Methods research

Group members also conduct methodological research relating either specifically to IPD meta-analysis or to inform the conduct of systematic reviews more generally.

Click on the links below for more information on some of the topics that have been addressed by members of the Methods Group

Please note: This is not a comprehensive list of all existing IPD methodological research publications, but rather those submitted by Methods Group members.

          - Analysis
          - Bias
          - Obtaining IPD
          - Use/applications of IPD

"State of the art of IPD" paper series

Uptake of systematic reviews and meta-analyses based on individual participant data in clinical practice guidelines: descriptive study. Vale C et al. BMJ 2015 (PMID: 25747860)

How individual participant data meta-analyses have influenced trial design, conduct and analysis. Tierney JF et al. J Clin Epidemiol 2015. (PMID: 26186982)

Individual participant data (IPD) meta-analyses of randomised controlled trials: guidance on their use. Tierney JF et al. PLoS Med 2015. (PMID: 26196287)

Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data: The PRISMA-IPD statement. Stewart L et al. JAMA 2015. (PMID: 25919529)

Individual participant data (IPD) meta-analysis of diagnostic and prognostic modeling studies: a practical introduction to their rationale and conduct. Debray T et al. PLoS Med 2015 (PMID: 26461078)



A Poisson approach to the validation of failure time surrogate endpoints in individual patient data meta-analyses. Rotolo F et al. Stat Methods Med Res 2017. (PMID: 28681681)

Meta-analytical methods to identify who benefits most from treatments: daft, deluded, or deft approach?. Fisher DJ et al. BMJ 2017. (PMID: 28258124)

Bias and precision of methods for estimating the difference in restricted mean survival time from an individual patient data meta-analysis. Lueza B et al. BMC Med Res Methodol 2016. (PMID: 27025706)

Erratum to: Bias and precision of methods for estimating the difference in restricted mean survival time from an individual patient data meta-analysis. Lueza B et al BMC Med Res Methodol 2016. (PMID: 27306030)

Difference in Restricted Mean Survival Time for Cost-Effectiveness Analysis Using Individual Patient Data Meta-Analysis: Evidence from a Case Study. Lueza B et al. PLoS One 2016. (PMID: 26960150)

Multivariate meta-analysis using individual participant data. Riley R et al. Res Syn Methods 2015. (PMID:26099484)

Get real in individual participant data (IPD) meta-analysis: a review of the methodology. Debray TPA et al. Res Syn Methods 2015. (PMID: 26287812)

Individual Participant Data Meta-Analysis for a Binary Outcome: One-Stage or Two-Stage? Debray T et al. PLoS One 2013. (PMID: 23585842)

Meta-analysis of randomised trials with a continuous outcome according to baseline imbalance and availability of individual participant data. Riley R et al. Stat Med 2013. (PMID: 23303608)

Two-stage meta-analysis of survival data from individual participants using percentile ratios. Barrett JK et al. Stat Med 2012. (PMID: 22825835)

Random-effects meta-analysis of time-to-event data using the expectation–maximisation algorithm and shrinkage estimators. Simmonds MC et al. Res Synth Methods 2012. (doi: 10.1002/jrsm.1067)

Statistical analysis of individual participant data meta-analyses: a comparison of methods and recommendations for practice. Stewart GB et al. PLoS One 2012 (PMID: 23056232)

Individual participant data meta-analysis of survival data using Poisson regression models. Crowther M et al. BMC Med Res Meth 2012. (PMID: 22443286)

Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics. Bowden J et al. BMC Med Res Methodol 2011. (PMID: 21473747)

A critical review of methods for the assessment of patient-level interactions in individual patient data (IPD) meta-analysis of randomised trials, and guidance for practitioners. Fisher DJ et al. J Clin Epidemiol 2011. (PMID: 21411280)

Meta-analysis of time-to-event data: a comparison of two-stage methods. Simmonds MC et al. Res Synth Methods 2011. (doi: 10.1002/jrsm.44)

Individual patient data meta-analysis of time-to-event outcomes: one-stage versus two-stage approaches for estimating the hazard ratio under a random effects model. Bowden J et al. Res Synthesis Method 2011. (doi: 10.1002/jrsm.45)

A joint model for the dependence between clustered times to tumor progression and deaths: a meta-analysis of chemotherapy in head and neck cancer. Rondeau V et al, on behalf of the MACH-NC collaborative Group. Stat Methods Med Res 2011. (PMID: 22025414)

Early mobilization after stroke: an example of an individual patient data meta-analysis of a complex intervention. Craig LE et al. Stroke 2010. (PMID: 20947855)

