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Simultaneous comparison of multiple treatments: Combining direct and indirect evidence.
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A randomized comparison between rasburicase and allopurinol in children with lymphoma or
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“network meta-analysis offers a methodological solution to provide more precise pooled head-to-head effect estimates than may otherwise be achieved 19, 20 .”
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“A random-effects network metaanalysis was performed subsequently, to compare simultaneously the relative effectiveness of all interventions [14].”
MethodRajadurai, S. G., Maharajan, M. K., Veettil, S. K., & Gopinath, D. (2021) · Journal of Fungi · doi:10.3390/jof7080637 · Cited by 24
“Unlike conventional meta-analysis, network meta-analysis would allow a direct and indirect comparison of different treatments, which would enable the production of more accurate detail on which antifungal is the most efficacious and safest [21].”
BackgroundYin, Z., Wang, F., Sun, M., Zhao, L., & Liang, F. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/3178154 · Cited by 25
“In this study, the efficacy of various therapies for PTN treatment was compared and reliable results were obtained [96, 97].”
ResultMost meta-analyses of drug interventions have narrow scopes and many focus on specific agents
Haidich, A., Pilalas, D., Contopoulos‐Ioannidis, D. G., & Ioannidis, J. P. A. (2013) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2012.10.014 · Cited by 25
“This can be done either by performing meta-analyses on all the diverse available pair-wise comparisons of different interventions and/or settings [16,17] or more formally in multiple treatment comparison (network) meta-analyses [18,19].”
MethodNetwork Meta-Analysis for Complex Social Interventions: Problems and Potential
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Chen, X., Huang, T., Cao, X., & Xu, G. (2017) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-017-0245-0 · Cited by 25
“A comprehensive traditional meta-analysis of randomized controlled trials (RCTs) relevant to this theme was undertaken in 2011 [9]; however, conventional pairwise meta-analysis could not simultaneously synthesize all evidence and rank the therapies because direct comparisons between treatments were lacking [10, 11].”
Leahy, J., O’Leary, A. C., Afdhal, N. H., Gray, E., Milligan, S., Wehmeyer, M. H., & Walsh, C. (2018) · Research Synthesis Methods · doi:10.1002/jrsm.1305 · Cited by 24
Veettil, S. K., Jinatongthai, P., Nathisuwan, S., Teerawattanapong, N., Ching, S. M., Lim, K. G., Saokaew, S., Phisalprapa, P., Reid, C. M., & Chaiyakunapruk, N. (2018) · Clinical Epidemiology · doi:10.2147/clep.s174120 · Cited by 24
“A random-effects NMA using consistency model was applied to compare all interventions using direct and indirect data.(46,47) Inconsistency assumption was evaluated using the global inconsistency test by fitting design-by-treatment in the inconsistency model.”
MethodWinder, C. B., Sargeant, J. M., Hu, D., Wang, C., Kelton, D. F., LeBlanc, S. J., Duffield, T. F., Glanville, J., Wood, H., Churchill, K. J., et al. (2019) · Animal Health Research Reviews · doi:10.1017/s1466252319000276 · Cited by 24
“…relative efficacy across many treatments by using both direct evidence (from studies that compare given treatments) and indirect evidence (from studies that share common comparators), and is a commonly used approach in the human medicine literature (Caldwell et al., 2005; Cipriani et al., 2013).”
BackgroundCao, G., Wu, X., Wang, Z., Tian, X., Zhang, C., Wu, X., Zhang, H., Jing, G., & Yan, T. (2020) · BMJ Open · doi:10.1136/bmjopen-2019-034626 · Cited by 26
Network meta-analysis of randomised controlled trials: direct and indirect treatment comparisons.
