431 - Success of blinding a procedural intervention from treating clinicians in a randomised controlled trial (RCT) in preterm infants with respiratory distress syndrome

Poster Number: 431
Publication Number: 431.223

Peter A. Dargaville, Royal Hobart Hospital, Hobart, Tasmania, Australia; Elizabeth Reid, Menzies Institute for Medical Research, Hobart, Tasmania, Australia; C.Omar O. Kamlin, Royal Women's Hospital, Melbourne, Victoria, Australia; Francesca Orsini, MCRI, Melbourne, Victoria, Australia; Antonio De Paoli, Royal Hobart Hospital, Hobart, Tasmania, Australia; Howard W. Clark, University College London, London, England, United Kingdom; Roger F. Soll, Robert Larner, M.D., College of Medicine at the University of Vermont, Hinesburg, VT, United States; John B. Carlin, Murdoch Children's Research Institute & University of Melbourne, Melbourne, Victoria, Australia; Peter G. Davis, University of Melbourne, Melbourne, Victoria, Australia

Background: Optimal methodology for neonatal RCTs includes blinding of treatment allocation from treating clinicians to minimise performance bias, but this is considerably harder to achieve with a procedural intervention. Success of blinding is rarely assessed in any neonatal RCT.

Objective: To examine the effectiveness of blinding a procedural intervention from treating clinicians in a multicentre RCT of minimally-invasive surfactant therapy (MIST) versus sham treatment in 485 preterm infants at 25-28 weeks’ gestation (the OPTIMIST-A trial, JAMA 2021, 326:2478).

Design/Methods: In the OPTIMIST-A trial a one-off intervention was performed in the first 6 h of life by a treatment team not involved in clinical care. The allocated intervention (MIST or sham) was administered with the bedspace screened from view; duration of the sham treatment and interactions of the treatment team were expected to mimic that in the active arm. After each intervention, three clinicians were asked via questionnaire whether they could discern which form of treatment had been given. These responses were evaluated using two recognized blinding indices, measuring success of blinding overall (James index) and by group allocation (Bang index) (Table 1 footnote). Blinding was assessed by staff role, and the influence of intervention duration and improvement in FiO2 post-procedure on blinding success was determined in weighted regression analysis of data clustered along the X-axis.

Results: Amongst 1345 responses, the clinician guess was correct in 441 (33%) and incorrect in 142 (11%), with “unsure” indicated in 762 (57%). These proportions were similar between treatment arms (Table 1). The James index was 0.67 in pooled data and the Bang index was 0.28 and 0.17 in the MIST and sham groups, respectively (Table 1); for both indices these results suggest successful blinding. Responses from neonatologists correctly identified group allocation with greater frequency (47%) than those of the current bedside nurse (36%), neonatal trainees (31%), and nurses caring for other infants (24%). For sham treatment, neither duration of the intervention nor post-intervention FiO2 change affected the Bang index. For the MIST group, the Bang index was linearly related to duration of the intervention, with blinding becoming less effective when the procedure lasted 10 min or longer. There was a similar relationship with FiO2 improvement post-procedure, with less effective blinding where FiO2 reduction was >0.10. Conclusion(s): Effective blinding of a procedural intervention from clinicians is both achievable and measurable in neonatal RCTs.
Table 1.