Investigating trial and treatment heterogeneity in an individual patient data meta-analysis of survival data by means of the penalized maximum likelihood approach. Rondeau V et al. Stat Med 2008. (PMID: 18069745)

Meta-analysis of continuous outcomes combining individual patient data and aggregate data. Riley RD, et al. Stat Med 2008. (PMID: 18069721)

Meta-analysis of individual patient data from randomised trials - a review of methods used in practice. Simmonds MC et al. Clinical Trials 2005. (PMID: 16279144)

Covariate heterogeneity in meta-analysis: criteria for deciding between meta-regression and individual patient data. Simmonds MC et al. Stat Med 2007. (PMID: 17195960)

Treating individuals 4: can meta-analysis help target interventions at individuals most likely to benefit? Thompson SG et al. Lancet 2005. (PMID: 15664231)

Random effects survival models gave a better understanding of heterogeneity in individual patient data meta-analyses. Michiels S et al. J Clin Epidemiol 2005. (PMID: 15718112

Meta-regression detected associations between heterogeneous treatment effects and study-level, but not patient-level, factors. Schmid C et al. J Clin Epidemiol 2004. (PMID: 15358396)

A graphical method for exploring heterogeneity in meta-analyses: application to a meta-analysis of 65 trials. Baujat B et al. Stat Med 2002. (PMID: 12228882)

Meta-analysis of ordinal outcomes using individual patient data. Whitehead A et al. Stat Med 2001. (PMID: 11468762)

Meta-analysis of continuous outcome data from individual patients. Higgins JPT et al. Stat Med 2001. (PMID: 11468761)

Exploring heterogeneity in randomized trials via meta-analysis. Schmid CH. Drug Inf J 1999. (Link to abstract)

Assessing treatment-time interaction in clinical trials with time to event data: a meta-analysis of hypertension trials. Boutitie F, et al. Stat Med. 1998. (PMID: 9921608)


IPD vs summary data meta-analysis

Selective cutoff reporting in studies of diagnostic test accuracy: A comparison of traditional and individual patient data meta-analyses of the Patient Health Questionnaire-9 depression screening tool. Levis B et al. Am J Epidemiol 2017. (PMID: 28419203)

Individual patient data meta-analyses compared with meta-analyses based on aggregate data. Tudur Smith C et al. Cochrane Database Syst Rev 2016. (PMID: 27595791)

Meta-analysis of individual patient data versus aggregate data from longitudinal clinical trials. Jones AP et al. Clin Trials 2009. (PMID: 19254930)

Empirical comparison of subgroup effects in conventional and individual patient data meta-analyses. Koopman L et al. Int J Technol Assess Health Care 2008. (PMID: 18601805)

An overview of methods and empirical comparison of aggregate data and individual patient data results for investigating heterogeneity in meta-analysis of time-to-event outcomes. Tudur Smith C et al. J Eval Clin Practice 2005. (PMID: 16164588)

Meta-analysis when only the median survival times are known: a comparison with individual patient data results. Michiels S et al. Int J Technol Assess Health Care 2005. (PMID: 15736523)

Individual patient-versus group-level data meta-regressions for the investigation of treatment effect modifiers: ecological bias rears its ugly head. Berlin JA et al. Anti-Lymphocyte Antibody Induction Therapy Study Group. Stat Med 2002 (PMID: 11813224)

Individual patient-versus literature-based meta-analysis of survival data: time to event and event rate at a particular time can make a difference, an example based on head and neck cancer. Duchateau L et al. Control Clin Trials 2001 (PMID: 11578787)

Estimating numbers of event from the Kaplan-Meier curve for incorporation in a literature-based meta-analysis: what you see is what you can't get! Duchateau L et al. Biometrics 2000 (PMID: 10985232)


IPD methodology for study designs other than RCTs

Explicit inclusion of treatment in prognostic modeling was recommended in observational and randomized settings. Groenwold et al. J Clin Epidemiol 2016. (PMID: 27045189)

A closed testing procedure to select an appropriate method for updating prediction models. Vergouwe et al. Stat Med 2017. (PMID: 27891652)

A comparison of bivariate, multivariate random-effects, and Poisson correlated gamma-frailty models to meta-analyze individual patient data of ordinal scale diagnostic tests. Simoneau et al. Biom J 2017 (PMID: 28692782)

A guide to systematic review and meta-analysis of prediction model performance. Debray TP et al. BMJ 2017. (PMID: 28057641)

