Temporal Trends in Clinical Evidence of 5-Year Survival Within Electronic Health Records Among Patients With Early-Stage Colon Cancer Managed With Laparoscopy-Assisted Colectomy vs Open Colectomy.
Temporal Trends in Clinical Evidence of 5-Year Survival Within Electronic Health Records Among Patients With Early-Stage Colon Cancer Managed With Laparoscopy-Assisted Colectomy vs Open Colectomy.
复制标题
通过腹腔镜辅助结肠切除术与开放式结肠切除术管理，早期结肠癌患者电子健康记录中5年生存的临床证据的时间趋势。
DOI：
10.1001/jamanetworkopen.2022.18371
复制
发表时间：
2022-06-01
影响因子：
13.8
通讯作者：
中科院分区：
文献类型：
--
作者：
研究人员如何适当评估和调整时间趋势，以纠正使用临床证据的研究中的混杂偏差？这项针对 943 名早期结肠癌患者的有效性比较研究，通过使用 2006 年至 2017 年的电子健康记录数据模拟手术治疗的临床结果 (COST) 研究组试验，发现了显着的时间趋势。通过日历时间分层和时变模型的协同训练，该模拟得出了与 COST 研究组试验一致的结论。这些发现表明，通过适当调整时间趋势的混杂偏差，利用涵盖较长时间跨度的数据进行的临床研究可以补充评估治疗结果及其随时间演变的随机临床试验。这项比较有效性研究使用早期结肠癌患者的电子健康记录数据来模拟一项已完成的随机临床试验，调查时间趋势并纠正其混杂偏差。临床知识和实践的时间变化需要根据临床证据的治疗结果评估进行调整。使用电子健康记录 (EHR) 数据 (1) 评估治疗决策和患者结果的时间趋势，以及 (2) 使用 EHR 数据模拟随机临床试验 (RCT)，并对时间趋势进行适当调整。选择评估 I 期至 III 期早期结肠癌患者总体生存率的手术治疗临床结果 (COST) 研究组试验作为目标试验。该随机对照试验是使用麻省总医院布里格姆总医院的单个医疗保健系统队列患者的 EHR 数据进行模拟的，这些患者从 2006 年 1 月 1 日至 2017 年 12 月 31 日接受了早期结肠癌结肠切除术，并随访至 2020 年 1 月 1 日。分析于2019年12月2日至2022年1月24日进行。腹腔镜辅助结肠切除术（LAC）与开腹结肠切除术（OC）。主要结局是 5 年总生存率。为了解决模拟中的混杂问题，选择并调整了预处理变量。当结肠切除术通过跨层联合训练进行时，时间趋势通过日历年的分层进行调整。 EHR 模拟队列中共有 943 名患者符合关键 RCT 资格标准，其中包括 518 名接受 LAC 的患者（中位年龄 63 [范围，20-95] 岁；268 名 [52%] 女性；121 名 [23%] 患有 I 期癌症，165 名 [32%] 患有 II 期癌症，232 名 [45%] 患有 III 期癌症；32 名 [6%] 患有结肠粘连；5 名患有结肠粘连的患者。 278 名 [54%] 患有右侧结肠癌；18 名 [3%] 患有左侧结肠癌；222 名 [43%] 患有乙状结肠癌）和 425 名接受 OC（中位年龄，65 [范围，28-99] 岁；223 名 [52%] 女性；61 名 [14%] 患有 I 期，153 名 [36%] 患有 II 期，以及211 名（50%）患有 III 期癌症；39 名（9%）患有结肠粘连；202 名（47%）患有右侧结肠癌；39 名（9%）患有左侧结肠癌；201 名（47%）患有乙状结肠癌。治疗分配 (χ2 = 60.3；P < .001) 和总生存率 (χ2 = 137.2；P < .001) 的时间趋势检验显着。调整后的 EHR 模拟得出了与 RCT 相同的结论：LAC 的总生存率并不逊色于 OC，5 年风险差为 -0.007（95% CI，–0.070 至 0.057）。每个时间段内的分层分析结果是一致的。这些发现表明，在进行长时间跨度的临床证据研究时，应考虑时间趋势的混杂偏差。日历时间分层和模型协同训练是一种解决方案。经过适当的调整，临床证据可以补充随机对照试验来评估一段时间内的治疗结果。
How might investigators assess and adjust for temporal trends appropriately to correct for confounding bias in studies using clinical evidence? This comparative effectiveness study of 943 patients with early-stage colon cancer detected substantial temporal trends by emulating the Clinical Outcomes of Surgical Therapy (COST) Study Group Trial using electronic health records data from 2006 to 2017. Through stratification by calendar time and cotraining of time-varying models, this emulation reached a conclusion agreeing with the COST Study Group Trial. These findings suggest that with proper adjustment of confounding bias from temporal trends, clinical studies conducted with data covering a long time span could supplement randomized clinical trials in the assessment of treatment outcome and its evolution over time. This comparative effectiveness study investigates temporal trends and corrects for their confounding bias in an emulation of a completed randomized clinical trial using electronic health record data of patients with early-stage colon cancer. Temporal shifts in clinical knowledge and practice need to be adjusted for in treatment outcome