Buti, J., Glenny, A., Worthington, H. V., Nieri, M., & Baccini, M. (2011) · PubMed · Cited by 24
Meeral, P. R., Doraikannan, S., & Indiran, M. A. (2024) · The Saudi Dental Journal · doi:10.1016/j.sdentj.2024.01.014 · Cited by 23
“…early caries lesions (Prestes et al., 2013; Higgins et al., 2008; Moher et al., 2009; Green, 2011) as well as its anti-cariogenic properties in laboratory, animal, and in situ human studies (DerSimonian and Laird, 1986; Caldwell et al., 2005; Higgins and Thompson, 2002; Fredrick et al., 2013).”
BackgroundMethodOrme, M. E., Fenici, P., Duprat-Lomon, I., Wygant, G. D., Townsend, R., & Roudaut, M. (2014) · Diabetology & Metabolic Syndrome · doi:10.1186/1758-5996-6-73 · Cited by 23
“Whereas standard meta-analyses evaluate the relative efficacy of just two treatments based on head-to-head trials only, NMA comprises an extension of these methods in which treatment effects are calculated for a network of treatments, using both direct and indirect evidence [36-38].”
MethodVeroniki, A. A., Straus, S. E., Ashoor, H. M., Hamid, J. S., Hemmelgarn, B. R., Holroyd-Leduc, J. M., Majumdar, S. R., McAuley, G., & Tricco, A. C. (2016) · BMJ Open · doi:10.1136/bmjopen-2015-010251 · Cited by 22
Network meta-analysis in health psychology and behavioural medicine: a primer
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“Such methods produce more precise effect sizes than using direct evidence alone (Caldwell et al., 2005; Ioannidis, 2006; Jansen et al., 2014).”
MethodSelf-citationKim, Y. J., Hwang, S. D., & Lim, S. K. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00553 · Cited by 24
Linked Pharmacometric‐Pharmacoeconomic Modeling and Simulation in Clinical Drug Development
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“Network meta-analysis (NMA) is a widely used method which integrates both direct and indirect comparisons based on frequentist model or Bayesian model (16).”
MethodRadadiya, D. K., Brahmbhatt, B. S., Reddy, C., & Devani, K. (2022) · PubMed · doi:10.1097/mcg.0000000000001523 · Cited by 8
Gopinath, D., Hui, L. M., Veettil, S. K., Nair, A. B., & Maharajan, M. K. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12081272 · Cited by 23
“Direct and indirect evidence were then combined and synthesized using random-effects network meta-analysis using consistency or inconsistency models [33,34] and the inconsistencies between the direct and indirect estimates which is known as network inconsistency assumption was assessed using a global inconsistency tes…”
MethodEllis, A. G., Reginster, J., Luo, X., Bushmakin, A. G., Williams, R., Sutradhar, S., Mirkin, S., & Jansen, J. P. (2014) · Current Medical Research and Opinion · doi:10.1185/03007995.2014.908279 · Cited by 23
Xiong, T., Bhurke, S., Loke, Y. K., Abdelhamid, A. S., Sutton, A. J., Eastwood, A. J., Holland, R., Chen, Y., Walsh, T., Glenny, A., et al. (2012) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2012.06.022 · Cited by 23
“Although quantitative methods are available to investigate heterogeneity across studies in meta-analysis and the inconsistency between direct and indirect comparisons, the assessment of trial similarity for adjusted indirect comparison is mainly based on subjective judgment [24].”
MethodWright, J., Yang, H., Walker, K., Pedley, S., Elliott, J., & Gundry, S. (2011) · Tropical Medicine & International Health · doi:10.1111/j.1365-3156.2011.02887.x · Cited by 23
“In clinical meta-analysis, techniques are developing to synthesize evidence from both direct comparisons within studies and indirect evidence across studies (Caldwell et al. 2005).”