Meta-analysis of prediction model performance across multiple studies: Which scale helps ensure between-study normality for the C-statistic and calibration measures. Snell KI et al. Stats Methods Med Res 2017. (PMID: 28480827)

External validation of clinical prediction models using big datasets from e-health records or IPD meta-analysis: opportunities and challenges. Riley RD et al. BMJ 2016. (PMID: 27334381)

Multivariate meta-analysis of individual participant data helped externally validate the performance and implementation of a prediction Snell KIE et al. JCE 2016. (PMID: 26142114)

A simulation study of sample size demonstrated the importance of the number of events per variable to develop prediciton models in clustered data. Wynants L et al. JCE 2015. (PMID: 25817942)

Imputation of systematically missing predictors in an individual participant data meta-analysis: a generalized approach using MICE. Jolani S et al. Stat Med 2015. (PMID: 25663182)

Developing and validating risk prediction models in an individual participant data meta-analysis. Ahmed I et al. BMC Med Res Methodol 2014. (PMID: 24397587)

Meta-analysis and aggregation of multiple published prediciton models. Debray TP et al. Stat Med 2014. (PMID: 24752993)

A framework for developing, implementing, and evaluating clinical prediction models in an individual participant data meta-analysis. Debray TP et al. Stat Med 2013. (PMID: 23307585)

Concordance measures in shared frailty models: application to clustered data in cancer prognosis. Mauguen A et al. Stat Med 2012. (PMID: 23729305)

Incorporating published univariable associations in diagnostic and prognostic modeling. Debray TP et al. BMC Med Res Methodol 2012 (PMID: 22883206)

Common carotid intima-media thickness measurements in cardiovascular risk prediction: a meta-analysis. Den Ruijter HM et al. JAMA 2012. (PMID: 22910757)

Aggregating published prediction models with individual participant data: a comparison of different approaches. Debray TP et al. Stat Med 2012. (PMID: 22733546)

Individual patient data meta-analysis of prognostic factor studies: state of the art? Abo Zaid G et al. BMC Med Res Meth 2012. (PMID: 22530717)

Constructing a database of individual clinical trials for longitudinal analysis. Schmid C et al. Control Clin Trials 2003. (PMID: 12757997)


Indirect comparisons / Network meta-analysis

Combining randomized and non-randomized evidence in network meta-analysis. Efthimiou et al. Stat Med 2017. (PMID: 2808391)

An overview of methods for network meta-analysis using individual participant data: when do benefits arise? Debray TPA et al. Technical report 2017. (PMID: 27487843)

Methodological guidance, recommendations and illustrative case studies for (network) meta-analysis and modelling to predict real-world effectiveness using individual participant and/or aggregate data. Debray TPA et al. Technical report 2017. (doi: 10.13140/RG.2.2.36349.36327)

A scoping review of indirect comparison methods and applications using individual patient data. Veroniki AA et al. BMC Med Res Methodol 2016. (PMID: 27116943)

GetReal in network meta-analysis: a review of the methodology. Efthimiou O et al. Res Synth Methods 2016. (PMID: 26754852)

Mixed treatment comparison meta-analysis of altered fractionated radiotherapy and chemotherapy in head and neck cancer. Blanchard P et al, on behalf of the MACH-NC and MARCH Collaborative Groups. J Clin Epidemiol 2011. (PMID: 21330105)



Can trial quality be reliably assessed from published reports of cancer trials: evaluation of risk of bias assessments in systematic reviews. Vale CL et al. BMJ 2013 (PMID: 23610376)

Assessment of publication bias, selection bias and unavailable data in meta-analyses using individual participant data: a database survey. Ahmed I et al. BMJ 2012. (PMID: 22214758)


 Obtaining IPD

Exploring changes over time and characteristics associated with data retrieval across individual participant data meta-analyses: systematic reviewNevitt S et al. BMJ 2017. (PMID: 28381561)

Contacting authors to retrieve individual patient data: study protocol for a randomized controlled trial. Veroniki AA et al. Trials 2016. (PMID: 26975720) (Webinar)


 Use/applications of IPD

Practical implications of using real-world-evidence (RWE) in comparative effectiveness research: learnings from IMI-GetReal. Makady et al. J Comp Eff Res 2017. (PMID: 28857631)

Resource implications of preparing individual participant data from a clinical trial to share with external researchers. Tudur Smith et al. Trials 2017 (PMID: 28712359)

Les nouvelles applications des méta-analyses d’essais randomisés sur données individuelles. Lueza B et al. Bull Cancer 2017. (PMID: 27908441)