Multiple Sclerosis (MS) is a chronic disease characterized by progressive or alternate impairment of neurological functions (motor, sensory, visual, and cognitive). Predicting disease progression with a probabilistic and time-dependent approach might help in suggesting interventions that can delay the progression of the disease. However, extracting informative knowledge from irregularly collected longitudinal data is difficult, and missing data pose significant challenges. MS progression is measured through the Expanded Disability Status Scale (EDSS), which quantifies and monitors disability in MS over time. EDSS assesses impairment in eight functional systems (FS). Frequently, only the EDSS score assigned by clinicians is reported, while FS sub-scores are missing. Imputing these scores might be useful, especially to stratify patients according to their phenotype assessed over the disease progression. This study aimed at i) exploring different methodologies for imputing missing FS sub-scores, and ii) predicting the EDSS score using complete clinical data. Results show that Exponential Weighted Moving Average achieved the lowest error rate in the missing data imputation task; furthermore, the combination of Classification and Regression Trees for the imputation and SVM for the prediction task obtained the best accuracy.

Applying Artificial Intelligence (AI) and Machine Learning (ML) in critical contexts, such as medicine, requires the implementation of safety measures to reduce risks of harm in case of prediction errors. Spotting ML failures is of paramount importance when ML predictions are used to drive clinical decisions. ML predictive reliability measures the degree of trust of a ML prediction on a new instance, thus allowing decision-makers to accept or reject it based on its reliability. To assess reliability, we propose a method that implements two principles. First, our approach evaluates whether an instance to be classified is coming from the same distribution of the training set. To do this, we leverage Autoencoders (AEs) ability to reconstruct the training set with low error. An instance is considered Out-of-Distribution (OOD) if the AE reconstructs it with a high error. Second, it is evaluated whether the ML classifier has good performances on samples similar to the newly classified instance by using a proxy model. We show that this approach is able to assess reliability both in a simulated scenario and on a model trained to predict disease progression of Multiple Sclerosis patients. We also developed a Python package, named relAI, to embed reliability measures into ML pipelines. We propose a simple approach that can be used in the deployment phase of any ML model to suggest whether to trust predictions or not. Our method holds the promise to provide effective support to clinicians by spotting potential ML failures during deployment.