Skip to main content
Erschienen in: Reproductive Health 1/2018

Open Access 01.12.2018 | Commentary

Features of randomised trials designed by the NPEU Perinatal Trials Service during Adrian Grant’s directorship

verfasst von: Diana Elbourne

Erschienen in: Reproductive Health | Ausgabe 1/2018

Abstract

Adrian Grant pioneered methodological innovations in the randomised trials organised by the Perinatal Trials Service established at the national Perinatal Epidemiology Unit in Oxford, UK. This Commentary discusses these innovations, and shows the wide range of trials designed under his directorship.

Background

In his article recording Adrian Grant’s pioneering use of evidence synthesis in perinatal medicine between 1980 and 1992, Iain Chalmers [1] quoted from a 1984 letter published in The Lancet which Iain and I had co-authored with Adrian [2]. In that letter we alluded to some of the additional principles - beyond the need for systematic review of existing evidence - which became methodological features of the wide range of randomised trials organised by the Perinatal Trials Service (PTS) established at the national Perinatal Epidemiology Unit (NPEU). The trials are listed in Appendix 1.

Methodological features

Appropriate size

Our 1984 letter concluded with a warning that, to avoid the dangers of false inferences from non-randomised comparisons and small randomised trials, many perinatal controlled trials require sample sizes larger than any single unit can generate within a reasonable length of time. Although one centre was sufficient to obtain sufficient sample sizes to address some questions, for other questions, multicentre (often international) trials were needed.

Secure, random allocation

The NPEU PTS used a variety of contextually appropriate methods for secure random allocation - sequentially numbered sealed opaque envelopes, sequentially numbered drug vials, and central random allocation when there was sufficient time to make a call and where reasonable telecommunications existed.

Appropriate design

Most of the trials used two-armed, individually randomised designs. Where appropriate, more complex designs were employed, including factorial trials and a cluster randomised trial.

Involving the views of care-givers and patients and their families

The PTS recognised that our work needed to address questions considered important by caregivers and families, so they were involved in deciding which questions to address, trial design and conduct, and dissemination of results. Taking account of families meant that many PTS trials investigated long term outcomes, such as pain, dyspareunia and incontinence for women, and disability for children.

Facilitating infrastructure

A programme of randomised trials to support these methodological underpinnings needed an infrastructure and the PTS was established in 1982 “to provide a service to busy clinicians who wish to mount large simple-in-design randomized trials...[aiming] to identify moderate, but clinically useful, effects of promising treatments for the most important problems in perinatal care” [3].
The PTS had a flexible five-person core staff and others employed to work on specific trials. This continuity of staff enabled us to build standard operating systems. International trials needed particularly careful coordination, and the provision of trials materials in a number of languages. The eclampsia trial [4], for example was preceded by a pilot study in Argentina, with materials in Spanish.

Adrian Grant’s legacy for perinatal trials

Over the years that Adrian Grant designed perinatal trials in the NPEU, the above methodological innovations and others are listed in the Table 1 below.
Table 1
Adrian Grant’s methodological innovations
• Identification and prioritisation of important questions
• Systematic reviews
• Alliance of patients, carers, and clinicians
• Efficient trial conduct
• Secure randomisation
• Appropriate design, outcomes, and size
• Support for participants
• Newsletters
• Integral economic evaluation
• Embedded methodological research
• Long term follow up
• Feedback of trial results
Adrian continued to support trials in Aberdeen after his move to direct the Health Services Research Unit there (https://​www.​abdn.​ac.​uk/​hsru) in 1994, and then for the National Institute for Health Research (http://​www.​nihr.​ac.​uk).

Conclusions

Many people are grateful for Adrian’s methodological rigor, his innovative approaches, and his generosity of support, mentoring and teaching. The lives of many babies and their families have been improved by Adrian’s pioneering work in perinatal trials, and the PTS that Adrian created has gone on to become a highly successful Clinical Trials Unit (https://​www.​npeu.​ox.​ac.​uk/​ctu).

Author’s contribution

DE is the sole contributor. The author read and approved the final manuscript.

