The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Clinical outcomes of a control group from a randomized controlled trial were successfully replicated by a synthetic control arm (SCA) based on historical controls, according to data presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.1

Adequate clinical trial enrollment can be challenging, and it is not uncommon for studies to be closed early due to low recruitment numbers. In addition, single-arm efficacy trials are sometimes required for difficult oncology indications, in rare diseases or populations, or for ethical or practical reasons. The goal of this study was to determine if an SCA can replicate a control arm, and, if so, what its potential applications could be.

The SCA was developed using data from historical clinical trials that were conducted using a similar experimental product and was statistically matched to the baseline characteristics of the experimental arm.

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“We use statistical methods, most commonly propensity score matching, to select the historical patients who will form a composition of patients that match the baseline characteristics of the experimentally treated patients in our target trial,” Ruthie Davi, PhD, of Medidata Solutions, and lead author of the study, told Cancer Therapy Advisor. “In this way, we create something that looks a lot like a randomized control for a setting where randomization is problematic,” she said.

In this study, historical data were used from trials of patients with stage III/IV NSCLC who had received prior platinum-based chemotherapy.

Given that the SCA includes patient data from prior clinical trials, Dr Davi said that they carefully considered how to prevent “cherry-picking” of historical control characteristics.

“Selection of the historical clinical trials and patients to be used in a synthetic control is done without knowledge of any outcomes of the trials or individual patients,” she said. During the selection process, she said that picking and choosing characteristics or specific patients is not possible. “The selection is made algorithmically solely based on the eligibility criteria of the historical trials and patient characteristics measured before randomization in the historical clinical trials,” Dr Davi said.

After propensity score matching, the overall survival (OS) outcomes of the SCA was similar to that of the historical pool (hazard ratio [HR], 1.04; 95% CI, 0.88-1.23; P =.65).

According to the authors, these data suggest that “in some setting[s], SCA can augment or replace a randomized control, mitigating many of the recruitment, retention, and crossover challenges when enrolling or maintaining a concurrent control.”

Although the authors believe that their work has contributed important advances to establishing scientific credibility of the use of an SCA, more research is needed to determine whether an SCA can replicate treatment effect or be expanded to additional indications. In addition, Dr Davi said that a future study is “exploring conclusions regarding treatment effect to the effect of unobserved confounders associated with outcome and is planned in collaboration with Friends of Cancer Research.”

“As it stands today, we believe synthetic control arms are a viable option for upholding the scientific rigor needed for drug development while easing the patient burden in indications where assignment to a control arm is considered undesirable,” Dr Davi said.

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.

Reference

  1. Davi R, Chandler M, Elashoff B, et al. Non-small cell lung cancer (NSCLC) case study examining whether results in a randomized control arm are replicated by a synthetic control arm (SCA). Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 9108.