Rapid, effective, and affordable randomisation for emergency neonatal research in a low-resource setting: a feasibility randomised controlled trial

BACKGROUND: Randomisation is an essential component of any clinical trial to eliminate selection bias and ensure similar distribution of confounders between the treatment groups. For randomisation to be successfully implemented, there must be adequate allocation concealment. Many low-cost randomisation and allocation concealment methods have the potential to introduce bias by ineffectively concealing the allocation sequence from the researcher and are now rarely used in high-resource settings. In such settings, centralised randomisation services have been developed to prepare the randomisation sequence, conceal the sequence, and provide a secure mechanism to acquire the allocation. Such services are often prohibitively expensive for researchers in low-resource settings or for small/pilot trials. We describe our experience of adopting a low-cost third-party randomisation and allocation concealment process for emergency neonatal research in a low-resource setting. METHODS: This was a single-site feasibility trial in Eastern Uganda, which randomly assigned neonates in a 1:1 ratio at birth to receive either early continuous positive airways pressure (intervention) or standard of care (control). Centralised third-party randomisation and allocation were used, with two researchers not involved in the trial serving as randomisation coordinators. The lead coordinator prepared a randomisation schedule using http://www.randomization.com/ . This was stored securely on a server with exclusive access granted to the randomisation coordinators. Randomly permuted block randomisation was used to ensure balance between the two arms and enhance concealment in group allocation. Block sizes were varied and kept confidential from the investigators and research assistants to prevent prediction of upcoming assignments, and the randomisation sequence was managed by an independent third party. After identifying and obtaining consent, the research assistant requested an allocation from the randomisation coordinators by SMS. Upon receiving the SMS request, the randomisation coordinators sent the allocation to a study tablet device by email. The time from sending the SMS request to the time the allocation email was received was used to evaluate the suitability of this method. RESULTS: One hundred participants were successfully randomised. Group allocation was received for 91/100 (91.0%; 95%CI 84–96%) of participants within 15 min of the research assistant sending the SMS request, and for 98/100 (98.0%; 95%CI 93–100%) within 30 min. CONCLUSION: This study demonstrates that a low-cost, third-party randomisation method is a feasible and effective approach for emergency neonatal research in low-resource settings. It enabled timely and concealed allocation without the high costs associated with centralised systems. This method presents a scalable solution for small to medium-sized trials where rapid and unbiased allocation is critical. TRIAL REGISTRATION: Study is registered on Pan African Clinical Trials Registry (PACTR) PACTR202208462613789. Registered 08 August 2022. https//pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=23,888 .