K, Altman DG, Arnaiz JA, Bloom J, Chan A-W, Cronin E, et al. Systematic review of the empirical evidence of study publication bias and outcome reporting bias. PLoS ONE. 2008;3(8):e3081. doi: 10.1371/journal.pone.0003081 18769481

25. Dwan K, Gamble C, Williamson PR, Kirkham JJ, Reporting Bias Group. Systematic review of the empirical evidence of study publication bias and outcome reporting bias—an updated review. PLoS ONE. 2013;8(7):e66844. doi: 10.1371/journal.pone.0066844 23861749

26. Scherer RW, Langenberg P, von Elm E. Full publication of results initially presented in abstracts. Cochrane Database Syst Rev. 2007;(2)MR000005. doi: 10.1002/14651858.MR000005.pub3 17443628

27. Wager E, Williams P, Project Overcome failure to Publish nEgative fiNdings Consortium. “Hardly worth the effort”? Medical journals’ policies and their editors’ and publishers’ views on trial registration and publication bias: quantitative and qualitative study. BMJ. 2013;347:f5248. doi: 10.1136/bmj.f5248 24014339

28. Stern JM, Simes RJ. Publication bias: evidence of delayed publication in a cohort study of clinical research projects. BMJ. 1997;315:640–5. doi: 10.1136/bmj.315.7109.640 9310565

29. Dickersin K, Chalmers I. Recognizing, investigating and dealing with incomplete and biased reporting of clinical research: from Francis Bacon to the WHO. J R Soc Med. 2011;104:532–8. doi: 10.1258/jrsm.2011.11k042 22179297

30. Sterne JA, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ. 2001;323:101–5. doi: 10.1136/bmj.323.7304.101 11451790

31. Guyatt GH, Oxman AD, Montori V, Vist G, Kunz R, Brozek J, et al. GRADE guidelines: 5. Rating the quality of evidence—publication bias. J Clin Epidemiol. 2011;64:1277–82. doi: 10.1016/j.jclinepi.2011.01.011 21802904

32. Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ. 2003;326:1167–70. doi: 10.1136/bmj.326.7400.1167 12775614

33. Melander H, Ahlqvist-Rastad J, Meijer G, Beermann B. Evidence b(i)ased medicine—selective reporting from studies sponsored by pharmaceutical industry: review of studies in new drug applications. BMJ. 2003;326:1171–3. doi: 10.1136/bmj.326.7400.1171 12775615

34. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008;358:252–60. doi: 10.1056/NEJMsa065779 18199864

35. Chaimani A, Salanti G. Using network meta-analysis to evaluate the existence of small-study effects in a network of interventions. Res Synth Methods. 2012;3:161–76. doi: 10.1002/jrsm.57 26062088

36. Chaimani A, Salanti G. Visualizing assumptions and results in network meta-analysis: the network graphs package. Stata J. 2015;15:905–50.

37. Mavridis D, Efthimiou O, Leucht S, Salanti G. Publication bias and small-study effects magnified effectiveness of antipsychotics but their relative ranking remained invariant. J Clin Epidemiol. 2016;69:161–9. doi: 10.1016/j.jclinepi.2015.05.027 26210055

38. Mavridis D, Sutton A, Cipriani A, Salanti G. A fully Bayesian application of the Copas selection model for publication bias extended to network meta-analysis. Stat Med. 2013;32:51–66. doi: 10.1002/sim.5494 22806991

39. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 8. Rating the quality of evidence—indirectness. J Clin Epidemiol. 2011;64:1303–10. doi: 10.1016/j.jclinepi.2011.04.014 21802903

40. Bartlett C, Doyal L, Ebrahim S, Davey P, Bachmann M, Egger M, et al. The causes and effects of socio-demographic exclusions from clinical trials. Health Technol Assess. 2005;9:iii–iv,ix–x,1–152. doi: 10.3310/hta9380 16181564

41. Caldwell DM, Ades AE, Higgins JPT. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ. 2005;331:897–900. doi: 10.1136/bmj.331.7521.897 16223826

42. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 7. Rating the quality of evidence—inconsistency. J Clin Epidemiol. 2011;64:1294–302. doi: 10.1016/j.jclinepi.2011.03.017 21803546

43. Dias S, Welton NJ, Caldwell DM, Ades AE. Checking consistency in mixed treatment comparison meta-analysis. Stat Med. 2010;29:932–44. doi: 10.1002/sim.3767 20213715

44. Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades AE. Evidence synthesis for decision making 4: inconsistency in networks of evidence based on randomized controlled trials. Med Decis Making. 2013;33:641–56. doi: 10.1177/0272989X12455847 23804508