Ethics approval

Not applicable.
Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.
Anhänge

Appendix

Randomised trials designed by the NPEU Perinatal Trials Service during Adrian Grant’s directorship

Table 2
Antenatal interventions
• Chorion villus sampling vs amniocentesis [5]
• Cervical cerclage [6, 7]
• Breast shells and Hoffman’s exercises [8]
• Formal fetal movement counting [9]
• Placental grading by ultrasonography [10]
• Anti-convulsants for eclampsia [4]
• Low dose aspirin [11, 12]
• Fish-oil supplementation [13]
• ‘Know your Midwife’ [14]
• Social support [15]
Table 3
Intrapartum interventions
• Dublin intrapartum fetal heart rate monitoring [1619]
• Vacuum extraction vs forceps (Portsmouth operative delivery) [2022]
• Vacuum extraction: different cups [23]
• Fetal scalp electrode [24]
• Perineal management (Berkshire) [25, 26]
• Perineal suture (Southmead) [27]
• Catgut for the repair of perineal trauma [28, 29]
• Ipswich perineal repair [3033]
Table 4
Postnatal interventions
• Pelvic floor exercises [34]
• Salt and Savlon bath concentrate [35]
• Ultrasound and pulsed electromagnetic energy treatment for perineal trauma [36, 37]
Table 5
Neonatal interventions
• Neonatal ventriculomegaly [38, 39]
• Dexamethasone [40, 41]
• Prophylactic ethamsylate [42, 43]
• Surfactant [44]
• Extracorporeal membrane oxygenation [4553]
Literatur
2.
Zurück zum Zitat Chalmers I, Elbourne D, Grant A. Phenobarbitone and periventricular haemorrhage. Lancet. 1984;1:286. Chalmers I, Elbourne D, Grant A. Phenobarbitone and periventricular haemorrhage. Lancet. 1984;1:286.
3.
Zurück zum Zitat Grant AM. Rationale for and work of the perinatal trials service. Early Hum Dev. 1992;29:305–8.CrossRefPubMed Grant AM. Rationale for and work of the perinatal trials service. Early Hum Dev. 1992;29:305–8.CrossRefPubMed
4.
Zurück zum Zitat The Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from the collaborative eclampsia trial. Lancet. 1995;345:1455–63.CrossRef The Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from the collaborative eclampsia trial. Lancet. 1995;345:1455–63.CrossRef
5.
Zurück zum Zitat MRC Working Party on the Evaluation of Chorion Villus Sampling. Medical Research Council European trial of chorion villus sampling. Lancet. 1991;337:1491–9.CrossRef MRC Working Party on the Evaluation of Chorion Villus Sampling. Medical Research Council European trial of chorion villus sampling. Lancet. 1991;337:1491–9.CrossRef
6.
Zurück zum Zitat Chalmers I, Grant AM. Cervical cerclage. Br J Obstet Gynaecol. 1982;89(7):497–8.CrossRef Chalmers I, Grant AM. Cervical cerclage. Br J Obstet Gynaecol. 1982;89(7):497–8.CrossRef
7.
Zurück zum Zitat Rush RW, Isaacs S, McPherson K, Jones L, Chalmers I, Grant AM. A randomized controlled trial of cervical cerclage in women at high risk of spontaneous preterm delivery. Br J Obstet Gynaecol. 1984;91(8):724–30.CrossRefPubMed Rush RW, Isaacs S, McPherson K, Jones L, Chalmers I, Grant AM. A randomized controlled trial of cervical cerclage in women at high risk of spontaneous preterm delivery. Br J Obstet Gynaecol. 1984;91(8):724–30.CrossRefPubMed
8.
Zurück zum Zitat Alexander JM, Grant AM, Campbell MJ. Randomized controlled trial of breast shells and Hoffman's exercises for inverted and non-protractile nipples. Br Med J. 1992;304:1030–2.CrossRef Alexander JM, Grant AM, Campbell MJ. Randomized controlled trial of breast shells and Hoffman's exercises for inverted and non-protractile nipples. Br Med J. 1992;304:1030–2.CrossRef
9.
