By Deborah Borfitz 

September 19, 2024 | The patient groups more likely to be treated at community practices with limited or no access to oncology clinical trials are the same groups historically underrepresented in such trials, finds a nationwide study conducted by Flatiron Health. The reasons for this are unknown, but the research effectively rules out quality of care and location of the practices, according to Ivy Altomare, M.D., head of research oncology, clinical research. 

One important clue was that the likelihood of research engagement greatly declined along with the practice's size. This led to the hypothesis that sites with fewer doctors treating fewer patients lack the resources to stand up and sustain a clinical research program, she says. Flatiron believes technology is the key to addressing that barrier by shouldering some of the most time-consuming operational tasks in conducting trials, notably patient screening and study-related data entry. 

Neal Meropol, vice president of research oncology at Flatiron Health, says he has come to believe that the biggest cause of low clinical trial participation is not the attitudes and knowledge of patients and clinicians. The greatest barrier is simply access to studies where patients receive their care—part of the drumbeat heard from federal regulators, government agencies, and patient advocacy organizations to make trials more “pragmatic” for investigators, clinicians, and would-be trial participants. 

As used here, pragmatic means simplifying the operational and design aspects of trials, so they are better suited to community-based practice settings and “look more like routine care,” he says. This implies loosening overly strict eligibility criteria and minimizing “extraneous” data collection but also implementing new technologies for the transfer of data directly from the electronic health record (EHR) to the study database, which is a major focus of Flatiron’s efforts. 

Lowering some of the barriers for small practices will require them to be equipped with the infrastructure and staffing necessary for running increasingly complex studies and having ways to mitigate the time commitment asked of study participants, Meropol says. Having close relationships with study sponsors who develop new therapies, care-providing clinicians, and evidence-producing clinical researchers, Flatiron Health finds itself in a unique position to facilitate and find shared goals between different constituents in the ecosystem, he adds. 

Search for Clues 

Flatiron Health, which owns and operates an EHR called OncoEMR, is in the business of providing technology to numerous oncology practices across the United States, says Altomare. “We noted some of those community practices offered trials to their patients and some did not, but very little is known about how those types of practices and the patients they treat might be different from each other.”

That question was the basis of the recent national study that was published in JNCI Cancer Spectrum (DOI: 10.1093/jncics/pkae060). The analysis tapped data from Flatiron’s deidentified real-world database, which encompasses data from more than 280 cancer clinics representing 800 sites of care across the U.S. 

The analysis looked at 550,000 patients with cancer treated at 178 community oncology practices and compared those in the high research engagement category (108) to those in the low research engagement category (70), says Altomare. The focus was on patient demographics (e.g., ethnicity and insurance and socioeconomic status) and practice characteristics (e.g., patient-to-physician ratio and number of active patients and percentages of those with evidence of biomarker testing).

The cancer treatment trial enrollment rate was calculated as the number of trial participants divided by the total number of active patients at a practice, she shares. The cutoff value to classify a practice as having high or low research engagement was set for practices within the highest two quintiles for trial enrollment rates. 

Evidence of structured biomarker testing served as a surrogate of the quality of care provided by the two practice groups, says Altomare, which looked “nearly identical” for the low and high research engagement sites. Although only a single performance indicator, genomic testing for molecular alterations in cancerous tumors is critical for guiding treatment decision-making, she adds. 

In terms of the location of practices, the breakdown by urban, suburban, and rural designations likewise turned up no significant differences in research engagement in either group. This contradicts the common belief that engagement is lower in less populated rural areas, says Altomare. 

Improving Study Conduct

The mission of Flatiron Health is to “improve and extend lives by learning from the experiences of every person with cancer,” says Meropol. This has historically been done using routinely collected EHR data to generate evidence, but “retrospective data can’t answer all questions that are of relevance to patients.” 

With that in mind, he continues, Flatiron Health began supplementing its curation and aggregation of EHR data with the prospective collection of information on patients—in this case, through their participation in clinical trials. Given its EHR-connected network of oncology practices and understanding of clinician workflows, the company builds tools for seamlessly integrating clinical research into routine clinical care that can help break down access barriers to trials. 

