Pilot implementation of short message service for randomisation in a multisite pragmatic factorial clinical trial in Kenya

Abstract

AbstractThe traditional use of sealed envelopes for randomisation is susceptible to manipulation and the risk of damage to envelopes during shipping and at storage. Additionally, the filling and sealing envelopes is, tedious, time-consuming, and error prone. Other randomisation alternatives such as web-based methods are preferred. However, they are expensive and unsuitable in settings with poor internet infrastructure. Mobile phone-based randomisation using Short Message Service (SMS) potentially offers a low-cost and reliable alternative.We developed an SMS-based method for random allocation of treatments. Plain text messaging or an Android app were used to formulate text messages using a fixed syntax consisting of participant unique identifier, trial site, stratum, and the trial name as input parameters. The system verified the input parameters and obtained an allocation from the database before returning a response to the sender. The text response contained the details of the treatment allocation. The study was done in two sites of a multi-site 3×2 factorial clinical trial in Kenya involving two interventions with up to nine possible allocations. We evaluated the accuracy of treatment allocations against the master randomisation list for each randomisation SMS processed, and SMS latency in seconds. A post-implementation survey was conducted to evaluate user feedback.A total of 218 participants were randomised between 7th February 2022 and 11th April 2022, out of which 179 were randomised to only one arm while 39 were randomised to both treatment arms. Allocation accuracy was 100%. Median latency was 22 seconds with the fastest message processed in 10 seconds and the slowest (non-network delayed) message processed in 2129 seconds. Four users completed a post-implementation survey. The pilot study demonstrated that SMS randomisation to be easy, user-friendly, fast, and accurate and a feasible alternative randomisation technique.Author SummaryWhile conducting a randomized clinical trial with a sample size of more than 4000 participants, in routine care settings in Kenya, we encountered a challenge with the approach to randomisation. In our study protocol we settled on the use of sealed opaque envelopes for allocation concealment. This approach, given our large sample size and nine possible treatment allocations, necessitated the preparation of an overwhelming (4000×9) envelope stratified across 12study sites. This manual process was tedious, time consuming and error prone, with issues arising such as mislabelling, empty envelopes, and some being damaged in storage or transit.Recognizing these challenges, our team was prompted to innovate an alternative digital solution, with the ultimate aim of establishing a proof of concept that could support future clinical trials in routine care settings. Given the high mobile penetration in Kenya, we sought to leverage SMS-based mobile communication as a means of determining treatment allocation for study participants. We developed a platform capable of accommodating both Android and feature phones using open-source tools. Our findings indicate that SMS is a fast, user-friendly, and low-cost method, presenting a viable solution that could potentially revolutionize randomisation in clinical studies. However, it is important to note that our testing of this method was limited to only two study sites. Despite this, our study lays the groundwork for digital randomisation and hopefully inspire future advancements in health research.