By Liz Beatty, Chief Strategy Officer, Inato
Twitter: @inatohealth
Tasked with reimagining patient-centric cancer clinical trials, the Bloomberg New Economy International Coalition has identified eliminating patient identification and enrollment barriers as top priorities for accelerating the development of novel cancer treatments, screening, and prevention. The priorities outlined in the April 2022 issue of Nature align with our long-standing call to broaden clinical trial accessibility and, subsequently, data diversity and generalizability by eliminating the obstacles preventing truly representative enrollment.
Diversity in clinical research is essential for advancing medicine and life-saving treatment options. A persistent lack of diverse participants has remained despite efforts to address the issue. But moving beyond addressing the problem requires an urgent paradigm shift. Deviating from what’s been considered the norm for decades is no small feat; however, a push for health equity is imperative, and it’s also our mission. With a focus on community-based clinical trials, we can ensure patients suffering from life-threatening diseases or chronic health problems can access advanced medicines where they live. Removing the barriers to inclusion means partnering with the community sites and physicians that patients already trust.
Barriers by the Numbers
In its Nature commentary, the coalition noted that local trial availability is a substantial barrier. While 74% of cancer patients receive treatment in the community, no clinical trials were offered in 36% of physician-owned oncology practices. Much of this is due to the concentration of trials within major academic institutions. The top 5% of research sites account for about 70% of clinical trials – which means a significant percentage of the population is excluded from study participation solely because they live too far away from academic research centers.
These barriers aligned with a study funded by the National Cancer Institute (NCI), which found that over 75% of patients don’t participate in trials simply because there are none in their area, meaning most studies draw patients primarily from populations within 40 miles of trial sites. This factor exacerbates the access issue plaguing clinical trials and severely limits racial, gender, and socioeconomic diversity.
According to the Food & Drug Administration (FDA) Drug Trials Snapshot, 75% of enrollees in trials that led to drug approvals in 2020 were white, while just 8% were Black and 6% were Asian. An example of gender limits can be seen in cardiovascular disease trials, of which less than 2% reported any female sex-specific cardiovascular risk factors. Finally, on the socioeconomic front, patients with household incomes below $50,000 are 27% less likely to participate in clinical trials.
Left unaddressed, these racial, gender, demographic, and geographic limitations drive up costs, diminish external validity, lengthen timelines, and limit the generalizability of findings to the population at large.
Data and Other Damage
Patient identification and enrollment challenges impact diversity, which hampers researchers’ ability to collect accurate, robust, and representative data and leads to failure to gain approval.
This trend can be seen in a recent retrospective review of 302 drug submissions to the FDA, which found that:
- Nearly 16% of submissions had insufficient data to determine safe dosages
- More than 11% had inconsistent results between study sites
- About 13% failed to demonstrate statistically significant benefits
Findings like these strongly suggest data limitations, including diversity, influenced the FDA’s rejection of 5 out of 6 submissions. The incomplete data that results from enrolling predominantly homogeneous populations should alarm any pharmaceutical manufacturer needing to understand the efficacy and side effects of the medications they intend to bring to market.
Testing on narrow demographic and geographic groups can also impact trial efficiency and costs. Recruiting from limited patient pools takes longer, creating inefficiencies and slowing timelines. Delays also add opportunity costs that can run from $600,000 to $8 million per day. Further, limited enrollment can result in an incomplete picture of the treatment’s actual impact on the broader population, impeding detection of side effects and leading to post-approval FDA black box designations and millions in lost revenues.
Leaning on Technology
The barriers preventing broader and more representative patient identification and enrollment must be eliminated if the goal is to make medications safe and effective for everyone. Designing trials around the patient is a solution that is growing in popularity among clinical trial sponsors. Advances in remote patient monitoring and telemedicine technologies enable hybrid trials, allowing a combination of virtual visits and visits to an easy-to-access community-based location, both of which eliminate barriers to participation.
Leveraging technology helps to:
- Enroll a greater number of patients for a more robust (and accurate) analysis
- Reduce administrative, intermediary, and clinical site costs
- Better capture the individual experience of patients in real-world settings
- Improve patient recruitment, retention, engagement, and adherence
- Enhance data collection, aggregation, and analysis
Cloud-based platforms help trial sponsors connect with underutilized community sites and provide sites with additional enrollment support. Doing so allows investigators to recruit a more diverse and representative patient population, improving data quality, avoiding delays, lowering costs, and accelerating FDA submission and approval. Importantly, by increasing the number of community trial sites, these platforms also remove the financial barriers that hit vulnerable populations hardest.
A Community-Based Trial Success Story
One sponsor found success by broadening its patient pool with a community-based approach in a Phase III Agitation in Alzheimer’s Dementia (AAD) clinical trial. Slow enrollment had forced many AAD research sites to close and convinced the study team that nearly all the patient pools in key AAD geographies had been exhausted. With remaining sites experiencing a screening success rate of just 21% and the 18-month enrollment deadline rapidly approaching, the trial sponsor decided to leverage our clinical trial platform to connect with experienced sites with the capacity to enroll qualified patients.
Within three weeks, 10 new sites were added. Further, by pivoting to the involvement of more community-based sites, screening success rates doubled, with sites the sponsor identified on the platform enrolling five times more patients and randomizing 10 times as many patients per month than sites identified by other means.
Keeping it Local
By enabling the participation of community-based research sites through a cloud-based platform, patient identification and enrollment improves representative data collection on a global scale. It can also salvage existing trials that are struggling with enrollment.
As a part of a patient-centric approach to clinical trials, community research sites bring access to patients worldwide, including those who have historically lacked access to clinical research. The result is more robust, diverse data to improve the overall drug development process through increased generalizability and effectiveness.