Multifaceted imaging strategies for clinical trials of knee osteoarthritis-a tightly interlinked value and precision chain.

Abstract

Osteoarthritis is a debilitating, whole-organ disease that involves all osteoarticular tissues. No effective treatments have yet been approved by the regulatory agencies for modifying the natural history of this disease and its structural progression. In this whitepaper, we will summarize concepts of "multi-faceted" (multi-contrast) magnetic resonance imaging (MRI), with a focus on its application in osteoarthritis clinical trials. The process described here encompasses a tightly interlinked value and precision chain, where all elements must be aligned seamlessly for the trial to succeed. The procedure should begin with careful patient characterization and selection, potentially aided by (multifaceted) imaging, so that the disease (sub-) types in these potential participant will match the mechanism of action (MOA) of the medical investigational product (i.e., the drug studied). This should be followed by a comprehensive yet efficient MRI acquisition protocol, employing sequences with various contrasts that permit the characterization of imaging-based joint pathologies and evaluation of the drug's MOA. Suitable image analysis tools must be employed, ideally adhering to regulatory compliance standards. Multiple validated endpoints can be derived from the various (multifaceted) contrasts, to be potentially combined to multi-component or composite endpoints, based on stringent a-priori rules. In conclusion, a robust value and precision chain needs to be fully functional for a disease-modifying osteoarthritis trial to be successful. Participant selection must be mindful of the drug's MOA, and a well-aligned and custom-tailored "multifaceted" image acquisition protocol, suitable image analysis tools, and meaningful endpoints should be in place, which should match the specific image contrasts.