Division of Infectious Diseases and Chronic Viral Illness Service, Department of Medicine, Glen Site, McGill University Health Centre, Montreal, QC, Canada.
Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montreal, QC, Canada.
Pharmacol Res Perspect. 2020 Oct;8(5):e00650. doi: 10.1002/prp2.650.
The World Health Organisation's goal of hepatitis C virus (HCV) elimination by 2030 will require lower drug prices. Estimates of comparative efficacy promote competition between pharmaceutical companies but direct acting antivirals have been approved for the treatment of HCV without comparative trials. We emulated a randomized trial to answer the question of whether easy to treat patients with genotype 1 HCV could be treated with sofosbuvir/ledipasvir (SOF/LDV) rather than sofosbuvir/velpatasvir (SOF/VEL). Patients without comorbidities or end stage liver disease were selected from the British Colombia Hepatitis Testers Cohort. To create a conceptual trial, we matched each patient starting SOF/VEL (a 'case') to the patient starting SOF/LDV with the closest propensity score (a 'control'). We estimated the probability of treatment failure under a Bayesian logistic model with a random effect for each case-control set and used that model to give an estimate of a risk difference for the conceptual trial. Treatment failure was recorded for 27 of 825 (3%) cases and for 29 of 602 (5%) matched controls. Estimates from our model were treatment success rates of 97% (95% credible interval, CrI, 95%-98%) for treatment with SOF/VEL, 95% (95% CrI 93%-97%) for treatment with SOF/LDV and a risk difference between treatments of 2% (95% CrI 0%-4%). This risk difference is evidence that SOF/LDV is not inferior to SOF/VEL for easy to treat patients with genotype 1 HCV. The approach is a template for comparing drugs when there are no data from comparative trials.
世界卫生组织（WHO）设定的 2030 年消除丙型肝炎病毒（HCV）的目标，需要降低药物价格。疗效比较估计值促进了制药公司之间的竞争，但直接作用抗病毒药物已被批准用于 HCV 的治疗，而无需进行比较试验。我们模拟了一项随机试验，以回答一个问题，即对于基因型 1 HCV 的易于治疗的患者，是否可以用索磷布韦/维帕他韦（SOF/LDV）而不是索磷布韦/伏西瑞韦（SOF/VEL）进行治疗。从不列颠哥伦比亚省肝炎检测者队列中选择没有合并症或终末期肝病的患者。为了创建一个概念性试验，我们将开始使用 SOF/VEL 的每位患者（“病例”）与开始使用 SOF/LDV 的患者（“对照”）进行匹配，这些患者的倾向评分最接近。我们使用贝叶斯逻辑模型对每个病例对照组的治疗失败概率进行估计，并使用该模型对概念性试验的风险差异进行估计。在 825 例病例中，有 27 例（3%）和 602 例对照中，有 29 例（5%）记录了治疗失败。我们的模型估计，SOF/VEL 治疗的治疗成功率为 97%（95%可信区间，95%-98%），SOF/LDV 治疗的治疗成功率为 95%（95% CrI 93%-97%），治疗之间的风险差异为 2%（95% CrI 0%-4%）。这一风险差异表明，对于基因型 1 HCV 的易于治疗的患者，SOF/LDV 并不逊于 SOF/VEL。当没有比较试验的数据时，这种方法是比较药物的模板。