assessment in clinical evidence. To use electronic health record (EHR) data to (1) assess the temporal trends in treatment decisions and patient outcomes and (2) emulate a randomized clinical trial (RCT) using EHR data with proper adjustment for temporal trends. The Clinical Outcomes of Surgical Therapy (COST) Study Group Trial assessing overall survival of patients with stages I to III early-stage colon cancer was chosen as the target trial. The RCT was emulated using EHR data of patients from a single health care system cohort who underwent colectomy for early-stage colon cancer from January 1, 2006, to December 31, 2017, and were followed up to January 1, 2020, from Mass General Brigham. Analyses were conducted from December 2, 2019, to January 24, 2022. Laparoscopy-assisted colectomy (LAC) vs open colectomy (OC). The primary outcome was 5-year overall survival. To address confounding in the emulation, pretreatment variables were selected and adjusted. The temporal trends were adjusted by stratification of the calendar year when the colectomies were performed with cotraining across strata. A total of 943 patients met key RCT eligibility criteria in the EHR emulation cohort, including 518 undergoing LAC (median age, 63 [range, 20-95] years; 268 [52%] women; 121 [23%] with stage I, 165 [32%] with stage II, and 232 [45%] with stage III cancer; 32 [6%] with colon adhesion; 278 [54%] with right-sided colon cancer; 18 [3%] with left-sided colon cancer; and 222 [43%] with sigmoid colon cancer) and 425 undergoing OC (median age, 65 [range, 28-99] years; 223 [52%] women; 61 [14%] with stage I, 153 [36%] with stage II, and 211 [50%] with stage III cancer; 39 [9%] with colon adhesion; 202 [47%] with right-sided colon cancer; 39 [9%] with left-sided colon cancer; and 201 [47%] with sigmoid colon cancer). Tests for temporal trends in treatment assignment (χ2 = 60.3; P < .001) and overall survival (χ2 = 137.2; P < .001) were significant. The adjusted EHR emulation reached the same conclusion as the RCT: LAC is not inferior to OC in overall survival rate with risk difference at 5 years of −0.007 (95% CI, –0.070 to 0.057). The results were consistent for stratified analysis within each temporal period. These findings suggest that confounding bias from temporal trends should be considered when conducting clinical evidence studies with long time spans. Stratification of calendar time and cotraining of models is one solution. With proper adjustment, clinical evidence may supplement RCTs in the assessment of treatment outcome over time.
登录
查看更多内容
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
39
作者：
Fralick, Michael;Kesselheim, Aaron S.;Schneeweiss, Sebastian
通讯作者：
Schneeweiss, Sebastian
影响因子：
50.5
作者：
Eisenhauer, E. A.
通讯作者：
Eisenhauer, E. A.
影响因子：
3.1
作者：
Parker, James Michael;Feldmann, Timothy F.;Cologne, Kyle G.
通讯作者：
Cologne, Kyle G.
影响因子：
1.7
作者：
Luglio, Gaetano;De Palma, Giovanni Domenico;Tarquini, Rachele;Giglio, Mariano Cesare;Sollazzo, Viviana;Esposito, Emanuela;Spadarella, Emanuela;Peltrini, Roberto;Liccardo, Filomena;Bucci, Luigi
通讯作者：
Bucci, Luigi