45. White IR, Barrett JK, Jackson D, Higgins JPT. Consistency and inconsistency in network meta-analysis: model estimation using multivariate meta-regression. Res Synth Methods. 2012;3:111–25. doi: 10.1002/jrsm.1045 26062085

46. Higgins JPT, Jackson D, Barrett JK, Lu G, Ades AE, White IR. Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies. Res Synth Methods. 2012;3:98–110. doi: 10.1002/jrsm.1044 26062084

47. Riley RD, Higgins JPT, Deeks JJ. Interpretation of random effects meta-analyses. BMJ. 2011;342:d549. doi: 10.1136/bmj.d549 21310794

48. Turner RM, Davey J, Clarke MJ, Thompson SG, Higgins JP. Predicting the extent of heterogeneity in meta-analysis, using empirical data from the Cochrane Database of Systematic Reviews. Int J Epidemiol. 2012;41:818–27. doi: 10.1093/ije/dys041 22461129

49. Rhodes KM, Turner RM, Higgins JPT. Predictive distributions were developed for the extent of heterogeneity in meta-analyses of continuous outcome data. J Clin Epidemiol. 2015;68:52–60. doi: 10.1016/j.jclinepi.2014.08.012 25304503

50. Lu G, Ades AE. Assessing evidence inconsistency in mixed treatment comparisons. J Am Stat Assoc. 2006;101:447–59. doi: 10.1198/016214505000001302

51. Lu G, Ades A. Modeling between-trial variance structure in mixed treatment comparisons. Biostatistics. 2009;10:792–805. doi: 10.1093/biostatistics/kxp032 19687150

52. 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;50:683–91. doi: 10.1016/s0895-4356(97)00049-8 9250266

53. Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades AE. NICE DSU technical support document 4: inconsistency in networks of evidence based on randomised controlled trials. London: National Institute for Health and Care Excellence; 2014 [cited 2020 Mar 6]. Available from:

54. Veroniki AA, Mavridis D, Higgins JP, Salanti G. Characteristics of a loop of evidence that affect detection and estimation of inconsistency: a simulation study. BMC Med Res Methodol. 2014;14:106. doi: 10.1186/1471-2288-14-106 25239546

55. Song F, Clark A, Bachmann MO, Maas J. Simulation evaluation of statistical properties of methods for indirect and mixed treatment comparisons. BMC Med Res Methodol. 2012;12:138. doi: 10.1186/1471-2288-12-138 22970794

56. Phillippo DM, Dias S, Welton NJ, Caldwell DM, Taske N, Ades AE. Threshold analysis as an alternative to GRADE for assessing confidence in guideline recommendations based on network meta-analyses. Ann Intern Med. 2019;170(8):538–46. doi: 10.7326/M18-3542 30909295

57. Kanters S, Ford N, Druyts E, Thorlund K, Mills EJ, Bansback N. Use of network meta-analysis in clinical guidelines. Bull World Health Organ. 2016;94:782–4. doi: 10.2471/BLT.16.174326 27843171

58. Petropoulou M, Nikolakopoulou A, Veroniki A-A, Rios P, Vafaei A, Zarin W, et al. Bibliographic study showed improving statistical methodology of network meta-analyses published between 1999 and 2015. J Clin Epidemiol. 2017;82:20–8. doi: 10.1016/j.jclinepi.2016.11.002 27864068

59. Papakonstantinou T, Nikolakopoulou A, Higgins JPT, Egger M, Salanti G. CINeMA: software for semiautomated assessment of the confidence in the results of network meta-analysis. Campbell Syst Rev. 2020;16:e1080. doi: 10.1002/cl2.1080

Článek vyšel v časopise

PLOS Medicine

2020 Číslo 4

Nejčtenější v tomto čísle

Zvyšte si kvalifikaci online z pohodlí domova

hyperpigmentace úvodní foto kurz
Efektivní redukce hyperpigmentace − od výzkumu k inovacím pro praxi
nový kurz
Autoři: dr. Ludger Kolbe, dr. Thierry Passeron, MD, PhD

zveme Vás k zapojení se do videokurzu s tématem Co je a není FENO? Nadhodnocené FENO a podhodnocené eozinofily v krvi u astmatu.
Autoři: doc. MUDr. Petr Čáp, Ph.D.

Postavení moxonidinu a indapamidu v léčbě hypertenze
Autoři: MUDr. Jan Vachek

Magnetická rezonance a diagnostika axiálních spondyloartritid - Virtuální trénink
Autoři: MUDr. Leona Procházková, Ph.D., MUDr. Monika Gregová, Ph.D., MUDr. Vladimír Červeňák, MUDr. Eva Korčáková, Ph.D.

Hybridní zubní náhrady – přežitek nebo perspektiva v moderní protetické péči?
Autoři: doc. MUDr. Hana Hubálková, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se