Multimethod quantitative benefit‐risk assessment of treatments for moderate‐to‐severe osteoarthritis

OBJECTIVE: Demonstrate how benefit‐risk profiles of systemic treatments for moderate‐to‐severe osteoarthritis (OA) can be compared using a quantitative approach accounting for patient preference. STUDY DESIGN AND SETTING: This study used a multimethod benefit‐risk modelling approach to quantifiably compare treatments of moderate‐to‐severe OA. In total four treatments and placebo were compared. Comparisons were based on four attributes identified as most important to patients. Patient Global Assessment of Osteoarthritis was included as a favourable effect. Unfavourable effects, or risks, included opioid dependence, nonfatal myocardial infarction and rapidly progressive OA leading to total joint replacement. Clinical data from randomized clinical trials, a meta‐analysis of opioid dependence and a long‐term study of celecoxib were mapped into value functions and weighted with patient preferences from a discrete choice experiment. RESULTS: Lower‐dose NGFi had the highest weighted net benefit‐risk score (0.901), followed by higher‐dose NGFi (0.889) and NSAIDs (0.852), and the lowest score was for opioids (0.762). Lower‐dose NGFi was the highest‐ranked treatment option even when assuming a low incidence (0.34% instead of 4.7%) of opioid dependence (ie, opioid benefit‐risk score 808) and accounting for both the uncertainty in clinical effect estimates (first rank probability 46% vs 20% for NSAIDs) and imprecision in patient preference estimates (predicted choice probability 0.26, 95% confidence interval [CI] 0.25‐0.28 vs 0.21, 95% CI 0.19‐0.23 for NSAIDs). CONCLUSION: The multimethod approach to quantitative benefit‐risk modelling allowed the interpretation of clinical data from the patient perspective while accounting for uncertainties in the clinical effect estimates and imprecision in patient preferences.