BackgroundResearch synthesis methods in ecology
Gurevitch, J., & Nakagawa, S. (2015) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780199672547.003.0010 · Cited by 21
Value and usability of unpublished data sources for systematic reviews and network meta-analyses
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Using structural equation modeling for network meta-analysis
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Edwards, S. J., Wakefield, V., Cain, P., Karner, C., Kew, K. M., Bacelar, M., Masento, N. A., & Salih, F. (2018) · Health Technology Assessment · doi:10.3310/hta22060 · Cited by 23
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“For the NMA, a frequentist random-effects model was used with the assumption of a common between-study covariance structure across the treatment arms; this is often referred to as a homogenous variance assumption [14, 15].”
MethodLee, Y. H., & Song, G. G. (2017) · Lupus · doi:10.1177/0961203317713143 · Cited by 23
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Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis
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Conceptos básicos del metaanálisis en red
Catalá-López, F., Tobías, A., & Roqué, M. (2014) · Atención Primaria · doi:10.1016/j.aprim.2014.01.006 · Cited by 21
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“References excluded: (25) Trial design out of scope (8) Patient pop.”
Horita, N., Nagashima, A., Nakashima, K., Shibata, Y., Ito, K., Goto, A., Yamanaka, T., & Kaneko, T. (2017) · Scientific Reports · doi:10.1038/s41598-017-13724-2 · Cited by 23
Multivariate network meta‐analysis to mitigate the effects of outcome reporting bias
Hwang, H., & DeSantis, S. M. (2018) · Statistics in Medicine · doi:10.1002/sim.7815 · Cited by 22
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“When multiple comparisons between large numbers of treatments are performed it is important to account for both direct evidence from head-to-head RCTs and indirect evidence utilizing chains of RCTs sharing common comparators [19, 20].”
BackgroundThe impact of covariance priors on arm‐based Bayesian network meta‐analyses with binary outcomes
Wang, Z., Lin, L., Hodges, J. S., & Chu, H. (2020) · Statistics in Medicine · doi:10.1002/sim.8580 · Cited by 22
Synthesizing cross‐design evidence and cross‐format data using network meta‐regression
Hamza, T., Chalkou, K., Pellegrini, F., Kühle, J., Benkert, P., Lorscheider, J., Zecca, C., Iglesias-Urrutia, C. P., Manca, A., Furukawa, T. A., et al. (2023) · Research Synthesis Methods · doi:10.1002/jrsm.1619 · Cited by 22
“We performed a sensitivity analysis to investigate the robustness of the results with less informative prior distributions for the bias probability h$ in both bias models 78Mx(10,1) and 78Mx(1,10) for studies at moderate and low RoB, respectively.”
BackgroundMethodInfluentialGiok, K. C., Veettil, S. K., & Menon, R. K. (2023) · Journal of Prosthetic Dentistry · doi:10.1016/j.prosdent.2023.08.022 · Cited by 28
Chemotherapy for patients with gastric cancer after complete resection: A network meta-analysis
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Fact or fiction: reducing the proportion and impact of false positives
Stahl, D. R., & Pickles, A. R. (2017) · Psychological Medicine · doi:10.1017/s003329171700294x · Cited by 23
Network meta-analysis of surgical management of gastro-oesophageal reflux disease in adults
Amer, M., Smith, M. D., Khoo, C. H., Herbison, P., & McCall, J. L. (2018) · British journal of surgery · doi:10.1002/bjs.10924 · Cited by 22
Arai, Y., Matsui, H., Jo, T., Kondo, T., & Takaori‐Kondo, A. (2018) · Platelets · doi:10.1080/09537104.2018.1543864 · Cited by 20
“Our current study is the first to answer all of three of these questions using the technique of network meta-analysis [14,15].”
BackgroundMethodQian, T., Zhao, M., Wan, Y., Li, M.-X., & Xu, X. (2018) · BMJ Open · doi:10.1136/bmjopen-2018-022700 · Cited by 23
A Network Meta-Analysis of Surgical Treatment in Patients With Early Breast Cancer
Gui, Y., Liu, X., Chen, X., Yang, X., Li, S., Pan, Q., Luo, X., & Chen, L. (2019) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djz105 · Cited by 22
“The Bayesian consistency model was used to analyze the data in which all the parameters were treated as random variables, and the Markov chain Monte Carlo method was used to estimate the posterior distribution of each parameter (25,26).”
