A protocol for a systematic Cochrane review has been published, with the primary objectives to identify and summarize multivariable prognostic models for quantifying the risk of clinical disease progression, worsening, and activity in MS. The review will describe the characteristics of the identified multivariable prognostic models, including prognostic factors considered and evaluation measures used, it will also describe changes in outcome definitions, time frames, prognostic factors and statistical methods over time. Further, it will qualitatively summarize the validation performance of the model, and summarize model performance across external validation studies via meta‐analysis, where possible. The risk of bias in the models will be assessed, moderating effects on model performance by meta‐regression will be evaluated, where possible; and recommendations for future MS prognostic research will be made.
We expect to find substantial heterogeneity, as diagnostic criteria for MS subtypes and available treatment options, as well as the technology used to assess disease activity, have evolved over time. Heterogeneity is also typically high in prognostic studies. We expect heterogeneity both between development studies and their corresponding validation studies for specific models and also between different development models for the same outcome. We will extract relevant information and will include a narrative summary of potential sources of heterogeneity. We will further investigate heterogeneity using meta‐regression.