Meeting Trial Participants Where They Are: Decentralized Clinical Trials as a Patient-Centered Paradigm for Enhancing Accrual and Diversity in Surgical and Multidisciplinary Trials in Oncology

Abstract

The COVID-19 pandemic significantly dislocated the operational model of traditional clinical trials as travel restrictions and the diversion of finite health care resources led to significant declines in trial activation, enrollment, and data collection. 1 However, the exigent need to continue therapeutic trials fostered an innovation in trial operations termed decentralized clinical trials (DCTs). 2,3 DCTs are trials wherein elements of research conduct (drug delivery, adverse event assessments, imaging, and laboratory draws) are delivered remote from the primary clinical trial site and closer to a patient's home. This approach leverages digital tools, mobile or community-based providers (imaging facilities, ambulatory clinics, and laboratory centers), and a supply chain to eliminate the need for routine in-person interactions. 2,4-6 Pandemic-related policies such as relaxation of the regulatory climate for telemedicine and improvements in the infrastructure supporting same-day home delivery of medications accelerated DCT adoption. Furthermore, the US Food and Drug Administration published regulatory guidance on the use of digital health tools for obtaining informed consent, remote safety monitoring, and clinical end point assessments. 7,8 In this article, we provide an overview of multidisciplinary DCTs with a focus on surgery, and draw attention to opportunities for enhancing trial accrual and participant diversity. Decentralized Clinical Trials In a fully decentralized model, all study phases (ie, recruitment, delivery of intervention, and acquisition of outcome data) are executed without a need for in-person contact. 9 However, DCTs exist along a continuum and most trials will never be fully decentralized because of sponsor-mandated in-person interactions for safety and regulatory purposes. DCTs have been successfully implemented in other specialties like cardiol-ogy (eg, DeTAP trial for atrial fibrillation 4) and offer several advantages over traditional trials including improved accessibility (70% of prospective participants live. 2 hours from study sites), faster accrual, 10 cost savings, expanded geographic reach, and potential to increase the diversity (race, age, and sex) of trial participants. 11,12 DCTs can also optimize trial sample size through the use of personalized thresholds for estimating treatment effects. For example, biometric sensors may facilitate more objective measurements of outcomes such as functional status and quality of life, leading to individual-level characterization of treatment responses and toxicities. 9 DCTs and Research Equity According to recent analysis of global clinical trials, 76% of participants were White, 11% were Asian, and only 7% were Black. 13,14 When assessed by ethnic distribution, only 13% of trial participants were Hispanic or Latino. 13 As highlighted in a recent National Academy of Medicine consensus report, lack of participant diversity limits our understanding of the safety and effectiveness of new treatments and hinders our ability to identify new biologic processes that would positively affect all patients. 15 In addition, the lack of diversity compounds the problem of low accrual rates, erodes trust in the research enterprise among certain populations, and entrenches health care disparities for those rare conditions wherein clinical trials are sometimes the only treatment option. 15 Although improving diversity is a shared responsibility across the entire research ecosystem, DCTs can facilitate more inclusion in research by reducing transportation-related barriers for potential minority participants via digital technologies, such as, remote consent, electronic surveys, and remote patient monitoring (RPM). 16 This is salient because the participants typically excluded from traditional trials, usually sited in urban academic medical centers, are disproportionately affected by geographical constraints. 17 In a recent systematic review, DCTs enrolled participants from an average of 40 states compared with traditional trials that enrolled participants from 11 states. 18 In addition, DCTs can establish a foundation of trust through sustained patient engagement within their