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Article ; Online: Estimating interactions and subgroup-specific treatment effects in meta-analysis without aggregation bias: A within-trial framework.

Godolphin, Peter J / White, Ian R / Tierney, Jayne F / Fisher, David J

2022 Volume 14, Issue 1, Page(s) 68–78

Abstract: Estimation of within-trial interactions in meta-analysis is crucial for reliable assessment of how treatment effects vary across participant subgroups. However, current methods have various limitations. Patients, clinicians and policy-makers need ... ...

Abstract	Estimation of within-trial interactions in meta-analysis is crucial for reliable assessment of how treatment effects vary across participant subgroups. However, current methods have various limitations. Patients, clinicians and policy-makers need reliable estimates of treatment effects within specific covariate subgroups, on relative and absolute scales, in order to target treatments appropriately-which estimation of an interaction effect does not in itself provide. Also, the focus has been on covariates with only two subgroups, and may exclude relevant data if only a single subgroup is reported. Therefore, in this article we further develop the "within-trial" framework by providing practical methods to (1) estimate within-trial interactions across two or more subgroups; (2) estimate subgroup-specific ("floating") treatment effects that are compatible with the within-trial interactions and make maximum use of available data; and (3) clearly present this data using novel implementation of forest plots. We described the steps involved and apply the methods to two examples taken from previously published meta-analyses, and demonstrate a straightforward implementation in Stata based upon existing code for multivariate meta-analysis. We discuss how the within-trial framework and plots can be utilised with aggregate (or "published") source data, as well as with individual participant data, to effectively demonstrate how treatment effects differ across participant subgroups.
MeSH term(s)	Humans ; Research Design ; Bias
Language	English
Publishing date	2022-07-28
Publishing country	England
Document type	Meta-Analysis ; Journal Article
ZDB-ID	2548499-0
ISSN	1759-2887 ; 1759-2879
ISSN (online)	1759-2887
ISSN	1759-2879
DOI	10.1002/jrsm.1590
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Duplicated network meta-analysis in advanced prostate cancer: a case study and recommendations for change.

Fisher, David J / Burdett, Sarah / Vale, Claire / White, Ian R / Tierney, Jayne F

Systematic reviews

2022 Volume 11, Issue 1, Page(s) 274

Abstract: Background: Research overlap and duplication is a recognised problem in the context of both pairwise and network systematic reviews and meta-analyses. As a case study, we carried out a scoping review to identify and examine duplicated network meta- ... ...

Abstract	Background: Research overlap and duplication is a recognised problem in the context of both pairwise and network systematic reviews and meta-analyses. As a case study, we carried out a scoping review to identify and examine duplicated network meta-analyses (NMAs) in a specific disease setting where several novel therapies have recently emerged: hormone-sensitive metastatic prostate cancer (mHSPC). Methods: MEDLINE and EMBASE were systematically searched, in January 2020, for indirect or mixed treatment comparisons or network meta-analyses of the systemic treatments docetaxel and abiraterone acetate in the mHSPC setting, with a time-to-event outcome reported on the hazard-ratio scale. Eligibility decisions were made, and data extraction performed, by two independent reviewers. Results: A total of 13 eligible reviews were identified, analysing between 3 and 8 randomised comparisons, and comprising between 1773 and 7844 individual patients. Although the included trials and treatments showed a high degree of overlap, we observed considerable variation between identified reviews in terms of review aims, eligibility criteria and included data, statistical methodology, reporting and inference. Furthermore, crucial methodological details and specific source data were often unclear. Conclusions and recommendations: Variation across duplicated NMAs, together with reporting inadequacies, may compromise identification of best-performing treatments. Particularly in fast-moving fields, review authors should be aware of all relevant studies, and of other reviews with potential for overlap or duplication. We recommend that review protocols be published in advance, with greater clarity regarding the specific aims or scope of the project, and that reports include information on how the work builds upon existing knowledge. Source data and results should be clearly and completely presented to allow unbiased interpretation.
MeSH term(s)	Male ; Humans ; Network Meta-Analysis ; Abiraterone Acetate ; Prostatic Neoplasms/drug therapy ; Docetaxel/therapeutic use
Chemical Substances	Abiraterone Acetate (EM5OCB9YJ6) ; Docetaxel (15H5577CQD)
Language	English
Publishing date	2022-12-16
Publishing country	England
Document type	Systematic Review ; Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2662257-9
ISSN	2046-4053 ; 2046-4053
ISSN (online)	2046-4053
ISSN	2046-4053
DOI	10.1186/s13643-022-02137-6
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Article ; Online: Meta-analyses based on summary data can provide timely, thorough and reliable evidence: don't dismiss them yet.

Godolphin, Peter J / Rogozińska, Ewelina / Fisher, David J / Vale, Claire L / Tierney, Jayne F

Nature medicine

2022 Volume 28, Issue 3, Page(s) 429–430

MeSH term(s)	Ivermectin
Chemical Substances	Ivermectin (70288-86-7)
Language	English
Publishing date	2022-02-10
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-021-01675-1
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Use of multiple covariates in assessing treatment-effect modifiers: A methodological review of individual participant data meta-analyses.

