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

Jue Hou, Rachel Zhao, Tianrun Cai, Brett Beaulieu-Jones, Thany Seyok, Kumar Dahal, Qianyu Yuan, Xin Xiong, Clara Lea Bonzel, Claire Fox, David C. Christiani, Thomas Jemielita, Katherine P. Liao, Kai Li Liaw, Tianxi Cai

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3 Scopus citations

Abstract

IMPORTANCE: Temporal shifts in clinical knowledge and practice need to be adjusted for in treatment outcome assessment in clinical evidence.

OBJECTIVE: 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.

DESIGN, SETTING, AND PARTICIPANTS: 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.

EXPOSURES: Laparoscopy-assisted colectomy (LAC) vs open colectomy (OC).

MAIN OUTCOMES AND MEASURES: 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.

RESULTS: 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.

CONCLUSIONS AND RELEVANCE: 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.

Original languageEnglish (US)
Pages (from-to)E2218371
JournalJAMA Network Open
Volume5
Issue number6
DOIs
StatePublished - Jun 23 2022

Bibliographical note

Funding Information:
Conflict of Interest Disclosures: Dr Hou reported receiving grants from Merck & Co, Inc, during the conduct of the study. Dr Beaulieu-Jones reported receiving grants from Merck SA during the conduct of the study. Dr Fox reported personal fees from and being an employee of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, outside the submitted work. Dr Jemielita reported being an employee of Merck & Co, Inc. Dr Liaw reported being an employee of Merck & Co, Inc. No other disclosures were reported. Funding/Support: The study was supported by Merck & Co, Inc; by grants P30 AR072577 (Dr Liao) and K99NS114850 (Dr Beaulieu-Jones) from the National Institutes of Health (NIH); and grant U01CA209414 from the National Cancer Institute of the NIH (Dr Christiani).

Publisher Copyright:
© 2022 American Medical Association. All rights reserved.

Keywords

  • Aged
  • Colectomy/methods
  • Electronic Health Records
  • Female
  • Humans
  • Laparoscopy/methods
  • Male
  • Middle Aged
  • Sigmoid Neoplasms

PubMed: MeSH publication types

  • Randomized Controlled Trial
  • Journal Article
  • Research Support, N.I.H., Extramural

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