Osteoarthritis clinical trials methodology

Abstract

Osteoarthritis (OA) is the most prevalent and disabling joint condition in the world. Presently, there are no pharmacological agents that have been approved by regulatory authorities for disease modification in OA, and of existing treatments available, the effectiveness of these agents is inconsistent. There are a multitude of challenges in the design of clinical trials for OA, spanning from the use of outcome measures to the identification of a clinically meaningful effect of the agent in question in comparison to placebo. The aim of this thesis is to explore factors that may impact the outcome of clinical trials in OA and that will allow for: better applicability of measurement devices as an outcome measure for monitoring patients in clinical trials; assessment of prognostic factors that may influence response to intra-articular corticosteroid therapy; improvement of our understanding of placebo responses and factors that will influence response to intra-articular delivery of drugs; assessment of the prognostic value of biomarkers and its relation to specific imaging changes over time.

This thesis provides further insight into the underlying issues of clinical trials methodology, and the potential outcome measures and participant cohort selection. The potential health care benefits from this thesis are envisioned to be: 1) advancing the understanding of participants’ responses to therapy in clinical trials, and allowing for more appropriate stratification of participants in order to enhance the ability to demonstrate more precise effects in clinical trials; 2) improvement in the utilisation of outcome measures in clinical trials with the use of objective measurements; 3) improving biomarker utilisation, that will not only encourage and promote development of new therapies but also 4) influencing regulatory agency approval process – the qualification of biomarkers will be informative towards future design of clinical trials.