Godolphin, Peter J / Marlin, Nadine / Cornett, Chantelle / Fisher, David J / Tierney, Jayne F / White, Ian R / Rogozińska, Ewelina

Research synthesis methods

2023 Volume 15, Issue 1, Page(s) 107–116

Abstract: Individual participant data (IPD) meta-analyses of randomised trials are considered a reliable way to assess participant-level treatment effect modifiers but may not make the best use of the available data. Traditionally, effect modifiers are explored ... ...

Abstract	Individual participant data (IPD) meta-analyses of randomised trials are considered a reliable way to assess participant-level treatment effect modifiers but may not make the best use of the available data. Traditionally, effect modifiers are explored one covariate at a time, which gives rise to the possibility that evidence of treatment-covariate interaction may be due to confounding from a different, related covariate. We aimed to evaluate current practice when estimating treatment-covariate interactions in IPD meta-analysis, specifically focusing on involvement of additional covariates in the models. We reviewed 100 IPD meta-analyses of randomised trials, published between 2015 and 2020, that assessed at least one treatment-covariate interaction. We identified four approaches to handling additional covariates: (1) Single interaction model (unadjusted): No additional covariates included (57/100 IPD meta-analyses); (2) Single interaction model (adjusted): Adjustment for the main effect of at least one additional covariate (35/100); (3) Multiple interactions model: Adjustment for at least one two-way interaction between treatment and an additional covariate (3/100); and (4) Three-way interaction model: Three-way interaction formed between treatment, the additional covariate and the potential effect modifier (5/100). IPD is not being utilised to its fullest extent. In an exemplar dataset, we demonstrate how these approaches lead to different conclusions. Researchers should adjust for additional covariates when estimating interactions in IPD meta-analysis providing they adjust their main effects, which is already widely recommended. Further, they should consider whether more complex approaches could provide better information on who might benefit most from treatments, improving patient choice and treatment policy and practice.
MeSH term(s)	Humans ; Models, Statistical ; Meta-Analysis as Topic ; Randomized Controlled Trials as Topic
Language	English
Publishing date	2023-09-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2548499-0
ISSN	1759-2887 ; 1759-2879
ISSN (online)	1759-2887
ISSN	1759-2879
DOI	10.1002/jrsm.1674
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A new approach to evaluating loop inconsistency in network meta-analysis.

Turner, Rebecca M / Band, Tim / Morris, Tim P / Fisher, David J / Higgins, Julian P T / Carpenter, James R / White, Ian R

Statistics in medicine

2023 Volume 42, Issue 27, Page(s) 4917–4930

Abstract: In network meta-analysis, studies evaluating multiple treatment comparisons are modeled simultaneously, and estimation is informed by a combination of direct and indirect evidence. Network meta-analysis relies on an assumption of consistency, meaning ... ...

Abstract	In network meta-analysis, studies evaluating multiple treatment comparisons are modeled simultaneously, and estimation is informed by a combination of direct and indirect evidence. Network meta-analysis relies on an assumption of consistency, meaning that direct and indirect evidence should agree for each treatment comparison. Here we propose new local and global tests for inconsistency and demonstrate their application to three example networks. Because inconsistency is a property of a loop of treatments in the network meta-analysis, we locate the local test in a loop. We define a model with one inconsistency parameter that can be interpreted as loop inconsistency. The model builds on the existing ideas of node-splitting and side-splitting in network meta-analysis. To provide a global test for inconsistency, we extend the model across multiple independent loops with one degree of freedom per loop. We develop a new algorithm for identifying independent loops within a network meta-analysis. Our proposed models handle treatments symmetrically, locate inconsistency in loops rather than in nodes or treatment comparisons, and are invariant to choice of reference treatment, making the results less dependent on model parameterization. For testing global inconsistency in network meta-analysis, our global model uses fewer degrees of freedom than the existing design-by-treatment interaction approach and has the potential to increase power. To illustrate our methods, we fit the models to three network meta-analyses varying in size and complexity. Local and global tests for inconsistency are performed and we demonstrate that the global model is invariant to choice of independent loops.
MeSH term(s)	Humans ; Network Meta-Analysis ; Algorithms ; Research Design
Language	English
Publishing date	2023-09-28
Publishing country	England
Document type	Meta-Analysis ; Journal Article
ZDB-ID	843037-8
ISSN	1097-0258 ; 0277-6715
ISSN (online)	1097-0258
ISSN	0277-6715
DOI	10.1002/sim.9872
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Book: High-entropy alloys - microstructures and properties

Fisher, David J

(Materials science foundations ; 86)

2015

Abstract: ... ...

Author's details	D. J. Fisher
Series title	Materials science foundations ; 86
Abstract	Literaturangaben
Language	English
Size	154 S., Ill., graph. Darst.
Publisher	TTP, Trans Tech Publ
Publishing place	Pfaffikon u.a.
Document type	Book
ISBN	9783038359937 ; 3038359939
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article ; Online: Comparison of aggregate and individual participant data approaches to meta-analysis of randomised trials: An observational study.

