Merola David, Young Jessica, Schrag Deborah, Lin Kueiyu Joshua, Robert Nicholas, Schneeweiss Sebastian
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
Clin Epidemiol. 2022 Oct 10;14:1135-1144. doi: 10.2147/CLEP.S373291. eCollection 2022.
The use of electronic health records (EHR) data to assess drug effectiveness in clinical oncology practice is of great interest to regulators, clinicians, and payers. However, the utility of EHR data in clinical effectiveness studies may be limited by missing data, unmeasured confounding, and imperfect outcome surveillance. This study sought to emulate and compare the results of a randomized controlled trial investigating the efficacy of palbociclib with fulvestrant vs letrozole in advanced breast cancer.
This was a cohort study using longitudinal EHR data derived from outpatient oncology practices in the United States. Eligibility criteria from the PARSIFAL trial were emulated as closely as possible. Patients were included if they had hormone-positive, human epidermal growth factor receptor - 2 (HER-2) negative metastatic breast cancer and had no record of prior treatment for metastatic disease. Patients initiating first-line treatment with palbociclib and fulvestrant following their first record of metastasis were compared to those initiating palbociclib and letrozole on the same day. Treatments were ascertained by oncology medication ordering records in the data source. The primary outcome was death as recorded in the oncologists' EHR systems.
There were 1886 eligible women in the study cohort. Although the 3-year survival was meaningfully lower in clinical practice (59%) compared to the randomized trial (78%), the relative effect size was a hazard ratio (HR) of 1.07 (95% CI: 0.86-1.35), similar to the randomized trial (HR = 1.00; 95% CI: 0.68-1.48).
Despite common challenges encountered in EHR-based studies, it is possible to achieve similar conclusions to emulated randomized trials with the application of analytic approaches that address missing data, confounding, and selection bias. This is a promising finding in light of other emulations and ongoing efforts to improve data from clinical practice and causal analytics.
监管机构、临床医生和支付方对利用电子健康记录（EHR）数据评估临床肿瘤学实践中的药物疗效非常感兴趣。然而，EHR数据在临床疗效研究中的效用可能受到数据缺失、未测量的混杂因素和不完美的结局监测的限制。本研究旨在模拟并比较一项随机对照试验的结果，该试验研究了哌柏西利联合氟维司群与来曲唑在晚期乳腺癌中的疗效。
这是一项队列研究，使用来自美国门诊肿瘤学实践的纵向EHR数据。尽可能紧密地模拟了PARSIFAL试验的纳入标准。如果患者患有激素阳性、人表皮生长因子受体-2（HER-2）阴性的转移性乳腺癌且没有转移性疾病的既往治疗记录，则纳入研究。将首次记录转移后开始一线使用哌柏西利和氟维司群治疗的患者与同一天开始使用哌柏西利和来曲唑治疗的患者进行比较。通过数据源中的肿瘤学药物订购记录确定治疗情况。主要结局是肿瘤学家的EHR系统中记录的死亡情况。
研究队列中有1886名符合条件的女性。尽管临床实践中的3年生存率（59%）明显低于随机试验（78%），但相对效应大小为风险比（HR）1.07（95%CI：0.86-1.35），与随机试验相似（HR = 1.00；95%CI：0.68-1.48）。
尽管基于EHR的研究面临常见挑战，但通过应用解决数据缺失、混杂因素和选择偏倚的分析方法，有可能得出与模拟随机试验相似的结论。鉴于其他模拟研究以及为改善临床实践数据和因果分析所做的持续努力，这是一个有希望的发现。
