Innovations in clinical trial designs and tools have the potential to unlock a new era of research that is more convenient for patients, more reflective of real-world treatment conditions, and more likely to enable participation of a diverse set of individuals. But a recent study reveals how far the U.S. is from realizing this potential: regions of the country with the worst social drivers of health are the least likely to host clinical trials.
The disconnect between need and where clinical trials are conducted is a longstanding one. But it was recently highlighted by University of Michigan researchers through an examination of demographic data for people enrolled in clinical trials for new cancer medicines. The most socially vulnerable counties were far less likely to have any nearby trial, a disparity that has worsened over time.
Research sponsors and the Food and Drug Administration can respond to this challenge by continuing to support community-based clinical trials. But the regulatory framework that governs these and other modern approaches has not kept pace with innovations in clinical trials and must be updated to enable expansion of trials into more communities.
Clinical trials are essential for establishing the safety and effectiveness of new medicines. Trial results have a greater impact when participants reflect the demographic diversity of those who could potentially benefit from the treatments being evaluated. The University of Michigan research is one more confirmation that the U.S.’s existing clinical trial infrastructure often fails to meet these goals.
Designing and implementing clinical trials is hard work. Reports over time suggest that up to 85% of clinical trials don’t meet their recruitment goals and up to 80% are delayed due to recruitment challenges.
Large-scale clinical trials are typically hosted by large research hospitals and academic institutions, most of which are in big cities. This can exclude people in rural communities from participating in clinical trials, and can present logistical challenges even for individuals who live relatively close to these centers because they may not have the economic means or schedule flexibility to attend multiple appointments.
Today’s clinical trial regulations were created for a different era, when the technology of the time necessitated that studies be conducted at a single location under the direct supervision of an investigator and staff who carried out all aspects of the trial. Participants were required to come to that location. Clinical research still largely relies on this outmoded approach, which frequently requires participants to organize their lives around the trial, and often includes traveling, finding a place to stay, and taking time off from work.
New tools and approaches developed by clinical trial sponsors, working with the FDA, should help make trials more representative. The FDA has signaled an openness to supporting trial designs that make them more accessible for participants, more reflective of real-world conditions, and enable more diverse participation. This modernization of the regulatory framework is critically needed and will contribute to healthier communities by speeding the development of new and better treatments that address unmet medical needs.
Community-based trials, also known as decentralized trials, have the potential to significantly increase participation and diversity in clinical research. By forcing a shift to this model, the Covid-19 pandemic showed just how successful these types of studies can be. To help ensure studies could continue during the pandemic, investigators, trial sponsors, and regulators worked collaboratively during the nationwide shutdown to reverse the process, bringing trials to participants rather than participants to trials.
Lilly, the company we work for, partnered with a leading decentralized research organization to bring our Covid-19 research to at-risk patients in long-term care facilities. An innovative cloud-based system helped recruit participants across multiple sites and make adjustments as needed in real time.
This model allowed Lilly to move quickly, reach more people who were traditionally underrepresented in clinical trials, and protect the health of participants and trial staff during the pandemic, all while maintaining the highest standards of scientific research, patient safety, and data integrity. To be sure, Lilly wasn’t alone in doing this: companies across the biopharmaceutical industry can share similar stories of leveraging innovative, community-based approaches to keep clinical trials running during the Covid-19 crisis.
These updated approaches shouldn’t fade away with the pandemic. Drug developers, investigators, and regulators must build on what was learned. Several key updates to the U.S. clinical trial regulatory framework will be crucial to supporting this progress:
Ease the burden on clinical trial investigators. Enabling better support from sponsor staff can create efficiencies and fill resource needs for community-based providers. Local health care professionals are essential to the success of community-based trials, but most of them do not have the resources or infrastructure to manage many of the demands of clinical studies, such as recruiting participants, providing them with logistical support, and shipping investigational products to them. Trial sponsor staff have the capability to perform tasks like these that involve limited or no contact with participants to avoid conflict of interest. Current regulatory rules, however, provide little guidance on what types of sponsor roles are appropriate, which creates uncertainty for sponsors that can discourage such support.
Update the role of investigators. The shift in clinical trial services to multiple care settings, such as community clinics, mobile medical units, and participants’ homes, must be accompanied by updating how clinical trial investigators provide oversight of these settings. Current regulations state that an investigator must personally conduct or supervise a trial. This requirement can create confusion for a community-based study that includes multiple care settings in numerous communities.
To better accommodate community-based trials without compromising patient safety or data integrity, FDA regulations should be updated to clarify that trial investigators may provide oversight by ensuring that study staff such as local health care providers are appropriately qualified and trained for the trial-related activities they will perform. Such assurance could include confirming proper education and qualifications and meeting state licensing requirements.
Current regulations also state that investigators may administer an investigational product only to study participants they personally supervise. Such regulations do not lend themselves to the flexibility needed to enable community-based research, where patients can receive clinical trial services in many types of settings.
Consistently support the use of digital health technologies. Wearable devices and other advances can help make trials more convenient for participants by enabling remote collection of data from them in real time as they go about their daily lives. This convenience can promote diversity by reducing the number of clinic visits needed, making it possible for people to participate in trials whose income, work, or travel issues would prevent multiple in-person visits. Yet current FDA guidance lacks clarity on what evidence is needed to validate the use of digital health technologies. A modernized approach for qualifying digital health technologies is needed. Sponsors of new drug trials are currently encouraged to use the drug development tools pathway, which was not designed for digital health technologies and can be cumbersome and complicated for this use.
It also is not clear how digital health technologies will be reviewed when multiple FDA divisions or offices are involved. Providing greater clarity on the evidence required for validation and on cross-agency standards will support acceleration of the application of digital health technologies, further enabling community-based clinical trials.
By the end of this decade, we believe that community-based clinical trials will become the norm, not the outlier. To achieve this, all clinical trial stakeholders — including the FDA, drug developers, and investigators — must work together to foster a patient-centric clinical trial culture that embraces innovation and brings trials closer to potential participants. The result will be a win for everyone.
Robert Metcalf, Ph.D., is group vice president for clinical design, delivery and analytics, China and Japan medical, for Lilly. Jeffrey Francer, J.D., is Lilly’s vice president, head of global regulatory policy and strategy.