Tierney, Jayne F / Fisher, David J / Burdett, Sarah / Stewart, Lesley A / Parmar, Mahesh K B

PLoS medicine

2020 Volume 17, Issue 1, Page(s) e1003019

Abstract: Background: It remains unclear when standard systematic reviews and meta-analyses that rely on published aggregate data (AD) can provide robust clinical conclusions. We aimed to compare the results from a large cohort of systematic reviews and meta- ... ...

Abstract	Background: It remains unclear when standard systematic reviews and meta-analyses that rely on published aggregate data (AD) can provide robust clinical conclusions. We aimed to compare the results from a large cohort of systematic reviews and meta-analyses based on individual participant data (IPD) with meta-analyses of published AD, to establish when the latter are most likely to be reliable and when the IPD approach might be required. Methods and findings: We used 18 cancer systematic reviews that included IPD meta-analyses: all of those completed and published by the Meta-analysis Group of the MRC Clinical Trials Unit from 1991 to 2010. We extracted or estimated hazard ratios (HRs) and standard errors (SEs) for survival from trial reports and compared these with IPD equivalents at both the trial and meta-analysis level. We also extracted or estimated the number of events. We used paired t tests to assess whether HRs and SEs from published AD differed on average from those from IPD. We assessed agreement, and whether this was associated with trial or meta-analysis characteristics, using the approach of Bland and Altman. The 18 systematic reviews comprised 238 unique trials or trial comparisons, including 37,082 participants. A HR and SE could be generated for 127 trials, representing 53% of the trials and approximately 79% of eligible participants. On average, trial HRs derived from published AD were slightly more in favour of the research interventions than those from IPD (HRAD to HRIPD ratio = 0.95, p = 0.007), but the limits of agreement show that for individual trials, the HRs could deviate substantially. These limits narrowed with an increasing number of participants (p < 0.001) or a greater number (p < 0.001) or proportion (p < 0.001) of events in the AD. On average, meta-analysis HRs from published AD slightly tended to favour the research interventions whether based on fixed-effect (HRAD to HRIPD ratio = 0.97, p = 0.088) or random-effects (HRAD to HRIPD ratio = 0.96, p = 0.044) models, but the limits of agreement show that for individual meta-analyses, agreement was much more variable. These limits tended to narrow with an increasing number (p = 0.077) or proportion of events (p = 0.11) in the AD. However, even when the information size of the AD was large, individual meta-analysis HRs could still differ from their IPD equivalents by a relative 10% in favour of the research intervention to 5% in favour of control. We utilised the results to construct a decision tree for assessing whether an AD meta-analysis includes sufficient information, and when estimates of effects are most likely to be reliable. A lack of power at the meta-analysis level may have prevented us identifying additional factors associated with the reliability of AD meta-analyses, and we cannot be sure that our results are generalisable to all outcomes and effect measures. Conclusions: In this study we found that HRs from published AD were most likely to agree with those from IPD when the information size was large. Based on these findings, we provide guidance for determining systematically when standard AD meta-analysis will likely generate robust clinical conclusions, and when the IPD approach will add considerable value.
MeSH term(s)	Data Interpretation, Statistical ; Decision Trees ; Humans ; Meta-Analysis as Topic ; Neoplasms/diagnosis ; Neoplasms/epidemiology ; Randomized Controlled Trials as Topic/standards ; Reproducibility of Results ; Systematic Reviews as Topic
Language	English
Publishing date	2020-01-31
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2185925-5
ISSN	1549-1676 ; 1549-1277
ISSN (online)	1549-1676
ISSN	1549-1277
DOI	10.1371/journal.pmed.1003019
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 6042: Show issues

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Book: [No title information]

Fisher, David J

Defects and diffusion in semiconductors

(Defect and diffusion forum ; 303/304 ; Defects and diffusion in semiconductors : an annual retrospective ; 12.2010)

2010

Series title	Defect and diffusion forum ; 303/304 Defects and diffusion in semiconductors : an annual retrospective ; 12.2010
Language	English
Size	VIII, 393 S., Ill., graph. Darst
Publisher	Trans Tech Publ
Publishing place	Stafa-Zuerich u.a.
Document type	Book
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Book: [No title information]

Fisher, David J

Defects and diffusion, theory and simulation

(Defect and diffusion forum ; 307 ; Defects and diffusion, theory and simulation : an annual retrospective ; 2.2010)

2010

Series title	Defect and diffusion forum ; 307 Defects and diffusion, theory and simulation : an annual retrospective ; 2.2010
Language	English
Size	VI, 215 S., Ill., graph. Darst.
Publisher	Trans Tech Publ
Publishing place	Stafa-Zürich u.a.
Document type	Book
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Book: [No title information]

Fisher, David J

Defects and diffusion in metals

(Defect and diffusion forum ; 305/306 ; Defects and diffusion in metals : an annual retrospective ; 12.2010)

2010

Series title	Defect and diffusion forum ; 305/306 Defects and diffusion in metals : an annual retrospective ; 12.2010
Language	English
Size	VII, 369 S., graph. Darst.
Publisher	Trans Tech Publ
Publishing place	Stafa-Zürich u.a.
Document type	Book
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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