The role of radiography and MRI as screening tools and outcome measures in clinical trials of knee osteoarthritis: a perspective on the current status and outlook.

To present an overview of the current role of imaging in clinical trials of knee osteoarthritis (OA), focusing on radiography and magnetic resonance imaging (MRI) in the context of their role as both inclusion criteria and structural outcome measures. A non-systematic literature search (PubMed) was performed, starting with a list of terms including the title of the current manuscript, followed by multiple search terms. The identified methodologies, findings, concepts, and recommendations were organized into a systematic framework, providing an overview of the current and future role of imaging in OA clinical trials. Conventional radiography is the most commonly used modality for the evaluation of OA in clinical trials of disease-modifying OA drugs (DMOADs). Radiography is used to define the severity of structural disease and to measure joint space width as an inclusionary criterion, and has also been employed as an outcome measure. Limitations include a lack of reproducibility, a lack of sensitivity, specificity, and responsiveness regarding structural progression, and an insufficient ability to depict diagnoses of exclusion. MRI is more sensitive and specific in assessing tissue damage and its progression. Using abbreviated imaging protocols and rapid image assessment, MRI may be applied at screening. Quantitative and semiquantitative approaches have been commonly used as outcome measures, and both have advantages and disadvantages. Reasons for the failure of past DMOAD trials are multifold and include patient selection based on imaging and application of imaging outcome measures that are either not sufficiently sensitive to change or are difficult to reliably reproduce longitudinally.