title: Individual patient data meta-analysis : Cervical stitch (cerclage) for preventing pregnancy loss in women.
abstract: BACKGROUND: Cervical cerclage is a surgical procedure involving suturing the cervix with a purse type stitch to keep it closed during pregnancy. This procedure has been used widely in the management of pregnancies considered at high risk of preterm delivery. Several observational studies into the efficacy of cervical cerclage have claimed high rates of successful pregnancy outcome in women with a poor obstetric history attributed to cervical incompetence. However, a recent aggregate data Cochrane review found no such conclusive evidence from seven included randomised studies. Current data suggests that cervical cerclage is likely to benefit women considered to be 'at very high risk' of a second trimester miscarriage due to a cervical factor, however identifying such women remains elusive and many women may be treated unnecessarily. Undertaking an individual patient data (IPD) meta-analysis of the studies will allow us to investigate whether treatment is more effective in particular subgroups. Such an analysis will also provide a more powerful analysis of the predictors of preterm delivery and pregnancy loss, including ultrasound measurement of cervical length, and will allow a more complete analysis of 'time to event' outcomes. METHODS/DESIGN: The analysis will include data from randomised trials comparing the intervention of elective cerclage versus no cerclage or bedrest to prevent miscarriage or pre-term labour. A specific list of data will be requested for each trial, including demographic and obstetric history data. The primary outcomes of interest will be neonatal mortality/morbidity. Attention will also be given to secondary outcomes such as time from randomisation to delivery, preterm delivery before 32 weeks and maternal morbidity. An intention to treat analysis will be performed, with attention paid to assessing clinical and statistical heterogeneity. Multilevel models with patients and trials as the two levels will be explored to investigate treatment effect on various outcomes. Patient-level covariates will be incorporated into the models in an attempt to account for statistical heterogeneity as well as to investigate interactions with treatment effect. DISCUSSION: Predictive models generated from our analysis should lead to more effective counselling of women at risk and a more cost effective use of cerclage.
authors.affiliation: Centre for Medical Statistics and Health Evaluation, University of Liverpool, Liverpool, L69 3BX, UK. a.l.jorgensen@liverpool.ac.uk.
authors.forename: Catrin
authors.initials: C
authors.lastname: Tudur-Smith
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Jorgensen
authors.forename: Zarko
authors.initials: Z
authors.lastname: Alfirevic
authors.forename: Paula R
authors.initials: PR
authors.lastname: Williamson
references.citation: Gynecol Obstet Invest. 1982;13(1):55-60
references.pmid: 7056503
references.citation: Br J Obstet Gynaecol. 1984 Aug;91(8):731-5
references.pmid: 6380565
references.citation: Ann N Y Acad Sci. 1993 Dec 31;703:156-63; discussion 163-5
references.pmid: 8192293
references.citation: Am J Obstet Gynecol. 2000 Oct;183(4):823-9
references.pmid: 11035320
references.citation: Am J Obstet Gynecol. 2004 Oct;191(4):1311-7
references.pmid: 15507959
references.citation: Int J Gynaecol Obstet. 2004 Jun;85(3):283-4
references.pmid: 15145270
references.citation: J Eval Clin Pract. 2002 Aug;8(3):353-9
references.pmid: 12164983
references.citation: BMJ. 1996 Sep 21;313(7059):735-8
references.pmid: 8819447
references.citation: Stat Med. 2002 Sep 30;21(18):2613-22
references.pmid: 12228880
references.citation: Stat Med. 2005 May 30;24(10):1547-61
references.pmid: 15580591
references.citation: Am J Obstet Gynecol. 2001 Nov;185(5):1106-12
references.pmid: 11717642
references.citation: Stat Med. 2005 May 15;24(9):1307-19
references.pmid: 15685717
references.citation: Br J Obstet Gynaecol. 1988 May;95(5):437-45
references.pmid: 2900021
references.citation: Am J Obstet Gynecol. 2000 Oct;183(4):830-5
references.pmid: 11035321
references.citation: Cochrane Database Syst Rev. 2003;(1):CD003253
references.pmid: 12535466
references.citation: Lancet. 1993 Feb 13;341(8842):418-22
references.pmid: 8094183
references.citation: Lancet. 2004 Jun 5;363(9424):1849-53
references.pmid: 15183621
references.citation: JAMA. 2004 May 26;291(20):2457-65
references.pmid: 15161896