Predictive models in SMA II natural history trajectories using machine learning: A proof of concept study

Abstract

It is known from previous literature that type II Spinal Muscular Atrophy (SMA) patients generally, after the age of 5 years, presents a steep deterioration until puberty followed by a relative stability, as most abilities have been lost. Although it is possible to identify points of slope indicating early improvement, steep decline and relative stabilizations, there is still a lot of variability within each age group and it’s not always possible to predict individual trajectories of progression from age only. The aim of the study was to develop a predictive model based on machine learning using an XGBoost algorithm for regression and report, explore and quantify, in a single centre longitudinal natural history study, the influence of clinical variables on the 6/12-months Hammersmith Motor Functional Scale Expanded score prediction (HFMSE). This study represents the first approach to artificial intelligence and trained models for the prediction of individualized trajectories of HFMSE disease progression using individual characteristics of the patient. The application of this method to larger cohorts may allow to identify different classes of progression, a crucial information at the time of the new commercially available therapies.

New therapies for spinal muscular atrophy: where we stand and what is next

“…Recent ongoing studies, including different dosages or modalities of administration and combination therapies, will be helpful to better understand the pros and cons of each treatment and guide families and clinicians. Further help may also come from the application of new statistical and Artificial Intelligence (AI) methods to real-world data that may allow a better interpretation of the results and the development of prognostic algorithms [77].…”

Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated spinal muscular atrophy patients: An international study

“…As part of the activities of the registry, the study was approved by the ethical committees (ethical/ institutional review board) of all participating centers, including as As part of the clinical routine at all participating centers, all patients are regularly assessed using the HFMSE, a functional scale designed to evaluate motor function in individuals with SMA. The HFMSE is a widely recognized and validated instrument that allows health care professionals to monitor changes in motor abilities over time, assess disease progression, and track the effectiveness of interventions or treatments [9,10,12,13,15,16,[28][29][30][31][32][33][34][35][36]38]. Its consistent use across centers ensures standardized and reliable data collection, enabling comprehensive evaluations of patients' functional status and facilitating comparisons and collaborations in multicenter studies.…”

“…Most of the natural history studies and performed or ongoing clinical trials have used the HFMSE to measure functional changes over time [12][13][14][15][16][28][29][30][31][32][33][34][35][36]. So far, there is limited information on MCID when using HFMSE, with only one cross-sectional study using distribution-based methods to identify values in adults with SMA [18].…”