“It was important to us to understand how and where and who was conducting clinical trials within this nationwide community network, which we believe is generally representative of oncology care across the United States,” says Meropol. The comparison study of low and high research engagement practices is helping Flatiron better leverage the network to improve the conduct of clinical research studies. 

The proportion of cancer patients enrolled in clinical trials hasn’t changed much over the past 20 years, says Altomare. “There has been a lot of funding and public and private initiatives focused on moving the needle, but this is only getting us so far.” 

Those efforts include the Community Oncology Research Institute established by the nonprofit Association of Cancer Care Centers, and the National Quality Minority Forum, which supports research programs in rural communities and communities serving high proportions of historically underrepresented minorities, she continues. There is also the Robert A. Winn Diversity in Clinical Trials award program, an application-based training program for new community investigators, and various private companies that provide paid end-to-end services for some or all research-related activities. The National Cancer Institute (NCI) also supports clinical trials in community settings through a national network called the Community Oncology Research Program. 

The overarching issue is that these options all require an investment of time and money that resource-strapped practices can generally ill afford, says Altomare. Flatiron is now in the process of measuring how technological tools could relieve some of the burden so they can “do more with less.” 

Making Headway

Among the tech tools of Flatiron is Flatiron Clinical Pipe that facilitates the automated transfer of study data from the EHR to a research database to reduce the burden of data entry, which is a major focus of company efforts to make clinical trials more efficient and broadly accessible, Meropol says. Flatiron Clinical Pipe “reduces both the time and effort related to copying information from one place to another for clinical trials and also reduces... the number of errors involved,” and thereby monitoring-related costs. 

Flatiron is very much in lockstep with the Food and Drug Administration (FDA), whose Oncology Center of Excellence is running a Project 5 in 5 initiative to crowdsource ideas for large pragmatic studies that could answer questions of clinical relevance, he says. The FDA’s Center for Drug Evaluation and Research has also set up a Streamlined Trials Embedded into clinical Practice (STEP) demonstration program that is “a call for sponsors to propose pragmatically designed studies of regulatory intent for which the FDA has committed to a close collaboration on design and execution” to facilitate the testing of novel approaches. 

Meropol himself served as co-chair of the National Cancer Institute’s Streamlining Clinical Trials Working Group that produced a report presented to the NCI that included six recommendations for improving the operational efficiency of late-phase clinical trials. One of them was to “endorse further testing and implementation of tools for extraction of clinical trial data from EHRs.” 

Solving the trial access problem will require a multi-pronged approach, says Altomare, including sponsors changing the way they design trials and providing funding in their study budgets to support community clinics in running them. Sites need resources to help train and certify their staff and utilize EHR-embedded technology that can offload some of the data-entry burden of conducting studies. 

Flatiron offers a comprehensive package of products and services to sponsors that are by extension of value to practices, says Meropol. In addition to simplifying data entry in clinical trials and Clinical Pipe, these include the use of curated EHR-derived data to assist with site selection for studies and improve patient identification for trials. 

In keeping with its “data for good” mantra, Flatiron has for the past five years partnered with the American Cancer Society to offer a Real-World Data Impact Award to three investigators annually to do research using Flatiron data for evidence generation. Among the notable takeaways from published research are a pair of studies highlighting the need to improve health equity and address systemic issues causing decreased survival and clinical trial participation across various demographics, three others on increased understanding of treatments effectiveness at the point of care, another two on the importance of assessing real-world clinical care in addition to traditional clinical trials that can exclude vulnerable populations, and four studies on the clinical necessity of ensuring equitable use of biomarker testing and novel treatments.  

“Advances in cancer care occur through the conduct of high-quality clinical trials that are representative of the patients we see in the clinic every day,” says Meropol. “It is a societal imperative to increase access to clinical trials for all patients wherever they receive their care such that everyone has the opportunity to participate in improving the outcomes for people with cancer.”