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. 2021 Apr 1;4(4):e214732.
doi: 10.1001/jamanetworkopen.2021.4732.

Comparison of Clinical Characteristics Between Clinical Trial Participants and Nonparticipants Using Electronic Health Record Data

James R Rogers  1 , Cong Liu  1 , George Hripcsak  1   2 , Ying Kuen Cheung  3 , Chunhua Weng  1
Affiliations

Comparison of Clinical Characteristics Between Clinical Trial Participants and Nonparticipants Using Electronic Health Record Data

James R Rogers et al. JAMA Netw Open. .

Abstract

Importance: Assessing generalizability of clinical trials is important to ensure appropriate application of interventions, but most assessments provide minimal granularity on comparisons of clinical characteristics.

Objective: To assess the extent of underlying clinical differences between clinical trial participants and nonparticipants by using a combination of electronic health record and trial enrollment data.

Design, setting, and participants: This cross-sectional study used data obtained from a single academic medical center between September 1996 and January 2019 to identify 1645 clinical trial participants from a diverse set of 202 available trials conducted at the center. Using an aggregated resampling procedure, nonparticipants were matched to participants 1:1 based on trial conditions, number of recent visits to a health care professional, and calendar time.

Exposures: Clinical trial enrollment vs no enrollment.

Main outcomes and measures: The primary outcome was standardized differences in clinical characteristics between participants and nonparticipants in clinical trials stratified into the 4 most common disease domains.

Results: This cross-sectional study included 1645 participants from 202 trials (929 [56.5%] male; mean [SD] age, 54.65 [21.38] years) and an aggregated set of 1645 nonparticipants (855 [52.0%] male; mean [SD] age, 57.24 [21.91] years). The most common disease domains for the selected trials were neoplastic disease (86 trials; 737 participants), disorders of the digestive system (31 trials; 321 participants), inflammatory disorders (28 trials; 276 participants), and disorders of the cardiovascular system (27 trials; 319 participants); trials could qualify for multiple disease domains. Among 31 conditions, the percentage of conditions for which the prevalence was lower among participants than among nonparticipants per standardized differences was 64.5% (20 conditions) for neoplastic disease trials, 61.3% (19) for digestive system trials, 58.1% (18) for inflammatory disorder trials, and 38.7% (12) for cardiovascular system trials. Among 17 medications, the percentage of medications for which use was less among participants than among nonparticipants per standardized differences was 64.7% (11) for neoplastic disease trials, 58.8% (10) for digestive system trials, 88.2% (15) for inflammatory disorder trials, and 52.9% (9) for cardiovascular system trials.

Conclusions and relevance: Using a combination of electronic health record and trial enrollment data, this study found that clinical trial participants had fewer comorbidities and less use of medication than nonparticipants across a variety of disease domains. Combining trial enrollment data with electronic health record data may be useful for better understanding of the generalizability of trial results.

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Conflict of interest statement

Conflict of Interest Disclosures: Mr Rogers and Dr Weng reported receiving grants from the National Library of Medicine during the conduct of the study. Dr Hripcsak reported receiving grants from the National Institutes of Health during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Associations Between Trial Participant Covariates and Trial Characteristics in Trials for Neoplastic Disease and Disorders of the Digestive System
Covariates above the dashed line are statistically significant. Covariates with the most statistically significant associations per each trial characteristic are as follows. A, Participant age with trial phase, number of treatment arms, and industry sponsorship; malignant tumor of urinary bladder with multisite trials and overall enrollment; malignant tumor of lung with use of a data monitoring committee (DMC); and use of opioids with randomization. B, Malignant neoplastic disease with trial phase and overall enrollment; antithrombotic agents with industry sponsorship; primary malignant neoplasm of prostate with randomization; immunosuppressant medications with use of a DMC; and heart disease with multisite trial.
Figure 2.
Figure 2.. Associations Between Trial Participant Covariates and Trial Characteristics in Trials for Inflammatory Disorders and Disorders of the Cardiovascular System
Covariates above the dashed line are statistically significant. Covariates with the most statistically significant associations per each trial characteristic are as follows. A, Viral hepatitis C infection with trial phase; heart disease with blinding; renal impairment with multisite trials and overall enrollment; antithrombotic agents with number of treatment arms and industry sponsorship; and immunosuppressant medications with use of a data monitoring committee (DMC). B, Age with randomization; peripheral vascular disease with trial phase and overall enrollment; atrial fibrillation with number of treatment arms; hyperlipidemia with blinding; heart disease with industry sponsorship; and heart failure with use of a DMC.
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