How Flexibility Can Strengthen The Sponsor-Site Relationship
By Lilian Lee, director of clinical science, Freenome
In 2020, Freenome launched its large validation study, PREEMPT CRC, to test the early diagnosis of colorectal cancer using a multiomics platform. The multiomics platform combines tumor and non-tumor signals with machine learning to detect cancer in its earliest stages using a standard blood draw. From the start, Freenome sought to have a representative and diverse population participating in this colorectal cancer screening study. That meant expanding beyond academic research centers to enlist community hospitals and clinics to reach patient populations that are historically underrepresented in clinical research.
As COVID-19 restrictions spread across the country, Freenome leaned into the study’s existing diversified strategies to further expand convenience to participants. It worked. Freenome enrolled more than 40,000 participants, with more than 200 sites across the continental United States contributing to the study.
From a data perspective, the study was well diversified across ethnic, socioeconomic, and geographic categories. But the sheer volume of participating sites added a level of complexity when it came to ensuring consistent clinical data and metrics while balancing the burden placed on participating sites.
Some sites had more resources dedicated to research. These sites, including some academic institutions, had multiple investigators who were more experienced managing clinical research. They were often located in major cities with access to a large patient population. In contrast, some sites were led by a single investigator with limited staff and less experience in conducting clinical trials. These were often located in rural communities with access to a smaller patient population. All were important to the study’s diversity and reach, but they required different approaches. In addition to the rigors of clinical research, Freenome leveraged key soft skills — communication, inclusivity, cultural sensitivity, and awareness of diverse site capabilities and needs — to successfully execute one of the largest, most diverse studies to date for colorectal cancer.
This experience provided helpful insights that can be applied to any multi-center, multi-site clinical study.
Starting With The Basics: Clear Lines Of Communication
Communication is key, so we started with extensive training for site coordinators, engaging in face-to-face interactions whenever possible to build strong relationships with our extended teams. This set the tone for collaboration and communication. We established clear expectations with specific roles and responsibilities outlined across all sites. And this set up a solid knowledge base among site staff, fostered communication, and enabled sites to appropriately allocate resources necessary for the duration of the study.
To maintain strong communication, we created an internal communication platform to keep Freenome team members up to date on new learnings and decisions. This was a key resource for all staff, regardless of whether they were on the data collection or execution side of the study. Small misalignments had the potential to translate into significant impacts across participating sites. We consolidated key learnings and shared them in communications to sites in regular newsletters. This provided an opportunity to clear up confusion and provide updates immediately and consistently across sites as the study progressed.
In addition, we expanded communication channels to include newsletters and frequent email communications. With these, we shared continuously evolving state and federal COVID-19 guidelines during the pandemic and responded to site staff questions. Multiple levels of communication, including the direct communications between site managers and study leads and sites, helped place emphasis on key messaging where needed.
Building strong relationships with site staff early on helped foster an understanding of communication styles and create a culture of collaboration. Participating sites became an extension of the Freenome team. That inclusive culture ensured every member of the team, no matter the level, location, or experience, had a clear pathway to communicate questions and concerns. Sites were not only welcomed to communicate but encouraged to do so.
We heard from sites that our unified, collaborative company culture and shared goals made sites feel like true partners. This feedback served — and continues to serve — as a true motivator for all of our clinical research.
Recognizing — And Respecting — The Differences Between Sites
Each of the more than 200 sites across the country was unique. It was important to recognize that the needs of a well-funded academic research center significantly differed from the needs of a rural clinic with a single investigator who had limited or no experience in clinical trials. This required flexibility and a solution-oriented approach.
Teams were structured to accommodate the differences between sites. Leads were assigned to manage groups of similar sites, such as those with little or no research experience. We implemented multiple touchpoints and frequent check-ins to help guide and answer any questions. That set expectations from the start and enabled leads to allocate the appropriate time and resources to support sites as needed. For example, for newer sites with less experience than research centers, we developed dashboards to track metrics such as patients, samples, eligibility requirements, and discrepancies, providing them with a system to easily manage a multitude of variables. By anticipating inconsistencies and challenges that may arise, team leads were prepared to respond with sensitivity to resolve issues quickly and collaboratively.
While core structural elements of the study were clearly and consistently defined across all sites, we allowed certain areas of flexibility that might facilitate operations and efficiency without jeopardizing data quality.
For some sites, gathering clinically relevant data places a heavy demand on the site’s time and resources. Site coordinators need to secure all necessary patient information accurately and completely, while still being able to communicate and identify complex factors that could negatively impact a study, including details and context that go beyond what are captured in study documents.
That’s why it was critical that everyone on staff was trained to be sensitive to nuances. For example, if a participant had been hospitalized, the event itself may not necessarily disqualify a participant from continuing in the study. But if a treatment during hospitalization was systemic, such as general anesthesia, that could have unknown consequences on the quality of the sample. So, while inclusion criteria were very specific, there can be exceptions. It was important to accommodate and respond to these unique circumstances throughout the study to ensure the quality of the patient data.
As diversity in clinical studies continues to shift to the forefront of research to better ensure increased availability of treatment options for all relevant populations, study designs must also be reevaluated. It is our hope that working with sites of all kinds will become the norm and protocols will need to reflect that. Despite the growth in research, a humanistic approach will always work best. Respect, communication, and collaboration will continue to determine the success of a future healthcare system representative of all populations.
About The Author:
Lilian Lee is the director of clinical science at Freenome, where she drives study design, medical review, and clinical evidence development for Freenome’s colorectal cancer and multi-cancer programs. With a specialty in clinical strategy, Lilian builds clinical evidence to support commercial success for medical device and medtech products. Prior to Freenome, Lilian held leadership roles at Medtronic CardioVascular in global evidence strategy, clinical study execution, and cross functional product development teams. Lilian has a Ph.D. in pharmaceutical sciences from the University of Southern California and a bachelor’s degree from the University of California, Berkeley, where she was a Chancellor’s Scholar. Based in the Bay Area, Lilian is an avid hiker and enjoys spending time outdoors.