Zurück zum Zitat Grant AM, Elbourne DR, Valentin L, Alexander S. Routine formal fetal movement counting and risk of antepartum late death in normally-formed singletons. Lancet. 1989;2:345–9.CrossRefPubMed Grant AM, Elbourne DR, Valentin L, Alexander S. Routine formal fetal movement counting and risk of antepartum late death in normally-formed singletons. Lancet. 1989;2:345–9.CrossRefPubMed
10.
Zurück zum Zitat Proud J, Grant AM. Third trimester placental grading by ultrasonography as a test of fetal wellbeing. Br Med J. 1987;294:1641–4.CrossRef Proud J, Grant AM. Third trimester placental grading by ultrasonography as a test of fetal wellbeing. Br Med J. 1987;294:1641–4.CrossRef
11.
Zurück zum Zitat CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet. 1994;343:619–29.CrossRef CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet. 1994;343:619–29.CrossRef
12.
Zurück zum Zitat Rotchell YE, Cruickshank JK, Phillips Gay M, Griffiths J, Stewart A, Farrell B, Ayers S, Hennis A, Grant AM, Duley L, Collins RE. Barbados low dose aspirin study in pregnancy (BLASP): a randomised trial for the prevention of pre-eclampsia and its complications. Br J Obstet Gynaecol. 1998;105:286–92.CrossRefPubMed Rotchell YE, Cruickshank JK, Phillips Gay M, Griffiths J, Stewart A, Farrell B, Ayers S, Hennis A, Grant AM, Duley L, Collins RE. Barbados low dose aspirin study in pregnancy (BLASP): a randomised trial for the prevention of pre-eclampsia and its complications. Br J Obstet Gynaecol. 1998;105:286–92.CrossRefPubMed
13.
Zurück zum Zitat Olsen SF, Sorensen JD, Secher NJ, Hedegaard M, Henriksen TB, Hansen HS, Grant AM. Randomized controlled trial of the effect of fish-oil supplementation on pregnancy duration. The lancet. 1992. 1992;339(8800):1003–7. Olsen SF, Sorensen JD, Secher NJ, Hedegaard M, Henriksen TB, Hansen HS, Grant AM. Randomized controlled trial of the effect of fish-oil supplementation on pregnancy duration. The lancet. 1992. 1992;339(8800):1003–7.
14.
Zurück zum Zitat Flint C, Poulengeris P, Grant AM. The ‘Know your Midwife’ scheme - a randomised trial of continuity of care by a team of midwives. Midwifery. 1989;5:11–6.CrossRefPubMed Flint C, Poulengeris P, Grant AM. The ‘Know your Midwife’ scheme - a randomised trial of continuity of care by a team of midwives. Midwifery. 1989;5:11–6.CrossRefPubMed
15.
Zurück zum Zitat Oakley A, Rajan L, Grant AM. Social support and pregnancy outcome. Br J Obstet Gynaecol. 1990;97:155–62.CrossRefPubMed Oakley A, Rajan L, Grant AM. Social support and pregnancy outcome. Br J Obstet Gynaecol. 1990;97:155–62.CrossRefPubMed
16.
Zurück zum Zitat MacDonald D, Grant AM, Sheridan-Pereira M, Boylan P, Chalmers I. The Dublin randomized controlled trial of intrapartum fetal heart rate monitoring. Am J Obstet Gynecol 1985. 1985;152(5):524–39.CrossRef MacDonald D, Grant AM, Sheridan-Pereira M, Boylan P, Chalmers I. The Dublin randomized controlled trial of intrapartum fetal heart rate monitoring. Am J Obstet Gynecol 1985. 1985;152(5):524–39.CrossRef
17.
Zurück zum Zitat Garcia J, Corry M, MacDonald D, Elbourne DR, Grant AM. Mothers’ views of continuous electronic fetal heart monitoring and intermittent auscultation in a randomized controlled trial. Birth. 1985;12(2):79–86.CrossRefPubMed Garcia J, Corry M, MacDonald D, Elbourne DR, Grant AM. Mothers’ views of continuous electronic fetal heart monitoring and intermittent auscultation in a randomized controlled trial. Birth. 1985;12(2):79–86.CrossRefPubMed
18.
Zurück zum Zitat Grant AM. Some answers to questions raised about the Dublin trial. Birth. 1986;13(4):255–6.CrossRef Grant AM. Some answers to questions raised about the Dublin trial. Birth. 1986;13(4):255–6.CrossRef
