Developing a systematic framework to identify, evaluate and report evidence for drug selection in motor neuron disease clinical trials

Motor neuron disease (MND) is a rapidly progressive, disabling and incurable disease with an average of time to death between 18-30 months from diagnosis. Despite decades of clinical trials, effective disease modifying treatment options remain limited. Motor Neuron Disease – Systematic Multi-Arm Adaptive Randomisation Trial (MND-SMART; ClinicalTrials.gov registration number: NCT04302870) is an adaptive platform trial aimed at testing a pipeline of candidate drugs in a timely and efficient way. To inform selection of future candidate drugs to take to trial, we identify, evaluate and report evidence from (i) published literature via Repurposing Living Systematic Review (ReLiSyR-MND), a machine learning assisted, crowdsourced, three-part living systematic review evaluating clinical literature of MND and other neurodegenerative diseases which may share similar pathways, animal in vivo MND studies and in vitro MND studies, (ii) experimental drug screening including high throughput screening of human induced pluripotent stem cell based assays, (iii) pathway and network analysis, (iv) drug and trial databases, and (v) expert opinion. Our workflow implements automation and text mining techniques for evidence synthesis, and uses R shiny to provide interactive, curated living evidence summaries to guide decision making.