MethodThe efficacy and safety of pulse vs. continuous therapy for dermatophyte toenail onychomycosis
Gupta, A. K., Stec, N., Bamimore, M. A., Foley, K. A., Shear, N. H., & Piguet, V. (2019) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.16101 · Cited by 22
Szabo, S. M., Hedegaard, M. S., Chan, K., Thorlund, K., Christensen, R., Vorum, H., & Jansen, J. P. (2015) · Current Medical Research and Opinion · doi:10.1185/03007995.2015.1084909 · Cited by 21
Cope, S. F., Zhang, J., Williams, J., & Jansen, J. P. (2012) · BMC Pulmonary Medicine · doi:10.1186/1471-2466-12-29 · Cited by 21
“The deviance information criterion (DIC), which provides a measure of model fit that penalizes model complexity, was used to select fixed effects models over random effects models [15,18,19].”
MethodWang, W., Zhang, L., Liu, W., Zhu, Q., Lan, Q., & Zhao, J. (2016) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2016.01.026 · Cited by 21
Safety of interferon-free therapies for chronic hepatitis C: a network meta-analysis
Ferreira, V. L., Jarek, N. A. A., Tonin, F. S., Borba, H. H. L., Wiens, A., & Pontarolo, R. (2016) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.12426 · Cited by 21
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Wudexi, I., Shokri, E., Abo-Aly, M. A., Shindo, K., & Abdel‐Latif, A. (2021) · Mediators of Inflammation · doi:10.1155/2021/5160728 · Cited by 21
“Informative prior was chosen to assume consistency between heterogeneity variances and ensure a realistic heterogeneity estimation [25].”
MethodRicci, C., Lamberti, G., Ingaldi, C., Mosconi, C., Pagano, N., Alberici, L., Ambrosini, V., Manuzzi, L., Monari, F., Malvi, D., et al. (2021) · Cancers · doi:10.3390/cancers13020358 · Cited by 22
Effect of rituximab dose on induction therapy in ABO-incompatible living kidney transplantation
Lee, H. R., Kim, K., Lee, S. W., Song, J. H., Lee, J. H., & Hwang, S. D. (2021) · Medicine · doi:10.1097/md.0000000000024853 · Cited by 21
“We performed a network meta-analysis of studies that recorded multiple treatments, which allowed estimation of the pooled effects within each treatment.([26]) For multiarm trials, correlations among treatment”
MethodHamza, T., Furukawa, T. A., Orsini, N., Cipriani, A., Iglesias, C. P., & Salanti, G. (2022) · Statistical Methods in Medical Research · doi:10.1177/09622802211070256 · Cited by 21
Wang, Y., Liu, W., Chen, J., Bai, J., Yu, H., Ma, H., Jiang, R., & Xu, G. (2023) · Therapeutic Advances in Chronic Disease · doi:10.1177/20406223231168754 · Cited by 22
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Rheinheimer, J., Ziegelmann, P. K., Carlessi, R., Remonti, L. R., Bauer, A. C., Leitão, C. B., & Crispim, D. (2014) · Islets · doi:10.4161/19382014.2014.977118 · Cited by 21
“However, we believe that our results are still robust since we applied a Bayesian model to explore the effects of indirect evidence between studies, which is thought to be the most appropriate method for MTC metaanalysis.(16,43) In summary, improvement of islet isolations and standardization of these procedures are im…”
MethodRequirements for benefit assessment in Germany and England – overview and comparison
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“Bayesian analysis, mixed-treatment-comparison metaanalyses [16], multiple-treatment-meta-analyses [17] or network meta-analysis [18].”
From Qualitative Reviews to Umbrella Reviews
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What is a multiple treatments meta-analysis?