19.
Zurück zum Zitat Grant AM, O'Brien N, Joy M-T, Hennessy E, MacDonald D. Cerebral palsy among children born during the Dublin randomized trial of intrapartum monitoring. Lancet 1989;ii(8674):1233–1236. Grant AM, O'Brien N, Joy M-T, Hennessy E, MacDonald D. Cerebral palsy among children born during the Dublin randomized trial of intrapartum monitoring. Lancet 1989;ii(8674):1233–1236.
20.
Zurück zum Zitat Vacca A, Grant AM, Wyatt G, Chalmers I. Portsmouth operative delivery trial: a comparison of vacuum extraction and forceps delivery. Br J Obstet Gynaecol. 1983;90(12):1107–12.CrossRefPubMed Vacca A, Grant AM, Wyatt G, Chalmers I. Portsmouth operative delivery trial: a comparison of vacuum extraction and forceps delivery. Br J Obstet Gynaecol. 1983;90(12):1107–12.CrossRefPubMed
21.
Zurück zum Zitat Garcia J, Anderson J, Vacca A, Elbourne DR, Grant AM, Chalmers I. Views of women and their medical and midwifery attendants about instrumental delivery using vacuum extraction and forceps. J Psychosom Obstet Gynaecol. 1985;4:1–9.CrossRef Garcia J, Anderson J, Vacca A, Elbourne DR, Grant AM, Chalmers I. Views of women and their medical and midwifery attendants about instrumental delivery using vacuum extraction and forceps. J Psychosom Obstet Gynaecol. 1985;4:1–9.CrossRef
22.
Zurück zum Zitat Carmody F, Grant AM, Mutch LM, Vacca A, Chalmers I. Follow up of babies delivered in a randomized controlled comparison of vacuum extraction and forceps delivery. Acta Obstet Gynecol Scand. 1986;65(7):763–6.CrossRefPubMed Carmody F, Grant AM, Mutch LM, Vacca A, Chalmers I. Follow up of babies delivered in a randomized controlled comparison of vacuum extraction and forceps delivery. Acta Obstet Gynecol Scand. 1986;65(7):763–6.CrossRefPubMed
23.
Zurück zum Zitat Carmody F, Grant AM, Somchiwong M. Vacuum extraction: a randomized controlled comparison of the new generation cup with the original bird cup. J Perinat Med. 1986;14:95–100.CrossRefPubMed Carmody F, Grant AM, Somchiwong M. Vacuum extraction: a randomized controlled comparison of the new generation cup with the original bird cup. J Perinat Med. 1986;14:95–100.CrossRefPubMed
24.
Zurück zum Zitat Needs L, Grant AM, Sleep J, Ayers S, Henson G. A randomized controlled trial to compare three types of fetal scalp electrode. Br J Obstet Gynaecol. 1992;99:302–6.CrossRefPubMed Needs L, Grant AM, Sleep J, Ayers S, Henson G. A randomized controlled trial to compare three types of fetal scalp electrode. Br J Obstet Gynaecol. 1992;99:302–6.CrossRefPubMed
25.
Zurück zum Zitat Sleep J, Grant AM, Garcia J, Elbourne DR, Spencer JAD, Chalmers I. West Berkshire perineal management trial. Br Med J. 1984;289:587–90.CrossRef Sleep J, Grant AM, Garcia J, Elbourne DR, Spencer JAD, Chalmers I. West Berkshire perineal management trial. Br Med J. 1984;289:587–90.CrossRef
26.
Zurück zum Zitat Sleep J, Grant AM. West Berkshire perineal management trial: three year follow up. Br Med J. 1987;295:749–51.CrossRef Sleep J, Grant AM. West Berkshire perineal management trial: three year follow up. Br Med J. 1987;295:749–51.CrossRef
27.
Zurück zum Zitat Mahomed K, Grant AM, Ashurst H, James D. The Southmead perineal suture study. A randomized comparison of suture materials and suturing techniques for repair of perineal trauma. Br J Obstet Gynaecol 1989 1989;96(11):1272–1280. Mahomed K, Grant AM, Ashurst H, James D. The Southmead perineal suture study. A randomized comparison of suture materials and suturing techniques for repair of perineal trauma. Br J Obstet Gynaecol 1989 1989;96(11):1272–1280.
