LIBERTI: A SMART study in plastic surgery

Abstract

Background/aims: Laser treatment of burns scars is considered by some providers to be standard of care. However, there is little evidence-based research as to the true benefit. A number of factors hinder evaluation of the benefit of laser treatment. These include significant heterogeneity in patient response and possible delayed effects from the laser treatment. Moreover, laser treatments are often provided sequentially using different types of equipment and settings, so there are effectively a large number of overall treatment options that need to be compared. We propose a trial capable of coping with these issues and that also attempts to take advantage of the heterogeneous response in order to estimate optimal treatment plans personalized to each individual patient. It will be the first large-scale randomized trial to compare the effectiveness of laser treatments for burns scars and, to our knowledge, the very first example of the utility of a Sequential Multiple Assignment Randomized Trial in plastic surgery. Methods: We propose using a Sequential Multiple Assignment Randomized Trial design to investigate the effect of various permutations of laser treatment on hypertrophic burn scars. We will compare and test hypotheses regarding laser treatment effects at a general population level. Simultaneously, we hope to use the data generated to discover possible beneficial personalized treatment plans, tailored to individual patient characteristics. Results: We show that the proposed trial has good power to detect laser treatment effect at the overall population level, despite comparing a large number of treatment combinations. The trial will simultaneously provide high-quality data appropriate for estimating precision-medicine treatment rules. We detail population-level comparisons of interest and corresponding sample size calculations. We provide simulations to suggest the power of the trial to detect laser effect and also the possible benefits of personalization of laser treatment to individual characteristics. Conclusion: We propose, to our knowledge, the first use of a Sequential Multiple Assignment Randomized Trial in surgery. The trial is rigorously designed so that it is reasonably straightforward to implement and powered to answer general overall questions of interest. The trial is also designed to provide data that are suitable for the estimation of beneficial precision-medicine treatment rules that depend both on individual patient characteristics and on-going real-time patient response to treatment.