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The challenges of interventional trials in fetal therapy
  1. R Katie Morris1,2,
  2. J Daniels1,3,
  3. J Deeks3,4,
  4. D Field5,
  5. M D Kilby1,2
  1. 1Centre for Women's & Children Health and the School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
  2. 2Fetal Medicine Centre, Birmingham Women's Hospital NHS Foundation Trust, Birmingham, UK
  3. 3Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK
  4. 4School of Health and Population Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
  5. 5Department of Health Sciences, University of Leicester, Leicester, UK
  1. Correspondence to Dr R Katie Morris, Birmingham Centre for Women and Children's Health, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham Women's Hospital, Edgbaston, Birmingham B15 2TG, UK; r.k.morris{at}

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Fetal therapy is an advancing specialty but the assessment of effectiveness for many therapies has been limited to observational data1 ,2 with randomised controlled trials (RCTs) employed with varying success.3 ,4 More recently systematic reviews have been used to assess the quality and summarise the outcomes of this evidence.5 ,6

Our experiences from one such trial (the PLUTO study4) highlight the difficulties of such research. Congenital lower urinary tract obstruction (LUTO) may be identified using prenatal ultrasound and is associated with high mortality and morbidity (perinatal and childhood), due to pulmonary hypoplasia and chronic renal impairment.7–9 Ultrasound-directed, in utero, vesicoamniotic shunting (VAS) bypasses the congenital urethral obstruction with the aim of improving fetal outcome.1 ,2 ,10 Counselling parents faced with the difficult and distressing news that their baby has a significant problem antenatally is complex and compounded by uncertainties around the effectiveness of the often limited number of options. Providing clinicians with high quality evidence on which to base their counselling affords parents the opportunity to make informed choices and can help to remove some of the anxiety. The PLUTO study aimed to determine the effectiveness, cost-effectiveness and patient acceptability of VAS for fetal LUTO, compared with conservative management. It comprised a multicentre, international RCT and a non-randomised cohort of pregnancies with LUTO (not recruited to the RCT due to patient or clinician preference).4 All fetal medicine centres within England, Scotland and The Republic of Ireland agreed to take part in the study along with the Dutch Obstetric Research Consortium. Expert opinions on the relative benefits of VAS and conservative management were elicited from fetal medicine specialists, paediatric nephrologists and paediatric urologists for use in a Bayesian analysis.11 The planned sample size of the trial was 150, …

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  • Contributors All authors drafted and revised the manuscript. All authors were involved in the PLUTO trial.

  • Funding Well-being of Women and the Hannah Eliza Guy Charity (Birmingham Children's Hospital Charity) funded the original commencement of the trial at Birmingham Women's Hospital NHS Trust in 2005 and then 2008–2012 was funded by the NIHR HTA programme. During the lifetime of this work Dr Morris was also funded by a MRC/RCOG Clinical Research Training Fellowship and a NIHR Clinical Lectureship. Other researchers were funded by the Mary Crosse Fellowship (Birmingham Women's Hospital NHS Foundation Trust Research and Development) and a MRC Midlands Hub for Trials Methodology Research at the University of Birmingham (Medical Research Council Grant ID G0800808).

  • Competing interests Professor Mark Kilby (Professor of Fetal Medicine) was the Chief Investigator for the PLUTO study. Dr Jane Daniels is Deputy Director Birmingham Clinical Trials Unit and was involved in the PLUTO trial design and management. Professor Jon Deeks is Professor of Biostatistics and Director of the Birmingham Clinical Trials Unit and was involved in this capacity in the PLUTO study. Dr Katie Morris was the research fellow for the trial. Professor David Field was a member of the PLUTO Trial Steering Committee.

  • Provenance and peer review Commissioned; externally peer reviewed.

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