28.
Zurück zum Zitat Spencer JAD, Grant AM, Elbourne DR, Garcia J, Sleep J. A randomized comparison of glycerol-impregnated chromic catgut with untreated chromic catgut for the repair of perineal trauma. Br J Obstet Gynaecol. 1986;93:426–30.CrossRefPubMed Spencer JAD, Grant AM, Elbourne DR, Garcia J, Sleep J. A randomized comparison of glycerol-impregnated chromic catgut with untreated chromic catgut for the repair of perineal trauma. Br J Obstet Gynaecol. 1986;93:426–30.CrossRefPubMed
29.
Zurück zum Zitat Grant AM, Sleep J, Ashurst H, Spencer JAD. Dyspareunia associated with the use of glycerol-impregnated catgut to repair perineal trauma - report of a three-year follow-up study. Br J Obstet Gynaecol. 1989;96:741–3.CrossRefPubMed Grant AM, Sleep J, Ashurst H, Spencer JAD. Dyspareunia associated with the use of glycerol-impregnated catgut to repair perineal trauma - report of a three-year follow-up study. Br J Obstet Gynaecol. 1989;96:741–3.CrossRefPubMed
30.
Zurück zum Zitat Mackrodt C, Gordon B, Fern E, Ayers S, Truesdale A, Grant AM. The Ipswich childbirth study: 2. A randomised comparison of polyglactin 910 with chromic catgut for postpartum perineal repair. Br J Obstet Gynaecol. 1998;105(4):441–5.CrossRefPubMed Mackrodt C, Gordon B, Fern E, Ayers S, Truesdale A, Grant AM. The Ipswich childbirth study: 2. A randomised comparison of polyglactin 910 with chromic catgut for postpartum perineal repair. Br J Obstet Gynaecol. 1998;105(4):441–5.CrossRefPubMed
31.
Zurück zum Zitat Gordon B, Mackrodt C, Fern E, Truesdale A, Ayers S, Grant AM. The Ipswich childbirth study: 1. A randomised evaluation of two stage postpartum perineal repair leaving the skin unsutured. Br J Obstet Gynaecol. 1998;105(4):435–40.CrossRefPubMed Gordon B, Mackrodt C, Fern E, Truesdale A, Ayers S, Grant AM. The Ipswich childbirth study: 1. A randomised evaluation of two stage postpartum perineal repair leaving the skin unsutured. Br J Obstet Gynaecol. 1998;105(4):435–40.CrossRefPubMed
32.
Zurück zum Zitat Grant AM, Gordon B, Mackrodt C, Fern E, Truesdale A, Ayers S. The Ipswich childbirth study: one year follow-up of alternative methods used in perineal repair. Br J Obstet Gynaecol. 2001;108:34–40. Grant AM, Gordon B, Mackrodt C, Fern E, Truesdale A, Ayers S. The Ipswich childbirth study: one year follow-up of alternative methods used in perineal repair. Br J Obstet Gynaecol. 2001;108:34–40.
33.
Zurück zum Zitat Petrou S, Gordon B, Mackrodt C, Fern E, Ayers S, Grant AM, Truesdale A, McCandlish R. How cost-effective is it to leave perineal skin unsutured? British J Midwifery. 2001;9(4):209–14.CrossRef Petrou S, Gordon B, Mackrodt C, Fern E, Ayers S, Grant AM, Truesdale A, McCandlish R. How cost-effective is it to leave perineal skin unsutured? British J Midwifery. 2001;9(4):209–14.CrossRef
34.
35.
Zurück zum Zitat Sleep J, Grant AM. Effects of salt and Savlon bath concentrate postpartum. Nurs Times. 1988;84:55–7.PubMed Sleep J, Grant AM. Effects of salt and Savlon bath concentrate postpartum. Nurs Times. 1988;84:55–7.PubMed
36.
Zurück zum Zitat Everett T, McIntosh J, Grant AM. Ultrasound therapy for persistent postnatal perineal pain and dyspareunia: a randomised placebo-controlled trial. Physiotherapy. 1992;78:263–7.CrossRef Everett T, McIntosh J, Grant AM. Ultrasound therapy for persistent postnatal perineal pain and dyspareunia: a randomised placebo-controlled trial. Physiotherapy. 1992;78:263–7.CrossRef
37.
