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Short Report
29 May 2026

Directly comparing randomized and real-world controls in adjuvant breast cancer

Authors: Brigham Walker https://orcid.org/0000-0002-5617-577X [email protected], Marley Boyd, Michelle Silver, Junxin Shi, Purva Bulsara, Nino Balanchivadze, and Nicholas J RobertAuthor Info & Affiliations
Volume 15, Number 6
https://doi.org/10.57264/cer-2025-0143
PDFFormats

Abstract

Aim: We sought to directly compare contemporaneous real-world (RW) and randomized controlled trial (RCT) control arms to assess the feasibility of utilizing RW controls in early breast cancer treatment. Materials & methods: Women with human epidermal growth factor receptor 2-negative high-risk breast cancer receiving adjuvant docetaxel, doxorubicin and cyclophosphamide for six cycles between 29 May 2007 and 21 November 2013 were included, mirroring the control arm and study timeframe from our reference trial ‘Anthracyclines in Early Breast Cancer: The ABC Trials’. Structured data was extracted from the iKnowMed electronic medical record system, which included both RW and trial patients allowing for their direct comparison. Propensity scores were used for baseline characteristic balancing, and Kaplan–Meier analysis was conducted. Results: In the final sample of 306 patients (153 per arm drawn from 155 RCT patients and 703 RW patients in the study timeframe), the matching process yielded balanced cohorts along available covariates. Kaplan–Meier curves and disease-free survival distributions did not suggest significant differences between RW and trial arms (log rank p = 0.98). Conclusion: Despite limitations, including the use of structured data only, the study suggests that RW data could have served as a synthetic control in this setting.

Plain language summary

What is this article about?

This article utilizes electronic medical records on patients who were in a clinical trial to evaluate whether similar patients who were not in the clinical trial but receiving the same treatment for early breast cancer had similar disease-free survival patterns. This is relevant to researchers because there is growing interest in understanding whether generating clinical evidence without a clinical trial control arm (and instead using a ‘real-world’ control arm) would be a reliable method for research.

What were the results?

After selecting real-world patients who on balance were most similar to the clinical trial patients, we find that the patients had very similar disease-free survival patterns.

What do the results mean?

These results suggest that, in this clinical setting, these patients would have likely served as reasonable substitutes for the clinical control arm of a clinical trial.

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