Cipriani, A., Barbui, C., Rizzo, C., & Salanti, G. (2012) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796011000837 · Cited by 21
“…has led to the development of meta-analytical techniques that allow the incorporation of evidence from both direct and indirect comparisons in a network of trials and different interventions to estimate summary treatment effects as comprehensively and precisely as possible (Caldwell et al. 2005).”
Backgroundvon Thiele Schwarz, U., Förberg, U., Sundell, K., & Hasson, H. (2018) · BMC Medical Research Methodology · doi:10.1186/s12874-018-0496-8 · Cited by 20
Methods to assess evidence consistency in dose‐response model based network meta‐analysis
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“4 By comparing Equations (2) and (7) it can be seen that the UME model relaxes both the dose-response relationship and the consistency assumption at the same time.”
BackgroundResultInfluentialSong, G. G., & Lee, Y. H. (2017) · Zeitschrift für Rheumatologie · doi:10.1007/s00393-017-0355-8 · Cited by 20
Drucker, A. M., Ellis, A. G., Jabbar‐Lopez, Z. K., Yiu, Z. Z. N., Arents, B. W. M., Burton, T., Spuls, P. I., Küster, D., Schmitt, J. M., & Flohr, C. (2018) · BMJ Open · doi:10.1136/bmjopen-2018-023061 · Cited by 21
“NMA is an extension of pairwise meta-analysis that simultaneously combines both the direct evidence (ie, interventions assessed head to head) and indirect evidence (ie, interventions assessed through a common comparator).(28) 29 Doing so improves precision of treatment effect estimates and also provides estimates for…”
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“To ensure sufficient similarity in the various treatment comparisons and provide valid indirect inferences, two authors (JCW and YHW) independently evaluated the transitivity assumption before statistical analyses by comparing and examining the clinical and methodological characteristics (eg, participant characteristi…”
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“NMA allows the synthesis of results from trials of interventions that form a connected network of intervention comparisons, so that direct (headto-head) and indirect (through common comparators in different RCTs) evidence can be statistically combined [24, 28, 29].”
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“More complex extensions are network meta-analysis (NMA) models that have been widely used during the last decade, which allow the simultaneous analysis of clinical trials involving different treatments.(16) 17 NMA is more advantageous than both pairwise MA and indirect comparison MA, as it provides the ability to (1)…”
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“An evidence network was constructed to show direct (A versus B, or B versus C) treatment comparisons along with the number of trials in each node [10, 11].”
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“Statistical methods for MTCs applied to univariate outcomes have been well studied in the previous decade; see, for examples, Lumley (2002), Lu and Ades (2006), Caldwell et al. (2005) and Salanti et al. (2008).”
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Metadata
- Authors
- Caldwell, D. M., Ades, A. E., & Higgins, J. P. T.
- Affiliations
- University of Bristol (GB)
- MRC Biostatistics Unit (GB)
- Corresponding author
- Caldwell, Deborah M
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2005-10-13
- Volume
- 331
- Issue
- 7521
- Pages
- 897-900
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC1255806
- OpenAlex
- W1967385770
- Cited by
- 1,600
- References
- 37
- Citations by year
- 2026: 53 · 2025: 63 · 2024: 72 · 2023: 67 · 2022: 91 · 2021: 105 · 2020: 136 · 2019: 115 · 2018: 115 · 2017: 108 · 2016: 95 · 2015: 107 · 2014: 101 · 2013: 79 · 2012: 80
- FWCI
- 16.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- BMJ (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (submittedVersion)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Health Sciences › Medicine › Hematology › Methemoglobinemia and Tumor Lysis Syndrome
- Keywords
- rasburicase, allopurinol, hyperuricemia, lymphoma, pediatric oncology, direct and indirect evidence, treatment comparison
- MeSH terms
- Data Interpretation, Statistical, Decision Making, Humans, Meta-Analysis as Topic, Bias, Randomized Controlled Trials as Topic, Evidence-Based Medicine
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