Zurück zum Zitat Grant AM, Sleep J, McIntosh J, Ashurst H. Ultrasound and pulsed electromagnetic energy treatment for perineal trauma. A randomized placebo-controlled trial. Br J Obstet Gynaecol. 1989;96:434–9.CrossRefPubMed Grant AM, Sleep J, McIntosh J, Ashurst H. Ultrasound and pulsed electromagnetic energy treatment for perineal trauma. A randomized placebo-controlled trial. Br J Obstet Gynaecol. 1989;96:434–9.CrossRefPubMed
38.
Zurück zum Zitat Ventriculomegaly Trial Group. Randomised trial of early tapping in neonatal posthaemorrhagic ventricular dilatation. Arch dis child. 1990. 1990;65(1):3–10. Ventriculomegaly Trial Group. Randomised trial of early tapping in neonatal posthaemorrhagic ventricular dilatation. Arch dis child. 1990. 1990;65(1):3–10.
39.
Zurück zum Zitat Ventriculomegaly Trial Group. Randomised trial of early tapping in neonatal posthaemorrhagic ventricular dilatation: results at 30 months. Arch dis child. 1994. 1994;70(2):F129–36. Ventriculomegaly Trial Group. Randomised trial of early tapping in neonatal posthaemorrhagic ventricular dilatation: results at 30 months. Arch dis child. 1994. 1994;70(2):F129–36.
40.
Zurück zum Zitat Collaborative Dexamethasone Trial Group. Dexamethasone therapy in neonatal chronic lung disease: an international placebo controlled trial. Pediatrics. 1991;88:421–7. Collaborative Dexamethasone Trial Group. Dexamethasone therapy in neonatal chronic lung disease: an international placebo controlled trial. Pediatrics. 1991;88:421–7.
41.
Zurück zum Zitat Jones RAK, Wincott E, Elbourne DR, Grant AM. Controlled trial of dexamethasone in neonatal chronic lung disease: a 3-year follow-up. Pediatrics. 1995;96:897–906.PubMed Jones RAK, Wincott E, Elbourne DR, Grant AM. Controlled trial of dexamethasone in neonatal chronic lung disease: a 3-year follow-up. Pediatrics. 1995;96:897–906.PubMed
42.
Zurück zum Zitat The EC Ethamsylate Trial Group. The EC randomised controlled trial of prophylatic ethamsylate for very preterm neonates: early mortality and morbidity. Arch Dis Child. 1994;70:F201–5.CrossRef The EC Ethamsylate Trial Group. The EC randomised controlled trial of prophylatic ethamsylate for very preterm neonates: early mortality and morbidity. Arch Dis Child. 1994;70:F201–5.CrossRef
43.
Zurück zum Zitat Elbourne DR, Ayers S, Dellagrammaticas H, Johnson A, Leloup M, Lenoir-Piat S. EC Ethamsylate trial group. Randomised controlled trial of prophylactic ethamsylate: follow up at 2 years of age. Arch Dis Child. 2001;84:F183–7.CrossRef Elbourne DR, Ayers S, Dellagrammaticas H, Johnson A, Leloup M, Lenoir-Piat S. EC Ethamsylate trial group. Randomised controlled trial of prophylactic ethamsylate: follow up at 2 years of age. Arch Dis Child. 2001;84:F183–7.CrossRef
44.
Zurück zum Zitat OSIRIS Collaborative Group. Early versus delayed neonatal administration of a synthetic surfactant - the judgment of OSIRIS. Lancet. 1992;340:1363–9.CrossRef OSIRIS Collaborative Group. Early versus delayed neonatal administration of a synthetic surfactant - the judgment of OSIRIS. Lancet. 1992;340:1363–9.CrossRef
45.
Zurück zum Zitat UK Collaborative ECMO Trial Group. UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation. Lancet. 1996;348:75–82.CrossRef UK Collaborative ECMO Trial Group. UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation. Lancet. 1996;348:75–82.CrossRef
46.
Zurück zum Zitat Howard S, Mugford M, Normand C, Elbourne DR, Grant AM, Field DJ, Johnson A. A cost effectiveness analysis of neonatal ECMO using existing evidence. Int J Technol Assess Health Care. 1996;12:80–92.CrossRefPubMed Howard S, Mugford M, Normand C, Elbourne DR, Grant AM, Field DJ, Johnson A. A cost effectiveness analysis of neonatal ECMO using existing evidence. Int J Technol Assess Health Care. 1996;12:80–92.CrossRefPubMed
