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

doi:10.1001/jamanetworkopen.2022.18371

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

Biostatistics

Research output: Contribution to journal › Article › peer-review

4 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 language	English (US)
Pages (from-to)	E2218371
Journal	JAMA Network Open
Volume	5
Issue number	6
DOIs	https://doi.org/10.1001/jamanetworkopen.2022.18371
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1001/jamanetworkopen.2022.18371

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Hou, J., Zhao, R., Cai, T., Beaulieu-Jones, B., Seyok, T., Dahal, K., Yuan, Q., Xiong, X., Bonzel, C. L., Fox, C., Christiani, D. C., Jemielita, T., Liao, K. P., Liaw, K. L., & Cai, T. (2022). 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. JAMA Network Open, 5(6), E2218371. https://doi.org/10.1001/jamanetworkopen.2022.18371

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. / Hou, Jue; Zhao, Rachel; Cai, Tianrun et al.
In: JAMA Network Open, Vol. 5, No. 6, 23.06.2022, p. E2218371.

Research output: Contribution to journal › Article › peer-review

Hou, J, Zhao, R, Cai, T, Beaulieu-Jones, B, Seyok, T, Dahal, K, Yuan, Q, Xiong, X, Bonzel, CL, Fox, C, Christiani, DC, Jemielita, T, Liao, KP, Liaw, KL & Cai, T 2022, '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', JAMA Network Open, vol. 5, no. 6, pp. E2218371. https://doi.org/10.1001/jamanetworkopen.2022.18371

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title = "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",

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.",

keywords = "Aged, Colectomy/methods, Electronic Health Records, Female, Humans, Laparoscopy/methods, Male, Middle Aged, Sigmoid Neoplasms",

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

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: {\textcopyright} 2022 American Medical Association. All rights reserved.",

year = "2022",

month = jun,

day = "23",

doi = "10.1001/jamanetworkopen.2022.18371",

language = "English (US)",

volume = "5",

pages = "E2218371",

journal = "JAMA Network Open",

issn = "2574-3805",

publisher = "American Medical Association",

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TY - JOUR

T1 - 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

AU - Hou, Jue

AU - Zhao, Rachel

AU - Cai, Tianrun

AU - Beaulieu-Jones, Brett

AU - Seyok, Thany

AU - Dahal, Kumar

AU - Yuan, Qianyu

AU - Xiong, Xin

AU - Bonzel, Clara Lea

AU - Fox, Claire

AU - Christiani, David C.

AU - Jemielita, Thomas

AU - Liao, Katherine P.

AU - Liaw, Kai Li

AU - Cai, Tianxi

N1 - 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.

PY - 2022/6/23

Y1 - 2022/6/23

N2 - 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.

AB - 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.

KW - Aged

KW - Colectomy/methods

KW - Electronic Health Records

KW - Female

KW - Humans

KW - Laparoscopy/methods

KW - Male

KW - Middle Aged

KW - Sigmoid Neoplasms

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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

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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