Re‐inventing the randomized controlled trial in medical oncology: The registry‐based trial

Abstract

Substantial progress has recently been made in optimizing the management of cancer patients, resulting in major gains in survival and quality of life. Much of this progress has resulted from the serial testing of promising treatment strategies, typically using prospective randomized controlled trials to compare outcomes achieved with the new approach versus the current standard(s) of care. However, there is an ever-expanding list of important questions that are difficult to investigate, particularly with respect to determining the optimal sequencing and combination of proven active agents. With the rapidly growing list of clinical, pathologic and molecular characteristics that promise to predict treatment benefit and/or risk for defined patient subsets, many new questions regarding how best to personalize our approach to treatment selection are emerging. These questions can be investigated in the context of registry-based randomized clinical trials. Recently, the potential of registry-based randomized clinical trials was demonstrated in cardiology, highlighting the ability to rapidly recruit large numbers of patients to a trial addressing an important clinical question, with minimal cost and high external validity. In this review, we discuss the challenges and limitations of conventional clinical trials in multidisciplinary cancer care, describe the potential advantages of registry-based randomized trials, and highlight several registry-based oncology studies that are already underway to demonstrate the feasibility of this approach.

Chemotherapy and biologic use in the routine management of metastatic colorectal cancer in Australia: is clinical practice following the evidence?

“…However, major limitations of standard randomised studies include the high costs and the limited external validity, meaning that the relevance of results achieved in a highly selected study population may not necessarily translate well to the real world population. Overall, these considerations are driving interest in the novel concept of registry based randomised controlled trials …”

Registration of Rectal Cancer-Related Clinical Trials on Chinese Clinical Trial Registry over past decades

“…RCT has been reported to be an ideal method to test the safety and e cacy of clinical interventions, and its conclusions are of great signi cance in guiding clinical practice and drug policy [12] . RCT reduces or eliminates the imbalance between the treatment group and the control group, occupies the top of the pyramid of clinical evidence, and is the best source of evidence-based medicine [13] . Randomization is an important principle in RCT where subjects are randomly assigned to the experimental group and the control group to balance the known and unknown confounding factors of the experimental group and the control group.…”

ENSAT registry-based randomized clinical trials for adrenocortical carcinoma

“…A randomized registry-based clinical trial is a prospective study using a clinical registry for patient identification, trial conduct and outcomes reporting. The registry-based randomized clinical trial maintains the strengths of a prospective clinical study, including high internal validity, stringent patient stratification, randomization to ensure unbiased study of interventions and analysing patient outcomes to determine the effect of the studied intervention (7,9,15). In variance to conventional trials, registry-based studies provide the opportunity to lower costs and ensure more rapid patient inclusion (7,9,15).…”

“…While clinical trials have the potential to explore strategies to approach these problems, the current research infrastructure fails in providing effective resources to perform such projects on rare diseases. In this context, registry-based clinical trials have emerged as a resource-efficient alternative solution to address clinical and translational research questions (7)(8)(9)(10). In this review, we aim to describe how registry-based trials could be used to advance care of patients with ACC.…”