47.
Zurück zum Zitat Snowdon C, Garcia J, Elbourne DR. Making sense of randomization: responses of parents of critically ill babies to random allocation of treatment in a clinical trial. Soc Sci Med. 1997;45:1337–55.CrossRefPubMed Snowdon C, Garcia J, Elbourne DR. Making sense of randomization: responses of parents of critically ill babies to random allocation of treatment in a clinical trial. Soc Sci Med. 1997;45:1337–55.CrossRefPubMed
48.
Zurück zum Zitat Snowdon C, Garcia J, Elbourne DR. Reactions of participants to the results of a randomised controlled trial: exploratory study. Br Med J. 1998;317:21–6.CrossRef Snowdon C, Garcia J, Elbourne DR. Reactions of participants to the results of a randomised controlled trial: exploratory study. Br Med J. 1998;317:21–6.CrossRef
49.
Zurück zum Zitat Snowdon C, Elbourne DR, Garcia J. Zelen randomization: attitudes of parents participating in a neonatal clinical trial. Control Clin Trials. 1999;20:149–71.CrossRefPubMed Snowdon C, Elbourne DR, Garcia J. Zelen randomization: attitudes of parents participating in a neonatal clinical trial. Control Clin Trials. 1999;20:149–71.CrossRefPubMed
50.
Zurück zum Zitat Bennett CC, Johnson A, Field DJ, Elbourne DR. For the UK collaborative ECMO trial group. UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation: follow-up to age 4 years. Lancet. 2001;357:1094–6.CrossRefPubMed Bennett CC, Johnson A, Field DJ, Elbourne DR. For the UK collaborative ECMO trial group. UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation: follow-up to age 4 years. Lancet. 2001;357:1094–6.CrossRefPubMed
51.
Zurück zum Zitat Petrou S, Edwards L. Cost-effectiveness analysis of neonatal extracorporeal membrane oxygenation based on four year results from the UK collaborative ECMO trial. Arch Dis Child. 2004;89:F263–F8.CrossRef Petrou S, Edwards L. Cost-effectiveness analysis of neonatal extracorporeal membrane oxygenation based on four year results from the UK collaborative ECMO trial. Arch Dis Child. 2004;89:F263–F8.CrossRef
52.
Zurück zum Zitat Petrou S, Bischof M, Bennett CC, Elbourne DR, Field DJ, McNally H. Cost-effectiveness of neonatal extracorporeal membrane oxygenation based on 7 year results from the United Kingdom collaborative ECMO trial. Pediatrics. 2006;117:1640–9.CrossRefPubMed Petrou S, Bischof M, Bennett CC, Elbourne DR, Field DJ, McNally H. Cost-effectiveness of neonatal extracorporeal membrane oxygenation based on 7 year results from the United Kingdom collaborative ECMO trial. Pediatrics. 2006;117:1640–9.CrossRefPubMed
53.
Zurück zum Zitat McNally H, Bennett CC, Elbourne DR, Field DJ. For the UK collaborative ECMO trial group. United Kingdom collaborative randomized trial of neonatal extracorporeal membrane oxygenation: follow-up to age 7 years. Pediatrics. 2006;117:845–54.CrossRef McNally H, Bennett CC, Elbourne DR, Field DJ. For the UK collaborative ECMO trial group. United Kingdom collaborative randomized trial of neonatal extracorporeal membrane oxygenation: follow-up to age 7 years. Pediatrics. 2006;117:845–54.CrossRef
Metadaten
Titel
Features of randomised trials designed by the NPEU Perinatal Trials Service during Adrian Grant’s directorship
verfasst von
Diana Elbourne
Publikationsdatum
01.12.2018
Verlag
BioMed Central
Erschienen in
Reproductive Health / Ausgabe 1/2018
Elektronische ISSN: 1742-4755
DOI
https://doi.org/10.1186/s12978-018-0567-7

Weitere Artikel der Ausgabe 1/2018

Reproductive Health 1/2018 Zur Ausgabe

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.