eprintid: 1490782 rev_number: 23 eprint_status: archive userid: 608 dir: disk0/01/49/07/82 datestamp: 2016-05-07 22:49:04 lastmod: 2021-10-04 00:52:36 status_changed: 2016-09-14 13:30:48 type: article metadata_visibility: show creators_name: Yelland, LN creators_name: Sullivan, TR creators_name: Pavlou, M creators_name: Seaman, SR title: Analysis of Randomised Trials Including Multiple Births When Birth Size Is Informative ispublished: pub divisions: UCL divisions: B04 divisions: C06 divisions: F61 keywords: clustering, generalised estimating equations, informative cluster size, multiple births, statistical methodology note: This is the peer reviewed version of the following article: Yelland, LN; Sullivan, TR; Pavlou, M; Seaman, SR; (2015) Analysis of Randomised Trials Including Multiple Births When Birth Size Is Informative. Paediatric and Perinatal Epidemiology, 29 (6) pp. 567-575, which has been published in final form at: http://dx.doi.org/10.1111/ppe.12228. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html#terms). abstract: BACKGROUND: Informative birth size occurs when the average outcome depends on the number of infants per birth. Although analysis methods have been proposed for handling informative birth size, their performance is not well understood. Our aim was to evaluate the performance of these methods and to provide recommendations for their application in randomised trials including infants from single and multiple births. METHODS: Three generalised estimating equation (GEE) approaches were considered for estimating the effect of treatment on a continuous or binary outcome: cluster weighted GEEs, which produce treatment effects with a mother-level interpretation when birth size is informative; standard GEEs with an independence working correlation structure, which produce treatment effects with an infant-level interpretation when birth size is informative; and standard GEEs with an exchangeable working correlation structure, which do not account for informative birth size. The methods were compared through simulation and analysis of an example dataset. RESULTS: Treatment effect estimates were affected by informative birth size in the simulation study when the effect of treatment in singletons differed from that in multiples (i.e. in the presence of a treatment group by multiple birth interaction). The strength of evidence supporting the effectiveness of treatment varied between methods in the example dataset. CONCLUSIONS: Informative birth size is always a possibility in randomised trials including infants from both single and multiple births, and analysis methods should be pre-specified with this in mind. We recommend estimating treatment effects using standard GEEs with an independence working correlation structure to give an infant-level interpretation. date: 2015-11 date_type: published official_url: http://dx.doi.org/10.1111/ppe.12228 oa_status: green full_text_type: other pmcid: PMC4847643 language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1051029 doi: 10.1111/ppe.12228 lyricists_name: Pavlou, Menelaos lyricists_id: MPAVL11 full_text_status: public publication: Paediatric and Perinatal Epidemiology volume: 29 number: 6 pagerange: 567-575 event_location: England issn: 1365-3016 citation: Yelland, LN; Sullivan, TR; Pavlou, M; Seaman, SR; (2015) Analysis of Randomised Trials Including Multiple Births When Birth Size Is Informative. Paediatric and Perinatal Epidemiology , 29 (6) pp. 567-575. 10.1111/ppe.12228 <https://doi.org/10.1111/ppe.12228>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1490782/1/Pavlou_Informative%20Cluster%20Size%20for%20Perinatal%20Trials%20Main%20Article%20Accepted.pdf