Pfizer, New York, NY, USA.
Eli Lilly & Co., Global Patient Safety, Indianapolis, IN, USA.
Br J Clin Pharmacol. 2022 Aug;88(8):3837-3846. doi: 10.1111/bcp.15309. Epub 2022 Apr 8.
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.
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.
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).
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.
展示如何使用定量方法来比较中度至重度骨关节炎（OA）的系统治疗的获益-风险概况，同时考虑到患者偏好。
本研究使用多方法获益-风险建模方法对中度至重度 OA 的治疗进行定量比较。总共比较了四种治疗方法和安慰剂。比较基于对患者最重要的四个属性。患者整体 OA 评估被视为有利影响。不利影响或风险包括阿片类药物依赖、非致命性心肌梗死和迅速进展的 OA 导致全关节置换。来自随机临床试验、阿片类药物依赖的荟萃分析和塞来昔布的长期研究的临床数据被映射到价值函数中，并根据离散选择实验中的患者偏好进行加权。
低剂量 NGFi 的加权净获益-风险评分最高（0.901），其次是高剂量 NGFi（0.889）和 NSAIDs（0.852），而阿片类药物的评分最低（0.762）。即使假设阿片类药物依赖的发生率较低（0.34%，而不是 4.7%）（即阿片类药物获益-风险评分 808），并考虑到临床效果估计的不确定性（第一顺位概率 46%比 NSAIDs 的 20%）和患者偏好估计的不精确性（预测选择概率 0.26，95%置信区间[CI] 0.25-0.28 与 NSAIDs 的 0.21，95% CI 0.19-0.23），低剂量 NGFi 仍是排名最高的治疗选择。
多方法定量获益-风险建模方法允许从患者角度解释临床数据，同时考虑到临床效果估计的不确定性和患者偏好估计的不精确性。
