M Sebastean; M Babu; M Morales; I Prabhu; P Montaldo; P Ivain; I Jahan; T Chatuga; P Bandiya; J Mendoza; V Oliveira; N Benakappa; S Mangalabharathi; S Kamalaratnam; V Prakash; Sajid M; R Chandramohan; S Manerkar; J Mondkar; S Moni; M Shahidullah; R Rodrigo; A Sreelar; SB Peters; S Kumar; S Saritha; R Ajit; S Ramji; R Swamy; S Shankaran; S Thayyil

Institutions

Imperial College London, UK; Indira Gandhi Institute of Child Health, Bangalore, Madras Medical College, Chennai; Sion Medical College, Mumbai; MAMC, New Delhi; Wayne State University, USA

Introduction (include hypothesis)

Informed parental consent for neonatal time critical trials is challenging, particularly in low and middle-income countries (LMIC). We examined the quality of the information provided to the parents prior to obtaining informed written consent in the HELIX (Hypothermia for Encephalopathy in Low and Middle-Income Countries) trial.

Methods (include source of funding and ethical approval if required)

We recruited a total of 408 babies from 7 large public teaching hospitals in India, Sri Lanka and Bangladesh, between Aug 2015 and Feb 2019. Following parental consent, encephalopathic babies were centrally randomised to whole body cooling for 72 h or usual care only, within 6 h of birth. Additional study procedures included: blood tests (total 3 ml blood), umbilical cord histology, 3Telsa MR imaging and spectroscopy and neurodevelopmental outcome assessments (Bayley III) at 18 to 22 months. Funding: Gates and Weston Garfield Foundations; Approvals: Imperial College and local research ethics committees.

The local clinical staff completed ICH-GCP certification and underwent training simulations on research consenting for the trial. During the recruitment, the consenting process for each eligible infant was video recorded and stored. This was reviewed at a later stage by two investigators, who were not involved in the original consenting process, using a predefined proforma of 17 questions under 3 domains: (A) Empathy (i.e. respectful communication in local language and avoidance of medical jargon) (B) Information (i.e. explanation of all study procedures and risk benefits (C) Autonomy (neutrality, free choice and avoidance of all coercion. Each question was scored from 1 (worst possible score) to 5 (best possible score), and the group differences were examined using Man Whitney U test.

Results

A total of 408 parental consents were obtained in 7 different south Asian regional languages; 177 (43%) were obtained between 9 am to 5 pm, and 231 (57%) between 5 pm and 9 am. Overall, consultants obtained the consent in 51 (13%) cases, and junior doctors (equivalent of ST3 to ST7 in the UK) in 357 (88%) cases, although this varied by the centre.

A total of 294 (58 are not analysed yet; 56 videos were lost) consecutive audio-visual recordings (30 to 60 minutes each) from the 6 (1 centre not yet analysed) recruiting centres were included in the analysis. The mean (SD) scores for empathy, information and autonomy were 4.9 (0.3), 4.3 (0.8) and 4.3 (0.9) respectively. The consent quality scores of day time (red dots) and night time (black dots) recruits, and those obtained by the consultants and the JD were similar (p>0.05) (Figure 1). The key study information including randomisation, cooling therapy and risk benefits were explained adequately in all cases. The JD were less likely to encourage the parents to ask questions than consultants, although the differences were not statistically significant.

Information not discussed during the consent process included data confidentiality (34 [12%] cases), regulatory approvals (30 [10%] cases), additional blood tests and umbilical cord histology (26 [9%] cases), and the freedom to withdraw from the study at any time without the clinical care being affected (18 [6%] cases).

Conclusions

Informed parental consent for time critical studies relies heavily on the neonatal junior doctors who provide the clinical care to the baby. With appropriate training, guidance and encouragement, high quality research consent can be obtained for randomised controlled trials in public sector neonatal intensive care units in middle-income countries.